FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Reynolds, KS AF Reynolds, K. S. TI Clinical Pharmacology and Viral Infections SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID DRUG DEVELOPMENT; RESISTANCE; DYNAMICS; MODEL C1 US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Reynolds, KS (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM kellie.reynolds@fda.hhs.gov NR 23 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 NOV PY 2010 VL 88 IS 5 BP 569 EP 573 DI 10.1038/clpt.2010.223 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 668UJ UT WOS:000283296500001 PM 20959836 ER PT J AU Arya, V Carter, WW Robertson, SM AF Arya, V. Carter, W. W. Robertson, S. M. TI The Role of Clinical Pharmacology in Supporting the Emergency Use Authorization of an Unapproved Anti-Influenza Drug, Peramivir SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material AB On 23 October 2009, the commissioner of the US Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for peramivir for intravenous injection, an unapproved neuraminidase inhibitor used for treating certain hospitalized adult and pediatric patients infected with 2009 H1N1 influenza. This was the first EUA of an unapproved drug product. This report summarizes the critical contributions of the clinical pharmacology review team in support of the peramivir EUA. C1 [Arya, V.; Robertson, S. M.] US FDA, Div Clin Pharmacol 4, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Carter, W. W.] US FDA, Div Antiviral Prod, Off Antimicrobial Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Arya, V (reprint author), US FDA, Div Clin Pharmacol 4, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM vikram.arya@fda.hhs.gov NR 5 TC 15 Z9 15 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 NOV PY 2010 VL 88 IS 5 BP 587 EP 589 DI 10.1038/clpt.2010.187 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 668UJ UT WOS:000283296500010 PM 20959843 ER PT J AU Marti, GE AF Marti, Gerald E. TI CELL COUNTING, HISTORY OF MBL AND THE CHANGING DIAGNOSIS OF CLL SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 10th Euroconference on Clinical Cell Analysis of the European-Society-for-Clinical-Cell-Analysis (ESCCA)/ Iberian Society-for-Cytometry (SIC) CY SEP 21-25, 2010 CL Valencia, SPAIN SP European Soc Clinical Cell Anal(ESCCA), Iberian Soc Cytometry(SIC) C1 [Marti, Gerald E.] US FDA, Silver Spring, 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 413 EP 413 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 677BW UT WOS:000283965100063 ER PT J AU Kuure, S Cebrian, C Quentin, M Lu, BS Chi, XA Deborah, H D'Agati, V Gurniak, C Walter, W Costantini, F AF Kuure, S. Cebrian, C. Quentin, Machingo Lu, Benson Chi, Xuan Deborah, Hyink D'Agati, Vivette Gurniak, Christine Walter, Witke Costantini, F. TI Actin depolymerizing factors Cfl1 and Dstn are required for ureteric bud branching morphogenesis SO DIFFERENTIATION LA English DT Meeting Abstract C1 [Kuure, S.] Univ Helsinki, Inst Biotechnol, Helsinki, Finland. [Cebrian, C.; Quentin, Machingo] Manhattan Coll, Sch Sci, Bronx, NY 10463 USA. [Lu, Benson; Chi, Xuan] Food & Drug Adm, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Deborah, Hyink; D'Agati, Vivette; Gurniak, Christine; Walter, Witke; Costantini, F.] Columbia Univ, Dept Genet & Dev Biol, New York, NY USA. EM Satu.Kuure@helsinki.fi RI Cebrian, Cristina/E-2185-2012 NR 0 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD NOV PY 2010 VL 80 SU 1 BP S46 EP S46 DI 10.1016/j.diff.2010.09.093 PG 1 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 672MT UT WOS:000283589700125 ER PT J AU Sjolund-Karlsson, M Howie, R Rickert, R Krueger, A Tran, TT Zhao, SH Ball, T Haro, J Pecic, G Joyce, K Fedorka-Cray, PJ Whichard, JM McDermott, PF AF Sjolund-Karlsson, Maria Howie, Rebecca Rickert, Regan Krueger, Amy Tran, Thu-Thuy Zhao, Shaohua Ball, Takiyah Haro, Jovita Pecic, Gary Joyce, Kevin Fedorka-Cray, Paula J. Whichard, Jean M. McDermott, Patrick F. TI Plasmid-mediated Quinolone Resistance among Non-Typhi Salmonella enterica Isolates, USA SO EMERGING INFECTIOUS DISEASES LA English DT Article ID FLUOROQUINOLONE BREAKPOINTS; UNITED-STATES; QNR GENES; PREVALENCE; AAC(6')-IB-CR; EMERGENCE AB We determined the prevalence of plasmid-mediated quinolone resistance mechanisms among non-Typhi Salmonella spp. isolated from humans, food animals, and retail meat in the United States in 2007. Six isolates collected from humans harbored aac(6')Ib-cr or a qnr gene. Most prevalent was qnrS1. No animal or retail meat isolates harbored a plasmid-mediated mechanism. C1 [Sjolund-Karlsson, Maria; Joyce, Kevin; Whichard, Jean M.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Howie, Rebecca; Pecic, Gary] IHRC Inc, Atlanta, GA USA. [Rickert, Regan; Krueger, Amy] Atlanta Res & Educ Fdn, Decatur, GA USA. [Tran, Thu-Thuy; Zhao, Shaohua; McDermott, Patrick F.] US FDA, Laurel, MD USA. [Ball, Takiyah; Haro, Jovita; Fedorka-Cray, Paula J.] USDA, Athens, GA USA. RP Sjolund-Karlsson, M (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd NE,Mailstop G29, Atlanta, GA 30333 USA. EM fwt4@cdc.gov FU CDC; USDA; FDA-CVM FX This work was supported by an interagency agreement between CDC, USDA, and FDA-CVM. NR 14 TC 17 Z9 18 U1 2 U2 9 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD NOV PY 2010 VL 16 IS 11 BP 1789 EP 1791 DI 10.3201/eid1611.100464 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 673YI UT WOS:000283699700027 PM 21029547 ER PT J AU Lu, CS Schenck, FJ Pearson, MA Wong, JW AF Lu, Chensheng Schenck, Frank J. Pearson, Melanie A. Wong, Jon W. TI Assessing Children's Dietary Pesticide Exposure: Direct Measurement of Pesticide Residues in 24-Hr Duplicate Food Samples SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE children's diets; dietary pesticide exposure; organophosphate pesticides; pesticide residue; pesticide risk assessment; pyrethroid insecticides ID FLAME PHOTOMETRIC DETECTION; GAS-CHROMATOGRAPHY; ORGANOPHOSPHORUS PESTICIDES; MULTIRESIDUE METHOD; MASS-SPECTROMETRY; ORGANIC DIETS; PRODUCE; HEALTH AB BACKGROUND: The data presented here are a response to calls for more direct measurements of pesticide residues in foods consumed by children and provide an opportunity to compare direct measures of pesticide residues in foods representing actual consumption with those reported by the U. S. Department of Agriculture Pesticide Data Program. OBJECTIVE: We measured pesticide residues in 24-hr duplicate food samples collected from a group of 46 young children participating in the Children's Pesticide Exposure Study (CPES). METHODS: Parents were instructed to collect 24-hr duplicate food samples of all conventional fruits, vegetables, and fruit juices equal to the quantity consumed by their children, similarly prewashed/prepared, and from the same source or batch. Individual or composite food items were analyzed for organophosphate (OP) and pyrethroid insecticide residues. RESULTS: We collected a total of 239 24-hr duplicate food samples collected from the 46 CPES children. We found 14% or 5% of those food samples contained at least one OP or pyrethroid insecticide, respectively. We measured a total of 11 OP insecticides, at levels ranging from 1 to 387 ng/g, and three pyrethroid insecticides, at levels ranging from 2 to 1,133 ng/g, in children's food samples. We found that many of the food items consumed by the CPES children were also on the list of the most contaminated food commodities reported by the Environmental Working Group. CONCLUSIONS: The frequent consumption of food commodities with episodic presence of pesticide residues that are suspected to cause developmental and neurological effects in young children supports the need for further mitigation. C1 [Lu, Chensheng] Harvard Univ, Sch Publ Hlth, Exposure Epidemiol & Risk Program, Dept Environm Hlth, Boston, MA 02115 USA. [Schenck, Frank J.] US FDA, SE Reg Lab, Atlanta, GA USA. [Pearson, Melanie A.] Emory Univ, Rollins Sch Publ Hlth, Dept Environm & Occupat Hlth, Atlanta, GA 30322 USA. [Wong, Jon W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Lu, CS (reprint author), 401 Pk Dr,Landmark Ctr W, Boston, MA 02215 USA. EM cslu@hsph.harvard.edu FU U.S. Environmental Protection Agency (EPA) [R-832244, R-829364] FX This work was supported by the U.S. Environmental Protection Agency (EPA) under the Science to Achieve Results research assistance program (R-832244 and R-829364). NR 25 TC 17 Z9 17 U1 10 U2 47 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2010 VL 118 IS 11 BP 1625 EP 1630 DI 10.1289/ehp.1002044 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 674CR UT WOS:000283711800037 PM 20639183 ER PT J AU Epstein, SL Price, GE AF Epstein, Suzanne L. Price, Graeme E. TI Cross-protective immunity to influenza A viruses SO EXPERT REVIEW OF VACCINES LA English DT Review DE animal models; conserved antigens; cross-protection; heterosubtypic immunity; human; influenza; pandemic; subtypes; universal vaccine; vaccine ID CYTOTOXIC T-LYMPHOCYTES; HETEROSUBTYPIC IMMUNITY; M2 PROTEIN; LETHAL INFLUENZA; CELL RESPONSES; HETEROTYPIC IMMUNITY; H5N1 INFLUENZA; EXTRACELLULAR DOMAIN; MATRIX PROTEIN-2; BROAD-SPECTRUM AB Antigenic changes in influenza virus occur gradually, owing to mutations (antigenic drift), and abruptly, owing to reassortment among subtypes (antigenic shift). Availability of strain-matched vaccines often lags behind these changes, resulting in a shortfall in public health. In animal models, cross-protection by vaccines based on conserved antigens does not completely prevent infection, but greatly reduces morbidity, mortality, virus replication and, thus, viral shedding and spread. Such immunity is especially effective and long-lasting with mucosal administration. Cross-protective immunity in humans is controversial, but is suggested by some epidemiological findings. 'Universal' vaccines protective against all influenza A viruses might substantially reduce severity of infection and limit spread of disease during outbreaks. These vaccines could be used 'off the shelf' early in an outbreak or pandemic, before strain-matched vaccines are available. C1 [Epstein, Suzanne L.; Price, Graeme E.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Epstein, SL (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. EM suzanne.epstein@fda.hhs.gov FU Center for Biologics Evaluation and Research/US FDA Division of Cellular and Gene Therapies; Center for Biologics Evaluation and Research Pandemic Influenza Initiative; National Vaccine Program; DHHS Office of Public Health Medical Emergency Counter-Measures; NIAID Trans-NIH/FDA Intramural Biodefense Program; FDA Chief Scientist's Challenge FX Funding of research in Suzanne Epstein's laboratory is provided by the Center for Biologics Evaluation and Research/US FDA Division of Cellular and Gene Therapies. Grants have been received from the Center for Biologics Evaluation and Research Pandemic Influenza Initiative, the National Vaccine Program, the DHHS Office of Public Health Medical Emergency Counter-Measures, the NIAID Trans-NIH/FDA Intramural Biodefense Program and the FDA Chief Scientist's Challenge Grant program. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 172 TC 50 Z9 54 U1 0 U2 5 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD NOV PY 2010 VL 9 IS 11 BP 1325 EP 1341 DI 10.1586/ERV.10.123 PG 17 WC Immunology SC Immunology GA 686GH UT WOS:000284684300014 PM 21087110 ER PT J AU Akbulut, H Tang, Y Akbulut, KG Maynard, J Deisseroth, A AF Akbulut, H. Tang, Y. Akbulut, K. G. Maynard, J. Deisseroth, A. TI Addition of adenoviral vector targeting of chemotherapy to the MUC-1/ecdCD40L VPPP vector prime protein boost vaccine prolongs survival of mice carrying growing subcutaneous deposits of Lewis lung cancer cells SO GENE THERAPY LA English DT Article DE chemotherapy; adenoviral vector; cytosine deaminase; MUC-1; lung cancer cell ID BREAST-CANCER; PROSTATE-CANCER; SIDE POPULATION; TUMOR-CELLS; STEM-CELLS; MUC1; IDENTIFICATION; ACTIVATION; EXPRESSION; SIGNATURE AB We studied the effect of adding chemotherapy or vector targeted chemotherapy to the administration of an Ad-sig-hMUC-1/ecdCD40L adenoviral vector prime-hMUC-1/ecdCD40L protein boost cancer vaccine (designated hMUC1/ecdCD40L VPPP vaccine), which were administered to test mice 10 days following subcutaneous (s.c.) inoculation of 500 000 Lewis Lung Carcinoma cells, at a time when the average volume of the s.c. tumors was 50 cu mm. The survival of hMUC-1/ecdCD40L VPPP vaccine-treated mice was twice as long as untreated mice. Addition of vector-targeted chemotherapy (AdCMVCDIRESE1A/5FC) to the hMUC-1/ecdCD40L VPPP vaccine 10 days after tumor inoculation significantly (P = 0.0062) prolonged the survival of the test mice over administration of the hMUC-1/ecdCD40L VPPP vaccine alone or the control mice (P < 0.00001). Interestingly, the combination of the AdCMVCDIRESE1A/5FC vector-targeted chemotherapy to the hMUC-1/ecdCD40L VPPP vaccine decreased the levels of CD44(+)CD24 cells in s.c. deposits of the human MUC-1-positive Lewis Lung Cancer cell line (LL2/LL1hMUC-1) by 20 fold. These results suggest that the addition of vector-targeted chemotherapy to an adenoviral-based cancer vaccine is a strategy that deserves further testing. Gene Therapy (2010) 17, 1333-1340; doi:10.1038/gt.2010.93; published online 1 July 2010 C1 [Akbulut, H.] Ankara Univ, Sch Med, Dept Med Oncol, TR-06100 Ankara, Turkey. [Tang, Y.; Maynard, J.; Deisseroth, A.] Sidney Kimmel Canc Ctr, Dept Genet Therapy, San Diego, CA USA. [Akbulut, K. G.] Gazi Univ, Sch Med, Dept Physiol, Ankara, Turkey. RP Deisseroth, A (reprint author), US FDA, 10903 New Hampshire Ave,Bldg 22,Room 6187, Silver Spring, MD 20903 USA. EM albert.deisseroth@fda.hhs.gov FU DOD [17999457, BC022063]; California Breast Cancer Research Program (CBCRP) [12IB-0159]; NIH [CA 104898]; Kaye and Richard Woltman Foundation; Breast Cancer Research Foundation; Turkish Academy of Sciences [TUBA-GEBIP-2001-1]; National Cancer Institute of United States of America; Lechner/Haag Foundation; UICC-Yamagiwa-Yoshida international FX We acknowledge support from the support of the SKCC by Sidney Kimmel and the following grants to Albert Deisseroth: DOD (Grants 17999457 and BC022063), the California Breast Cancer Research Program (CBCRP 12IB-0159), the NIH Grant PPG (CA 104898), a grant from the Kaye and Richard Woltman Foundation, and a grant from the Breast Cancer Research Foundation. We acknowledge support to Hakan Akbulut from the Turkish Academy of Sciences (TUBA-GEBIP-2001-1), the National Cancer Institute of United States of America, The Lechner/Haag Foundation and UICC-Yamagiwa-Yoshida international study grants. The views expressed are the result of independent work and do not represent the views or findings of the US FDA or the US government. NR 33 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 0969-7128 J9 GENE THER JI Gene Ther. PD NOV PY 2010 VL 17 IS 11 BP 1333 EP 1340 DI 10.1038/gt.2010.93 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 678VG UT WOS:000284109600004 PM 20596057 ER PT J AU Guan, Y Anderson, S Starost, M Despres, D Fritz, T Tabak, L AF Guan, Yu Anderson, Stasia Starost, Matthew Despres, Daryl Fritz, Timothy Tabak, Lawrence TI Normal Heart Development in Mice is Dependent on Mucin-Type O-Linked Glycosylation SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Conference of the Society-for-Glycobiology CY NOV 07-10, 2010 CL St. Pete Beach, FL SP Soc Glycobiol C1 [Guan, Yu; Anderson, Stasia; Starost, Matthew; Despres, Daryl; Tabak, Lawrence] NIH, Bethesda, MD 20892 USA. [Fritz, Timothy] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2010 VL 20 IS 11 MA 26 BP 1457 EP 1457 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 661TF UT WOS:000282750300036 ER PT J AU Giffin, RB Woodcock, J AF Giffin, Robert B. Woodcock, Janet TI Comparative Effectiveness Research: Who Will Do The Studies? SO HEALTH AFFAIRS LA English DT Article ID CLINICAL-RESEARCH AB A key tenet of comparative effectiveness research is that it should be conducted in real-world health care settings. This article addresses a basic question: What is the capacity of the clinical research enterprise to conduct such studies? We argue that the clinical trial system is already at capacity and will not be able to absorb large amounts of comparative effectiveness research without diverting resources from other needs. We propose a federally funded national clinical research infrastructure that would increase comparative effectiveness research capacity by encouraging community-based clinicians and their patients to participate in trials. C1 [Giffin, Robert B.] Ctr Med Technol Policy, Baltimore, MD USA. [Woodcock, Janet] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Giffin, RB (reprint author), Ctr Med Technol Policy, Baltimore, MD USA. EM robert.giffin@cmtpnet.org NR 10 TC 8 Z9 8 U1 0 U2 0 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV PY 2010 VL 29 IS 11 BP 2075 EP 2081 DI 10.1377/hlthaff.2010.0669 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 673MX UT WOS:000283668700017 PM 21041751 ER PT J AU Soneson, JE Myers, MR AF Soneson, Joshua E. Myers, Matthew R. TI Thresholds for Nonlinear Effects in High-Intensity Focused Ultrasound Propagation and Tissue Heating SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article ID BEAMS; ATTENUATION AB For a variety of reasons, including their simplicity and ability to capitalize upon superposition, linear acoustic propagation models are preferable to nonlinear ones in modeling the propagation of high-intensity focused ultrasound (HIFU) beams. However, under certain conditions, nonlinear models are necessary to accurately model the beam propagation and heating. In analyzing the performance of a HIFU system, it is advantageous to know before the analysis whether a linear model suffices. This paper examines the problem of determining the thresholds at which nonlinear effects become important. It is demonstrated that nonlinear interaction has different effects on different physical and derived quantities, such as compressional pressure, rarefactional pressure, intensity, heat rate, temperature rise, and thermal lesion volume. Thresholds are determined as a function of the dimensionless gain, nonlinearity, and absorption parameters. The relative difference between linear and nonlinear predictions is plotted as a series of contours, enabling practicioners to locate their system in parameter space and determine whether nonlinearity significantly affects the quantities of interest. C1 [Soneson, Joshua E.] US FDA, Ctr Devices & Radiol Hlth, Div Solid & Fluid Mech, Silver Spring, MD USA. RP Soneson, JE (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Solid & Fluid Mech, Silver Spring, MD USA. EM joshua.soneson@fda.hhs.gov NR 10 TC 7 Z9 7 U1 1 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0885-3010 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD NOV PY 2010 VL 57 IS 11 BP 2450 EP 2459 DI 10.1109/TUFFC.2010.1711 PG 10 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 676UU UT WOS:000283944900008 PM 21041132 ER PT J AU Mahajan, B Berzofsky, JA Boykins, RA Majam, V Zheng, H Chattopadhyay, R de la Vega, P Moch, JK Haynes, JD Belyakov, IM Nakhasi, HL Kumar, S AF Mahajan, Babita Berzofsky, Jay A. Boykins, Robert A. Majam, Victoria Zheng, Hong Chattopadhyay, Rana de la Vega, Patricia Moch, J. Kathleen Haynes, J. David Belyakov, Igor M. Nakhasi, Hira L. Kumar, Sanjai TI Multiple Antigen Peptide Vaccines against Plasmodium falciparum Malaria SO INFECTION AND IMMUNITY LA English DT Article ID B-CELL EPITOPES; RED-BLOOD-CELLS; CIRCUMSPOROZOITE PROTEIN; T-CELL; SYNTHETIC PEPTIDES; SPOROZOITE VACCINE; IMMUNE-RESPONSE; SURFACE-ANTIGEN; ANTIBODIES; IMMUNOGENICITY AB The multiple antigen peptide (MAP) approach is an effective method to chemically synthesize and deliver multiple T-cell and B-cell epitopes as the constituents of a single immunogen. Here we report on the design, chemical synthesis, and immunogenicity of three Plasmodium falciparum MAP vaccines that incorporated antigenic epitopes from the sporozoite, liver, and blood stages of the life cycle. Antibody and cellular responses were determined in three inbred (C57BL/6, BALB/c, and A/J) strains, one congenic (HLA-A2 on the C57BL/6 background) strain, and one outbred strain (CD1) of mice. All three MAPs were immunogenic and induced both antibody and cellular responses, albeit in a somewhat genetically restricted manner. Antibodies against MAP-1, MAP-2, and MAP-3 had an antiparasite effect that was also dependent on the mouse major histocompatibility complex background. Anti-MAP-1 (CSP-based) antibodies blocked the invasion of HepG2 liver cells by P. falciparum sporozoites (highest, 95.16% in HLA-A2 C57BL/6; lowest, 11.21% in BALB/c). Furthermore, antibodies generated following immunizations with the MAP-2 (PfCSP, PfLSA-1, PfMSP-1(42), and PfMSP-3b) and MAP-3 (PfRAP-1, PfRAP-2, PfSERA, and PfMSP-1(42)) vaccines were able to reduce the growth of blood stage parasites in erythrocyte cultures to various degrees. Thus, MAP-based vaccines remain a viable option to induce effective antibody and cellular responses. These results warrant further development and preclinical and clinical testing of the next generation of candidate MAP vaccines that are based on the conserved protective epitopes from Plasmodium antigens that are widely recognized by populations of divergent HLA types from around the world. C1 [Kumar, Sanjai] US FDA, Malaria Res Program, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Berzofsky, Jay A.; Belyakov, Igor M.] NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [de la Vega, Patricia; Moch, J. Kathleen; Haynes, J. David] USN, Med Res Ctr, Silver Spring, MD USA. [de la Vega, Patricia; Moch, J. Kathleen; Haynes, J. David] Walter Reed Army Inst Res, Silver Spring, MD USA. RP Kumar, S (reprint author), US FDA, Malaria Res Program, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. EM Sanjai.kumar@fda.hhs.gov NR 63 TC 24 Z9 29 U1 0 U2 2 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 NOV PY 2010 VL 78 IS 11 BP 4613 EP 4624 DI 10.1128/IAI.00533-10 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 665RB UT WOS:000283052100018 PM 20823210 ER PT J AU Bousquet, J Mantzouranis, E Cruz, AA Ait-Khaled, N Baena-Cagnani, CE Bleecker, ER Brightling, CE Burney, P Bush, A Busse, WW Casale, TB Chan-Yeung, M Chen, RC Chowdhury, B Chung, KF Dahl, R Drazen, JM Fabbri, LM Holgate, ST Kauffmann, F Haahtela, T Khaltaev, N Kiley, JP Masjedi, MR Mohammad, Y O'Byrne, P Partridge, MR Rabe, KF Togias, A van Weel, C Wenzel, S Zhong, NS Zuberbier, T AF Bousquet, Jean Mantzouranis, Eva Cruz, Alvaro A. Ait-Khaled, Nadia Baena-Cagnani, Carlos E. Bleecker, Eugene R. Brightling, Chris E. Burney, Peter Bush, Andrew Busse, William W. Casale, Thomas B. Chan-Yeung, Moira Chen, Rongchang Chowdhury, Badrul Chung, Kian Fan Dahl, Ronald Drazen, Jeffrey M. Fabbri, Leonardo M. Holgate, Stephen T. Kauffmann, Francine Haahtela, Tari Khaltaev, Nikolai Kiley, James P. Masjedi, Mohammad R. Mohammad, Yousser O'Byrne, Paul Partridge, Martyn R. Rabe, Klaus F. Togias, Alkis van Weel, Christiaan Wenzel, Sally Zhong, Nanshan Zuberbier, Torsten TI Uniform definition of asthma severity, control, and exacerbations: Document presented for the World Health Organization Consultation on Severe Asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Asthma; severity; control; risk; definition; GARD ID TO-TREAT ASTHMA; LUNG-FUNCTION; INHALED CORTICOSTEROIDS; PRESCHOOL-CHILDREN; CHILDHOOD ASTHMA; RESEARCH-PROGRAM; LOW-INCOME; FOLLOW-UP; DEVELOPING-COUNTRIES; CLUSTER-ANALYSIS AB Asthma is a global health problem affecting around 300 million individuals of all ages, ethnic groups and countries. It is estimated that around 250,000 people die prematurely each year as a result of asthma. Concepts of asthma severity and control are important in evaluating patients and their response to treatment, as well as for public health, registries, and research (clinical trials, epidemiologic, genetic, and mechanistic studies), but the terminology applied is not standardized, and terms are often used interchangeably. A common international approach is favored to define severe asthma, uncontrolled asthma, and when the 2 coincide, although adaptation may be required in accordance with local conditions. A World Health Organization meeting was convened April 5-6, 2009, to propose a uniform definition of severe asthma. An article was written by a group of experts and reviewed by the Global Alliance against Chronic Respiratory Diseases review group. Severe asthma is defined by the level of current clinical control and risks as "Uncontrolled asthma which can result in risk of frequent severe exacerbations (or death) and/or adverse reactions to medications and/or chronic morbidity (including impaired lung function or reduced lung growth in children)." Severe asthma includes 3 groups, each carrying different public health messages and challenges: (1) untreated severe asthma, (2) difficult-to-treat severe asthma, and (3) treatment-resistant severe asthma. The last group includes asthma for which control is not achieved despite the highest level of recommended treatment and asthma for which control can be maintained only with the highest level of recommended treatment. (J Allergy Clin Immunol 2010; 126: 926-38.) C1 [Bousquet, Jean] Hop Arnaud Villeneuve, Serv Malad Resp, Univ Hosp, F-34295 Montpellier 5, France. [Bousquet, Jean; Kauffmann, Francine] INSERM, CESP Ctr Res Epidemiol & Populat Hlth, U1018, Villejuif, France. [Bousquet, Jean; Kauffmann, Francine] UMRS 1018, Villejuif, France. [Mantzouranis, Eva] WHO, Geneva, Switzerland. [Cruz, Alvaro A.] Univ Fed Bahia, ProAR FMB, Salvador, BA, Brazil. [Ait-Khaled, Nadia] Union, Paris, France. [Baena-Cagnani, Carlos E.] Catholic Univ, Fac Med, Cordoba, Argentina. [Baena-Cagnani, Carlos E.] Univ Genoa, Sch Specializat, I-16126 Genoa, Italy. [Bleecker, Eugene R.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Brightling, Chris E.] Inst Lung Hlth, Leicester, Leics, England. [Burney, Peter; Bush, Andrew; Chung, Kian Fan] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW7 2AZ, England. [Bush, Andrew] Univ London Imperial Coll Sci Technol & Med, Royal Brompton Hosp, London SW7 2AZ, England. [Chung, Kian Fan] Royal Brompton Hosp, Biomed Res Unit, London, England. [Partridge, Martyn R.] Univ London Imperial Coll Sci Technol & Med, Charing Cross Hosp, NHLI Div, London SW7 2AZ, England. [Busse, William W.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53706 USA. [Casale, Thomas B.] Creighton Univ, Omaha, NE 68178 USA. [Chan-Yeung, Moira] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Chen, Rongchang; Zhong, Nanshan] Guangzhou Med Coll, Guangzhou Inst Resp Dis, Guangzhou, Guangdong, Peoples R China. [Chowdhury, Badrul] US FDA, Silver Spring, MD USA. [Dahl, Ronald] Aarhus Univ Hosp, Aarhus, Denmark. [Drazen, Jeffrey M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Fabbri, Leonardo M.] Univ Modena & Reggio Emilia, Modena, Italy. [Holgate, Stephen T.] Southampton Gen Hosp, Southampton, Hants, England. [Haahtela, Tari] Helsinki Univ Hosp, Skin & Allergy Hosp, Helsinki, Finland. [Khaltaev, Nikolai] Global Alliance Chron Resp Dis, Geneva, Switzerland. [Kiley, James P.] NHLBI, NIH, DHHS, Bethesda, MD 20892 USA. [Togias, Alkis] NIAID, Bethesda, MD 20892 USA. [Masjedi, Mohammad R.] NRITLD, CRDRC, Tehran, Iran. [Mohammad, Yousser] Tishreen Univ, Sch Med, Latakia, Syria. [O'Byrne, Paul] McMaster Univ, Dept Med, Hamilton, ON L8S 4L8, Canada. [Rabe, Klaus F.] Leiden Univ, Med Ctr, NL-2300 RA Leiden, Netherlands. [van Weel, Christiaan] Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands. [Wenzel, Sally] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Zuberbier, Torsten] Charite Univ Med Berlin, Dept Dermatol & Allergy, Allergy Ctr Charite, Berlin, Germany. RP Bousquet, J (reprint author), Hop Arnaud Villeneuve, Serv Malad Resp, Univ Hosp, 371 Ave Doyen Gaston Giraud, F-34295 Montpellier 5, France. EM jean.bousquet@inserm.fr RI Dahl, Ronahl/F-8170-2013; Casale, Thomas/K-4334-2013; van Weel, Chris/D-4375-2009; Fabbri, Leonardo/I-4055-2012; Cruz, Alvaro/I-1676-2012; OI Casale, Thomas/0000-0002-3149-7377; van Weel, Chris/0000-0003-3653-4701; Fabbri, Leonardo/0000-0001-8894-1689; Cruz, Alvaro/0000-0002-7403-3871; O'Byrne, Paul/0000-0003-0979-281X; Masjedi, Mohammadreza/0000-0003-4964-3851; Chung, Kian Fan/0000-0001-7101-1426 FU EU [FOOD-CT-2004-506378]; World Health Organization Collaborating Center on Asthma and Rhinitis, Montpellier; Chiesi; Mantecorp (Brazil); CNPq (Brazil); National Research Council; Brazilian Ministry of Health; FAPESB State of Brazil Agency for Research; Wellcome Trust (UK); Novartis; GlaxoSmithKline; NIH/NHLBI; MedImmune; AstraZeneca; Department of Health (UK); NIH-NIAID; NIH-NHLBI; Ception; MRC UK; Asthma UK; Wellcome Trust; Abbott; Boehringer Ingelheim; Merck Sharp Dohme,; Nycomed; Roche; Pfizer; Menarini; Schering-Plough; Merck Sharp Dohme; UCB; Italian Ministry of Health; Italian Ministry for University and Research; Merck; Wyeth; Schering; Alexion; Forest; AZ; BI; Pearl; MSD; AS; Dutch Asthma Foundation (NAF); Netherlands Medical Research Council (Zon/Mw); Aerovance; Amgen FX In collaboration with the Global Allergy and Asthma European Network (GA2LEN), supported by the Sixth EU Framework program for research (contract no. FOOD-CT-2004-506378) and the World Health Organization Collaborating Center on Asthma and Rhinitis, Montpellier.; Disclosure of potential conflict of interest: J. Bousquet has received honorarium for scientific and advisory boards, lectures, and press conferences from Stallergenes, Actelion, Almirall, AstraZeneca, Chiesi, Ask, Merck, MSD, Novartis, OM Pharma, Sanofi-Aventis, Schering-Plough, Teva, and Uriach. A. A. Cruz has given talks for Novartis and GlaxoSmithKline; has received research support from Chiesi, Mantecorp (Brazil), CNPq (Brazil), National Research Council, Brazilian Ministry of Health, FAPESB State of Brazil Agency for Research, Wellcome Trust (UK), Novartis, and GlaxoSmithKline; is a member of the Planning Group for the Global Alliance against Chronic Respiratory Diseases; and is a member of the Executive Committee for the Global Initiative for Asthma and Allergic Rhinitis and its Impact on Asthma. E. R. Bleecker is a consultant for Aerovance, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Pfizer and has received research support from the NIH/NHLBI. C. E. Brightling is a consultant for MedImmune, AstraZeneca, and Roche and has received research support from MedImmune, AstraZeneca, and GlaxoSmithKline. P. Burney has received research support from the Department of Health (UK). W. W. Busse is on the Advisory Board for Altair, Amgen, Centocor, GlaxoSmithKline, Merck, Pfizer, Wyeth, and Johnson & Johnson; is a consultant for AstraZeneca, Boehringer Ingelheim, Novartis, TEVA, and GlaxoSmithKline; is a speaker for Merck; and has received research support from NIH-NIAID, NIH-NHLBI, Novartis, AstraZeneca, GlaxoSmithKline, MedImmune, and Ception. T. B. Casale is executive vice president of the AAAAI and is on the board of directors for WAO. R. Chen is a consultant on asthma and COPD for AstraZeneca and GlaxoSmithKline and has served as an expert witness on the topic of management of asthma. K. F. Chung is a consultant for Gilead; is on the advisory board for Merck and GlaxoSmithKline; and has received research support from MRC UK, Asthma UK, and Wellcome Trust. R. Dahl is a speaker for MSD, AstraZeneca, ALK, and GlaxoSmithKline; is a speaker and is on the advisory board for TEVA, Boehringer Ingelheim, UCB, Airsonett, Novartis, and Pfizer; is chairman for the Danish Respiratory Society; and is president of Interasma. L. M. Fabbri is a consultant for Nycomed, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Sigma Tau, AstraZeneca, Merck Sharp & Dohme, Novartis, Roche, and Pfizer; has received paid lecture fees from Abbott, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Nycomed, Roche, and Pfizer; and has received research support from Nycomed, Abbott, AstraZeneca, Boehringer Ingelheim, Menarini, Novartis, Schering-Plough, Chiesi, GlaxoSmithKline, Merck Sharp & Dohme, UCB, Pfizer, the Italian Ministry of Health, and the Italian Ministry for University and Research. S. T. Holgate is a consultant for MSD, Novartis, Synergen, Altair, Amgen, and Almiral and owns shares in Synergen. T. Haahtela has received honoraria from Astellas, AstraZeneca, Leiras, MSD, and Orion Pharma. P. O'Byrne is on the advisory board and has received speakers' honoraria from AstraZeneca and GlaxoSmithKline; is on the advisory board for Topigen, Wyeth, and Schering; and has received research support from AstraZeneca, GlaxoSmithKline, Merck, Wyeth, Schering, and Alexion. K. F. Rabe has received remuneration from Nycomed, Forest, AZ, BI, Chiesi, Pearl, MSD, and GlaxoSmithKline and has received research support from Chiesi, AS, BI, and Novartis. C.; van Weel has received research support from Boehringer Ingelheim, GlaxoSmithline, Novartis, the Dutch Asthma Foundation (NAF), and the Netherlands Medical Research Council (Zon/Mw). S. Wenzel is a consultant for Altair, Merck, GlaxoSmithKline, Amgen, and Pearl Therapeutics; is on the scientific advisory board for Amira; and has received research support from MedImmune, GlaxoSmithKline, Aerovance, and Amgen. T. Zuberbier is a consultant for Schering-Plough, Novartis, Leti, Stallergenes, Bayer Schering, Ansell, Kryolan, UCB, MSD, DST, Sanofi-Aventis, and Procter & Gamble; is on the editorial board of the Journal of Allergy, the scientific advisory board of the German Society for Allergy and Clinical Immunology, and the Expert Commission "Novel Food" of the German Federal Ministry of Consumer Protection; is chairman of the European Academy of Allergology and Clinical Immunology, Dermatology Section; is head of the European Center for Allergy Research Foundation; is a committee member of the WHO Initiative Allergic Rhinitis and its Impact on Asthma; is a member of the World Allergy Organization Communications Council; and is secretary general of the Global Allergy and Asthma European Network. E. Mantzouranis, N. Ait-Khaled, C. E. Baena-Cagnani, A. Bush, M. Chan-Yeung, B. Chowdhury, J. M. Drazen, F. Kauffmann, N. Khaltaev, J. P. Kiley, M. R. Masjedi, Y. Mohammad, M. R. Partridge, A. Togias, and N. Zhong have declared that they have no conflict of interest. NR 112 TC 242 Z9 251 U1 3 U2 36 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 NOV PY 2010 VL 126 IS 5 BP 926 EP 938 DI 10.1016/j.jaci.2010.07.019 PG 13 WC Allergy; Immunology SC Allergy; Immunology GA 674HB UT WOS:000283727100005 PM 20926125 ER PT J AU Tian, P Yang, D Jiang, X Zhong, W Cannon, JL Burkhardt, W Woods, JW Hartman, G Lindesmith, L Baric, RS Mandrell, R AF Tian, P. Yang, D. Jiang, X. Zhong, W. Cannon, J. L. Burkhardt, W., III Woods, J. W. Hartman, G. Lindesmith, L. Baric, R. S. Mandrell, R. TI Specificity and kinetics of norovirus binding to magnetic bead-conjugated histo-blood group antigens SO JOURNAL OF APPLIED MICROBIOLOGY LA English DT Article DE binding kinetics; histo-blood group antigen; magnetic beads; norovirus; virus concentration ID NORWALK-LIKE VIRUSES; UNITED-STATES; GASTROENTERITIS; CELLS; OUTBREAK; SUSCEPTIBILITY; CALICIVIRUSES; PARTICLES; INFECTION; SAMPLES AB Aims: To characterize the specificity and effect of pH and ionic strength on the kinetics of virus binding to histo-blood group antigens (HBGA)-conjugated magnetic beads. Methods and Results: HBGAs from porcine gastric mucin (PGM) have been conjugated to magnetic beads (PGM-MB) for concentration of NoV. A GII.4 virus was used for the detailed binding kinetics study and a panel of genogroup I (GI) NoVs, genogroup II (GII) NoVs and recombinant NoVs (rNoVs) were used for specificity and binding efficiency assays. We determined that NoV can be captured after 15 min of incubation with PGM-MB, and virus recovery efficiency is decreased after extended incubation times. rNoV binding as measured by ELISA and NoV recovery as measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), were both enhanced significantly at acidic pH conditions. rNoV binding to PGM as measured by ELISA was increased up to 66%. While real-time RT-PCR analyses suggest that NoV could be concentrated as much as 1000-fold at neutral pH, up to 3 center dot 4-fold further increase of NoV recovery was achieved by adjusting the pH of the sample to 3 center dot 0-4 center dot 2. Variation between GI and GII viral binding to the PGM-MB at basic pH was observed. All five GI rNoVs tested and 6 of 9 GII rNoVs were captured by PGM. All eight GI strains tested were concentrated by PGM-MB, ranging from 28-fold (GI.4) to 1502-fold (GI.1). Eleven of 13 GII strains were concentrated from 30-fold (GII.5) to 1014-fold (GII.4, lab strain) by PGM-MB. GI and GII rNoVs viral capsid proteins were recovered with high salt conditions, but results were inconsistent for whole virus recovery. Conclusions: All GI and 85% of GII NoVs tested could be captured and concentrated by PGM-MB method. The binding occurred rapidly and was enhanced at low pH. Significance and Impact of the Study: These results facilitated development of a prototype method for sensitive detection of NoV in samples requiring larger volumes. C1 [Tian, P.; Yang, D.; Mandrell, R.] ARS, Produce Safety & Microbiol Res Unit, WRRC, USDA, Albany, CA 94547 USA. [Jiang, X.; Zhong, W.] Univ Cincinnati, Med Ctr, Cincinnati Childrens Hosp, Div Infect Dis,Coll Med, Cincinnati, OH 45267 USA. [Cannon, J. L.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Burkhardt, W., III; Woods, J. W.] US FDA, CFSAN, Off Food Safety, Gulf Coast Seafood Lab, Dauphin Isl, AL USA. [Hartman, G.] US FDA, ORA, San Francisco Dist Lab, Alameda, CA USA. [Lindesmith, L.; Baric, R. S.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA. RP Tian, P (reprint author), ARS, Produce Safety & Microbiol Res Unit, WRRC, USDA, 800 Buchanan St, Albany, CA 94547 USA. EM peng.tian@ars.usda.gov RI Robertson, Simon/D-1549-2012 FU USDA Agricultural Research Service CRIS [5325-42000-021-044, 5325-42000-021-045] FX We thank Dr. Jan Vinje (CDC, Atlanta, GA) for providing a panel of GI and GII NOV samples, Dr. Reilly (Wyeth Research, Pearl River NY) for providing two polyclonal antibodies and Dr. Schnurr (California Dept. Health Service, Richmond, CA) for providing clinical samples. This work was supported by USDA Agricultural Research Service CRIS project 5325-42000-021-044 and 5325-42000-021-045. NR 30 TC 36 Z9 37 U1 10 U2 85 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 NOV PY 2010 VL 109 IS 5 BP 1753 EP 1762 DI 10.1111/j.1365-2672.2010.04812.x PG 10 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 662NK UT WOS:000282813800027 PM 21040268 ER PT J AU Balakumar, P Jagadeesh, G AF Balakumar, Pitchai Jagadeesh, Gowraganahalli TI Cardiovascular and Renal Pathologic Implications of Prorenin, Renin, and the (Pro)renin Receptor: Promising Young Players From the Old Renin-Angiotensin-Aldosterone System SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Review DE prorenin; renin; (pro)renin receptor; handle region protein; aliskiren; cardiovascular-renal lesions; end-organ damage; Wnt signaling; vacuolar H(+)-ATPase ID HUMAN CHORIONIC-GONADOTROPIN; DEPENDENT DIABETES-MELLITUS; HANDLE-REGION PEPTIDE; HIGH PLASMA PRORENIN; SMOOTH-MUSCLE-CELLS; VACUOLAR H+-ATPASE; TRANSGENIC RATS; BLOOD-PRESSURE; NONPROTEOLYTIC ACTIVATION; RENIN/PRORENIN RECEPTOR AB The overactivation of the renin-angiotensin-aldosterone system accounts for many cardiovascular and renal abnormalities. At several levels of its cascade, the renin-angiotensin-aldosterone system can be efficiently inhibited, of which interruption of the generation of angiotensin I by renin inhibition is considered most efficacious. All of these interruptions (renin inhibition, angiotensin-converting enzyme inhibition, and AT(1) receptor blockade) increase plasma renin levels by inhibiting the negative feedback loop exerted by angiotensin II on renin production. Recent studies show that both prorenin and renin activate angiotensin II-independent signaling cascade through (pro)renin receptor, a new-fangled player of the old renin-angiotensin-aldosterone system. The probable mechanisms by which prorenin, renin, and (pro)renin receptors are functionally interrelated in pathophysiological conditions have been debated over the past decade without satisfactory conclusion. We revisited these areas and critically examined the relationship between elevated levels of circulating prorenin and renin-induced activation of the (pro)renin receptor and incidences of hypertension and end-organ damage. The complexity of the (pro)renin receptor has grown up with recent reports that this multifunctional receptor is a component of the Wnt receptor complex. This complexity and the receptor's function as an adaptor between the Wnt receptor and the vacuolar H(+)-ATPase complex has also been addressed in this review. C1 [Jagadeesh, Gowraganahalli] US FDA, Div Cardiovasc & Renal Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Balakumar, Pitchai] SB Coll Pharm, Dept Pharmacol, Sivakasi, India. RP Jagadeesh, G (reprint author), US FDA, Div Cardiovasc & Renal Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Room 4128, Silver Spring, MD 20993 USA. EM gowra.jagadeesh@fda.hhs.gov RI Jagadeesh, Gowraganahalli/G-6408-2010 NR 115 TC 24 Z9 24 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD NOV PY 2010 VL 56 IS 5 BP 570 EP 579 DI 10.1097/FJC.0b013e3181f21576 PG 10 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 678FJ UT WOS:000284059200018 PM 21108514 ER PT J AU Mason, JW Florian, JA Garnett, CE Moon, TE Selness, DS Spaulding, RR AF Mason, Jay W. Florian, Jeffry A., Jr. Garnett, Christine E. Moon, Thomas E. Selness, Daniel S. Spaulding, Randol R. TI Pharmacokinetics and Pharmacodynamics of Three Moxifloxacin Dosage Forms: Implications for Blinding in Active-Controlled Cardiac Repolarization Studies SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE Cardiac repolarization; QT interval; moxifloxacin; controlled randomized trial ID POPULATION PHARMACOKINETICS; HEALTHY-SUBJECTS; CLINICAL-TRIALS; SAFETY PROFILE; QT; LEVOFLOXACIN; FLUOROQUINOLONES; GATIFLOXACIN; ADULTS; RISK AB Moxifloxacin is used in thorough QT studies to assess sensitivity for detection of an increase in QTc. Moxifloxacin is usually over-encapsulated for blinding. However, there is concern that over-encapsulation alters its pharmacokinetics. In a 4-arm, randomized crossover study, 22 volunteers received over-encapsulated moxifloxacin, over-encapsulated placebo, bare moxifloxacin, and intravenous (IV) moxifloxacin. Placebo capsules and IV infusions were administered so that treatments in each arm, except for bare moxifloxacin, were indistinguishable. Pharmacokinetics of the oral treatments were found to be nearly identical and to meet Food and Drug Administration criteria for bioequivalency. Relative to the IV infusion administered over 1 hour, the tablet formulation was bioequivalent to total exposure but not peak exposure maximum plasma concentration, which was lower by 22%. Median time to maximum plasma concentration of the IV infusion was 1.00 hour. A 2-compartment model with oral absorption and linear elimination adequately described the observed moxifloxacin data. Changes in QTcF mirrored the pharmacokinetic changes, and there was a linear relationship between plasma concentration of moxifloxacin and change in QTcF. A 2-stage infusion scheme for IV moxifloxacin mimics the oral plasma concentration versus time curve. Over-encapsulation of moxifloxacin did not alter its peak or total systemic exposures or pharmacodynamics after oral administration. C1 [Mason, Jay W.] Univ Utah, Salt Lake City, UT USA. [Mason, Jay W.; Moon, Thomas E.; Selness, Daniel S.; Spaulding, Randol R.] Spaulding Clin Res, W Bend, WI USA. [Florian, Jeffry A., Jr.; Garnett, Christine E.] US FDA, Off Clin Pharmacol, Silver Spring, MD USA. RP Mason, JW (reprint author), 105 Londonderry Court, Reno, NV 89511 USA. EM jwm@jaywmason.com NR 27 TC 14 Z9 15 U1 0 U2 3 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 NOV PY 2010 VL 50 IS 11 BP 1249 EP 1259 DI 10.1177/0091270009356298 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 661SP UT WOS:000282748700003 PM 20145260 ER PT J AU Hubinger, JC AF Hubinger, Jean C. TI A survey of phthalate esters in consumer cosmetic products SO JOURNAL OF COSMETIC SCIENCE LA English DT Article ID EXPOSURE; METABOLITES; HEALTH; ACID AB Certain phthalate esters have been shown to cause reproductive toxicity in animal models. For this reason, the FDA has been monitoring the use of phthalate esters in cosmetics. In this study, the U.S. Food and Drug Administration (FDA) conducted a limited survey of 84 adult-use and baby-care cosmetic products for the presence of five phthalate esters: dimethyl phthalate (DMP), diethyl phthalate (DEP), benzylbutyl phthalate (BBP), dibutyl phthalate (DBP), and diethylhexyl phthalate (DEHP) (Figure 1). The analytes were extracted from a cosmetic product/Celite mixture with hexane, and the extract was then analyzed using reversed-phase high-performance chromatography (HPLC) on an instrument equipped with an ultraviolet radiation (UV) detector set at 230 nm. The analytes were separated on a Partisil octadecylsilane (ODS)-3 column (250 mm x 4.6 mm I.D., 5 mu m). The mobile phase consisted of a mixture of 50% water, 34% acetonitrile, 13% 2-propanol, and 3% methanol that was changed linearly (35 minutes) to 15% water, 55% acetonitrile, 25% 2-propanol, and 5% methanol and held for an additional ten minutes. Spiked recoveries in antiperspirant and nail color ranged from 88% to 104%. Thirty-one of the 60 adult-use cosmetic products were found to contain at least one phthalate ester. Twenty products contained DEP and 11 nail products contained DBP. Concentrations of DBP ranged from 123 mu g/g to 62,607 mu g/g. Concentrations of DEP ranged from 80 mu g/g to 36,006 mu g/g. Five of the 24 baby-care products contained DEP at concentrations ranging from 10 mu g/g to 274 mu g/g. C1 US FDA, College Pk, MD 20740 USA. RP Hubinger, JC (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 23 TC 19 Z9 19 U1 7 U2 30 PU SOC COSMETIC CHEMISTS PI NEW YORK PA 120 WALL STREET, SUITE 2400, NEW YORK, NY 10005-4088 USA SN 1525-7886 J9 J COSMET SCI JI J. Cosmet. Sci. PD NOV-DEC PY 2010 VL 61 IS 6 BP 457 EP 465 PG 9 WC Chemistry, Applied; Dermatology SC Chemistry; Dermatology GA 768FM UT WOS:000290919000003 PM 21241635 ER PT J AU Chen, Y Song, KY Brown, EW Lampel, KA AF Chen, Yi Song, Kwang-yong Brown, Eric W. Lampel, Keith A. TI "Development of an Improved Protocol for the Isolation and Detection of Enterobacter sakazakii (Cronobacter) from Powdered Infant Formula," A Comment on: J. Food Prot. 73(6):1016-1022 (2010) Response SO JOURNAL OF FOOD PROTECTION LA English DT Letter C1 [Chen, Yi; Song, Kwang-yong; Brown, Eric W.; Lampel, Keith A.] US FDA, College Pk, MD 20740 USA. RP Chen, Y (reprint author), US FDA, 5100 Paint Branch Pkwy,HFS 711, College Pk, MD 20740 USA. RI Zhou, Tian/J-7175-2012 NR 0 TC 0 Z9 0 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 NOV PY 2010 VL 73 IS 11 BP 1965 EP 1966 PG 2 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 680QR UT WOS:000284250000003 ER PT J AU Klontz, KC Klontz, JC Mody, RK Hoekstra, RM AF Klontz, Karl C. Klontz, Joshua C. Mody, Rajal K. Hoekstra, Robert M. TI Analysis of Tomato and Jalapeno and Serrano Pepper Imports into the United States from Mexico before and during a National Outbreak of Salmonella Serotype Saintpaul Infections in 2008 SO JOURNAL OF FOOD PROTECTION LA English DT Article AB Case-control studies conducted during a multistate outbreak of Salmonella enterica serotype Saintpaul infections in 2008 revealed associations between illness and the consumption of jalapeno peppers, Serrano peppers, and tomatoes. Traceback investigations of implicated jalapeno and Serrano peppers led to farms in Tamaulipas and Nuevo Leon, Mexico. We conducted a novel analysis of a U.S. Food and Drug Administration database of tomatoes and jalapeno and Serrano peppers imported from Mexico during the first half of 2008 to describe the temporal and spatial flow of these items into the United States. Shipments of all three produce items followed a south-to-northwest corridor; 87% of peppers and 97% of tomatoes produced in Mexican states located west of the Sierra Madre Occidental were transported to ports in California and Arizona, and 90% of peppers and 100% of tomatoes produced in states east of the Sierra Madre Occidental were transported to ports east of Arizona. We found a significant correlation between state-specific infection rates and quantity of imported Mexican jalapeno and Serrano peppers to U.S. states by the first-level consignee but not for imported Mexican tomatoes. We localized production regions of interest by finding that quantities of both peppers and tomatoes imported from the states of Nuevo Leon and Tamaulipas were correlated with infection rates. In outbreaks possibly caused by agricultural commodities, analysis of import databases may foster a better understanding of growing seasons, harvest sites, shipment itineraries, and consignee destinations, thereby adding valuable insight into findings derived from epidemiologic studies. C1 [Klontz, Karl C.] US FDA, Off Food Def Commun & Emergency Response, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Klontz, Joshua C.] Harvey Mudd Coll, Claremont, CA 91711 USA. [Mody, Rajal K.; Hoekstra, Robert M.] Ctr Dis Control & Prevent, Div Foodborne Bacterial & Mycot Dis, Atlanta, GA 30333 USA. RP Klontz, KC (reprint author), US FDA, Off Food Def Commun & Emergency Response, Ctr Food Safety & Appl Nutr, HFS 005, College Pk, MD 20740 USA. EM karl.klontz@fda.hhs.gov NR 4 TC 13 Z9 13 U1 1 U2 5 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD NOV PY 2010 VL 73 IS 11 BP 1967 EP 1974 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 680QR UT WOS:000284250000004 PM 21219707 ER PT J AU Szlachta, K Keller, SE Shazer, A Chirtel, S AF Szlachta, Kinga Keller, Susanne E. Shazer, Arlette Chirtel, Stuart TI Thermal Resistance of Listeria monocytogenes Scott A in Ultrafiltered Milk as Related to the Effect of Different Milk Components SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ESCHERICHIA-COLI O157-H7; SHORT-TIME PASTEURIZATION; HEAT-RESISTANCE; YERSINIA-ENTEROCOLITICA; BOVINE-MILK; GROWTH TEMPERATURE; PREDICTIVE MODEL; CELL MORPHOLOGY; DAIRY-PRODUCTS; MINCED BEEF AB Pasteurization parameters for grade A milk are well established and set by regulation. However, as solids levels increase, an increased amount of heat is required to destroy any pathogens present. This effect is not well characterized. In this work, the effect of increased dairy solids levels on the thermal resistance of Listeria monocytogenes was examined through the use of ultrafiltered (UF) milk, reconstituted milk powder, and the milk components lactose and caseinate. From the results obtained, lactose and caseinate did not appear to affect thermal resistance. In addition, the level of milk fat, up to 10% of the total solids in UF whole milk, did not result in statistically significant changes to thermal resistance when compared with UF skim milk. Reconstituted skim milk powder at 27% total solids (D(62)-value = 1.16 +/- 0.2 [SD] min, z = 5.7) did result in increased thermal resistance, as compared with reconstituted skim milk powder at 17.5% (D(62)-value = 0.86 +/- 0.02 min, z = 5.57) and UF whole milk at 27% total solids (D(62)-value = 0.66 +/- 0.07 min, z = 5.16). However, that increase appeared to be due to the increase in salt levels, not to increases in caseinate, fat, or lactose. Consequently, total solids, as a single measure, could not be used to predict increased thermal resistance of L. monocytogenes in concentrated milk. C1 [Keller, Susanne E.; Shazer, Arlette] US FDA, Summit Argo, IL 60501 USA. [Chirtel, Stuart] US FDA, College Pk, MD 20740 USA. [Szlachta, Kinga] IIT, Summit Argo, IL 60501 USA. RP Keller, SE (reprint author), US FDA, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM susanne.keller@fda.hhs.gov NR 52 TC 1 Z9 1 U1 0 U2 5 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD NOV PY 2010 VL 73 IS 11 BP 2110 EP 2115 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 680QR UT WOS:000284250000024 PM 21219727 ER PT J AU Alcaraz-Estrada, SL Manzano, MIM Del Angel, RM Levis, R Padmanabhan, R AF Alcaraz-Estrada, Sofia L. Manzano, Mark Irvin M. Del Angel, Rosa M. Levis, Robin Padmanabhan, R. TI Construction of a dengue virus type 4 reporter replicon and analysis of temperature-sensitive mutations in non-structural proteins 3 and 5 SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID WEST-NILE-VIRUS; RNA CAP; SUBGENOMIC REPLICONS; MOLECULAR-BIOLOGY; DRUG DISCOVERY; NS5 PROTEIN; POLYMERASE; REPLICATION; TRANSCOMPLEMENTATION; METHYLTRANSFERASE AB Replicon systems have been useful to study mechanisms of translation and replication of flavivirus RNAs. In this study, we constructed a dengue virus 4 replicon encoding a Renilla luciferase (R(luc)) reporter, and six single-residue substitution mutants were generated: L128F and S158P in the non-structural protein (NS) 3 protease domain gene, and N96I, N390A, K437R and M805I in the NS5 gene. The effects of these substitutions on viral RNA translation and/or replication were examined by measuring R(luc) activities in wild-type and mutant replicon RNA-transfected Vero cells incubated at 35, 37 and 39 degrees C. Our results show that none of the mutations affected translation of replicon RNAs; however, L128F and S158P of NS3 at 39 degrees C, and N96I of NS5 at 37 and 39 degrees C, presented temperature-sensitive (ts) phenotypes for replication. Furthermore, using in vitro methyltransferase assays, we identified that the N96I mutation in NS5 exhibited a ts phenotype for N7-methylation, but not for 2'-O-methylation. C1 [Alcaraz-Estrada, Sofia L.; Manzano, Mark Irvin M.; Padmanabhan, R.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. [Alcaraz-Estrada, Sofia L.; Del Angel, Rosa M.] IPN, CINVESTAV, Mexico City 07738, DF, Mexico. [Levis, Robin] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Padmanabhan, R (reprint author), Georgetown Univ, Med Ctr, Washington, DC 20007 USA. EM rp55@georgetown.edu RI del Angel, Rosa/E-3711-2013; OI del Angel, Rosa/0000-0002-3241-9565; del Angel, Rosa/0000-0002-6785-2035 FU National Institutes of Health [AI54776, AI57705, AI70791, AI082068] FX This research was supported by grants from the National Institutes of Health (AI54776, AI57705, AI70791 and AI082068). The authors are grateful to Dr Richard Kuhn for critical reading and his comments for improving the manuscript. NR 37 TC 11 Z9 12 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD NOV PY 2010 VL 91 BP 2713 EP 2718 DI 10.1099/vir.0.024083-0 PN 11 PG 6 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 677CG UT WOS:000283966100007 PM 20631089 ER PT J AU White, JF Werkmeister, JA Hilbert, SL Ramshaw, JAM AF White, Jacinta F. Werkmeister, Jerome A. Hilbert, Stephen L. Ramshaw, John A. M. TI Heart Valve Collagens: Cross-Species Comparison Using Immunohistological Methods SO JOURNAL OF HEART VALVE DISEASE LA English DT Article ID VI COLLAGEN; TISSUE AB Background and aim of the study: Tissue engineering is an emerging strategy for the development of replacement heart valves where the properties of native tissues are to be replicated. The complexity of the distribution of various collagens in the aortic, mitral, and pulmonary valve leaflets of porcine, bovine, and ovine origin, has been examined. Methods: Immunohistological and transmission electron microscopy analyses using monoclonal antibodies to types I, III, IV, V and VI collagens were performed. Results: The results indicated that each collagen type has its own distinct distribution, with minimal variation between heart valve anatomic sites and species. Of particular interest was type VI collagen, which had an asymmetric distribution that was principally localized along the outflow surface of the valve. Conclusion: Successful tissue engineering constructs of heart valves may need to replicate the complex distribution of different collagens found in heart valve tissues. C1 [White, Jacinta F.; Werkmeister, Jerome A.; Ramshaw, John A. M.] CSIRO Mol & Hlth Technol, Clayton, Vic 3169, Australia. [Hilbert, Stephen L.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Ramshaw, JAM (reprint author), CSIRO Mol & Hlth Technol, Bayview Ave, Clayton, Vic 3169, Australia. EM John.Ramshaw@csiro.au RI White, Jacinta/D-6961-2013; Ramshaw, John/A-9411-2011 OI White, Jacinta/0000-0002-4855-0170; NR 7 TC 3 Z9 4 U1 0 U2 5 PU I C R PUBLISHERS PI NORTHWOOD PA CRISPIN HOUSE, 12/A SOUTH APPROACH, MOOR PARK, NORTHWOOD HA6 2ET, ENGLAND SN 0966-8519 J9 J HEART VALVE DIS JI J. Heart Valve Dis. PD NOV PY 2010 VL 19 IS 6 BP 766 EP 771 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 694FT UT WOS:000285281100015 PM 21214102 ER PT J AU Bhattacharjee, A Mulya, A Pal, S Roy, B Feldman, GM Cathcart, MK AF Bhattacharjee, Ashish Mulya, Anny Pal, Srabani Roy, Biswajit Feldman, Gerald M. Cathcart, Martha K. TI Monocyte 15-Lipoxygenase Gene Expression Requires ERK1/2 MAPK Activity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID AIRWAY SMOOTH-MUSCLE; CREB-BINDING-PROTEIN; CENTRIFUGAL ELUTRIATION CCE; MONONUCLEAR CELL SUBSETS; SIGNAL-REGULATED KINASE; EARLY GROWTH RESPONSE-1; E-DEFICIENT MICE; TRANSCRIPTION FACTOR; LIPID MEDIATORS; IN-VIVO AB IL-13 induces profound expression of 15-lipoxygenase (15-LO) in primary human monocytes. Our studies have defined the functional IL-13R complex, association of Jaks with the receptor components, and the tyrosine phosphorylation of several Stat molecules in response to IL-13. Furthermore, we identified both p38MAPK and protein kinase C delta as critical regulators of 15-LO expression. In this study, we report an ERK1/2-dependent signaling cascade that regulates IL-13-mediated 15-LO gene expression. We show the rapid phosphorylation/activation of ERK1/2 upon IL-13 exposure. Our results indicate that Tyk2 kinase is required for the activation of ERK1/2, which is independent of the Jak2, p38MAPK, and protein kinase C delta pathways, suggesting bifurcating parallel regulatory pathways downstream of the receptor. To investigate the signaling mechanisms associated with the ERK1/2-dependent expression of 15-LO, we explored the involvement of transcription factors, with predicted binding sites in the 15-LO promoter, in this process including Elk1, early growth response-1 (Egr-1), and CREB. Our findings indicate that IL-13 induces Egr-1 nuclear accumulation and CREB serine phosphorylation and that both are markedly attenuated by inhibition of ERK1/2 activity. We further show that ERK1/2 activity is required for both Egr-1 and CREB DNA binding to their cognate sequences identified within the 15-LO promoter. Furthermore, by transfecting monocytes with the decoy oligodeoxyribonucleotides specific for Egr-1 and CREB, we discovered that Egr-1 and CREB are directly involved in regulating 15-LO gene expression. These studies characterize an important regulatory role for ERK1/2 in mediating IL-13-induced monocyte 15-LO expression via the transcription factors Egr-1 and CREB. The Journal of Immunology, 2010, 185: 5211-5224. C1 [Bhattacharjee, Ashish; Mulya, Anny; Pal, Srabani; Roy, Biswajit; Cathcart, Martha K.] Case Western Reserve Univ, Cleveland Clin, Dept Cell Biol, Lerner Res Inst, Cleveland, OH 44195 USA. [Bhattacharjee, Ashish; Mulya, Anny; Pal, Srabani; Roy, Biswajit; Cathcart, Martha K.] Case Western Reserve Univ, Cleveland Clin, Dept Mol Med, Lerner Coll Med, Cleveland, OH 44195 USA. [Feldman, Gerald M.] US FDA, Div Monoclonal Antibodies, Off Therapeut Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Cathcart, MK (reprint author), Case Western Reserve Univ, Cleveland Clin, Dept Cell Biol, Lerner Res Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM cathcam@ccf.org FU National Institutes of Health [HL051068, HL087018] FX This work was supported by National Institutes of Health Grants HL051068 and HL087018 (to M.K.C.). NR 80 TC 9 Z9 9 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2010 VL 185 IS 9 BP 5211 EP 5224 DI 10.4049/jimmunol.1000514 PG 14 WC Immunology SC Immunology GA 668DL UT WOS:000283248700035 PM 20861348 ER PT J AU Lee, HH Meyer, EH Goya, S Pichavant, M Kim, HY Bu, X Umetsu, SE Jones, JC Savage, PB Iwakura, Y Casasnovas, JM Kaplan, G Freeman, GJ DeKruyff, RH Umetsu, DT AF Lee, Hyun-Hee Meyer, Everett H. Goya, Sho Pichavant, Muriel Kim, Hye Young Bu, Xia Umetsu, Sarah E. Jones, Jennifer C. Savage, Paul B. Iwakura, Yoichiro Casasnovas, Jose M. Kaplan, Gerardo Freeman, Gordon J. DeKruyff, Rosemarie H. Umetsu, Dale T. TI Apoptotic Cells Activate NKT Cells through T Cell Ig-Like Mucin-Like-1 Resulting in Airway Hyperreactivity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HEPATITIS-A VIRUS; MUCIN-DOMAIN; KOREAN POPULATION; ALLERGIC DISEASES; EXON-4 VARIATIONS; EPITHELIAL-CELLS; DENDRITIC CELLS; TIM-1 GENE; PHOSPHATIDYLSERINE; ASTHMA AB T cell Ig-like mucin-like-1 (TIM-1) is an important asthma susceptibility gene, but the immunological mechanisms by which TIM-1 functions remain uncertain. TIM-1 is also a receptor for phosphatidylserine (PtdSer), an important marker of cells undergoing programmed cell death, or apoptosis. We now demonstrate that NKT cells constitutively express TIM-1 and become activated by apoptotic cells expressing PtdSer. TIM-1 recognition of PtdSer induced NKT cell activation, proliferation, and cytokine production. Moreover, the induction of apoptosis in airway epithelial cells activated pulmonary NKT cells and unexpectedly resulted in airway hyperreactivity, a cardinal feature of asthma, in an NKT cell-dependent and TIM-1-dependent fashion. These results suggest that TIM-1 serves as a pattern recognition receptor on NKT cells that senses PtdSer on apoptotic cells as a damage-associated molecular pattern. Furthermore, these results provide evidence for a novel innate pathway that results in airway hyperreactivity and may help to explain how TIM-1 and NKT cells regulate asthma. The Journal of Immunology, 2010, 185: 5225-5235. C1 [Lee, Hyun-Hee; Pichavant, Muriel; Kim, Hye Young; Umetsu, Sarah E.; DeKruyff, Rosemarie H.; Umetsu, Dale T.] Harvard Univ, Sch Med, Childrens Hosp Boston, Karp Labs,Div Immunol & Allergy,Dept Pediat, Boston, MA 02115 USA. [Bu, Xia; Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bu, Xia; Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Meyer, Everett H.; Jones, Jennifer C.] Stanford Univ, Stanford, CA 94305 USA. [Goya, Sho] Osaka Univ, Grad Sch Med, Dept Resp Med Allergy & Rheumat Dis, Suita, Osaka 5650871, Japan. [Iwakura, Yoichiro] Univ Tokyo, Inst Med Sci, Ctr Med Expt, Tokyo, Japan. [Savage, Paul B.] Brigham Young Univ, Dept Chem & Biochem, Provo, UT 84602 USA. [Casasnovas, Jose M.] Consejo Super Invest Cient, Ctr Nacl Biotecnol, Madrid 28049, Spain. [Kaplan, Gerardo] US FDA, Ctr Biol Res & Evaluat, Bethesda, MD 20892 USA. RP Umetsu, DT (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Karp Labs,Div Immunol & Allergy,Dept Pediat, Room 10127,1 Blackfan Circle, Boston, MA 02115 USA. EM dale.umetsu@childrens.harvard.edu RI Iwakura, Yoichiro/E-5457-2011; Casasnovas, Jose/L-6299-2014; Jones, Jennifer/C-8691-2015 OI Iwakura, Yoichiro/0000-0002-9934-5775; Casasnovas, Jose/0000-0002-2873-6410; Jones, Jennifer/0000-0002-9488-7719 FU National Institutes of Health [R01HL62348, RO1AI02632, PO1AI05546]; American Lung Association; Bunning Food Allergy Project; Harvard Digestive Diseases Center Imaging Core [DK-034854] FX This work was supported by National Institutes of Health Grants R01HL62348, RO1AI02632, and PO1AI05546; by a fellowship from the American Lung Association; by an award from the Bunning Food Allergy Project; and by Harvard Digestive Diseases Center Imaging Core Grant B, DK-034854. NR 69 TC 37 Z9 41 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2010 VL 185 IS 9 BP 5225 EP 5235 DI 10.4049/jimmunol.1001116 PG 11 WC Immunology SC Immunology GA 668DL UT WOS:000283248700036 PM 20889552 ER PT J AU Fang, H Sun, C Xu, LX Owen, RJ Auth, RD Snoy, PJ Frucht, DM AF Fang, Hui Sun, Chen Xu, Lixin Owen, Robert J. Auth, Roger D. Snoy, Philip J. Frucht, David M. TI Neutrophil Elastase Mediates Pathogenic Effects of Anthrax Lethal Toxin in the Murine Intestinal Tract SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-LYMPHOCYTE ACTIVATION; BACILLUS-ANTHRACIS; TNF-ALPHA; MICE; INNATE AB Neutrophils isolated from BALB/c or C57BL/6 mice and treated in vitro with anthrax lethal toxin release bioactive neutrophil elastase, a proinflammatory mediator of tissue destruction. Similarly, neutrophils isolated from mice treated with anthrax lethal toxin in vivo and cultured ex vivo release greater amounts of elastase than neutrophils from vehicle-treated controls. Direct measurements from murine intestinal tissue samples demonstrate an anthrax lethal toxin-dependent increase in neutrophil elastase activity in vivo as well. These findings correlate with marked lethal toxin-induced intestinal ulceration and bleeding in neutrophil elastase(+/+) animals, but not in neutrophil elastase(-/-) animals. Moreover, neutrophil elastase(-/-) mice have a significant survival advantage over neutrophil elastase(+/+) animals following exposure to anthrax lethal toxin, thereby establishing a key role for neutrophil elastase in mediating the deleterious effects of anthrax lethal toxin. The Journal of Immunology, 2010, 185: 5463-5467. C1 [Fang, Hui; Sun, Chen; Xu, Lixin; Owen, Robert J.; Auth, Roger D.; Frucht, David M.] US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Snoy, Philip J.] US FDA, Div Vet Serv, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Frucht, DM (reprint author), US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bldg 29B,Room 4NN12, Bethesda, MD 20892 USA. EM david.frucht@fda.hhs.gov NR 24 TC 9 Z9 9 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2010 VL 185 IS 9 BP 5463 EP 5467 DI 10.4049/jimmunol.1002471 PG 5 WC Immunology SC Immunology GA 668DL UT WOS:000283248700059 PM 20921524 ER PT J AU Tavris, DR Liu, CH Gross, TP Greenfield, LJ AF Tavris, Dale R. Liu, Chih-hsin Gross, Thomas P. Greenfield, Lazar J. TI Aneurysm-Related Mortality Rates in the US AneuRx Clinical Trial SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID ABDOMINAL-AORTIC-ANEURYSM; OPEN SURGICAL REPAIR; ENDOVASCULAR REPAIR; STENT-GRAFT; FOLLOW-UP; EXPERIENCE; COMPLICATIONS; POPULATION; EXCLUSION; OUTCOMES AB BACKGROUND: The AneuRx (Medtronic) stent graft was approved by the FDA in September 1999. The purpose of this study was to ascertain the aneurysm-related mortality rate of a subgroup of the patient cohort from Medtronic's investigational premarket study. STUDY DESIGN: There were 931 study subjects, from 19 medical centers, who were followed for an average of 3.48 years. Abdominal aortic aneurysm (AAA)-related mortality rates were examined, using death certificates and medical records. RESULTS: The 1-month postimplant death rate was 1.61%. Not counting deaths related to the initial implant, there was an increase in the rate of AAA-related mortality after 3 years, from an average of 0.18% in the first 3 years to an average of 1.39% in years 4 and 5. CONCLUSIONS: Mortality in patients implanted with an AneuRx graft (as determined in this study) probably exceeds that of open procedure patients (based on medical literature) at some point in time, likely within 4 years after implant. (J Am Coll Surg 2010;211:646-651. (C) 2010 by the American College of Surgeons) C1 [Greenfield, Lazar J.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Tavris, Dale R.; Liu, Chih-hsin; Gross, Thomas P.] US FDA, Silver Spring, MD USA. RP Tavris, DR (reprint author), 10903 New Hampshire Ave,Bldg 66,Room 4204, Silver Spring, MD 20993 USA. NR 41 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD NOV PY 2010 VL 211 IS 5 BP 646 EP 651 DI 10.1016/j.jamcollsurg.2010.08.007 PG 6 WC Surgery SC Surgery GA 681FS UT WOS:000284297400010 PM 21035045 ER PT J AU Freedman, AN Sansbury, LB Figg, WD Potosky, AL Smith, SRW Khoury, MJ Nelson, SA Weinshilboum, RM Ratain, MJ McLeod, HL Epstein, RS Ginsburg, GS Schilsky, RL Liu, G Flockhart, DA Ulrich, CM Davis, RL Lesko, LJ Zineh, I Randhawa, G Ambrosone, CB Relling, MV Rothman, N Xie, H Spitz, MR Ballard-Barbash, R Doroshow, JH Minasian, LM AF Freedman, Andrew N. Sansbury, Leah B. Figg, William D. Potosky, Arnold L. Smith, Sheila R. Weiss Khoury, Muin J. Nelson, Stefanie A. Weinshilboum, Richard M. Ratain, Mark J. McLeod, Howard L. Epstein, Robert S. Ginsburg, Geoffrey S. Schilsky, Richard L. Liu, Geoffrey Flockhart, David A. Ulrich, Cornelia M. Davis, Robert L. Lesko, Lawrence J. Zineh, Issam Randhawa, Gurvaneet Ambrosone, Christine B. Relling, Mary V. Rothman, Nat Xie, Heng Spitz, Margaret R. Ballard-Barbash, Rachel Doroshow, James H. Minasian, Lori M. TI Cancer Pharmacogenomics and Pharmacoepidemiology: Setting a Research Agenda to Accelerate Translation SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID RECEIVING ADJUVANT TAMOXIFEN; BREAST-CANCER; COLORECTAL-CANCER; LUNG-CANCER; THERAPY; CYP2D6; SURVIVAL; CYP2D6-ASTERISK-10; ASSOCIATION; MUTATIONS AB Recent advances in genomic research have demonstrated a substantial role for genomic factors in predicting response to cancer therapies. Researchers in the fields of cancer pharmacogenomics and pharmacoepidemiology seek to understand why individuals respond differently to drug therapy, in terms of both adverse effects and treatment efficacy. To identify research priorities as well as the resources and infrastructure needed to advance these fields, the National Cancer Institute (NCI) sponsored a workshop titled "Cancer Pharmacogenomics: Setting a Research Agenda to Accelerate Translation" on July 21, 2009, in Bethesda, MD. In this commentary, we summarize and discuss five science-based recommendations and four infrastructure-based recommendations that were identified as a result of discussions held during this workshop. Key recommendations include 1) supporting the routine collection of germline and tumor biospecimens in NCI-sponsored clinical trials and in some observational and population-based studies; 2) incorporating pharmacogenomic markers into clinical trials; 3) addressing the ethical, legal, social, and biospecimen- and data-sharing implications of pharmacogenomic and pharmacoepidemiologic research; and 4) establishing partnerships across NCI, with other federal agencies, and with industry. Together, these recommendations will facilitate the discovery and validation of clinical, sociodemographic, lifestyle, and genomic markers related to cancer treatment response and adverse events, and they will improve both the speed and efficiency by which new pharmacogenomic and pharmacoepidemiologic information is translated into clinical practice. C1 [Freedman, Andrew N.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Figg, William D.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Rothman, Nat] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Minasian, Lori M.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Potosky, Arnold L.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Hlth Serv Res, Washington, DC USA. [Smith, Sheila R. Weiss] Univ Maryland, Sch Pharm, Ctr Drug Safety, Baltimore, MD 21201 USA. [Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA. [Weinshilboum, Richard M.] Mayo Clin, Coll Med, Div Clin Pharmacol, Rochester, MN USA. [Ratain, Mark J.] Univ Chicago, Med Ctr, Canc Res Ctr, Chicago, IL 60637 USA. [McLeod, Howard L.] Univ N Carolina, UNC Inst Pharmacogenom & Individualized Therapy, Chapel Hill, NC USA. [Epstein, Robert S.] Medco Hlth Solut Inc, Franklin Lakes, NJ USA. [Ginsburg, Geoffrey S.] Duke Univ, Duke Inst Genome Sci & Policy, Ctr Genom Med, Durham, NC USA. [Schilsky, Richard L.] Univ Chicago, Med Ctr, Hematol Oncol Sect, Chicago, IL 60637 USA. [Liu, Geoffrey] Univ Toronto, Ontario Canc Inst, Princess Margaret Hosp, Toronto, ON, Canada. [Flockhart, David A.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Ulrich, Cornelia M.] German Canc Res Ctr, Div Prevent Oncol, D-6900 Heidelberg, Germany. [Ulrich, Cornelia M.] Natl Ctr Tumor Dis, Heidelberg, Germany. [Ulrich, Cornelia M.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Davis, Robert L.] Kaiser Permanente, Ctr Hlth Res, Atlanta, GA USA. [Lesko, Lawrence J.; Zineh, Issam] US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Randhawa, Gurvaneet] Agcy Healthcare Res & Qual, Ctr Outcomes & Evidence, Rockville, MD USA. [Ambrosone, Christine B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Relling, Mary V.] St Jude Childrens Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA. [Xie, Heng] NIH, Natl Ctr Res Resources, Div Clin Res Resources, Bethesda, MD 20892 USA. [Spitz, Margaret R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Freedman, AN (reprint author), NCI, Div Canc Control & Populat Sci, NIH, 6130 Execut Blvd,Rm 5128, Bethesda, MD 20892 USA. EM andrew_freedman@nih.gov RI Figg Sr, William/M-2411-2016 FU NCI NIH HHS [R01 CA132780] NR 22 TC 26 Z9 26 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV PY 2010 VL 102 IS 22 BP 1698 EP 1705 DI 10.1093/jnci/djq390 PG 8 WC Oncology SC Oncology GA 682VW UT WOS:000284432100008 PM 20944079 ER PT J AU Rezapkin, G Neverov, A Cherkasova, E Vidor, E Sarafanov, A Kouiavskaia, D Dragunsky, E Chumakov, K AF Rezapkin, Gennady Neverov, Alexander Cherkasova, Elena Vidor, Emmanuel Sarafanov, Andrei Kouiavskaia, Diana Dragunsky, Eugenia Chumakov, Konstantin TI Repertoire of antibodies against type 1 poliovirus in human sera SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE Monoclonal antibodies; Epitopes; Antigenic sites; Blocking-ELISA; Vaccine ID VACCINE-DERIVED POLIOVIRUSES; MEMORY B-CELLS; MONOCLONAL-ANTIBODIES; NEUTRALIZATION EPITOPES; 3-DIMENSIONAL STRUCTURE; ANTIGENIC STRUCTURE; ELISA; SITE; QUANTITATION; SEROTYPE-1 AB A blocking-ELISA procedure was used to quantify antibodies in sera of humans immunized with poliovirus vaccines. Titers determined by this method demonstrated an excellent correlation with the results of neutralization test. Testing of serum potency with a panel of type 1 poliovirus strains altered antigenically was used to evaluate the composition of polyclonal sera with respect to the epitope specificity of constituent antibodies. Paratope profiles of various polyclonal sera determined by this new method differed, depending on the type of vaccine used for immunization. Antibodies induced in response to inactivated poliovirus vaccine (IPV) contained antibodies directed primarily against antigenic site 1, while sera from recipients of the oral poliovirus vaccine (OPV) contained antibodies to site 3. Antibodies to antigenic sites 2 and 4 were minor constituents in both types of sera. Pre-immunization sera had paratope profiles similar to OPV-induced antisera, allowing the discrimination between antibodies induced by IPV and maternal antibodies. The new method may be useful for analyzing results of clinical trials and to compare immunity induced by different poliovirus vaccines. Published by Elsevier B.V. C1 [Rezapkin, Gennady; Neverov, Alexander; Cherkasova, Elena; Sarafanov, Andrei; Kouiavskaia, Diana; Dragunsky, Eugenia; Chumakov, Konstantin] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Vidor, Emmanuel] Sanofi Pasteur, Marcy Letoile, France. RP Chumakov, K (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. EM konstantin.chumakov@fda.hhs.gov NR 36 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD NOV PY 2010 VL 169 IS 2 BP 322 EP 331 DI 10.1016/j.jviromet.2010.07.037 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 670GU UT WOS:000283410000010 PM 20691212 ER PT J AU Mehta, H Muller, J Markovitz, NS AF Mehta, Hina Muller, Jacqueline Markovitz, Nancy S. TI Ultrastructural Analysis of ICP34.5(-) Herpes Simplex Virus 1 Replication in Mouse Brain Cells In Vivo SO JOURNAL OF VIROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; CEREBROSPINAL-FLUID; EPENDYMAL CELLS; INFECTED-CELLS; GENE-THERAPY; STEM-CELLS; EGRESS; DELETION; NEUROVIRULENCE; PROTEIN AB Replication-competent forms of herpes simplex virus 1 (HSV-1) defective in the viral neurovirulence factor infected cell protein 34.5 (ICP34.5) are under investigation for use in the therapeutic treatment of cancer. In mouse models, intratumoral injection of ICP34.5-defective oncolytic HSVs (oHSVs) has resulted in the infection and lysis of tumor cells, an associated decrease in tumor size, and increased survival times. The ability of these oHSVs to infect and lyse cells is frequently characterized as exclusive to or selective for tumor cells. However, the extent to which ICP34.5-deficient HSV-1 replicates in and may be neurotoxic to normal brain cell types in vivo is poorly understood. Here we report that HSV-1 defective in ICP34.5 expression is capable of establishing a productive infection in at least one normal mouse brain cell type. We show that gamma 34.5 deletion viruses replicate productively in and induce cellular damage in infected ependymal cells. Further evaluation of the effects of oHSVs on normal brain cells in animal models is needed to enhance our understanding of the risks associated with the use of current and future oHSVs in the brains of clinical trial subjects and to provide information that can be used to create improved oHSVs for future use. C1 [Mehta, Hina; Markovitz, Nancy S.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Muller, Jacqueline] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Markovitz, NS (reprint author), Hoffmann La Roche Inc, 340 Kingsland St, Nutley, NJ 07110 USA. EM nancymarkovitz@yahoo.com FU U.S. Food and Drug Administration (FDA) through CBER; FDA; Oak Ridge Institute for Science and Education (ORISE) FX This work was supported by the U.S. Food and Drug Administration (FDA) through CBER funding allocated through the Division of Cellular and Gene Therapies to N.S.M. A postdoctoral fellowship to H. M. was funded by the FDA through an interagency agreement between the FDA and the Oak Ridge Institute for Science and Education (ORISE). NR 36 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2010 VL 84 IS 21 BP 10982 EP 10990 DI 10.1128/JVI.00337-10 PG 9 WC Virology SC Virology GA 660LE UT WOS:000282643400005 PM 20702618 ER PT J AU Lutterodt, H Luther, M Slavin, M Yin, JJ Parry, J Gao, JM Yu, LL AF Lutterodt, Herman Luther, Marla Slavin, Margaret Yin, Jun-Jie Parry, John Gao, Jin-Ming Yu, Liangli (Lucy) TI Fatty acid profile, thymoquinone content, oxidative stability, and antioxidant properties of cold-pressed black cumin seed oils SO LWT-FOOD SCIENCE AND TECHNOLOGY LA English DT Article DE Black cumin seed oil; Thymoquinone; TPC; Antioxidant; lipid oxidation; ESR ID NIGELLA-SATIVA; ANTIMICROBIAL PROPERTIES; WHEAT; RASPBERRY; EXTRACTS AB Six different batches of cold-pressed black cumin seed oils (BCSO) were evaluated for their fatty acid profiles, thymoquinone contents, oxidative stability, and antioxidant properties. Linoleic, oleic, and palmitic acids were the major fatty acids in the tested oils. The cold-pressed BCSO samples differed in their oxidative stability measured as the oxidative stability index (OSI). The greatest OSI was about 155 h, and the lowest OSI was proximately 76 h, reflecting a 2-fold difference in their oxidative stability. These BCSO contained significant level of phenolic components with a concentration ranging from 1.02 to 1.40 mg gallic acid equivalents/g oil. In addition, BCSO contained about 3.48-8.73 mg/g thymoquinone and trace amount of dithymoquinone. Electron spin resonance (ESR) analysis showed that cold-pressed BCSO contained natural antioxidants and was able to suppress radical mediated lipid peroxidation in fish oil. The methanol extracts of BCSO could directly react with and quench DPPH radicals, which further confirmed the antioxidant property of these BCSO. The results from the present study suggest that cold-pressed black cumin seed oil may serve as an excellent dietary source of thymoquinone and natural antioxidants. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Lutterodt, Herman; Luther, Marla; Slavin, Margaret; Yu, Liangli (Lucy)] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Parry, John] Virginia State Univ, Agr Res Stn, Petersburg, VA 23805 USA. [Gao, Jin-Ming] NW A&F Univ, Coll Sci, Res Ctr Nat Med Chem, Yangling 712100, Shanxi, Peoples R China. RP Yu, LL (reprint author), Univ Maryland, Dept Nutr & Food Sci, 0112 Skinner Bldg, College Pk, MD 20742 USA. EM lyu5@umd.edu RI Yin, Jun Jie /E-5619-2014; Gao, Jin-Ming/K-5663-2014 FU USDA CSREES [20043550314852]; Maryland Grain Producers Utilization Board (MGPUB) [207198, 208198]; National Science Foundation [CBET-0650650]; Maryland Soybean Board; Maryland Agricultural Experiment Station FX This research was supported by a grant from USDA CSREES National Research Initiatives with a federal grant number of 20043550314852, grants from the Maryland Grain Producers Utilization Board (MGPUB) with MGPUB grant proposal numbers of 207198 and 208198, a grant from National Science Foundation with a federal grant number of CBET-0650650, Maryland Soybean Board and the Maryland Agricultural Experiment Station. NR 21 TC 37 Z9 39 U1 3 U2 33 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0023-6438 J9 LWT-FOOD SCI TECHNOL JI LWT-Food Sci. Technol. PD NOV PY 2010 VL 43 IS 9 BP 1409 EP 1413 DI 10.1016/j.lwt.2010.04.009 PG 5 WC Food Science & Technology SC Food Science & Technology GA 624YC UT WOS:000279857200018 ER PT J AU Moore, MM Schisler, MR Gollapudi, BB AF Moore, Martha M. Schisler, Melissa R. Gollapudi, B. Bhaskar TI Evaluation of U. S. National Toxicology Program (NTP) mouse lymphoma assay data using International Work-shop on Genotoxicity Tests (IWGT) criteria SO MUTAGENESIS LA English DT Meeting Abstract C1 [Moore, Martha M.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Schisler, Melissa R.; Gollapudi, B. Bhaskar] Dow Chem Co USA, Midland, MI 48674 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD NOV PY 2010 VL 25 IS 6 MA 53 BP 649 EP 649 PG 1 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 676PG UT WOS:000283923900066 ER PT J AU Castillo-Lluva, S Tatham, MH Jones, RC Jaffray, EG Edmondson, RD Hay, RT Malliri, A AF Castillo-Lluva, Sonia Tatham, Michael H. Jones, Richard C. Jaffray, Ellis G. Edmondson, Ricky D. Hay, Ronald T. Malliri, Angeliki TI SUMOylation of the GTPase Rac1 is required for optimal cell migration SO NATURE CELL BIOLOGY LA English DT Article ID RHO-FAMILY GTPASES; GROWTH-FACTOR; IN-VIVO; NUCLEAR-LOCALIZATION; POLYBASIC REGION; PIAS PROTEINS; KINASE; SUMO; UBIQUITIN; IDENTIFICATION AB The Rho-like GTPase, Rac1, induces cytoskeletal rearrangements required for cell migration. Rac activation is regulated through a number of mechanisms, including control of nucleotide exchange and hydrolysis, regulation of subcellular localization or modulation of protein-expression levels(1-3). Here, we demonstrate that (the small ubiquitin-like modifier) SUMO E3-ligase, PIAS3, interacts with Rac1 and is required for increased Rac activation and optimal cell migration in response to hepatocyte growth factor (HGF) signalling. Rac1 can be conjugated to SUMO-1 in response to hepatocyte growth factor treatment and SUMOylation is enhanced by PIAS3. Furthermore, we identify non-consensus sites within the polybasic region of Rac1 as the main location for SUMO conjugation. PIAS3-mediated SUMOylation of Rac1 controls the levels of Rac1-GTP and the ability of Rac1 to stimulate lamellipodia, cell migration and invasion. The finding that a Ras superfamily member can be SUMOylated provides insights into the regulation of these critical mediators of cell behaviour. Our data reveal a role for SUMO in the regulation of cell migration and invasion. C1 [Castillo-Lluva, Sonia; Malliri, Angeliki] Univ Manchester, Cell Signalling Grp, Canc Res UK Paterson Inst Canc Res, Manchester M20 4BX, Lancs, England. [Tatham, Michael H.; Jaffray, Ellis G.; Hay, Ronald T.] Univ Dundee, Wellcome Trust Ctr Gene Regulat & Express, Sir James Black Ctr Coll Life Sci, Dundee DD1 5EH, Scotland. [Jones, Richard C.; Edmondson, Ricky D.] US FDA, NCTR, Jefferson, AR 72079 USA. RP Malliri, A (reprint author), Univ Manchester, Cell Signalling Grp, Canc Res UK Paterson Inst Canc Res, Manchester M20 4BX, Lancs, England. EM amalliri@picr.man.ac.uk RI Tatham, Michael/E-9622-2010; Hay, Ronald/F-9338-2011; OI Hay, Ronald/0000-0001-7113-9024; Castillo-LLuva, Sonia/0000-0001-5357-7178; Tatham, Michael/0000-0001-6986-1691 FU CRUK [C147/A6058]; EMBO FX This study was supported by CRUK grant C147/A6058 and an EMBO Long-Term fellowship to S.C.L. M.H.T. and E.G.J. were supported by CRUK. We thank N. Maurice (Glasgow, UK) for mass spectrometry analysis, I. Matic (Dundee, UK) for help with SUMO-Rac1 branched-peptide data interpretation, H. Yokosawa, L. Trusolino and L. Vidali for reagents, N. Mack for help with the calcium-switch experiments, I. Arozarena and C. Wellbrock for help with invasion assays, and members of the Cell Signalling Group, A. Hurlstone, N. Divecha, J. Perez-Martin and C. Wilkinson, for critical reading of the manuscript and helpful discussions. NR 38 TC 47 Z9 49 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD NOV PY 2010 VL 12 IS 11 BP 1078 EP U70 DI 10.1038/ncb2112 PG 21 WC Cell Biology SC Cell Biology GA 674CO UT WOS:000283711500011 PM 20935639 ER PT J AU Ohmann, EL Burckart, GJ Chen, Y Pravica, V Brooks, MM Zeevi, A Webber, SA AF Ohmann, Erin L. Burckart, Gilbert J. Chen, Yan Pravica, Vera Brooks, Maria M. Zeevi, Adriana Webber, Steven A. TI Inosine 5'-monophosphate dehydrogenase 1 haplotypes and association with mycophenolate mofetil gastrointestinal intolerance in pediatric heart transplant patients SO PEDIATRIC TRANSPLANTATION LA English DT Article DE inosine 5'-monophosphate dehydrogenase I; haplotype; mycophenolate mofetil; pediatric heart transplantation; adverse event ID SINGLE-NUCLEOTIDE POLYMORPHISMS; ACUTE REJECTION; GENETIC POLYMORPHISMS; KIDNEY-TRANSPLANTATION; ACID PHARMACOKINETICS; RECIPIENTS; RISK AB MMF, the most commonly used adjuvant immunosuppressant in pediatric heart transplantation, has frequent GI adverse events. SNPs in inosine 5'-monophosphate dehydrogenase I (IMPDH1) may contribute to MMF GI intolerance. Phased haplotypes may have more utility than individual SNPs in candidate gene association studies for complex traits. This study defined common IMPDH1 haplotypes and investigated whether these haplotypes influence MMF GI intolerance in 59 pediatric heart recipients. Genotypes were assessed by Taqman analysis of IMPDH1 rs2288553, rs2288549, rs2278293, rs2278294, and rs2228075, and haplotypes were inferred using Arlequin 3.01 software. GI intolerance was defined as diarrhea, vomiting, nausea, or abdominal pain requiring MMF dose holding for > 48 h or MMF discontinuation. GI intolerance occurred in 21 patients (35.6%). Ten IMPDH1 haplotypes were identified in this population. In univariable analyses, one haplotype was strongly associated with MMF GI intolerance with 59.1% of carriers of this haplotype experiencing MMF GI intolerance compared to 21.6% of non-carriers (p = 0.005). In this study, we identify a common IMPDH1 haplotype associated with MMF GI intolerance in a population of pediatric heart transplant patients. This haplotype of interest did not demonstrate stronger association with MMF GI intolerance than an individual IMPDH1 SNP. C1 [Ohmann, Erin L.; Webber, Steven A.] Univ Pittsburgh, Dept Pediat, Pittsburgh, PA 15260 USA. [Burckart, Gilbert J.] US FDA, Off Clin Pharmacol, Silver Spring, MD USA. [Chen, Yan; Pravica, Vera] Univ So Calif, Dept Pharm, Los Angeles, CA USA. [Brooks, Maria M.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Zeevi, Adriana] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. RP Webber, SA (reprint author), Childrens Hosp Pittsburgh, Div Cardiol, 45th St,Penn Ave, Pittsburgh, PA 15201 USA. EM steve.webber@chp.edu OI Brooks, Maria/0000-0002-2030-7873 FU NIH [5P50HL074732-05]; University of Pittsburgh School of Medicine; Doris Duke Clinical Research Fellowship program FX Grant support: NIH 5P50HL074732-05. Other support: Ms. 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 Doris Duke Clinical Research Fellowship program. NR 21 TC 6 Z9 7 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1397-3142 J9 PEDIATR TRANSPLANT JI Pediatr. Transplant. PD NOV PY 2010 VL 14 IS 7 BP 891 EP 895 DI 10.1111/j.1399-3046.2010.01367.x PG 5 WC Pediatrics; Transplantation SC Pediatrics; Transplantation GA 665WR UT WOS:000283067800019 PM 20649757 ER PT J AU Amur, S Zineh, I Abernethy, DR Huang, SM Lesko, LJ AF Amur, Shashi Zineh, Issam Abernethy, Darrell R. Huang, Shiew-Mei Lesko, Lawrence J. TI Pharmacogenomics and adverse drug reactions SO PERSONALIZED MEDICINE LA English DT Review DE adverse drug reaction; CYP; drug label; drug-metabolizing enzymes; drug safety; genetic; genomic; polymorphism; variant ID ABACAVIR HYPERSENSITIVITY; CLINICAL-PRACTICE; RATES; TOXICITY; INDUSTRY; HLA-B-ASTERISK-5701; POLYMORPHISMS; TRANSPORTERS; INTEGRATION; BIOMARKERS AB Adverse drug reactions (ADRs) observed during drug development have been the cause for discontinuing development of many drugs. In addition, serious but rare ADRs observed after marketing have led to withdrawal of some drugs. A priori identification of individuals at risk of developing ADRs for a given drug will help develop strategies to reduce the risk for ADRs in these patients. US FDA initiatives and efforts at reducing ADRs to make drugs safer are described, including updating of drug labels to include genomic information intended to reduce ADRs. Pharmacogenomics can also be harnessed to identify individuals at risk of developing serious ADRs and to treat these individuals with alternative therapy, thus converting ADRs that are traditionally considered unavoidable to avoidable ADRs. C1 [Amur, Shashi; Zineh, Issam; Abernethy, Darrell R.; Huang, Shiew-Mei; Lesko, Lawrence J.] Ctr Drug Evaluat & Res, Off Translat Sci, Off Clin Pharmacol, PDA, Silver Spring, MD 20998 USA. RP Amur, S (reprint author), Ctr Drug Evaluat & Res, Off Translat Sci, Off Clin Pharmacol, PDA, Bldg 51,10903 New Hampshire Ave, Silver Spring, MD 20998 USA. NR 53 TC 8 Z9 9 U1 1 U2 6 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 J9 PERS MED JI Pers. Med. PD NOV PY 2010 VL 7 IS 6 BP 633 EP 642 DI 10.2217/PME.10.63 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 699ZL UT WOS:000285701800008 ER PT J AU Balakumar, P Jagadeesh, G AF Balakumar, Pitchai Jagadeesh, Gowraganahalli TI Multifarious molecular signaling cascades of cardiac hypertrophy: Can the muddy waters be cleared? SO PHARMACOLOGICAL RESEARCH LA English DT Review DE Cardiac hypertrophy; Heart failure; Genetic alterations; Transcription factors; Signaling mechanisms; Pharmacological interventions ID TUMOR-NECROSIS-FACTOR; ACTIVATED PROTEIN-KINASE; LEFT-VENTRICULAR HYPERTROPHY; NF-KAPPA-B; SPONTANEOUSLY HYPERTENSIVE-RATS; CHRONIC HEART-FAILURE; INDUCED CARDIOMYOCYTE HYPERTROPHY; ACUTE MYOCARDIAL-INFARCTION; P38 MAP KINASE; PRESSURE-OVERLOAD HYPERTROPHY AB The mammalian heart during its development and in response to physiological or pathological stimuli undergoes hypertrophic enlargement, a consequence of an increase in cardiac myocyte size. Cardiac hypertrophy in response to biomechanical stress stimuli may be initially a compensatory event, but gradually becomes a pathological event if the mechanical stress on the myocardium persists. In fact, studies have shown cardiac hypertrophy as a dominant risk factor for the development of heart failure and coronary artery disease. A number of complex signaling cascades were identified that regulate the cardiac hypertrophic response. Much progress has been made previously in identifying various target sites and understanding the molecular and cellular processes that are involved in the development of cardiac hypertrophy and heart failure. This has led drug discovery research in developing effective therapies to treat various cardiovascular diseases. However, the available therapeutic agents for the treatment of heart failure have limited effectiveness in halting the progression of the disease. Therefore, novel therapeutic strategies are being identified to inhibit the development of cardiac hypertrophy before heart failure develops. In this review, we describe multifarious molecular signaling mechanisms involved in the pathogenesis of cardiac hypertrophy, including tumor necrosis factor-alpha, Wnt/Frizzled signals, calcineurin, mitofusin-2, mitogen-activated protein kinases, Janus kinase, Rho kinase, poly (ADP-ribose) polymerase, transcription factors, oxidative signals and G-protein-coupled-receptor-associated signaling system. Elucidation of signaling cascades that initiate cardiac hypertrophy will open up a new area of research in developing innovative therapeutics for the treatment of pathological cardiac hypertrophy. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Balakumar, Pitchai] SB Coll Pharm, Dept Pharmacol, Sivakasi 626130, India. [Jagadeesh, Gowraganahalli] US FDA, Ctr Drug Evaluat & Res, Div Cardiovasc & Renal Prod, Silver Spring, MD 20993 USA. RP Balakumar, P (reprint author), SB Coll Pharm, Dept Pharmacol, Sivakasi 626130, India. EM pbala2006@gmail.com; gowra.jagadeesh@fda.hhs.gov RI Jagadeesh, Gowraganahalli/G-6408-2010; Max, Mad/E-5238-2010 OI Max, Mad/0000-0001-6966-6829 NR 302 TC 38 Z9 42 U1 2 U2 15 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-6618 J9 PHARMACOL RES JI Pharmacol. Res. PD NOV PY 2010 VL 62 IS 5 BP 365 EP 383 DI 10.1016/j.phrs.2010.07.003 PG 19 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 670FZ UT WOS:000283407900001 PM 20643208 ER PT J AU Doerge, DR Twaddle, NC Churchwell, MI Newbold, RR Delclos, KB AF Doerge, Daniel R. Twaddle, Nathan C. Churchwell, Mona I. Newbold, Retha R. Delclos, K. Barry TI Lactational transfer of the soy isoflavone, genistein, in Sprague-Dawley rats consuming dietary genistein (vol 21, pg 307, 2006) SO REPRODUCTIVE TOXICOLOGY LA English DT Correction C1 [Doerge, Daniel R.; Twaddle, Nathan C.; Churchwell, Mona I.; Delclos, K. Barry] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Newbold, Retha R.] NIEHS, Dev Endocrinol & Endocrine Disrupter Sect, Mol Toxicol Lab, NIH DHHS, Res Triangle Pk, NC 27709 USA. RP Doerge, DR (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM daniel.doerge@fda.hhs.gov NR 1 TC 0 Z9 0 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD NOV PY 2010 VL 30 IS 3 BP 493 EP 493 DI 10.1016/j.reprotox.2010.06.005 PG 1 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 654JT UT WOS:000282165000022 ER PT J AU Zhou, Y Little, RJA Kalbfleisch, JD AF Zhou, Yan Little, Roderick J. A. Kalbfleisch, John D. TI Block-Conditional Missing at Random Models for Missing Data SO STATISTICAL SCIENCE LA English DT Article DE Block-sequential missing data models; block-conditional MAR models; EM algorithm; categorical data ID MAXIMUM-LIKELIHOOD-ESTIMATION; PATTERN-MIXTURE-MODELS; CONTINGENCY-TABLES; INCOMPLETE DATA; NONRESPONSE MODELS; NONCOMPLIANCE; ALGORITHM; RESPONSES; SELECTION; SUBJECT AB Two major ideas in the analysis of missing data are (a) the EM algorithm [Dempster, Laird and Rubin, J. Roy. Statist. Soc. Ser. B 39 (1977) 1-38] for maximum likelihood (ML) estimation, and (b) the formulation of models for the joint distribution of the data Z and missing data indicators M, and associated "missing at random" (MAR) condition under which a model for M is unnecessary [ Rubin, Biometrika 63 (1976) 581-592]. Most previous work has treated Z and M as single blocks, yielding selection or pattern-mixture models depending on how their joint distribution is factorized. This paper explores "block-sequential" models that interleave subsets of the variables and their missing data indicators, and then make parameter restrictions based on assumptions in each block. These include models that are not MAR. We examine a subclass of block-sequential models we call block-conditional MAR (BCMAR) models, and an associated block-monotone reduced likelihood strategy that typically yields consistent estimates by selectively discarding some data. Alternatively, full ML estimation can often be achieved via the EM algorithm. We examine in some detail BCMAR models for the case of two multinomially distributed categorical variables, and a two block structure where the first block is categorical and the second block arises from a (possibly multivariate) exponential family distribution. C1 [Zhou, Yan] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Little, Roderick J. A.; Kalbfleisch, John D.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. RP Zhou, Y (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM yan.zhou@fda.hhs.gov; rlittle@umich.edu; jdkalbfl@umich.edu RI Little, Roderick/H-2440-2011 NR 27 TC 2 Z9 2 U1 0 U2 8 PU INST MATHEMATICAL STATISTICS PI CLEVELAND PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA SN 0883-4237 J9 STAT SCI JI Stat. Sci. PD NOV PY 2010 VL 25 IS 4 BP 517 EP 532 DI 10.1214/10-STS344 PG 16 WC Statistics & Probability SC Mathematics GA 736LW UT WOS:000288497200007 ER PT J AU Wang, SJ AF Wang, Sue-Jane TI The Bias Issue Under the Complete Null With Response Adaptive Randomization: Commentary on "Adaptive and Model-Based Dose-Ranging Trials: Quantitative Evaluation and Recommendation" SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH LA English DT Editorial Material ID CLINICAL-TRIALS C1 US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, 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 8 TC 0 Z9 0 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 1946-6315 J9 STAT BIOPHARM RES JI Stat. Biopharm. Res. PD NOV PY 2010 VL 2 IS 4 BP 458 EP 461 DI 10.1198/sbr.2010.09054COMM2 PG 4 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 791QV UT WOS:000292680600003 ER PT J AU Hung, HMJ Wang, SJ AF Hung, H. M. James Wang, Sue-Jane TI Comment on "PISC Expert Team White Paper: Toward a Consistent Standard of Evidence When Evaluating the Efficacy of an Experimental Treatment From a Randomized Active-Controlled Trial" SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH LA English DT Editorial Material ID PLACEBO ARM C1 [Hung, H. M. James] US FDA, Div Biometr 1, Off Biostat, OTS,CDER, Rockville, MD 20857 USA. RP Hung, HMJ (reprint author), US FDA, Div Biometr 1, Off Biostat, OTS,CDER, Rockville, MD 20857 USA. NR 6 TC 3 Z9 3 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 1946-6315 J9 STAT BIOPHARM RES JI Stat. Biopharm. Res. PD NOV PY 2010 VL 2 IS 4 BP 532 EP 534 DI 10.1198/sbr.2010.09016COMM1 PG 3 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 791QV UT WOS:000292680600010 ER PT J AU Trickler, WJ Lantz, SM Murdock, RC Schrand, AM Robinson, BL Newport, GD Schlager, JJ Oldenburg, SJ Paule, MG Slikker, W Hussain, SM Ali, SF AF Trickler, William J. Lantz, Susan M. Murdock, Richard C. Schrand, Amanda M. Robinson, Bonnie L. Newport, Glenn D. Schlager, John J. Oldenburg, Steven J. Paule, Merle G. Slikker, William, Jr. Hussain, Saber M. Ali, Syed F. TI Silver Nanoparticle Induced Blood-Brain Barrier Inflammation and Increased Permeability in Primary Rat Brain Microvessel Endothelial Cells SO TOXICOLOGICAL SCIENCES LA English DT Article DE blood-brain barrier; neuroinflamation; silver nanoparticles; rat brain microvessel endothelial cells; neurotoxicity ID NECROSIS-FACTOR-ALPHA; IN-VITRO; TNF-ALPHA; EXPOSURE; MODEL; TRANSPORT; INTERLEUKIN-1-BETA; DYSFUNCTION; ACTIVATION; EXPRESSION AB The current report examines the interactions of silver nanoparticles (Ag-NPs) with the cerebral microvasculature to identify the involvement of proinflammatory mediators that can increase blood-brain barrier (BBB) permeability. Primary rat brain microvessel endothelial cells (rBMEC) were isolated from adult Sprague-Dawley rats for an in vitro BBB model. The Ag-NPs were characterized by transmission electron microscopy (TEM), dynamic light scattering, and laser Doppler velocimetry. The cellular accumulation, cytotoxicity (6.25-50 mu g/cm(3)) and potential proinflammatory mediators (interleukin [IL]-1 beta, IL-2, tumor necrosis factor [TNF] alpha, and prostaglandin E(2) [PGE(2)]) of Ag-NPs (25, 40, or 80 nm) were determined spectrophotometrically, cell proliferation assay (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide) and ELISA. The results show Ag-NPs-induced cytotoxic responses at lower concentrations for 25 and 40 nm when compared with 80-nm Ag-NPs. The proinflammatory responses in this study demonstrate both Ag-NPs size and time-dependent profiles, with IL-1B preceding both TNF and PGE(2) for 25 nm. However, larger Ag-NPs (40 and 80 nm) induced significant TNF responses at 4 and 8 h, with no observable PGE(2) response. The increased fluorescein transport observed in this study clearly indicates size-dependent increases in BBB permeability correlated with the severity of immunotoxicity. Together, these data clearly demonstrate that larger Ag-NPs (80 nm) had significantly less effect on rBMEC, whereas the smaller particles induced significant effects on all the end points at lower concentrations and/or shorter times. Further, this study suggests that Ag-NPs may interact with the cerebral microvasculature producing a proinflammatory cascade, if left unchecked; these events may further induce brain inflammation and neurotoxicity. C1 [Trickler, William J.; Lantz, Susan M.; Robinson, Bonnie L.; Newport, Glenn D.; Paule, Merle G.; Slikker, William, Jr.; Ali, Syed F.] US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Murdock, Richard C.; Schrand, Amanda M.; Schlager, John J.; Hussain, Saber M.] USAF, Appl Biotechnol Branch, Human Effectiveness Directorate, Res Lab, Wright Patterson AFB, OH 45433 USA. [Oldenburg, Steven J.] NanoComposix Inc, San Diego, CA 92111 USA. RP Ali, SF (reprint author), US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, HFT 132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM syed.ali@fda.hhs.gov FU U.S. Air Force Research Laboratory at the National Center for Toxicological Research/FDA (Jefferson, AR) FX The contents of this manuscript do not necessarily reflect the views and policies of the U.S. Food & Drug Administration, and the mention of trade names or commercial products does not constitute endorsement or recommendation for use. This research was supported in part by an appointment to the Postgraduate Research Participation Program with the U.S. Air Force Research Laboratory at the National Center for Toxicological Research/FDA (Jefferson, AR) administered by the Oak Ridge Institute of Science and Education (Oak Ridge, TN) through an interagency agreement between U.S. Department of Energy, U.S. Air Force Research Laboratory/Applied Biotechnology Branch, and the U.S. Food and Drug Administration. NR 60 TC 111 Z9 116 U1 3 U2 67 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD NOV PY 2010 VL 118 IS 1 BP 160 EP 170 DI 10.1093/toxsci/kfq244 PG 11 WC Toxicology SC Toxicology GA 666DN UT WOS:000283092200018 PM 20713472 ER PT J AU Ross, IA Boyle, T Johnson, WD Sprando, RL O'Donnell, MW Ruggles, D Kim, CS AF Ross, Ivan A. Boyle, Thomas Johnson, Widmark D. Sprando, Robert L. O'Donnell, Michael W. Ruggles, Dennis Kim, Chung S. TI Free fatty acids profile of the fetal brain and the plasma, liver, brain and kidneys of pregnant rats treated with sodium arsenite at mid-organogenesis SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE Arsenic; sodium arsenite; fatty acids; environmental toxicants; organogenesis ID NH2-TERMINAL BLOCKING GROUP; PROTEIN N-MYRISTOYLATION; DRINKING-WATER; MYRISTIC ACID; CANCER; PALMITOYLATION; KINASE; MYRISTOYLTRANSFERASE; IDENTIFICATION; EXPRESSION AB Free fatty acids (FFAs) are known to be markers of cellular membrane degradation through lipid peroxidation and are substrates for the production of reactive oxygen species (ROS). Oxidative stress, due to overproduction of ROS, may facilitate cellular insult by various toxicants. The ability of the rat conceptus to respond to toxic stress may be critical for normal development. In this study, the effects of the environmental toxicant sodium arsenite (NaAsO2) on FFAs were investigated after administering a single oral dose, in water and in a lipid medium, to pregnant rats on gestational day (GD) 10, a time point at mid-organogenesis. NaAsO2 was administered in deionized water (AsH2O) or in half and half dairy cream (AsHH) at a dose of 41 mg sodium arsenite (NaAsO2)/kg body weight. Control animals were treated with either dairy cream (HH) or deionized water (H2O). The animals were sacrificed on GD 20. The fetal brain and the maternal liver, brain, plasma and kidneys were harvested. The FFAs were extracted and analyzed by gas chromatography. In the liver, there was an increase of myristic acid (1200%), myristoleic acid (174%), palmitic acid (47%), elaidic acid (456%), oleic acid (165%) and docosahexaenoic acid (224%) in the AsH2O group as compared to the AsHH group. Oleic acid and arachidonic acid were increased by 192% and 900%, respectively, in the AsH2O group as compared to the H2O group, and myristic acid was decreased by 90% in the AsHH group as compared to the HH group. In the maternal brain, myristoleic acid was decreased by 91% in the AsH2O group as compared to the H2O group, and DHA increased by 148% in the AsHH group as compared to the HH group. In the fetal brain, myristic and stearic acids were decreased by 87% and 89%, respectively, in the AsH2O group as compared to the AsHH group. Myristic, stearic and arachidonic acids were increased by 411%, 265%, and 144%, respectively, in the AsHH group as compared to the HH group. There was no effect on the fatty acids concentrations in the kidney or plasma as compared to controls. This study shows that NaAsO2 produced a differential effect on the fatty acid profiles in rats. Further investigation is needed to elucidate the role of fatty acids in differential signaling and regulation by either the palmitoylation or myristoylation process of cellular functions in these target organs. C1 [Ross, Ivan A.; Boyle, Thomas; Johnson, Widmark D.; Sprando, Robert L.; Kim, Chung S.] Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Div Toxicol, Laurel, MD USA. [O'Donnell, Michael W.; Ruggles, Dennis] Off Food Def Commun & Emergency Response, Biostat Branch, Div Publ Hlth & Biostat, Laurel, MD USA. RP Ross, IA (reprint author), 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM rossivan@msn.com NR 40 TC 1 Z9 1 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0748-2337 EI 1477-0393 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD NOV PY 2010 VL 26 IS 10 BP 657 EP 666 DI 10.1177/0748233710375952 PG 10 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 670PD UT WOS:000283438900003 PM 20630983 ER PT J AU Joshi, G Tremblay, RT Martin, SA Fisher, JW AF Joshi, G. Tremblay, R. T. Martin, S. A. Fisher, J. W. TI Partition coefficients for nonane and its isomers in the rat SO TOXICOLOGY MECHANISMS AND METHODS LA English DT Article DE Partition coefficient; alkane hydrocarbons; JP-8 fuel; octanol:water; physiologically-based pharmacokinetic modelling ID ORGANIC-CHEMICALS; HYDROCARBON MIXTURES; RISK-ASSESSMENT; JET FUEL; LOG-P; MODELS; SEMIVOLATILE; INHALATION; TOXICITY; TISSUES AB Jet Fuel 8 (JP-8) is a major fuel source used by US and NATO military. JP-8 is a complex mixture of aliphatic and aromatic isomers of hydrocarbons. Tissue/blood partition coefficient (PC) values are chemical-specific parameters used in modeling the kinetic behavior of chemicals. The partition coefficient values for n-alkanes tend to increase with the increasing carbon number, but less is known about the trend for isomers of n-alkanes. PC values were obtained for the n-alkane nonane (C9) and five of its isomers, namely 3-methyloctane, 4-ethylheptane, 2,3-dimethylheptane, 2,2,4-trimethylhexane, 2,2,4,4-tetramethylpentane. The blood: air and tissue: air PC values correlated with the published log octanol/water (O:W) PC values for n-nonane and its isomers. Experimentally determined blood: air and tissue: air PC values for n-nonane with the largest O:W value were greatest and smallest for the isomer 2,2,4,4-tetramethylpentane with the lowest O:W value. As expected the fat tissue had the highest PC values and muscle the lowest for n-nonane and its isomers. For each tissue, a linear relationship was observed between the tissue/blood PC values for the isomers of n-nonane and n-nonane. This suggests that tissue/blood PC values for all isomers of an alkane could be estimated using data collected from only a sub-set of alkanes of equal carbon number. These reported tissue/blood PC values will support the development of a jet fuel physiologically-based pharmacokinetic (PBPK) model. C1 [Joshi, G.; Tremblay, R. T.; Martin, S. A.; Fisher, J. W.] Univ Georgia, Coll Publ Hlth, Dept Environm Hlth Sci, Athens, GA 30602 USA. RP Fisher, JW (reprint author), US FDA, NCTR, 3900 NCTR Rd, Jefferson, AR USA. EM jeffrey.fisher@hhs.fda.gov FU AFOSR [FA9550-07-1-0132] FX This research was funded by AFOSR (FA9550-07-1-0132). NR 31 TC 2 Z9 2 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1537-6516 J9 TOXICOL MECH METHOD JI Toxicol. Mech. Methods PD NOV PY 2010 VL 20 IS 9 BP 594 EP 599 DI 10.3109/15376516.2010.518175 PG 6 WC Toxicology SC Toxicology GA 668ZA UT WOS:000283314300010 PM 20919799 ER PT J AU Basch, E Reeve, B Cleeland, C Sloan, J Schrag, D Atkinson, TM Mendoza, T Hay, J Abernethy, A Minasian, L Kwitkowski, V Trentacosti, AM Burke, L Sit, L Bruner, D AF Basch, E. Reeve, B. Cleeland, C. Sloan, J. Schrag, D. Atkinson, T. M. Mendoza, T. Hay, J. Abernethy, A. Minasian, L. Kwitkowski, V Trentacosti, A. M. Burke, L. Sit, L. Bruner, D. TI DEVELOPMENT OF THE PATIENT-REPORTED VERSION OF THE COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS (PRO-CTCAE) SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Basch, E.; Atkinson, T. M.; Hay, J.; Sit, L.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Reeve, B.] NCI, Bethesda, MD 20892 USA. [Cleeland, C.; Mendoza, T.] UTMD Anderson Canc Ctr, Houston, TX USA. [Sloan, J.] Mayo Clin, Rochester, MN USA. [Schrag, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Abernethy, A.] Duke Univ, Durham, NC USA. [Minasian, L.] NCI, Rockville, MD USA. [Burke, L.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Bruner, D.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV PY 2010 VL 13 IS 7 BP A274 EP A275 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 662ON UT WOS:000282818001176 ER PT J AU Zheng, YL Amin, ND Hu, YF Rudrabhatla, P Shukla, V Kanungo, J Kesavapany, S Grant, P Albers, W Pant, HC AF Zheng, Ya-Li Amin, Niranjana D. Hu, Ya-Fang Rudrabhatla, Parvathi Shukla, Varsha Kanungo, Jyotshnabala Kesavapany, Sashi Grant, Philip Albers, Wayne Pant, Harish C. TI A 24-Residue Peptide (p5), Derived from p35, the Cdk5 Neuronal Activator, Specifically Inhibits Cdk5-p25 Hyperactivity and Tau Hyperphosphorylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYCLIN-DEPENDENT KINASE-5; ALZHEIMERS-DISEASE; SYNAPTIC PLASTICITY; CELL-CYCLE; IN-VIVO; NEURODEGENERATIVE DISEASES; TRANSGENIC MODEL; NERVOUS-SYSTEM; A-BETA; PROTEIN AB The activity of Cdk5-p35 is tightly regulated in the developing and mature nervous system. Stress-induced cleavage of the activator p35 to p25 and a p10 N-terminal domain induces deregulated Cdk5 hyperactivity and perikaryal aggregations of hyperphosphorylated Tau and neurofilaments, pathogenic hallmarks in neurodegenerative diseases, such as Alzheimer disease and amyotrophic lateral sclerosis, respectively. Previously, we identified a 125-residue truncated fragment of p35 called CIP that effectively and specifically inhibited Cdk5-p25 activity and Tau hyperphosphorylation induced by A beta peptides in vitro, in HEK293 cells, and in neuronal cells. Although these results offer a possible therapeutic approach to those neurodegenerative diseases assumed to derive from Cdk5-p25 hyperactivity and/or A beta induced pathology, CIP is too large for successful therapeutic regimens. To identify a smaller, more effective peptide, in this study we prepared a 24-residue peptide, p5, spanning CIP residues Lys(245)-Ala(277). p5 more effectively inhibited Cdk5-p25 activity than did CIP in vitro. In neuron cells, p5 inhibited deregulated Cdk5-p25 activity but had no effect on the activity of endogenous Cdk5-p35 or on any related endogenous cyclin-dependent kinases in HEK293 cells. Specificity of p5 inhibition in cortical neurons may depend on the p10 domain in p35, which is absent in p25. Furthermore, we have demonstrated that p5 reduced A beta(1-42)-induced Tau hyperphosphorylation and apoptosis in cortical neurons. These results suggest that p5 peptide may be a unique and useful candidate for therapeutic studies of certain neurodegenerative diseases. C1 [Zheng, Ya-Li; Amin, Niranjana D.; Rudrabhatla, Parvathi; Shukla, Varsha; Grant, Philip; Albers, Wayne; Pant, Harish C.] NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. [Zheng, Ya-Li] Ningxia Peoples Hosp, Dept Nephrol, Ningxia 750021, Peoples R China. [Hu, Ya-Fang] NIDCR, Lab Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. [Kanungo, Jyotshnabala] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Kesavapany, Sashi] Natl Univ Singapore, Dept Biochem, Yong Loo Lin Sch Med, Singapore 117697, Singapore. RP Pant, HC (reprint author), NINDS, Neurochem Lab, NIH, Bldg 49,Rm 2A28,9000 Rockville Pike, Bethesda, MD 20892 USA. EM panth@ninds.nih.gov RI Shukla, Varsha/G-5136-2010 FU National Institutes of Health, NINDS FX This work was supported, in whole or in part, by National Institutes of Health, NINDS, intramural funds. NR 74 TC 36 Z9 39 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 OCT 29 PY 2010 VL 285 IS 44 BP 34202 EP 34212 DI 10.1074/jbc.M110.134643 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 669MD UT WOS:000283354000065 PM 20720012 ER PT J AU Patterson, TA Li, M Hotchkiss, CE Mauz, A Eddie, M Greischel, A Stierstorfer, B Deschl, U Paule, MG AF Patterson, Tucker A. Li, Mi Hotchkiss, Charlotte E. Mauz, Annerose Eddie, Malcolm Greischel, Andreas Stierstorfer, Birgit Deschl, Ulrich Paule, Merle G. TI Toxicity assessment of pramipexole in juvenile rhesus monkeys SO TOXICOLOGY LA English DT Article DE Dopamine; Development; Parkinson's disease ID NMDA RECEPTOR ANTAGONISTS; NONHUMAN-PRIMATES; MACACA-MULATTA; DOPAMINE; D-3; PROLACTIN; AGONIST; PERFORMANCE; INHIBITION; PARAMETERS AB Pramipexole (PPX) is a dopamine agonist approved for the treatment of the signs and symptoms of idiopathic Parkinson's disease as well as restless leg syndrome. The objective of this study was to investigate the toxicity of PPX when administered orally to juvenile rhesus monkeys once daily for 30 weeks, and to assess the reversibility of toxicity during a 12-week recovery. Rhesus monkeys (N = 4 males and 4 females/group; 22-24 months of age) were orally treated daily for 30 weeks with 0.0, 0.1, 0.5 or 2.0 mg/kg PPX, and subjects were assessed daily using the NCTR Operant Test Battery (OTB). Clinical chemistry, hematology, ophthalmology and other standard postmortem toxicological evaluations, including histopathology and neuropathology as well as toxicokinetics were performed. The systemic exposure to PPX was higher than that at therapeutic doses in man and AUC(0-24 h)-data increased proportionally to dose. Blood pressure significantly decreased over time in all groups including control. Near the end of treatment, there were statistically significant decreases in heart rate for the 0.5 and 2.0 mg/kg/day groups compared to control. After 4 weeks of dosing, serum prolactin was significantly decreased in all treatment groups compared to control. This decrease remained at the end of treatment in the 0.5 and 2.0 mg/kg/day groups. In summary, administration of PPX at doses of up to 2.0 mg/kg/day for 30 weeks to juvenile rhesus monkeys produced adverse findings which were attributable to its pharmacological properties, including hypoprolactinemia. Published by Elsevier Ireland Ltd. C1 [Patterson, Tucker A.; Li, Mi; Paule, Merle G.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Hotchkiss, Charlotte E.] Bionetics Corp, Jefferson, AR 72079 USA. [Mauz, Annerose; Eddie, Malcolm; Greischel, Andreas; Stierstorfer, Birgit; Deschl, Ulrich] Boehringer Ingelheim Pharma GmbH & Co KG, D-88397 Biberach, Germany. RP Patterson, TA (reprint author), HFT 132 Natl Ctr Toxicol Res FDA, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM tucker.patterson@fda.hhs.gov; mi.li@fda.hhs.gov; chotchki@wanprc.org; annerose.mauz@boehringer-ingelheim.com; malcolm.eddie@boehringer-ingelheim.com; andreas.greischel@boehringer-ingelheim.com; birgit.stierstorfer@boehringer-ingelheim.com; ulrich.deschl@boehringer-ingelheim.com; merle.paule@fda.hhs.gov FU Cooperative Research and Development Agreement (CRADA) [119-06]; National Center for Toxicological Research/FDA; Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, USA FX The authors would like to express their appreciation to Johanne Bouchard and colleagues at SGS Cephac Europe (90 Avenue des Hauts de la Chaume, 86281 Saint-Benoit Cedex, France) for their expertise and assistance with the sample bionalyses. This work was supported by a Cooperative Research and Development Agreement (CRADA 119-06) between the National Center for Toxicological Research/FDA and Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT 06877, USA. NR 25 TC 7 Z9 7 U1 0 U2 3 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 OCT 29 PY 2010 VL 276 IS 3 BP 164 EP 171 DI 10.1016/j.tox.2010.08.002 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 674QC UT WOS:000283761300003 PM 20705114 ER PT J AU Li, ZG Branham, WS Dial, SL Wang, YX Guo, L Shi, LM Chen, T AF Li, Zhiguang Branham, William S. Dial, Stacey L. Wang, Yexun Guo, Lei Shi, Leming Chen, Tao TI Genomic analysis of microRNA time-course expression in liver of mice treated with genotoxic carcinogen N-ethyl-N-nitrosourea SO BMC GENOMICS LA English DT Article ID GENE-EXPRESSION; TUMOR-SUPPRESSOR; CELL-DIFFERENTIATION; ALKYLATING-AGENTS; RAT-LIVER; CANCER; ETHYLNITROSOUREA; APOPTOSIS; DNA; GROWTH AB Background: Dysregulated expression of microRNAs (miRNAs) has been previously observed in human cancer tissues and shown promise in defining tumor status. However, there is little information as to if or when expression changes of miRNAs occur in normal tissues after carcinogen exposure. Results: To explore the possible time-course changes of miRNA expression induced by a carcinogen, we treated mice with one dose of 120 mg/kg N-ethyl-N-nitrosourea (ENU), a model genotoxic carcinogen, and vehicle control. The miRNA expression profiles were assessed in the mouse livers in a time-course design. miRNAs were isolated from the livers at days 1, 3, 7, 15, 30 and 120 after the treatment and their expression was determined using a miRNA PCR Array. Principal component analysis of the miRNA expression profiles showed that miRNA expression at post-treatment days (PTDs) 7 and 15 were different from those at the other time points and the control. The number of differentially expressed miRNAs (DEMs) changed over time (3, 5, 14, 32, 5 and 5 at PTDs 1, 3, 7, 15, 30 and 120, respectively). The magnitude of the expression change varied with time with the highest changes at PTDs 7 or 15 for most of the DEMs. In silico functional analysis of the DEMs at PTDs 7 and 15 indicated that the major functions of these ENU-induced DEMs were associated with DNA damage, DNA repair, apoptosis and other processes related to carcinogenesis. Conclusion: Our results showed that many miRNAs changed their expression to respond the exposure of the genotoxic carcinogen ENU and the number and magnitude of the changes were highest at PTDs 7 to 15. Thus, one to two weeks after the exposure is the best time for miRNA expression sampling. C1 [Li, Zhiguang; Dial, Stacey L.; Chen, Tao] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Branham, William S.; Shi, Leming] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Guo, Lei] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Wang, Yexun] SABiosci Corp, Frederick, MD 21703 USA. RP Chen, T (reprint author), US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM tao.chen@fda.hhs.gov RI Guo, Lei/E-9232-2011 FU NCTR FX This research was supported by an appointment (Z. Li) to the Postgraduate Research Program at the NCTR administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the US Food and Drug Administration. We would like to thank Drs. Tao Han and Joshua Kwekel for their enlightening comments and hearty discussions in reviewing the manuscript. The views presented in this article do not necessarily reflect those of the Food and Drug Administration. NR 64 TC 20 Z9 22 U1 0 U2 1 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 OCT 28 PY 2010 VL 11 AR 609 DI 10.1186/1471-2164-11-609 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 682NY UT WOS:000284411500001 PM 21029445 ER PT J AU Zhang, K Akpek, EK Weiblinger, RP Kim, DH Kang, JU Ilev, IK AF Zhang, K. Akpek, E. K. Weiblinger, R. P. Kim, D. H. Kang, J. U. Ilev, I. K. TI Noninvasive volumetric quality evaluation of post-surgical clear corneal incision via high-resolution Fourier-domain optical coherence tomography SO ELECTRONICS LETTERS LA English DT Article ID ANTERIOR SEGMENT AB A novel approach for post-surgical evaluation of clear corneal incision quality is presented. The complete volumetric information of an ex-vivo bovine cornea with incision and suture is obtained by high-resolution Fourier-domain optical coherence tomography and illustrated by various computer graphics technologies. This method provides more comprehensive information to evaluate surgery quality and monitor the healing process. C1 [Zhang, K.; Kang, J. U.] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. [Akpek, E. K.] Johns Hopkins Univ Hosp, Wilmer Eye Inst, Baltimore, MD 21287 USA. [Weiblinger, R. P.; Kim, D. H.; Ilev, I. K.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Zhang, K (reprint author), Johns Hopkins Univ, Dept Elect & Comp Engn, 3400 N Charles St, Baltimore, MD 21218 USA. EM kzhang8@jhu.edu RI Kang, Jin/A-3228-2010 NR 6 TC 2 Z9 2 U1 0 U2 4 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 OCT 28 PY 2010 VL 46 IS 22 BP 1482 EP U17 DI 10.1049/el.2010.8667 PG 2 WC Engineering, Electrical & Electronic SC Engineering GA 673MS UT WOS:000283668200006 ER PT J AU Altshuler, D Durbin, RM Abecasis, GR Bentley, DR Chakravarti, A Clark, AG Collins, FS De la Vega, FM Donnelly, P Egholm, M Flicek, P Gabriel, SB Gibbs, RA Knoppers, BM Lander, ES Lehrach, H Mardis, ER McVean, GA Nickerson, D Peltonen, L Schafer, AJ Sherry, ST Wang, J Wilson, RK Gibbs, RA Deiros, D Metzker, M Muzny, D Reid, J Wheeler, D Wang, J Li, JX Jian, M Li, G Li, RQ Liang, HQ Tian, G Wang, B Wang, J Wang, W Yang, HM Zhang, XQ Zheng, HS Lander, ES Altshuler, DL Ambrogio, L Bloom, T Cibulskis, K Fennell, TJ Gabriel, SB Jaffe, DB Shefler, E Sougnez, CL Bentley, DR Gormley, N Humphray, S Kingsbury, Z Koko-Gonzales, P Stone, J McKernan, KJ Costa, GL Ichikawa, JK Lee, CC Sudbrak, R Lehrach, H Borodina, TA Dahl, A Davydov, AN Marquardt, P Mertes, F Nietfeld, W Rosenstiel, P Schreiber, S Soldatov, AV Timmermann, B Tolzmann, M Egholm, M Affourtit, J Ashworth, D Attiya, S Bachorski, M Buglione, E Burke, A Caprio, A Celone, C Clark, S Conners, D Desany, B Gu, L Guccione, L Kao, K Kebbel, A Knowlton, J Labrecque, M McDade, L Mealmaker, C Minderman, M Nawrocki, A Niazi, F Pareja, K Ramenani, R Riches, D Song, W Turcotte, C Wang, S Mardis, ER Dooling, D Fulton, L Fulton, R Weinstock, G Durbin, RM Burton, J Carter, DM Churcher, C Coffey, A Cox, A Palotie, A Quail, M Skelly, T Stalker, J Swerdlow, HP Turner, D De Witte, A Giles, S Gibbs, RA Wheeler, D Bainbridge, M Challis, D Sabo, A Yu, F Yu, J Wang, J Fang, XD Guo, XS Li, RQ Li, YR Luo, RB Tai, S Wu, HL Zheng, HC Zheng, XL Zhou, Y Yang, HM Marth, GT Garrison, EP Huang, W Indap, A Kural, D Lee, WP Leong, WF Huang, WC Indap, A Kural, D Lee, WP Leong, WF Quinlan, AR Stewart, C Stromberg, MP Ward, AN Wu, JT Lee, C Mills, RE Shi, XH Daly, MJ DePristo, MA Altshuler, DL Ball, AD Banks, E Bloom, T Browning, BL Cibulskis, K Fennell, TJ Garimella, KV Grossman, SR Handsaker, RE Hanna, M Hartl, C Jaffe, DB Kernytsky, AM Korn, JM Li, H Maguire, JR McCarroll, SA McKenna, A Nemesh, JC Philippakis, AA Poplin, RE Price, A Rivas, MA Sabeti, PC Schaffner, SF Shefler, E Shlyakhter, IA Cooper, DN Ball, EV Mort, M Phillips, AD Stenson, PD Sebat, J Makarov, V Ye, K Yoon, SC Bustamante, CD Clark, AG Boyko, A Degenhardt, J Gravel, S Gutenkunst, RN Kaganovich, M Keinan, A Lacroute, P Ma, X Reynolds, A Clarke, L Flicek, P Cunningham, F Herrero, J Keenen, S Kulesha, E Leinonen, R McLaren, W Radhakrishnan, R Smith, RE Zalunin, V Zheng-Bradley, XQ Korbel, JO Stutz, AM Humphray, S Bauer, M Cheetham, RK Cox, T Eberle, M James, T Kahn, S Murray, L Ye, K De La Vega, FM Fu, YT Hyland, FCL Manning, JM McLaughlin, SF Peckham, HE Sakarya, O Sun, YA Tsung, EF Batzer, MA Konkel, MK Walker, JA Sudbrak, R Albrecht, MW Amstislavskiy, VS Herwig, R Parkhomchuk, DV Sherry, ST Agarwala, R Khouri, H Morgulis, AO Paschall, JE Phan, LD Rotmistrovsky, KE Sanders, RD Shumway, MF Xiao, CL McVean, GA Auton, A Iqbal, Z Lunter, G Marchini, JL Moutsianas, L Myers, S Tumian, A Desany, B Knight, J Winer, R Craig, DW Beckstrom-Sternberg, SM Christoforides, A Kurdoglu, AA Pearson, J Sinari, SA Tembe, WD Haussler, D Hinrichs, AS Katzman, SJ Kern, A Kuhn, RM Przeworski, M Hernandez, RD Howie, B Kelley, JL Melton, SC Abecasis, GR Li, Y Anderson, P Blackwell, T Chen, W Cookson, WO Ding, J Kang, HM Lathrop, M Liang, LM Moffatt, MF Scheet, P Sidore, C Snyder, M Zhan, XW Zollner, S Awadalla, P Casals, F Idaghdour, Y Keebler, J Stone, EA Zilversmit, M Jorde, L Xing, JC Eichler, EE Aksay, G Alkan, C Hajirasouliha, I Hormozdiari, F Kidd, JM Sahinalp, SC Sudmant, PH Mardis, ER Chen, K Chinwalla, A Ding, L Koboldt, DC McLellan, MD Dooling, D Weinstock, G Wallis, JW Wendl, MC Zhang, QY Durbin, RM Albers, CA Ayub, Q Balasubramaniam, S Barrett, JC Carter, DM Chen, YA Conrad, DF Danecek, P Dermitzakis, ET Hu, M Huang, N Hurles, ME Jin, HJ Jostins, L Keane, TM Keane, TM Le, SQ Lindsay, S Long, QA MacArthur, DG Montgomery, SB Parts, L Stalker, J Tyler-Smith, C Walter, K Zhang, YJ Gerstein, MB Snyder, M Abyzov, A Abyzov, A Balasubramanian, S Bjornson, R Du, JA Grubert, F Habegger, L Haraksingh, R Jee, J Khurana, E Lam, HYK Leng, J Mu, XJ Urban, AE Zhang, ZD Li, YR Luo, RB Marth, GT Garrison, EP Kural, D Quinlan, AR Stewart, C Stromberg, MP Ward, AN Wu, JT Lee, C Mills, RE Shi, XH McCarroll, SA Banks, E DePristo, MA Handsaker, RE Hartl, C Korn, JM Li, H Nemesh, JC Sebat, J Makarov, V Ye, K Yoon, SC Degenhardt, J Kaganovich, M Clarke, L Smith, RE Zheng-Bradley, XQ Korbel, JO Humphray, S Cheetham, RK Eberle, M Kahn, S Murray, L Ye, K De la Vega, FM Fu, YT Peckham, HE Sun, YA Batzer, MA Konkel, MK Xiao, CL Iqbal, Z Desany, B Blackwell, T Snyder, M Xing, JC Eichler, EE Aksay, G Alkan, C Hajirasouliha, I Hormozdiari, F Kidd, JM Chen, K Chinwalla, A Ding, L McLellan, MD Wallis, JW Hurles, ME Conrad, DF Walter, K Zhang, YJ Gerstein, MB Snyder, M Abyzov, A Du, JA Grubert, F Haraksingh, R Jee, J Khurana, E Lam, HYK Leng, J Mu, XJ Urban, AE Zhang, ZD Gibbs, RA Bainbridge, M Challis, D Coafra, C Dinh, H Kovar, C Lee, S Muzny, D Nazareth, L Reid, J Sabo, A Yu, FL Yu, J Marth, GT Garrison, EP Indap, A Leong, WF Quinlan, AR Stewart, C Ward, AN Wu, JT Cibulskis, K Fennell, TJ Gabriel, SB Garimella, KV Hartl, C Shefler, E Sougnez, CL Wilkinson, J Clark, AG Gravel, S Grubert, F Clarke, L Flicek, P Smith, RE Zheng-Bradley, XQ Sherry, ST Khouri, HM Paschall, JE Shumway, MF Xiao, CL McVean, GA Katzman, SJ Abecasis, GR Blackwell, T Mardis, ER Dooling, D Fulton, L Fulton, R Koboldt, DC Durbin, RM Balasubramaniam, S Coffey, A Keane, TM MacArthur, DG Palotie, A Scott, C Stalker, J Tyler-Smith, C Gerstein, MB Balasubramanian, S Chakravarti, A Knoppers, BM Peltonen, L Abecasis, GR Bustamante, CD Gharani, N Gibbs, RA Jorde, L Kaye, JS Kent, A Li, T McGuire, AL McVean, GA Ossorio, PN Rotimi, CN Su, YY Toji, LH Tyler-Smith, C Brooks, LD Felsenfeld, AL McEwen, JE Abdallah, A Christopher, R Clemm, NC Collins, FS Duncanson, A Green, ED Guyer, MS Peterson, JL Schafer, AJ Abecasis, GR Altshuler, DL Auton, A Brooks, LD Durbin, RM Gibbs, RA Hurles, ME McVean, GA AF Altshuler, David Durbin, Richard M. Abecasis, Goncalo R. Bentley, David R. Chakravarti, Aravinda Clark, Andrew G. Collins, Francis S. De la Vega, Francisco M. Donnelly, Peter Egholm, Michael Flicek, Paul Gabriel, Stacey B. Gibbs, Richard A. Knoppers, Bartha M. Lander, Eric S. Lehrach, Hans Mardis, Elaine R. McVean, Gil A. Nickerson, DebbieA. Peltonen, Leena Schafer, Alan J. Sherry, Stephen T. Wang, Jun Wilson, Richard K. Gibbs, Richard A. Deiros, David Metzker, Mike Muzny, Donna Reid, Jeff Wheeler, David Wang, Jun Li, Jingxiang Jian, Min Li, Guoqing Li, Ruiqiang Liang, Huiqing Tian, Geng Wang, Bo Wang, Jian Wang, Wei Yang, Huanming Zhang, Xiuqing Zheng, Huisong Lander, Eric S. Altshuler, David L. Ambrogio, Lauren Bloom, Toby Cibulskis, Kristian Fennell, Tim J. Gabriel, Stacey B. Jaffe, David B. Shefler, Erica Sougnez, Carrie L. Bentley, David R. Gormley, Niall Humphray, Sean Kingsbury, Zoya Koko-Gonzales, Paula Stone, Jennifer McKernan, Kevin J. Costa, Gina L. Ichikawa, Jeffry K. Lee, Clarence C. Sudbrak, Ralf Lehrach, Hans Borodina, Tatiana A. Dahl, Andreas Davydov, Alexey N. Marquardt, Peter Mertes, Florian Nietfeld, Wilfiried Rosenstiel, Philip Schreiber, Stefan Soldatov, Aleksey V. Timmermann, Bernd Tolzmann, Marius Egholm, Michael Affourtit, Jason Ashworth, Dana Attiya, Said Bachorski, Melissa Buglione, Eli Burke, Adam Caprio, Amanda Celone, Christopher Clark, Shauna Conners, David Desany, Brian Gu, Lisa Guccione, Lorri Kao, Kalvin Kebbel, Andrew Knowlton, Jennifer Labrecque, Matthew McDade, Louise Mealmaker, Craig Minderman, Melissa Nawrocki, Anne Niazi, Faheem Pareja, Kristen Ramenani, Ravi Riches, David Song, Wanmin Turcotte, Cynthia Wang, Shally Mardis, Elaine R. Dooling, David Fulton, Lucinda Fulton, Robert Weinstock, George Durbin, Richard M. Burton, John Carter, David M. Churcher, Carol Coffey, Alison Cox, Anthony Palotie, Aarno Quail, Michael Skelly, Tom Stalker, James Swerdlow, Harold P. Turner, Daniel De Witte, Anniek Giles, Shane Gibbs, Richard A. Wheeler, David Bainbridge, Matthew Challis, Danny Sabo, Aniko Yu, Fuli Yu, Jin Wang, Jun Fang, Xiaodong Guo, Xiaosen Li, Ruiqiang Li, Yingrui Luo, Ruibang Tai, Shuaishuai Wu, Honglong Zheng, Hancheng Zheng, Xiaole Zhou, Yan Yang, Huanming Marth, Gabor T. Garrison, Erik P. Huang, Weichun Indap, Amit Kural, Deniz Lee, Wan-Ping Leong, Wen Fung Huang, Weichun Indap, Amit Kural, Deniz Lee, Wan-Ping Leong, Wen Fung Quinlan, Aaron R. Stewart, Chip Stromberg, Michael P. Ward, Alistair N. Wu, Jiantao Lee, Charles Mills, Ryan E. Shi, Xinghua Daly, Mark J. DePristo, Mark A. Altshuler, David L. Ball, Aaron D. Banks, Eric Bloom, Toby Browning, Brian L. Cibulskis, Kristian Fennell, Tim J. Garimella, Kiran V. Grossman, Sharon R. Handsaker, Robert E. Hanna, Matt Hartl, Chris Jaffe, David B. Kernytsky, Andrew M. Korn, Joshua M. Li, Heng Maguire, Jared R. McCarroll, Steven A. McKenna, Aaron Nemesh, James C. Philippakis, Anthony A. Poplin, Ryan E. Price, Alkes Rivas, Manuel A. Sabeti, Pardis C. Schaffner, Stephen F. Shefler, Erica Shlyakhter, Ilya A. Cooper, David N. Ball, Edward V. Mort, Matthew Phillips, Andrew D. Stenson, Peter D. Sebat, Jonathan Makarov, Vladimir Ye, Kenny Yoon, Seungtai C. Bustamante, Carlos D. Clark, Andrew G. Boyko, Adam Degenhardt, Jeremiah Gravel, Simon Gutenkunst, Ryan N. Kaganovich, Mark Keinan, Alon Lacroute, Phil Ma, Xia Reynolds, Andy Clarke, Laura Flicek, Paul Cunningham, Fiona Herrero, Javier Keenen, Stephen Kulesha, Eugene Leinonen, Rasko McLaren, WilliamM. Radhakrishnan, Rajesh Smith, Richard E. Zalunin, Vadim Zheng-Bradley, Xiangqun Korbel, Jan O. Stuetz, Adrian M. Humphray, Sean Bauer, Markus Cheetham, R. Keira Cox, Tony Eberle, Michael James, Terena Kahn, Scott Murray, Lisa Ye, Kai De La Vega, Francisco M. Fu, Yutao Hyland, Fiona C. L. Manning, Jonathan M. McLaughlin, Stephen F. Peckham, Heather E. Sakarya, Onur Sun, Yongming A. Tsung, Eric F. Batzer, Mark A. Konkel, Miriam K. Walker, Jerilyn A. Sudbrak, Ralf Albrecht, Marcus W. Amstislavskiy, Vyacheslav S. Herwig, Ralf Parkhomchuk, Dimitri V. Sherry, Stephen T. Agarwala, Richa Khouri, Hodam. Morgulis, Aleksandr O. Paschall, Justin E. Phan, Lon D. Rotmistrovsky, Kirill E. Sanders, Robert D. Shumway, Martin F. Xiao, Chunlin McVean, Gil A. Auton, Adam Iqbal, Zamin Lunter, Gerton Marchini, Jonathan L. Moutsianas, Loukas Myers, Simon Tumian, Afidalina Desany, Brian Knight, James Winer, Roger Craig, David W. Beckstrom-Sternberg, Steve M. Christoforides, Alexis Kurdoglu, Ahmet A. Pearson, Johnv. Sinari, Shripad A. Tembe, Waibhav D. Haussler, David Hinrichs, Angie S. Katzman, Sol J. Kern, Andrew Kuhn, Robert M. Przeworski, Molly Hernandez, Ryan D. Howie, Bryan Kelley, Joanna L. Melton, S. Cord Abecasis, Goncalo R. Li, Yun Anderson, Paul Blackwell, Tom Chen, Wei Cookson, William O. Ding, Jun Kang, Hyun Min Lathrop, Mark Liang, Liming Moffatt, Miriam F. Scheet, Paul Sidore, Carlo Snyder, Matthew Zhan, Xiaowei Zoellner, Sebastian Awadalla, Philip Casals, Ferran Idaghdour, Youssef Keebler, John Stone, Eric A. Zilversmit, Martine Jorde, Lynn Xing, Jinchuan Eichler, Evan E. Aksay, Gozde Alkan, Can Hajirasouliha, Iman Hormozdiari, Fereydoun Kidd, Jeffrey M. Sahinalp, S. Cenk Sudmant, Peter H. Mardis, Elaine R. Chen, Ken Chinwalla, Asif Ding, Li Koboldt, Daniel C. McLellan, Mike D. Dooling, David Weinstock, George Wallis, John W. Wendl, Michael C. Zhang, Qunyuan Durbin, Richard M. Albers, Cornelis A. Ayub, Qasim Balasubramaniam, Senduran Barrett, Jeffrey C. Carter, David M. Chen, Yuan Conrad, Donald F. Danecek, Petr Dermitzakis, Emmanouil T. Hu, Min Huang, Ni Hurles, Matt E. Jin, Hanjun Jostins, Luke Keane, Thomas M. Keane, Thomas M. Le, Si Quang Lindsay, Sarah Long, Quan MacArthur, Daniel G. Montgomery, Stephen B. Parts, Leopold Stalker, James Tyler-Smith, Chris Walter, Klaudia Zhang, Yujun Gerstein, Mark B. Snyder, Michael Abyzov, Alexej Abyzov, Alexej Balasubramanian, Suganthi Bjornson, Robert Du, Jiang Grubert, Fabian Habegger, Lukas Haraksingh, Rajini Jee, Justin Khurana, Ekta Lam, Hugo Y. K. Leng, Jing Mu, Xinmeng Jasmine Urban, Alexander E. Zhang, Zhengdong Li, Yingrui Luo, Ruibang Marth, Gabor T. Garrison, Erik P. Kural, Deniz Quinlan, Aaron R. Stewart, Chip Stromberg, Michael P. Ward, Alistair N. Wu, Jiantao Lee, Charles Mills, Ryan E. Shi, Xinghua McCarroll, Steven A. Banks, Eric DePristo, Mark A. Handsaker, Robert E. Hartl, Chris Korn, Joshua M. Li, Heng Nemesh, James C. Sebat, Jonathan Makarov, Vladimir Ye, Kenny Yoon, Seungtai C. Degenhardt, Jeremiah Kaganovich, Mark Clarke, Laura Smith, Richard E. Zheng-Bradley, Xiangqun Korbel, Jan O. Humphray, Sean Cheetham, R. Keira Eberle, Michael Kahn, Scott Murray, Lisa Ye, Kai De la Vega, Francisco M. Fu, Yutao Peckham, Heather E. Sun, Yongming A. Batzer, Mark A. Konkel, Miriam K. Xiao, Chunlin Iqbal, Zamin Desany, Brian Blackwell, Tom Snyder, Matthew Xing, Jinchuan Eichler, Evan E. Aksay, Gozde Alkan, Can Hajirasouliha, Iman Hormozdiari, Fereydoun Kidd, Jeffrey M. Chen, Ken Chinwalla, Asif Ding, Li McLellan, Mike D. Wallis, John W. Hurles, Matt E. Conrad, Donald F. Walter, Klaudia Zhang, Yujun Gerstein, Mark B. Snyder, Michael Abyzov, Alexej Du, Jiang Grubert, Fabian Haraksingh, Rajini Jee, Justin Khurana, Ekta Lam, Hugo Y. K. Leng, Jing Mu, Xinmeng Jasmine Urban, Alexander E. Zhang, Zhengdong Gibbs, Richard A. Bainbridge, Matthew Challis, Danny Coafra, Cristian Dinh, Huyen Kovar, Christie Lee, Sandy Muzny, Donna Nazareth, Lynne Reid, Jeff Sabo, Aniko Yu, Fuli Yu, Jin Marth, Gabor T. Garrison, Erik P. Indap, Amit Leong, Wen Fung Quinlan, Aaron R. Stewart, Chip Ward, Alistair N. Wu, Jiantao Cibulskis, Kristian Fennell, Tim J. Gabriel, Stacey B. Garimella, Kiran V. Hartl, Chris Shefler, Erica Sougnez, Carrie L. Wilkinson, Jane Clark, Andrew G. Gravel, Simon Grubert, Fabian Clarke, Laura Flicek, Paul Smith, Richard E. Zheng-Bradley, Xiangqun Sherry, Stephen T. Khouri, Hoda M. Paschall, Justin E. Shumway, Martin F. Xiao, Chunlin McVean, Gil A. Katzman, Sol J. Abecasis, Goncalo R. Blackwell, Tom Mardis, Elaine R. Dooling, David Fulton, Lucinda Fulton, Robert Koboldt, Daniel C. Durbin, Richard M. Balasubramaniam, Senduran Coffey, Allison Keane, Thomas M. MacArthur, Daniel G. Palotie, Aarno Scott, Carol Stalker, James Tyler-Smith, Chris Gerstein, Mark B. Balasubramanian, Suganthi Chakravarti, Aravinda Knoppers, Bartha M. Peltonen, Leena Abecasis, Goncalo R. Bustamante, Carlos D. Gharani, Neda Gibbs, Richard A. Jorde, Lynn Kaye, Jane S. Kent, Alastair Li, Taosha McGuire, Amy L. McVean, Gil A. Ossorio, Pilar N. Rotimi, Charles N. Su, Yeyang Toji, Lorraine H. Tyler-Smith, Chris Brooks, Lisa D. Felsenfeld, Adam L. McEwen, Jean E. Abdallah, Assya Juenger, Christopher R. Clemm, Nicholas C. Collins, Francis S. Duncanson, Audrey Green, Eric D. Guyer, Mark S. Peterson, Jane L. Schafer, Alan J. Abecasis, Goncalo R. Altshuler, David L. Auton, Adam Brooks, Lisa D. Durbin, Richard M. Gibbs, Richard A. Hurles, Matt E. McVean, Gil A. CA 1000 Genomes Project Consortium TI A map of human genome variation from population-scale sequencing SO NATURE LA English DT Article ID WIDE ASSOCIATION; GENE-EXPRESSION; RECOMBINATION HOTSPOTS; MEIOTIC RECOMBINATION; GENOTYPE IMPUTATION; RARE VARIANTS; HAPLOTYPE MAP; NUCLEOTIDE; DISEASES; COMMON AB The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype. Here we present results of the pilot phase of the project, designed to develop and compare different strategies for genome-wide sequencing with high-throughput platforms. We undertook three projects: low-coverage whole-genome sequencing of 179 individuals from four populations; high-coverage sequencing of two mother-father-child trios; and exon-targeted sequencing of 697 individuals from seven populations. We describe the location, allele frequency and local haplotype structure of approximately 15 million single nucleotide polymorphisms, 1 million short insertions and deletions, and 20,000 structural variants, most of which were previously undescribed. We show that, because we have catalogued the vast majority of common variation, over 95% of the currently accessible variants found in any individual are present in this data set. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders. We demonstrate how these results can be used to inform association and functional studies. From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 10(-8) per base pair per generation. We explore the data with regard to signatures of natural selection, and identify a marked reduction of genetic variation in the neighbourhood of genes, due to selection at linked sites. These methods and public data will support the next phase of human genetic research. C1 [Gabriel, Stacey B.; Lander, Eric S.; Lander, Eric S.; Ambrogio, Lauren; Cibulskis, Kristian; Fennell, Tim J.; Jaffe, David B.; Shefler, Erica; Sougnez, Carrie L.; Daly, Mark J.; DePristo, Mark A.; Ball, Aaron D.; Banks, Eric; Bloom, Toby; Cibulskis, Kristian; Fennell, Tim J.; Garimella, Kiran V.; Handsaker, Robert E.; Hanna, Matt; Hartl, Chris; Jaffe, David B.; Kernytsky, Andrew M.; Korn, Joshua M.; Li, Heng; Maguire, Jared R.; McCarroll, Steven A.; McKenna, Aaron; Nemesh, James C.; Philippakis, Anthony A.; Poplin, Ryan E.; Rivas, Manuel A.; Sabeti, Pardis C.; Schaffner, Stephen F.; Fu, Yutao; Banks, Eric; DePristo, Mark A.; Hartl, Chris; Korn, Joshua M.; Nemesh, James C.; Garimella, Kiran V.; Sougnez, Carrie L.; Wilkinson, Jane; Altshuler, David L.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Churcher, Carol; Coffey, Alison; Cox, Anthony; Palotie, Aarno; Tyler-Smith, Chris; Coffey, Allison; Palotie, Aarno; Scott, Carol; Tyler-Smith, Chris] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Altshuler, David L.] Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02115 USA. [Abecasis, Goncalo R.; Korbel, Jan O.; Li, Yun; Anderson, Paul; Chen, Wei; Ding, Jun; Kang, Hyun Min; Sidore, Carlo; Snyder, Matthew; Zhan, Xiaowei; Zoellner, Sebastian; Blackwell, Tom; Snyder, Matthew] Univ Michigan, Ctr Stat Genet & Biostat, Ann Arbor, MI 48109 USA. [Bentley, David R.; Gormley, Niall; Humphray, Sean; Kingsbury, Zoya; Koko-Gonzales, Paula; Stone, Jennifer; Timmermann, Bernd; Bauer, Markus; Cheetham, R. Keira; Cox, Tony; Eberle, Michael; James, Terena; Kahn, Scott; Murray, Lisa; Kahn, Scott] Illumina Cambridge Ltd, Saffron Walden CB10 1XL, Essex, England. [Chakravarti, Aravinda; Abdallah, Assya] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. [Clark, Andrew G.; Degenhardt, Jeremiah; Keinan, Alon; Ma, Xia; Reynolds, Andy] Cornell Univ, Ctr Comparative & Populat Genom, Ithaca, NY 14850 USA. [De la Vega, Francisco M.; Hyland, Fiona C. L.; Sakarya, Onur; Sun, Yongming A.] Life Technol, Foster City, CA 94404 USA. [Donnelly, Peter; Auton, Adam; Iqbal, Zamin; Lunter, Gerton; Marchini, Jonathan L.; Myers, Simon; McVean, Gil A.] Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Egholm, Michael] Pall Corp, Port Washington, NY 11050 USA. [Flicek, Paul; Clarke, Laura; Cunningham, Fiona; Herrero, Javier; Keenen, Stephen; Kulesha, Eugene; Leinonen, Rasko; McLaren, WilliamM.; Radhakrishnan, Rajesh; Smith, Richard E.; Zalunin, Vadim; Zheng-Bradley, Xiangqun] European Bioinformat Inst, Cambridge CB10 1SD, England. [Gibbs, Richard A.; Deiros, David; Metzker, Mike; Muzny, Donna; Reid, Jeff; Bainbridge, Matthew; Challis, Danny; Sabo, Aniko; Yu, Fuli; Yu, Jin; Coafra, Cristian; Dinh, Huyen; Kovar, Christie; Lee, Sandy; Nazareth, Lynne] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Knoppers, Bartha M.; Parkhomchuk, Dimitri V.] McGill Univ, Ctr Genom & Policy, Montreal, PQ H3A 1A4, Canada. [Lehrach, Hans; Sudbrak, Ralf; Borodina, Tatiana A.; Davydov, Alexey N.; Marquardt, Peter; Mertes, Florian; Nietfeld, Wilfiried; Soldatov, Aleksey V.; Timmermann, Bernd; Tolzmann, Marius; Albrecht, Marcus W.; Amstislavskiy, Vyacheslav S.; Herwig, Ralf] Max Planck Inst Mol Genet, D-14195 Berlin, Germany. [Mardis, Elaine R.; Wilson, Richard K.; Dooling, David; Fulton, Lucinda; Fulton, Robert; Weinstock, George; McLellan, Mike D.; Weinstock, George; Wallis, John W.; Wendl, Michael C.; Zhang, Qunyuan; Chen, Ken; Chinwalla, Asif; Ding, Li; McLellan, Mike D.; Wallis, John W.; Koboldt, Daniel C.] Washington Univ, Sch Med, Genome Ctr, St Louis, MO 63108 USA. [Marchini, Jonathan L.; Moutsianas, Loukas; Myers, Simon; Tumian, Afidalina; McVean, Gil A.] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Nickerson, DebbieA.; Aksay, Gozde; Sudmant, Peter H.; Kidd, Jeffrey M.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. [Schafer, Alan J.; Duncanson, Audrey] Wellcome Trust Res Labs, London NW1 2BE, England. [Sherry, Stephen T.; Agarwala, Richa; Khouri, Hodam.; Morgulis, Aleksandr O.; Paschall, Justin E.; Phan, Lon D.; Rotmistrovsky, Kirill E.; Sanders, Robert D.; Shumway, Martin F.; Xiao, Chunlin; Khouri, Hoda M.] US Natl Inst Hlth, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. [Wang, Jun; Li, Jingxiang; Jian, Min; Li, Guoqing; Li, Ruiqiang; Liang, Huiqing; Tian, Geng; Wang, Bo; Wang, Jian; Wang, Wei; Yang, Huanming; Zhang, Xiuqing; Zheng, Huisong; Fang, Xiaodong; Guo, Xiaosen; Li, Yingrui; Luo, Ruibang; Tai, Shuaishuai; Wu, Honglong; Zheng, Hancheng; Zheng, Xiaole; Zhou, Yan; Luo, Ruibang; Li, Taosha; Su, Yeyang] BGI Shenzhen, Shenzhen 518083, Peoples R China. Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark. [McKernan, Kevin J.; Costa, Gina L.; Ichikawa, Jeffry K.; Lee, Clarence C.; Fu, Yutao; Manning, Jonathan M.; McLaughlin, Stephen F.; Peckham, Heather E.; Tsung, Eric F.] Life Technol, Beverly, MA 01915 USA. [Dahl, Andreas] Biotechnol Ctr TU Dresden, Deep Sequencing Grp, D-01307 Dresden, Germany. [Rosenstiel, Philip; Schreiber, Stefan] Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany. [Affourtit, Jason; Ashworth, Dana; Attiya, Said; Bachorski, Melissa; Buglione, Eli; Burke, Adam; Caprio, Amanda; Celone, Christopher; Clark, Shauna; Conners, David; Desany, Brian; Gu, Lisa; Guccione, Lorri; Kao, Kalvin; Kebbel, Andrew; Knowlton, Jennifer; Labrecque, Matthew; McDade, Louise; Mealmaker, Craig; Minderman, Melissa; Nawrocki, Anne; Niazi, Faheem; Pareja, Kristen; Ramenani, Ravi; Riches, David; Song, Wanmin; Turcotte, Cynthia; Wang, Shally; Knight, James; Winer, Roger] Roche Appl Sci, Branford, CT 06405 USA. [Palotie, Aarno; Palotie, Aarno] Univ Helsinki, Dept Med Genet, Inst Mol Med FIMM, FIN-00290 Helsinki, Finland. [Palotie, Aarno; Palotie, Aarno] Helsinki Univ Hosp, Helsinki 00290, Finland. [De Witte, Anniek; Giles, Shane] Agilent Technol, Santa Clara, CA 95051 USA. [Marth, Gabor T.; Garrison, Erik P.; Indap, Amit; Kural, Deniz; Lee, Wan-Ping; Leong, Wen Fung; Stewart, Chip; Ward, Alistair N.; Wu, Jiantao] Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. [Huang, Weichun] US Natl Inst Hlth, Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. [Quinlan, Aaron R.] Univ Virginia, Sch Med, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. [Stromberg, Michael P.] Illumina, San Diego, CA 92121 USA. [Lee, Charles; Mills, Ryan E.; Shi, Xinghua; Altshuler, David L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Shi, Xinghua; Altshuler, David L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Browning, Brian L.] Univ Washington, Dept Med, Div Gen Med, Seattle, WA 98195 USA. [Grossman, Sharon R.; Sabeti, Pardis C.; Shlyakhter, Ilya A.] Harvard Univ, Ctr Syst Biol, Dept Organism & Evolut Biol, Cambridge, MA 02138 USA. [Price, Alkes] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Cooper, David N.; Ball, Edward V.; Mort, Matthew; Phillips, Andrew D.; Stenson, Peter D.] Cardiff Univ, Inst Med Genet, Cardiff CF14 4XN, Wales. [Sebat, Jonathan] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. [Makarov, Vladimir] Mt Sinai Sch Med, Seaver Autism Ctr, New York, NY 10029 USA. [Makarov, Vladimir] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Ye, Kenny] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Yoon, Seungtai C.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA. [Bustamante, Carlos D.; Boyko, Adam; Gravel, Simon; Kaganovich, Mark; Lacroute, Phil; Du, Jiang; Lam, Hugo Y. K.; Urban, Alexander E.; Kidd, Jeffrey M.; Snyder, Michael; Grubert, Fabian; Lam, Hugo Y. K.; Urban, Alexander E.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Gutenkunst, Ryan N.] Univ Arizona, Dept Mol & Cellular Biol, Tucson, AZ 85721 USA. [Korbel, Jan O.; Stuetz, Adrian M.] Genome Biol Res Unit, European Mol Biol Lab, D-69117 Heidelberg, Germany. [Ye, Kai] Leiden Univ Med Ctr, Mol Epidemiol Sect, NL-2333 ZA Leiden, Netherlands. [Batzer, Mark A.; Konkel, Miriam K.; Walker, Jerilyn A.] Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA. [Craig, David W.; Beckstrom-Sternberg, Steve M.; Christoforides, Alexis; Kurdoglu, Ahmet A.; Pearson, Johnv.; Sinari, Shripad A.; Tembe, Waibhav D.] Translat Genom Res Inst, Phoenix, AZ 85004 USA. [Haussler, David; Hinrichs, Angie S.; Katzman, Sol J.; Kern, Andrew; Kuhn, Robert M.] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA. [Przeworski, Molly] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Przeworski, Molly] Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA. [Hernandez, Ryan D.; Howie, Bryan; Kelley, Joanna L.; Melton, S. Cord] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Cookson, William O.; Moffatt, Miriam F.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW7 2, England. [Lathrop, Mark] Ctr Natl Genotypage, F-91000 Evry, France. [Liang, Liming] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Liang, Liming] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Scheet, Paul] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Awadalla, Philip] Univ Montreal, Fac Med, Dept Pediat, Ste Justine Hosp Res Ctr, Montreal, PQ H3T IC5, Canada. [Casals, Ferran; Idaghdour, Youssef; Keebler, John; Stone, Eric A.; Zilversmit, Martine] Univ Montreal, Dept Med, Ctr Hosp, Univ Montreal Res Ctr, Montreal, PQ H2L 2W5, Canada. [Jorde, Lynn; Xing, Jinchuan; Xing, Jinchuan; Jorde, Lynn] Univ Utah, Sch Med, Eccles Inst Human Genet, Salt Lake City, UT 84112 USA. [Eichler, Evan E.; Alkan, Can; Alkan, Can] Univ Washington, Sch Med, Depat Genome Sci, Seattle, WA 98195 USA. [Eichler, Evan E.; Alkan, Can; Alkan, Can] Howard Hughes Med Inst, Seattle, WA 98195 USA. [Hajirasouliha, Iman; Hormozdiari, Fereydoun; Sahinalp, S. Cenk; Hajirasouliha, Iman; Hormozdiari, Fereydoun] Simon Fraser Univ, Dept Comp Sci, Burnaby, BC V5A 1S6, Canada. [Albers, Cornelis A.] Univ Cambridge, Dept Haematol, Cambridge CB2 1TN, England. [Albers, Cornelis A.] Natl Hlth Serv Blood & Transplant, Cambridge CB2 1TN, England. [Dermitzakis, Emmanouil T.; Montgomery, Stephen B.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. [Jin, Hanjun] Korea Natl Inst Hlth, Ctr Genome Sci, Seoul 122701, South Korea. [Abyzov, Alexej; Habegger, Lukas; Haraksingh, Rajini; Gerstein, Mark B.; Abyzov, Alexej; Haraksingh, Rajini; Jee, Justin; Leng, Jing; Mu, Xinmeng Jasmine] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA. [Balasubramanian, Suganthi; Bjornson, Robert; Gerstein, Mark B.; Du, Jiang] Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA. [Abyzov, Alexej; Khurana, Ekta; Urban, Alexander E.; Zhang, Zhengdong; Balasubramanian, Suganthi] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. [Urban, Alexander E.; Urban, Alexander E.] Stanford Univ, Dept Psychiat & Behav Studies, Stanford, CA 94305 USA. [Gharani, Neda; Toji, Lorraine H.] Corell Inst, Camden, NJ 08103 USA. [Kaye, Jane S.] Univ Oxford, Ctr Hlth Law & Emerging Technol, Oxford OX3 7LF, England. [Kent, Alastair] Genet Alliance, London N1 3QP, England. [McGuire, Amy L.] Baylor Coll Med, Ctr Med Eth & Hlth Policy, Houston, TX 77030 USA. [Ossorio, Pilar N.] Univ Wisconsin Madison, Dept Med Hist & Bioeth, Madison, WI 53706 USA. [Rotimi, Charles N.] US Natl Inst Hlth, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA. [Brooks, Lisa D.; Felsenfeld, Adam L.; McEwen, Jean E.; Clemm, Nicholas C.; Green, Eric D.; Guyer, Mark S.; Peterson, Jane L.; Brooks, Lisa D.] US Natl Inst Hlth, NHGRI, Bethesda, MD 20892 USA. [Abdallah, Assya] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20037 USA. [Juenger, Christopher R.] US FDA, Rockville, MD 20857 USA. RP Durbin, RM (reprint author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SA, England. RI Wang, Jun/B-9503-2016; Casals, Ferran/H-4347-2015; Wang, Jun/C-8434-2016; Lunter, Gerton/H-4939-2016; Pearson, John/F-2249-2011; Mu, Xinmeng/P-2562-2016; Stone, Eric/Q-7840-2016; Mills, Ryan/A-1979-2011; Dahl, Andreas/E-3783-2017; Ye, Kai/B-3640-2012; Cartwright, Reed/A-9707-2009; Wendl, Michael/A-2741-2008; Rosenstiel, Philip/A-5137-2009; Korbel, Jan/G-6470-2012; Kelley, Joanna/H-1693-2012; Dermitzakis, Emmanouil/B-7687-2013; Khurana, Ekta/C-4933-2013; Abyzov, Alexej/M-4284-2013; Le, Quang/A-4861-2012; Myers, Simon/A-6792-2015; Tumian, Afidalina/J-4404-2014; Li, Yingrui/K-1064-2015; Albers, Kees/A-4170-2015; Li, Heng/D-9344-2011; De La Vega, Francisco/H-3832-2011; Cooper, David/H-4384-2011; Xing, Jinchuan/A-2489-2012; Sincan, Murat /A-3794-2010; Alkan, Can/D-2982-2009; Abecasis, Goncalo/B-7840-2010; Chen, Ken/A-1074-2009; Altshuler, David/A-4476-2009; MacArthur, Daniel/E-3275-2010; Browning, Brian/A-1178-2010; Schreiber, Stefan/B-6748-2008; Schaffner, Stephen/D-1189-2011; Ding, Jun/G-3918-2011 OI Hinrichs, Angie/0000-0002-1697-1130; Lunter, Gerton/0000-0002-3798-2058; Iqbal, Zamin/0000-0001-8466-7547; Keane, Thomas/0000-0001-7532-6898; Abecasis, Goncalo/0000-0003-1509-1825; Ayub, Qasim/0000-0003-3291-0917; Herrero, Javier/0000-0001-7313-717X; Clarke, Laura/0000-0002-5989-6898; Yu, Jin/0000-0002-2990-6602; Flicek, Paul/0000-0002-3897-7955; McLaren, William/0000-0001-6218-1116; Walter, Klaudia/0000-0003-4448-0301; Wang, Jun/0000-0002-2113-5874; Leinonen, Rasko/0000-0002-2639-7187; Kulesha, Eugene/0000-0002-4285-6232; Haraksingh, Rajini/0000-0002-6644-8874; Zalunin, Vadim/0000-0002-7722-1958; Kelley, Joanna/0000-0002-7731-605X; Zheng Bradley, Xiangqun/0000-0002-9324-2708; Abyzov, Alexej/0000-0001-5405-6729; Keenan, Stephen/0000-0002-9141-7690; Sebat, Jonathan/0000-0002-9087-526X; Sudmant, Peter/0000-0002-9573-8248; Kidd, Jeffrey/0000-0002-9631-1465; Radhakrishnan, Rajesh/0000-0001-7170-699X; Sidore, Carlo/0000-0001-7504-7477; Lindsay, Sarah/0000-0002-0965-3070; Casals, Ferran/0000-0002-8941-0369; Wang, Jun/0000-0002-8540-8931; Pearson, John/0000-0003-0904-4598; Mu, Xinmeng/0000-0002-8079-0828; Mills, Ryan/0000-0003-3425-6998; Dahl, Andreas/0000-0002-2668-8371; Stuetz, Adrian/0000-0001-7650-3470; Cunningham, Fiona/0000-0002-7445-2419; Quinlan, Aaron/0000-0003-1756-0859; Durbin, Richard/0000-0002-9130-1006; Rosenstiel, Philip/0000-0002-9692-8828; Korbel, Jan/0000-0002-2798-3794; Le, Quang/0000-0002-3715-210X; Myers, Simon/0000-0002-2585-9626; Tumian, Afidalina/0000-0003-2763-6677; Albers, Kees/0000-0003-4115-3727; Li, Heng/0000-0003-4874-2874; Cooper, David/0000-0002-8943-8484; Alkan, Can/0000-0002-5443-0706; Altshuler, David/0000-0002-7250-4107; Browning, Brian/0000-0001-6454-6633; Schreiber, Stefan/0000-0003-2254-7771; FU Wellcome Trust [WT089088/Z/09/Z, WT085532AIA, WT086084/Z/08/Z, WT081407/Z/06/Z, WT075491/Z/04, WT077009]; Medical Research Council [G0801823]; British Heart Foundation [RG/09/012/28096]; The Leverhulme Trust; EPSRC; Louis-Jeantet Foundation; Swiss National Science Foundation; NGI/EBI [050-72-436]; National Basic Research Program of China (973 program) [2011CB809200]; National Natural Science Foundation of China [30725008, 30890032, 30811130531, 30221004]; Chinese 863 program [2006AA02Z177, 2006AA02Z334, 2006AA02A302, 2009AA022707]; Shenzhen Municipal Government of China [JC200903190767A, JC200903190772A, CXB200903110066A, ZYC200903240077A, ZYC200903240076A, ZYC200903240080A]; Danish Natural Science Research Council; German Research Foundation (Deutsche Forschungsgemeinschaft); BMBF [01GS08201, PREDICT 0315428A]; BMBF NGFN PLUS; EU [242257]; Max Planck Society; Genome Quebec; Ministry of Economic Development, Innovation and Trade [PSR-SIIRI-195]; National Library of Medicine; National Institute of Environmental Health Sciences; NIH [P41HG4221, U01HG5209, P41HG4222, R01GM59290, R01GM72861, R01HG2651, R01MH84698, U01HG5214, P01HG4120, U54HG2750, U54HG2757, U01HG5210, U01HG5208, U01HG5211, R01HG3698, R01HG4719, RC2HG5552, R01HG3229, P50HG2357, R01HG4960, P41HG2371, U41HG4568, R01HG4333]; BWF and Packard Foundation; Pew Charitable Trust; NSF; [S10RR025056] FX We thank many people who contributed to this project: K. Beal, S. Fitzgerald, G. Cochrane, V. Silventoinen, P. Jokinen, E. Birney and J. Ahringer for comments on the manuscript; T. Hunkapiller and Q. Doan for their advice and coordination; N. Kalin, F. Laplace, J. Wilde, S. Paturej, I. Kuhndahl, J. Knight, C. Kodira and M. Boehnke for valuable discussions; Z. Cheng, S. Sajjadian and F. Hormozdiari for assistance in managing data sets; and D. Leja for help with the figures. We thank the Yoruba in Ibadan, Nigeria, the Han Chinese in Beijing, China, the Japanese in Tokyo, Japan, the Utah CEPH community, the Luhya in Webuye, Kenya, the Toscani in Italia, and the Chinese in Denver, Colorado, for contributing samples for research. This research was supported in part by Wellcome Trust grants WT089088/Z/09/Z to R. M. D.; WT085532AIA to P. F.; WT086084/Z/08/Z to G. A. M.; WT081407/Z/06/Z to J. S. K.; WT075491/Z/04 to G. L.; WT077009 to C.T.-S.; Medical Research Council grant G0801823 to J. L. M.; British Heart Foundation grant RG/09/012/28096 to C. A.; The Leverhulme Trust and EPSRC studentships to L. M. and A. T.; the Louis-Jeantet Foundation and Swiss National Science Foundation in support of E. T. D. and S. B. M.; NGI/EBI fellowship 050-72-436 to K.Y.; a National Basic Research Program of China (973 program no. 2011CB809200); the National Natural Science Foundation of China (30725008, 30890032, 30811130531, 30221004); the Chinese 863 program (2006AA02Z177, 2006AA02Z334, 2006AA02A302, 2009AA022707); the Shenzhen Municipal Government of China (grants JC200903190767A, JC200903190772A, ZYC200903240076A, CXB200903110066A, ZYC200903240077A, ZYC200903240076A and ZYC200903240080A); the Ole Romer grant from the Danish Natural Science Research Council; an Emmy Noether Fellowship of the German Research Foundation (Deutsche Forschungsgemeinschaft) to J.O.K.; BMBF grant 01GS08201; BMBF grant PREDICT 0315428A to R. H.; BMBF NGFN PLUS and EU 6th framework READNA to S. S.; EU 7th framework 242257 to A. V. S.; the Max Planck Society; a grant from Genome Quebec and the Ministry of Economic Development, Innovation and Trade, PSR-SIIRI-195 to P. A.; the Intramural Research Program of the NIH; the National Library of Medicine; the National Institute of Environmental Health Sciences; and NIH grants P41HG4221 and U01HG5209 to C. L.; P41HG4222 to J. S.; R01GM59290 to L. B. J. and M. A. B.; R01GM72861 to M. P.; R01HG2651 and R01MH84698 to G. R. A.; U01HG5214 to G. R. A. and A. C.; P01HG4120 to E. E. E.; U54HG2750 to D. L. A.; U54HG2757 to A. C.; U01HG5210 to D. C.; U01HG5208 to M. J. D.; U01HG5211 to R. A. G.; R01HG3698, R01HG4719 and RC2HG5552 to G. T. M.; R01HG3229 to C. D. B. and A. G. C.; P50HG2357 to M. S.; R01HG4960 to B. L. B; P41HG2371 and U41HG4568 to D. H.; R01HG4333 to A. M. L.; U54HG3273 to R. A. G.; U54HG3067 to E. S. L.; U54HG3079 to R. K. W.; N01HG62088 to the Coriell Institute; S10RR025056 to the Translational Genomics Research Institute; Al Williams Professorship funds for M. B. G.; the BWF and Packard Foundation support for P. C. S.; the Pew Charitable Trusts support for G. R. A.; and an NSF Minority Postdoctoral Fellowship in support of R. D. H. E. E. E. is an HHMI investigator, M. P. is an HHMI Early Career Scientist, and D. M. A. is Distinguished Clinical Scholar of the Doris Duke Charitable Foundation. NR 50 TC 2999 Z9 3054 U1 70 U2 580 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD OCT 28 PY 2010 VL 467 IS 7319 BP 1061 EP 1073 DI 10.1038/nature09534 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 671XW UT WOS:000283548600039 ER PT J AU Lo, SC Pripuzova, N Li, BJ Komaroff, AL Hung, GC Wang, R Alter, HJ AF Lo, Shyh-Ching Pripuzova, Natalia Li, Bingjie Komaroff, Anthony L. Hung, Guo-Chiuan Wang, Richard Alter, Harvey J. TI Reply to Erlwein et al. and Martin: On detection of murine leukemia virus-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Letter C1 [Lo, Shyh-Ching; Pripuzova, Natalia; Li, Bingjie; Hung, Guo-Chiuan] US FDA, Tissue Microbiol Lab, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. [Lo, Shyh-Ching; Pripuzova, Natalia; Li, Bingjie; Hung, Guo-Chiuan] US FDA, Div Human Tissues, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Komaroff, Anthony L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Wang, Richard; Alter, Harvey J.] NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Lo, SC (reprint author), US FDA, Tissue Microbiol Lab, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. EM shyhching.lo@fda.hhs.gov NR 5 TC 1 Z9 1 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 26 PY 2010 VL 107 IS 43 BP E163 EP E164 DI 10.1073/pnas.1012780107 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 673QG UT WOS:000283677400003 ER PT J AU Vellozzi, C Broder, KR Haber, P Guh, A Nguyen, M Cano, M Lewis, P McNeil, MM Bryant, M Singleton, J Martin, D DeStefano, F AF Vellozzi, Claudia Broder, Karen R. Haber, Penina Guh, Alice Nguyen, Michael Cano, Maria Lewis, Paige McNeil, Michael M. Bryant, Marthe Singleton, James Martin, David DeStefano, Frank TI Adverse events following influenza A (H1N1) 2009 monovalent vaccines reported to the Vaccine Adverse Event Reporting System, United States, October 1, 2009-January 31, 2010 SO VACCINE LA English DT Article DE H1N1 vaccines; Vaccine safety; Post-marketing surveillance ID GUILLAIN-BARRE-SYNDROME; ROTAVIRUS VACCINE; SAFETY; CHILDREN; IMMUNIZATION; INTUSSUSCEPTION; ASSOCIATION; ANAPHYLAXIS; PROGRAM; ADULTS AB The United States (US) influenza A (H1N1) 2009 monovalent (2009-H1N1) vaccination program began in October 2009. Reports to the vaccine adverse event reporting system (VAERS), a US spontaneous reporting system, were reviewed to identify potential rare events or unusual adverse event (AE) patterns after 2009-H1N1 vaccination. The adverse event profile after 2009-H1N1 vaccine in VAERS (similar to 10,000 reports) was consistent with that of seasonal influenza vaccines, although the reporting rate was higher after 2009-H1N1 than seasonal influenza vaccines, this may be, at least in part, a reflection of stimulated reporting. Death, Guillain-Barre syndrome and anaphylaxis reports after 2009-H1N1 vaccination were rare (each <2 per million doses administered). Published by Elsevier Ltd. C1 [Vellozzi, Claudia; Broder, Karen R.; Haber, Penina; Guh, Alice; Cano, Maria; Lewis, Paige; McNeil, Michael M.; DeStefano, Frank] Ctr Dis Control & Prevent, Immunizat Safety Off, Div Hlth Care Qual Promot, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA. [Nguyen, Michael; Bryant, Marthe; Martin, David] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Singleton, James] Ctr Dis Control & Prevent, Immunizat Serv Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. RP Vellozzi, C (reprint author), Ctr Dis Control & Prevent, ISO DHQP, 1600 Clifton Rd NE,Mailstop D-26, Atlanta, GA 30333 USA. EM bno1@cdc.gov FU CDC; FDA FX The study was implemented by the Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA). The only funds used were from CDC and FDA budgets. This study had no external sponsors. NR 45 TC 79 Z9 82 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD OCT 21 PY 2010 VL 28 IS 45 BP 7248 EP 7255 DI 10.1016/j.vaccine.2010.09.021 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 677WY UT WOS:000284026600004 PM 20850534 ER PT J AU Merkel, TJ Perera, PY Kelly, VK Verma, A Llewellyn, ZN Waldmann, TA Mosca, JD Perera, LP AF Merkel, Tod J. Perera, Pin-Yu Kelly, Vanessa K. Verma, Anita Llewellyn, Zara N. Waldmann, Thomas A. Mosca, Joseph D. Perera, Liyanage P. TI Development of a highly efficacious vaccinia-based dual vaccine against smallpox and anthrax, two important bioterror entities SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE biodefense; IL-15; bioterrorism ID BACILLUS-ANTHRACIS; PROTECTIVE ANTIGEN; T-CELLS; SPORES; MICE; INTERLEUKIN-15; ANTIBODIES; CHALLENGE; CORRELATE; IMMUNITY AB Bioterrorism poses a daunting challenge to global security and public health in the 21st century. Variola major virus, the etiological agent of smallpox, and Bacillus anthracis, the bacterial pathogen responsible for anthrax, remain at the apex of potential pathogens that could be used in a bioterror attack to inflict mass casualties. Although licensed vaccines are available for both smallpox and anthrax, because of inadequacies associated with each of these vaccines, serious concerns remain as to the deployability of these vaccines, especially in the aftermath of a bioterror attack involving these pathogens. We have developed a single vaccine (Wyeth/IL15/PA) using the licensed Wyeth smallpox vaccine strain that is efficacious against both smallpox and anthrax due to the integration of immune-enhancing cytokine IL-15 and the protective antigen (PA) of B. anthracis into the Wyeth vaccinia virus. Integration of IL-15 renders Wyeth vaccinia avirulent in immunodeficient mice and enhances anti-vaccinia immune responses. Wyeth/IL-15/PA conferred sterile protection against a lethal challenge of B. anthracis Ames strain spores in rabbits. A single dose of Wyeth/IL-15/PA protected 33% of the vaccinated A/J mice against a lethal spore challenge 72 h later whereas a single dose of licensed anthrax vaccine protected only 10%. Our dual vaccine Wyeth/IL-15/PA remedies the inadequacies associated with the licensed vaccines, and the inherent ability of Wyeth vaccinia virus to be lyophilized without loss of potency makes it cold-chain independent, thus simplifying the logistics of storage, stockpiling, and field delivery in the event of a bioterror attack involving smallpox or anthrax. C1 [Waldmann, Thomas A.; Perera, Liyanage P.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Merkel, Tod J.; Kelly, Vanessa K.; Verma, Anita] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Perera, Pin-Yu] Vet Affairs Med Ctr, Washington, DC 20422 USA. [Llewellyn, Zara N.] So Res Inst, Birmingham, AL 35255 USA. [Mosca, Joseph D.] JDM Technol, Ellicott City, MD 21042 USA. RP Waldmann, TA (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM tawald@helix.nih.gov; pereral@mail.nih.gov FU National Cancer Institute; Trans-National Institutes of Health/Food and Drug Administration; Center for Cancer Research; National Institutes of Health FX We thank Dr. Toyoko Hiroi for assistance with the graphics and Ms. Jean R. Decker for contractual administrative support. We gratefully acknowledge the receipt of reagents from the Biodefense and Emerging Infections Research Resources Repository (BEI Resources, National Institute of Allergy and Infectious Diseases) for this study. This work was supported in part by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research, National Institutes of Health, and by a 3-y competitive research funding award (to L. P. P.) from the Trans-National Institutes of Health/Food and Drug Administration Intramural Biodefense Program. NR 35 TC 14 Z9 15 U1 2 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 19 PY 2010 VL 107 IS 42 BP 18091 EP 18096 DI 10.1073/pnas.1013083107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 667HV UT WOS:000283184800046 PM 20921397 ER PT J AU Chu, C Lugovtsev, V Lewis, A Betenbaugh, M Shiloach, J AF Chu, Chia Lugovtsev, Vladimir Lewis, Andrew Betenbaugh, Michael Shiloach, Joseph TI Production and antigenic properties of influenza virus from suspension MDCK-siat7e cells in a bench-scale bioreactor SO VACCINE LA English DT Article DE Hemagglutinin; Mammalian cell line; Anchorage-independent; Vaccine ID PANDEMIC INFLUENZA; VACCINES; CULTURE; GROWTH; REPLICATION; SERUM; VERO; EGG AB In efforts to overcome limitations associated with egg-based influenza vaccines, mammalian cell substrates have gradually emerged as potential production platforms. Recently, a suspension Madin Darby canine kidney (MDCK) cell line for influenza virus production was created by expressing the human siat7e gene. To examine the broad susceptibility of this novel cell line, the scalability of the production process, and the antigenic stability of cell-derived progeny viruses, infection experiments using four current influenza vaccine strains (A/California/07/2009 X-179A H1N1, A/Brisbane/59/2007 IVR-148 H1N1, A/Uruguay/716/2007 X-175C H3N2, and B/Brisbane/60/2008) were performed. In small-scale experiments, this cell line was found to support high-titer replication of all four virus strains. Subsequently, production in a bench-scale bioreactor and the antigenic characteristics of progeny viruses were assessed. High titers of hemagglutinin (at least 1:512) were produced in a 2-L bench-scale bioreactor with all four strains. Immunoblot results demonstrated higher yields in the cells than those obtained in chicken embryonated eggs with three of the four tested strains. Progeny viruses collected after serial passages in this cell line exhibited minimal mutations in the HA-encoding gene. Hemagglutination inhibition (HAI) assays using ferret antiserum confirmed the antigenic stability. As a proof-of-concept this work demonstrates that by using a proper strategy, high yields of biologically active hemagglutinin can be produced from scalable cultures of suspension MDCK-siat7e cells. Published by Elsevier Ltd. C1 [Chu, Chia; Shiloach, Joseph] NIDDK, NIH, Bethesda, MD 20892 USA. [Chu, Chia; Betenbaugh, Michael] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA. [Lugovtsev, Vladimir; Lewis, Andrew] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Shiloach, J (reprint author), 9000 Rockville Pike Bldg 14A Rm 173, Bethesda, MD 20892 USA. EM chuchia@mail.nih.gov; vladimir.lugovtsev@fda.hhs.gov; andrew.lewis@fda.hhs.gov; beten@jhu.edu; yossi@nih.gov RI Betenbaugh, Michael J./A-3252-2010 OI Betenbaugh, Michael J./0000-0002-6336-4659 FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health FX Funding was provided by the Intramural program at the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. The authors would like to thank Gideon Foseh for his assistance in the characterization of the MDCK cell tumorigenic phenotype Dr. Alejandro Negrete for his assistance with bioreactor setups, and Mrs. D. Livnat for critical proof reading of the manuscript. NR 26 TC 6 Z9 7 U1 3 U2 18 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD OCT 18 PY 2010 VL 28 IS 44 BP 7193 EP 7201 DI 10.1016/j.vaccine.2010.08.059 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 677HT UT WOS:000283980400009 PM 20800699 ER PT J AU Teeparuksapun, K Hedstrom, M Wong, EY Tang, SX Hewlett, IK Mattiasson, B AF Teeparuksapun, Kosin Hedstrom, Martin Wong, Eric Y. Tang, Shixing Hewlett, Indira K. Mattiasson, Bo TI Ultrasensitive Detection of HIV-1 p24 Antigen Using Nanofunctionalized Surfaces in a Capacitive Immunosensor SO ANALYTICAL CHEMISTRY LA English DT Article ID BIOSENSOR; PREVENTION; ELECTRODES; CAMEROON; TYPE-1; TESTS AB The HIV-1 capsid protein, p24 antigen, is of considerable diagnostic interest because following HIV exposure it is detectable several days earlier than host-generated HIV antibodies (which are the target of almost all current tests used in the field) and can be used to design very sensitive assays without the need for PCR. Here, we present an ultrasensitive capacitive immunosensor that is capable of detecting subattogram per milliliter concentrations of p24 antigen, which to our knowledge is the lowest level of detection ever reported. Dilution studies using p24-spiked human plasma samples indicate that the immunosensor is robust against the interfering effects of a complex biological matrix. Moreover, the capacitive immunosensor assay is rapid (<20 min), label-free, and generates data in real-time, with a portable format in development. Additional optimization of the capture agents and/or surface chemistries may further improve performance, highlighting the potential of this platform to serve as a diagnostic tool for early detection of HIV in field settings. C1 [Teeparuksapun, Kosin; Hedstrom, Martin; Mattiasson, Bo] Lund Univ, Dept Biotechnol, SE-22100 Lund, Sweden. [Wong, Eric Y.; Tang, Shixing; Hewlett, Indira K.] US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Mattiasson, B (reprint author), Lund Univ, Dept Biotechnol, POB 124, SE-22100 Lund, Sweden. EM Bo.Mattiasson@biotek.lu.se NR 28 TC 32 Z9 32 U1 1 U2 27 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 OCT 15 PY 2010 VL 82 IS 20 BP 8406 EP 8411 DI 10.1021/ac102144a PG 6 WC Chemistry, Analytical SC Chemistry GA 663BX UT WOS:000282859100009 PM 20873850 ER PT J AU Holthoff, JH Woodling, KA Doerge, DR Burns, ST Hinson, JA Mayeux, PR AF Holthoff, Joseph H. Woodling, Kellie A. Doerge, Daniel R. Burns, Samuel T. Hinson, Jack A. Mayeux, Philip R. TI Resveratrol, a dietary polyphenolic phytoalexin, is a functional scavenger of peroxynitrite SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE Resveratrol; Peroxynitrite; Nitration; SIN-1; Cytotoxicity ID NITROGEN SPECIES GENERATION; CISPLATIN-INDUCED NEPHROTOXICITY; ACUTE KIDNEY INJURY; NITRIC-OXIDE; RENAL ISCHEMIA; TYROSINE NITRATION; OXIDATIVE STRESS; IN-VIVO; EBSELEN; SUPEROXIDE AB Oxidant damage from reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a major contributor to the cellular damage seen in numerous types of renal injury. Resveratrol (trans-3,4',5-trihydroxystilbene) is a phytoalexin found naturally in many common food sources. The anti-oxidant properties of resveratrol are of particular interest because of the fundamental role that oxidant damage plays in numerous forms of kidney injury. To examine whether resveratrol could block damage to the renal epithelial cell line, mIMCD-3, cells were exposed to the peroxynitrite donor 5-amino-3-(4-morpholinyl)-1,2,3-oxadiazolium chloride (SIN-1). Resveratrol produced a concentration-dependent inhibition of cytotoxicity induced by SIN-1. To examine the mechanism of protection, resveratrol was incubated with authentic peroxynitrite and found to block nitration of bovine serum albumin with an EC(50) value of 22.7 mu M, in contrast to the known RNS scavenger, N-acetyl-L-cysteine, which inhibited nitration with an EC(50) value of 439 mu M. These data suggested that resveratrol could provide functional protection by directly scavenging peroxynitrite. To examine whether resveratrol was a substrate for peroxynitrite oxidation, resveratrol was reacted with authentic peroxynitrite. Resveratrol nitration products and dimers were detected using liquid chromatograph with tandem electrospray mass spectrometry. Similar products were detected in the media of cells treated with SIN-1 and resveratrol. Taken collectively, the data suggest that resveratrol is able to provide functional protection of renal tubular cells, at least in part, by directly scavenging the RNS peroxynitrite. This property of resveratrol may contribute to the understanding of its anti-oxidant activities. (C) 2010 Elsevier Inc.Elsevier Inc. All rights reserved. C1 [Holthoff, Joseph H.; Burns, Samuel T.; Hinson, Jack A.; Mayeux, Philip R.] Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. [Woodling, Kellie A.; Doerge, Daniel R.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Mayeux, PR (reprint author), Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. EM prmayeux@uams.edu FU Nation Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [F30 DK085705, R01 DK075991] FX This work was supported by the Nation Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases Grants F30 DK085705 (JHH) and R01 DK075991 (PRM). The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration. NR 51 TC 43 Z9 48 U1 0 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD OCT 15 PY 2010 VL 80 IS 8 BP 1260 EP 1265 DI 10.1016/j.bcp.2010.06.027 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 651OK UT WOS:000281936800016 PM 20599800 ER PT J AU Malik, SM Liu, K Qiang, X Sridhara, R Tang, SH McGuinn, WD Verbois, SL Marathe, A Williams, GM Bullock, J Tornoe, C Lin, SC Ocheltree, T Vialpando, M Kacuba, A Justice, R Pazdur, R AF Malik, Shakun M. Liu, Ke Qiang, Xu Sridhara, Rajeshwari Tang, Shenghui McGuinn, W. David, Jr. Verbois, S. Leigh Marathe, Anshu Williams, Gene M. Bullock, Julie Tornoe, Christoffer Lin, Sue Ching Ocheltree, Terrance Vialpando, Milinda Kacuba, Alice Justice, Robert Pazdur, Richard TI Folotyn (Pralatrexate Injection) for the Treatment of Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma: U.S. Food and Drug Administration Drug Approval Summary SO CLINICAL CANCER RESEARCH LA English DT Article ID NON-HODGKINS-LYMPHOMAS; REAL CLASSIFICATION; PROGNOSTIC-FACTORS AB Purpose: On September 24, 2009, the U. S. Food and Drug Administration granted accelerated approval for Folotyn (pralatrexate injection, Allos Therapeutics, Inc.) as a single agent for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL); it is the first drug approved for this indication. Experimental Design: This review was based on study PDX-008, a phase II, single-arm, nonrandomized, open-label, international, multicenter trial, designed to evaluate the safety and efficacy of pralatrexate when administered concurrently with vitamin B(12) and folic acid supplementation in patients with relapsed or refractory PTCL. Results: The overall response rate was 27% in 109 evaluable patients [95% confidence interval (CI), 19-36%]. Twelve percent of 109 evaluable patients (95% CI, 7-20%)] had a response duration of >= 14 weeks. Six of these 13 patients achieved a complete response, and one patient had complete response unconfirmed. The most common grade 3 and 4 toxicities were thrombocytopenia, mucositis, and neutropenia. Conclusion: This accelerated approval was based on a response rate that is reasonably likely to predict clinical benefit in this heavily pretreated patient population with this rare disease. The applicant has committed to conducting postmarketing clinical trials to assess clinical benefit. The recommended starting dose of pralatrexate in patients with relapsed or refractory PTCL is 30 mg/m(2) via intravenous push over 3 to 5 min weekly for 6 weeks followed by a one-week rest (one cycle). Intramuscular injection of 1 mg vitamin B(12) should be administered every 8 to 10 weeks along with 1.0 mg folic acid given orally once a day. Clin Cancer Res; 16(20); 4921-7. (C) 2010 AACR. C1 [Malik, Shakun M.; Liu, Ke; Qiang, Xu; Sridhara, Rajeshwari; Tang, Shenghui; McGuinn, W. David, Jr.; Verbois, S. Leigh; Marathe, Anshu; Williams, Gene M.; Bullock, Julie; Tornoe, Christoffer; Lin, Sue Ching; Ocheltree, Terrance; Vialpando, Milinda; Kacuba, Alice; Justice, Robert; Pazdur, Richard] US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Malik, SM (reprint author), US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM shakun.malik@fda.hhs NR 18 TC 23 Z9 25 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 15 PY 2010 VL 16 IS 20 BP 4921 EP 4927 DI 10.1158/1078-0432.CCR-10-1214 PG 7 WC Oncology SC Oncology GA 663IT UT WOS:000282877700004 PM 20739433 ER PT J AU Hoffmann, M Fischer, M Whittaker, P AF Hoffmann, Maria Fischer, Markus Whittaker, Paul TI Evaluating the use of fatty acid profiles to identify deep-sea Vibrio isolates SO FOOD CHEMISTRY LA English DT Article DE Gas chromatography; Fatty acids; Vibrio species; Deep-sea Vibrio isolates ID SOUTHERN CHILE; PARAHAEMOLYTICUS AB Capillary gas chromatography with flame ionisation detection (GC-FID) was used to determine the cellular fatty acid (CFA) profiles of a number of Vibrio strains obtained from ATCC and grown on various media. This initial determination for optimal growth conditions, including type of medium and incubation temperature, for these various ATCC Vibrio species, was important for use in the subsequent evaluation of deep-sea Vibrio strains. The deep-sea Vibrios were obtained from Harbor Branch Oceanographic Institution (Fort Pierce, FL), and GC-FID analysis was used to determine whole cell fatty acid methyl esters (FAMEs) from the cells. The Vibrio strains were cultured for 24 h on a specific medium which included brain heart infusion (BHI) agar, trypticase soy agar (TSA), trypticase soy broth agar (TSBA), and Luria-Bertani (LB) agar. The temperature of incubation was 28 C for cells grown on TSA. TSBA, and LB and 35 C for BHI. A data set for each Vibrio species was prepared, using fatty acid profiles for a specific medium. Major fatty acids of the Vibrio strains evaluated in this study were straight-chain C(12:0), C(14:0), C16:0, and unsaturated summed C(16:1) omega 7C/C(16:1) omega 6c, C(18:1) omega 7c, and summed C(14:0) 3-OH/iso-C16:1. Most of the deep-sea Vibrio isolates were identified as Vibrio parahaemolyticus and Vibrio harveyi. Analysis of FAMEs from Vibro strains grown on a specific medium by this rapid GC-FID method can provide a sensitive procedure for the identification of these organisms, and the differentiation between Vibrio species. Published by Elsevier Ltd. C1 [Hoffmann, Maria; Whittaker, Paul] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Hoffmann, Maria; Fischer, Markus] Univ Hamburg, Dept Chem, Inst Food Chem, D-20146 Hamburg, Germany. RP Whittaker, P (reprint author), US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM paul.whittaker@fda.hhs.gov RI Fischer, Markus/G-9477-2012 FU Research Fellowship Program for the Center for Food Safety and Applied Nutrition FX The authors would like to thank Peter J. McCarthy of the Harbor Branch Oceanographic Institution at Florida Atlantic University and Jose V. Lopez of the Nova Southeastern University for supplying the deep-sea Vibrio isolates used in this study. This project was supported by an appointment of Maria Hoffmann to the Research Fellowship Program for the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Associated Universities. NR 19 TC 7 Z9 7 U1 2 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0308-8146 J9 FOOD CHEM JI Food Chem. PD OCT 15 PY 2010 VL 122 IS 4 BP 943 EP 950 DI 10.1016/j.foodchem.2010.04.015 PG 8 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA 608KI UT WOS:000278582400002 ER PT J AU Pogribny, IP Filkowski, JN Tryndyak, VP Golubov, A Shpyleva, SI Kovalchuk, O AF Pogribny, Igor P. Filkowski, Jody N. Tryndyak, Volodymyr P. Golubov, Andrey Shpyleva, Svitlana I. Kovalchuk, Olga TI Alterations of microRNAs and their targets are associated with acquired resistance of MCF-7 breast cancer cells to cisplatin SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID DRUG-RESISTANCE; MESENCHYMAL TRANSITION; TAMOXIFEN RESISTANCE; MULTIDRUG-RESISTANCE; MOLECULAR-MECHANISMS; TUMOR PROGRESSION; EXPRESSION; FAMILY; CHEMOTHERAPY; METHYLATION C1 [Pogribny, Igor P.; Tryndyak, Volodymyr P.; Shpyleva, Svitlana I.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Filkowski, Jody N.; Golubov, Andrey; Kovalchuk, Olga] Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. [Shpyleva, Svitlana I.] RE Kavetsky Inst Expt Pathol Oncol & Radiobiol, Dept Mech Anticanc Therapy, Kiev, Ukraine. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov; olga.kovalchuk@uleth.ca FU Alberta Health Services/Alberta Cancer Board; NSERC; AHFMR FX Grant sponsors: Alberta Health Services/Alberta Cancer Board, NSERC and AHFMR Graduate Scholarships NR 44 TC 167 Z9 173 U1 1 U2 16 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD OCT 15 PY 2010 VL 127 IS 8 BP 1785 EP 1794 PG 10 WC Oncology SC Oncology GA 657HX UT WOS:000282404900005 PM 20099276 ER PT J AU Vaithiyalingam, SR Sayeed, VA AF Vaithiyalingam, Sivakumar R. Sayeed, Vilayat A. TI Critical factors in manufacturing multi-layer tablets-Assessing material attributes, in-process controls, manufacturing process and product performance SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Review DE Bi-layer tablets; Multi-layer tablets; Compaction; Material attributes; Process parameter; Tensile strength; Tablet breaking force ID POWDER COMPACTION; TENSILE STRENGTHS; EXTENDED-RELEASE; BINARY-MIXTURES; BEHAVIOR; MATRIX; HYDROCHLORIDE; FORMULATION; LUBRICANT; STABILITY AB Advancement in the fields of material science, analytical methodologies, instrumentation, automation, continuous monitoring, feed forward/feed back control and comprehensive data collection have led to continual improvement of pharmaceutical tablet manufacturing technology, notably the multi-layer tablets. This review highlights the material attributes, formulation design, process parameters that impact the performance, and manufacturability of the multi-layer tablets. It also highlights on critical-to-quality elements that needs to be addressed in the regulatory submission. Published by Elsevier B.V. C1 [Vaithiyalingam, Sivakumar R.; Sayeed, Vilayat A.] US FDA, Div Chem 3, OGD, Ctr Drug Evaluat & Res, Rockville, MD USA. RP Sayeed, VA (reprint author), US FDA, Div Chem 3, OGD, Ctr Drug Evaluat & Res, 7500 Standish Pl, Rockville, MD USA. EM vilayat.sayeed@fda.hhs.gov NR 32 TC 16 Z9 20 U1 0 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARMACEUT JI Int. J. Pharm. PD OCT 15 PY 2010 VL 398 IS 1-2 BP 9 EP 13 DI 10.1016/j.ijpharm.2010.07.025 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 663WF UT WOS:000282920200002 PM 20656000 ER PT J AU Smith, AP Moore, TW Westenberger, BJ Doub, WH AF Smith, Anjanette P. Moore, Terry W. Westenberger, Benjamin J. Doub, William H. TI In vitro dissolution of oral modified-release tablets and capsules in ethanolic media SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE Dose dumping; Ethanol; Dissolution; Modified release; Tablets and capsules ID ALCOHOL; PHARMACOKINETICS; FORMULATION AB In 2005, Palladone, an extended-release capsule, was withdrawn from the market after clinical testing showed subjects who took the product with alcohol had increased levels of drug in their blood. To better understand this phenomenon, we studied the in vitro drug release of 27 oral modified-release products in alcohol-containing media. In 40% alcoholic medium, 9 of 10 capsules and 2 of 17 tablets show accelerated drug release. When a high percentage of the total dose is released in a short period of time, the extended-release product is then performing like an immediate release formulation. Products were also tested in 5% and 20% alcoholic media and in simulated gastric fluid (without enzyme) containing 20% alcohol. No tested capsules or tablets exhibited a significant increase in drug release in media containing only 5% alcohol. The current study indicates that in vitro dissolution may provide evidence regarding the ruggedness of formulations to ingested alcohol. Published by Elsevier B.V. C1 [Smith, Anjanette P.; Moore, Terry W.; Westenberger, Benjamin J.; Doub, William H.] US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Smith, AP (reprint author), US FDA, Div Pharmaceut Anal, 1114 Market St,Room 1002, St Louis, MO 63101 USA. EM anjanette.smith@fda.hhs.gov NR 16 TC 13 Z9 14 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARMACEUT JI Int. J. Pharm. PD OCT 15 PY 2010 VL 398 IS 1-2 BP 93 EP 96 DI 10.1016/j.ijpharm.2010.07.031 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 663WF UT WOS:000282920200012 PM 20667505 ER PT J AU Deuel, LM Chesire, AM Eason, SM Como, PG Biglan, KM AF Deuel, Lisa M. Chesire, Amy M. Eason, Sheelah M. Como, Peter G. Biglan, Kevin M. TI Reply: An Exploration of the Burden Experienced by Spousal Caregivers of Individuals with Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Letter C1 [Deuel, Lisa M.; Chesire, Amy M.; Biglan, Kevin M.] Univ Rochester, Dept Neurol, Rochester, NY 14627 USA. [Eason, Sheelah M.] Lifetime Care, Rochester, NY USA. [Como, Peter G.] US FDA, Silver Spring, MD USA. RP Deuel, LM (reprint author), Univ Rochester, Dept Neurol, Rochester, NY 14627 USA. EM lisa_deuel@urmc.rochester.edu NR 4 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD OCT 15 PY 2010 VL 25 IS 13 BP 2254 EP 2255 DI 10.1002/mds.23273 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 665HV UT WOS:000283026900039 PM 20803516 ER PT J AU Huang, L Tiwari, RC Pickle, L Zou, ZH AF Huang, Lan Tiwari, Ram C. Pickle, LindaW. Zou, Zhaohui TI Covariate adjusted weighted normal spatial scan statistics with applications to study geographic clustering of obesity and lung cancer mortality in the United States SO STATISTICS IN MEDICINE LA English DT Article DE cluster detection; covariate adjustment; lung cancer mortality; obesity; regional continuous data; weighted normal spatial scan statistic ID TESTS; PREVALENCE; MODEL; MAPS AB In the field of cluster detection, a weighted normal model-based scan statistic was recently developed to analyze regional continuous data and to evaluate the clustering pattern of pre-defined cells (such as state, county, tract, school, hospital) that include many individuals. The continuous measures of interest are, for example, the survival rate, mortality rate, length of physical activity, or the obesity measure, namely, body mass index, at the cell level with an uncertainty measure for each cell. In this paper, we extend the method to search for clusters of the cells after adjusting for single/multiple categorical/continuous covariates. We apply the proposed method to 1999-2003 obesity data in the United States (US) collected by CDC's Behavioral Risk Factor Surveillance System with adjustment for age and race, and to 1999-2003 lung cancer age-adjusted mortality data by gender in the United States from the Surveillance Epidemiology and End Results (SEER Program) with adjustment for smoking and income. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Huang, Lan; Tiwari, Ram C.] US FDA, Off Biostat, CDER, Silver Spring, MD 20993 USA. [Pickle, LindaW.] StatNet Consulting LLC, Gaithersburg, MD 20879 USA. [Zou, Zhaohui] Informat Management Serv Inc, Silver Spring, MD 20904 USA. RP Huang, L (reprint author), US FDA, Off Biostat, CDER, Silver Spring, MD 20993 USA. EM lan.huang@fda.hhs.gov FU National Cancer Institute, NIH FX Lan Huang's most of the work was done while he was a contractor at the National Cancer Institute, NIH. Ram C. Tiwari's most of the work was done while he was a program director at the National Cancer Institute, NIH. The views expressed in this article do not necessarily represent those of the US Food and Drug Administration. NR 33 TC 8 Z9 8 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD OCT 15 PY 2010 VL 29 IS 23 BP 2410 EP 2422 DI 10.1002/sim.3990 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 660EH UT WOS:000282622200004 PM 20690110 ER PT J AU Woodcock, J Sharfstein, JM Hamburg, M AF Woodcock, Janet Sharfstein, Joshua M. Hamburg, Margaret TI Regulatory Action on Rosiglitazone by the US Food and Drug Administration SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Woodcock, Janet] Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Sharfstein, Joshua M.; Hamburg, Margaret] US FDA, Dept Hlth & Human Serv, Silver Spring, MD USA. RP Woodcock, J (reprint author), Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 7 TC 81 Z9 82 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 OCT 14 PY 2010 VL 363 IS 16 BP 1489 EP 1491 DI 10.1056/NEJMp1010788 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 663KP UT WOS:000282887100001 PM 20942663 ER PT J AU Zhao, JQ Tang, SX Storhoff, J Marla, S Bao, YP Wang, X Wong, EY Ragupathy, V Ye, ZP Hewlett, IK AF Zhao, Jiangqin Tang, Shixing Storhoff, James Marla, Sudhakar Bao, Y. Paul Wang, Xue Wong, Eric Y. Ragupathy, Viswanath Ye, Zhiping Hewlett, Indira K. TI Multiplexed, rapid detection of H5N1 using a PCR-free nanoparticle-based genomic microarray assay SO BMC BIOTECHNOLOGY LA English DT Article ID INFLUENZA-A VIRUS; REVERSE TRANSCRIPTION-PCR; FLUCHIP DIAGNOSTIC MICROARRAY; PATHOGENIC AVIAN INFLUENZA; HOST-SPECIFICITY; RT-PCR; IDENTIFICATION; DNA; HYBRIDIZATION; AMPLIFICATION AB Background: For more than a decade there has been increasing interest in the use of nanotechnology and microarray platforms for diagnostic applications. In this report, we describe a rapid and simple gold nanoparticle (NP)-based genomic microarray assay for specific identification of avian influenza virus H5N1 and its discrimination from other major influenza A virus strains (H1N1, H3N2). Results: Capture and intermediate oligonucleotides were designed based on the consensus sequences of the matrix (M) gene of H1N1, H3N2 and H5N1 viruses, and sequences specific for the hemaglutinin (HA) and neuraminidase (NA) genes of the H5N1 virus. Viral RNA was detected within 2.5 hours using capture-target-intermediate oligonucleotide hybridization and gold NP-mediated silver staining in the absence of RNA fragmentation, target amplification, and enzymatic reactions. The lower limit of detection (LOD) of the assay was less than 100 fM for purified PCR fragments and 10(3) TCID50 units for H5N1 viral RNA. Conclusions: The NP-based microarray assay was able to detect and distinguish H5N1 sequences from those of major influenza A viruses (H1N1, H3N2). The new method described here may be useful for simultaneous detection and subtyping of major influenza A viruses. C1 [Zhao, Jiangqin; Tang, Shixing; Wang, Xue; Wong, Eric Y.; Ragupathy, Viswanath; Hewlett, Indira K.] US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Storhoff, James; Marla, Sudhakar; Bao, Y. Paul] Nanosphere Inc, Northbrook, IL 60062 USA. [Ye, Zhiping] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Zhao, JQ (reprint author), US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM Jiangqin.Zhao@fda.hhs.gov; Indira.Hewlett@fda.hhs.gov FU CBER FX The authors wish to acknowledge Drs. Robert Duncan, Mingjie Zhang and Hira Nakhasi for review of the manuscript. We thank Dr Maryna Eichelberger, Kanta Subbarao for providing influenza A virus samples and for reviewing this manuscript. This work was a collaboration with Nanosphere, Inc. through CRADA (# 147-09), and was funded partly through CBER intramural funds. The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy. NR 40 TC 17 Z9 22 U1 1 U2 22 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6750 J9 BMC BIOTECHNOL JI BMC Biotechnol. PD OCT 13 PY 2010 VL 10 AR 74 DI 10.1186/1472-6750-10-74 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 669MH UT WOS:000283354400001 PM 20942949 ER PT J AU Formeister, EJ Tsuchiya, M Fujii, H Shpyleva, S Pogribny, IP Rusyn, I AF Formeister, Eric J. Tsuchiya, Masato Fujii, Hideki Shpyleva, Svitlana Pogribny, Igor P. Rusyn, Ivan TI Comparative analysis of promoter methylation and gene expression endpoints between tumorous and non-tumorous tissues from HCV-positive patients with hepatocellular carcinoma SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE Hepatocellular carcinoma; Epigenetics; Time to recurrence ID CPG ISLAND HYPERMETHYLATION; DNA METHYLATION; MOLECULAR PATHOGENESIS; ABERRANT METHYLATION; SUPPRESSOR GENE; RISK-FACTORS; CANCER; HYPOMETHYLATION; LIVER; EPIDEMIOLOGY AB Transcriptional silencing of tumor suppressor genes and other cancer-related genes induced by promoter CpG island hypermethylation is an important epigenetic mechanism of hepatocarcinogenesis. Previous studies have established methylation profiles of hepatocellular carcinomas (HCCs) and demonstrated that methylation of several candidate genes in resected tissues may be associated with time to recurrence. The goals of our study were to test whether specific promoter methylation and mRNA levels of candidate genes, as well as global changes in DNA methylation, can be linked with time to recurrence and clinicopathological variables in a homogenous study group of HCC patients. Forty-three tumorous and 45 non-tumorous liver tissue samples from the surgical margin were obtained from HCV-positive, HBV-negative HCC patients who underwent tumor resection surgery and who were monitored for tumor recurrence thereafter (median follow-up time: 16 months (range, 0-79 months)). Methylation-specific PCR was used to assess the promoter methylation status of P16(INK4a), SOCS-1, RASSF1A,APC,GSTP1, RIZ1, and MGMT genes, while the level of LINE-1 methylation was used as marker of global DNA methylation levels. Methylation frequencies in P16(INK4a), RASSF1A, APC, GSTP1, and RIZ1 genes were significantly greater in tumorous versus non-tumorous tissues. Methylation of RIZ1 in non-tumorous tissues was significantly associated with time to recurrence. Additionally, genomic DNA was significantly more hypomethylated in tumorous tissues, and this change was associated with shorter recurrence, but not with clinicopathological features. In conclusion, this study supports the role of aberrant methylation in the pathobiology of HCV-positive HCCs. The finding that RIZ1 methylation and increased levels of LINE-1 hypomethylation in non-tumorous tissues are associated with time to recurrence underscores the importance of assessing the epigenetic state of the liver remnant. (C) 2010 Elsevier B.V. All rights reserved. C1 [Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Gillings Sch Global Publ Hlth, Michael Hooker Res Ctr 0031, Chapel Hill, NC 27599 USA. [Tsuchiya, Masato; Fujii, Hideki] Univ Yamanashi, Dept Surg 1, Chuo Ku, Yamanashi, Japan. [Shpyleva, Svitlana; Pogribny, Igor P.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Rusyn, I (reprint author), Univ N Carolina, Dept Environm Sci & Engn, Gillings Sch Global Publ Hlth, Michael Hooker Res Ctr 0031, CB 7431, Chapel Hill, NC 27599 USA. EM iir@unc.edu RI Rusyn, Ivan/S-2426-2016 FU National Institutes of Health [R01 AA016285, R01 ES015241]; UNC Graduate School FX Financial support for these studies was provided, in part, by grants from the National Institutes of Health: R01 AA016285 and R01 ES015241. EJF was also supported, in part, by the UNC Graduate School Competitive Merit Assistantship. NR 37 TC 32 Z9 35 U1 0 U2 7 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 OCT 13 PY 2010 VL 692 IS 1-2 BP 26 EP 33 DI 10.1016/j.mrfmmm.2010.07.013 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 676FF UT WOS:000283894800005 PM 20736025 ER PT J AU Schnackenberg, BJ Saini, UT Robinson, BL Ali, SF Patterson, TA AF Schnackenberg, B. J. Saini, U. T. Robinson, B. L. Ali, S. F. Patterson, T. A. TI AN ACUTE DOSE OF GAMMA-HYDROXYBUTYRIC ACID ALTERS GENE EXPRESSION IN MULTIPLE MOUSE BRAIN REGIONS SO NEUROSCIENCE LA English DT Article DE microarray; PCR array; oxidative stress; memory; long-term potentiation; GHB ID LONG-TERM-MEMORY; RAT-BRAIN; NEUROFIBROMATOSIS TYPE-1; SYNAPTIC PLASTICITY; OXIDATIVE STRESS; CEREBRAL-CORTEX; C-FOS; RECEPTOR; MICE; DEFICITS AB Gamma-hydroxybutyric acid (GHB) is normally found in the brain in low concentrations and may function as a neurotransmitter, although the mechanism of action has not been completely elucidated. GHB has been used as a general anesthetic and is currently used to treat narcolepsy and alcoholism. Recreational use of GHB is primarily as a "club drug" and a "date rape drug," due to its amnesic effects. For this study, the hypothesis was that behavioral and neurochemical alterations may parallel gene expression changes in the brain after GHB administration. Adult male C57/B6N mice (n=5/group) were administered a single dose of 500 mg/kg GHB (i.p.) and were sacrificed 1, 2 and 4 h after treatment. Control mice were administered saline. Brains were removed and regionally dissected on ice. Total RNA from the hippocampus, cortex and striatum was extracted, amplified and labeled. Gene expression was evaluated using Agilent whole mouse genome 4 x 44K oligonucleotide microarrays. Microarray data were analyzed by ArrayTrack(TM) and differentially expressed genes (DEGs) were identified using P <= 0.01 and a fold change >= 1.7 as the criteria for significance. Principal component analysis (PCA) and Hierarchical Cluster Analysis (HCA) showed that samples from each time point clustered into distinct treatment groups with respect to sacrifice time. Ingenuity pathways analysis (IPA) was used to identify involved pathways. The results show that GHB induces gene expression alterations in hundreds of genes in the hippocampus, cortex and striatum, and the number of affected genes increases throughout a 4-h time course. Many of these DEGs are involved in neurological disease, apoptosis, and oxidative stress. Published by Elsevier Ltd on behalf of IBRO. C1 [Schnackenberg, B. J.; Saini, U. T.; Robinson, B. L.; Ali, S. F.; Patterson, T. A.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Schnackenberg, BJ (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM Bradley.Schnackenberg@fda.hhs.gov FU NCTR [E-7257]; FDA FX The findings and conclusions in this report are those of the author(s) and do not necessarily represent the views of the FDA. 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. This work was supported in part by NCTR E-7257 and the FDA Commissioner's Fellowship Program. NR 51 TC 4 Z9 5 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD OCT 13 PY 2010 VL 170 IS 2 BP 523 EP 541 DI 10.1016/j.neuroscience.2010.06.049 PG 19 WC Neurosciences SC Neurosciences & Neurology GA 651PH UT WOS:000281939100015 PM 20654702 ER PT J AU Sullivan, SZ Ghosh, A Biris, AS Pulla, S Brezden, AM Collom, SL Woods, RM Munshi, P Schnackenberg, L Pierce, BS Kannarpady, GK AF Sullivan, Shane Z. Ghosh, Anindya Biris, Alexandru S. Pulla, Sharon Brezden, Anna M. Collom, Samulel L. Woods, Ross M. Munshi, Pradip Schnackenberg, Laura Pierce, Brad S. Kannarpady, Ganesh K. TI Fe-complex of a tetraamido macrocyclic ligand: Spectroscopic characterization and catalytic oxidation studies SO CHEMICAL PHYSICS LETTERS LA English DT Article ID HYDROGEN-PEROXIDE; METAL-ION; IRON; ACTIVATION; MODELS; EPR; EPOXIDATION; RELAXATION; SATURATION; REACTIVITY AB This work presents the spectroscopic characterization and reaction studies of a Fe(III)-complex (2) of a tetraamido macrocyclic ligand (1, 15,15-dimethyl-5,8,13,17-tetrahydro-5,8,13,17-tetraaza-dibenzo[ a,g]cyclotridecene- 6,7,14,16-tetraone). 2 was characterized primarily by means of EPR. In agreement with the magnetic moment (mu(eff) = 3.87 BM), EPR spectroscopy of 2 shows signals consistent with S = 3/2 intermediate- spin ferric-iron. Besides EPR, mass spectrometry, UV/vis spectroscopy and cyclic voltammetry were used to further characterize 2. 2 is soluble in water and activates hydrogen peroxide under ambient conditions. 2 catalytically bleaches dyes, pulp and paper effluents and oxidizes several amines to their corresponding N-oxides with high turnover number and good yields. (C) 2010 Elsevier B.V. All rights reserved. C1 [Sullivan, Shane Z.; Ghosh, Anindya; Pulla, Sharon; Brezden, Anna M.; Collom, Samulel L.] Univ Arkansas, Dept Chem, Little Rock, AR 72204 USA. [Biris, Alexandru S.; Woods, Ross M.; Kannarpady, Ganesh K.] Univ Arkansas, Nanotechnol Ctr, Little Rock, AR 72204 USA. [Munshi, Pradip] Reliance Ind Ltd, Res Ctr, Vadodara, India. [Schnackenberg, Laura] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Pierce, Brad S.] Univ Texas Arlington, Dept Chem & Biochem, Arlington, TX 76019 USA. RP Ghosh, A (reprint author), Univ Arkansas, Dept Chem, Little Rock, AR 72204 USA. EM axghosh@ualr.edu RI Biris, Alexandru/A-8507-2010; Collom, Samuel/L-9287-2013 FU Department of Chemistry (and Biochemistry) at UALR; UTA; Department of Energy [DE-FG36-06GO86072] FX We thank the department of Chemistry (and Biochemistry) at UALR and UTA, respectively for financial assistance (AG and BSP). AG also likes to thank Department of Energy (Grant number DE-FG36-06GO86072) for financial assistance to complete the work too. NR 34 TC 4 Z9 4 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-2614 J9 CHEM PHYS LETT JI Chem. Phys. Lett. PD OCT 8 PY 2010 VL 498 IS 4-6 BP 359 EP 365 DI 10.1016/j.cplett.2010.09.002 PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 656TW UT WOS:000282361000025 ER PT J AU Ding, D Xu, L Fang, H Hong, HX Perkins, R Harris, S Bearden, ED Shi, LM Tong, WD AF Ding, Don Xu, Lei Fang, Hong Hong, Huixiao Perkins, Roger Harris, Steve Bearden, Edward D. Shi, Leming Tong, Weida TI The EDKB: an established knowledge base for endocrine disrupting chemicals SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 7th Annual Midsouth Computational Biology and Bioinformatics (MCBIOS) CY FEB 19-20, 2010 CL Jonesboro, AR ID LARGE DIVERSE SET; ENVIRONMENTAL-HEALTH INFORMATION; ESTROGEN-RECEPTOR BINDING; ANDROGEN RECEPTOR; RISK-ASSESSMENT; TOXICOLOGY; DATABASE; MODEL; MECHANISMS; TOXNET AB Background: Endocrine disruptors (EDs) and their broad range of potential adverse effects in humans and other animals have been a concern for nearly two decades. Many putative EDs are widely used in commercial products regulated by the Food and Drug Administration (FDA) such as food packaging materials, ingredients of cosmetics, medical and dental devices, and drugs. The Endocrine Disruptor Knowledge Base (EDKB) project was initiated in the mid 1990's by the FDA as a resource for the study of EDs. The EDKB database, a component of the project, contains data across multiple assay types for chemicals across a broad structural diversity. This paper demonstrates the utility of EDKB database, an integral part of the EDKB project, for understanding and prioritizing EDs for testing. Results: The EDKB database currently contains 3,257 records of over 1,800 EDs from different assays including estrogen receptor binding, androgen receptor binding, uterotropic activity, cell proliferation, and reporter gene assays. Information for each compound such as chemical structure, assay type, potency, etc. is organized to enable efficient searching. A user-friendly interface provides rapid navigation, Boolean searches on EDs, and both spreadsheet and graphical displays for viewing results. The search engine implemented in the EDKB database enables searching by one or more of the following fields: chemical structure (including exact search and similarity search), name, molecular formula, CAS registration number, experiment source, molecular weight, etc. The data can be cross-linked to other publicly available and related databases including TOXNET, Cactus, ChemIDplus, ChemACX, Chem Finder, and NCI DTP. Conclusion: The EDKB database enables scientists and regulatory reviewers to quickly access ED data from multiple assays for specific or similar compounds. The data have been used to categorize chemicals according to potential risks for endocrine activity, thus providing a basis for prioritizing chemicals for more definitive but expensive testing. The EDKB database is publicly available and can be found online at http://edkb.fda.gov/webstart/edkb/index.html. Disclaimer: The views presented in this article do not necessarily reflect those of the US Food and Drug Administration. C1 [Ding, Don; Fang, Hong; Tong, Weida] US FDA, Div Bioinformat, Z Tech Corp, NCTR, Jefferson, AR 72079 USA. RP Tong, WD (reprint author), US FDA, Div Bioinformat, Z Tech Corp, NCTR, Jefferson, AR 72079 USA. EM weida.tong@fda.hhs.gov NR 28 TC 33 Z9 34 U1 1 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD OCT 7 PY 2010 VL 11 SU 6 AR S5 DI 10.1186/1471-2105-11-S6-S5 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 759CB UT WOS:000290216600005 PM 20946616 ER PT J AU Fang, H Xu, J Ding, D Jackson, SA Patel, IR Frye, JG Zou, W Nayak, R Foley, S Chen, J Su, ZQ Ye, YB Turner, S Harris, S Zhou, GX Cerniglia, C Tong, WD AF Fang, Hong Xu, Joshua Ding, Don Jackson, Scott A. Patel, Isha R. Frye, Jonathan G. Zou, Wen Nayak, Rajesh Foley, Steven Chen, James Su, Zhenqiang Ye, Yanbin Turner, Steve Harris, Steve Zhou, Guangxu Cerniglia, Carl Tong, Weida TI An FDA bioinformatics tool for microbial genomics research on molecular characterization of bacterial foodborne pathogens using microarrays SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 7th Annual Midsouth Computational Biology and Bioinformatics (MCBIOS) CY FEB 19-20, 2010 CL Jonesboro, AR ID ANTIMICROBIAL RESISTANCE GENES; DNA MICROARRAY; OLIGONUCLEOTIDE MICROARRAY; ANTIBIOTIC-RESISTANCE; SALMONELLA-ENTERICA; NATIONAL-CENTER; EXPRESSION; CLASSIFICATION; ARRAYTRACK; COLI AB Background: Advances in microbial genomics and bioinformatics are offering greater insights into the emergence and spread of foodborne pathogens in outbreak scenarios. The Food and Drug Administration (FDA) has developed a genomics tool, ArrayTrack (TM), which provides extensive functionalities to manage, analyze, and interpret genomic data for mammalian species. ArrayTrack (TM) has been widely adopted by the research community and used for pharmacogenomics data review in the FDA's Voluntary Genomics Data Submission program. Results: ArrayTrack (TM) has been extended to manage and analyze genomics data from bacterial pathogens of human, animal, and food origin. It was populated with bioinformatics data from public databases such as NCBI, Swiss-Prot, KEGG Pathway, and Gene Ontology to facilitate pathogen detection and characterization. ArrayTrack (TM)'s data processing and visualization tools were enhanced with analysis capabilities designed specifically for microbial genomics including flag-based hierarchical clustering analysis (HCA), flag concordance heat maps, and mixed scatter plots. These specific functionalities were evaluated on data generated from a custom Affymetrix array (FDA-ECSG) previously developed within the FDA. The FDA-ECSG array represents 32 complete genomes of Escherichia coli and Shigella. The new functions were also used to analyze microarray data focusing on antimicrobial resistance genes from Salmonella isolates in a poultry production environment using a universal antimicrobial resistance microarray developed by the United States Department of Agriculture (USDA). Conclusion: The application of ArrayTrack (TM) to different microarray platforms demonstrates its utility in microbial genomics research, and thus will improve the capabilities of the FDA to rapidly identify foodborne bacteria and their genetic traits (e. g., antimicrobial resistance, virulence, etc.) during outbreak investigations. ArrayTrack (TM) is free to use and available to public, private, and academic researchers at http://www.fda.gov/ArrayTrack. C1 [Fang, Hong; Xu, Joshua; Ding, Don; Su, Zhenqiang; Ye, Yanbin; Turner, Steve; Zhou, Guangxu] US FDA, Z Tech Corp, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Jackson, Scott A.; Patel, Isha R.; Cerniglia, Carl] US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div Mol Biol, Laurel, MD USA. [Frye, Jonathan G.] ARS, Bacterial Epidemiol & Antimicrobial Resistance Re, Richard B Russell Res Ctr, USDA, Athens, GA USA. RP Tong, WD (reprint author), US FDA, Z Tech Corp, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM weida.tong@fda.hhs.gov RI Su, Zhenqiang/H-3914-2012; Frye, Jonathan/I-6382-2013; Luan, Gan/B-3211-2015 OI Frye, Jonathan/0000-0002-8500-3395; FU Dept. of Homeland Security, FDA's Center for Food Safety and Applied Nutrition, Office of Applied Research and Safety Assessment; USDA CRIS [6612-32000-002-00] FX The design and development of the FDA-ECSG array was funded by the Dept. of Homeland Security as part of an Interagency Agreement with FDA's Center for Food Safety and Applied Nutrition, Office of Applied Research and Safety Assessment. The FDA-ECSG array is available to the general scientific community and can be ordered online at http://pfgrc.jcvi.org/index.php/microarray/affy_array_description/ecoli_ shigella/version1.html; more information can be found at http://phx.corporate-ir.net/preview/phoenix.zhtml?c=116408&p=irol-newsAr ticle&ID=1317038&highlight=ECSG. For USDA CRIS funding project number 6612-32000-002-00, the authors thank Rebecca L, Lindsey, Jennifer Bauer-Turpin, and Jonathan Cudnik (USDA) for their technical assistance. NR 29 TC 14 Z9 14 U1 1 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD OCT 7 PY 2010 VL 11 SU 6 AR S4 DI 10.1186/1471-2105-11-S6-S4 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 759CB UT WOS:000290216600004 PM 20946615 ER PT J AU Wen, ZN Wang, C Shi, Q Huang, Y Su, ZQ Hong, HX Tong, WD Shi, LM AF Wen, Zhining Wang, Charles Shi, Quan Huang, Ying Su, Zhenqiang Hong, Huixiao Tong, Weida Shi, Leming TI Evaluation of gene expression data generated from expired Affymetrix GeneChip (R) microarrays using MAQC reference RNA samples SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 7th Annual Midsouth Computational Biology and Bioinformatics (MCBIOS) CY FEB 19-20, 2010 CL Jonesboro, AR ID CELL MOLECULAR SIGNATURE; ADULT STEM-CELLS; DNA MICROARRAY; PLATFORMS; CONSISTENCY; ARRAYS; NOISE AB Background: The Affymetrix GeneChip (R) system is a commonly used platform for microarray analysis but the technology is inherently expensive. Unfortunately, changes in experimental planning and execution, such as the unavailability of previously anticipated samples or a shift in research focus, may render significant numbers of pre-purchased GeneChip (R) microarrays unprocessed before their manufacturer's expiration dates. Researchers and microarray core facilities wonder whether expired microarrays are still useful for gene expression analysis. In addition, it was not clear whether the two human reference RNA samples established by the MAQC project in 2005 still maintained their transcriptome integrity over a period of four years. Experiments were conducted to answer these questions. Results: Microarray data were generated in 2009 in three replicates for each of the two MAQC samples with either expired Affymetrix U133A or unexpired U133Plus2 microarrays. These results were compared with data obtained in 2005 on the U133Plus2 microarray. The percentage of overlap between the lists of differentially expressed genes (DEGs) from U133Plus2 microarray data generated in 2009 and in 2005 was 97.44%. While there was some degree of fold change compression in the expired U133A microarrays, the percentage of overlap between the lists of DEGs from the expired and unexpired microarrays was as high as 96.99%. Moreover, the microarray data generated using the expired U133A microarrays in 2009 were highly concordant with microarray and TaqMan (R) data generated by the MAQC project in 2005. Conclusions: Our results demonstrated that microarray data generated using U133A microarrays, which were more than four years past the manufacturer's expiration date, were highly specific and consistent with those from unexpired microarrays in identifying DEGs despite some appreciable fold change compression and decrease in sensitivity. Our data also suggested that the MAQC reference RNA samples, stored at -80 degrees C, were stable over a time frame of at least four years. C1 [Wen, Zhining; Hong, Huixiao; Tong, Weida; Shi, Leming] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Wang, Charles] City Hope Comprehens Canc Ctr, Beckman Res Inst, Duarte, CA 91010 USA. [Wang, Charles] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Shi, Quan; Huang, Ying] Western Univ Hlth Sci, Coll Pharm, Pomona, CA 91766 USA. [Su, Zhenqiang] US FDA, Z Tech ICF Int, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Shi, LM (reprint author), US FDA, Div Syst Biol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM leming.shi@fda.hhs.gov RI Su, Zhenqiang/H-3914-2012 FU National Center for Toxicological Research of the US FDA through Oak Ridge Institute for Science and Education (ORISE) FX We are grateful to Dr. Donna L. Mendrick for critical reading of the manuscript. ZW was supported by a postdoctoral fellowship from the National Center for Toxicological Research of the US FDA through the Oak Ridge Institute for Science and Education (ORISE). QS is grateful to the College of Pharmacy of Western University of Health Sciences for allowing her to use its equipment. The views presented in this article do not necessarily reflect those of the US FDA. NR 23 TC 6 Z9 7 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD OCT 7 PY 2010 VL 11 SU 6 AR S10 DI 10.1186/1471-2105-11-S6-S10 PG 13 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 759CB UT WOS:000290216600010 PM 20946593 ER PT J AU Xu, J Wise, C Varma, V Fang, H Ning, BT Hong, HX Tong, WD Kaput, J AF Xu, Joshua Wise, Carolyn Varma, Vijayalakshmi Fang, Hong Ning, Baitang Hong, Huixiao Tong, Weida Kaput, Jim TI Two new ArrayTrack libraries for personalized biomedical research SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 7th Annual Midsouth Computational Biology and Bioinformatics (MCBIOS) CY FEB 19-20, 2010 CL Jonesboro, AR ID POPULATION DIFFERENTIATION; DISEASE; DATABASE; LEVEL; SNPS AB Background: Recent advances in high-throughput genotyping technology are paving the way for research in personalized medicine and nutrition. However, most of the genetic markers identified from association studies account for a small contribution to the total risk/benefit of the studied phenotypic trait. Testing whether the candidate genes identified by association studies are causal is critically important to the development of personalized medicine and nutrition. An efficient data mining strategy and a set of sophisticated tools are necessary to help better understand and utilize the findings from genetic association studies. Description: SNP (single nucleotide polymorphism) and QTL (quantitative trait locus) libraries were constructed and incorporated into ArrayTrack, with user-friendly interfaces and powerful search features. Data from several public repositories were collected in the SNP and QTL libraries and connected to other domain libraries (genes, proteins, metabolites, and pathways) in ArrayTrack. Linking the data sets within ArrayTrack allows searching of SNP and QTL data as well as their relationships to other biological molecules. The SNP library includes approximately 15 million human SNPs and their annotations, while the QTL library contains publically available QTLs identified in mouse, rat, and human. The QTL library was developed for finding the overlap between the map position of a candidate or metabolic gene and QTLs from these species. Two use cases were included to demonstrate the utility of these tools. The SNP and QTL libraries are freely available to the public through ArrayTrack at http://www.fda.gov/ArrayTrack. Conclusions: These libraries developed in ArrayTrack contain comprehensive information on SNPs and QTLs and are further cross-linked to other libraries. Connecting domain specific knowledge is a cornerstone of systems biology strategies and allows for a better understanding of the genetic and biological context of the findings from genetic association studies. C1 [Xu, Joshua; Fang, Hong] Natl Ctr Toxicol Res, Z Tech Corp, Jefferson, AR 72079 USA. [Wise, Carolyn; Varma, Vijayalakshmi; Ning, Baitang; Kaput, Jim] Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. [Hong, Huixiao; Tong, Weida] Natl Ctr Toxicol Res, Ctr Toxicoinformat, Div Syst Toxicol, Jefferson, AR 72079 USA. RP Xu, J (reprint author), Natl Ctr Toxicol Res, Z Tech Corp, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Zhihua.xu@fda.hhs.gov NR 21 TC 7 Z9 8 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD OCT 7 PY 2010 VL 11 SU 6 AR S6 DI 10.1186/1471-2105-11-S6-S6 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 759CB UT WOS:000290216600006 PM 20946617 ER PT J AU Woodcock, J Okada, S AF Woodcock, Janet Okada, Sarah TI Incentives for Drug Development -- The Curious Case of Colchicine. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Woodcock, Janet; Okada, Sarah] US FDA, Silver Spring, MD USA. RP Woodcock, J (reprint author), US FDA, Silver Spring, MD USA. NR 2 TC 5 Z9 5 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 7 PY 2010 VL 363 IS 15 BP 1484 EP 1484 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 659NV UT WOS:000282575100025 PM 20925555 ER PT J AU Farb, A Brown, SA Wolf, DA Zuckerman, B AF Farb, Andrew Brown, Sheila A. Wolf, Deborah A. Zuckerman, Bram TI Interventional Cardiology Live Case Presentations Regulatory Considerations SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE angiography; complications adult cath/intervention; coronary; percutaneous coronary intervention C1 [Farb, Andrew] US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Silver Spring, MD 20993 USA. RP Farb, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, 10903 New Hampshire Ave,WO66-1116, Silver Spring, MD 20993 USA. EM andrew.farb@fda.hhs.gov NR 4 TC 2 Z9 2 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 OCT 5 PY 2010 VL 56 IS 15 BP 1283 EP 1285 DI 10.1016/j.jacc.2010.08.601 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 655VA UT WOS:000282279400023 PM 20883943 ER PT J AU Arsava, EM Ballabio, E Benner, T Cole, JW Delgado-Martinez, MP Dichgans, M Fazekas, F Furie, KL Illoh, K Jood, K Kittner, S Lindgren, AG Majersik, JJ Macleod, MJ Meurer, WJ Montaner, J Olugbodi, AA Pasdar, A Redfors, P Schmidt, R Sharma, P Singhal, AB Sorensen, AG Sudlow, C Thijs, V Worrall, BB Rosand, J Ay, H AF Arsava, E. M. Ballabio, E. Benner, T. Cole, J. W. Delgado-Martinez, M. P. Dichgans, M. Fazekas, F. Furie, K. L. Illoh, K. Jood, K. Kittner, S. Lindgren, A. G. Majersik, J. J. Macleod, M. J. Meurer, W. J. Montaner, J. Olugbodi, A. A. Pasdar, A. Redfors, P. Schmidt, R. Sharma, P. Singhal, A. B. Sorensen, A. G. Sudlow, C. Thijs, V. Worrall, B. B. Rosand, J. Ay, H. CA Int Stroke Genetics Consortium TI The Causative Classification of Stroke system An international reliability and optimization study SO NEUROLOGY LA English DT Article ID MODIFIED RANKIN SCALE; ACUTE ISCHEMIC-STROKE; CLINICAL-TRIALS AB Background: Valid and reliable ischemic stroke subtype determination is crucial for well-powered multicenter studies. The Causative Classification of Stroke System (CCS, available at http://ccs.mgh.harvard.edu) is a computerized, evidence-based algorithm that provides both causative and phenotypic stroke subtypes in a rule-based manner. We determined whether CCS demonstrates high interrater reliability in order to be useful for international multicenter studies. Methods: Twenty members of the International Stroke Genetics Consortium from 13 centers in 8 countries, who were not involved in the design and development of the CCS, independently assessed the same 50 consecutive patients with acute ischemic stroke through reviews of abstracted case summaries. Agreement among ratings was measured by kappa statistic. Results: The kappa value for causative classification was 0.80 (95% confidence interval [ CI] 0.78-0.81) for the 5-subtype, 0.79 (95% CI 0.77-0.80) for the 8-subtype, and 0.70 (95% CI 0.69-0.71) for the 16-subtype CCS. Correction of a software-related factor that generated ambiguity improved agreement: kappa = 0.81 (95% CI 0.79-0.82) for the 5-subtype, 0.79 (95% CI 0.77-0.80) for the 8-subtype, and 0.79 (95% CI 0.78-0.80) for the 16-subtype CCS. The kappa value for phenotypic classification was 0.79 (95% CI 0.77-0.82) for supra-aortic large artery atherosclerosis, 0.95 (95% CI 0.93-0.98) for cardioembolism, 0.88 (95% CI 0.85-0.91) for small artery occlusion, and 0.79 (0.76-0.82) for other uncommon causes. Conclusions: CCS allows classification of stroke subtypes by multiple investigators with high reliability, supporting its potential for improving stroke classification in multicenter studies and ensuring accurate means of communication among different researchers, institutions, and eras. Neurology (R) 2010;75:1277-1284 C1 [Arsava, E. M.; Benner, T.; Sorensen, A. G.; Ay, H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, AA Martinos Ctr Biomed Imaging,Dept Radiol, Charlestown, MA 02129 USA. [Furie, K. L.; Singhal, A. B.; Rosand, J.; Ay, H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke Serv, Charlestown, MA 02129 USA. [Rosand, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Charlestown, MA 02129 USA. [Ballabio, E.] Natl Neurol Inst, Milan, Italy. [Cole, J. W.; Kittner, S.] Univ Maryland, Baltimore, MD 21201 USA. [Cole, J. W.; Kittner, S.] Dept Vet Affairs Med Ctr, Baltimore, MD USA. [Delgado-Martinez, M. P.; Montaner, J.] Vall dHebron Hosp, Neurovasc Res Lab, Dept Neurol, Barcelona, Spain. [Dichgans, M.] Univ Munich, Inst Stroke & Dementia Res, Munich, Germany. [Dichgans, M.] Univ Munich, Neurol Klin, Munich, Germany. [Fazekas, F.; Schmidt, R.] Med Univ Graz, Dept Neurol, Graz, Austria. [Illoh, K.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden. [Jood, K.; Redfors, P.] Sahlgrens Univ Hosp, Dept Neurol, Gothenburg, Sweden. [Lindgren, A. G.] Univ Lund Hosp, Dept Neurol, S-22185 Lund, Sweden. [Majersik, J. J.] Univ Utah, Stroke Ctr, Salt Lake City, UT USA. [Pasdar, A.] Univ Aberdeen, Dept Mental Hlth, Aberdeen, Scotland. [Macleod, M. J.] Univ Aberdeen, Div Appl Med, Aberdeen, Scotland. [Meurer, W. J.] Univ Michigan, Dept Emergency Med, Ann Arbor, MI USA. [Meurer, W. J.] Univ Michigan, Dept Neurol, Ann Arbor, MI USA. [Olugbodi, A. A.] Obafemi Awolowo Univ, Coll Hlth Sci, Dept Med, Ife, Osun State, Nigeria. [Sharma, P.] Hammersmith Hosp, Dept Clin Neurosci, London, England. [Sharma, P.] Univ London Imperial Coll Sci Technol & Med, London, England. [Sudlow, C.] Univ Edinburgh, Div Clin Neurosci, Edinburgh, Midlothian, Scotland. [Sudlow, C.] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. [Thijs, V.] Katholieke Univ Leuven Hosp, Dept Neurol, Louvain, Belgium. [Worrall, B. B.] Univ Virginia, Ctr Publ Hlth Genom, Dept Publ Hlth Sci, Charlottesville, VA USA. Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Rosand, J.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. RP Ay, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, AA Martinos Ctr Biomed Imaging,Dept Radiol, 13th St,Bldg 149,Room 2301, Charlestown, MA 02129 USA. EM hay@partners.org RI Thijs, Vincent/C-3647-2009; Arsava, Ethem Murat/I-9197-2013; OI Thijs, Vincent/0000-0002-6614-8417; Arsava, Ethem Murat/0000-0002-6527-4139; Macleod, Mary Joan/0000-0003-2115-8184 FU US Department of Veterans Affairs; NIH [NINDS R01 NS045012-05, NINDS 1RO1NS045012-01A1, 1U01NS069208, NHGI 1U01HG004436-01A1, NINDS P50NS044283, NINDS NS38477, NCI CA137254, NINDS NS063925, NINDS NS061119, NHGRI/NIH U-01 HG005160, U01 NS069208-01, NINDS R25 NS065733, NINDS R01 NS42147]; BMB; NGFN-Plus; Wellcome Trust; Foundation for Vascular Dementia Research; Bayer Schering Pharma; Bayer Vital GmbH; Baxter International Inc.; Biogen Idec; Merck Serono; Teva Pharmaceutical Industries Ltd./Sanofi-Aventis; NIH/NINDS [R01-HS011392, P50-NS051343, P50 NS051343, R01NS051412, P01 NS035611, R01NS059775-01, R01NS38477]; American Heart Association; Deane Institute; Yngve Land foundation for neurological research; Swedish Research Council; Lund University; Region Skane; Strokeriksforbundet; Emergency Medicine Foundation; Pfizer Inc.; Novartis; Merz Pharmaceuticals; LLC; Lundbeck Inc.; Takeda Pharmaceutical Company Limited; UK Department of Health; Genentech, Inc.; Siemens Medical Solutions; Millennium Pharmaceuticals, Inc.; AstraZeneca; Genentech Inc.; Schering Plough Corp; Scottish Executive Health Department; UK Binks Trust; Boehringer Ingelheim; Shire plc; SERVIER; Schering-Plough Corp; SYGNIS AG; CoAxia, Inc.; Medtronic, Inc.; Novo Nordisk; Bristol-Myers Squibb; ThromboGenics NV; Eli Lilly and Company; Sanofi- Aventis; Daiichi Sankyo; Asubio Pharmaceuticals, Inc.; FWO Flanders; Vlaams Instituut voor Biotechnologie; University of Virginia-CTSA; Deane Institute for Integrative Research in Atrial Fibrillation and Stroke FX Dr. Arsava and Dr. Ballabio report no disclosures. Dr. Benner serves/has served as a consultant for Siemens Medical Solutions, Bayer Schering Pharma, and Perceptive Informatics. Dr. Cole receives royalties from the publication of Stroke Essentials for Primary Care (Springer, 2009); received a speaker honorarium from Concentric Medical Inc.; serves as a consultant for Wyeth; and receives research support from the US Department of Veterans Affairs and the NIH (NINDS R01 NS045012-05 [Co-I]). Dr. Delgado-Martinez reports no disclosures. Dr. Dichgans served as Genetics Section Editor for Stroke and receives research support from BMB, NGFN-Plus, Wellcome Trust, and the Foundation for Vascular Dementia Research. Dr. Fazekas serves on scientific advisory boards for Biogen Idec and Teva Pharmaceutical Industries Ltd./Sanofi-Aventis; serves on the editorial advisory boards of Cerebrovascular Diseases, the Polish Journal of Neurology and Neurosurgery, the Journal of Neurology, Stroke, and the Swiss Archives of Neurology and Psychiatry; and has received consulting fees, speaker honoraria, and grant support from Bayer Schering Pharma, Bayer Vital GmbH, Baxter International Inc., Biogen Idec, Merck Serono, and Teva Pharmaceutical Industries Ltd./Sanofi-Aventis. Dr. Furie has served on scientific advisory boards for Novartis and GE Healthcare and receives research support from the NIH/NINDS [R01-HS011392 (PI) and P50-NS051343 (PI)], the American Heart Association, and the Deane Institute. Dr. Illoh reports no disclosures. Dr. Jood has received research support from the Yngve Land foundation for neurological research. Dr. Kittner receives research support from the NIH (NINDS 1RO1NS045012-01A1 [PI], NINDS 1U01NS069208 [Co-PI], and NHGI 1U01HG004436-01A1 [Co-I]) and the US Department of Veterans Affairs; and has provided expert witness testimony in medico-legal cases. Dr. Lindgren serves on scientific advisory boards for Boehringer Ingelheim and Sanofi-Aventis/Bristol-Myers Squibb; has received speaker honoraria from AstraZeneca; and receives research support from the Swedish Research Council, Lund University, Region Skane, and Strokeriksforbundet. Dr. Majersik and Dr. Macleod report no disclosures. Dr. Meurer receives research support from the NIH (NINDS P50NS044283 [Site PI]) and the Emergency Medicine Foundation. Dr. Montaner, Dr. Olugbodi, Dr. Pasdar, and Dr. Redfors report no disclosures. Dr. Schmidt serves on a scientific advisory board for Novartis; has received funding for travel and speaker honoraria from Pfizer Inc., Novartis, Merz Pharmaceuticals, LLC, Lundbeck Inc., and Takeda Pharmaceutical Company Limited; and serves on the editorial boards of Clinical Neurology and Neurosurgery and Neuropsychiatrie. Dr. Sharma has served on a scientific advisory board for Boehringer Ingelheim; has received speaker honoraria from Sanofi-Aventis and Bristol-Myers Squibb; and receives fellowship support from the UK Department of Health. Dr. Singhal has received research support from the NIH/NINDS (P50 NS051343 [Project PI], R01NS051412 [PI], P01 NS035611 [Co-I], R01NS059775-01 [Co-I], and R01NS38477 [Co-I]); his wife is an employee of and holds stock options in Vertex Pharmaceuticals; and has served as a medical expert witness in medicolegal cases concerning stroke. Dr. Sorensen has served on scientific advisory boards for Olea Medical and Breakaway Imaging; has received funding for travel from Genentech, Inc., Siemens Medical Solutions, Millennium Pharmaceuticals, Inc.; , and AstraZeneca; serves as a Section Editor of Stroke and on the editorial boards of Th Oncologist and the Journal of Clinical Oncology; holds patents re: Method for evaluating novel, stroke treatments using a tissue risk map, Imaging system for obtaining quantitative perfusion indices, Delay-compensated calculation of tissue blood flow, High-flow oxygen delivery system and methods of use thereof, and Magnetic resonance spatial risk map for tissue outcome prediction; receives royalties from the publication of Cerebral MR Perfusion Imaging (Thieme, 2000); has received speaker honoraria from Siemens Medical Solutions, Novartis, and GE Healthcare; has served as a consultant to Mitsubishi Tanabe Pharma Corporation, AstraZeneca, and Genentech, Inc.; receives research support from Millennium Pharmaceuticals, Inc., Siemens Medical Solutions, AstraZeneca, Genentech Inc., Novartis, Merck Serono, Schering Plough Corp, and the NIH [NINDS NS38477 (PI), NCI CA137254 (PI), NINDS NS063925 (PI), and NINDS NS061119 (PI)]; and holds stock and stock options in Epix Pharmaceuticals. Dr. Sudlow serves/has served on the editorial boards of Stroke, BioMed Central Cardiovascular Disorders, the British Medical Journal, and the Cochrane Stroke Group; receives royalties from the publication of Stroke: A Practical Guide to Management, 3rd ed. (Blackwell, 2008); and receives research support from the Scottish Executive Health Department, the Wellcome Trust, and the UK Binks Trust Research Fellowship. Dr. Thijs serves/has served on scientific advisory boards for Shire plc, Merck Serono, and SYGNIS AG; had received funding for travel from Boehringer Ingelheim and Shire plc; served as an Associate Editor for Acta Neurologica Belgica; has received speaker honoraria from Shire plc, Abbott, Pfizer Inc., Boehringer Ingelheim, and Medtronic, Inc.; receives research support from SERVIER, Schering-Plough Corp., SYGNIS AG, CoAxia, Inc., Medtronic, Inc., Novo Nordisk, Bristol-Myers Squibb, Pfizer Inc., Shire plc, AstraZeneca, ThromboGenics NV, Eli Lilly and Company, Sanofi- Aventis, Boehringer Ingelheim, Daiichi Sankyo, Asubio Pharmaceuticals, Inc., FWO Flanders, and Vlaams Instituut voor Biotechnologie; and holds stock in Novo Nordisk. Dr. Worrall serves as an Associate Editor of Neurology (R) and on the editorial board of Seminars in Neurology; receives royalties from the publication of Merritt's Neurology, 10th, 11th, and 12th ed. (chapter author); receives/has received research support from the NIH (NHGRI/NIH U-01 HG005160 [Co-PI], U01 NS069208-01[Co-PI], NHLBI contract [PI], NINDS R25 NS065733 [Mentor], NINDS R01 NS42147 [Site PI], NINDS R01 NS 39987 [Executive committee, Site PI], NINDS R01 NS039512 [Executive committee, Co-I], NHLBI contract [Physician investigator], K08-NS45802 [PI], and R01-NS42733 [Site PI]), and the University of Virginia-CTSA Pilot Project. Dr. Rosand serves on the editorial board of Stroke and receives research support from the NIH (5R01NS059727-02 [PI], 3RO1NS059727-01A1S1 [PI], and U01 NS069208-01 [Site PI]), the American Heart Association, and the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke. Dr. Ay receives research support from the NIH (R01-NS059710 [PI] and U01 NS069208-01. NR 20 TC 28 Z9 28 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 5 PY 2010 VL 75 IS 14 BP 1277 EP 1284 DI 10.1212/WNL.0b013e3181f612ce PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 663JW UT WOS:000282883900013 PM 20921513 ER PT J AU Flynn, TJ Ferguson, MS AF Flynn, Thomas J. Ferguson, Martine S. TI An in vitro system for studying potential biological mechanisms of human sex differences in susceptibility to acute liver injury SO TOXICOLOGY LETTERS LA English DT Article DE Sex differences; Hepatotoxicity; Cytokines; Sex hormones ID ACUTE-PHASE RESPONSE; HUMAN HEPATOMA-CELLS; HUMAN HEPATOCYTES; XENOBIOTIC METABOLISM; HERBAL HEPATOTOXICITY; RAT HEPATOCYTES; UNITED-STATES; HEPG2 CELLS; CYTOCHROME-P450; INFLAMMATION AB Women are more susceptible than men to acute liver injury from drugs and other xenobiotics. The biological mechanisms for this sex difference are unknown, but known sex differences in steroid hormone levels and immune response could play a role. A human hepatocyte cell line, HepG2, was cultured for 8 days in either a male hormone, female hormone, or sex hormone-free medium. The cells were then exposed to a mixture of pro-inflammatory cytokines (interleukin (IL)-1 beta, IL-6, TNF alpha) for 72 h to simulate acute inflammation. Cell viability (total DNA) and various metabolic functions (reactive oxygen species (ROS), neutral and polar lipid (PL) accumulation, mitochondrial membrane potential, cytochrome P450 (CYP) activities) were measured fluorometrically. Acute phase proteins (albumin, IL-1ra) were measured in the culture medium by ELISA. This model gave both significant hormone only effects (ROS, PL accumulation) and cytokine only effects (total DNA, CYP1A, neutral and PL accumulation, albumin, IL-1ra) consistent with known biological responses. Significant hormone-cytokine interactions were observed for several endpoints (total DNA, ROS, neutral and PL accumulation, albumin). These findings suggest that sex hormones and pro-inflammatory cytokines can interact to alter liver metabolism in ways that may contribute to the marked sex difference in susceptibility to chemical-induced acute liver injury. Published by Elsevier Ireland Ltd. C1 [Flynn, Thomas J.] US FDA, MOD Labs 1, Ctr Food Safety & Appl Nutr, Div Toxicol, Laurel, MD 20708 USA. [Ferguson, Martine S.] US FDA, Ctr Food Safety & Appl Nutr, Div Publ Hlth & Biostat, College Pk, MD 20740 USA. RP Flynn, TJ (reprint author), US FDA, MOD Labs 1, Ctr Food Safety & Appl Nutr, Div Toxicol, 8301 Muirkirk Road, Laurel, MD 20708 USA. EM thomas.flynn@fda.hhs.gov; martine.ferguson@fda.hhs.gov OI Flynn, Thomas/0000-0002-7248-0643 FU FDA Office of Women's Health FX This work was funded by a grant from the FDA Office of Women's Health. The authors would like to thank the late Dr. John Strong, FDA Center for Drug Evaluation and Research for his helpful suggestions during development of the experimental protocol. NR 50 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD OCT 5 PY 2010 VL 198 IS 2 BP 232 EP 236 DI 10.1016/j.toxlet.2010.07.003 PG 5 WC Toxicology SC Toxicology GA 651QS UT WOS:000281942800019 PM 20621171 ER PT J AU Price, GE Soboleski, MR Lo, CY Misplon, JA Quirion, MR Houser, KV Pearce, MB Pappas, C Tumpey, TM Epstein, SL AF Price, Graeme E. Soboleski, Mark R. Lo, Chia-Yun Misplon, Julia A. Quirion, Mary R. Houser, Katherine V. Pearce, Melissa B. Pappas, Claudia Tumpey, Terrence M. Epstein, Suzanne L. TI Single-Dose Mucosal Immunization with a Candidate Universal Influenza Vaccine Provides Rapid Protection from Virulent H5N1, H3N2 and H1N1 Viruses SO PLOS ONE LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; A VIRUS; RECOMBINANT ADENOVIRUS; DENDRITIC CELLS; IMMUNE-RESPONSES; IN-VIVO; HETEROSUBTYPIC IMMUNITY; INTRANASAL IMMUNIZATION; MATRIX PROTEIN-2; ANTIGENIC DRIFT AB Background: The sudden emergence of novel influenza viruses is a global public health concern. Conventional influenza vaccines targeting the highly variable surface glycoproteins hemagglutinin and neuraminidase must antigenically match the emerging strain to be effective. In contrast, "universal'' vaccines targeting conserved viral components could be used regardless of viral strain or subtype. Previous approaches to universal vaccination have required protracted multi-dose immunizations. Here we evaluate a single dose universal vaccine strategy using recombinant adenoviruses (rAd) expressing the conserved influenza virus antigens matrix 2 and nucleoprotein. Methodology/Principal Findings: In BALB/c mice, administration of rAd via the intranasal route was superior to intramuscular immunization for induction of mucosal responses and for protection against highly virulent H1N1, H3N2, or H5N1 influenza virus challenge. Mucosally vaccinated mice not only survived, but had little morbidity and reduced lung virus titers. Protection was observed as early as 2 weeks post-immunization, and lasted at least 10 months, as did antibodies and lung T cells with activated phenotypes. Virus-specific IgA correlated with but was not essential for protection, as demonstrated in studies with IgA-deficient animals. Conclusion/Significance: Mucosal administration of NP and M2-expressing rAd vectors provided rapid and lasting protection from influenza viruses in a subtype-independent manner. Such vaccines could be used in the interval between emergence of a new virus strain and availability of strain-matched vaccines against it. This strikingly effective single-dose vaccination thus represents a candidate off-the-shelf vaccine for emergency use during an influenza pandemic. C1 [Price, Graeme E.; Soboleski, Mark R.; Lo, Chia-Yun; Misplon, Julia A.; Quirion, Mary R.; Epstein, Suzanne L.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Houser, Katherine V.; Pearce, Melissa B.; Pappas, Claudia; Tumpey, Terrence M.] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA. RP Price, GE (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM suzanne.epstein@fda.hhs.gov FU National Institute of Allergy and Infectious Diseases Trans-NIH/FDA; Office of Public Health Medical Emergency Counter-Measures; FDA's Center for Biologics Evaluation and Research (CBER) pandemic influenza initiative FX This work was supported by grants from the National Institute of Allergy and Infectious Diseases Trans-NIH/FDA Intramural Biodefense Program, the Office of Public Health Medical Emergency Counter-Measures, and the FDA's Center for Biologics Evaluation and Research (CBER) pandemic influenza initiative. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 72 TC 67 Z9 68 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 4 PY 2010 VL 5 IS 10 AR e13162 DI 10.1371/journal.pone.0013162 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 657OZ UT WOS:000282423300009 PM 20976273 ER PT J AU Kachko, A Kochneva, G Sivolobova, G Grazhdantseva, A Lupan, T Zubkova, I Wells, F Merchlinsky, M Williams, O Watanabe, H Ivanova, A Shvalov, A Loktev, VB Netesov, S Major, ME AF Kachko, Alla Kochneva, Galina Sivolobova, Galina Grazhdantseva, Antonina Lupan, Tatyana Zubkova, Iryna Wells, Frances Merchlinsky, Michael Williams, Ollie Watanabe, Hisayoshi Ivanova, Alla Shvalov, Aleksander Loktev, Valeriy B. Netesov, Sergey Major, Marian E. TI NEW NEUTRALIZING ANTIBODY EPITOPES IN HEPATITIS C VIRUS ENVELOPE GLYCOPROTEINS ARE REVEALED BY DISSECTING PEPTIDE RECOGNITION PROFILES SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Kachko, Alla; Zubkova, Iryna; Wells, Frances; Merchlinsky, Michael; Williams, Ollie; Major, Marian E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Kochneva, Galina; Sivolobova, Galina; Grazhdantseva, Antonina; Lupan, Tatyana; Ivanova, Alla; Shvalov, Aleksander; Loktev, Valeriy B.] State Res Ctr Virol & Biotechnol Vector, Novosibirsk, Russia. [Netesov, Sergey] Novosibirsk State Univ, Novosibirsk 630090, Russia. [Watanabe, Hisayoshi] Yamagata Univ, Sch Med, Dept Gastroenterol, Yamagata 99023, Japan. RI Kochneva, Galina/B-7356-2012; Loktev, Valery/J-5195-2012; Netesov, Sergey/A-3751-2013; Shvalov, Alexander/A-6611-2014 OI Netesov, Sergey/0000-0002-7786-2464; Shvalov, Alexander/0000-0001-6890-1575 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 142 BP 391A EP 391A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775600143 ER PT J AU Mishra, P Gelperin, K Lee, J Gilbert, J Boucher, R Brinker, AD Graham, DJ Choi, L Avigan, M Senior, JR AF Mishra, Poonam Gelperin, Kate Lee, Joann Gilbert, Jane Boucher, Robert Brinker, Allen D. Graham, David J. Choi, Lauren Avigan, Mark Senior, John R. TI DRUG-INDUCED LIVER INJURY (DILI) ASSOCIATED WITH LEFLUNOMIDE USE IN RHEUMATOID ARTHRITIS PATIENTS: CASE SEVERITY AND CAUSALITY ADJUDICATION USING THE DILIN (DRUG-INDUCED LIVER INJURY NETWORK) CRITERIA SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Mishra, Poonam] US FDA, Off Antimicrobial Prod, Silver Spring, MD USA. [Gelperin, Kate; Lee, Joann; Gilbert, Jane; Boucher, Robert; Brinker, Allen D.; Graham, David J.; Choi, Lauren; Avigan, Mark; Senior, John R.] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 271 BP 458A EP 458A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775600277 ER PT J AU Mirjani, R Rafii, F Sharifzadeh, M Amanlou, M Shahverdi, AR AF Mirjani, Ruhollah Rafii, Fatemeh Sharifzadeh, Mohammad Amanlou, Massoud Shahverdi, Ahmad R. TI Post-antibiotic and post-antibiotic sub-MIC effects of gentamicin, sophoraflavanone G, and their combination against a clinical isolate of Staphylococcus aureus SO ASIAN BIOMEDICINE LA English DT Article DE Gentamicin; post-antibiotic effect; sophoraflavanone G; Staphylococcus aureus ID SOPHORA-FLAVESCENS; ANTIBACTERIAL ACTIVITY; ANTIBIOTICS; RESISTANCE AB Background: Post-antibiotic effect (PAE) defines the potential of a drug to delay re-growth of a bacterial population after short-term exposure and removal of a drug. Determination of the PAE is recommended in preclinical evaluation of all new antimicrobial agents, because it influences optimal antimicrobial dosing intervals. Objective: Evaluate the PAE and PA-SME of gentamicin and sophoraflavanone G against Staphylococcus aureus (S. aureus) itself and in combination. Methods: A spectrophotometric method was used to determine the PAR and PA-SME. Results: Sophoraflavanone G and gentamicin, showed considerable PAE and PA-SME at the tested concentrations against S. aureus. The increased duration of PAE caused by sophoraflavanone G and gentamicin was dose-dependent. In addition, sophoraflavanone G at sub-MIC concentrations enhanced the PAE and PA-SME of gentamicin in a dose-dependent manner. The highest enhancing effect was observed for gentamicin at the synergistic MIC and 1/2 the synergistic MIC levels against S. aureus 0.03 mu g/mL (30 ng/mL) of sophoraflavanone G (with PAE=55 minutes). It enhanced the post-antibiotic sub-MIC effect (PA-SME) duration of gentamicin at concentrations of 4 mu g/mL from 15 minutes to 80 minutes (a six-fold increase). Conclusion: Sophoraflavanone G is promising for the preparation of an effective therapeutic formulation against gentamicin-resistant S. aureus. C1 [Mirjani, Ruhollah; Shahverdi, Ahmad R.] Univ Tehran Med Sci, Dept Pharmaceut Biotechnol & Pharmaceut Sci, Res Ctr, Fac Pharm, Tehran 1417614411, Iran. [Sharifzadeh, Mohammad] Univ Tehran Med Sci, Dept Pharmacol & Toxicol, Res Ctr, Fac Pharm, Tehran 1417614411, Iran. [Amanlou, Massoud] Univ Tehran Med Sci, Dept Med Chem, Res Ctr, Fac Pharm, Tehran 1417614411, Iran. [Rafii, Fatemeh] Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Shahverdi, AR (reprint author), Univ Tehran Med Sci, Dept Pharmaceut Biotechnol & Pharmaceut Sci, Res Ctr, Fac Pharm, Tehran 1417614411, Iran. EM shahverd@sina.tums.ac.ir OI sharifzadeh, mohammad/0000-0003-2991-7384 FU Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Iran FX This work was supported by Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Iran. The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration. The authors have no conflict of interest to report. NR 16 TC 1 Z9 1 U1 0 U2 1 PU CHULALONGKORN UNIV, FAC MED PI BANGKOK PA CHULALONGKORN UNIV, FAC MED, 1873, RAMA 4, BANGKOK, 10330, THAILAND SN 1905-7415 J9 ASIAN BIOMED JI Asian Biomed. PD OCT PY 2010 VL 4 IS 5 BP 821 EP 826 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 677DM UT WOS:000283969300021 ER PT J AU Fujisawa, T Joshi, BH Puri, RK AF Fujisawa, Toshio Joshi, Bharat H. Puri, Raj K. TI Histone Modification Upregulates Expression of IL-13R alpha 2 in Human Pancreatic Cancer Cells and Enhances the Effectiveness of IL-13 Receptor Targeted Immunotoxin IL-13-PE in Animal Model of Human Pancreatic Cancer SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract C1 [Fujisawa, Toshio; Joshi, Bharat H.; Puri, Raj K.] US FDA, Ctr Biol Evaluat & Res, Div Cellular Gene Therapy, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 2010 VL 33 IS 8 BP 897 EP 897 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 653XQ UT WOS:000282131800131 ER PT J AU Al-Khatib, SM Calkins, H Eloff, BC Kowey, P Hammill, SC Ellenbogen, KA Marinac-Dabic, D Waldo, AL Brindis, RG Wilbur, DJ Jackman, WM Yaross, MS Russo, AM Prystowsky, E Varosy, PD Gross, T Pinnow, E Turakhia, MP Krucoff, MW AF Al-Khatib, Sana M. Calkins, Hugh Eloff, Benjamin C. Kowey, Peter Hammill, Stephen C. Ellenbogen, Kenneth A. Marinac-Dabic, Danica Waldo, Albert L. Brindis, Ralph G. Wilbur, David J. Jackman, Warren M. Yaross, Marcia S. Russo, Andrea M. Prystowsky, Eric Varosy, Paul D. Gross, Thomas Pinnow, Ellen Turakhia, Mintu P. Krucoff, Mitchell W. TI Developing the Safety of Atrial Fibrillation Ablation Registry Initiative (SAFARI) as a collaborative pan-stakeholder critical path registry model: A Cardiac Safety Research Consortium "Incubator" Think Tank SO AMERICAN HEART JOURNAL LA English DT Article ID ANTIARRHYTHMIC-DRUG THERAPY; PULMONARY-VEIN ABLATION; RADIOFREQUENCY ABLATION; CATHETER ABLATION; RANDOMIZED-TRIAL AB Although several randomized clinical trials have demonstrated the safety and efficacy of catheter ablation of atrial fibrillation (AF) in experienced centers, the outcomes of this procedure in routine clinical practice and in patients with persistent and long-standing persistent AF remain uncertain. Brisk adoption of this therapy by physicians with diverse training and experience highlights potential concerns regarding the safety and effectiveness of this procedure. Some of these concerns could be addressed by a national registry of AF ablation procedures such as the Safety of Atrial Fibrillation Ablation Registry Initiative that was initially proposed at a Cardiac Safety Research Consortium Think Tank meeting in April 2009. In January 2010, the Cardiac Safety Research Consortium, in collaboration with the Duke Clinical Research Institute, the US Food and Drug Administration, the American College of Cardiology, and the Heart Rhythm Society, held a follow-up meeting of experts in the field to review the construct and progress to date. Other participants included the National Heart, Lung, and Blood Institute; the Centers for Medicare and Medicaid Services; the Agency for Healthcare Research and Quality; the AdvaMed AF working group; and additional industry representatives. This article summarizes the discussions that occurred at the meeting of the state of the Safety of Atrial Fibrillation Ablation Registry Initiative, the identification of a clear pathway for its implementation, and the exploration of solutions to potential issues in the execution of this registry. (Am Heart J 2010; 160: 619-626.e1.) C1 [Al-Khatib, Sana M.; Krucoff, Mitchell W.] Duke Univ, Duke Clin Res Inst, Med Ctr, Durham, NC 27715 USA. [Calkins, Hugh] Johns Hopkins Univ, Baltimore, MD USA. [Eloff, Benjamin C.; Marinac-Dabic, Danica; Gross, Thomas; Pinnow, Ellen] US FDA, Silver Spring, MD USA. [Kowey, Peter] Main Line Hlth Heart Ctr, Philadelphia, PA USA. [Hammill, Stephen C.] Mayo Clin, Rochester, MN USA. [Ellenbogen, Kenneth A.] Virginia Commonwealth Univ, Sch Med, Richmond, VA USA. [Waldo, Albert L.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Brindis, Ralph G.] Amer Coll Cardiol, Washington, DC USA. [Brindis, Ralph G.] Oakland Kaiser Permanente, Oakland, CA USA. [Wilbur, David J.] Loyola Univ, Med Ctr, Chicago, IL 60611 USA. [Jackman, Warren M.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Yaross, Marcia S.] Biosense Webster, Diamond Bar, CA USA. [Russo, Andrea M.] Cooper Univ Hosp, Robert Wood Johnson Med Sch, Camden, NJ USA. [Prystowsky, Eric] Care Grp, Indianapolis, IN USA. [Varosy, Paul D.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Varosy, Paul D.] Univ Colorado, Denver, CO 80202 USA. [Turakhia, Mintu P.] Palo Alto VA Hlth Care Syst, Palo Alto, CA USA. [Turakhia, Mintu P.] Stanford Univ, Stanford, CA 94305 USA. RP Al-Khatib, SM (reprint author), Duke Univ, Duke Clin Res Inst, Med Ctr, POB 17969, Durham, NC 27715 USA. EM alkha001@mc.duke.edu FU CSRC, DCRI, ACC, HRS; FDA; AdvaMed FX This conference was funded by the CSRC, DCRI, ACC, HRS; registration fees and in-kind support from the FDA and AdvaMed. NR 16 TC 10 Z9 10 U1 1 U2 3 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 OCT PY 2010 VL 160 IS 4 BP 619 EP U249 DI 10.1016/j.ahj.2010.06.044 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 660WN UT WOS:000282677300010 PM 20934554 ER PT J AU Rodriguez, I Erdman, A Padhi, D Garnett, CE Zhao, H Targum, SL Balakrishnan, S Strnadova, C Viner, N Geiger, MJ Newton-Cheh, C Litwin, J Pugsley, MK Sager, PT Krucoff, MW Finkle, JK AF Rodriguez, Ignacio Erdman, Andrew Padhi, Desmond Garnett, Christine E. Zhao, Hong Targum, Shari L. Balakrishnan, Suchitra Strnadova, Colette Viner, Norman Geiger, Mary Jane Newton-Cheh, Christopher Litwin, Jeffrey Pugsley, Michael K. Sager, Philip T. Krucoff, Mitchell W. Finkle, John K. TI Electrocardiographic assessment for therapeutic proteins-scientific discussion SO AMERICAN HEART JOURNAL LA English DT Article ID HERG POTASSIUM CHANNELS; LONG QT SYNDROME; MONOCLONAL-ANTIBODIES; INTERVAL PROLONGATION; PROARRHYTHMIC RISK; K+ CHANNEL; CARDIOTOXICITY; REPOLARIZATION; TRASTUZUMAB; VASOPRESSIN AB Electrocardiographic monitoring is an integral component of the clinical assessment of cardiac safety of all compounds in development. The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use E14 guideline recommends a dedicated study to evaluate drug-induced effects on cardiac repolarization ("thorough QT/QTc study"). There has been limited published information on QT interval changes secondary to therapeutic proteins; however, in theory, biologic therapies may affect cardiac electrical activity either directly or indirectly. This article summarizes scientific discussions of members of the Cardiac Safety Research Consortium and includes possible approaches to consider for the clinical evaluation of drug-induced QT prolongation in development programs of therapeutic proteins. (Am Heart J 2010; 160: 627-34.) C1 [Rodriguez, Ignacio] Roche, Nutley, NJ USA. [Erdman, Andrew] Amgen Inc, San Francisco, CA USA. [Padhi, Desmond] Amgen Inc, Thousand Oaks, CA USA. [Garnett, Christine E.; Zhao, Hong; Targum, Shari L.; Balakrishnan, Suchitra] US FDA, Silver Spring, MD USA. [Strnadova, Colette; Viner, Norman] Hlth Canada, Ottawa, ON K1A 0L2, Canada. [Geiger, Mary Jane] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Broad Inst Harvard, Cambridge, MA USA. [Newton-Cheh, Christopher] MIT, Cambridge, MA 02139 USA. [Litwin, Jeffrey] ERT, Philadelphia, PA USA. [Pugsley, Michael K.] Johnson & Johnson, Raritan, NJ USA. [Sager, Philip T.] Sager Consulting Partners, San Francisco, CA USA. [Krucoff, Mitchell W.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Finkle, John K.] GlaxoSmithKline Inc, Upper Providence, PA USA. RP Rodriguez, I (reprint author), 340 Kingsland St, Nutley, NJ 07110 USA. EM ignacio.rodriguez.ir1@roche.com NR 36 TC 19 Z9 19 U1 0 U2 2 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 OCT PY 2010 VL 160 IS 4 BP 627 EP 634 DI 10.1016/j.ahj.2010.07.001 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 660WN UT WOS:000282677300011 PM 20934555 ER PT J AU Burwen, DR Ball, R Bryan, WW Izurieta, HS La Voie, L Gibbs, NA Kliman, R Braun, MM AF Burwen, Dale R. Ball, Robert Bryan, Wilson W. Izurieta, Hector S. La Voie, Lawrence Gibbs, Neville A. Kliman, Rebecca Braun, M. Miles TI Evaluation of Guillain-Barre Syndrome Among Recipients of Influenza Vaccine in 2000 and 2001 SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID UNITED-STATES; EPIDEMIOLOGIC FEATURES; IMMUNIZATION-PROGRAM; ASSOCIATION; SURVEILLANCE; POPULATION; CRITERIA; SAFETY; SWEDEN; GREECE AB Background: The 1976-1977 swine influenza vaccine was associated with an elevated risk of Guillain-Barre Syndrome (GBS), especially within 6 weeks after vaccination. A 2004 IOM report concluded that evidence was inadequate to accept or reject a causal relationship between subsequent influenza vaccine formulations and GBS. Studies published after the IOM report have been limited by passively reported data or lack of validation of coded diagnoses. Purpose: To evaluate whether influenza vaccine is associated with GBS. Methods: Controlled observational study using national data from the Medicare program, which ensures a predominantly elderly population. People included had a Medicare claim for influenza vaccination during September-December in 2000 or 2001. Medical records were reviewed to classify definite, probable, or possible GBS (or not a case) using a standardized case definition. In a risk interval design, the incidence rate of GBS during Weeks 0-6 after vaccination (exposed period) was compared to Weeks 9-14 after vaccination (comparison period). Data collection occurred during 2003-2007, and analysis was conducted during 2007-2009. Results: Primary analysis included 22.2 million vaccinees, among whom 164 definite or probable GBS cases with onset during Weeks 0-6 or 9-14 were identified. The incidence rate ratio (IRR [95% CIs]) based on the GBS rate in the vaccine-exposed versus comparison periods, was 1.04 (0.76, 1.43) for combined years; 0.86 (0.52, 1.41) among people vaccinated in 2000; and 1.21 (0.79, 1.86) among people vaccinated in 2001. Secondary analysis additionally included 74 possible GBS cases; results were similar. Conclusions: Overall, the results do not support an association between influenza vaccine receipt and GBS among the elderly for the years studied (2000-2001 and 2001-2002 formulations). (Am J Prev Med 2010;39(4):296-304) Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine C1 [Burwen, Dale R.; Ball, Robert; Izurieta, Hector S.; Braun, M. Miles] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Bryan, Wilson W.; Gibbs, Neville A.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Kliman, Rebecca] Ctr Medicare, Qual Improvement Grp, Off Clin Stand & Qual, Baltimore, MD USA. [Kliman, Rebecca] Ctr Medicaid Serv, Qual Improvement Grp, Off Clin Stand & Qual, Baltimore, MD USA. [La Voie, Lawrence] Ctr Medicare, Kansas City Reg Off, Kansas City, MO USA. [La Voie, Lawrence] Ctr Medicare, Kansas City Reg Off, Kansas City, MO USA. RP Burwen, DR (reprint author), US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 222,Suite 200S, Rockville, MD 20852 USA. EM dale.burwen@fda.hhs.gov FU National Vaccine Program Office, USDHHS FX We thank Benjamin Robertson of CMS for assistance with project coordination, and Tina Khoie, MD, MPH, Azra Dobardzic, MD, MSc, PhD, and Manette Niu, MD, FDA, for contributions to data acquisition. We also thank Tamar Lasky, PhD, University of Rhode Island, and A. Marshall McBean, MD, MSc, University of Minnesota, for sharing some unpublished materials from prior studies. This work was supported in part by funding from the National Vaccine Program Office, USDHHS. NR 40 TC 19 Z9 19 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2010 VL 39 IS 4 BP 296 EP 304 DI 10.1016/j.amepre.2010.05.022 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 650QY UT WOS:000281867100002 PM 20837279 ER PT J AU Jain, L Abraham, S Shord, SS AF Jain, Lokesh Abraham, Sophia Shord, Stacy S. TI The Interactions of Anti-Cancer Drugs Approved in the Last Decade in the United States with Membrane Transporters SO ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY LA English DT Article DE Cytotoxic agents; drug resistance; drug-drug interactions; hormonal therapies; pharmacokinetics; targeted anticancer therapies; transporters ID CANCER RESISTANCE PROTEIN; CHRONIC MYELOID-LEUKEMIA; TYROSINE KINASE INHIBITOR; P-GLYCOPROTEIN ABCB1; T-CELL LYMPHOMA; REVERSES MULTIDRUG-RESISTANCE; ORGANIC CATION TRANSPORTER-1; SUBFAMILY-B MEMBER-1; IN-VITRO; PHASE-I AB Membrane transporters play a role in determining the absorption, distribution, metabolism and excretion of small molecule anticancer drugs and mediating chemosensitivity and resistance of tumor cells to these drugs. Our understanding of the influence of these transporters on the pharmacokinetics, clinical effectiveness and tolerability has considerably increased in the last decade. We reviewed the interaction of the small molecule anticancer drugs approved in the last decade with the more common membranes transporters, such as ABCB1, ABCG2, and OATP. The drugs were divided into three categories: targeted therapies, cytotoxic agents and hormonal therapies. The literature appears to focus on the interaction of the targeted therapies compared to the remaining two categories. Furthermore, most data stemmed from nonclinical studies with only a few clinical examples where transporters corresponded with systemic exposure, clinical effectiveness, or tolerability. More nonclinical and clinical studies are needed to improve the ability to use the findings from these nonclinical studies to predict clinical outcomes, but the literature appears to be rapidly expanding as our understanding of these transporters grows. Therefore, determining the interaction of membrane transporters with small molecule anticancer drugs can facilitate the development of effective and safe treatments. C1 [Jain, Lokesh] US FDA, CDER, OTS, OCP,DCP2, Silver Spring, MD 20993 USA. [Abraham, Sophia; Shord, Stacy S.] US FDA, Div Clin Pharmacol 5, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Jain, L (reprint author), US FDA, CDER, OTS, OCP,DCP2, 10903 New Hampshire Ave,Bldg 51,Room 2219, Silver Spring, MD 20993 USA. EM Lokesh.Jain@fda.hhs.gov NR 156 TC 2 Z9 2 U1 0 U2 9 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5206 J9 ANTI-CANCER AGENT ME JI Anti-Cancer Agents Med. Chem. PD OCT PY 2010 VL 10 IS 8 BP 601 EP 616 PG 16 WC Oncology; Chemistry, Medicinal SC Oncology; Pharmacology & Pharmacy GA 734FD UT WOS:000288318500004 PM 21194401 ER PT J AU Wang, QZ Shastri, K Pfefer, TJ AF Wang, Quanzeng Shastri, Karthik Pfefer, T. Joshua TI Experimental and theoretical evaluation of a fiber-optic approach for optical property measurement in layered epithelial tissue SO APPLIED OPTICS LA English DT Article ID DIFFUSE-REFLECTANCE SPECTRA; MONTE-CARLO-SIMULATION; 2-LAYER TURBID MEDIA; IN-VIVO; CERVICAL NEOPLASIA; LIGHT TRANSPORT; MODEL; SPECTROSCOPY; FLUORESCENCE; SCATTERING AB Improvements in measurement of epithelial tissue optical properties (OPs) in the ultraviolet and visible (UV-Vis) may lead to enhanced understanding of optical techniques for neoplasia detection. In this study, we investigated an approach based on fiber-optic measurement of reflectance to determine absorption and reduced scattering coefficients (mu(a) and mu'(s)) in two-layer turbid media. Neural network inverse models were trained on simulation data for a wide variety of OP combinations (mu(a) = 1-22.5, mu'(s) = 5-42.5cm(-1)). Experimental measurements of phantoms with top-layer thicknesses (D) ranging from 0.22 to 0.66mm were performed at three UV-Vis wavelengths. OP estimation accuracy was calculated and compared to theoretical results. Mean prediction errors were strongly correlated with D and ranged widely, from 1.5 to 12.1cm(-1). Theoretical analyses indicated the potential for improving accuracy with alternate probe geometries. Although numerous challenges remain, this initial experimental study of an unconstrained approach for fiber-optic-based OP determination in two-layer epithelial tissue indicates the potential to provide useful measurements. (C) 2010 Optical Society of America C1 [Wang, Quanzeng; Pfefer, T. Joshua] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Shastri, Karthik] Univ Virginia, Dept Chem, Charlottesville, VA 22904 USA. RP Wang, QZ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM quanzeng.wang@fda.hhs.gov RI Pfefer, Josh/I-9055-2012 NR 38 TC 16 Z9 17 U1 1 U2 9 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 OCT 1 PY 2010 VL 49 IS 28 BP 5309 EP 5320 DI 10.1364/AO.49.005309 PG 12 WC Optics SC Optics GA 657WO UT WOS:000282449800016 PM 20885467 ER PT J AU Park, M Rooney, AP Hecht, DW Li, JH McClane, BA Nayak, R Paine, DD Rafii, F AF Park, Miseon Rooney, Alejandro P. Hecht, David W. Li, Jihong McClane, Bruce A. Nayak, Rajesh Paine, Donald D. Rafii, Fatemeh TI Phenotypic and genotypic characterization of tetracycline and minocycline resistance in Clostridium perfringens SO ARCHIVES OF MICROBIOLOGY LA English DT Article DE Clostridium perfringens; Tetracycline; Resistance ID ANTIMICROBIAL RESISTANCE; GENES; SUSCEPTIBILITY; DETERMINANTS; ANTIBIOTICS; PREVALENCE; PROTEINS; REVEALS; STRAINS; TETA(P) AB The aim of this study was to determine the incidence of tetracycline resistance and the prevalence of tetracycline-resistance genes in strains of Clostridium perfringens isolated from different sources between 1994 and 2005. Susceptibility to tetracycline and minocycline in strains from humans (35 isolates), chickens (15 isolates), food (21 isolates), soil (16 isolates) and veterinary sources (6 isolates) was determined, and tetracycline-resistance genes were detected. Resistance was most common in strains isolated from chickens, followed by those from soils, clinical samples and foods. The most highly resistant strains were found among clinical and food isolates. tetA(P) was the most common resistance gene, and along with tetB(P) was found in all resistant strains and some sensitive strains. One tetracycline-resistant food isolate had an intact tet(M) gene. However, PCR fragments of 0.4 or 0.8 kb with high degrees of identity to parts of the tet(M) sequences of other bacteria were found, mainly in clinical isolates, and often in isolates with tetB(P). No correlation between level of sensitivity to tetracycline or minocycline and the presence of tetA(P), tetB(P) or part of tet(M) was found. The presence of part of tet(M) in some strains of C. perfringens containing tetB(P) may have occurred by recent gene transfer. C1 [Park, Miseon; Nayak, Rajesh; Paine, Donald D.; Rafii, Fatemeh] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Rooney, Alejandro P.] ARS, Natl Ctr Agr Utilizat Res, USDA, Peoria, IL 61604 USA. [Hecht, David W.] Loyola Univ, Med Ctr, Dept Microbiol & Immunol, Maywood, IL 60153 USA. [Li, Jihong; McClane, Bruce A.] Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. RP Rafii, F (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM Fatemeh.rafii@fda.hhs.gov NR 31 TC 4 Z9 5 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0302-8933 J9 ARCH MICROBIOL JI Arch. Microbiol. PD OCT PY 2010 VL 192 IS 10 BP 803 EP 810 DI 10.1007/s00203-010-0605-5 PG 8 WC Microbiology SC Microbiology GA 650IN UT WOS:000281842600003 PM 20661548 ER PT J AU Bonaventura, C Henkens, R De Jesus-Bonilla, W Lopez-Garriga, J Jia, YP Alayash, AI Siburt, CJP Crumbliss, AL AF Bonaventura, Celia Henkens, Robert De Jesus-Bonilla, Walleska Lopez-Garriga, Juan Jia, Yiping Alayash, Abdu I. Siburt, Claire J. Parker Crumbliss, Alvin L. TI Extreme differences between Hemoglobins I and II of the Clam Lucina pectinalis in their reactions with nitrite SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Article DE Hemoglobin; Dynamics; Adaptations; Nitrite; Heme oxidation; Heme accessibility ID AUTOCATALYTIC OXIDATION; NITRATE RESPIRATION; OXYGEN; OXIDE; DEOXYHEMOGLOBIN; OXYHEMOGLOBIN; REACTIVITY; REDUCTION; MECHANISM; MYOGLOBIN AB The clam Lucina pectinalis supports its symbiotic bacteria by H(2)S transport in the open and accessible heme pocket of Lucina Hb I and by O(2) transport in the narrow and crowded heme pocket of Lucina Hb II. Remarkably, air-equilibrated samples of Lucina Hb I were found to be more rapidly oxidized by nitrite than any previously studied Hb, while those of Lucina Hb II showed an unprecedented resistance to oxidation induced by nitrite. Nitrite-induced oxidation of Lucina Hb II was enabled only when O(2) was removed from its active site. Structural analysis revealed that O(2) "clams up" the active site by hydrogen bond formation to B10Tyr and other distal-side residues. Quaternary effects further restrict nitrite entry into the active site and stabilize the hydrogen-bonding network in oxygenated Lucina Hb II dimers. The dramatic differences in nitrite reactivities of the Lucina Hbs are not related to their O(2) affinities or anaerobic redox potentials, which were found to be similar, but are instead a result of differences in accessibility of nitrite to their active sites; i.e. these differences are due to a kinetic rather than thermodynamic effect. Comparative studies revealed heme accessibility to be a factor in human Hb oxidation by nitrite as well, as evidenced by variations of rates of nitrite-induced oxidation that do not correlate with R and T state differences and inhibition of oxidation rate in the presence of O(2). These results provide a dramatic illustration of how evolution of active sites with varied heme accessibility can moderate the rates of inner-sphere oxidative reactions of Hb and other heme proteins. (C) 2010 Elsevier B.V. All rights reserved. C1 [Bonaventura, Celia; Henkens, Robert] Duke Univ, Marine Lab, Nicholas Sch Environm, Beaufort, NC 28516 USA. [De Jesus-Bonilla, Walleska; Lopez-Garriga, Juan] Univ Puerto Rico, Dept Chem, Mayaguez, PR 00681 USA. [Jia, Yiping; Alayash, Abdu I.] US FDA, Lab Biochem & Vasc Biol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Henkens, Robert; Siburt, Claire J. Parker; Crumbliss, Alvin L.] Duke Univ, Dept Chem, Durham, NC 27708 USA. RP Bonaventura, C (reprint author), Duke Univ, Marine Lab, Nicholas Sch Environm, Beaufort, NC 28516 USA. EM bona@duke.edu RI Rinaldi2, Carlos/D-4479-2011 FU NIH [5P01-HL-071064-04]; NSF [CHE-0809466, MCB-0843608, NIGMS MBRS-SCORE 2 S06GM08103-34] FX CB thanks Giulia Ferruzi for excellent technical assistance and NIH for financial support (5P01-HL-071064-04). ALC thanks NSF for support (CHE-0809466). JLG gratefully acknowledges partial support from NSF (MCB-0843608) and NIH (NIGMS MBRS-SCORE 2 S06GM08103-34). The opinions and assertions contained herein are the scientific views of the author and are not to be construed as policy of the United States Food and Drug Administration. NR 38 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD OCT PY 2010 VL 1804 IS 10 BP 1988 EP 1995 DI 10.1016/j.bbapap.2010.06.016 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 651IB UT WOS:000281920300005 PM 20601225 ER PT J AU Miller, S James, R Landry, R Pfefer, J AF Miller, Sharon James, Robert Landry, Robert Pfefer, Joshua TI Optical characterization of cutaneous transilluminators for eye safety SO BIOMEDICAL OPTICS EXPRESS LA English DT Article AB Cutaneous transilluminators are light-emitting devices used to localize blood vessels for various medical procedures. They are often used in populations that may be at increased risk for skin burns, such as neonates and the elderly. While there is a known potential for skin burns, little is known about the ophthalmic risk from the use of these devices. This paper will report on the laboratory evaluation of the potential ocular hazards from transilluminators (TIs). Our results indicate that transilluminators which incorporate white-light LEDs have emissions that have the potential for producing injury to the retina, especially in patients who may have a reduced aversion response. 2010 Optical Society of America C1 [Miller, Sharon; James, Robert; Landry, Robert; Pfefer, Joshua] US FDA, Div Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Miller, S (reprint author), US FDA, Elect Prod Branch, Div Mammog Qual & Radiat Programs, Off Commun Educ & Radiat Programs,Ctr Devices & R, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM sharona.miller@fda.hhs.gov RI Pfefer, Josh/I-9055-2012 NR 24 TC 1 Z9 1 U1 0 U2 0 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD OCT 1 PY 2010 VL 1 IS 3 BP 771 EP 779 PG 9 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA V21LM UT WOS:000208209100004 ER PT J AU Goldin, LR Lanasa, MC Slager, SL Cerhan, JR Vachon, CM Strom, SS Camp, NJ Spector, LG Leis, JF Morrison, VA Glenn, M Rabe, KG Achenbach, SJ Algood, SD Abbasi, F Fontaine, L Yau, M Rassenti, LZ Kay, NE Call, TG Hanson, CA Weinberg, JB Marti, GE Caporaso, NE AF Goldin, Lynn R. Lanasa, Mark C. Slager, Susan L. Cerhan, James R. Vachon, Celine M. Strom, Sara S. Camp, Nicola J. Spector, Logan G. Leis, Jose F. Morrison, Vicki A. Glenn, Martha Rabe, Kari G. Achenbach, Sara J. Algood, Sallie D. Abbasi, Fatima Fontaine, Laura Yau, Michelle Rassenti, Laura Z. Kay, Neil E. Call, Timothy G. Hanson, Curtis A. Weinberg, J. Brice Marti, Gerald E. Caporaso, Neil E. TI Common occurrence of monoclonal B-cell lymphocytosis among members of high-risk CLL families SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE chronic lymphocytic leukaemia; high risk families; monoclonal B-cell lymphocytosis; flow cytometry ID NATURAL-HISTORY; FLOW-CYTOMETRY; LEUKEMIA; BLOOD; GUIDELINES; DIAGNOSIS; RELATIVES; CLONES AB P>Monoclonal B-cell lymphocytosis (MBL) is an asymptomatic haematological condition characterized by low absolute levels of B-cell clones with a surface immunophenotype similar to that of chronic lymphocytic leukaemia (CLL). In the general population, MBL increases with age with a prevalence of 5-9% in individuals over age 60 years. It has been reported to be higher among first-degree relatives from CLL families. We report results of multi-parameter flow cytometry among 505 first-degree relatives with no personal history of lymphoproliferative disease from 140 families having at least two cases of CLL. Seventeen percent of relatives had MBL. Age was the most important determinant where the probability for developing MBL by age 90 years was 61%. MBL clustered in certain families but clustering was independent of the number of known CLL cases in a family. As is the case with CLL, males had a significantly higher risk for MBL than did females (P = 0 center dot 04). MBL patients had significantly higher mean absolute lymphocyte counts (2 center dot 4 x 109/l) and B-cell counts (0 center dot 53 x 109/l) than those with a normal B-cell immuno-phenotype. Our findings show that MBL occurs at a very high rate in high risk CLL families. Both the age and gender distribution of MBL are parallel to CLL, implying a shared inherited risk. C1 [Goldin, Lynn R.] NCI, Genet Epidemiol Branch, DCEG, Bethesda, MD 20892 USA. [Lanasa, Mark C.; Algood, Sallie D.; Weinberg, J. Brice] Duke Univ, Med Ctr, Durham, NC USA. [Slager, Susan L.; Cerhan, James R.; Vachon, Celine M.; Rabe, Kari G.; Achenbach, Sara J.; Kay, Neil E.; Call, Timothy G.; Hanson, Curtis A.] Mayo Clin, Coll Med, Rochester, MN USA. [Strom, Sara S.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Camp, Nicola J.; Glenn, Martha] Univ Utah, Salt Lake City, UT USA. [Spector, Logan G.; Morrison, Vicki A.] Univ Minnesota, Minneapolis, MN USA. [Leis, Jose F.] Mayo Clin Arizona, Phoenix, AZ USA. [Morrison, Vicki A.] VA Med Ctr, Minneapolis, MN USA. [Abbasi, Fatima; Marti, Gerald E.] US FDA, Cellular & Tissue Therapy Branch, CBER, OCTGC, Rockville, MD USA. [Fontaine, Laura] Westat Corp, Rockville, MD USA. [Rassenti, Laura Z.] Moores UCSD Canc Ctr, La Jolla, CA USA. [Weinberg, J. Brice] VA Med Ctr, Durham, NC USA. RP Goldin, LR (reprint author), NCI, Genet Epidemiol Branch, DCEG, 6120 Execut Blvd,Rm 7008,MSC 7236, Bethesda, MD 20892 USA. EM goldinl@mail.nih.gov OI Cerhan, James/0000-0002-7482-178X; Spector, Logan/0000-0003-2516-0222 FU National Cancer Institute, National Institutes of Health, Bethesda, Maryland; National Cancer Institute [CA118444, CA116237, CA137941, N01-PC-35141]; Leukemia and Lymphoma Society [61006]; Veterans Affairs Research Service; National Institutes of Health [AI-51445] FX This material is based upon work supported by the Intramural Program of the National Cancer Institute, National Institutes of Health, Bethesda, Maryland, and by grants CA118444 and CA116237 from the National Cancer Institute. JBW is also supported in part by grant CA137941 from the National Cancer Institute, grant # 61006 from the Leukemia and Lymphoma Society, and the Veterans Affairs Research Service. MCL is a Fellow of the Leukemia and Lymphoma Society of America. Flow cytometry was performed in the Duke Human Vaccine Institute Flow Cytometry Core Facility that is supported by the National Institutes of Health award AI-51445. Data collection in Utah was made possible by the Utah Population DataBase (UPDB) and the Utah Cancer Registry (UCR). Partial support for all data in the UPDB was provided by the University of Utah Huntsman Cancer Institute. The UCR is funded by contract N01-PC-35141 from the NCI's SEER program with additional support from the Utah State Department of Health and the University of Utah. NR 22 TC 29 Z9 31 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2010 VL 151 IS 2 BP 152 EP 158 DI 10.1111/j.1365-2141.2010.08339.x PG 7 WC Hematology SC Hematology GA 656XN UT WOS:000282374500004 PM 20738309 ER PT J AU Burke, KA Freeman, SN Imoisili, MA Cote, TR AF Burke, K. A. Freeman, S. N. Imoisili, M. A. Cote, T. R. TI The Impact of the Orphan Drug Act on the Development and Advancement of Neurological Products for Rare Diseases: A Descriptive Review SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material AB Many neurological diseases or conditions are rare disorders. The Orphan Drug Act (ODA) of 1983 was promulgated to promote the development of products for such conditions. In this Opinion piece, we discuss how the ODA has affected neurological diseases, note how current and future sponsors (any person(s) or entity (i.e., academic, corporate body, individual, manufacturer) that applies for an official regulatory action) of products for rare neurological diseases can take advantage of ODA incentives, identify areas of success and continuing needs, and review data that can help drive the future development of products for rare neurological conditions. C1 [Burke, K. A.; Freeman, S. N.; Imoisili, M. A.; Cote, T. R.] US FDA, Off Orphan Prod Dev, Silver Spring, MD USA. RP Cote, TR (reprint author), US FDA, Off Orphan Prod Dev, Silver Spring, MD USA. EM timothy.cote@fda.hhs.gov NR 3 TC 3 Z9 3 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 OCT PY 2010 VL 88 IS 4 BP 449 EP 453 DI 10.1038/clpt.2010.193 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 653CR UT WOS:000282064000011 PM 20856241 ER PT J AU Wang, SJ O'Neill, RT Hung, HMJ AF Wang, Sue-Jane O'Neill, Robert T. Hung, H. M. James TI Statistical considerations in evaluating pharmacogenomics-based clinical effect for confirmatory trials SO CLINICAL TRIALS LA English DT Article; Proceedings Paper CT Annual Conference on Statistical Issues on Clinical Trials - Statistical Issues in Developing Targeted Therapies CY APR 29, 2009 CL Univ Pennsylvania, Philadelphia, PA SP Amer Stat Assoc, Soc Clinical Trials HO Univ Pennsylvania ID BIOMARKER AB Background The current practice for seeking genomically favorable patients in randomized controlled clinical trials using genomic convenience samples. Purpose To discuss the extent of imbalance, confounding, bias, design efficiency loss, type I error, and type II error that can occur in the evaluation of the convenience samples, particularly when they are small samples. To articulate statistical considerations for a reasonable sample size to minimize the chance of imbalance, and, to highlight the importance of replicating the subgroup finding in independent studies. Methods Four case examples reflecting recent regulatory experiences are used to underscore the problems with convenience samples. Probability of imbalance for a pre-specified subgroup is provided to elucidate sample size needed to minimize the chance of imbalance. We use an example drug development to highlight the level of scientific rigor needed, with evidence replicated for a pre-specified subgroup claim. Results The convenience samples evaluated ranged from 18% to 38% of the intent-to-treat samples with sample size ranging from 100 to 5000 patients per arm. The baseline imbalance can occur with probability higher than 25%. Mild to moderate multiple confounders yielding the same directional bias in favor of the treated group can make treatment group incomparable at baseline and result in a false positive conclusion that there is a treatment difference. Conversely, if the same directional bias favors the placebo group or there is loss in design efficiency, the type II error can increase substantially. Limitations Pre-specification of a genomic subgroup hypothesis is useful only for some degree of type I error control. Conclusion Complete ascertainment of genomic samples in a randomized controlled trial should be the first step to explore if a favorable genomic patient subgroup suggests a treatment effect when there is no clear prior knowledge and understanding about how the mechanism of a drug target affects the clinical outcome of interest. When stratified randomization based on genomic biomarker status cannot be implemented in designing a pharmacogenomics confirmatory clinical trial, if there is one genomic biomarker prognostic for clinical response, as a general rule of thumb, a sample size of at least 100 patients may be needed to be considered for the lower prevalence genomic subgroup to minimize the chance of an imbalance of 20% or more difference in the prevalence of the genomic marker. The sample size may need to be at least 150, 350, and 1350, respectively, if an imbalance of 15%, 10% and 5% difference is of concern. Clinical Trials 2010; 7: 525-536. http://ctj.sagepub.com C1 [Wang, Sue-Jane; Hung, H. M. James] US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res,Div Biometr 1, Silver Spring, MD 20993 USA. RP Wang, SJ (reprint author), US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res,Div Biometr 1, HFD 700,WO 21,Mail Stop Room 3562,10903 New Hamps, Silver Spring, MD 20993 USA. EM suejane.wang@fda.hhs.gov NR 8 TC 24 Z9 25 U1 1 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD OCT PY 2010 VL 7 IS 5 BP 525 EP 536 DI 10.1177/1740774510375455 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 653KK UT WOS:000282089800003 PM 20595242 ER PT J AU Liu, AY Liu, CL Li, QZ Yu, KF Yuan, VW AF Liu, Aiyi Liu, Chunling Li, Qizhai Yu, Kai F. Yuan, Vivian W. TI A threshold sample-enrichment approach in a clinical trial with heterogeneous subpopulations SO CLINICAL TRIALS LA English DT Article; Proceedings Paper CT Annual Conference on Statistical Issues on Clinical Trials - Statistical Issues in Developing Targeted Therapies CY APR 29, 2009 CL Univ Pennsylvania, Philadelphia, PA SP Amer Stat Assoc, Soc Clinical Trials HO Univ Pennsylvania ID PREECLAMPSIA; PREVENTION; SUBGROUP; CALCIUM AB Background Large comparative clinical trials usually target a wide-range of patients population in which subgroups exist according to certain patients' characteristics. Often, scientific knowledge or existing empirical data support the assumption that patients' improvement is larger among certain subgroups than others. Such information can be used to design a more cost-effective clinical trial. Purpose The goal of the article is to use such information to design a more cost-effective clinical trial. Methods A two-stage sample-enrichment design strategy is proposed that begins with enrollment from certain subgroup of patients and allows the trial to be terminated for futility in that subgroup. Results Simulation studies show that the two-stage sample-enrichment strategy is cost-effective if indeed the null hypothesis of no treatment improvement is true, as also so illustrated with data from a completed trial of calcium to prevent preeclampsia. Limitations Feasibility of the proposed enrichment design relies on the knowledge prior to the start of the trial that certain patients can benefit more than others from the treatment. Prolonged accrual and longer-waited outcomes may hinder utilization of the proposed design. Conclusions The two-stage sample-enrichment approach borrows strength from treatment heterogeneity among target patients in a large-scale comparative clinical trial, and is more cost-effective if the treatment arms are indeed of no difference. Clinical Trials 2010; 7: 537-545. http://ctj.sagepub.com C1 [Liu, Aiyi; Liu, Chunling; Yu, Kai F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Rockville, MD 20852 USA. [Li, Qizhai] Chinese Acad Sci, Acad Math & Syst Sci, Beijing, Peoples R China. [Yuan, Vivian W.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Liu, AY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Rockville, MD 20852 USA. EM liua@mail.nih.gov RI Liu, Chunling/A-4827-2015; OI Liu, Chunling/0000-0003-3410-445X; Liu, Aiyi/0000-0002-6618-5082 FU Intramural NIH HHS [Z99 HD999999] NR 9 TC 14 Z9 14 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD OCT PY 2010 VL 7 IS 5 BP 537 EP 545 DI 10.1177/1740774510378695 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 653KK UT WOS:000282089800004 PM 20685769 ER PT J AU Ellenberg, S Ruberg, S Simon, R Wang, SJ Xu, LA Anderson, K AF Ellenberg, Susan Ruberg, Stephen Simon, Richard Wang, Sue-Jane Xu, Li-an Anderson, Keaven TI Prospective alpha allocation in the clarification of optimal anticoagulation through genetics (COAG) trial Closing discussion SO CLINICAL TRIALS LA English DT Editorial Material C1 [Ellenberg, Susan] Univ Penn, Philadelphia, PA 19104 USA. [Ruberg, Stephen] Eli Lilly & Co, Indianapolis, IN USA. [Simon, Richard] NCI, Bethesda, MD 20892 USA. [Wang, Sue-Jane] US FDA, Rockville, MD 20857 USA. [Xu, Li-an] Bristol Myers Squibb Co, New York, NY 10154 USA. RP Ellenberg, S (reprint author), Univ Penn, Philadelphia, PA 19104 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD OCT PY 2010 VL 7 IS 5 BP 611 EP 616 DI 10.1177/1740774510380503 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 653KK UT WOS:000282089800013 ER PT J AU Sisler, JD Szelag, M Potla, R Zhang, QF Szczepanek, K Derecka, M Wegrzyn, J Dulak, J Zou, WX Hamed, H Shutt, T Cichy, J Chen, XM Baker, DP Dent, P Feldman, GM Shadel, G Larner, AC AF Sisler, Jennifer D. Szelag, Magdalena Potla, Ramesh Zhang, Qifang Szczepanek, Karol Derecka, Marta Wegrzyn, Joanna Dulak, Jozef Zou, Wenxin Hamed, Hossein Shutt, Timothy Cichy, Joanna Chen, Xiaomin Baker, Darren P. Dent, Paul Feldman, Gerald M. Shadel, Gerald Larner, Andrew C. TI The role of STAT1 in regulation of mitochondrial gene expression SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Sisler, Jennifer D.; Szelag, Magdalena; Zhang, Qifang; Szczepanek, Karol; Derecka, Marta; Wegrzyn, Joanna; Hamed, Hossein; Dent, Paul; Larner, Andrew C.] Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Richmond, VA 23298 USA. [Sisler, Jennifer D.; Szelag, Magdalena; Zhang, Qifang; Szczepanek, Karol; Derecka, Marta; Wegrzyn, Joanna; Hamed, Hossein; Dent, Paul; Larner, Andrew C.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA 23298 USA. [Potla, Ramesh] Natl Inst Neurol Disorders & Stroke, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Szelag, Magdalena; Szczepanek, Karol; Wegrzyn, Joanna; Dulak, Jozef] Jagiellonian Univ, Dept Med Biotechnol, Fac Biochem Biophys & Biotechnol, Krakow, Poland. [Zou, Wenxin; Chen, Xiaomin] Univ Texas MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA. [Shutt, Timothy; Shadel, Gerald] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA. [Baker, Darren P.] Biogen Idec Inc, Cambridge Ctr 14, Cambridge, MA 02142 USA. [Feldman, Gerald M.; Larner, Andrew C.] US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, Off Biotechnol Prod,CDER, Bethesda, MD 20892 USA. [Derecka, Marta; Cichy, Joanna] Jagiellonian Univ, Dept Immunol, Fac Biochem Biophys & Biotechnol, Krakow, Poland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 29 EP 29 DI 10.1016/j.cyto.2010.07.130 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400112 ER PT J AU Dickensheets, H Sheikh, F Pos, Z Marincola, F Donnelly, RP AF Dickensheets, Harold Sheikh, Faruk Pos, Zoltan Marincola, Francesco Donnelly, Raymond P. TI COmparative analysis of responsiveness to IFN-alpha and IFN-lambda by normal human bronchial epithelial cells and hepatocytes SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Dickensheets, Harold; Sheikh, Faruk; Donnelly, Raymond P.] US FDA, Ctr Drug Evaluat & Res, Div Therapeut Proteins, Bethesda, MD 20014 USA. [Pos, Zoltan; Marincola, Francesco] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 34 EP 34 DI 10.1016/j.cyto.2010.07.151 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400133 ER PT J AU Donnelly, RP AF Donnelly, Raymond P. TI Primary human hepatocytes can produce and respond to interferon-lambda (IFN-lambda) SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Donnelly, Raymond P.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 48 EP 49 DI 10.1016/j.cyto.2010.07.202 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400179 ER PT J AU Gold, DM Hillyer, P Raviv, N Heuer, MA Chi, B Rabin, RL AF Gold, Doria M. Hillyer, Philippa Raviv, Nataly Heuer, Melissa A. Chi, B. Rabin, Ronald L. TI Differential effects of human interferon-alpha subtypes on CD4 Tcell function SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Gold, Doria M.; Hillyer, Philippa; Raviv, Nataly; Heuer, Melissa A.; Chi, B.; Rabin, Ronald L.] US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 65 EP 65 DI 10.1016/j.cyto.2010.07.276 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400252 ER PT J AU Savan, R Reynolds, DA McFarland, AP Feigenbaum, L Ramakrishnan, K Shirota, H Klinman, DM Dunleavy, K Pittaluga, S Anderson, SK Donnelly, RP Wilson, WH Young, H AF Savan, Ram Reynolds, Della A. McFarland, Adelle P. Feigenbaum, Lionel Ramakrishnan, Karthika Shirota, Hidekazu Klinman, Dennis M. Dunleavy, Kieron Pittaluga, Stefania Anderson, Stephen K. Donnelly, Raymond P. Wilson, Wyndham H. Young, Howard TI A novel role of IL-22R1 as a possible driver of inflammation in ALK(+) anaplastic large cell lymphoma SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Savan, Ram; Reynolds, Della A.; McFarland, Adelle P.; Ramakrishnan, Karthika; Shirota, Hidekazu; Klinman, Dennis M.; Anderson, Stephen K.; Young, Howard] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Feigenbaum, Lionel] NCI, Lab Anim Sci Program, Ctr Canc Res, Frederick, MD 21702 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 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 69 EP 69 DI 10.1016/j.cyto.2010.07.291 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400266 ER PT J AU Hillyer, P Chen, A Schramm, LM Mane, VP Navarro, M Gold, DM Raviv, N Rabin, RL AF Hillyer, Philippa Chen, Aaron Schramm, Lynnsie M. Mane, Viraj P. Navarro, Maria Gold, Doria M. Raviv, Nataly Rabin, Ronald L. TI Differences in magnitude and timing of human monocyte derived dendritic cell innate immune responses to two strains of respiratory syncytial virus SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Hillyer, Philippa; Chen, Aaron; Schramm, Lynnsie M.; Mane, Viraj P.; Navarro, Maria; Gold, Doria M.; Raviv, Nataly; Rabin, Ronald L.] US FDA, Ctr Biol Evaluat & Res, Lab Immunobiochem, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 83 EP 83 DI 10.1016/j.cyto.2010.07.345 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400313 ER PT J AU Murphy, AA Zhang, XZ Yang, J Donnelly, R Young, H Lempicki, RA Kottilil, S AF Murphy, Alison A. Zhang, Xiaozhen Yang, Jun Donnelly, Raymond Young, Howard Lempicki, Richard A. Kottilil, Shyam TI Differential transcriptosome profiles and antiviral effect of interferon-lambda and interferon-alpha on HCV-infected and uninfected hepatoma cells SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Murphy, Alison A.; Zhang, Xiaozhen; Kottilil, Shyam] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Yang, Jun; Lempicki, Richard A.] SAIC Frederick, Frederick, MD USA. [Donnelly, Raymond] US FDA, CDER, Bethesda, MD 20014 USA. [Young, Howard] NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA. RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 92 EP 92 DI 10.1016/j.cyto.2010.07.389 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400353 ER PT J AU Donnelly, RP Sheikh, F Dickensheets, H Savan, R Young, HA Walter, MR AF Donnelly, Raymond P. Sheikh, Faruk Dickensheets, Harold Savan, Ram Young, Howard A. Walter, Mark R. TI Interleukin-26: An IL-10-related cytokine produced by Th17 cells SO CYTOKINE & GROWTH FACTOR REVIEWS LA English DT Review DE IL-26; Th17 cells; IL-20R1; STAT3; Inflammation ID HUMAN IL-10 RECEPTOR; CRYSTAL-STRUCTURE; INTERFERON-GAMMA; CUTTING EDGE; SEQUENCE ALIGNMENT; COMMON CHAIN; IL-22; EXPRESSION; COMPLEX; IDENTIFICATION AB IL-26 is classified as a member of the IL-10 cytokine family because it has limited sequence homology to IL-10 and the IL-10-related cytokines. The human IL-26 gene, IL26, is located on chromosome 12q15 between the genes for two other important class-2 cytokines, IFNG (IFN-gamma) and IL22 (IL-22). IL-26 is often co-expressed with IL-22 by activated T cells, especially Th17 cells. It signals through a heterodimeric receptor complex composed of the IL-20R1 and IL-10R2 chains. I1-26 receptors are primarily expressed on non-hematopoietic cell types, particularly epithelial cells. Signaling through IL-26 receptor complexes results in the activation of STAT1 and STAT3 with subsequent induction of IL-26-responsive genes. The biological functions of IL-26 have only begun to be defined. Published by Elsevier Ltd. C1 [Donnelly, Raymond P.; Sheikh, Faruk; Dickensheets, Harold] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Savan, Ram; Young, Howard A.] NCI, Expt Immunol Lab, Canc & Inflammat Program, NIH, Frederick, MD 21702 USA. [Walter, Mark R.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. RP Donnelly, RP (reprint author), US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bldg 29A,Room 3B15,29 Lincoln Dr, Bethesda, MD 20892 USA. EM Raymond.Donnelly@fda.hhs.gov FU National Institutes of Health (NIH) [AI47300, AI47300-08S]; National Cancer Institute (NCI) FX This work was supported in part by U.S. Public Health Service Grants AI47300 and AI47300-08S from the National Institutes of Health (NIH) to M.R.W and by the Intramural Research Program of the National Cancer Institute (NCI). NR 53 TC 33 Z9 35 U1 3 U2 15 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6101 J9 CYTOKINE GROWTH F R JI Cytokine Growth Factor Rev. PD OCT PY 2010 VL 21 IS 5 SI SI BP 393 EP 401 DI 10.1016/j.cytogfr.2010.09.001 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 705IU UT WOS:000286122900008 PM 20947410 ER PT J AU Morris, SM Aidoo, A Dobrovolsky, V Heflich, R Manjanatha, M McKinzie, P Parsons, B AF Morris, Suzanne M. Aidoo, Anane Dobrovolsky, Vasily Heflich, Robert Manjanatha, Mugimane McKinzie, Page Parsons, Barbara TI The 40th Anniversary of the Environmental Mutagen Society SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Editorial Material C1 [Morris, Suzanne M.; Aidoo, Anane; Dobrovolsky, Vasily; Heflich, Robert; Manjanatha, Mugimane; McKinzie, Page; Parsons, Barbara] Natl Ctr Toxicol Res, EMS 40th Anniversary Project, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA. RP Morris, SM (reprint author), Natl Ctr Toxicol Res, EMS 40th Anniversary Project, Div Genet & Mol Toxicol, Jefferson, AR 72079 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD OCT-DEC PY 2010 VL 51 IS 8-9 SI SI BP 743 EP 743 DI 10.1002/em.20623 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 666GI UT WOS:000283102100001 PM 20857435 ER PT J AU Morris, S Bishop, J Parsons, B AF Morris, Suzanne Bishop, Jack Parsons, Barbara TI Memorial for John Wassom SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Biographical-Item C1 [Morris, Suzanne; Bishop, Jack; Parsons, Barbara] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Morris, S (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD OCT-DEC PY 2010 VL 51 IS 8-9 SI SI BP 744 EP 745 DI 10.1002/em.20620 PG 2 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 666GI UT WOS:000283102100002 ER PT J AU Dobrovolsky, VN Miura, D Heflich, RH Dertinger, SD AF Dobrovolsky, Vasily N. Miura, Daishiro Heflich, Robert H. Dertinger, Stephen D. TI The In Vivo Pig-a Gene Mutation Assay, A Potential Tool For Regulatory Safety Assessment SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Review DE mutagenesis; flow cytometry; erythrocytes; GPI; aerolysin ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; RED-BLOOD-CELLS; DISCRIMINATE RODENT CARCINOGENS; FLOW-CYTOMETRIC DETECTION; VITRO GENOTOXICITY TESTS; SPLEEN T-CELLS; ANCHOR BIOSYNTHESIS; RISK-ASSESSMENT; RAT; IDENTIFICATION AB The Pig-a (phosphatidylinositol glycan, Class A) gene codes for a catalytic subunit of the N-acetyl-glucosamine transferase complex involved in an early step of glycosylphosphatidyl inositol (GPI) cell surface anchor synthesis. Pig-a is the only gene involved in GPI anchor synthesis that is on the X-chromosome, and research into the origins of an acquired genetic disease involving GPI anchor deficiency (paroxysmal nocturnal hemoglobinuria) indicates that cells lacking GPI anchors, or GPI-anchored cell surface proteins, almost always have mutations in the Pig-a gene. These properties of the Pig-a gene and the GPI anchor system have been exploited in a series of assays for measuring in vivo gene mutation in blood cells from humans, rats, mice, and monkeys. In rats, flow cytometric measurement of Pig-a mutation in red blood cells requires microliter volumes of blood and data can be generated in hours. Spontaneous mutant frequencies are relatively low (<5 x 10(-6)) and rats treated with multiple doses of the potent mutagen, N-ethyl-N-nitrosourea, display Pig-a mutant frequencies that are close to the sum of the frequencies produced by the individual exposures. A general observation is that induced mutant frequencies are manifested earlier in reticulocytes (about 2 weeks after treatment) than in total red blood cells (about 2 months after exposure). Based on data from a limited number of test agents, the assay shows promise for regulatory applications, including integration of gene mutation measurement into repeat-dose toxicology studies. Environ. Mol. Mutagen. 51:825-835, 2010. Published 2010 Wiley-Liss, Inc.(dagger) C1 [Dobrovolsky, Vasily N.; Heflich, Robert H.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Miura, Daishiro] Teijin Pharma Ltd, Tokyo, Japan. [Dertinger, Stephen D.] Litron Labs, Rochester, NY USA. RP Dobrovolsky, VN (reprint author), US FDA NCTR, 3900 NCTR Rd, Jefferson, AR 72279 USA. EM vasily.dobrovolsky@fda.hhs.gov NR 55 TC 62 Z9 71 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD OCT-DEC PY 2010 VL 51 IS 8-9 SI SI BP 825 EP 835 DI 10.1002/em.20627 PG 11 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 666GI UT WOS:000283102100011 PM 20857433 ER PT J AU Parsons, BL Myers, MB Meng, FX Wang, YY McKinzie, PB AF Parsons, Barbara L. Myers, Meagan B. Meng, Fanxue Wang, Yiying McKinzie, Page B. TI Oncomutations as Biomarkers of Cancer Risk SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Review DE mutation; mutation detection; dose-response assessment; carcinogenesis; risk assessment; K-Ras ID METASTATIC COLORECTAL-CANCER; K-RAS MUTATIONS; CELL LUNG-CANCER; POLYCYCLIC AROMATIC-HYDROCARBONS; BASE SUBSTITUTION MUTATIONS; COMPETITIVE BLOCKER PCR; STRAIN A/J MICE; GENOTYPIC SELECTION; ENVIRONMENTAL MUTAGENS; ONCOGENE MUTATIONS AB Cancer risk assessment impacts a range of societal needs, from the regulation of chemicals to achieving the best possible human health outcomes. Because oncogene and tumor suppressor gene mutations are necessary for the development of cancer, such mutations are ideal biomarkers to use in cancer risk assessment. Consequently, DNA-based methods to quantify particular tumor-associated hotspot point mutations (i.e., oncomutations) have been developed, including allele-specific competitive blocker-PCR (ACB-PCR). Several studies using ACB-PCR and model mutagens have demonstrated that significant induction of tumor-associated oncomutations are measureable at earlier time points than are used to score tumors in a bioassay. In the particular case of benzo[a]pyrene induction of K-Ras codon 12 TGT mutation in the A/J mouse lung, measurement of tumor-associated oncomutation was shown to be an earlier and more sensitive endpoint than tumor response. The measurement of oncomutation by ACB-PCR led to two unexpected findings. First, oncomutations are present in various tissues of control rodents and "normal" human colonic mucosa samples at relatively high frequencies. Approximately 60% of such samples (88/146) have mutant fractions (MFs) >10(-5), and some have MFs as high as 10(-3) or 10(-4). Second, preliminary data indicate that oncomutations are present frequently as sub-populations in tumors. These findings are integrated into a hypothesis that the predominant preexisting mutations in particular tissues may be useful as generic reporters of carcinogenesis. Future research opportunities using oncomutation as an endpoint are described, including rodent to human extrapolation, dose-response assessment, and personalized medicine. Environ. Mol. Mutagen. 51:836-850, 2010. Published 2010 Wiley-Liss, Inc. C1 [Parsons, Barbara L.; Myers, Meagan B.; Meng, Fanxue; Wang, Yiying; McKinzie, Page B.] Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Parsons, BL (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM barbara.parsons@fda.hhs.gov NR 85 TC 16 Z9 16 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD OCT-DEC PY 2010 VL 51 IS 8-9 SI SI BP 836 EP 850 DI 10.1002/em.20600 PG 15 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 666GI UT WOS:000283102100012 PM 20740637 ER PT J AU Stinchcombe, JR Izem, R Heschel, MS McGoey, BV Schmitt, J AF Stinchcombe, John R. Izem, Rima Heschel, M. Shane McGoey, Brechann V. Schmitt, Johanna TI ACROSS-ENVIRONMENT GENETIC CORRELATIONS AND THE FREQUENCY OF SELECTIVE ENVIRONMENTS SHAPE THE EVOLUTIONARY DYNAMICS OF GROWTH RATE IN IMPATIENS CAPENSIS SO EVOLUTION LA English DT Review ID SHADE-AVOIDANCE RESPONSES; RANDOM REGRESSION-MODELS; RESTRICTED MAXIMUM-LIKELIHOOD; VARIANCE-COVARIANCE MATRIX; CONTINUOUS REACTION NORMS; FUNCTION-VALUED TRAITS; LIFE-HISTORY TRAITS; PHENOTYPIC PLASTICITY; QUANTITATIVE GENETICS; NATURAL-SELECTION AB Trade-offs can exist within and across environments, and constrain evolutionary trajectories. To examine the effects of competition and resource availability on trade-offs, we grew individuals of recombinant inbred lines of Impatiens capensis in a factorial combination of five densities with two light environments (full light and neutral shade) and used a Bayesian logistic growth analysis to estimate intrinsic growth rates. To estimate across-environment constraints, we developed a variance decomposition approach to principal components analysis, which accounted for sample size, model-fitting, and within-RIL variation prior to eigenanalysis. We detected negative across-environment genetic covariances in intrinsic growth rates, although only under full-light. To evaluate the potential importance of these covariances, we surveyed natural populations of I. capensis to measure the frequency of different density environments across space and time. We combined our empirical estimates of across-environment genetic variance-covariance matrices and frequency of selective environments with hypothetical (yet realistic) selection gradients to project evolutionary responses in multiple density environments. Selection in common environments can lead to correlated responses to selection in rare environments that oppose and counteract direct selection in those rare environments. Our results highlight the importance of considering both the frequency of selective environments and the across-environment genetic covariances in traits simultaneously. C1 [Stinchcombe, John R.; McGoey, Brechann V.] Univ Toronto, Dept Ecol & Evolutionary Biol, Toronto, ON M5S 3B2, Canada. [Stinchcombe, John R.] Univ Toronto, Ctr Anal Genome Evolut & Funct, Toronto, ON M5S 3B2, Canada. [Izem, Rima] US FDA, CDER OTS OB White Oak DB4, Silver Spring, MD 20993 USA. [Heschel, M. Shane] Colorado Coll, Dept Biol, Colorado Springs, CO 80903 USA. [Schmitt, Johanna] Brown Univ, Dept Ecol & Evolutionary Biol, Providence, RI 02912 USA. RP Stinchcombe, JR (reprint author), Univ Toronto, Dept Ecol & Evolutionary Biol, Toronto, ON M5S 3B2, Canada. EM john.stinchcombe@utoronto.ca; Rima.Izem@fda.hhs.gov; shane.heschel@coloradocollege.edu; brechann.mcgoey@utoronto.ca; Johanna_Schmitt@brown.edu RI Stinchcombe, John/A-2941-2008 OI Stinchcombe, John/0000-0003-3349-2964 FU NSF [DEB-0129018, EF-0328594]; NSERC CGS; University of Toronto; NSERC Canada FX We thank A. Aguilera, B. Leib, and F. Jackson for expert assistance in line maintenance and plant care, and E. von Wettberg, K. Gravuer, and J. Kelley for assistance with data collection. Our research was supported by NSF grants DEB-0129018 (to JS), EF-0328594 (to R. Gomulkiewicz, P. Carter, and J.S.), NSERC CGS and University of Toronto Fellowships (BVM), and an NSERC Canada Discovery grant to JRS. All views expressed in this article are the views of the authors, and do not necessarily represent the views of, and should not be attributed to, the Food and Drug Administration. NR 113 TC 18 Z9 19 U1 3 U2 28 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-3820 EI 1558-5646 J9 EVOLUTION JI Evolution PD OCT PY 2010 VL 64 IS 10 BP 2887 EP 2903 DI 10.1111/j.1558-5646.2010.01060.x PG 17 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA 659NN UT WOS:000282573800007 PM 20662920 ER PT J AU Reimschuessel, R Evans, ER Stine, CB Hasbrouck, N Mayer, TD Nochetto, C Gieseker, CM AF Reimschuessel, R. Evans, E. R. Stine, C. B. Hasbrouck, N. Mayer, T. D. Nochetto, C. Gieseker, C. M. TI Renal crystal formation after combined or sequential oral administration of melamine and cyanuric acid SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Melamine; Cyanuric acid; Kidney; Crystal; No observable adverse effect level; Fish ID URINARY-BLADDER; INDUCED STONES; RAINBOW-TROUT; FATTY-ACIDS; ZEBRAFISH; DISEASE; TOXICITY; NEPHROPATHY; KIDNEY; MODEL AB We evaluated renal melamine-cyanurate crystal spherulite formation after single and repeated ingestion of both melamine (MEL) and cyanuric acid (CYA) in catfish and trout. MEL and CYA were co-administered orally over a range of doses, 0.1-20 mg/kg body weight (bw) of each compound, either once or repeatedly for 4, 14 or 28 days (d). In catfish, the No Observable Adverse Effects Levels (NOAELs) for crystal formation for single, 4 d or 14 d dosing were 10, 2.5 and 0.5 mg/kg bw, respectively. In trout, the respective NOAELs were 2.5, 2.5 and 0.5 mg/kg bw. No renal crystals formed in catfish fed 0.1 mg/kg bw of each compound for 28 d. Sequential administration of 20 mg/kg bw of MEL followed by 20 mg/kg bw of CYA or vise-versa, with waiting periods of 1, 3, 7, 14 or 21 d between compound dosing also induced renal crystal formation in fish. These studies show that both catfish and trout are sensitive, non-mammalian models, for renal crystal formation following MEL and CYA ingestion. Since fish generally excrete chemicals more slowly than mammals, they may provide a "worst case scenario" model for higher risk populations, such as infants or persons with compromised renal function. Published by Elsevier Ltd. C1 [Reimschuessel, R.; Evans, E. R.; Stine, C. B.; Hasbrouck, N.; Mayer, T. D.; Nochetto, C.; Gieseker, C. M.] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Reimschuessel, R (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM Renate.reimschuessel@fda.hhs.gov RI Stine, Cynthia/F-1040-2011 NR 84 TC 38 Z9 41 U1 2 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD OCT PY 2010 VL 48 IS 10 BP 2898 EP 2906 DI 10.1016/j.fct.2010.07.024 PG 9 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 659BW UT WOS:000282543000051 PM 20674644 ER PT J AU Farb, A Brown, SA Wolf, DA Zuckerman, B AF Farb, Andrew Brown, Sheila A. Wolf, Deborah A. Zuckerman, Bram TI Interventional Cardiology Live Case Presentations Regulatory Considerations SO HEART RHYTHM LA English DT Article DE complications adult cath/intervention; angiography; coronary; percutaneous coronary intervention AB Live case presentations are increasingly common at interventional cardiology conferences. Taking advantage of significant advances in communication technology, broadcasts of procedures can be viewed as an extension of traditional medical education targeted to large groups of practitioners. However, there are important ethical, commercial, and patient safety issues associated with live cases that deserve attention. Use of investigational devices in live case demonstrations is subject to review and approval by FDA's Center for Devices and Radiological Health (CDRH), and the outcomes of patients participating in live cases are considered in the overall clinical study results. This article discusses CDRH's regulatory view of live case presentations with a focus on patient safety, clinical trial integrity, and concerns regarding improper medical device promotion. C1 [Farb, Andrew] US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Farb, A (reprint author), US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,WO66-1116, Silver Spring, MD 20993 USA. EM andrew.farb@fda.hhs.gov NR 4 TC 1 Z9 1 U1 0 U2 0 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 OCT PY 2010 VL 7 IS 10 BP E1 EP E3 DI 10.1016/j.hrthm.2010.08.024 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 654SC UT WOS:000282187300038 PM 20869626 ER PT J AU Gavrielides, MA Zeng, RP Kinnard, LM Myers, KJ Petrick, N AF Gavrielides, Marios A. Zeng, Rongping Kinnard, Lisa M. Myers, Kyle J. Petrick, Nicholas TI Information-Theoretic Approach for Analyzing Bias and Variance in Lung Nodule Size Estimation With CT: A Phantom Study SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Lung nodule; matched filter; phantom study; thoracic computed tomography (CT); volume estimation ID SMALL PULMONARY NODULES; SEMIAUTOMATED VOLUME MEASUREMENTS; COMPUTED-TOMOGRAPHY IMAGES; MULTISLICE CT; THORACIC CT; HELICAL CT; AUTOMATIC SEGMENTATION; CANCER; VARIABILITY; RECONSTRUCTION AB This work is a part of our more general effort to probe the interrelated factors impacting the accuracy and precision of lung nodule measurement tasks. For such a task a low-bias size estimator is needed so that the true effect of factors such as acquisition and reconstruction parameters, nodule characteristics and others can be assessed. Towards this goal, we have developed a matched filter based on an adaptive model of the object acquisition and reconstruction process. Our model derives simulated reconstructed data of nodule objects (templates) which are then matched to computed tomography data produced from imaging the actual nodule in a phantom study using corresponding imaging parameters. This approach incorporates the properties of the imaging system and their effect on the discrete 3-D representation of the object of interest. Using a sum of absolute differences cost function, the derived matched filter demonstrated low bias and variance in the volume estimation of spherical synthetic nodules ranging in density from -630 to +100 HU and in size from 5 to 10 mm. This work could potentially lead to better understanding of sources of error in the task of lung nodule size measurements and may lead to new techniques to account for those errors. C1 [Gavrielides, Marios A.; Zeng, Rongping; Kinnard, Lisa M.; Myers, Kyle J.; Petrick, Nicholas] US FDA, DIAM, OSEL, CDRH, Silver Spring, MD 20993 USA. RP Gavrielides, MA (reprint author), US FDA, DIAM, OSEL, CDRH, Silver Spring, MD 20993 USA. EM marios.gavrielides@fda.hhs.gov; rongping.zeng@fda.hhs.gov; lisa.kinnard@amedd.army.mil; kyle.myers@fda.hhs.gov; nicholas.petrick@fda.hhs.gov FU U.S. Food and Drug Administration; National Institute of Biomedical Imaging and Bioengineering; National Cancer Institute through IAG [224-07-6030]; Center for Interventional Oncology at the National Institutes of Health (NIH) [Mx8000]; NIH; U.S. Food and Drug Administration (FDA) FX This research was funded though a Critical Path grant from the U.S. Food and Drug Administration. The intramural research program of the National Institute of Biomedical Imaging and Bioengineering and the National Cancer Institute through IAG no. 224-07-6030 provided partial support for this work. Phantom scans on the Philips IDT Mx8000 were supported in part by the Center for Interventional Oncology at the National Institutes of Health (NIH) and an Interagency Agreement between the NIH and the U.S. Food and Drug Administration (FDA). The mention of commercial products in this manuscript does not constitute endorsement by the U.S. Food and Drug Administration. The content of this publication does not necessarily reflect the position of the U.S. Food and Drug Administration, and no official endorsement of any equipment or product of any company mentioned in the publication should be inferred. NR 42 TC 19 Z9 20 U1 0 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD OCT PY 2010 VL 29 IS 10 BP 1795 EP 1807 DI 10.1109/TMI.2010.2052466 PG 13 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 669LR UT WOS:000283352700008 PM 20562039 ER PT J AU Barallon, R Bauer, SR Butler, J Capes-Davis, A Dirks, WG Elmore, E Furtado, M Kline, MC Kohara, A Los, GV MacLeod, RAF Masters, JRW Nardone, M Nardone, RM Nims, RW Price, PJ Reid, YA Shewale, J Sykes, G Steuer, AF Storts, DR Thomson, J Taraporewala, Z Alston-Roberts, C Kerrigan, L AF Barallon, Rita Bauer, Steven R. Butler, John Capes-Davis, Amanda Dirks, Wilhelm G. Elmore, Eugene Furtado, Manohar Kline, Margaret C. Kohara, Arihiro Los, Georgyi V. MacLeod, Roderick A. F. Masters, John R. W. Nardone, Mark Nardone, Roland M. Nims, Raymond W. Price, Paul J. Reid, Yvonne A. Shewale, Jaiprakash Sykes, Gregory Steuer, Anton F. Storts, Douglas R. Thomson, Jim Taraporewala, Zenobia Alston-Roberts, Christine Kerrigan, Liz TI Recommendation of short tandem repeat profiling for authenticating human cell lines, stem cells, and tissues SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Review DE Cell authentication; STR profiling; Consensus standard; Quality control ID CONTAMINATION AB Cell misidentification and cross-contamination have plagued biomedical research for as long as cells have been employed as research tools. Examples of misidentified cell lines continue to surface to this day. Efforts to eradicate the problem by raising awareness of the issue and by asking scientists voluntarily to take appropriate actions have not been successful. Unambiguous cell authentication is an essential step in the scientific process and should be an inherent consideration during peer review of papers submitted for publication or during review of grants submitted for funding. In order to facilitate proper identity testing, accurate, reliable, inexpensive, and standardized methods for authentication of cells and cell lines must be made available. To this end, an international team of scientists is, at this time, preparing a consensus standard on the authentication of human cells using short tandem repeat (STR) profiling. This standard, which will be submitted for review and approval as an American National Standard by the American National Standards Institute, will provide investigators guidance on the use of STR profiling for authenticating human cell lines. Such guidance will include methodological detail on the preparation of the DNA sample, the appropriate numbers and types of loci to be evaluated, and the interpretation and quality control of the results. Associated with the standard itself will be the establishment and maintenance of a public STR profile database under the auspices of the National Center for Biotechnology Information. The consensus standard is anticipated to be adopted by granting agencies and scientific journals as appropriate methodology for authenticating human cell lines, stem cells, and tissues. C1 [Elmore, Eugene] Univ Calif Irvine, Dept Radiat Oncol, Irvine, CA 92697 USA. [Barallon, Rita; Thomson, Jim] LGC, Teddington TW11 0LY, Middx, England. [Bauer, Steven R.] FDA Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies, Bethesda, MD 20892 USA. [Butler, John; Kline, Margaret C.] NIST, Biochem Sci Div 831, Adv Chem Sci Lab 227, Gaithersburg, MD 20899 USA. [Capes-Davis, Amanda] Childrens Med Res Inst, CellBank Australia, Westmead, NSW, Australia. [Dirks, Wilhelm G.; MacLeod, Roderick A. F.] DSMZ German Collect Microorganisms & Cell Culture, D-38124 Braunschweig, Germany. [Furtado, Manohar; Shewale, Jaiprakash] Appl Markets Genet Syst Life Technol, Foster City, CA 94404 USA. [Kohara, Arihiro] Natl Inst Biomed Innovat, Dept Biomed Resources, Lab Cell Cultures, Osaka 5670085, Japan. [Los, Georgyi V.] Univ Wisconsin, Neurosci Training Program, Madison, WI 53706 USA. [Masters, John R. W.] UCL, Inst Urol, London W1W 7EJ, England. [Nardone, Mark] NIH, Biotrac Program, Fdn Adv Educ Sci, Bethesda, MD 20892 USA. [Nardone, Roland M.] Catholic Univ Amer, Washington, DC 20064 USA. [Nims, Raymond W.] RMC Pharmaceut Solut Inc, Longmont, CO 80501 USA. [Price, Paul J.] D Finit Cell Technol, Charleston, SC 29407 USA. [Steuer, Anton F.] BioReliance, Rockville, MD 20850 USA. [Storts, Douglas R.] Promega Corp, Nucle Acid Technol, Madison, WI 53711 USA. [Taraporewala, Zenobia] FDA Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies, Rockville, MD 20852 USA. [Reid, Yvonne A.; Sykes, Gregory; Alston-Roberts, Christine; Kerrigan, Liz] Amer Type Culture Collect, Manassas, VA 20110 USA. RP Elmore, E (reprint author), Univ Calif Irvine, Dept Radiat Oncol, B146D, Irvine, CA 92697 USA. EM eelmore@uci.edu RI Butler, John/C-7812-2011; Bauer, Steven/G-5559-2012; OI Bauer, Steven/0000-0003-2831-846X; Capes-Davis, Amanda/0000-0003-4184-6339 NR 15 TC 38 Z9 39 U1 2 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD OCT PY 2010 VL 46 IS 9 BP 727 EP 732 DI 10.1007/s11626-010-9333-z PG 6 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 672OC UT WOS:000283594200001 PM 20614197 ER PT J AU Isayeva, I Das, SS Chang, A Defoe, J Do Luu, HM Vorvolakos, K Patwardhan, D Whang, J Pollack, S AF Isayeva, Irada Das, Srilekha Sarkar Chang, Andrew DeFoe, Jacqueline Do Luu, Hoan-My Vorvolakos, Katherine Patwardhan, Dinesh Whang, Joyce Pollack, Steven TI pH effect on the synthesis, shear properties, and homogeneity of iron-crosslinked hyaluronic acid-based gel/adhesion barrier SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE hyaluronic acid gel; weak gels; iron crosslinking; shear properties; adhesion barrier; pH effect ID RHEOLOGICAL CHARACTERIZATION; IRON(III); ADHESIONS; CHITOSAN; COMPLEXES; HYDROGELS; TURNOVER; POLYMERS AB Iron-crosslinked hyaluronic acid hydrogel (FeHA) has been used to reduce postsurgical adhesions in patients undergoing open, gynecological surgery. The performance of FeHA gel as an adhesion barrier device is influenced by many factors, including the physicochemical gel properties, which, in turn, depend on the chemistry and conditions of the device manufacturing. In this work, we demonstrate the effect of reaction pH on rheology and homogeneity of FeHA gels formulated in house and also compare the viscoelastic properties of FeHA gels with that of uncrosslinked HA solution of similar HA concentration and ionic strength. Dynamic mechanical analyses provide evidence that the reaction of HA with Fe(III) ions leads to the formation of "weak" gels. The viscoelastic properties and homogeneity of FeHA gels vary depending on the pH at which crosslinking was initiated. When solution pH, at the start of crosslinking, varied between 1.5 and 3, the low-shear rate viscosity of FeHA varied between 10,000 and 40,000 cPoise (10-40 Pa s). The highest steady-state shear viscosity and viscoelasticity were measured when pH was around 2.6, which is similar to the pH-dependent viscoelasticity of pure HA solution. Initiating HA crosslinking at pH <= 3 led to relatively homogenous solutions, while crosslinking higher pH > 3 caused instantaneous gel precipitation and inhomogeneities. Sensitivity of FeHA gel properties to small variations in reaction pH clearly supports the need for a tight manufacturing control during medical device fabrication. (C) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 95B: 9-18,2010. C1 [Isayeva, Irada; Das, Srilekha Sarkar; Do Luu, Hoan-My; Vorvolakos, Katherine; Patwardhan, Dinesh; Pollack, Steven] US FDA, DCMS, OSEL, CDRH, Silver Spring, MD 20903 USA. [Chang, Andrew] Univ Maryland, Gemstone Program, College Pk, MD 20742 USA. [DeFoe, Jacqueline] Univ Chicago, Dept Chem, Chicago, IL 60637 USA. [Whang, Joyce] US FDA, DRARD, ODE, CDRH, Silver Spring, MD 20903 USA. RP Isayeva, I (reprint author), US FDA, DCMS, OSEL, CDRH, Silver Spring, MD 20903 USA. EM irada.isayeva@fda.hhs.gov FU Office of Science and Engineering Laboratories at CDRH/FDA FX Authors thank Dr. Julia Corrado, MD, Obstetrics and Gynecology Device Branch, DRARD/CDRH/FDA for her clinical discussions and recommendations, Dr. Sandy Stewart for the review and help in calculating the possible shear rates in the abdominal cavity under normal physiological conditions, Dr. Raghu Samy, CDER/FDA, for the review and chemistry-related comments, and the Office of Science and Engineering Laboratories at CDRH/FDA for the support and opportunity to work on the project. NR 47 TC 6 Z9 7 U1 1 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4973 EI 1552-4981 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD OCT PY 2010 VL 95B IS 1 BP 9 EP 18 DI 10.1002/jbm.b.31677 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 647YD UT WOS:000281655900002 PM 20665680 ER PT J AU Zhu, H Wang, YN Gobburu, JV Garnett, CE AF Zhu, Hao Wang, Yaning Gobburu, Jogarao V. Garnett, Christine E. TI Considerations for Clinical Trial Design and Data Analyses of Thorough QT Studies Using Drug-Drug Interaction SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Editorial Material DE Concentration-QTc analysis; pharmacodynamic interaction; pharmacokinetic interaction; drug-drug interaction; metabolic enzyme inhibitor ID KETOCONAZOLE C1 [Zhu, Hao; Wang, Yaning; Gobburu, Jogarao V.; Garnett, Christine E.] US FDA, Div Pharmacometr, Off Clin Pharmacol, CDER, Silver Spring, MD 20993 USA. RP Zhu, H (reprint author), US FDA, Div Pharmacometr, Off Clin Pharmacol, CDER, 10903 New Hampshire Ave,Room 3150,Bldg 51, Silver Spring, MD 20993 USA. EM Hao.Zhu@fda.hhs.gov NR 9 TC 10 Z9 10 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0091-2700 EI 1552-4604 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD OCT PY 2010 VL 50 IS 10 BP 1106 EP 1111 DI 10.1177/0091270009358710 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 650PQ UT WOS:000281862400001 PM 20457587 ER PT J AU Lubran, MB Pouillot, R Bohm, S Calvey, EM Meng, J Dennis, S AF Lubran, M. B. Pouillot, R. Bohm, S. Calvey, E. M. Meng, J. Dennis, S. TI Observational Study of Food Safety Practices in Retail Deli Departments SO JOURNAL OF FOOD PROTECTION LA English DT Article ID LISTERIA-MONOCYTOGENES; UNITED-STATES AB In order to improve the safety of refrigerated ready-to-eat food products prepared at retail deli departments, a better understanding of current practices in these establishments is needed. Food employees in deli departments at six chain and three independent retail establishments in Maryland and Virginia were observed, using notational analysis, as they prepared deli products for sale. The frequency of contact with objects and deli products before sale, hand washing and glove changing during preparation, and equipment, utensil, and surface cleaning and sanitizing was determined. Compliance with the U.S. Food and Drug Administration's 2005 model Food Code recommendations, which must be adopted by the individual state and local jurisdictions that are responsible for directly regulating retail establishments, was also assessed. Observations indicated there were a large number of actions for which hand washing was recommended at independent and chain stores (273 recommended of 1,098 total actions and 439 recommended of 3,073 total actions, respectively). Moreover, 67% (295 of 439) of the actions for which hand washing was recommended at the chain stores and 86% (235 of 273) of those at the independent stores resulted from employees touching non food contact surfaces prior to handling ready-to-eat food. Compliance with hand washing recommendations was generally low and varied depending on store type with independent stores exhibiting lower compliance than chain stores (5 instances of compliance for 273 recommended actions and 73 instances of compliance for 439 recommended actions, respectively). Potential risk mitigation measures that may reduce the frequency of hand washing actions needed during ready-to-eat food preparation in retail deli departments are discussed. More research is needed to determine the impact of such measures on food safety. C1 [Lubran, M. B.; Meng, J.] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Pouillot, R.; Bohm, S.; Calvey, E. M.; Dennis, S.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Lubran, MB (reprint author), Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM Meryl.Lubran@fsis.usda.gov RI Pouillot, Regis/E-8103-2010 OI Pouillot, Regis/0000-0002-6107-5212 FU Joint Institute for Food Safety and Applied Nutrition; University of Maryland; Center for Food Safety and Applied Nutrition FX The authors thank the Food and Drug Administration, the U.S. Department of Agriculture Food Safety and Inspection Service, and the members of the Interagency Retail Lm Risk Assessment Workgroup for their input, comments, and suggestions for this study. The authors also acknowledge Caren Kieswetter, MD (Food and Drug Administration), for her help with the implementation of the study. In addition, the authors gratefully acknowledge the Food Marketing Institute for their help in identifying participating stores, as well as the stores for their participation and assistance. This project was supported by the Joint Institute for Food Safety and Applied Nutrition, University of Maryland, 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. NR 21 TC 11 Z9 11 U1 1 U2 11 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD OCT PY 2010 VL 73 IS 10 BP 1849 EP 1857 PG 9 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 663CF UT WOS:000282859900010 PM 21067673 ER PT J AU Principato, M Njoroge, JM Perlloni, A Donnell, MO Boyle, T Jones, RL AF Principato, MaryAnn Njoroge, Joyce M. Perlloni, Andrei Donnell, Michael O' Boyle, Thomas Jones, Robert L., Jr. TI Detection of Target Staphylococcal Enterotoxin B Antigen in Orange Juice and Popular Carbonated Beverages Using Antibody-Dependent Antigen-Capture Assays SO JOURNAL OF FOOD SCIENCE LA English DT Article DE carbonated beverages; ELISA; lateral flow detector; orange juice; SEB ID LINKED-IMMUNOSORBENT-ASSAY; LATERAL FLOW DEVICES; MONOCLONAL-ANTIBODIES; ESCHERICHIA-COLI; PEANUT PROTEINS; MILK-PRODUCTS; FOOD; ELISA; VALIDATION; IMMUNOASSAY AB There is a critical need for qualitative and quantitative methodologies that provide the rapid and accurate detection of food contaminants in complex food matrices. However, the sensitivity of the assay can be affected when antigen-capture is applied to certain foods or beverages that are extremely acidic. This study was undertaken to assess the effects of orange juice and popular carbonated soft drink upon the fidelity of antibody-based antigen-capture assays and to develop simple approaches that could rescue assay performance without the introduction of additional or extensive extraction procedures. We examined the effects of orange juice and a variety of popular carbonated soft drink beverages upon a quantitative Interleukin-2 (IL-2) enzyme-linked immunosorbent assay (ELISA) assay system and a lateral flow device (LFD) adapted for the detection of staphylococcal enterotoxin B (SEB) in foods. Alterations in the performance and sensitivity of the assay were directly attributable to the food matrix, and alterations in pH were especially critical. The results demonstrate that approaches such as an alteration of pH and the use of milk as a blocking agent, either singly or in combination, will partially rescue ELISA performance. The same approaches permit lateral flow to efficiently detect antigen. Practical Application The authors present ways to rescue an ELISA assay compromised by acidity in beverages and show that either the alteration of pH, or the use of milk as a blocking agent are not always capable of restoring the assay to its intended efficiency. However, the same methods, when employed with lateral flow technology, are rapid and extremely successful. C1 [Principato, MaryAnn; Njoroge, Joyce M.; Jones, Robert L., Jr.] US FDA, CFSAN, Laurel, MD 20708 USA. [Donnell, Michael O'] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20708 USA. [Perlloni, Andrei] US FDA, Off Emergency Operat, Rockville, MD 20857 USA. RP Principato, M (reprint author), US FDA, CFSAN, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM maryann.principato@fda.hhs.gov NR 27 TC 2 Z9 2 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD OCT PY 2010 VL 75 IS 8 BP T141 EP T147 DI 10.1111/j.1750-3841.2010.01806.x PG 7 WC Food Science & Technology SC Food Science & Technology GA 663IW UT WOS:000282878200002 PM 21535520 ER PT J AU Alusta, P Im, I Pearc, BA Beger, RD Kretzer, RM Buzatu, DA Wilkes, JG AF Alusta, Pierre Im, Inessa Pearc, Bruce A. Beger, Richard D. Kretzer, Ryan M. Buzatu, Dan A. Wilkes, Jon G. TI Improving Proton MR Spectroscopy of Brain Tissue for Noninvasive Diagnostics SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE MRS; pattern recognition; chemical shift recalibration; variance weighting; biomarker ID H-1; CLASSIFICATION; BIOPSY; VIVO AB Purpose: To examine preprocessing methods affecting the potential use of Magnetic Resonance Spectroscopy (MRS) as a noninvasive modality for detection and characterization of brain lesions and for directing therapy progress. Materials and Methods: Two reference point re-calibration with linear interpolation (to compensate for magnetic field nonhomogeneity), weighting of spectra (to emphasize consistent peaks and depress chemical noise), and modeling based on chemical shift locations of 97 biomarkers were investigated. Results for 139 categorized scans were assessed by comparing Leave-One-Out (LOO) cross-validation and external validation. Results: For distinction of nine brain tissue categories, use of re-calibration, variance weighting, and biomarker modeling improved LOO classification of MRS spectra from 31% to 95%. External validation of the two best nine-category models on 47 unknown samples gave 96% or 100% accuracy, respectively, compared with pathological diagnosis. Conclusion: Preprocessing of MRS spectra can significantly improve their diagnostic utility for automated consultation of pattern recognition models. Use of several techniques in combination greatly increases available proton MRS information content. Accurate assignment of unknowns among nine tissue classes represents a significant improvement, for a much more demanding task, than has been previously reported. C1 [Alusta, Pierre; Pearc, Bruce A.; Beger, Richard D.; Buzatu, Dan A.; Wilkes, Jon G.] USDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Im, Inessa] Inessa Im Consulting, Little Rock, AR USA. [Kretzer, Ryan M.] Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21205 USA. RP Wilkes, JG (reprint author), Ctr Innovat Technol, Div Syst Toxicol, 3900 NCTR Rd,HFT 233, Jefferson, AR 72079 USA. EM jon.wilkes@fda.hhs.gov NR 17 TC 8 Z9 8 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD OCT PY 2010 VL 32 IS 4 BP 818 EP 829 DI 10.1002/jmri.22332 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 661WZ UT WOS:000282764800007 PM 20882612 ER PT J AU Akahata, Y Abrams, A Oh, U Maloney, E Jacobson, S AF Akahata, Yoshimi Abrams, Anna Oh, Unsong Maloney, Elizabeth Jacobson, Steven TI The use of a luciferase immunoprecipitation systems (LIPS) assay in the detection of anti-HTLV-I antibody responses in HAM/TSP, ATL, and asymptomatic HTLV-I carriers SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 10th International Symposium on NeuroVirology CY OCT 12-16, 2010 CL Milan, ITALY C1 [Akahata, Yoshimi; Abrams, Anna; Oh, Unsong; Jacobson, Steven] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Maloney, Elizabeth] US FDA, Div Epidemiol, Silver Spring, MD USA. 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 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD OCT PY 2010 VL 16 SU 1 BP 3 EP 4 PG 2 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 670GS UT WOS:000283409800008 ER PT J AU Sharma, A Honnold, SP Bhattacharya, B Puri, RK Maheshwari, RK AF Sharma, Anuj Honnold, Shelley P. Bhattacharya, Bhaskar Puri, Raj K. Maheshwari, Radha K. TI Venezuelan equine encephalitis virus infection induces a complex host innate immune response in brain SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 10th International Symposium on NeuroVirology CY OCT 12-16, 2010 CL Milan, ITALY C1 [Sharma, Anuj; Honnold, Shelley P.; Maheshwari, Radha K.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Bhattacharya, Bhaskar; Puri, Raj K.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD OCT PY 2010 VL 16 SU 1 BP 80 EP 81 PG 2 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 670GS UT WOS:000283409800174 ER PT J AU Wear, KA AF Wear, Keith A. TI Cancellous bone analysis with modified least squares Prony's method and chirp filter: Phantom experiments and simulation SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID ULTRASONIC WAVE-PROPAGATION; BIOT-ATTENBOROUGH MODEL; TRABECULAR BONE; PHASE-VELOCITY; NEGATIVE DISPERSION; TIME-DOMAIN; IN-VITRO; ACOUSTIC PROPAGATION; FREQUENCY RANGE; HUMAN CALCANEUS AB The presence of two longitudinal waves in porous media is predicted by Biot's theory and has been confirmed experimentally in cancellous bone. When cancellous bone samples are interrogated in through-transmission, these two waves can overlap in time. Previously, the Modified Least-Squares Prony's (MLSP) method was validated for estimation of amplitudes, attenuation coefficients, and phase velocities of fast and slow waves, but tended to overestimate phase velocities by up to about 5%. In the present paper, a pre-processing chirp filter to mitigate the phase velocity bias is derived. The MLSP/chirp filter (MLSPCF) method was tested for decomposition of a 500 kHz-center-frequency signal containing two overlapping components: one passing through a low-density-polyethylene plate (fast wave) and another passing through a cancellous-bone-mimicking phantom material (slow wave). The chirp filter reduced phase velocity bias from 100 m/s (5.1%) to 69 m/s (3.5%) (fast wave) and from 29 m/s (1.9%) to 10 m/s (0.7%) (slow wave). Similar improvements were found for 1) measurements in polycarbonate (fast wave) and a cancellous-bone-mimicking phantom (slow wave), and 2) a simulation based on parameters mimicking bovine cancellous bone. The MLSPCF method did not offer consistent improvement in estimates of attenuation coefficient or amplitude. [DOI: 10.1121/1.3478779) C1 US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Room 3108,Bldg 62,10903 New Hampshire Blvd, Silver Spring, MD 20993 USA. EM keith.wear@fda.hhs.gov FU FDA Office of Women's Health FX The author is grateful to Robert F. Wagner for discussions in the early 1990s regarding Prony's method for applications other than ultrasonic characterization of bone. The author is grateful for funding from the FDA Office of Women's Health. The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services. NR 61 TC 17 Z9 17 U1 1 U2 3 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD OCT PY 2010 VL 128 IS 4 BP 2191 EP 2203 DI 10.1121/1.3478779 PN 1 PG 13 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 669FA UT WOS:000283331100072 PM 20968389 ER PT J AU Saldanha, LG Dwyer, JT Andrews, KW Bailey, RL Gahche, JJ Hardy, CJ Holden, JM Picciano, MF Roseland, JM Thomas, PR Wolf, WR AF Saldanha, Leila G. Dwyer, Johanna T. Andrews, Karen W. Bailey, Regan L. Gahche, Jaime J. Hardy, Constance J. Holden, Joanne M. Picciano, Mary Frances Roseland, Janet M. Thomas, Paul R. Wolf, Wayne R. TI Online Dietary Supplement Resources SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article C1 [Saldanha, Leila G.] NIH, Off Dietary Supplements, Alexandria, VA USA. [Dwyer, Johanna T.; Bailey, Regan L.; Picciano, Mary Frances; Thomas, Paul R.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Andrews, Karen W.; Holden, Joanne M.; Roseland, Janet M.] ARS, USDA, Nutrient Data Lab, Beltsville, MD USA. [Gahche, Jaime J.] CDC, Natl Hlth & Nutr Examinat Survey Planning Branch, Natl Ctr Hlth Stat, Hyattsville, MD USA. [Hardy, Constance J.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Wolf, Wayne R.] Food Composit & Methods Dev Lab, Beltsville, MD USA. RP Saldanha, LG (reprint author), NIH, Off Dietary Supplements, Alexandria, VA USA. OI Dwyer, Johanna/0000-0002-0783-1769 FU Office of Dietary Supplements, National Institutes of Health; ODS FX Funds for the preparation of this article were provided by the Office of Dietary Supplements, National Institutes of Health.; Describes the ODS programs and offers links to research resources and research sponsored by ODS. NR 2 TC 7 Z9 8 U1 0 U2 1 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD OCT PY 2010 VL 110 IS 10 BP 1426 EP + DI 10.1016/j.jada.2010.08.013 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 657DJ UT WOS:000282392600003 PM 20869478 ER PT J AU Karanian, JW Peregoy, JA Chiesa, OA Murray, TL Ahn, C Pritchard, WF AF Karanian, John W. Peregoy, Jennifer A. Chiesa, O. Alberto Murray, Tracy L. Ahn, Chul Pritchard, William F. TI Efficiency of Drug Delivery to the Coronary Arteries in Swine Is Dependent on the Route of Administration: Assessment of Luminal, Intimal, and Adventitial Coronary Artery and Venous Delivery Methods SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID LOCAL PACLITAXEL DELIVERY; POROUS BALLOON CATHETERS; RAT CAROTID ARTERIES; GENE DELIVERY; NEOINTIMA FORMATION; ELUTING STENTS; POLYMERIC NANOPARTICLES; IN-VIVO; INJURY; RESTENOSIS AB PURPOSE: To compare the efficiency of five different drug delivery methods to the coronary artery in swine. MATERIALS AND METHODS: A nanoparticle-albumin-bound, nonradioactive isotopic marker was administered within the left anterior descending coronary artery (LAD) through a microinfusion catheter (MIC: adventitial, n = 8, and luminal, n = 4), a porous drug infusion balloon (DIB: intimal, n = 4), and a straight catheter (SC: luminal, n = 2) and within the superior vena cava (SC: intravenous, luminal, n = 2). The distribution of the marker in heart, lung, liver, kidney, muscle, blood, urine, and bile was determined 68-84 minutes after delivery. The heart was sectioned into six axial slices and each slice divided into four quadrants. The marker content was assayed by neutron bombardment and the total counts of disintegrations per minute (DPM) expressed as a percentage of the control for each device delivery control. RESULTS: After luminal delivery with the nonactuated MIC (MIC-NA) or intimal delivery with the DIB, 0.17% +/- 0.07 and 0.39% +/- 0.09, respectively, less than 0.39% of the total marker was detected in the heart. After adventitial delivery with the actuated MIC (MIC-A), 63.1% +/- 9.9 of the total marker was detected in the heart. Marker was only detected in quadrants containing the coronary LAD, with the highest level in the middle slice and lower marker levels in consecutive proximal and distal heart slices. The nonactuated MIC-NA and DIB drug infusion balloon patterns of marker distribution were similar to those of actuated MIC-A, although with reduced levels. These delivery methods were also associated with considerably more marker detected in the lungs and liver: at least 22% compared with 1.34% +/- 1.34 for the actuated MIC-A There was one delivery failure with the actuated MIC. CONCLUSIONS: Catheter-based adventitial delivery with the MIC-A represents a more efficient delivery method for retention of vascular therapeutics. C1 [Karanian, John W.; Peregoy, Jennifer A.; Chiesa, O. Alberto; Murray, Tracy L.; Pritchard, William F.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Lab Cardiovasc & Intervent Therapeut, Silver Spring, MD USA. [Ahn, Chul] Off Surveillance & Biostat, Div Biostat, Silver Spring, MD USA. RP Karanian, JW (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Lab Cardiovasc & Intervent Therapeut, Silver Spring, MD USA. EM john.karanian@fda.hhs.gov FU Center for Interventional Oncology at the National Institutes of Health, Bethesda, MD FX This work was supported in part by the Center for Interventional Oncology at the National Institutes of Health, Bethesda, MD. NR 39 TC 8 Z9 9 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD OCT PY 2010 VL 21 IS 10 BP 1555 EP 1564 DI 10.1016/j.jvir.2010.05.030 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 663TE UT WOS:000282912000014 PM 20813544 ER PT J AU Sweet, M Morrison, T Abel, D Fillinger, M AF Sweet, Matthew Morrison, Tina Abel, Dorothy Fillinger, Mark TI The Influence of Gender on Eligibility for Endovascular Aneurysm Repair SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract C1 [Sweet, Matthew; Fillinger, Mark] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Morrison, Tina; Abel, Dorothy] US FDA, Rockville, MD 20857 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 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD OCT PY 2010 VL 52 IS 4 BP 1115 EP 1115 DI 10.1016/j.jvs.2010.06.114 PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 660RF UT WOS:000282660300047 ER PT J AU Martinez, MN Whittem, T AF Martinez, M. N. Whittem, T. TI Letter to the Editors regarding the Scientific Paper by Gonzalez, Moreno, Fumuso, et al. SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Letter C1 [Martinez, M. N.] US FDA, Ctr Vet Med, Rockville, MD 20857 USA. [Whittem, T.] Univ Melbourne, Fac Vet Sci, Melbourne, Vic, Australia. RP Martinez, MN (reprint author), US FDA, Ctr Vet Med, Rockville, MD 20857 USA. RI Whittem, Ted/H-7203-2013 OI Whittem, Ted/0000-0002-4182-903X NR 5 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD OCT PY 2010 VL 33 IS 5 BP 416 EP 416 DI 10.1111/j.1365-2885.2010.01238.x PG 1 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 650ED UT WOS:000281831100002 PM 20840383 ER PT J AU Martinez, MN Hunter, RP AF Martinez, M. N. Hunter, R. P. TI Current challenges facing the determination of product bioequivalence in veterinary medicine SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Review ID HIGHLY-VARIABLE DRUGS; BIOPHARMACEUTICS CLASSIFICATION-SYSTEM; PERFUSED BOVINE UDDER; CONFIDENCE-INTERVALS; PHARMACOKINETIC PARAMETERS; CLINICAL IMPLICATIONS; TISSUE DISTRIBUTION; ABSORPTION RATES; RELEASE PRODUCTS; PEAK PHENOMENON AB Despite the pharmacological and statistical advances that have occurred since the early days of bioequivalence assessments, there remain many unresolved issues associated with the bioequivalence evaluation of human and veterinary pharmaceuticals. While many of these issues are common to both human and veterinary medicine, there are also challenges specific to veterinary drug products. Examples of complex problems that remain to be resolved include the assessment of drugs associated with complex kinetics (e.g., sustained release formulations that produce multiple peaks), the evaluation of intramammary formulations, uncertainty associated with conditions under which specific enantiomers of metabolites need to be factored into the bioequivalence evaluation, the study design for products and active pharmaceutical ingredients that exhibit highly variable kinetics, equivalence of biomass products, methods for evaluating topical formulations or formulations with very long duration of release, the evaluation of products where destructive sampling is necessary (e.g., aquaculture products), and the evaluation of bioequivalence for Type A medicated articles. This manuscript highlights many of the unresolved challenges currently impacting the evaluation of product bioequivalence in veterinary medicine, and provides a summary of the associated scientific complexities with each of these issues. C1 [Martinez, M. N.] US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. [Hunter, R. P.] Eli Lilly & Co, Food Anim Therapeut, Elanco Anim Hlth, Greenfield, IN USA. RP Martinez, MN (reprint author), US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. EM marilyn.martinez@fda.hhs.gov RI Hunter, Robert/A-2306-2008 OI Hunter, Robert/0000-0003-1224-2376 NR 101 TC 9 Z9 9 U1 0 U2 10 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD OCT PY 2010 VL 33 IS 5 BP 418 EP 433 DI 10.1111/j.1365-2885.2010.01180.x PG 16 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 650ED UT WOS:000281831100004 PM 20840385 ER PT J AU Pogribny, IP Starlard-Davenport, A Tryndyak, VP Han, T Ross, SA Rusyn, I Beland, FA AF Pogribny, Igor P. Starlard-Davenport, Athena Tryndyak, Volodymyr P. Han, Tao Ross, Sharon A. Rusyn, Ivan Beland, Frederick A. TI Difference in expression of hepatic microRNAs miR-29c, miR-34a, miR-155, and miR-200b is associated with strain-specific susceptibility to dietary nonalcoholic steatohepatitis in mice SO LABORATORY INVESTIGATION LA English DT Article DE methyl-deficient diet; mice; microRNA; nonalcoholic steatohepatitis; strain difference. ID FATTY LIVER-DISEASE; BINDING-PROTEIN-BETA; HUMAN HEPATOCELLULAR-CARCINOMA; MITOCHONDRIAL-DNA DAMAGE; INDUCED OXIDATIVE STRESS; HUMAN BREAST-CANCER; GENE-EXPRESSION; DOWN-REGULATION; E-CADHERIN; C/EBP-BETA AB The importance of dysregulation of microRNA (miRNA) expression in nonalcoholic steatohepatitis (NASH) has been increasingly recognized; however, the association between altered expression of miRNAs and pathophysiological features of NASH and whether there is a connection between susceptibility to NASH and altered expression of miRNAs are largely unknown. In this study, male inbred C57BL/6J and DBA/2J mice were fed a lipogenic methyl-deficient diet that causes liver injury similar to human NASH, and the expression of miRNAs and the level of proteins targeted by these miRNAs in the livers were determined. Administration of the methyl-deficient diet triggered NASH-specific changes in the livers of C57BL/6J and DBA/2J mice, with the magnitude being more severe in DBA/2J mice. This was evidenced by a greater extent of expression of fibrosis-related genes in the livers of methyl-deficient DBA/2J mice. The development of NASH was accompanied by prominent changes in the expression of miRNAs, including miR-29c, miR-34a, miR-155, and miR-200b. Interestingly, changes in the expression of these miRNAs and protein levels of their targets, including Cebp-b, Socs 1, Zeb-1, and E-cadherin, in the livers of DBA/2J mice fed a methyl-deficient diet were more pronounced as compared with those in C57BL/6J mice. These results show that alterations in the expression of miRNAs are a prominent event during development of NASH induced by methyl deficiency and strongly suggest that severity of NASH and susceptibility to NASH may be determined by variations in miRNA expression response. More important, our data provide a mechanistic link between alterations in miRNA expression and pathophysiological and pathomorphological features of NASH. Laboratory Investigation (2010) 90, 1437-1446; doi: 10.1038/labinvest.2010.113; published online 14 June 2010 C1 [Pogribny, Igor P.; Starlard-Davenport, Athena; Tryndyak, Volodymyr P.; Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Han, Tao] Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. [Ross, Sharon A.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3990 NCTR Rd,HFT-140, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov RI Rusyn, Ivan/S-2426-2016 FU NIEHS NIH HHS [R01 ES015241] NR 50 TC 87 Z9 95 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD OCT PY 2010 VL 90 IS 10 BP 1437 EP 1446 DI 10.1038/labinvest.2010.113 PG 10 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 655TY UT WOS:000282273900004 PM 20548288 ER PT J AU Huang, Y Lei, YF Zhang, H Zhang, MJ Dayton, A AF Huang, Yong Lei, YingFeng Zhang, Hai Zhang, Mingjie Dayton, Andrew TI Role of interleukin-18 in human natural killer cell is associated with interleukin-2 SO MOLECULAR IMMUNOLOGY LA English DT Article DE Natural killer cell; Interleukin-18; Interleukin-2; Expansion; Apoptosis ID GAMMA-INDUCING FACTOR; CYTOTOXIC ACTIVITY; HIV-INFECTION; CANCER; APOPTOSIS; CYTOKINE; THERAPY; BIOLOGY; IL-18; AIDS AB Human natural killer (NK) cells constitute an important cellular component of innate immunity, capable of killing infected and transformed cells. The proliferation and activation of NK cells are regulated by various cytokines. Interleukin-18 (IL-18) promotes NK cell activation; however, whether the effects of IL-18 on NK cell are associated with other cytokines is still unknown. In this study, we observed that IL-18 induced NK cell apoptosis and inhibited NK cell expansion in the presence of low concentrations of interleukin-2 (IL-2), while high concentrations of IL-2 overcame these effects of IL-18, and high concentrations of IL-2 promoted the stimulatory activity of IL-18 on NK cells. At a low concentration of IL-2, IL-18 induced NK cell apoptosis in part through activation of the FasL/Fas- and TNF alpha/TNFR-mediated death receptor signaling by enhancing FasL expression and inhibiting c-FLIP - long expression. However, high concentrations of IL-2 strongly blocked IL-18-induced NK cell apoptosis through alleviating IL-18-induced FasL expression and activation of Fas-mediated death signaling and increasing anti-apoptosis molecule (BcI-X(L)). These results reveal that the effects of IL-18 on human NK cell are associated with IL-2 concentration and suggest the importance of IL-2 level in cytokine immunotherapy. Published by Elsevier Ltd. C1 [Huang, Yong; Lei, YingFeng; Zhang, Hai; Zhang, Mingjie; Dayton, Andrew] US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Rockville, MD 20892 USA. [Huang, Yong] NW Polytech Univ, Dept Life Sci, Xian 710072, Shaanxi, Peoples R China. [Lei, YingFeng; Zhang, Hai] Fourth Mil Med Univ, Dept Microbiol, Xian 710032, Shaanxi, Peoples R China. RP Zhang, MJ (reprint author), US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20892 USA. EM ming.zhang@fda.hhs.gov; andrew.dayton@fda.hhs.gov RI Huang, Yong/G-9365-2011 NR 31 TC 6 Z9 9 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD OCT PY 2010 VL 47 IS 16 BP 2604 EP 2610 DI 10.1016/j.molimm.2010.05.290 PG 7 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 693OP UT WOS:000285233700009 PM 21035858 ER PT J AU Reefhuis, J Whitney, CG Mann, EA AF Reefhuis, Jennita Whitney, Cynthia G. Mann, Eric A. TI A Public Health Perspective on Cochlear Implants and Meningitis in Children SO OTOLOGY & NEUROTOLOGY LA English DT Editorial Material ID PNEUMOCOCCAL CONJUGATE VACCINE; BACTERIAL-MENINGITIS; RISK; EXPERIENCE; MODEL C1 [Reefhuis, Jennita] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA. [Mann, Eric A.] US FDA, Bethesda, MD 20014 USA. RP Reefhuis, J (reprint author), Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, 1600 Clifton Rd NE,MS E-86, Atlanta, GA 30333 USA. EM nzr5@cdc.gov RI Reefhuis, Jennita/E-1793-2011 OI Reefhuis, Jennita/0000-0002-4747-4831 NR 21 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD OCT PY 2010 VL 31 IS 8 BP 1329 EP 1330 DI 10.1097/MAO.0b013e3181f2f05f PG 2 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 656DR UT WOS:000282306900027 PM 20802368 ER PT J AU Kundoor, V Ahmed, MKK AF Kundoor, Vipra Ahmed, Mueen K. K. TI Uncovering negative results: Introducing an open access journal "Journal of Pharmaceutical Negative Results" SO PHARMACOGNOSY MAGAZINE LA English DT Letter C1 [Ahmed, Mueen K. K.] King Faisal Univ, Coll Clin Pharm, Dept Pharm Sci, Al Hasa, Saudi Arabia. [Kundoor, Vipra] US FDA, Rockville, MD 20857 USA. RP Ahmed, MKK (reprint author), King Faisal Univ, Coll Clin Pharm, Dept Pharm Sci, Al Hasa, Saudi Arabia. EM mueen.ahmed@gmail.com RI Ahmed, Mueen/A-8370-2011 OI Ahmed, Mueen/0000-0002-6705-4949 NR 0 TC 4 Z9 4 U1 0 U2 4 PU PHARMACOGNOSY NETWORK WORLDWIDE PI BANGALORE PA AL-AMEEN COLL PHARMACY, HOSUR RD, BANGALORE, 560 027, INDIA SN 0973-1296 J9 PHARMACOGN MAG JI Pharmacogn. Mag. PD OCT-DEC PY 2010 VL 6 IS 24 BP 345 EP 347 DI 10.4103/0973-1296.71783 PG 3 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 676OW UT WOS:000283922900019 PM 21120041 ER PT J AU Ma, J Whittaker, P Keller, AC Mazzola, EP Pawar, RS White, KD Callahan, JH Kennelly, EJ Krynitsky, AJ Rader, JI AF Ma, Jun Whittaker, Paul Keller, Amy C. Mazzola, Eugene P. Pawar, Rahul S. White, Kevin D. Callahan, John H. Kennelly, Edward J. Krynitsky, Alexander J. Rader, Jeanne I. TI Cucurbitane-Type Triterpenoids from Momordica charantia SO PLANTA MEDICA LA English DT Article DE Momordica charantia; Cucurbitaceae; cucurbitane-type triterpenoid; momordicoside U ID OVIPOSITION DETERRENT; LIRIOMYZA-TRIFOLII; GLYCOSIDES; CONSTITUENTS; LEAFMINER; LEAVES; FRUITS AB One new cucurbitane-type triterpenoid glycoside, momordicoside U (1), together with five known cucurbitane-type triterpenoids and related glycosides, 3 beta,7 beta,25-trihydroxycucurbita-5,23 (E)-dien-19-al (2), momordicine I(3), momordicine II(4), 3-hydroxycucurbita-5,24-dien-19-al-7,23-di-O-beta-glucopyranoside (5), and kuguaglycoside G (6), were isolated from the whole plant of Momordica charantia. Their structures were determined by chemical and spectroscopic methods. Momordicoside U (1) was evaluated for insulin secretion activity in an in vitro insulin secretion assay and displayed moderate activity. C1 [Ma, Jun; Whittaker, Paul; Mazzola, Eugene P.; Pawar, Rahul S.; White, Kevin D.; Callahan, John H.; Krynitsky, Alexander J.; Rader, Jeanne I.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Keller, Amy C.; Kennelly, Edward J.] CUNY Herbert H Lehman Coll, Dept Biol Sci, Bronx, NY 10468 USA. [Keller, Amy C.; Kennelly, Edward J.] CUNY, Grad Ctr, Bronx, NY USA. RP Ma, J (reprint author), US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM jun.ma@fda.hhs.gov NR 20 TC 18 Z9 22 U1 0 U2 8 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD OCT PY 2010 VL 76 IS 15 BP 1758 EP 1761 DI 10.1055/s-0030-1249807 PG 4 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 676MY UT WOS:000283917300025 PM 20379957 ER PT J AU Basch, E Reeve, B Cleeland, CS Sloan, JA Schrag, D Atkinson, TM Mendoza, TR Hay, JL Abernethy, AP Minasian, L Kwitkowski, V Trentacosti, AM Burke, L Sit, L Bruner, DW AF Basch, Ethan Reeve, Bryce Cleeland, Charles S. Sloan, Jeff A. Schrag, Deborah Atkinson, Thomas M. Mendoza, Tito R. Hay, Jennifer L. Abernethy, Amy P. Minasian, Lori Kwitkowski, Virginia Trentacosti, Ann Marie Burke, Laurie Sit, Laura Bruner, Deborah W. TI Development of the Patient-Reported Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) SO QUALITY OF LIFE RESEARCH LA English DT Meeting Abstract C1 [Basch, Ethan; Sit, Laura] Mem Sloan Kettering Canc Ctr, Epidemiol & Biostat, New York, NY 10021 USA. [Reeve, Bryce] NCI, Outcomes Res, Bethesda, MD 20892 USA. [Cleeland, Charles S.; Mendoza, Tito R.] Univ Texas MD Anderson Canc Ctr, Symptom Res, Houston, TX 77030 USA. [Sloan, Jeff A.] Mayo Clin, Biomed Stat & Informat, Rochester, MN USA. [Schrag, Deborah] Dana Farber Canc Inst, Med, Boston, MA 02115 USA. [Atkinson, Thomas M.; Hay, Jennifer L.] Mem Sloan Kettering Canc Ctr, Psychiat & Behav Sci, New York, NY 10021 USA. [Abernethy, Amy P.] Duke Univ, Sch Med, Med, Durham, NC USA. [Minasian, Lori] NCI, Canc Prevent, Rockville, MD USA. [Kwitkowski, Virginia] US FDA, Drug Oncol Prod, Silver Spring, MD USA. [Burke, Laurie] US FDA, Study Endpoints & Labeling Dev, Silver Spring, MD USA. [Bruner, Deborah W.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 EI 1573-2649 J9 QUAL LIFE RES JI Qual. Life Res. PD OCT PY 2010 VL 19 SU 1 MA 161439 BP 50 EP 51 PG 2 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA V38QU UT WOS:000209358700153 ER PT J AU Twaddle, NC Churchwell, MI Vanlandingham, M Doerge, DR AF Twaddle, Nathan C. Churchwell, Mona I. Vanlandingham, Michelle Doerge, Daniel R. TI Quantification of deuterated bisphenol A in serum, tissues, and excreta from adult Sprague-Dawley rats using liquid chromatography with tandem mass spectrometry SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID HPLC-MS/MS METHOD; ENVIRONMENTAL PHENOLS; EXPOSURES; URINE AB Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products, epoxy resin-based food can liners, and paper products. The presence of BPA in urine of >90% of Americans aged 6-60 suggests ubiquitous and frequent exposure and is problematic because of the potential for endocrine disruption. The ubiquity of environmental BPA in common laboratory supplies used for sample collection, storage, and analysis greatly increases the likelihood of false positive determinations, particularly at trace levels. The current study validated using liquid chromatography/tandem mass spectrometry (LC/MS/MS) in conjunction with deuterated BPA as the dosing material to circumvent contamination for high sensitivity quantifications in rat serum, tissues, urine, and feces. The methods described provided measurements of both estrogen receptor-active aglycone and metabolically deactivated conjugated forms of BPA, a distinction that is critical to assessing toxicological potential. The adequacy of the described methodology was substantiated by its utility in analyzing samples from rats treated orally with a 100 mu g/kg body weight dose of d6-BPA. These results emphasize the challenges inherent in measuring BPA in biological samples and how employing stable isotope labeled dosing can facilitate pharmacokinetic studies needed to understand BPA metabolism and disposition. Such studies conducted in experimental animal models, in conjunction with properly validated human biomonitoring data, will be the basis for PBPK modeling of BPA in environmentally exposed humans. Published in 2010 by John Wiley & Sons, Ltd. C1 [Twaddle, Nathan C.; Churchwell, Mona I.; Vanlandingham, Michelle; Doerge, Daniel R.] 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, 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 have no conflicts of interest to report. NR 24 TC 34 Z9 34 U1 0 U2 20 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 OCT PY 2010 VL 24 IS 20 BP 3011 EP 3020 DI 10.1002/rcm.4733 PG 10 WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA 666GR UT WOS:000283103000011 PM 20872634 ER PT J AU Idowu, OR Peggins, JO Cullison, R von Bredow, J AF Idowu, O. R. Peggins, J. O. Cullison, R. von Bredow, J. TI Comparative pharmacokinetics of enrofloxacin and ciprofloxacin in lactating dairy cows and beef steers following intravenous administration of enrofloxacin SO RESEARCH IN VETERINARY SCIENCE LA English DT Article DE Enrofloxacin; Ciprofloxacin; Pharmacokinetics; Lactating cows; Steers ID METABOLITE CIPROFLOXACIN; DISPOSITION; SINGLE; SHEEP; INJECTIONS; RABBITS; MILK AB The comparative pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin were investigated in lactating cows and beef steers. The plasma elimination half-life of either enrofloxacin or ciprofloxacin was shorter in cows than in steers. The overall production of ciprofloxacin was slightly higher in steers than in cows (metabolite ratio: 64% and 59%, respectively). There was no significant difference in plasma protein binding of enrofloxacin between cows (percent bound: 59.4%) and steers (percent bound: 60.8%). Ciprofloxacin was more extensively bound to plasma proteins in steers (percent bound: 49.6%) than in cows (percent bound: 33.8%). The steady state volume of distribution of enrofloxacin is comparable in cows (1.55 L/kg) and steers (1.59 L/kg). Within either bovine class, plasma elimination half-life of enrofloxacin and ciprofloxacin are comparable, while plasma protein binding was higher for enrofloxacin than for ciprofloxacin. Ciprofloxacin was more concentrated in milk than enrofloxacin. Published by Elsevier Ltd. C1 [Idowu, O. R.; Peggins, J. O.; Cullison, R.; von Bredow, J.] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Idowu, OR (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM olutosin.idowu@fda.hhs.gov NR 17 TC 21 Z9 21 U1 1 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0034-5288 J9 RES VET SCI JI Res. Vet. Sci. PD OCT PY 2010 VL 89 IS 2 BP 230 EP 235 DI 10.1016/j.rvsc.2009.12.019 PG 6 WC Veterinary Sciences SC Veterinary Sciences GA 653TS UT WOS:000282120400019 PM 20129633 ER PT J AU Xu, C Yin, JJ Zhao, BL AF Xu Chao Yin JunJie Zhao BaoLu TI Structural characteristics of the hydrophobic patch of azurin and its interaction with p53: a site-directed spin labeling study SO SCIENCE CHINA-LIFE SCIENCES LA English DT Article DE azurin; p53; spin label; protein-protein interaction; anticancer; ESR ID TUMOR-SUPPRESSOR PROTEIN; PSEUDOMONAS-AERUGINOSA AZURIN; BACTERIAL CUPREDOXIN AZURIN; CRYSTAL-STRUCTURE; DISULFIDE BRIDGE; HETEROLOGOUS EXPRESSION; CONFORMATIONAL-CHANGES; ESCHERICHIA-COLI; MAMMALIAN-CELLS; APOPTOSIS AB Site-directed spin labeling (SDSL) is a powerful tool for monitoring protein structure, dynamics and conformational changes. In this study, the domain-specific properties of azurin and its interaction with p53 were studied using this technique. Mutations of six residues, that are located in the hydrophobic patch of azurin, were prepared and spin labeled. Spectra of the six azurin mutants in solution showed that spin labeled residues 45 and 63 are in a very restricted environment, residues 59 and 65 are in a spacious environment and have free movement, and residues 49 and 51 are located in a relatively closed pocket. Polarity experiments confirmed these results. The changes observed in the spectra of spin labeled azurin upon interaction with p53 indicate that the hydrophobic patch is involved in this interaction. Our results provide valuable insight into the topographic structure of the hydrophobic domain of azurin, as well as direct evidence of its interaction with p53 in solution via the hydrophobic patch. Cytotoxicity studies of azurin mutants showed that residues along the hydrophobic patch are important for its cytotoxicity. C1 [Xu Chao; Zhao BaoLu] Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, Beijing 100101, Peoples R China. [Xu Chao; Zhao BaoLu] Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China. [Yin JunJie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Zhao, BL (reprint author), Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, Beijing 100101, Peoples R China. EM zhaobl@sun5.ibp.ac.cn RI Yin, Jun Jie /E-5619-2014 FU National Natural Science Foundation of China [30370361]; National Basic Research Program of China [2006CB500700]; Key Laboratory of Mental Health, Chinese Academy of Sciences FX We thank Professors Gao Jin and Bi LiJun for their kind gifts of plasmids for azurin and p53 expression, and Chen YongSheng for technical support with the ESR measurements. This work was supported by the National Natural Science Foundation of China (Grant No. 30370361), the National Basic Research Program of China (Grant No. 2006CB500700), and was partially supported by the Key Laboratory of Mental Health, Chinese Academy of Sciences. NR 38 TC 2 Z9 2 U1 0 U2 1 PU SCIENCE CHINA PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1674-7305 J9 SCI CHINA LIFE SCI JI Sci. China-Life Sci. PD OCT PY 2010 VL 53 IS 10 BP 1181 EP 1188 DI 10.1007/s11427-010-4069-2 PG 8 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 666MR UT WOS:000283120000004 PM 20953940 ER PT J AU Shomron Dobkin, A AF Shomron Dobkin, Alexandra TI A splice variant of ADAMTS13 is expressed in human hepatic stellate cells and cancerous tissues (vol 104, pg 531, 2010) SO THROMBOSIS AND HAEMOSTASIS LA English DT Correction C1 [Dobkin, Alexandra] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM alexandradobkin@hotmail.com NR 1 TC 0 Z9 0 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD OCT PY 2010 VL 104 IS 4 BP 861 EP 861 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 671PD UT WOS:000283517300027 ER PT J AU Zhang, J DeFelice, AF Hanig, JP Colatsky, T AF Zhang, Jun DeFelice, Albert F. Hanig, Joseph P. Colatsky, Thomas TI Biomarkers of Endothelial Cell Activation Serve as Potential Surrogate Markers for Drug-induced Vascular Injury SO TOXICOLOGIC PATHOLOGY LA English DT Review DE endothelial cell activation; biomarkers; drug-induced vascular injury ID INTERCELLULAR-ADHESION MOLECULE-1; VON-WILLEBRAND-FACTOR; TUMOR-NECROSIS-FACTOR; SPRAGUE-DAWLEY RATS; NF-KAPPA-B; NITRIC-OXIDE SYNTHASE; ACUTE-PHASE PROTEINS; KAWASAKI-DISEASE; E-SELECTIN; IN-VITRO AB Drug-induced vascular injury (DIVI) is a nonclinical finding that often confounds the toxicological evaluation of investigational drugs, but there is an absence of qualified biomarkers that can be used to detect and monitor its appearance in animals and patients during drug development and clinical use. It is well known that endothelial cell (EC) activation plays a key role in the expression and evolution of DIVI, and the various immunological and inflammatory factors involved in its expression may serve as potential biomarker candidates. Activated ECs change their morphology and gene expression, generating endothelial adhesion molecules, pro-coagulant molecules, cytokines, chemokines, vasodilators, nitric oxide, and acute-phase reactants. This review provides a brief historical background of EC activation and the search for biomarkers of early EC activation for monitoring DIVI. At present, no biomarkers of EC activation have been qualified to predict DIVI in the nonclinical or clinical context, and a robust pathologic foundation for their use is still lacking. We propose three categories of EC activation biomarkers: recommended surrogate markers, potentially useful markers, and emerging candidate markers. This review alerts pharmaceutical companies, research institutions, and regulatory agencies to the continuing need for reliable biomarkers of EC activation in drug development. C1 [Zhang, Jun; Colatsky, Thomas] US FDA, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [DeFelice, Albert F.] US FDA, Div Cardiovasc & Renal Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Hanig, Joseph P.] US FDA, Off Testing & Res, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Zhang, J (reprint author), Food & Drug Adm HFD 910, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM jun.zhang@fda.hhs.gov FU The Office of Testing and Research, Center for Drug Evaluation and Research, Food and Drug Administration FX This work was supported by The Office of Testing and Research, Center for Drug Evaluation and Research, Food and Drug Administration. The authors wish to thank Dr. Vincent Vilker (OTR, CDER, FDA) for his encouragement and support in preparation for the manuscript and for critical review of this article. The authors also thank Joanne Berger (FDA Biosciences Library) for technical assistance with database searching and reference management and Alan D. Knapton (Division of Applied Pharmacology research, FDA) for help in Figure 1 preparation. NR 134 TC 30 Z9 34 U1 1 U2 8 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 OCT PY 2010 VL 38 IS 6 BP 856 EP 871 DI 10.1177/0192623310378866 PG 16 WC Pathology; Toxicology SC Pathology; Toxicology GA 707VA UT WOS:000286315700003 PM 20716788 ER PT J AU Doerge, DR Twaddle, NC Woodling, KA Fisher, JW AF Doerge, Daniel R. Twaddle, Nathan C. Woodling, Kellie A. Fisher, Jeffrey W. TI Pharmacokinetics of bisphenol A in neonatal and adult rhesus monkeys SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Bisphenol A; Rhesus monkey; Pharmacokinetics; Mass spectrometry; Neonatal ID HUMAN UDP-GLUCURONOSYLTRANSFERASES; SPRAGUE-DAWLEY RATS; DEVELOPMENTAL EXPRESSION; REPRODUCTIVE TOXICITY; HUMAN-LIVER; IN-VITRO; GLUCURONIDATION; DISPOSITION; METABOLISM; EXPOSURE AB Bisphenol A (BPA) is a high-production volume industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA in urine of >90% of Americans aged 6-60 is controversial because of the potential for endocrine disruption, particularly during perinatal development, as suggested by in vitro, experimental animal, and epidemiological studies. The current study used LC/MS/MS to measure serum pharmacokinetics of aglycone (active) and conjugated (inactive) BPA in adult and neonatal rhesus monkeys by oral (PND 5,35, 70) and intravenous injection (PND 77) routes using d6-BPA to avoid sample contamination. The concentration-time profiles observed in adult monkeys following oral administration of 100 mu g/kg bw were remarkably similar to those previously reported in human volunteers given a similar dose: moreover, minimal pharmacokinetic differences were observed between neonatal and adult monkeys for the receptor-active aglycone form of BPA. Circulating concentrations of BPA aglycone were quite low following oral administration (< 1% of total), which reflects the redundancy of active UDP-glucuronosyl transferase isoforms in both gut and liver. No age-related changes were seen in internal exposure metrics for aglycone BPA in monkeys, a result clearly different from developing rats where significant inverse age-related changes, based on immaturity of Phase II metabolism and renal excretion, were recently reported. These observations imply that any toxicological effect observed in rats from early postnatal exposures to BPA could over-predict those possible in primates of the same age, based on significantly higher internal exposures and overall immaturity at birth. Published by Elsevier Inc. C1 [Doerge, Daniel R.; Twaddle, Nathan C.; Woodling, Kellie A.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Fisher, Jeffrey W.] Univ Georgia, Coll Publ Hlth, Dept Environm Hlth Sci, Athens, GA 30602 USA. RP Doerge, DR (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, 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 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. The assistance of Melissa Ferguson (Alpha Genesis Inc.) in conducting the monkey procedures and helpful discussions with Dr. John Young are gratefully acknowledged. 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 author(s) and do not necessarily represent the views of the FDA. The authors have no conflicts of interest to report. NR 41 TC 60 Z9 61 U1 3 U2 25 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD OCT 1 PY 2010 VL 248 IS 1 BP 1 EP 11 DI 10.1016/j.taap.2010.07.009 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 652HS UT WOS:000281995100001 PM 20655935 ER PT J AU Gelderman, MP Yazer, MH Jia, Y Wood, F Alayash, AI Vostal, JG AF Gelderman, M. P. Yazer, M. H. Jia, Y. Wood, F. Alayash, A. I. Vostal, J. G. TI Serial oxygen equilibrium and kinetic measurements during RBC storage SO TRANSFUSION MEDICINE LA English DT Article DE 2,3-DPG; haemoglobin; oxygen dissociation; rate constants; red blood cell; storage lesion ID STORED-BLOOD; NITRIC-OXIDE; HEMOGLOBIN AB Objectives: To contribute to the understanding of the biochemical changes associated with the RBC storage lesion. Aim: To investigate changes in O(2) equilibrium and on/off kinetic rates during routine cold storage. Background: As RBCs are stored between 1 and 6 degrees C numerous biochemical changes occur within the RBCs, including changes in the properties of the haemoglobin itself. This study serially analysed for the first time the O(2) equilibrium and on/off kinetic rates across the RBC membrane during routine storage. Methods/Materials: The oxygen binding (k(on)) and offloading (k(off)) constants were measured in fresh RBCs and then in AS-5-preserved RBCs at weekly intervals, along with oxygen equilibrium curves (OECs), 2,3-Diphosphoglycerate (2,3-DPG), p50 and the Hill number (n). Results: The k(on) increased slightly as the 2,3-DPG and p50 decreased during storage, whereas the k(off) remained largely unchanged. The OECs demonstrated the expected increase in O(2) affinity, whereas the Hill number was unchanged during storage. Conclusion: In spite of the biochemical, structural and functional changes associated with the storage of RBCs, their in vitro interactions with oxygen were largely preserved through 42 days of storage. C1 [Yazer, M. H.] Univ Pittsburgh, Inst Transfus Med, Pittsburgh, PA 15213 USA. [Yazer, M. H.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA. [Gelderman, M. P.; Vostal, J. G.] US FDA, Lab Cellular Hematol, Div Hematol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Jia, Y.; Wood, F.; Alayash, A. I.] US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Yazer, MH (reprint author), Univ Pittsburgh, Inst Transfus Med, 3636 Blvd Allies, Pittsburgh, PA 15213 USA. EM myazer@itxm.org NR 11 TC 13 Z9 14 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0958-7578 J9 TRANSFUSION MED JI Transfus. Med. PD OCT PY 2010 VL 20 IS 5 BP 341 EP 345 DI 10.1111/j.1365-3148.2010.01016.x PG 5 WC Hematology SC Hematology GA 655KN UT WOS:000282249000007 PM 20534030 ER PT J AU Buehler, PW D'Agnillo, F Schaer, DJ AF Buehler, Paul W. D'Agnillo, Felice Schaer, Dominik J. TI Hemoglobin-based oxygen carriers: from mechanisms of toxicity and clearance to rational drug design SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID CROSS-LINKED HEMOGLOBIN; CELL-FREE HEMOGLOBIN; INDUCED RENAL-FAILURE; NITRIC-OXIDE; SCAVENGER RECEPTOR; BLOOD SUBSTITUTES; ENDOTHELIAL-CELLS; HEME OXYGENASE-1; BACTERIAL-ENDOTOXIN; ELECTRON-MICROSCOPY AB Hemoglobin-based oxygen carriers (HBOCs) have been developed to support blood oxygen transport capacity during hemorrhagic shock, hemolysis and ischemic insult. Existing product candidates have demonstrated considerable efficacy in experimental animal models and in clinical trial subjects; however, severe adverse safety signals that appeared in recent phase II and phase Ill clinical trials involving certain HBOCs have in part hindered further development and licensing. Emerging insights into hemoglobin (Hb) toxicity as well as physiologic Hb scavengers such as haptoglobin and CD163 that are capable of detoxifying extracellular Hb in vivo suggest that alternative product candidates could be designed. Together with novel animal models and biomarkers tailored to monitor the effects of extracellular Hb, a new generation of HBOCs can be envisioned. C1 [Schaer, Dominik J.] Univ Zurich, Zurich, Switzerland. [Buehler, Paul W.; D'Agnillo, Felice] US FDA, Lab Biochem & Vasc Biol, Div Hematol, CBER, Bethesda, MD 20014 USA. RP Schaer, DJ (reprint author), Univ Zurich, Zurich, Switzerland. EM dominik.schaer@usz.ch FU FDA Critical Path Initiative; Swiss National Science Foundation [31-120658]; Fonds fur Akademische Nachwuchforderung (FAN) (University of Zurich) FX This work was supported a FDA Critical Path Initiative grant to (P.W.B and F.D). A Swiss National Science Foundation grant (# 31-120658) and Fonds fur Akademische Nachwuchforderung (FAN) funding (University of Zurich) to (D.J.S.). NR 100 TC 43 Z9 43 U1 3 U2 24 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD OCT PY 2010 VL 16 IS 10 BP 447 EP 457 DI 10.1016/j.molmed.2010.07.006 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 673QS UT WOS:000283678700002 PM 20708968 ER PT J AU Subbotina, E Dadaeva, A Kachko, A Chepurnov, A AF Subbotina, Ekaterina Dadaeva, Alexandra Kachko, Alla Chepurnov, Alexander TI Genetic factors of Ebola virus virulence in guinea pigs SO VIRUS RESEARCH LA English DT Article DE Filoviridae; RNA viruses; Ebola virus; Pathogenicity; Virulence; Genome; VP24; NP ID SECONDARY STRUCTURE PREDICTION; HEMORRHAGIC FEVERS; PROTEIN; SEQUENCE; VP24; INFECTION; PHOSPHORYLATION; NUCLEOPROTEIN; GLYCOSYLATION; GLYCOPROTEIN AB Zaire ebolavirus (ZEBOV) causes severe hemorrhagic fever in primates, whereas in guinea pigs it induces a nonlethal infection with a mild fever and subsequent recovery. We performed 7 selective passages in guinea pigs resulted in obtaining of guinea pig-adapted strain (GPA-P7) strain. By the 7th passage, the infection with EBOV induced a lethal disease in animals accompanied by the characteristic hematological changes: leukocytosis (primarily due to neutrophilia) as well as pronounced deficiencies in platelets, lymphocytes, monocytes and significant decrease of blood neutrophils phagocytic capacity. Increasing of virulence correlated with appearance of several nucleotide substitutions: in the genes NP, A2166G (N566S), VP24, U10784C (L147P), G10557A (M71I), G10805U (R154L), and L, G12286A (V236I). It has been theoretically calculated that the mutations associated with an increase in EBOV virulence can confer characteristic secondary structure on the proteins NP (C-terminal region) and full-sized VP24. Published by Elsevier B.V. C1 [Kachko, Alla] US FDA, Lab Hepatitis Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Subbotina, Ekaterina; Dadaeva, Alexandra; Kachko, Alla] State Res Ctr Virol & Biotechnol Vector, Dept Mol Virol, Koltsov 630559, Russia. [Chepurnov, Alexander] Russian Acad Med Sci, Siberian Branch, Res Inst Clin Immunol, Novosibirsk 630099, Russia. RP Kachko, A (reprint author), US FDA, Lab Hepatitis Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bldg 29A,Rm 1D10,HFM 448,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Subbotina@ngs.ru; Alla.Kachko@fda.hhs.gov; Alexa.Che.purnov@gmail.com FU Russian Foundation for Basic Research [93-04-6712]; Russian Ministry of Industry and Science [43.035.1.1.1529] FX We are grateful to Antonina Presnyakova for excellent technical assistance. We thank Dr. Marian Major for editing the manuscript. This work was supported by the Russian Foundation for Basic Research (project no. 93-04-6712) and Russian Ministry of Industry and Science (project no. 43.035.1.1.1529). NR 59 TC 16 Z9 16 U1 0 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD OCT PY 2010 VL 153 IS 1 BP 121 EP 133 DI 10.1016/j.virusres.2010.07.015 PG 13 WC Virology SC Virology GA 658JK UT WOS:000282486100016 PM 20654661 ER PT J AU Ruzante, JM Lombard, JE Wagner, B Fossler, CP Karns, JS Van Kessel, JAS Gardner, IA AF Ruzante, J. M. Lombard, J. E. Wagner, B. Fossler, C. P. Karns, J. S. Van Kessel, J. A. S. Gardner, I. A. TI Factors Associated with Salmonella Presence in Environmental Samples and Bulk Tank Milk from US Dairies SO ZOONOSES AND PUBLIC HEALTH LA English DT Article DE Environmental samples; dairy cattle; bulk tank milk; milk filters; Salmonella; National Animal Health Monitoring System ID ESCHERICHIA-COLI O157-H7; AVIUM SSP PARATUBERCULOSIS; UNITED-STATES; RAW-MILK; TYPHIMURIUM INFECTION; RISK-FACTORS; LISTERIA-MONOCYTOGENES; RESISTANT SALMONELLA; MULTISTATE OUTBREAK; FECAL PREVALENCE AB The objective of this study was to evaluate herd characteristics and management practices associated with presence of Salmonella in the farm environment and in bulk tank milk (BTM) in US dairy herds. Herd management data, environmental culture, BTM and in-line milk filter polymerase chain reaction results for Salmonella from 260 US dairy herds surveyed during the National Animal Health Monitoring System Dairy 2007 study were analysed. Herd characteristics and management practices were screened by univariate analysis, and selected variables were used to construct a logistic regression model to identify factors associated with the presence of Salmonella in environmental samples. To identify factors associated with the occurrence of Salmonella in BTM and milk filters, a priori selected variables that were related to milking procedures were analysed univariately and a logistic regression model was constructed. The presence of Salmonella in the farm environment was associated with location of the operation in the East (OR = 4.8; CI: 1.9-11.6), not using a broadcast manure spreader (OR = 3.2; CI: 1.4-7.5), use of bovine somatotropin (BST) (OR = 2.7; CI: 1.5-5.0) and use of anionic salts (OR = 2.2; CI: 1.2-3.9). In the final multivariable model, herds with fewer than 100 cows were at decreased odds (OR = 0.3; CI: 0.1-0.7) of being culture positive for Salmonella as were herds with between 100 and 499 cows (OR = 0.4; CI: 0.2-0.8) compared with herds having 500 or more cows. The presence of culture-positive environmental samples and herd size were significantly associated with Salmonella BTM contamination. The herd-level factors identified in this study were in agreement with prior studies but also identified other potential factors that can be targeted in Salmonella control programmes. C1 [Lombard, J. E.] USDA, APHIS, Ctr Epidemiol & Anim Hlth, VS, Ft Collins, CO 80526 USA. [Ruzante, J. M.] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. [Karns, J. S.; Van Kessel, J. A. S.] ARS, USDA, Beltsville, MD USA. [Gardner, I. A.] Univ Calif Davis, Sch Vet Med, Dept Med & Epidemiol, Davis, CA 95616 USA. RP Lombard, JE (reprint author), USDA, APHIS, Ctr Epidemiol & Anim Hlth, VS, CEAH 2150,Ctr Ave, Ft Collins, CO 80526 USA. EM jason.e.lombard@aphis.usda.gov NR 40 TC 15 Z9 15 U1 2 U2 13 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1863-1959 J9 ZOONOSES PUBLIC HLTH JI Zoonoses Public Health PD OCT PY 2010 VL 57 IS 7-8 BP E217 EP E225 DI 10.1111/j.1863-2378.2010.01333.x PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases; Veterinary Sciences SC Public, Environmental & Occupational Health; Infectious Diseases; Veterinary Sciences GA 682AR UT WOS:000284369000034 PM 20529209 ER PT J AU Burvall, A Barrett, HH Myers, KJ Dainty, C AF Burvall, Anna Barrett, Harrison H. Myers, Kyle J. Dainty, Christopher TI Singular-value decomposition of a tomosynthesis system SO OPTICS EXPRESS LA English DT Article ID DIGITAL BREAST TOMOSYNTHESIS; MAMMOGRAPHY; ACQUISITION; OBSERVER; IMAGES; NOISE; ANGLE; MODEL AB Tomosynthesis is an emerging technique with potential to replace mammography, since it gives 3D information at a relatively small increase in dose and cost. We present an analytical singular-value decomposition of a tomosynthesis system, which provides the measurement component of any given object. The method is demonstrated on an example object. The measurement component can be used as a reconstruction of the object, and can also be utilized in future observer studies of tomosynthesis image quality. (C) 2010 Optical Society of America C1 [Burvall, Anna] AlbaNova Univ Ctr, Royal Inst Technol, SE-10691 Stockholm, Sweden. [Barrett, Harrison H.] Univ Arizona, Coll Opt Sci, Tucson, AZ 85724 USA. [Barrett, Harrison H.] Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA. [Myers, Kyle J.] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, CDRH, Rockville, MD 20857 USA. [Dainty, Christopher] Natl Univ Ireland, Sch Phys, Galway, Ireland. RP Burvall, A (reprint author), AlbaNova Univ Ctr, Royal Inst Technol, SE-10691 Stockholm, Sweden. EM anna.burvall@biox.kth.se FU Science Foundation Ireland [07/IN.1/1906]; Center for Gamma-Ray Imaging [5 P41EB002035-11]; SPECT [5 R37 EB000803-19]; Swedish Research Council FX C. Dainty acknowledges support from Science Foundation Ireland Grant No 07/IN.1/1906, H. Barrett from the Center for Gamma-Ray Imaging Grant 5 P41EB002035-11 and the SPECT Imaging and Parallel Computing Grant 5 R37 EB000803-19, and A. Burvall from the Swedish Research Council. NR 27 TC 0 Z9 0 U1 0 U2 4 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD SEP 27 PY 2010 VL 18 IS 20 BP 20699 EP 20711 DI 10.1364/OE.18.020699 PG 13 WC Optics SC Optics GA 673QX UT WOS:000283679200018 PM 20940966 ER PT J AU Dube, D Schornberg, KL Shoemaker, CJ Delos, SE Stantchev, TS Clouse, KA Broder, CC White, JM AF Dube, Derek Schornberg, Kathryn L. Shoemaker, Charles J. Delos, Sue E. Stantchev, Tzanko S. Clouse, Kathleen A. Broder, Christopher C. White, Judith M. TI Cell adhesion-dependent membrane trafficking of a binding partner for the ebolavirus glycoprotein is a determinant of viral entry SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE filovirus; negative strand RNA virus; virus receptor; lymphocytes; macrophages ID TRANS-GOLGI NETWORK; VIRUS GLYCOPROTEIN; ENDOSOMAL CATHEPSINS; HEMORRHAGIC-FEVER; MARBURG VIRUSES; PRIMATE MODELS; T-LYMPHOCYTES; LIVING CELLS; INFECTION; RECEPTOR AB Ebolavirus is a hemorrhagic fever virus associated with high mortality. Although much has been learned about the viral lifecycle and pathogenesis, many questions remain about virus entry. We recently showed that binding of the receptor binding region (RBR) of the ebolavirus glycoprotein (GP) and infection by GP pseudovirions increase on cell adhesion independently of mRNA or protein synthesis. One model to explain these observations is that, on cell adhesion, an RBR binding partner translocates from an intracellular vesicle to the cell surface. Here, we provide evidence for this model by showing that suspension 293F cells contain an RBR binding site within a membrane-bound compartment associated with the trans-Golgi network andmicrotubule-organizing center. Consistently, trafficking of the RBR binding partner to the cell surface depends on micro-tubules, and the RBR binding partner is internalized when adherent cells are placed in suspension. Based on these observations, we reexamined the claim that lymphocytes, which are critical for ebolavirus pathogenesis, are refractory to infection because they lack an RBR binding partner. We found that both cultured and primary human lymphocytes (in suspension) contain an intracellular pool of an RBR binding partner. Moreover, we identified two adherent primate lymphocytic cell lines that bind RBR at their surface and strikingly, support GP-mediated entry and infection. In summary, our results reveal a mode of determining viral entry by a membrane-trafficking event that translocates an RBR binding partner to the cell surface, and they suggest that this process may be operative in cells important for ebolavirus pathogenesis (e.g., lymphocytes and macrophages). C1 [Dube, Derek; White, Judith M.] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA. [Schornberg, Kathryn L.; Shoemaker, Charles J.; Delos, Sue E.; White, Judith M.] Univ Virginia, Dept Cell Biol, Charlottesville, VA 22908 USA. [Stantchev, Tzanko S.; Broder, Christopher C.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. [Stantchev, Tzanko S.; Clouse, Kathleen A.] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP White, JM (reprint author), Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA. EM jw7g@virginia.edu FU National Institutes of Health [U54 AI057168, A122470]; [5T32 AI07046]; [5T32 AI055432] FX We thank colleagues for reagents (SI Materials and Methods) and Edward Park for excellent technical assistance. D.D., K.L.S., and C.J.S. were supported in part by Training Grants 5T32 AI07046 and 5T32 AI055432 to the University of Virginia. The work was supported by Research Grants from the National Institutes of Health: U54 AI057168 (to C.C.B.) and A122470 and U54 AI057168 (to J.M.W.). NR 31 TC 18 Z9 21 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 21 PY 2010 VL 107 IS 38 BP 16637 EP 16642 DI 10.1073/pnas.1008509107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 652JW UT WOS:000282003700047 PM 20817853 ER PT J AU Gusev, PA Gubin, AN AF Gusev, Pavel A. Gubin, Alexander N. TI Recent and remote memory recalls modulate different sets of stereotypical interlaminar correlations in Arc/Arg3.1 mRNA expression in cortical areas SO BRAIN RESEARCH LA English DT Article DE Neocortex; Stereotypy; Memory consolidation; Water-maze; Immediate-early gene; Functional connectivity ID IMMEDIATE-EARLY GENE; RAT BARREL CORTEX; LONG-TERM-MEMORY; SPATIAL MEMORY; VISUAL-CORTEX; WATER-MAZE; IN-VIVO; FUNCTIONAL CONNECTIVITY; COLUMNAR ORGANIZATION; SOMATOSENSORY CORTEX AB Detailed organization of interlaminar relations in neuronal activity underlying recent and remote memory recall is unknown but essential for deciphering interlaminar connections involved in systems-level memory consolidation and permanent information storage. We mapped Arc/Arg3.1 (Arc) mRNA expression, a neuronal activity marker, at multiple rostro-caudal levels of the brain in Wistar rats following a platform search in a water-maze task. Strength of interlaminar correlations in Arc expression and modulation of the strength by memory recall in sensory, motor and association cortical areas were measured at 24 h and 1 month in memory retention. In order to estimate the extent of modular organization in neocortical function underlying memory recall, we studied multiple profiles of interlaminar coupling. At the level of cortical areas, we captured two robust stereotypical laminar patterns for distribution of strong and weak interlaminar correlations. These patterns emerged during both control swimming and navigation, at both retention delays. Within limits of these patterns, we established task-, time- and area-dependent modulations of the Arc correlations. Relative to swimming control, during memory recall, changes in strength of analogous interlaminar relations occurred largely in parallel but recent and remote recall modulated mostly distinct correlations. An effective remote memory recall was accompanied by fewer strengthened correlations as compared to recent recall. Thus, a behavioral experience is accompanied by a well-ordered or stereotypical spatial organization of interlaminar relations in neuronal activity distribution. Interlaminar correlations in Arc expression modulated by recent and remote memory recall could guide future inactivation and detection studies necessary to decipher interlaminar connections involved in systems-level consolidation and to reveal mnemonic plasticity specific to spatial memory. Published by Elsevier B.V. C1 [Gusev, Pavel A.] Blanchette Rockefeller Neurosci Inst, Rockville, MD 20850 USA. [Gubin, Alexander N.] US FDA, Dev Biol Lab, Bethesda, MD 20892 USA. RP Gusev, PA (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pharmacol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM pgusev@usuhs.mil FU Blanchette Rockefeller Neurosciences Institute FX We thank Drs. Marco Atzori, M. Catherine Bennett, Rui Costa, Changhai Cui, Paul Frankland, Michael J. Schell, Bernard G. Schreurs and colleagues at BRNI for helpful advice on manuscript, and Madelon Cook for manuscript assistance. Funding for this project was provided by the Blanchette Rockefeller Neurosciences Institute. NR 104 TC 3 Z9 3 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 17 PY 2010 VL 1352 BP 118 EP 139 DI 10.1016/j.brainres.2010.06.064 PG 22 WC Neurosciences SC Neurosciences & Neurology GA 654IR UT WOS:000282162200012 PM 20599428 ER PT J AU Sarkar, S Schmued, L AF Sarkar, Sumit Schmued, Larry TI Kainic acid and 3-Nitropropionic acid induced expression of laminin in vascular elements of the rat brain SO BRAIN RESEARCH LA English DT Article DE Laminin; Kainic acid; 3-NPA; Fluoro-Jade C; Neurodegeneration ID FLUORO-JADE; NEURONAL DEGENERATION; INJURY; NEOVASCULARIZATION; LOCALIZATION; MICROGLIA; DISEASE; BARRIER; NEUROPATHOLOGY; ANGIOGENESIS AB Laminin is a glycoprotein component of the basement membrane and has been reported to be found in different areas of the nervous system including brain endothelial cells, Schwann cells and peripheral nerves. Although the in-vitro studies suggest that laminin plays an important role in growth and neurite extension of cultured neurons, localization of laminin in the brain has been controversial and inconsistent results have been reported. Recently, laminin immunoreactivity has been used as a marker for vascular elements in the brain. In this study, we have investigated the effect of two mechanistically different neurotoxins, kainic acid (ICA), an NMDA agonist and 3-Nitropropionic acid (3-NPA), an inhibitor of mitochondrial respiration, on brain vascular elements revealed by laminin immunolabeling. We also explored whether administration of these two neurotoxic drugs correlate with the neuronal degeneration observed after neurotoxic insult by staining with Fluoro-Jade C dye. We have employed single immunolabeling to localize laminin in the brains. In ICA treated rats, most of the laminin immunoreactivity is present in the piriform cortex, corpus callosum (myelinated tracts) amygdala, hippocampus, ventral thalamus and tenia tacta. In 3-NPA treated animals, laminin immunoreactivity was confined mostly to the striatum. In contrast, saline treated rats showed very little laminin immunolabeling around capillaries, arteries and in the meningeal membranes. To determine the effects of these neurotoxins on the integrity of the blood brain barrier (BBB), endothelial brain barrier antigen (EBA) immunolabeling was also performed. In addition, we performed CD11b immunolabeling to evaluate the effect of 3-NPA and ICA on the activation of microglia in the brain. CD11b was dramatically increased in KA and 3-NPA treated animals. We have also combined laminin immunolabeling with Fluoro-Jade C labeling to evaluate the spatio-temporal association of degenerating neurons and the expression of laminin containing microvessels. Areas which showed intense laminin immunolabeling following KA or 3-NPA exposure correlated with those exhibiting the greatest number of degenerating neurons observed after Fluoro-Jade C staining. EBA-laminin double immunolabeling demonstrated that the expressions of laminin were predominantly localized in the areas (cortex, thalamus and hippocampus) where EBA has been either reduced or is absent. Our results from these experiments demonstrate that vascular laminin expression increases after treatment with KA or 3-NPA, suggesting the occurrence of neovascularization. Microglia may also contribute to the neurotoxic induced neovascularization and neurodegeneration. Published by Elsevier B.V. C1 [Sarkar, Sumit; Schmued, Larry] Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Schmued, L (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. EM lschmued@nctr.fda.gov FU FDA [E 7312] FX This work was supported by FDA protocol E 7312. NR 37 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 17 PY 2010 VL 1352 BP 239 EP 247 DI 10.1016/j.brainres.2010.07.011 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 654IR UT WOS:000282162200024 PM 20624377 ER PT J AU Michele, TM Pinheiro, S Iyasu, S AF Michele, Theresa M. Pinheiro, Simone Iyasu, Solomon TI The Safety of Tiotropium -- The FDA's Conclusions. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Michele, Theresa M.] US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Div Pulm Allergy & Rheumatol Prod, Silver Spring, MD USA. [Pinheiro, Simone; Iyasu, Solomon] US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Div Epidemiol, Silver Spring, MD USA. RP Michele, TM (reprint author), US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Div Pulm Allergy & Rheumatol Prod, Silver Spring, MD USA. NR 4 TC 61 Z9 63 U1 1 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 16 PY 2010 VL 363 IS 12 BP 1097 EP 1099 DI 10.1056/NEJMp1008502 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 649TD UT WOS:000281795800001 PM 20843240 ER PT J AU Bauch, CT Bhattacharyya, S Ball, RF AF Bauch, Chris T. Bhattacharyya, Samit Ball, Robert F. TI Rapid Emergence of Free-Riding Behavior in New Pediatric Immunization Programs SO PLOS ONE LA English DT Article ID VACCINATING BEHAVIOR; INFECTIOUS-DISEASES; SELF-INTEREST; DYNAMICS; EPIDEMIOLOGY; OUTBREAKS; SPREAD; SAFETY; POLICY; GAME AB Background: Mathematical models have formalized how free-rider effects can threaten the stability of high vaccine coverage levels under established voluntary vaccination programs. However, little research has addressed the question of when free-riding begins to develop when a new vaccine is first introduced in a population. Methodology/Principal Findings: Here, we combine a game theoretical model of vaccinating behavior with an age-structured compartmental model to analyze rational vaccinating behavior in the first years of a universal immunization program, where a new vaccine is free to all children of a specified age. The model captures how successive birth cohorts face different epidemiological landscapes that have been shaped by the vaccinating decisions of previous birth cohorts, resulting in a strategic interaction between individuals in different birth cohorts. The model predicts a Nash equilibrium coverage level of 100% for the first few birth cohorts under the new program. However, free-riding behavior emerges very quickly, with the Nash equilibrium vaccine coverage dropping significantly within 2-5 years after program initiation. Subsequently, a rich set of coupled dynamics between infection prevalence and vaccinating behaviors is possible, ranging from relatively stable (but reduced) coverage in later birth cohorts to wide fluctuations in vaccine coverage from one birth cohort to the next. Individual tolerance for vaccine risk also starts out at relatively high levels before dropping significantly within a few years. Conclusions/Significance: These results suggest that even relatively new immunization programs can be vulnerable to drops in vaccine coverage caused by vaccine scares and exacerbated by herd immunity effects, necessitating vigilance from the start. C1 [Bauch, Chris T.; Bhattacharyya, Samit] Univ Guelph, Dept Math & Stat, Guelph, ON N1G 2W1, Canada. [Ball, Robert F.] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Bauch, CT (reprint author), Univ Guelph, Dept Math & Stat, Guelph, ON N1G 2W1, Canada. EM cbauch@uoguelph.ca FU Ministry of Research and Innovation of Ontario; United States Food and Drug Administration; University of Guelph FX This work was funded by the Ministry of Research and Innovation of Ontario, the United States Food and Drug Administration, and the University of Guelph. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 15 Z9 16 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 15 PY 2010 VL 5 IS 9 AR e12594 DI 10.1371/journal.pone.0012594 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 649ZP UT WOS:000281815800003 PM 20856798 ER PT J AU Bakare, N Menschik, D Tiernan, R Hua, W Martin, D AF Bakare, Nyasha Menschik, David Tiernan, Rosemary Hua, Wei Martin, David TI Severe combined immunodeficiency (SCID) and rotavirus vaccination: Reports to the Vaccine Adverse Events Reporting System (VAERS) SO VACCINE LA English DT Article DE Vaccine safety; Rotavirus vaccine; Severe combined immunodeficiency; Vaccine adverse events reporting system; VAERS ID GASTROENTERITIS; CHILDREN; INFANTS; DISEASE AB Background: Rotavirus vaccines are the only live vaccines recommended for infants in the US. Postmarketing reports have described severe gastroenteritis with vaccine viral shedding in infants who received rotavirus vaccine and were later diagnosed with SCID. The US Food and Drug Administration recently approved labeling changes for RotaTeq and Rotarix contraindicating administration to individuals with a history of SCID. We queried VAERS to characterize reports of SCID after rotavirus vaccination. Methods: VAERS inclusion criteria included current US-licensed rotavirus vaccines, report dates from February 3, 2006 to January 15, 2010, and queries for the MedDRA preferred term "combined immunodeficiency" as well as any text containing the terms, "SCID" or "combined immunodeficiency." Results: We identified nine reports of SCID and rotavirus vaccination in infants between 3 and 9 months of age. All but one case presented with diarrhea among other symptoms. All infants were hospitalized and had workups leading to the SCID diagnosis. Stool rotavirus testing was positive in all cases and the virus was identified as the vaccine strain in six cases. Prolonged viral shedding was documented in five cases. No deaths were reported. Conclusion: The aforementioned labeling changes were warranted given the risk posed by live rotavirus vaccine to individuals with SCID, as illustrated by these VAERS cases. Although congenital, SCID was not diagnosed in these infants until after rotavirus vaccination. Earlier identification of SCID (e.g., from expanded newborn screening or heightened clinical vigilance) could prevent inadvertent live rotavirus vaccine administration and also potentially result in earlier life-saving stem cell transplants. Published by Elsevier Ltd. C1 [Menschik, David] US FDA, OBE, CBER, DE, Rockville, MD 20852 USA. [Bakare, Nyasha] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Tiernan, Rosemary] US FDA, Off Vaccine Res & Review, CBER, Rockville, MD 20852 USA. RP Menschik, D (reprint author), US FDA, OBE, CBER, DE, 1401 Rockville Pike,Suite 4005, Rockville, MD 20852 USA. EM david.menschik@fda.hhs.gov NR 17 TC 30 Z9 32 U1 0 U2 3 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 SEP 14 PY 2010 VL 28 IS 40 BP 6609 EP 6612 DI 10.1016/j.vaccine.2010.07.039 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 656ZF UT WOS:000282379000009 PM 20674876 ER PT J AU Graham, DJ Gelperin, K AF Graham, David J. Gelperin, Kate TI FDA on rosiglitazone More on advisory committee decision SO BRITISH MEDICAL JOURNAL LA English DT Letter C1 [Graham, David J.; Gelperin, Kate] Food & Drug Adm, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. RP Graham, DJ (reprint author), Food & Drug Adm, Off Surveillance & Epidemiol, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM david.graham1@fda.hhs.gov NR 3 TC 0 Z9 0 U1 0 U2 1 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 SEP 7 PY 2010 VL 341 AR c4868 DI 10.1136/bmj.c4868 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 649ZI UT WOS:000281814900014 PM 20823021 ER PT J AU Lo, SC Pripuzova, N Li, BJ Komaroff, AL Hung, GC Wang, R Alter, HJ AF Lo, Shyh-Ching Pripuzova, Natalia Li, Bingjie Komaroff, Anthony L. Hung, Guo-Chiuan Wang, Richard Alter, Harvey J. TI Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors (Retracted article. See vol. 109, pg. 346, 2012) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Retracted Publication DE xenotropic murine leukemia virus-related virus; murine leukemia virus-like virus; viral gag gene sequence; polytropic; mouse mitochondria DNA PCR ID MURINE LEUKEMIA-VIRUS; PROSTATE-CANCER; RETROVIRUS XMRV; PATHOGENESIS; PREVALENCE; RELEASE; ABSENCE; RNA AB Chronic fatigue syndrome (CFS) is a serious systemic illness of unknown cause. A recent study identified DNA from a xenotropic murine leukemia virus-related virus (XMRV) in peripheral blood mononuclear cells (PBMCs) from 68 of 101 patients (67%) by nested PCR, as compared with 8 of 218 (3.7%) healthy controls. However, four subsequent reports failed to detect any murine leukemia virus (MLV)-related virus gene sequences in blood of CFS patients. We examined 41 PBMC-derived DNA samples from 37 patients meeting accepted diagnostic criteria for CFS and found MLV-like virus gag gene sequences in 32 of 37 (86.5%) compared with only 3 of 44 (6.8%) healthy volunteer blood donors. No evidence of mouse DNA contamination was detected in the PCR assay system or the clinical samples. Seven of 8 gag-positive patients tested again positive in a sample obtained nearly 15 y later. In contrast to the reported findings of near-genetic identity of all XMRVs, we identified a genetically diverse group of MLV-related viruses. The gag and env sequences from CFS patients were more closely related to those of polytropic mouse endogenous retroviruses than to those of XMRVs and were even less closely related to those of ecotropic MLVs. Further studies are needed to determine whether the same strong association with MLV-related viruses is found in other groups of patients with CFS, whether these viruses play a causative role in the development of CFS, and whether they represent a threat to the blood supply. C1 [Lo, Shyh-Ching; Pripuzova, Natalia; Li, Bingjie; Hung, Guo-Chiuan] US FDA, Tissue Microbiol Lab, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. [Lo, Shyh-Ching; Pripuzova, Natalia; Li, Bingjie; Hung, Guo-Chiuan] US FDA, Off Cellular Tissue & Gene Therapy, Div Human Tissues, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Komaroff, Anthony L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Wang, Richard; Alter, Harvey J.] NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Lo, SC (reprint author), US FDA, Tissue Microbiol Lab, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. EM shyhching.lo@FDA.hhs.gov; halter@mail.nih.gov FU National Institute of Allergy and Infectious Diseases [R01-A127314, U01-A132246]; De Young Foundation FX We thank Richard Schacterle, Ph.D., and Jennifer Redd, who helped collect the specimens and clinical data. Drs. Jakob Reiser and Paolo Lusso kindly helped to review the manuscript. Support for this work was provided in part by National Institute of Allergy and Infectious Diseases Grants R01-A127314 and U01-A132246 and by a gift from the De Young Foundation to A.L.K. NR 22 TC 138 Z9 141 U1 4 U2 26 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 7 PY 2010 VL 107 IS 36 BP 15874 EP 15879 DI 10.1073/pnas.1006901107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 647RY UT WOS:000281637800046 PM 20798047 ER PT J AU Keire, DA Mans, DJ Ye, HP Kolinski, RE Buhse, LF AF Keire, David A. Mans, Daniel J. Ye, Hongping Kolinski, Richard E. Buhse, Lucinda F. TI Assay of possible economically motivated additives or native impurities levels in heparin by H-1 NMR, SAX-HPLC, and anticoagulation time approaches SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Carbohydrates; Heparin; NMR; SAX-H PLC; Oversulfated; Glycosaminoglycans ID OVERSULFATED CHONDROITIN SULFATE; MAGNETIC-RESONANCE-SPECTROSCOPY; ADVERSE CLINICAL EVENTS; CONTAMINANT; SEPARATION AB New assays have been developed to detect the presence of economically motivated additives (EMAs) and poor manufacturing processes in heparin Here, selected oversulfated glycosaminoglycans that are possible EMAs to hepar in wet e synthesized and the utility of curt cut H-1 NMR, SAX-HPLC or anticoagulation time protocols were evaluated for the detection of native impurities (chondroitin sulfate A or B (CSA or CSB), or heparan sulfate (HS)), or synthetic contaminants (oversulfated-(OS)-CSA, OS-CSB, OS-HS or OS-Heparin) spiked into heparin sodium active pharmaceutical ingredients (APIs) The range of w/w percent LOD values from the SAX-HPLC analysis for heparin spiked with CSA, CSB, HS, OS-CSA, OS-CSB, OS-HS, OS-Heparin and two partially oversulfated CSA analogs was 0 05-0.12%. The 500 MHz 1D-H-1 NMR spectra of heparin spiked with 1 0-10% CSA, CSB, OS-CSA, or OS-CSB showed unique signal pattern changes while the samples spiked with HS, OS-HS, OS-Heparin or partially sulfated CSA were more difficult to identify using NMR data. The ratio of anticoagulation time values obtained with factor Xa and factor Ila were found to remain within USP specifications in the presence of 10% amounts of these impurities or contaminants In a separate test, using OS-CSA spiked API heparin samples, the factor Xa or factor Ila to USP standard ratio were found to fall below the USP 09 specification value in samples spiked at ca. weight percent of 15% or greater of OSCS. We conclude that the SAX-HPLC assay is the most sensitive and robust assay to identify and quantitate possible GAG-based EMAs in heparin Published by Elsevier B V C1 [Keire, David A.; Mans, Daniel J.; Ye, Hongping; Kolinski, Richard E.; Buhse, Lucinda F.] US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Keire, DA (reprint author), US FDA, Div Pharmaceut Anal, 1114 Market St, St Louis, MO 63101 USA. NR 25 TC 27 Z9 28 U1 2 U2 18 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 SEP 5 PY 2010 VL 52 IS 5 BP 656 EP 664 DI 10.1016/j.jpba.2010.02.019 PG 9 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 584WU UT WOS:000276785400003 PM 20233649 ER PT J AU Freeman, SN Burke, KA Imoisili, MA Cote, TR AF Freeman, Scott N. Burke, Kathryn A. Imoisili, Menfo A. Cote, Timothy R. TI The Orphan Drug Act and the Development of Stem Cell-Based Products for Rare Diseases SO CELL STEM CELL LA English DT Editorial Material ID FDA REGULATION; THERAPIES AB The Orphan Drug Act encourages the development of products for rare diseases and conditions. Many conditions that stand to benefit from stem cell-based products are rare diseases. We address the Orphan Drug Act in relation to the development of stem cell-based products. C1 [Freeman, Scott N.; Burke, Kathryn A.; Imoisili, Menfo A.; Cote, Timothy R.] US FDA, Off Orphan Prod Dev, Off Special Med Programs, Off Commissioner, Silver Spring, MD 20993 USA. RP Cote, TR (reprint author), US FDA, Off Orphan Prod Dev, Off Special Med Programs, Off Commissioner, Silver Spring, MD 20993 USA. EM timothy.cote@fda.hhs.gov NR 9 TC 5 Z9 5 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD SEP 3 PY 2010 VL 7 IS 3 BP 283 EP 287 DI 10.1016/j.stem.2010.08.003 PG 5 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 652VC UT WOS:000282037800006 PM 20804965 ER PT J AU Wysowski, DK AF Wysowski, Diane K. TI Oral bisphosphonates and oesophageal cancer SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID ALENDRONATE; FEATURES C1 US FDA, Div Epidemiol, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. RP Wysowski, DK (reprint author), US FDA, Div Epidemiol, Off Surveillance & Epidemiol, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM diane.wysowski@fda.hhs.gov NR 12 TC 11 Z9 11 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD SEP 2 PY 2010 VL 341 AR c4506 DI 10.1136/bmj.c4506 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 647JV UT WOS:000281615700005 PM 20813821 ER PT J AU Zidan, AS Rahman, Z Khan, MA AF Zidan, Ahmed S. Rahman, Ziyaur Khan, Mansoor A. TI Online Monitoring of PLGA Microparticles Formation Using Lasentec Focused Beam Reflectance (FBRM) and Particle Video Microscope (PVM) SO AAPS JOURNAL LA English DT Article DE biodegradable polymers; FBRM and PVM; Lasentec; microparticles; particle sizing ID AGITATED SUSPENSIONS; POLY(L-LACTIC ACID); SIZE DISTRIBUTION; MOLECULAR-WEIGHT; PLASMID DNA; RELEASE; MICROSPHERES; ENCAPSULATION; NANOSPHERES; DELIVERY AB Knowledge of the effects of different product and process variability on microparticle characterization is essential for the successful development, optimization, and scale-up of an encapsulation process. In the current research, the qualitative application of the Lasentec focused beam reflectance (FBRM) system for online monitoring of microparticle size distribution was demonstrated. lasentec particle vision and measurement (PVM) images were also employed to follow up the steps of microparticle formation and ripening. The drug entrapment efficiency and drug release characteristics were found to be dependent on the polymer, drug, and surfactant concentrations. DSC, FTIR, and XRD data revealed that the drug was compatible with the matrix forming polymer in the solid state. As indicated from the chord count data, FBRM was sensitive to the amount of the solid materials and the number of microparticles formed. Linear relationships with good correlations were obtained between polymer, drug, and surfactant levels and the disappearance rate of 5 to 36.8, 18.4 to 135.9, and 63 to 398 mu m chord length fractions. Upon organic solvent evaporation, PVM imaging detected various stages of microemulsion droplets, sheath formation, and solidification with subsequent microparticle hardening. This study illustrated the utility of FBRM and PVM in monitoring the progress of particle formation during drug encapsulation. C1 [Zidan, Ahmed S.; Rahman, Ziyaur; Khan, Mansoor A.] US FDA, Div Prod Qual & Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Zidan, Ahmed S.] Zagazig Univ, Fac Pharm, Zagazig, Egypt. RP Khan, MA (reprint author), US FDA, Div Prod Qual & Res, Ctr Drug Evaluat & Res, 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 acknowledge the Oak Ridge Institute for Science and Education (ORISE) for its support with a research postdoctoral fellowship. The views presented in this article do not necessarily reflect those of the US Food and Drug Administration. NR 30 TC 7 Z9 7 U1 4 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD SEP PY 2010 VL 12 IS 3 BP 254 EP 262 DI 10.1208/s12248-010-9184-2 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 735NU UT WOS:000288425000001 PM 20352538 ER PT J AU Shah, RB Collier, JS Sayeed, VA Bryant, A Habib, MJ Khan, MA AF Shah, Rakhi B. Collier, Jarrod S. Sayeed, Vilayat A. Bryant, Arthur Habib, Muhammad J. Khan, Mansoor A. TI Tablet Splitting of a Narrow Therapeutic Index Drug: A Case with Levothyroxine Sodium SO AAPS PHARMSCITECH LA English DT Article DE content uniformity; hand splitting; levothyroxine sodium; narrow therapeutic index; splitter; tablet splitting ID SCORED TABLETS; ACCURACY; EXCIPIENTS; STABILITY; BREAKING; SAVINGS; COST; HALF AB Levothyroxine is a narrow therapeutic index, and to avoid adverse effect associated with under or excessive dosage, the dose response is carefully titrated. The tablets are marketed with a score providing an option to split. However, there are no systematic studies evaluating the effect of splitting on dose accuracy, and current study was undertaken to evaluate effects of splitting and potential causes for uniformity failures by measuring assay and content uniformity in whole and split tablets. Stability was evaluated by assaying drug for a period of 8 weeks. Effect of formulation factors on splittability was evaluated by a systematic investigation of formulation factors by preparing levothyroxine tablets in house by varying the type of excipients (binder, diluent, disintegrant, glidant) or by varying the processing factors (granulating liquid, mixing type, compression pressure). The tablets were analyzed using novel analytical tool such as near infrared chemical imaging to visualize the distribution of levothyroxine. Assay was not significantly different for whole versus split tablets irrespective of method of splitting (hand or splitter), and splitting also had no measurable impact on the stability. Split tablets either by hand or splitter showed higher rate of content uniformity failures as compared to whole tablets. Tablet splitter produced more fragmentation and, hence, more content uniformity and friability failures. Chemical imaging data revealed that the distribution of levothyroxine was heterogeneous and was dependent on type of binder and the process used in the manufacture of tablets. Splitting such tablets could prove detrimental if sub- or super-potency becomes an issue. C1 [Shah, Rakhi B.; Collier, Jarrod S.; Bryant, Arthur; Khan, Mansoor A.] US FDA, Div Prod Qual Res, Off Testing & Res, OPS,CDER, Silver Spring, MD 20993 USA. [Collier, Jarrod S.; Habib, Muhammad J.] Howard Univ, Dept Pharmaceut Sci, Sch Pharm, Washington, DC 20059 USA. [Sayeed, Vilayat A.] US FDA, Div Chem 3, Off Gener Drugs, OPS,CDER, Silver Spring, MD 20993 USA. RP Khan, MA (reprint author), US FDA, Div Prod Qual Res, Off Testing & Res, OPS,CDER, 10903 New Hampshire Ave,Life Sci Bldg 64, Silver Spring, MD 20993 USA. EM Mansoor.khan@fda.hhs.gov FU critical path project; Office of Generic Drugs, FDA FX The study was partially funded as a critical path project and also by the Office of Generic Drugs, FDA. Authors also wish to thank Christopher Ellison and Abhay Gupta for their technical help. NR 33 TC 17 Z9 18 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PD SEP PY 2010 VL 11 IS 3 BP 1359 EP 1367 DI 10.1208/s12249-010-9515-8 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 735OS UT WOS:000288427400043 PM 20740332 ER PT J AU Hussong, D AF Hussong, David TI Sterile Products: Advances and Challenges in Formulation, Manufacturing and Regulatory Aspects-A Regulatory Review Perspective SO AAPS PHARMSCITECH LA English DT Article DE drug safety; endotoxins; process controls; safe use; sterilization AB For several decades, the FDA has undertaken many initiatives to improve the quality and safety of sterile drug products. In recent years, efforts have also been undertaken to accelerate the rate for application approval by adding earlier involvement of microbiology reviewers in drug development. Product and manufacturing process development, as well as safe use and product design, are among the elements of enhanced technical involvement. An overview of the product quality microbiology aspects for sterile drugs is provided. C1 US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Hussong, D (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Bldg 51,Room 4166,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM david.hussong@fda.hhs.gov NR 11 TC 0 Z9 0 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 SEP PY 2010 VL 11 IS 3 BP 1482 EP 1484 DI 10.1208/s12249-010-9503-z PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 735OS UT WOS:000288427400058 PM 20845091 ER PT J AU Paquerault, S Hardy, PT Wersto, N Chen, J Smith, RC AF Paquerault, Sophie Hardy, Paul T. Wersto, Nancy Chen, John Smith, Robert C. TI Investigation of Optimal Use of Computer-Aided Detection Systems: The Role of the "Machine" in Decision Making Process SO ACADEMIC RADIOLOGY LA English DT Article DE Computer-aided detection; decision making process; computerized models; personalized medical practice; free-response receiver operating characteristic ID SCREENING MAMMOGRAPHY; CANCER-DETECTION; DIAGNOSIS; PERFORMANCE; RADIOLOGISTS; EXPERIENCE; WORKLOAD; TRENDS AB Rationale and Objectives: The aim of this study was to explore different computerized models (the "machine") as a means to achieve optimal use of computer-aided detection (CAD) systems and to investigate whether these models can play a primary role in clinical decision making and possibly replace a clinician's subjective decision for combining his or her own assessment with that provided by a CAD system. Materials and Methods: Data previously collected from a fully crossed, multiple-reader, multiple-case observer study with and without CAD by seven observers asked to identify simulated small masses on two separate sets of 100 mammographic images (low-contrast and high-contrast sets; ie, low-contrast and high-contrast simulated masses added to random locations on normal mammograms) were used. This allowed testing two relative sensitivities between the observers and CAD. Seven models that combined detection assessments from CAD standalone, unaided read, and CAD-aided read (second read and concurrent read) were developed using the leave-one-out technique for training and testing. These models were personalized for each observer. Detection performance accuracies were analyzed using the area under a portion of the free-response receiver-operating characteristic curve (AUFC), sensitivity, and number of false-positives per image. Results: For the low-contrast set, the use of computerized models resulted in significantly higher AUFCs compared to the unaided read mode for all readers, whereas the increased AUFCs between CAD-aided (second and concurrent reads; ie, decisions made by the readers) and unaided read modes were statistically significant for a majority, but not all, of the readers (four and five of the seven readers, respectively). For the high-contrast set, there were no significant trends in the AUFCs whether or not a model was used to combine the original reading modes. Similar results were observed when using sensitivity as the figure of merit. However, the average number of false-positives per image resulting from the computerized models remained the same as that obtained from the unaided read modes. Conclusions: Individual computerized models (the machine) that combine image assessments from CAD standalone, unaided read, and CAD-aided read can increase detection performance compared to the reading done by the observer. However, relative sensitivity (ie, the difference in sensitivity between CAD standalone and unaided read) was a critical factor that determined incremental improvement in decision making, whether made by the observer or using computerized models. C1 [Paquerault, Sophie; Hardy, Paul T.; Wersto, Nancy; Chen, John; Smith, Robert C.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Imaging & Appl Math, Silver Spring, MD 20993 USA. RP Paquerault, S (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Imaging & Appl Math, 10903 New Hampshire Ave,Bldg 62,Room 3110, Silver Spring, MD 20993 USA. EM sophie.paquerault@fda.hhs.gov NR 25 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 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD SEP PY 2010 VL 17 IS 9 BP 1112 EP 1121 DI 10.1016/j.acra.2010.04.010 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 643PL UT WOS:000281310500008 PM 20605489 ER PT J AU Zhao, JQ Tang, SX Ragupathy, V Carr, JK Wolfe, ND Awazi, B Hewlett, I AF Zhao, Jiangqin Tang, Shixing Ragupathy, Viswanath Carr, Jean K. Wolfe, Nathan D. Awazi, Bih Hewlett, Indira TI Identification and Genetic Characterization of a Novel CRF22_01A1 Recombinant Form of HIV Type 1 in Cameroon SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID CIRCULATING RECOMBINANT; INTERSUBTYPE RECOMBINANTS; CENTRAL-AFRICA; BLOOD-DONORS; SUBTYPE-E; IMMUNODEFICIENCY; INFECTION; STRAINS; DIVERSITY; SEQUENCES AB Cameroon is a country in West Central Africa in which all four groups of HIV-1 (M, N, O, and P), some circulating recombinant forms (CRFs) and unique recombinant forms (URFs) are prevalent. The CRF22 was initially identified through a novel URF strain, 01CM53122, and later defined from two additional sequences; however, the genomic properties of CRF22 have never been demonstrated in detail. In this study, we describe the characterization of five CRF22_01A1 strains, 02CMLT72, 01CM1867LE, 01CM001BBY, 02CM3097MN, and 02CM1917LE, identified in Cameroon without apparent epidemiological links. A typical CRF22_01A1 strain contains five fragments that can be assigned to the CRF01_AE and subsubtype A1 radiations. Forty-eight percent of the genome is classified as CRF01_AE, spanning the entire region of the gag gene, part of the pol gene, and accessory genes as well as the beginning and the end of the env gene and nef gene. Fifty-two percent of the genome is subsubtype A1 including regions mostly in the pol, vif, and env genes. The five CRF22_01A1 viruses formed a deep branch outside the groups of CRF01_AE and displayed similar mosaic structure but were moderately different from the original strain of CRF22_01A1, 01CM53122. Further analysis of the 01CM53122 genome showed that this virus represents a diverse set of mosaic genomes from CRF22_01A1, including a 446-nt segment of 01CM53122 in the env region, but unlike other CRF22 strains, clustered with CRF01_AE rather than the A1 sequence, suggesting that the 01CM53122 strain is a recombinant of CRF22_01A1 and CRF01_AE. C1 [Zhao, Jiangqin; Tang, Shixing; Ragupathy, Viswanath; Hewlett, Indira] US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Carr, Jean K.] Univ Maryland, Sch Med, Inst Human Virol, Div Epidemiol & Prevent, Baltimore, MD 21201 USA. [Wolfe, Nathan D.] Global Viral Forecasting Initiat, San Francisco, CA 94104 USA. [Wolfe, Nathan D.] Stanford Univ, Program Human Biol, Stanford, CA 94305 USA. RP Hewlett, I (reprint author), US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bldg 29B,Room 4NN16,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Indira.hewlett@fda.hhs.gov FU National Heart, Lung, and Blood Institute [BY1-HB-5026-01]; Global Viral Forecasting Initiative FX The authors wish to acknowledge The National Heart, Lung, and Blood Institute for funding part of this work through an IAA-National Heart, Lung and Blood Inter-Agency Agreement BY1-HB-5026-01. This work was also supported in part by the Global Viral Forecasting Initiative. We wish to acknowledge Drs. Jinhai Wang, Krishnakumar Devadas, and Hira Nakhasi for review of the manuscript. The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy. NR 48 TC 7 Z9 7 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP PY 2010 VL 26 IS 9 BP 1033 EP 1045 DI 10.1089/aid.2009.0197 PG 13 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 646BN UT WOS:000281510000014 PM 20812894 ER PT J AU Wysowski, DK Swartz, L Borders-Hemphill, BV Goulding, MR Dormitzer, C AF Wysowski, Diane K. Swartz, Lynette Borders-Hemphill, B. Vicky Goulding, Margie R. Dormitzer, Catherine TI Use of parenteral iron products and serious anaphylactic-type reactions SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID FERRIC GLUCONATE COMPLEX; DRUG EVENT SURVEILLANCE; AMERICAN CLINICAL-TRIAL; HEMODIALYSIS-PATIENTS; INTRAVENOUS IRON; ADVERSE REACTIONS; DEXTRAN; SAFETY; SUCROSE; DEFICIENCY AB Controversy exists about the safety of the parenteral iron dextran products, Dexferrum and INFeD, which have been associated with rare, serious anaphylactic-type reactions. In the United States, their product labels carry boxed warnings of this adverse event; some have called for the withdrawal from marketing of the higher molecular weight Dexferrum. Between 2002 and 2007, sales of Dexferrum, INFeD, and iron gluconate Ferrlecit declined 32.5%, 21%, and 4.8%, respectively, while sales of iron sucrose Venofer increased 160%. Voluntary reports submitted to the Food and Drug Administration show anaphylactic reactions and symptoms for the four parenteral iron products. Because of underreporting, possible differential reporting, absence of iron dextran brand names, and incomplete use (denominator) data, incidence rates and relative risk estimates cannot be calculated. U.S. death certificate data show that for most years from 1979 through 2006, no more than 3 deaths per year were coded to "adverse events in therapeutic use of iron preparations;" brand names were not consistently recorded. Emergency department data show small numbers of visits for treatment of allergic reactions with intravenous iron preparations. The data presented herein show that allergic reactions are possible with all four parenteral iron products, and it is difficult to determine which product has the largest risk based on sales data, voluntarily submitted adverse event reports, death certificates, ED visits, and observational studies performed to date. To help differentiate risk among the parenteral iron products, the brand name of the product always should be provided on medical records, death certificates, and adverse drug reaction reports. Am. J. Hematol. 85:650-654, 2010. Published 2010 Wiley-Liss, Inc.(dagger) C1 [Wysowski, Diane K.] US FDA, Div Epidemiol, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. RP Wysowski, DK (reprint author), US FDA, Div Epidemiol, Off Surveillance & Epidemiol, 10903 New Hampshire Ave,Bldg 22,Room 2406, Silver Spring, MD 20993 USA. EM diane.wysowski@fda.hhs.gov NR 31 TC 45 Z9 46 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD SEP PY 2010 VL 85 IS 9 BP 650 EP 654 DI 10.1002/ajh.21794 PG 5 WC Hematology SC Hematology GA 647EZ UT WOS:000281601900004 PM 20661919 ER PT J AU Zhang, YF Kubachka, KM Caruso, JA AF Zhang, Yaofang Kubachka, Kevin M. Caruso, Joseph A. TI Enhancing determination of organophosphate species in high inorganic phosphate matrices: application to nerve agent degradation products SO ANALYTICAL METHODS LA English DT Article ID CHEMICAL WARFARE AGENTS; PLASMA-MASS SPECTROMETRY; SOLID-PHASE MICROEXTRACTION; CAPILLARY-ELECTROPHORESIS; SEPARATION TECHNIQUES; GAS-CHROMATOGRAPHY; WATER SAMPLES; IONIZATION; SPECIATION; IDENTIFICATION AB Developing a reliable and robust trace level method for organophosphates in the presence of relatively high inorganic phosphate is an area of interest for further method development. Since the advent of collision/reaction cell technology, inductively coupled plasma mass spectrometry (ICPMS) has been used with a variety of sample types for elemental phosphorus detection at m/z = 31. However, with many samples inorganic phosphate may be orders of magnitude higher than organophosphates, presenting a major interference to quantification. Therefore, removal of inorganic phosphate to levels low enough to minimize the interference would prove beneficial for more effective organophosphate analyses. In this study, applicable to most organophosphate containing samples, the illustration is to nerve agent degradation products as they might contaminate food and environmental systems after their initial formation. Calcium chloride was chosen as a coagulant mix and ammonium hydroxide was chosen to adjust the pH in order to remove inorganic phosphate at the sample preparation step. High performance liquid chromatography (HPLC) coupled with ICPMS was utilized for analysis. The results show that inorganic phosphate, at concentrations as high as 10 000 mu g, mL(-1), can be sufficiently removed by precipitation with calcium at pH > 9 while the organophosphorus chemical warfare agent degradation products, CWADPs, remain intact. Applications to apple juice and cola drink indicate that this method is suitable for more complex matrices containing relatively high levels of inorganic phosphate. C1 [Zhang, Yaofang; Kubachka, Kevin M.; Caruso, Joseph A.] Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. [Kubachka, Kevin M.] US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Caruso, JA (reprint author), Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. EM joseph.caruso@uc.edu FU NIEHS [ES04908] FX YZ and JAC would like to thank NIEHS grant # ES04908 for partial funding this research. We also acknowledge Agilent Technologies for their continuing support of our studies at the University of Cincinnati/Agilent Technologies Metallomics Center of the Americas. NR 30 TC 6 Z9 6 U1 1 U2 11 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1759-9660 J9 ANAL METHODS-UK JI Anal. Methods PD SEP PY 2010 VL 2 IS 9 BP 1243 EP 1248 DI 10.1039/c0ay00230e PG 6 WC Chemistry, Analytical; Food Science & Technology; Spectroscopy SC Chemistry; Food Science & Technology; Spectroscopy GA 660BI UT WOS:000282612800008 ER PT J AU Mozley, PD Schwartz, LH Bendtsen, C Zhao, B Petrick, N Buckler, AJ AF Mozley, P. D. Schwartz, L. H. Bendtsen, C. Zhao, B. Petrick, N. Buckler, A. J. TI Change in lung tumor volume as a biomarker of treatment response: a critical review of the evidence SO ANNALS OF ONCOLOGY LA English DT Review DE cancer; CT; image analysis; imaging; lung cancer; tomography; computed ID PULMONARY NODULES; INTRAOBSERVER VARIABILITY; COMPUTED-TOMOGRAPHY; CT; CANCER; INTEROBSERVER; EXPERIENCE; RECIST; RADIOTHERAPY; METASTASES AB Specific Aim: To review the evidence indicating that volumetric image analysis of computed tomography scans meets specifications for qualification as a biomarker in clinical trials or the management of individual patients with lung cancer. Methods: Claims of value were broken down into questions about technical feasibility, accuracy, the precision of measurement, sensitivity, the correlations with health outcomes, and the risks of producing misleading information. For each claim, the pertinent literature was reviewed. Results: Technical feasibility has now been shown, but only in limited contexts. Accuracy has been demonstrated, but only for tumors with favorable anatomical features. Measurement error still makes the assessment of change in small nodules precarious in diagnostic settings unless rigorous image acquisition and analysis procedures are followed. Precision is sufficient in some larger masses to make volumetrics a sensitive biomarker. In a few trials, correlations with clinical outcomes have been higher for volumetric-based measures than for unidimensional or bidimensional diameters. Value in clinical practice settings and clinical trials has been suggested, but not proven. Conclusion: The weight of the evidence indicates there are circumstances in which volumetric image analysis adds value to clinical trial science and the practice of medicine. C1 [Mozley, P. D.] Merck Res Labs, Dept Imaging, West Point, PA 19486 USA. [Schwartz, L. H.; Zhao, B.] Columbia Univ, Dept Radiol, New York, NY USA. [Bendtsen, C.] Merck Res Labs, Dept Appl Comp Sci & Math, Rome, Italy. [Petrick, N.] USA Food & Drug Adm, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Buckler, A. J.] Buckler Biomed LLC, Boston, MA USA. RP Mozley, PD (reprint author), Merck Res Labs, Dept Imaging, 770 Sumneytown Pike,WP42-305, West Point, PA 19486 USA. EM mozley@merck.com OI Bendtsen, Claus/0000-0002-8338-987X; Buckler, Andrew/0000-0002-0786-4835 NR 41 TC 37 Z9 37 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2010 VL 21 IS 9 BP 1751 EP 1755 DI 10.1093/annonc/mdq051 PG 5 WC Oncology SC Oncology GA 643UJ UT WOS:000281324500003 PM 20332135 ER PT J AU Mentari, EK Stone, M Hammad, TA AF Mentari, Evelyn K. Stone, Marc Hammad, Tarek A. TI Antiepileptic Drugs and Suicide Attempts in Patients With Bipolar Disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Letter C1 [Mentari, Evelyn K.; Stone, Marc; Hammad, Tarek A.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Mentari, EK (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,HFD-120, Silver Spring, MD 20993 USA. EM evelyn.mentari@fda.hhs.gov NR 3 TC 6 Z9 6 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 2010 VL 67 IS 9 BP 972 EP 972 PG 1 WC Psychiatry SC Psychiatry GA 649JD UT WOS:000281764000013 PM 20819991 ER PT J AU Woodcock, J AF Woodcock, Janet TI Interview with Janet Woodcock SO BIOANALYSIS LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Research, Silver Spring, MD 20903 USA. RP Woodcock, J (reprint author), US FDA, Ctr Drug Evaluat & Research, 10903 New Hampshire Ave,Bldg 51,Suite 6100, Silver Spring, MD 20903 USA. EM janet.woodcock@fda.hhs.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 J9 BIOANALYSIS JI Bioanalysis PD SEP PY 2010 VL 2 IS 9 BP 1535 EP 1538 DI 10.4155/BIO.10.113 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 654IW UT WOS:000282162700006 PM 21083281 ER PT J AU Rocca-Serra, P Brandizi, M Maguire, E Sklyar, N Taylor, C Begley, K Field, D Harris, S Hide, W Hofmann, O Neumann, S Sterk, P Tong, WD Sansone, SA AF Rocca-Serra, Philippe Brandizi, Marco Maguire, Eamonn Sklyar, Nataliya Taylor, Chris Begley, Kimberly Field, Dawn Harris, Stephen Hide, Winston Hofmann, Oliver Neumann, Steffen Sterk, Peter Tong, Weida Sansone, Susanna-Assunta TI ISA software suite: supporting standards-compliant experimental annotation and enabling curation at the community level SO BIOINFORMATICS LA English DT Article ID ONTOLOGIES; PROJECT; FORMAT; TOOL; TAB AB The first open source software suite for experimentalists and curators that (i) assists in the annotation and local management of experimental metadata from high- throughput studies employing one or a combination of omics and other technologies; (ii) empowers users to uptake community- defined checklists and ontologies; and (iii) facilitates submission to international public repositories. C1 [Rocca-Serra, Philippe; Brandizi, Marco; Maguire, Eamonn; Sklyar, Nataliya; Taylor, Chris; Sansone, Susanna-Assunta] European Bioinformat Inst, Cambridge CB10 1SD, England. [Rocca-Serra, Philippe; Maguire, Eamonn; Sansone, Susanna-Assunta] Univ Oxford, Oxford E Res Ctr, Oxford OX1 3QG, England. [Taylor, Chris; Field, Dawn; Sterk, Peter] Wallingford CEH, Environm Bioinformat Ctr, Nat Environm Res Council, Wallingford OX10 8BB, Oxon, England. [Begley, Kimberly; Hide, Winston; Hofmann, Oliver] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Field, Dawn; Sterk, Peter] Wellcome Trust Sanger Inst, Genom Stand Consortium, Cambridge CB10 1SD, England. [Harris, Stephen; Tong, Weida] US FDA, Ctr Bioinformat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Neumann, Steffen] Leibniz Inst Plant Biochem, Dept Stress & Dev Biol, D-06120 Halle, Germany. RP Sansone, SA (reprint author), European Bioinformat Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SD, England. EM isatools@googlegroups.com RI Hide, Winston Hide/C-7217-2009; Field, Dawn/C-1653-2010; Neumann, Steffen/K-5554-2012; Hofmann, Oliver/F-1800-2013; OI Sterk, Peter/0000-0003-1668-7778; Hide, Winston Hide/0000-0002-8621-3271; Brandizi, Marco/0000-0002-5427-2496; Neumann, Steffen/0000-0002-7899-7192; Hofmann, Oliver/0000-0002-7738-1513; Sansone, Susanna-Assunta/0000-0001-5306-5690 FU CarcinoGENOMICS; NuGO; BBSRC [BB/I000917/1, BB/G000638/1, BB/E025080/1]; NERC-NEBC; EMBL FX CarcinoGENOMICS, NuGO, BBSRC (BB/I000917/1, BB/G000638/1, BB/E025080/1), NERC-NEBC and EMBL. NR 18 TC 103 Z9 103 U1 2 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD SEP PY 2010 VL 26 IS 18 BP 2354 EP 2356 DI 10.1093/bioinformatics/btq415 PG 3 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 648SK UT WOS:000281714100062 PM 20679334 ER PT J AU Cook, AJ Li, Y Arterburn, D Tiwari, RC AF Cook, Andrea J. Li, Yi Arterburn, David Tiwari, Ram C. TI Spatial Cluster Detection for Weighted Outcomes Using Cumulative Geographic Residuals SO BIOMETRICS LA English DT Article DE Body mass index; Cumulative residuals; Generalized estimating equations; Socioeconomic status; Spatial cluster detection; Weighted linear regression ID LINEAR MIXED MODELS; NEIGHBORHOOD ENVIRONMENT; OBJECTIVE MEASURES; PHYSICAL-ACTIVITY AB P>Spatial cluster detection is an important methodology for identifying regions with excessive numbers of adverse health events without making strong model assumptions on the underlying spatial dependence structure. Previous work has focused on point or individual-level outcome data and few advances have been made when the outcome data are reported at an aggregated level, for example, at the county- or census-tract level. This article proposes a new class of spatial cluster detection methods for point or aggregate data, comprising of continuous, binary, and count data. Compared with the existing spatial cluster detection methods it has the following advantages. First, it readily incorporates region-specific weights, for example, based on a region's population or a region's outcome variance, which is the key for aggregate data. Second, the established general framework allows for area-level and individual-level covariate adjustment. A simulation study is conducted to evaluate the performance of the method. The proposed method is then applied to assess spatial clustering of high Body Mass Index in a health maintenance organization population in the Seattle, Washington, USA area. C1 [Cook, Andrea J.; Arterburn, David] Grp Hlth Res Inst, Biostat Unit, Seattle, WA 98101 USA. [Cook, Andrea J.] Univ Washington, Dept Biostat, Seattle, WA 98105 USA. [Li, Yi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Li, Yi] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tiwari, Ram C.] US FDA, Off Biostat, CDR, Silver Spring, MD 20993 USA. RP Cook, AJ (reprint author), Grp Hlth Res Inst, Biostat Unit, Seattle, WA 98101 USA. EM cook.aj@ghc.org FU NIH [5P20RR020774, RO1 CA95747] FX The authors would like to thank the associate editor and reviewers for their helpful feedback. This work was supported for by NIH Roadmap 5P20RR020774 (AJC) and NIH RO1 CA95747(YL). NR 23 TC 3 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2010 VL 66 IS 3 BP 783 EP 792 DI 10.1111/j.1541-0420.2009.01323.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 651TM UT WOS:000281950000013 PM 19751250 ER PT J AU Li, MJ Reilly, C Hanson, T AF Li, Meijuan Reilly, Cavan Hanson, Tim TI Association Tests for a Censored Quantitative Trait and Candidate Genes in Structured Populations with Multilevel Genetic Relatedness SO BIOMETRICS LA English DT Article DE Association mapping; Gaussian conditional autoregressive (CAR); Kinship coefficient; Mixture of Polya trees (MPT); Population structure; Principal component analysis (PCA); Time-to-event data ID FAILURE TIME MODEL; DETECT ASSOCIATIONS; SEMIPARAMETRIC TEST; INFERENCE; ONSET AB P>Several statistical methods for detecting associations between quantitative traits and candidate genes in structured populations have been developed for fully observed phenotypes. However, many experiments are concerned with failure-time phenotypes, which are usually subject to censoring. In this article, we propose statistical methods for detecting associations between a censored quantitative trait and candidate genes in structured populations with complex multiple levels of genetic relatedness among sampled individuals. The proposed methods correct for continuous population stratification using both population structure variables as covariates and the frailty terms attributable to kinship. The relationship between the time-at-onset data and genotypic scores at a candidate marker is modeled via a parametric Weibull frailty accelerated failure time (AFT) model as well as a semiparametric frailty AFT model, where the baseline survival function is flexibly modeled as a mixture of Polya trees centered around a family of Weibull distributions. For both parametric and semiparametric models, the frailties are modeled via an intrinsic Gaussian conditional autoregressive prior distribution with the kinship matrix being the adjacency matrix connecting subjects. Simulation studies and applications to the Arabidopsis thaliana line flowering time data sets demonstrated the advantage of the new proposals over existing approaches. C1 [Li, Meijuan; Reilly, Cavan; Hanson, Tim] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA. RP Li, MJ (reprint author), CDRH FDA, Div Biostat, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM meijuan.li@fda.hhs.gov RI Hanson, Timothy/A-9127-2016 NR 26 TC 2 Z9 2 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2010 VL 66 IS 3 BP 925 EP 933 DI 10.1111/j.1541-0420.2009.01352.x PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 651TM UT WOS:000281950000028 PM 19912178 ER PT J AU Frasca, DR AF Frasca, Dominic R. TI THE MEDICAL RESERVE CORPS AS PART OF THE FEDERAL MEDICAL AND PUBLIC HEALTH RESPONSE IN DISASTER SETTINGS SO BIOSECURITY AND BIOTERRORISM-BIODEFENSE STRATEGY PRACTICE AND SCIENCE LA English DT Article AB The Secretary of the Department of Health and Human Services (HHS), through the Office of the Assistant Secretary for Preparedness and Response (ASPR), coordinates federal Emergency Support Function (ESF) #8 preparedness, response, and recovery actions. To address these needs, the ASPR can draw on trained personnel from a variety of sources, both from within and outside HHS. Among the resources under the domain of HHS is the Medical Reserve Corps (MRC), directed by the Office of the Civilian Volunteer Medical Reserve Corps (OCVMRC) in the Office of the Surgeon General. MRC units are community based and function as a way to locally organize and utilize medical and public health professionals, such as physicians, nurses, pharmacists, dentists, veterinarians, and epidemiologists. Nonclinical volunteers, such as interpreters, chaplains, office workers, legal advisors, and others, can fill logistical and support roles in MRC units. This article discusses locally controlled (Hurricanes Gustav and Ike) and federalized (Hurricanes Katrina and Rita) MRC activations, and it describes the advantages of using medical volunteers in a large-scale disaster response setting. C1 US FDA, Off Crisis Management, Off Emergency Operat, Rockville, MD 20852 USA. RP Frasca, DR (reprint author), US FDA, Off Crisis Management, Off Emergency Operat, Room 12A55 Parklawn,5600 Fishers Lane, Rockville, MD 20852 USA. EM dominic.frasca@fda.hhs.gov NR 8 TC 9 Z9 9 U1 0 U2 3 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 SEP PY 2010 VL 8 IS 3 BP 265 EP 271 DI 10.1089/bsp.2010.0006 PG 7 WC Public, Environmental & Occupational Health; International Relations SC Public, Environmental & Occupational Health; International Relations GA 648BY UT WOS:000281666600013 PM 20825337 ER PT J AU Varma, V Wise, C Kaput, J AF Varma, Vijayalakshmi Wise, Carolyn Kaput, Jim TI Carbohydrate metabolic pathway genes associated with quantitative trait loci (QTL) for obesity and type 2 diabetes: Identification by data mining SO BIOTECHNOLOGY JOURNAL LA English DT Article DE Carbohydrate metabolism genes; CNVs; Nutrigenomics; QTL; SNPs ID COPY-NUMBER VARIATION; GENOME-WIDE ASSOCIATION; POPULATION DIFFERENTIATION; CARDIOVASCULAR-DISEASE; DIETARY FRUCTOSE; GLUCOSE; MELLITUS; HUMANS; SUGARS; RISK AB Increasing consumption of refined carbohydrates is now being recognized as a primary contributor to the development of nutritionally related chronic diseases such as obesity and type 2 diabetes mellitus (T2DM). A data mining approach was used to evaluate the role of carbohydrate metabolic pathway genes in the development of obesity and T2DM. Data from public databases were used to map the position of the carbohydrate metabolic pathway genes to known quantitative trait loci (QTL) for obesity and T2DM and for examining the pathway genes for the presence of sequence and structural genetic variants such as single nucleotide polymorphisms (SNPs) and copy number variants (CNS), respectively. The results demonstrated that a majority of the genes of the carbohydrate metabolic pathways are associated with QTL for obesity and many for T2DM. In addition, some key genes of the pathways also encode non-synonymous SNPs that exhibit significant differences in population frequencies. This study emphasizes the significance of the metabolic pathways genes in the development of disease phenotypes, its differential occurrence across populations and between individuals, and a strategy for interpreting an individuals' risk for disease. C1 [Varma, Vijayalakshmi] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Varma, V (reprint author), US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, HFT-020,3900 NCTR Rd, Jefferson, AR 72079 USA. EM vijayalakshmi.varma@fda.hhs.gov NR 59 TC 3 Z9 3 U1 1 U2 11 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1860-6768 J9 BIOTECHNOL J JI Biotechnol. J. PD SEP PY 2010 VL 5 IS 9 SI SI BP 942 EP 949 DI 10.1002/biot.201000067 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 662CW UT WOS:000282785700006 PM 20845384 ER PT J AU Satyanarayanajois, SD Buyuktimkin, B Gokhale, A Ronald, S Siahaan, TJ Latendresse, JR AF Satyanarayanajois, Seetharama D. Buyuktimkin, Barlas Gokhale, Ameya Ronald, Sharon Siahaan, Teruna J. Latendresse, John R. TI A Peptide from the Beta-strand Region of CD2 Protein that Inhibits Cell Adhesion and Suppresses Arthritis in a Mouse Model SO CHEMICAL BIOLOGY & DRUG DESIGN LA English DT Article DE arthritis mouse model; beta hairpin; CD2 peptides CD2; CD58; cell adhesion; immunomodulation; NMR ID COLLAGEN-INDUCED ARTHRITIS; RENAL-TRANSPLANTATION; DESIGNING PEPTIDE; SYNOVIAL-FLUID; MOLECULES; RESIDUES; ANTIBODY; BTI-322; CD58; RECOGNITION AB Cell adhesion molecules play a central role at every step of the immune response. The function of leukocytes can be regulated by modulating adhesion interactions between cell adhesion molecules to develop therapeutic agents against autoimmune diseases. Among the different cell adhesion molecules that participate in the immunologic response, CD2 and its ligand CD58 (LFA-3) are two of the best-characterized adhesion molecules mediating the immune response. To modulate the cell adhesion interaction, peptides were designed from the discontinuous epitopes of the beta-strand region of CD2 protein. The two strands were linked by a peptide bond. beta-Strands in the peptides were nucleated by inserting a beta-sheet-inducing Pro-Gly sequence with key amino acid sequences from CD2 protein that binds to CD58. Using a fluorescence assay, peptides that exhibited potential inhibitory activity in cell adhesion were evaluated for their ability to bind to CD58 protein. A model for peptide binding to CD58 protein was proposed based on docking studies. Administration of one of the peptides, P3 in collagen-induced arthritis in the mouse model, indicated that peptide P3 was able to suppress rheumatoid arthritis in mice. C1 [Satyanarayanajois, Seetharama D.; Gokhale, Ameya; Ronald, Sharon] Univ Louisiana Monroe, Dept Basic Pharmaceut Sci, Coll Pharm, Monroe, LA 71201 USA. [Buyuktimkin, Barlas; Siahaan, Teruna J.] Univ Kansas, Dept Pharmaceut Chem, Lawrence, KS 66047 USA. [Latendresse, John R.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Satyanarayanajois, SD (reprint author), Univ Louisiana Monroe, Dept Basic Pharmaceut Sci, Coll Pharm, Monroe, LA 71201 USA. EM jois@ulm.edu FU Louisiana Board of Regents [LEQSF(2009-12)-RD-A-23(SJ)]; NIH [R01 AI063002, T32 GM-08359] FX Part of the work described in this paper was supported by the Louisiana Board of Regents grant LEQSF(2009-12)-RD-A-23(SJ). Docking calculations were performed using Dell Clusters, Louisiana Optical Network Initiative (LONI) computer resources. TJS was supported by NIH R01 AI063002 and BB was supported by NIH training grant T32 GM-08359. Ms. Sumana Giddu performed some preliminary studies on CIA mice models. NR 41 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1747-0277 J9 CHEM BIOL DRUG DES JI Chem. Biol. Drug Des. PD SEP PY 2010 VL 76 IS 3 BP 234 EP 244 DI 10.1111/j.1747-0285.2010.01001.x PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 635HR UT WOS:000280646700004 PM 20572813 ER PT J AU Brady, RA Verma, A Meade, BD Burns, DL AF Brady, Rebecca A. Verma, Anita Meade, Bruce D. Burns, Drusilla L. TI Analysis of Antibody Responses to Protective Antigen-Based Anthrax Vaccines through Use of Competitive Assays SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID BACILLUS-ANTHRACIS; DOMAIN SPECIFICITY; GUINEA-PIGS; EFFICACY; TOXIN; CHALLENGE; INFECTION; IMMUNOGENICITY; RECEPTOR; MICE AB The licensed anthrax vaccine and many of the new anthrax vaccines being developed are based on protective antigen (PA), a nontoxic component of anthrax toxin. For this reason, an understanding of the immune response to PA vaccination is important. In this study, we examined the antibody response elicited by PA-based vaccines and identified the domains of PA that contribute to that response in humans as well as nonhuman primates (NHPs) and rabbits, animal species that will be used to generate efficacy data to support approval of new anthrax vaccines. To this end, we developed a competitive enzyme-linked immunosorbent assay (ELISA), using purified recombinant forms of intact PA and its individual domains. We found that PA-based vaccines elicited IgG antibodies to each of the four PA domains in all three species. We also developed a competitive toxin neutralization assay, which showed that rabbits, NHPs, and humans all have functional antibody populations that bind to domains 1, 3, and 4. While the domain specificities of the antibody responses elicited by PA-based vaccines were similar in humans, NHPs, and rabbits, competitive assays suggested that humans may have a more significant secondary population of IgG antibodies that bind to partially unfolded or incorrectly folded PA. These findings provide information that will be useful when linking animal protection data to humans via an antibody bridge to establish efficacy of new anthrax vaccines. C1 [Brady, Rebecca A.; Verma, Anita; Burns, Drusilla L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Meade, Bruce D.] Meade Biol, Hillsborough, NC 27278 USA. RP Burns, DL (reprint author), FDA HFM 434, CBER, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM drusilla.burns@fda.hhs.gov FU CBER/FDA-NIAID/NIH [YI-AI-6153-01]; Center for Biologics Evaluation and Research FX This work was supported in part by CBER/FDA-NIAID/NIH Interagency Agreement YI-AI-6153-01. R. B. was partially funded by a program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education. The following reagents were obtained from the NIH Biodefense and Emerging Infections Research Resources Repository, NIAID, NIH: anthrax LF, recombinant from Bacillus anthracis, NR-142; anthrax PA, recombinant from Bacillus anthracis, NR-164 and NR-140; J774A. 1 monocyte/macrophage (mouse) working cell bank, NR-28; rabbit anti-PA reference serum pool, NR-3839; NHP anti-PA reference serum pool, NR-9329; human anti-AVA reference serum pool, AVR801; and mouse anti-PA monoclonal antibody DD-508. NR 30 TC 5 Z9 5 U1 0 U2 4 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 SEP PY 2010 VL 17 IS 9 BP 1390 EP 1397 DI 10.1128/CVI.00145-10 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 645HW UT WOS:000281444300014 PM 20631338 ER PT J AU Jain, RK Brar, SS Lesko, LJ AF Jain, Rajul K. Brar, Satjit S. Lesko, Lawrence J. TI Food and Oral Antineoplastics: More Than Meets the Eye SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID CLINICAL PHARMACOKINETICS; BIOAVAILABILITY; LAPATINIB AB Food can alter the bioavailability of orally administered drugs. Description of food effects in product labels and information about administration in relation to food are influenced by a variety of factors. Because food effects can change drug efficacy and toxicity, it is important that physicians and patients be aware of them. Clin Cancer Res; 16(17); 4305-7 (C) 2010 AACR. C1 [Jain, Rajul K.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Brar, Satjit S.; Lesko, Lawrence J.] US FDA, Silver Spring, MD USA. RP Lesko, LJ (reprint author), CDER Off Bldg 21,Room 4546,10903 New Hampshire Av, Silver Spring, MD 20993 USA. EM lawrence.lesko@fda.hhs.gov NR 11 TC 13 Z9 13 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 SEP 1 PY 2010 VL 16 IS 17 BP 4305 EP 4307 DI 10.1158/1078-0432.CCR-10-1857 PG 3 WC Oncology SC Oncology GA 645IA UT WOS:000281444700001 PM 20736331 ER PT J AU Lemery, SJ Zhang, J Rothmann, MD Yang, J Earp, J Zhao, H McDougal, A Pilaro, A Chiang, R Gootenberg, JE Keegan, P Pazdur, R AF Lemery, Steven J. Zhang, Jenny Rothmann, Mark D. Yang, Jun Earp, Justin Zhao, Hong McDougal, Andrew Pilaro, Anne Chiang, Raymond Gootenberg, Joseph E. Keegan, Patricia Pazdur, Richard TI US Food and Drug Administration Approval: Ofatumumab for the Treatment of Patients with Chronic Lymphocytic Leukemia Refractory to Fludarabine and Alemtuzumab SO CLINICAL CANCER RESEARCH LA English DT Article ID CLINICAL-TRIALS; GUIDELINES; DIAGNOSIS AB Purpose: To describe the data and analyses that led to the U. S. Food and Drug Administration (FDA) approval of ofatumumab (Arzerra, GlaxoSmithKline) for the treatment of patients with chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab. Experimental Design: The FDA reviewed the results of a planned interim analysis of a single-arm trial, enrolling 154 patients with CLL refractory to fludarabine, and a supportive dose-finding, activity-estimating trial in 33 patients with CLL. Patients in the primary efficacy study received ofatumumab weekly for eight doses, then every 4 weeks for an additional four doses; patients in the supportive trial received four weekly doses. In the primary efficacy study, endpoints were objective response rate and response duration. Results: For regulatory purposes, the primary efficacy population consisted of 59 patients with CLL refractory to fludarabine and alemtuzumab. In this subgroup, the investigator-determined objective response rate was 42% [99% confidence interval (CI), 26-60], with a median duration of response of 6.5 months (95% CI, 5.8-8.3); all were partial responses. The most common adverse reactions in the primary efficacy study were neutropenia, pneumonia, pyrexia, cough, diarrhea, anemia, fatigue, dyspnea, rash, nausea, bronchitis, and upper respiratory tract infections. Infusion reactions occurred in 44% of patients with the first infusion (300 mg) and 29% with the second infusion (2,000 mg). The most common serious adverse reactions were infections, neutropenia, and pyrexia. Conclusions: On October 26, 2009, the FDA granted accelerated approval to ofatumumab for the treatment of patients with CLL refractory to fludarabine and alemtuzumab, on the basis of demonstration of durable tumor shrinkage. Clin Cancer Res; 16(17); 4331-8. (C) 2010 AACR. C1 [Lemery, Steven J.] US FDA, Div Biol Oncol Prod, Ctr Drug Evaluat & Res, Off Oncol Drug Prod,Off New Drugs, Silver Spring, MD 20993 USA. [Zhang, Jenny; Rothmann, Mark D.] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Yang, Jun; Earp, Justin; Zhao, Hong] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Lemery, SJ (reprint author), US FDA, Div Biol Oncol Prod, Ctr Drug Evaluat & Res, Off Oncol Drug Prod,Off New Drugs, 10903 New Hampshire Ave,Bldg 22,Room 2374, Silver Spring, MD 20993 USA. EM steven.lemery@fda.hhs.gov NR 10 TC 50 Z9 58 U1 0 U2 1 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 SEP 1 PY 2010 VL 16 IS 17 BP 4331 EP 4338 DI 10.1158/1078-0432.CCR-10-0570 PG 8 WC Oncology SC Oncology GA 645IA UT WOS:000281444700007 PM 20601446 ER PT J AU Chen, ML Shah, VP Ganes, D Midha, KK Cao, J Nambiar, P Rocci, ML Thombre, AG Abrahamsson, B Conner, D Davit, B Fackler, P Farrell, C Gupta, S Katz, R Mehta, M Preskorn, SH Sanderink, G Stavchansky, S Temple, R Wang, YN Winklel, H Yu, L AF Chen, Mei-Ling Shah, Vinod P. Ganes, Derek Midha, Kamal K. Cao, James Nambiar, Prabu Rocci, Mario L., Jr. Thombre, Avinash G. Abrahamsson, Bertil Conner, Dale Davit, Barbara Fackler, Paul Farrell, Colm Gupta, Suneel Katz, Russell Mehta, Mehul Preskorn, Sheldon H. Sanderink, Gerard Stavchansky, Salomon Temple, Robert Wang, Yaning Winklel, Helen Yu, Lawrence TI Challenges and Opportunities in Establishing Scientific and Regulatory Standards for Determining Therapeutic Equivalence of Modified-Release Products: Workshop Summary Report SO CLINICAL THERAPEUTICS LA English DT Article DE bioequivalence; modified release; pharmaceutical equivalence; interchangeability; therapeutic equivalence ID DESIGN AB Background: Modified-release (MR) products are complex dosage forms designed to release drug in a controlled manner to achieve the desired efficacy and safety profiles. Inappropriate control of drug release from such products may result in reduced efficacy or increased toxicity. Objective: This paper is a summary report of the American Association of Pharmaceutical Scientists, International Pharmaceutical Federation, and Product Quality Research Institute workshop titled "Challenges and Opportunities in Establishing Scientific and Regulatory Standards for Assuring Therapeutic Equivalence of Modified Release Products," held October 1-2, 2009, in Baltimore, Maryland. Methods: The workshop provided an opportunity for pharmaceutical scientists from academia, industry, and regulatory agencies to discuss current regulatory expectations and industry practices for evaluating the pharmaceutical equivalence and bioequivalence of oral MR products. Results: In the case of conventional monophasic MR formulations, the current regulatory approaches and criteria for bioequivalence evaluation were considered adequate for the assessment of therapeutic equivalence and interchangeability of drug products. Additional measures may occasionally be needed to determine the bioequivalence of multiphasic MR products. The metric of partial AUC proposed by the US Food and Drug Administration received broad support as an additional measure for evaluating bioequivalence of multiphasic MR products designed to have a rapid onset of drug action followed by sustained response. The cutoff for partial AUCs may be based on the pharmacokinetic/pharmacodynamic or pharmacokinetic/response characteristics of the products under examination. If the new metric is highly variable, the bioequivalence limits may be set based on the known within-subject variability for the reference product. Conclusions: The current regulatory approaches and criteria for bioequivalence evaluation were considered adequate for the assessment of therapeutic equivalenceand interchangeability of conventional monophasic MR products. Additional measures may occasionally be needed to establish the bioequivalence of multiphasic MR products, and development of such measures is an important objective. The metric of partial AUC was proposed for products designed to have a rapid drug action followed by sustained response. (Clin Ther. 2010;32:1704-1712) (C) 2010 Excerpta Medica Inc. C1 [Chen, Mei-Ling; Mehta, Mehul; Temple, Robert; Wang, Yaning; Winklel, Helen] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Shah, Vinod P.; Midha, Kamal K.] Int Pharmaceut Federat, The Hague, Netherlands. [Ganes, Derek] Taro Pharmaceut, Hawthorne, NY USA. [Midha, Kamal K.] Univ Saskatchewan, Saskatoon, SK, Canada. [Cao, James] Sanofi Aventis, Washington, DC USA. [Nambiar, Prabu] Vertex Pharmaceut Inc, Cambridge, MA USA. [Rocci, Mario L., Jr.] ICON Dev Solut, Ellicott City, MD USA. [Thombre, Avinash G.] Pfizer Inc, Groton, CT 06340 USA. [Abrahamsson, Bertil] AstraZeneca, Molndal, Sweden. [Conner, Dale; Davit, Barbara; Yu, Lawrence] US FDA, Rockville, MD 20857 USA. [Fackler, Paul] Teva Pharmaceut Ind Ltd, N Wales, PA USA. [Gupta, Suneel] Impax Labs Inc, Hayward, CA USA. [Preskorn, Sheldon H.] Clin Res Inst, Wichita, KS USA. [Preskorn, Sheldon H.] Univ Kansas, Wichita, KS USA. [Preskorn, Sheldon H.] Clin Res Inst, Wichita, KS USA. [Sanderink, Gerard] Sanofi Aventis, Paris, France. [Stavchansky, Salomon] Univ Texas Austin, Austin, TX 78712 USA. RP Chen, ML (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51,Room 4108, Silver Spring, MD 20993 USA. EM meiling.chen@fda.hhs.gov RI Preskorn, Sheldon/L-9839-2016 FU Abbott; AstraZeneca; Biovail; Boehringer Ingelheim; Cetero; Cyberonics, Inc.; Dainippon Sumitomo Pharma; Eli Lilly Company; En Vivo; Evotec; GlaxoSmithKline; Link Medicine; Mylan; Pfizer; Quintiles; Roche; Sonexa Therapeutics; Takeda; Targacept; Trimel Biopharma Inc.; University of North Carolina at Chapel Hill; Wyeth FX Dr. Gupta was previously employed by Johnson & Johnson, in which he holds stock. Dr. Preskorn has received grants and research support from Abbott; AstraZeneca; Biovail; Boehringer Ingelheim; Cetero, Cyberonics, Inc.; Dainippon Sumitomo Pharma; Eli Lilly & Company; En Vivo; Evotec; GlaxoSmithKline; Link Medicine; Mylan; Pfizer; Quintiles; Roche; Sonexa Therapeutics; Takeda; Targacept; Trimel Biopharma Inc.; University of North Carolina at Chapel Hill; and Wyeth. He has acted as a consultant or served on advisory boards for Allergan, Auspex Pharmaceuticals, Covidien, Dainippon Sumitomo Pharma, Eisai, Eli Lilly & Company, Evotec, Lundbeck/Takeda, Psylin, and Wyeth; and has been a speakers' bureau member for Bristol-Myers Squibb Company. The authors have indicated that they have no other conflicts of interest regarding the content of this article. NR 17 TC 6 Z9 6 U1 1 U2 3 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD SEP PY 2010 VL 32 IS 10 BP 1704 EP 1712 DI 10.1016/j.clinthera.2010.09.014 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 661HB UT WOS:000282715500002 PM 21194592 ER PT J AU Tu, EY Joslin, CE Shoff, ME AF Tu, Elmer Y. Joslin, Charlotte E. Shoff, Megan E. TI Successful Treatment of Chronic Stromal Acanthamoeba Keratitis With Oral Voriconazole Monotherapy SO CORNEA LA English DT Article DE Acanthamoeba; voriconazole; keratitis; stromal interstitial keratitis ID CHLORHEXIDINE; INFECTION AB Purpose: To describe the treatment of chronic stromal Acanthamoeba keratitis (AK) with oral voriconazole monotherapy. Methods: All cases of chronic stromal AK recalcitrant to traditional therapy subsequently treated with systemic voriconazole seen at the University of Illinois Eye and Ear Infirmary between June 2003 and July 2009 were reviewed for clinical presentation, clinical course, and outcome. Results: Three eyes of 2 patients were identified with culture-confirmed chronic stromal AK unresponsive to traditional anti-acanthamoebal therapies, requiring topical corticosteroids to maintain corneal clarity. Oral voriconazole 200 mg twice daily achieved a rapid but transient reduction of inflammation and elimination of corticosteroid dependency but, in both patients, recrudesced approximately 6 weeks after its discontinuation. Subsequent repeated and/or extended use of oral voriconazole alone resulted in complete resolution ranging from 7 to 11 months off all medications with final best-corrected visual acuity ranging from 20/20 to 20/25.. Conclusions: Recalcitrant chronic Acanthamoeba stromal keratitis was successfully treated with extended systemic voriconazole administration with good preservation of vision. The clinical resolution of chronic stromal keratitis in our 2 cases suggests that voriconazole may have a larger role in the treatment of AK. C1 [Tu, Elmer Y.; Joslin, Charlotte E.] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA. [Joslin, Charlotte E.] Univ Illinois, Sch Publ Hlth & Epidemiol, Chicago, IL 60612 USA. [Shoff, Megan E.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Tu, EY (reprint author), Univ Illinois, Dept Ophthalmol & Visual Sci, 1855 W Taylor St M-C 648,Rm 3-164, Chicago, IL 60612 USA. EM etu@uic.edu FU NEI NIH HHS [K23 EY015689, K23 EY015689-03] NR 15 TC 18 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD SEP PY 2010 VL 29 IS 9 BP 1066 EP 1068 DI 10.1097/ICO.0b013e3181cbfa2c PG 3 WC Ophthalmology SC Ophthalmology GA 641UO UT WOS:000281155500020 PM 20539217 ER PT J AU Chen, L Ng, MJ van der Vlugt, TH Price, PH Orencia, A AF Chen, Ling Ng, Moh-Jee van der Vlugt, Theresa H. Price, Phill H. Orencia, Anthony TI Statistical Considerations for the Efficacy Assessment of Clinical Studies of Vulvar and Vaginal Atrophy SO DRUG INFORMATION JOURNAL LA English DT Article DE Atrophic vaginitis; Coprimary endpoints; Efficacy assessment; Menopause; Vulvar and vaginal atrophy indication AB The US Food and Drug Administration, Center for Drug Evaluation and Research, Office of New Drugs, Division of Reproductive and Urologic Products (DRUP) released its draft "Guidance for Industry: Estrogen and Estrogen/Progestin Drug Products to Treat Vasomotor Symptoms and Vulvar and Vaginal Atrophy Symptoms Recommendations for Clinical Evaluation" in 2003. The guidance references the assessment of safety and efficacy of estrogen and estrogen and progestin drugs indicated for the treatment of moderate to severe vasomotor symptoms and the treatment of moderate to severe symptoms of vulvar and vaginal atrophy (VVA) due to menopause. Since the release of the draft guidance, DRUP has reviewed several VVA clinical studies in new drug applications. Statistical issues with the coprimary endpoints in VVA studies have been raised by the pharmaceutical industry and some reviewers within the FDA. In this article, we discuss statistical issues in VVA studies and provide methodologies to improve the efficacy assessment for the VVA indication. These include the following recommendations: (a) that the "most bothersome symptom designation" be removed from the coprimary endpoint of mean change from baseline to week 12 in the moderate to severe symptom that has been identified by the patient as being the most bothersome to her; and (b) that the drug efficacy assessment criteria be modified. C1 [Chen, Ling; Ng, Moh-Jee] US FDA, Div Biometr 6, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [van der Vlugt, Theresa H.; Price, Phill H.] US FDA, Div Reprod & Urol Prod, Off Drug Evaluat 3, Ctr Drug Evaluat & Res,Off New Drugs, Silver Spring, MD 20993 USA. [Orencia, Anthony] US FDA, Div Sci Investigat, Off Compliance, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Chen, L (reprint author), US FDA, Div Biometr 6, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 21,Room 4644, Silver Spring, MD 20993 USA. EM ling.chen@fda.hhs.gov FU US Food and Drug Administration FX This research was funded by the 2007 Regulatory Science Review Enhancement Program in the Center for Drug Evaluation and Research at the US Food and Drug Administration. Special thanks to Drs. Mohammad F. Huque, Mahboob Sobhan, Shelley R. Slaughter, Scott Monroe, and Stella G. Machado for their helpful discussion and support. NR 9 TC 4 Z9 4 U1 0 U2 1 PU DRUG INFORMATION ASSOC PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD SEP PY 2010 VL 44 IS 5 BP 581 EP 588 PG 8 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 645NZ UT WOS:000281469800005 ER PT J AU Sharma, HS Zimmermann-Meinzingen, S Sharma, A Ali, SF AF Sharma, H. S. Zimmermann-Meinzingen, S. Sharma, A. Ali, S. F. TI Cerebrolysin reduces MDMA induced blood-brain barrier breakdown and heat shock protein response in rats SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 14th Congress of European-Federation-of-Neurological-Societies CY SEP, 2010 CL Geneva, SWITZERLAND SP European Federat Neurol Soc C1 [Sharma, H. S.] Uppsala Univ, Uppsala, Sweden. [Sharma, H. S.; Sharma, A.] Univ Hosp, Uppsala, Sweden. [Zimmermann-Meinzingen, S.] EVER Neuro Pharma GmbH, Unterach, Austria. [Ali, S. F.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RI Sharma, Hari/G-4508-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2010 VL 17 SU 3 SI SI BP 241 EP 241 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 800BD UT WOS:000293331100461 ER PT J AU Rahman, Z Zidan, AS Khan, MA AF Rahman, Ziyaur Zidan, Ahmed S. Khan, Mansoor A. TI Non-destructive methods of characterization of risperidone solid lipid nanoparticles SO EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS LA English DT Article DE Risperidone; Compritol 888 ATO; SLN; NIR; NIR-CI ID BIODEGRADABLE POLYMERIC MICROSPHERES; DRUG-DELIVERY; REFLECTANCE SPECTRA; RELEASE PROFILES; BRAIN; THERAPY; MORPHOLOGY; PEPTIDES; SLN(TM); DESIGN AB The objective of this investigation is to evaluate compositional variations and their interaction of the solid lipid nanoparticle (SLN) formulation of risperidone using response surface methodology of design of experiment (DOE) and subsequently, characterize the SLN by non-destructive methods of analysis. Box-Behnken DOE was constructed using drug (X(1)), lipid (X(2)) and surfactant (X(3)) level as independent factors. Compritol 888 ATO and sodium lauryl sulphate were used as lipid and surfactant, respectively. The SLN was prepared by solvent evaporation method and characterized by transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), fourier infrared spectroscopy (FTIR), near infrared spectroscopy (NIR) and NIR-chemical imaging (NIR-CI). Responses measured were entrapment efficiency (Y(1)), D(90) (Y(2)), zeta potential (Y(3)), burst effect (Y(4)) and cumulative release in 8 h (Y5). Statistically significant (p <0.05) effect of XI on the Y(1), Y(2), Y(3) and Y(4) were seen. FTIR revealed no interaction between risperidone and compritol 888 ATO. TEM showed spherical and smooth surface SLN. Compritol retained its crystalline nature in the SLN formulation revealed by DSC and XRD studies. Homogenous distribution of risperidone and compritol 888 ATO was revealed by NIR-CI. Principal component analysis (PCA) and partial least square (PLS) were carried out on NIR data of SLN formulation. PLS showed correlation coefficient > 0.996 for prediction and calibration model of both risperidone and compritol 888 ATO. The accuracy of models in predicting risperidone and compritol 888 ATO were 1.60% and 11.27%, respectively. In conclusion, the DOE reveals significant effect of drug loading on SLN characteristics, and chemometric models based on NIR and NIR-CI data provided non-destructive method of estimation of components of SLN. Published by Elsevier B.V. C1 [Rahman, Ziyaur; Zidan, Ahmed S.; Khan, Mansoor A.] FDA, DPQR, CDER, Silver Spring, MD 20993 USA. RP Khan, MA (reprint author), 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. The views presented in this article do not necessarily reflect the official policy of the US Food and Drug Administration. NR 35 TC 69 Z9 69 U1 2 U2 28 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0939-6411 J9 EUR J PHARM BIOPHARM JI Eur. J. Pharm. Biopharm. PD SEP PY 2010 VL 76 IS 1 BP 127 EP 137 DI 10.1016/j.ejpb.2010.05.003 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 650YY UT WOS:000281892000015 PM 20470882 ER PT J AU Cokic, V Bhattacharya, B Beleslin-Cokic, B Noguchi, C Puri, R Schechter, A AF Cokic, V. Bhattacharya, B. Beleslin-Cokic, B. Noguchi, C. Puri, R. Schechter, A. TI GLOBIN GENES VERSUS COMMON GENES EXPRESSION PROFILING IN ERYTHROID CELLS DURING ONTOGENY SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the ISEH - Society-for-Hematology-and-Stem-Cells CY SEP 15-18, 2010 CL Melbourne, AUSTRALIA SP Soc Hematol Stem Cell C1 [Cokic, V.] Inst Med Res, Belgrade, Serbia. [Bhattacharya, B.; Puri, R.] US FDA, Ctr Biol Eval & Res, Div Cellular & Gene Therapies, Bethesda, MD USA. [Beleslin-Cokic, B.] Inst Endocrinol Diabet & Dis Metab, Belgrade, Serbia. [Noguchi, C.; Schechter, A.] NIDDK, Mol Med Branch, NIH, Bethesda, MD USA. NR 0 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2010 VL 38 IS 9 SU 1 MA 060 BP S29 EP S29 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 641YM UT WOS:000281168900059 ER PT J AU Woods, JW Burkhardt, W AF Woods, Jacquelina W. Burkhardt, William, III TI Occurrence of Norovirus and Hepatitis A Virus in US Oysters SO FOOD AND ENVIRONMENTAL VIROLOGY LA English DT Article DE Norovirus; Hepatitis A virus; Market survey; Virus detection ID REVERSE TRANSCRIPTION-PCR; NORWALK-LIKE VIRUS; UNITED-STATES; MOLECULAR EPIDEMIOLOGY; MULTISTATE OUTBREAK; FOODBORNE VIRUSES; STOOL SAMPLES; ILLNESS; WATERS; CONTAMINATION AB Noroviruses (NoV) and hepatitis A virus (HAV) are the leading causes of non-bacterial gastroenteritis in shellfish consumers worldwide. This study determined the seasonal and geographical distribution of NoV (genogroups I and II) and HAV in live U. S. market oysters. Samples were analyzed to determine the occurrence and levels of NoV and HAV using RT-qPCR and conventional RT-PCR. NoV and HAV were detected in 3.9 and 4.4%, respectively. NoV genogroups I and II were detected, with genogroup II predominating. Sequencing identified genotypes II.4, II.3, and II.7. The GII.4 strain showed >= 98% similarity with 2006-2007 circulating strains, Minerva and Laurens. HAV sequences from the 5' non-coding region (NCR) of the genome were from genotypes I, II, or III. The incidence of NoV in oysters harvested from Atlantic Coast states was higher than that in oysters from other regions and its occurrence was greatest during the cooler months (December to February). HAV was detected at a higher frequency in shellfish harvested from the Gulf Coast and also predominated during cooler months. The seasonal occurrence of viruses in this study corresponded to the reported incidence of shellfish-associated viral illnesses. This investigation provides an overview of the occurrence and distribution of NoV and HAV in U.S. market shellfish. C1 [Woods, Jacquelina W.; Burkhardt, William, III] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Woods, JW (reprint author), US FDA, Gulf Coast Seafood Lab, 1 Iberville Dr, Dauphin Isl, AL 36528 USA. EM jacquelina.woods@fda.hhs.gov FU ISSC FX We would like to thank the GCSL retail study team (Angelo DePaola, Jessica Jones, Kevin Calci, and Jeffrey Krantz); individuals at participating FDA-ORA laboratories (Emily Jacobs and Angela Swinford-FDA SRL, Khamphet Nabe and June Wetherington-FDA PRL-NW, Kuppuswamy Kasturi and Jose Obano-FDA NRL, and Donna Hill-Williams and Nelly Tran-FDA PRL-SW. We thank the ISSC for financial support and FDA personnel and individuals from the collecting states. We would also like to thank Susan McCarthy for review of this manuscript. NR 43 TC 24 Z9 24 U1 0 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1867-0334 J9 FOOD ENVIRON VIROL JI Food Environ. Virol. PD SEP PY 2010 VL 2 IS 3 SI SI BP 176 EP 182 DI 10.1007/s12560-010-9040-7 PG 7 WC Environmental Sciences; Microbiology; Virology SC Environmental Sciences & Ecology; Microbiology; Virology GA 637NS UT WOS:000280825600008 ER PT J AU Shrivas, K Patel, DK AF Shrivas, Kamlesh Patel, Devesh Kumar TI Liquid-phase microextraction combined with gas chromatography mass spectrometry for rapid determination of nicotine in one-drop of nightshades vegetables and commercial food products SO FOOD CHEMISTRY LA English DT Article DE Nicotine; Ultrasound; Hollow fibre-liquid-phase microextraction; Gas chromatography-mass spectrometry ID SOLVENT MICROEXTRACTION; CAPILLARY-ELECTROPHORESIS; SINGLE-DROP; TOBACCO; COTININE; FORMULATIONS; ALKALOIDS; SMOKE; HAIR AB A simple, rapid and sensitive ultrasound-assisted hollow fibre liquid-phase microextraction (UA-HF-LPME) is evaluated for the determination of nicotine in one-drop of nightshade vegetables and some of the commercial food products. The optimum extraction of nicotine was obtained by using 1.5 mu L as an extracting solvent in 1.0 cm of hollow fibre for 10 min extraction time with addition of salt. The calculated calibration curves showed a high level of linearity in the range 2-100 ng g(-1) with correlation coefficients >0.998. The limit of detection (LOD) for the target analyte was found to be in the range of 0.2-0.5 ng g(-1) and the relative standard deviations (RSD) of 2.3-4.5% were obtained. The results showed that under the optimised experimental conditions, the method showed good sensitivity and relative recoveries, as well as advantages such as linearity, simplicity, low cost and high feasibility. The extraction performance of present method to the target compound was also compared with drop-to-drop solvent microextraction (DDSME) and we found that the present approach showed better extraction efficiency of target molecule from sample solution. Finally, the proposed method was successfully applied for the determination of nicotine in nightshade vegetables (potatoes, tomatoes, peppers and eggplants) and commercial food products (tomato sauce, tomato juice, and pepper sauce). (C) 2010 Elsevier Ltd. All rights reserved. C1 [Shrivas, Kamlesh] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Patel, Devesh Kumar] Govt Sci Coll, Dept Chem, Rajnandgaon 491441, CG, India. RP Shrivas, K (reprint author), US FDA, Ctr Biol Evaluat & Res, 8800 Rockville Pike,Bldg 29 A,Room 2B20, Bethesda, MD 20892 USA. EM shrikam@rediffmail.com NR 24 TC 30 Z9 30 U1 2 U2 25 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0308-8146 J9 FOOD CHEM JI Food Chem. PD SEP 1 PY 2010 VL 122 IS 1 BP 314 EP 318 DI 10.1016/j.foodchem.2010.02.035 PG 5 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA 596RG UT WOS:000277702200048 ER PT J AU Meseda, CA Weir, JP AF Meseda, Clement A. Weir, Jerry P. TI Third-generation smallpox vaccines: challenges in the absence of clinical smallpox SO FUTURE MICROBIOLOGY LA English DT Review ID MONKEYPOX VIRUS-INFECTION; CELL-MEDIATED-IMMUNITY; ANTIBODY-RESPONSES; PROTECTS MICE; DNA VACCINE; ENVELOPE PROTEIN; RABBITPOX VIRUS; PUBLIC-HEALTH; MOUSE MODEL; POXVIRUS CHALLENGE AB Smallpox, a disease caused by variola virus, is estimated to have killed hundreds of millions to billions of people before it was certified as eradicated in 1980. However, there has been renewed interest in smallpox vaccine development due in part to zoonotic poxvirus infections and the possibility of a re-emergence of smallpox, as well as the fact that first-generation smallpox vaccines are associated with relatively rare, but severe, adverse reactions in some vaccinees. An understanding of the immune mechanisms of vaccine protection and the use of suitable animal models for vaccine efficacy assessment are paramount to the development of safer and effective smallpox vaccines. This article focuses on studies aimed at understanding the immune responses elicited by vaccinia virus and the various animal models that can be used to evaluate smallpox vaccine efficacy. Harnessing this information is necessary to assess the effectiveness and potential usefulness of new-generation smallpox vaccines. C1 [Meseda, Clement A.; Weir, Jerry P.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Meseda, CA (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 457, Rockville, MD 20852 USA. EM clement.meseda@fda.hhs.gov NR 148 TC 4 Z9 4 U1 0 U2 6 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0913 J9 FUTURE MICROBIOL JI Future Microbiol. PD SEP PY 2010 VL 5 IS 9 BP 1367 EP 1382 DI 10.2217/FMB.10.98 PG 16 WC Microbiology SC Microbiology GA 660VM UT WOS:000282674600010 PM 20860482 ER PT J AU Johansson, BE Eichelberger, MC AF Johansson, Bert E. Eichelberger, Maryna C. TI Influenza: a unique problem in vaccination SO FUTURE VIROLOGY LA English DT Review DE hemagglutinin; influenza; M2e; neuraminidase; vaccines ID DIVALENT-CATION REQUIREMENTS; BROADENED IMMUNE-RESPONSE; VIRUS-LIKE PARTICLES; ANTIGENIC DRIFT; T-CELLS; IMMUNOLOGICAL RESPONSE; AVIAN INFLUENZA; YOUNG-CHILDREN; DNA VACCINE; NEURAMINIDASE VACCINES AB The genetic attributes of the influenza virus lead to unique problems in vaccination. First, a highly mutable RNA genome, resulting in sequential antigenic variation, could potentially manifest as a vaccine failure or epidemic influenza. Second, a segmented genome that engenders the virus with the capacity for genetic reassortment and the introduction of new antigens into a host population could possibly result in a pandemic. The core problem in combating influenza is the need for continual vaccine revision and induction of broader heterovariant immunity. Current vaccines - the conventional inactivated vaccine and the live attenuated vaccine - rely on technology of strain selection and production methods that is decades old. The immunity induced by these vaccines is dominated by the response to hemagglutinin (HA) and, therefore, the vaccines are most effective when there is sufficient antigenic relatedness between the vaccine strain HA and the circulating wild-type virus HA. Consequently, these vaccines are susceptible to failure when an antigenically distinct virus emerges after the selection of the vaccine candidate strain. New vaccine strategies need to include immunization with other viral antigens in addition to HA, thereby broadening the immune response against influenza. Inclusion of the more slowly evolving neuraminidase and/or M2e in a vaccine against influenza could reduce the vulnerability to antigenic changes, and conserved antigens from internal proteins - nucleoprotein and M1 - delivered to induce T-cell helper and cytotoxic T cells, could ensure the presence of activated T cells that facilitate clearance of pandemic strains. Alternative production technologies, such as recombinant baculovirus and yeast, and different delivery methods, such as virus-like particles, should be explored to decrease vaccine production times and reduce reliance on embryonated eggs. C1 [Eichelberger, Maryna C.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Johansson, BE (reprint author), Texas Tech Univ, Hlth Sci Ctr, Ctr Excellence Infect Dis, Paul H Foster Sch Med, MSB1 5001 El Paso Dr, El Paso, TX 79922 USA. EM bert.johansson@ttuhsc.edu NR 112 TC 1 Z9 1 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 1746-0794 J9 FUTURE VIROL JI Future Virol. PD SEP PY 2010 VL 5 IS 5 BP 651 EP 664 DI 10.2217/FVL.10.46 PG 14 WC Virology SC Virology GA 660VK UT WOS:000282674400014 ER PT J AU Dahari, H Feinstone, SM Major, ME AF Dahari, Harel Feinstone, Stephen M. Major, Marian E. TI Meta-Analysis of Hepatitis C Virus Vaccine Efficacy in Chimpanzees Indicates an Importance for Structural Proteins SO GASTROENTEROLOGY LA English DT Article DE Correlates of Protection; Viral Kinetics; ELISPOT Responses ID CELLULAR IMMUNE-RESPONSES; INFECTIOUS IN-VIVO; RECOVERED CHIMPANZEES; PERSISTENT INFECTION; ENVELOPE PROTEIN; MOLECULAR CLONE; HCV; REPLICATION; GENOTYPE; IMMUNIZATION AB BACKGROUND & AIMS: Studies in patients and chimpanzees that spontaneously cleared hepatitis C virus (HCV) infections demonstrated that natural immunity to the virus is induced during primary infections and that this immunity can be cross protective. These discoveries led to optimism about prophylactic HCV vaccines, and several studies were performed in chimpanzees, although most included fewer than 6 animals. To draw meaningful conclusions about the efficacy of HCV vaccines in chimpanzees, we performed statistical analyses of data from previously published studies from different groups. METHODS: We performed a meta-analysis that compared parameters among naive (n = 63), vaccinated (n = 53), and rechallenged (n = 36) animals, including peak RNA titer post-challenge, time points of peak RNA titer, duration of viremia, and proportion of persistent infections. RESULTS: Each vaccination study induced immune responses that were effective in rapidly controlling HCV replication. Levels of induced T-cell responses did not indicate vaccine success. There was no reduction in the rate of HCV persistence in vaccinated animals, compared with naive animals, when nonstructural proteins were included in the vaccine. Vaccines that contained only structural proteins had clearance rates that were significantly higher than vaccines that contained nonstructural components (P = .015). CONCLUSIONS: The inclusion of nonstructural proteins in HCV vaccines might be detrimental to protective immune responses, and/or structural proteins might activate T-cell responses that mediate viral clearance. C1 [Feinstone, Stephen M.; Major, Marian E.] US FDA, Div Viral Prod, Lab Hepatitis Viruses, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Dahari, Harel] Univ Illinois, Dept Med, Chicago, IL USA. RP Major, ME (reprint author), US FDA, Div Viral Prod, Lab Hepatitis Viruses, Ctr Biol Evaluat & Res, Bldg 29A Rm 1D10-HFM 448,8800 Rockville Pike, Bethesda, MD 20892 USA. EM marian.major@fda.hhs.gov FU Food and Drug Administration; NIH [P20RR18754]; University of Illinois Walter Payton Liver Center GUILD FX Supported by intramural funds from the Food and Drug Administration, by NIH grant number P20RR18754, and by the University of Illinois Walter Payton Liver Center GUILD (to H.D.). NR 71 TC 53 Z9 53 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2010 VL 139 IS 3 BP 965 EP 974 DI 10.1053/j.gastro.2010.05.077 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 644HR UT WOS:000281365500037 PM 20621699 ER PT J AU van Ommen, B Bouwman, J Dragsted, LO Drevon, CA Elliott, R de Groot, P Kaput, J Mathers, JC Muller, M Pepping, F Saito, J Scalbert, A Radonjic, M Rocca-Serra, P Travis, A Wopereis, S Evelo, CT AF van Ommen, Ben Bouwman, Jildau Dragsted, Lars O. Drevon, Christian A. Elliott, Ruan de Groot, Philip Kaput, Jim Mathers, John C. Mueller, Michael Pepping, Fre Saito, Jahn Scalbert, Augustin Radonjic, Marijana Rocca-Serra, Philippe Travis, Anthony Wopereis, Suzan Evelo, Chris T. TI Challenges of molecular nutrition research 6: the nutritional phenotype database to store, share and evaluate nutritional systems biology studies SO GENES AND NUTRITION LA English DT Review DE Nutritional phenotype; Nutrigenomics; Database ID GENE-EXPRESSION; METABOLIC PHENOTYPES; ASSOCIATION; FRAMEWORK; SERVICES; NETWORK; COMPLEX; HEALTH; DIET AB The challenge of modern nutrition and health research is to identify food-based strategies promoting life-long optimal health and well-being. This research is complex because it exploits a multitude of bioactive compounds acting on an extensive network of interacting processes. Whereas nutrition research can profit enormously from the revolution in 'omics' technologies, it has discipline-specific requirements for analytical and bioinformatic procedures. In addition to measurements of the parameters of interest (measures of health), extensive description of the subjects of study and foods or diets consumed is central for describing the nutritional phenotype. We propose and pursue an infrastructural activity of constructing the "Nutritional Phenotype database" (dbNP). When fully developed, dbNP will be a research and collaboration tool and a publicly available data and knowledge repository. Creation and implementation of the dbNP will maximize benefits to the research community by enabling integration and interrogation of data from multiple studies, from different research groups, different countries and different-omics levels. The dbNP is designed to facilitate storage of biologically relevant, pre-processed-omics data, as well as study descriptive and study participant phenotype data. It is also important to enable the combination of this information at different levels (e.g. to facilitate linkage of data describing participant phenotype, genotype and food intake with information on study design and-omics measurements, and to combine all of this with existing knowledge). The biological information stored in the database (i.e. genetics, transcriptomics, proteomics, biomarkers, metabolomics, functional assays, food intake and food composition) is tailored to nutrition research and embedded in an environment of standard procedures and protocols, annotations, modular data-basing, networking and integrated bioinformatics. The dbNP is an evolving enterprise, which is only sustainable if it is accepted and adopted by the wider nutrition and health research community as an open source, pre-competitive and publicly available resource where many partners both can contribute and profit from its developments. We introduce the Nutrigenomics Organisation (NuGO, http://www.nugo.org) as a membership association responsible for establishing and curating the dbNP. Within NuGO, all efforts related to dbNP (i.e. usage, coordination, integration, facilitation and maintenance) will be directed towards a sustainable and federated infrastructure. C1 [van Ommen, Ben; Bouwman, Jildau; Radonjic, Marijana; Wopereis, Suzan] TNO Qual Life, NL-6700 AJ Zeist, Netherlands. [Dragsted, Lars O.] Univ Copenhagen, Inst Human Nutr, DK-1958 Frederiksberg C, Denmark. [Drevon, Christian A.] Univ Oslo, Inst Basic Med Sci, Fac Med, Dept Nutr, Oslo, Norway. [Elliott, Ruan] Inst Food Res, Norwich NR4 7UA, Norfolk, England. [de Groot, Philip; Mueller, Michael] TI Food & Nutr, Nutrigenom Consortium, NL-6700 AN Wageningen, Netherlands. [de Groot, Philip; Mueller, Michael; Pepping, Fre] Wageningen Univ, Div Human Nutr, NL-6700 EV Wageningen, Netherlands. [Kaput, Jim] Natl Ctr Toxicol Res, Div Personalized Nutr & Med, US FDA, Jefferson, AR 72079 USA. [Mathers, John C.] Newcastle Univ, Inst Ageing & Hlth, Human Nutr Res Ctr, Newcastle Upon Tyne NE44 6HE, Tyne & Wear, England. [Saito, Jahn; Evelo, Chris T.] Maastricht Univ, Dept Bioinformat BiGCaT, Maastricht, Netherlands. [Saito, Jahn] Maastricht Univ, DKE, Maastricht, Netherlands. [Scalbert, Augustin] INRA, Unite Nutr Humaine, Ctr Rech Clermont Ferrand Theix, UMR 1019, F-63122 St Genes Champanelle, France. [Rocca-Serra, Philippe] European Bioinformat Inst, Microarray Informat Team, Cambridge, England. [Travis, Anthony] Univ Aberdeen, Rowett Inst Nutr & Hlth, Aberdeen AB21 9SB, Scotland. RP van Ommen, B (reprint author), TNO Qual Life, POB 360, NL-6700 AJ Zeist, Netherlands. EM ben.vanommen@tno.nl; jildau.bouwman@tno.nl; ldra@life.ku.dk; c.a.drevon@medisin.uio.no; James.Kaput@fda.hhs.gov; john.mathers@ncl.ac.uk; jsaito@bigcat.unimaas.nl; scalbert@clermont.inra.fr; marijana.radonjic@tno.nl; rocca@ebi.ac.uk; a.travis@abdn.ac.uk; suzan.wopereis@tno.nl; chris.evelo@bigcat.unimaas.nl RI Drevon, Christian /F-6012-2010; Muller, Michael/B-5795-2008; Dragsted, Lars/N-3384-2014; Evelo, Chris/D-2914-2009; OI Muller, Michael/0000-0002-5930-9905; Dragsted, Lars/0000-0003-0609-6317; Evelo, Chris/0000-0002-5301-3142; Mathers, John/0000-0003-3406-3002 FU The European Nutrigenomics Organisation; The Netherlands Nutrigenomics Consortium; The Netherlands Metabolomics Center; The EU FP6 Network of Excellence Eurreca; EU FX Work on dbNP is currently funded primarily from the following sources: The European Nutrigenomics Organisation (http://www.nugo.org). The Netherlands Nutrigenomics Consortium (http://www.nutrigenomicsconsortium.nl). The Netherlands Metabolomics Center (http://www.metabolomicscentre.nl/). The EU FP6 Network of Excellence Eurreca (http://www.eurreca.org). It is emphasized that dbNP is an open source project, with many individual contributions, not specifically linked to research projects. NR 37 TC 39 Z9 41 U1 2 U2 18 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1555-8932 J9 GENES NUTR JI Genes Nutr. PD SEP PY 2010 VL 5 IS 3 BP 189 EP 203 DI 10.1007/s12263-010-0167-9 PG 15 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 648DS UT WOS:000281671200002 PM 21052526 ER PT J AU Penn, L Boeing, H Boushey, CJ Dragsted, LO Kaput, J Scalbert, A Welch, AA Mathers, JC AF Penn, Linda Boeing, Heiner Boushey, Carol J. Dragsted, Lars Ove Kaput, Jim Scalbert, Augustin Welch, Ailsa A. Mathers, John C. TI Assessment of dietary intake: NuGO symposium report SO GENES AND NUTRITION LA English DT Review DE Dietary intake; Assessment; Nutrigenomics; Phenotype; Exposure ID QUESTIONNAIRE; TECHNOLOGY; POPULATION; NUTRITION; BIOMARKER; RECALL; CAMERA; COHORT AB Advances in genomics science and associated bioinformatics and technology mean that excellent tools are available for characterising human genotypes. At the same time, approaches for characterising individual phenotypes are developing rapidly. In contrast, there has been much less investment in novel methodology for measuring dietary exposures so that there is now a significant gap in the toolkit for those investigating how diet interacts with genotype to determine phenotype. This symposium reviewed the strengths and limitations of current tools used in assessment of dietary intake and the potential to improve these tools through, for example, the use of statistical techniques that combine information from different sources (such as modelling and calibration methods) to ameliorate measurement error and to provide validity checks. Speakers examined the use of approaches based on technologies such as mobile 'phones, digital cameras and Web-based systems which offer the potential for more acceptable (for study participants) and less laborious (for researchers and participants) routes to more robust data collection. In addition, the application of omics, especially metabolomics, tools to biofluids to identify new biomarkers of intake offers great potential to provide objective measures of food consumption with the advantage that data may be collected in forms that can be integrated readily with other high throughput (nutrigenomic) technologies. C1 [Penn, Linda; Mathers, John C.] Newcastle Univ, Inst Ageing & Hlth, Human Nutr Res Ctr, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Boeing, Heiner] German Inst Human Nutr, Dept Epidemiol, Potsdam, Germany. [Boushey, Carol J.] Purdue Univ, Dept Foods & Nutr, W Lafayette, IN 47907 USA. [Dragsted, Lars Ove] Univ Copenhagen, Dept Human Nutr, Fac Life Sci, Copenhagen, Denmark. [Kaput, Jim] Natl Ctr Toxicol Res, Div Personalized Nutr & Med, US FDA, Jefferson, AR 72079 USA. [Scalbert, Augustin] INRA, Unite Nutr Humaine, UMR 1019, F-63122 St Genes Champanelle, France. [Welch, Ailsa A.] Univ E Anglia, Sch Med, Diet & Hlth Grp, Norwich NR4 7TJ, Norfolk, England. RP Penn, L (reprint author), Newcastle Univ, Inst Ageing & Hlth, Human Nutr Res Ctr, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. EM l.d.penn@ncl.ac.uk RI Dragsted, Lars/N-3384-2014; OI Dragsted, Lars/0000-0003-0609-6317; Mathers, John/0000-0003-3406-3002 FU Nordforsk; Nordic Council of Ministers FX The European Nutrigenomics Organisation (NuGO): linking genomics, nutrition and health research, is a European funded Network of Excellence. NuGO was founded in January 2004 and there are currently 23 NuGO partner organisations from 10 European countries. This symposium on assessment of dietary intake was organised by NuGO Work Package Protocols and Procedures and held on 1st September 2009 in Montecatini Terme, Italy, as part of NuGO week 2009. The views of the authors do not reflect those of the FDA. LOD was supported in part by a Grant from Nordforsk, the Nordic Council of Ministers, for the Nordic Centre of Excellence on Systems biology in controlled dietary interventions and cohort studies (SYSDIET). NR 27 TC 28 Z9 31 U1 2 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1555-8932 J9 GENES NUTR JI Genes Nutr. PD SEP PY 2010 VL 5 IS 3 BP 205 EP 213 DI 10.1007/s12263-010-0175-9 PG 9 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 648DS UT WOS:000281671200003 PM 21052527 ER PT J AU Mandal, B Roe, BE Fein, SB AF Mandal, Bidisha Roe, Brian Eric Fein, Sara Beck TI The differential effects of full-time and part-time work status on breastfeeding SO HEALTH POLICY LA English DT Article DE Full-time work; Part-time work; Breastfeeding initiation; Breastfeeding duration ID SUPPLEMENTAL NUTRITION PROGRAM; UNITED-STATES; MATERNAL EMPLOYMENT; HUMAN-MILK; DURATION; WOMEN; INITIATION; LEAVE; POSTPARTUM; INFANTS AB Objectives: Return to work is associated with diminished breastfeeding. Although more mothers breastfeed after returning to work compared to a decade ago, research has not documented the variations in breastfeeding initiation and duration based on full-time and part-time (less than 35 h/week) work status. In this study, we clarify these differences. Methods: Longitudinal data from the Infant Feeding Practices Study II. collected between 2005 and 2007, for over 1400 mothers are used. In analyzing initiation, mother's work status was categorized by the expected number of hours she planned to work postpartum. In the duration model, work status was categorized based on the actual number of hours worked upon mother's return to employment after controlling for baby's age when she returned to work. Covariates in logistic and censored regressions included demographics, maternity leave, parity, past breastfeeding experience, hospital experience, and social support. Results: Compared with expecting not to work, expecting to work <35 h/week was not associated with breastfeeding initiation while expecting to work full-time decreased breastfeeding initiation. Compared with breastfeeding mothers who did not work, returning to work within 12 weeks regardless of work status and returning to work after 12 weeks while working more than 34 h/week were associated with significantly shorter breastfeeding duration. Conclusion: Part-time work and increased amount of leave taken promote breastfeeding initiation and duration. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Mandal, Bidisha] Washington State Univ, Sch Econ Sci, Pullman, WA 99164 USA. [Fein, Sara Beck] US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. [Roe, Brian Eric] Ohio State Univ, Dept Agr Environm & Dev Econ, Columbus, OH 43210 USA. RP Mandal, B (reprint author), Washington State Univ, Sch Econ Sci, POB 646210,Hulbert Hall 103F, Pullman, WA 99164 USA. EM bmandal@wsu.edu RI Roe, Brian/A-7386-2009 OI Roe, Brian/0000-0003-4228-2889 NR 40 TC 33 Z9 34 U1 0 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8510 J9 HEALTH POLICY JI Health Policy PD SEP PY 2010 VL 97 IS 1 BP 79 EP 86 DI 10.1016/j.healthpol.2010.03.006 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 639RQ UT WOS:000280992600011 PM 20400199 ER PT J AU Venkatasubramanian, KK Gupta, SKS Jetley, RP Jones, PL AF Venkatasubramanian, K. K. Gupta, S. K. S. Jetley, R. P. Jones, P. L. TI Interoperable Medical Devices SO IEEE PULSE LA English DT Article C1 [Gupta, S. K. S.] Arizona State Univ, IMPACT Lab, Sch Comp Informat & Decis Syst Engn, Tempe, AZ USA. [Jetley, R. P.; Jones, P. L.] US FDA, Div Elect & Software Engn, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Venkatasubramanian, KK (reprint author), Univ Penn, Dept Comp & Informat Sci, 200 S 33Rd St, Philadelphia, PA 19104 USA. EM vkris@cis.upenn.edu; sandeep.gupta@asu.edu; raoul.jetley@fda.hhs.gov; paull.jones@fda.hhs.gov FU NSF [CNS-0617671] FX This work was done when the primary author was volunteering at the FDA. The work is partly funded by NSF grant CNS-0617671. NR 36 TC 4 Z9 4 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 2154-2287 J9 IEEE PULSE JI IEEE Pulse PD SEP-OCT PY 2010 VL 1 IS 2 BP 16 EP 27 DI 10.1109/MPUL.2010.937905 PG 12 WC Engineering, Biomedical SC Engineering GA V24SI UT WOS:000208429700005 ER PT J AU Miller, HI Carpenter, D AF Miller, Henry I. Carpenter, Daniel TI Reputation and Power: Organizational Image and Pharmaceutical Regulation at the FDA SO ISSUES IN SCIENCE AND TECHNOLOGY LA English DT Book Review C1 [Miller, Henry I.] Stanford Univ, Hoover Inst, Stanford, CA 94305 USA. [Miller, Henry I.] US FDA, Rockville, MD 20857 USA. [Miller, Henry I.] Stanford Univ, Competit Enterprise Inst, Stanford, CA 94305 USA. EM henry.miller@stanford.edu NR 1 TC 0 Z9 0 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0748-5492 J9 ISSUES SCI TECHNOL JI Issues Sci. Technol. PD FAL PY 2010 VL 27 IS 1 BP 89 EP 92 PG 4 WC Engineering, Multidisciplinary; Engineering, Industrial; Multidisciplinary Sciences; Social Issues SC Engineering; Science & Technology - Other Topics; Social Issues GA 676MC UT WOS:000283914700033 ER PT J AU Heller, DN Lehotay, SJ Martos, PA Hammack, W Fernandez-Alba, AR AF Heller, David N. Lehotay, Steven J. Martos, Perry A. Hammack, Walter Fernandez-Alba, Amaneo R. TI Issues in Mass Spectrometry Between Bench Chemists and Regulatory Laboratory Managers: Summary of the Roundtable on Mass Spectrometry Held at the 123rd AOAC INTERNATIONAL Annual Meeting SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID CHROMATOGRAPHY; RESIDUES; FOOD AB At the 123rd AOAC INTERNATIONAL Annual Meeting in Philadelphia, PA, 45 residue chemists gathered for a roundtable discussion of mass spectrometry (MS) used for regulatory chemical residues analysis. The session was conceived to address current technical and communication issues about MS between "bench chemists and their bosses." The topics covered a range of practical, routine, and recurring issues on capabilities and limitations of MS techniques, and suggestions on how chemists may better communicate their MS results with customers. The customers in this sense include laboratory managers, quality assurance officers, laboratory clients, regulatory officials, policy-makers, lawyers, and others who have interest in the data. The stated goals devised by the roundtable panelists were to provide independent advice, describe limitations, give practical tips, help set realistic expectations, and answer questions from the attendees. The panelists divided the topics into three main themes: practical aspects in routine analysis using MS, choice of MS technique depending on the purpose for analysis, and qualitative identification and confirmation concepts. This report was written to summarize and expand upon the discussion, frame the current issues, and provide advice on handling common situations in MS analysis and reporting of results. Topics included LODs, data quality objectives, quantification and reporting results, matrix effects, calibration, terminology, differences in performance across MS platforms, proficiency testing, qualitative analysis, and laboratory accreditation. Conclusions are presented as a set of questions for structuring a dialog between bench chemists and laboratory managers. C1 [Heller, David N.] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [Lehotay, Steven J.] ARS, USDA, Eastern Reg Res Ctr, Wyndmoor, PA 19038 USA. [Martos, Perry A.] Univ Guelph Agr & Food Lab, W Guelph, ON N1H 8J7, Canada. [Hammack, Walter] Florida Dept Agr & Consumer Serv, Tallahassee, FL 32399 USA. [Fernandez-Alba, Amaneo R.] Univ Almeria, Fac Expt Sci, Dept Hydrogeol & Analyt Chem, Almeria 04071, Spain. RP Heller, DN (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM david.heller@fda.hhs.gov NR 12 TC 13 Z9 13 U1 0 U2 9 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2010 VL 93 IS 5 BP 1625 EP 1632 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 679WG UT WOS:000284190900035 PM 21140676 ER PT J AU Bibb, LA Schmitt, MP AF Bibb, Lori A. Schmitt, Michael P. TI The ABC Transporter HrtAB Confers Resistance to Hemin Toxicity and Is Regulated in a Hemin-Dependent Manner by the ChrAS Two-Component System in Corynebacterium diphtheriae SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SIGNAL-TRANSDUCTION SYSTEM; STAPHYLOCOCCUS-AUREUS; IRON ACQUISITION; TOXIN REPRESSOR; HMUO PROMOTER; DTXR; SIDEROPHORE; EXPRESSION; PROTEIN; GENE AB Corynebacterium diphtheriae, the causative agent of the severe respiratory disease diphtheria, utilizes hemin and hemoglobin as iron sources for growth in iron-depleted environments. Because of the toxicity of high levels of hemin and iron, these compounds are often tightly regulated in bacterial systems. In this report, we identify and characterize the C. diphtheriae hrtAB genes, which encode a putative ABC type transporter involved in conferring resistance to the toxic effects of hemin. Deletion of the hrtAB genes in C. diphtheriae produced increased sensitivity to hemin, which was complemented by a plasmid harboring the cloned hrtAB locus. The HrtAB system was not involved in the uptake and use of hemin as an iron source. The hrtAB genes are located on the C. diphtheriae genome upstream from the chrSA operon, which encodes a previously characterized two-component signal transduction system that regulates gene expression in a heme-dependent manner. The hrtB promoter is activated by the ChrAS system in the presence of hemin or hemoglobin, and mutations in the chrSA genes abolish heme-activated expression from the hrtB promoter. It was also observed that transcription from the hrtB promoter is reduced in a dtxR deletion mutant, suggesting that DtxR is required for optimal expression of hrtAB. Previous studies proposed that the ChrS sensor kinase may be responsive to an environmental signal, such as hemin. We show that specific point mutations in the ChrS N-terminal transmembrane domain result in a reduced ability to activate the hrtB promoter in the presence of a heme source, suggesting that this putative sensor region is essential for the detection of a signal produced in response to hemin exposure. This study shows that the HrtAB system is required for protection from hemin toxicity and that expression of the hrtAB genes is regulated by the ChrAS two-component system. This study demonstrates a direct correlation between the detection of heme or a heme-associated signal by the N-terminal sensor domain of ChrS and the transcriptional activation of the hrtAB genes. C1 [Bibb, Lori A.; Schmitt, Michael P.] US FDA, Lab Resp & Special Pathogens, DBPAP, CBER, Bethesda, MD 20892 USA. RP Schmitt, MP (reprint author), US FDA, Lab Resp & Special Pathogens, DBPAP, CBER, Bldg 29,Room 108,8800 Rockville Pike, Bethesda, MD 20892 USA. EM michael.schmitt@fda.hhs.gov NR 51 TC 25 Z9 25 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 2010 VL 192 IS 18 BP 4606 EP 4617 DI 10.1128/JB.00525-10 PG 12 WC Microbiology SC Microbiology GA 643VO UT WOS:000281327900009 PM 20639324 ER PT J AU Lyle, DB Breger, JC Baeva, LF Shallcross, JC Durfor, CN Wang, NS Langone, JJ AF Lyle, Daniel B. Breger, Joyce C. Baeva, Larissa F. Shallcross, Jonathan C. Durfor, Charles N. Wang, Nam Sun Langone, John J. TI Low molecular weight hyaluronic acid effects on murine macrophage nitric oxide production SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE biomaterials; nitric oxide; inflammation; macrophage; hyaluronic acid ID NF-KAPPA-B; RAT ALVEOLAR MACROPHAGES; CHEMOKINE GENE-EXPRESSION; MOUSE MACROPHAGES; FRAGMENTS INDUCE; CELL-DEATH; IFN-GAMMA; TECHNICAL CONSIDERATIONS; ARTICULAR CHONDROCYTES; INTERFERON-GAMMA AB Hyaluronic acid (HA) is increasingly used for a number of medical device applications. Since the chemical structure of HA is identical no matter its bacterial or animal origin, it should be the ideal biomaterial. However, short term transient inflammatory reactions are common, while rare long-term adverse events may correlate with subclinical chronic inflammation. Concern has been raised that low molecular weight components or degradation fragments from implanted HA may directly stimulate inflammatory reactions. This study examined a panel of HA molecular weights from the unitary disaccharide up to 1.7 x 10(6) Dalton lengths, in which endotoxin was assayed at a very low level (less than 0.03 EU/mg). The murine cell line RAW 264.7, rat splenocytes, and rat adherent differentiated primary macrophages were assayed for nitric oxide production under a variety of inflammatory conditions plus or minus HA. Under the highest inflammatory states, nitric oxide production was mildly suppressed by HMW-HA while slightly augmented by LMW-HA at mg/mL concentrations. However, at micromolar concentrations fragments below 5000 Daltons, thought to have drug-like qualities, were without effect. These data support the hypothesis that if endotoxin is reduced to an extremely low level, LMW-HA may not directly provoke normal tissue macrophage-mediated inflammatory reactions. (C) 2010 Wiley Periodicals, Inc.* J Biomed Mater Res Part A: 94A: 893-904, 2010 C1 [Lyle, Daniel B.; Breger, Joyce C.; Baeva, Larissa F.; Shallcross, Jonathan C.; Durfor, Charles N.; Langone, John J.] US FDA, Ctr Devices & Radiol Hlth, Off Sci, Silver Spring, MD 20993 USA. [Lyle, Daniel B.; Breger, Joyce C.; Baeva, Larissa F.; Shallcross, Jonathan C.; Durfor, Charles N.; Langone, John J.] US FDA, Engn Labs, Silver Spring, MD 20993 USA. [Breger, Joyce C.; Wang, Nam Sun] Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA. RP Langone, JJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM john.langone@fda.hhs.gov RI Wang, Nam Sun/E-4253-2016 NR 85 TC 10 Z9 12 U1 1 U2 11 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1549-3296 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD SEP 1 PY 2010 VL 94A IS 3 BP 893 EP 904 DI 10.1002/jbm.a.32760 PG 12 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 633WA UT WOS:000280536300026 PM 20336750 ER PT J AU Farb, A AF Farb, Andrew TI From histology to computed tomography: Every picture tells a story SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Editorial Material C1 US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Farb, A (reprint author), US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,WO66-1116, Silver Spring, MD 20993 USA. EM andrew.farb@fda.hhs.gov NR 13 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD SEP-OCT PY 2010 VL 4 IS 5 BP 309 EP 311 DI 10.1016/j.jcct.2010.08.001 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA V26BS UT WOS:000208521700004 PM 20801734 ER PT J AU Zou, W Lin, WJ Foley, SL Chen, CH Nayak, R Chen, JJ AF Zou, Wen Lin, Wei-Jiun Foley, Steven L. Chen, Chun-Houh Nayak, Rajesh Chen, James J. TI Evaluation of Pulsed-Field Gel Electrophoresis Profiles for Identification of Salmonella Serotypes SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID MICROARRAY DATA; FOOD ANIMALS; ENTERICA; PCR; CLASSIFICATION; ENTERITIDIS; HEIDELBERG; SWINE AB Pulsed-field gel electrophoresis (PFGE) is a standard typing method for isolates from Salmonella outbreaks and epidemiological investigations. Eight hundred sixty-six Salmonella enterica isolates from eight serotypes, including Heidelberg (n = 323), Javiana (n = 200), Typhimurium (n = 163), Newport (n = 93), Enteritidis (n = 45), Dublin (n = 25), Pullorum (n = 9), and Choleraesuis (n = 8), were subjected to PFGE, and their profiles were analyzed by random forest classification and compared to conventional hierarchical cluster analysis to determine potential predictive relationships between PFGE banding patterns and particular serotypes. Cluster analysis displayed only the underlying similarities and relationships of the isolates from the eight serotypes. However, for serotype prediction of a nonserotyped Salmonella isolate from its PFGE pattern, random forest classification provided better accuracy than conventional cluster analysis. Discriminatory DNA band class markers were identified for distinguishing Salmonella serotype Heidelberg, Javiana, Typhimurium, and Newport isolates. C1 [Zou, Wen; Lin, Wei-Jiun; Chen, James J.] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Foley, Steven L.; Nayak, Rajesh] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Chen, Chun-Houh] Acad Sinica, Inst Stat Sci, Taipei 11529, Taiwan. [Chen, James J.] China Med Univ, Grad Inst Biostat, Taichung, Taiwan. RP Chen, JJ (reprint author), US FDA, Div Personalized Nutr & Med HFT 20, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM jamesj.chen@fda.hhs.gov FU Oak Ridge Institute for Science and Education FX Wei-Jiun Lin acknowledges support of a fellowship from the Oak Ridge Institute for Science and Education, administered through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 20 TC 27 Z9 27 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 2010 VL 48 IS 9 BP 3122 EP 3126 DI 10.1128/JCM.00645-10 PG 5 WC Microbiology SC Microbiology GA 645QZ UT WOS:000281480400012 PM 20631109 ER PT J AU Romero, K Corrigan, B Tornoe, CW Gobburu, JV Danhof, M Gillespie, WR Gastonguay, MR Meibohm, B Derendorf, H AF Romero, Klaus Corrigan, Brian Tornoe, Christoffer W. Gobburu, Jogarao V. Danhof, Meindert Gillespie, William R. Gastonguay, Marc R. Meibohm, Bernd Derendorf, Hartmut TI Pharmacometrics as a Discipline Is Entering the "Industrialization" Phase: Standards, Automation, Knowledge Sharing, and Training Are Critical for Future Success SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID DRUG DEVELOPMENT; QUANTITATIVE PHARMACOLOGY; CLINICAL-PHARMACOLOGY; LABELING DECISIONS; CRITICAL PATH; MODEL; DISEASE; ALZHEIMERS; APPROVAL; IMPACT C1 [Romero, Klaus] Crit Path Inst, Coalit Major Dis, Tucson, AZ 85718 USA. [Corrigan, Brian] Pfizer, New London, CT USA. [Tornoe, Christoffer W.; Gobburu, Jogarao V.] US FDA, Div Pharmacometr, Silver Spring, MD USA. [Danhof, Meindert] Leiden Univ, Leiden Amsterdam Ctr Drug Res, Leiden, Netherlands. [Danhof, Meindert] Top Inst Pharma, Leiden, Netherlands. [Gillespie, William R.; Gastonguay, Marc R.] Metrum Inst, Tariffville, CT USA. [Meibohm, Bernd] Univ Tennessee, Ctr Hlth Sci, Coll Pharm, Memphis, TN 38163 USA. [Derendorf, Hartmut] Univ Florida, Gainesville, FL USA. RP Romero, K (reprint author), Crit Path Inst, Coalit Major Dis, 1730 E River Rd 200, Tucson, AZ 85718 USA. EM kromero@c-path.org RI Derendorf, Hartmut/B-4628-2012 OI Derendorf, Hartmut/0000-0003-4016-1370 FU American Conference on Pharmacometrics FX The articles in this supplement are sponsored by the American Conference on Pharmacometrics. NR 28 TC 5 Z9 5 U1 2 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2010 VL 50 IS 9 SU S BP 9S EP 19S DI 10.1177/0091270010377788 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 650OZ UT WOS:000281860400003 PM 20881213 ER PT J AU Jadhav, PR Neal, L Florian, J Chen, Y Naeger, L Robertson, S Soon, G Birnkrant, D AF Jadhav, Pravin R. Neal, Lauren Florian, Jeff Chen, Ying Naeger, Lisa Robertson, Sarah Soon, Guoxing Birnkrant, Debra TI Antiviral Information Management System (AIMS): A Prototype for Operational Innovation in Drug Development SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE Drug development; knowledge management; hepatitis C virus (HCV); pharmacometrics; Antiviral Information Management System (AIMS); structural database; clinical trial simulations, learn-apply AB This article presents a prototype for an operational innovation in knowledge management (KM). These operational innovations are geared toward managing knowledge efficiently and accessing all available information by embracing advances in bioinformatics and allied fields. The specific components of the proposed KM system are (1) a database to archive hepatitis C virus (HCV) treatment data in a structured format and retrieve information in a query-capable manner and (2) an automated analysis tool to inform trial design elements for HCV drug development. The proposed framework is intended to benefit drug development by increasing efficiency of dose selection and improving the consistency of advice from US Food and Drug Administration (FDA). It is also hoped that the framework will encourage collaboration among FDA, industry, and academic scientists to guide the HCV drug development process using model-based quantitative analysis techniques. C1 [Jadhav, Pravin R.; Neal, Lauren; Florian, Jeff; Chen, Ying; Naeger, Lisa; Robertson, Sarah; Soon, Guoxing; Birnkrant, Debra] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20093 USA. RP Jadhav, PR (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51,Rm 3160, Silver Spring, MD 20093 USA. EM Pravin.Jadhav@fda.hhs.gov FU FDA's Critical Path Initiative; American Conference on Pharmacometrics FX Funding for this project was provided by the FDA's Critical Path Initiative. The articles in this supplement are sponsored by the American Conference on Pharmacometrics. NR 8 TC 7 Z9 7 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2010 VL 50 IS 9 SU S BP 50S EP 55S DI 10.1177/0091270010376771 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 650OZ UT WOS:000281860400007 PM 20881217 ER PT J AU Jadhav, PR Kern, SE AF Jadhav, Pravin R. Kern, Steven E. TI The Need for Modeling and Simulation to Design Clinical Investigations in Children SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE Clinical pharmacology; clinical trials; pediatrics; pharmacokinetics and drug metabolism; pharmacodynamics; regulatory/scientific affairs ID CONGESTIVE-HEART-FAILURE; POPULATION PHARMACOKINETICS; HYPERTENSIVE CHILDREN; CANDESARTAN CILEXETIL; PEDIATRIC-PATIENTS; DRUG DEVELOPMENT; YOUNG INFANTS; CARVEDILOL; TRIAL; SAFETY AB Recent legislation in the United States and Europe has resulted in an increased number of clinical trials of pharmaceutical agents in children. Creating a well-designed clinical trial that can be successfully completed is a challenging task, particularly as the study population includes younger and smaller children. Although there are some established principles for initially estimating appropriate doses of pharmaceutical agents in children based on known effective doses in adults, these rules are inadequate as the sole basis for designing a clinical trial in children. Factors such as maturation of metabolizing enzymes, relative physical maturation of the child, and altered absorption because of physiological differences in adults and children may contribute to alterations in the dose-exposure relationship. To account for the impact of these potential factors on a clinical trial, the use of modeling and simulation is necessary to anticipate the influence these variables can have on the desired clinical question to be addressed. The examples presented in this article highlight the principle that modeling and simulation is critical for adequately designing pediatrics trials. C1 [Kern, Steven E.] Univ Utah, Dept Pharmaceut & Pharmaceut Chem, Pediat Pharmacol Program, Salt Lake City, UT 84108 USA. [Jadhav, Pravin R.] Food & Drug Adm, Div Pharmacometr, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Kern, SE (reprint author), Univ Utah, Dept Pharmaceut & Pharmaceut Chem, Pediat Pharmacol Program, 421 Wakara Way,Suite 318, Salt Lake City, UT 84108 USA. EM steven.kern@utah.edu FU American Conference on Pharmacometrics FX The articles in this supplement are sponsored by the American Conference on Pharmacometrics. NR 30 TC 11 Z9 11 U1 2 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 SEP PY 2010 VL 50 IS 9 SU S BP 121S EP 129S DI 10.1177/0091270010376968 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 650OZ UT WOS:000281860400015 PM 20881225 ER PT J AU Gobburu, JVS AF Gobburu, Jogarao V. S. TI Pharmacometrics 2020 SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE Clinical pharmacology; clinical trials; pharmaceutical research and development; regulatory/scientific affairs; pharmacodynamics ID DRUG DEVELOPMENT; PHARMACOKINETICS; IMPACT; MODEL; PHARMACODYNAMICS; INTEGRATION; EXPERIENCE; DECISIONS; KINETICS AB This special issue of the Journal of Clinical Pharmacology is dedicated to pharmacometrics, covering topics related to methodological research, application to decisions, standardization, PhRMA survey, and growth strategy. Innovative methodological and technological advances in analyzing disease, drug, and trial data have equipped pharmacometricians with the know-how to influence high-level decisions, which in turn creates more pharmacometric opportunities. Pharmacometrics is revolutionizing drug development and regulatory decision making. To sustain the success and growth of this field, we need to up the ante. Strategic goals for pharmacometric groups in industry, regulatory agencies, and academia are proposed in this report. These goals should be of significance to all stakeholders who have a vested interest in drug development and therapeutics. The future of pharmacometrics depends on how well we all can deliver on the strategic goals. C1 [Gobburu, Jogarao V. S.] Food & Drug Adm, Ctr Drug Evaluat & Res, Div Pharmacometr, Off Clin Pharmacol, Silver Spring, MD USA. RP Gobburu, JVS (reprint author), 10903 New Hampshire Ave,Bldg 51,Rm 3186, Silver Spring, MD 20993 USA. EM jogarao.gobburu@fda.hhs.gov FU American Conference on Pharmacometrics FX The articles in this supplement are sponsored by the American Conference on Pharmacometrics. NR 31 TC 13 Z9 14 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2010 VL 50 IS 9 SU S BP 151S EP 157S DI 10.1177/0091270010376977 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 650OZ UT WOS:000281860400019 PM 20881229 ER PT J AU Agarwal, S Zhang, L Huang, SM AF Agarwal, Sheetal Zhang, Lei Huang, Shiew-Mei TI REVIEW OF TRANSPORTER INFORMATION IN RECENTLY APPROVED NEW DRUG APPLICATION (NDAs) SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 39th Annual Meeting on American-College-of-Clinical-Pharmacology CY SEP 12-14, 2010 CL Baltimore, MD SP Amer coll Pharmacol C1 [Agarwal, Sheetal; Zhang, Lei; Huang, Shiew-Mei] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2010 VL 50 IS 9 MA 53 BP 1068 EP 1068 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 650OD UT WOS:000281858000049 ER PT J AU Zhang, LJ Zhang, L Amur, S Siegel, J Ding, X Lau, O Rochester, G Tornoe, CW Doddapaneni, S Sahajwalla, C Nallani, SC AF Zhang, Lijun Zhang, Li Amur, Shashi Siegel, Jeff Ding, Xiao Lau, Olivia Rochester, George Tornoe, Christoffer W. Doddapaneni, Suresh Sahajwalla, Chandrahas Nallani, Srikanth C. TI BIOMARKERS FOR EARLY TREATMENT RESPONSE TO BIOLOGICS IN TREATMENT OF RHEUMATOID ARTHRITIS. SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 39th Annual Meeting on American-College-of-Clinical-Pharmacology CY SEP 12-14, 2010 CL Baltimore, MD SP Amer coll Pharmacol C1 [Zhang, Lijun; Doddapaneni, Suresh; Sahajwalla, Chandrahas; Nallani, Srikanth C.] Div Clin Pharmacol, Silver Spring, MD USA. [Zhang, Li; Amur, Shashi] Genom Grp, Silver Spring, MD USA. [Siegel, Jeff] Div Anesthesia Analgesia & Rheumatol Prod, Silver Spring, MD USA. [Ding, Xiao; Lau, Olivia; Rochester, George] Off Biostatist, Silver Spring, MD USA. [Tornoe, Christoffer W.] Food & Drug Adm, CDER, Div Pharmacometr, 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 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2010 VL 50 IS 9 MA 114 BP 1083 EP 1083 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 650OD UT WOS:000281858000109 ER PT J AU Chaurasia, CS Raines-Isler, KW Conner, DP Davit, BM AF Chaurasia, Chandra S. Raines-Isler, Kimberley W. Conner, Dale P. Davit, Barbara M. TI ISSUES AND CHALLENGES IN THE DEVELOPMENT OF TRANSDERMAL DRUG DELIVERY SYSTEM SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 39th Annual Meeting on American-College-of-Clinical-Pharmacology CY SEP 12-14, 2010 CL Baltimore, MD SP Amer coll Pharmacol C1 [Chaurasia, Chandra S.; Raines-Isler, Kimberley W.; Conner, Dale P.; Davit, Barbara M.] US FDA, Off Gener Drugs, Div Bioequivalence, Rockville, MD 20855 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 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2010 VL 50 IS 9 MA 126 BP 1086 EP 1086 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 650OD UT WOS:000281858000121 ER PT J AU Laughren, TP AF Laughren, Thomas P. TI What's Next After 50 Years of Psychiatric Drug Development: An FDA Perspective SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID CLINICAL-TRIALS; ADMINISTRATION PERSPECTIVE; DOUBLE-BLIND; SCHIZOPHRENIA; FOOD; DISORDERS; CARBAMAZEPINE; SUICIDALITY; ILLNESS; RISK AB This article discusses changes in psychiatric drug development from a US Food and Drug Administration (FDA) standpoint. It first looks back at changes that have been influenced by regulatory process and then looks forward at FDA initiatives that are likely to affect psychiatric drug development in the future. FDA protects the public health by ensuring the safety and efficacy of drug products introduced into the US market. FDA works with drug sponsors during development, and, when applications are submitted, reviews the safety and efficacy data and the proposed labeling. Drug advertising and promotion and postmarketing surveillance also fall within FDA's responsibility. Among the many changes in psychiatric drug development over the past 50 years, several have been particularly influenced by FDA. Populations studied have expanded diagnostically and demographically, and approved psychiatric indications have become more focused on the clinical entities actually studied, including in some cases specific symptom domains of recognized syndromes. Trial designs have become increasingly complex and informative, and approaches to data analysis have evolved to better model the reality of clinical trials. This article addresses 2 general areas of innovation at FDA that will affect psychiatric drug development in years to come. Several programs falling under the general heading of the Critical Path Initiative, ie, biomarkers, adaptive design, end-of-phase 2A meetings, and data standards, are described. In addition, a number of important safety initiatives, including Safety First, the Sentinel Initiative, the Safe Use Initiative, and meta-analysis for safety, are discussed. J Clin Psychiatry 2010;71(9):1196 1204 (C) Copyright 2010 Physicians Postgraduate Press, Inc. C1 US FDA, Div Psychiat Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Laughren, TP (reprint author), US FDA, Div Psychiat Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM thomas.laughren@fda.hhs.gov NR 45 TC 13 Z9 13 U1 2 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 2010 VL 71 IS 9 BP 1196 EP 1204 DI 10.4088/JCP.10m06262gry PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 661EF UT WOS:000282705700012 PM 20923624 ER PT J AU Deer, DM Lampel, KA AF Deer, Deanne M. Lampel, Keith A. TI Development of a Multiplex Real-Time PCR Assay with Internal Amplification Control for the Detection of Shigella Species and Enteroinvasive Escherichia coli SO JOURNAL OF FOOD PROTECTION LA English DT Article ID GLOBAL BURDEN; STRATEGIES; INFECTION; SEQUENCE; OUTBREAK; LETTUCE; SONNEI; SPP. AB Shigella species, particularly S sonnei and S flexneri remain some of the leading, bacterial etiological agents of gastrointestinal diseases in the United States and globally The isolation and detection of these foodborne pathogens are critical or preventing the spread of disease and facilitating epidemiological investigations aimed at determining the source of a Shigella infection outbreak A multiplex real-time PCR-based assay was developed that targets all four species of Shigella plus enteromvasive Escherichia coli The assay incorporates primers directed to the wall genes located on both the virulence plasmid and chromosome, the plasmid-encoded virulence gene mxiC. a mutated mxiC gene (mxiC(..)kan) that differentiates wild-type strains from a laboratory control strain, and an internal amplification control More than 50 isolates of all four Shigella species were tested for inclusivity and specificity of the multiplex PCR assay, and more than 30 non-Shigella isolates were tested for exclusivity of the assay The sensitivity of the assay was I to 3 CFU and 5 to 50 fg of target (total) DNA for the wall. mxiC. and matC kan gene targets. The assay performed equally well and with no measurable inhibition in the Shigella target reactions when rinsates of several high-risk produce commodities (parsley, cilantro, alfalfa sprouts. and lettuce) were added to the reactions This multiplex PCR assay is sensitive and specific and has the added dimension of discriminating all Shigella species from the positive control strain so that in any sample analysis other strains can be excluded as a source of contamination C1 [Deer, Deanne M.; Lampel, Keith A.] US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Lampel, KA (reprint author), US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 29 TC 8 Z9 9 U1 0 U2 3 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X EI 1944-9097 J9 J FOOD PROTECT JI J. Food Prot. PD SEP PY 2010 VL 73 IS 9 BP 1618 EP 1625 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 647KP UT WOS:000281617700004 PM 20828467 ER PT J AU Jones, YL Oliver, HF Deeds, JR Yancy, HF AF Jones, Yolanda L. Oliver, Haley F. Deeds, Jonathan R. Yancy, Haile F. TI Real-Time PCR Assay for the Detection of Pufferfish Products SO JOURNAL OF FOOD PROTECTION LA English DT Article ID SPECIES IDENTIFICATION; 2-DIMENSIONAL ELECTROPHORESIS; TETRODOTOXIN; FISH; MUSCLE; SHELL AB An assay was developed for the rapid detection of products containing tissues from potentially toxic pufferfish (family Tetraodontidae), as part of the U.S. Food and Drug Administration Center for Veterinary Medicine and Center for Food Safety and Applied Nutrition's charter to protect human health In this study, we developed a TaqMan assay derived from DNA barcode data (650 bp starting at the 5' end of the mitochondrial cytochrome e oxidase I gene) for the specific detection or pufferfish. The method requires only 1 h of total run time, a significant improvement over current methods, which can require 24 to 96 h for completion The probes were tested against 105 species of fish and were able to detect 20 species of pufferfish; no cross-reactivity was shown with 85 species of nonpufferfish, including 20 related species from the same order (Tetraodontiformes). These results demonstrate that this assay is suitable for the rapid and specific detection of pufferfish and that it could be a useful regulatory tool to protect human health C1 [Jones, Yolanda L.; Oliver, Haley F.; Yancy, Haile F.] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. [Oliver, Haley F.] Cornell Univ, Dept Food Sci, Ithaca, NY 14860 USA. [Deeds, Jonathan R.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Jones, YL (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkuk Rd, Laurel, MD 20708 USA. NR 27 TC 5 Z9 5 U1 3 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 SEP PY 2010 VL 73 IS 9 BP 1698 EP 1702 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 647KP UT WOS:000281617700016 PM 20828479 ER PT J AU Vesnovsky, O Casamento, JP Brooks, ME Schwerin, MR Herman, WA Pollack, SK Flack, MN Collins, BW Grossman, LW AF Vesnovsky, Oleg Casamento, Jon P. Brooks, Mary E. Schwerin, Matthew R. Herman, William A. Pollack, Steven K. Flack, Marilyn N. Collins, Betty W. Grossman, Laurence W. TI Performance Testing of Huber Needles for Coring of Port Septa SO JOURNAL OF MEDICAL DEVICES-TRANSACTIONS OF THE ASME LA English DT Article AB The Food and Drug Administration received complaints of Huber needles mating cores in the septa of ports of gastric banding devices One of these complaints represented a cluster of similar events even though no deviations from design specifications or recommended practices were subsequently identified by the manufacturer The authors conducted this comparative investigation of off the shelf Huber needles and ports from several manufacturers to determine if engineering parameters could be identified that could account for the coring complaints Huber needles from ten manufacturers were evaluated for coring using intravascular access ports from five manufacturers A detailed optical analysis was also performed to identify needle features that would possibly account for coring The majority of the tested needles performed as they should 1 e they perforated the port septa without creating cores However needles that did product cores were found to have sharp edges at the heel edge of the needle lumen the edge of the ground bevel opposite from the needle tip that opens to the inner surface of the cannula tube Manufacturing processes which dulled or rounded the sharp heel of the bevel after bevel grinding prevented coring As a result of this investigation one manufacturer voluntarily recalled their product and another manufacturer implemented coring testing as part of their quality control To prevent coring needles from entering the market as a result of manufacturing flaws optical inspection of the heel edge and coring testing should be performed as part of routine quality control [DOI 10 1115/1 4001866] C1 [Vesnovsky, Oleg; Casamento, Jon P.; Schwerin, Matthew R.; Herman, William A.; Pollack, Steven K.; Grossman, Laurence W.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Brooks, Mary E.; Flack, Marilyn N.] US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Collins, Betty W.] US FDA, Off Compliance, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Vesnovsky, O (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. NR 9 TC 2 Z9 2 U1 0 U2 2 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA SN 1932-6181 J9 J MED DEVICES JI J. Med. Devices PD SEP PY 2010 VL 4 IS 3 AR 031008 DI 10.1115/1.4001866 PG 7 WC Engineering, Biomedical SC Engineering GA 682EK UT WOS:000284383100008 ER PT J AU Labiner-Wolfe, J Lin, CTJ Verrill, L AF Labiner-Wolfe, Judith Lin, Chung-Tung Jordan Verrill, Linda TI Effect of Low-carbohydrate Claims on Consumer Perceptions about Food Products' Healthfulness and Helpfulness for Weight Management SO JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR LA English DT Article DE food labeling; low carbohydrate diet; weight ID NUTRITION INFORMATION; HEALTH CLAIMS; DIETS AB Objective: Evaluate effect of low-carbohydrate claims on consumer perceptions about food products' healthfulness and helpfulness for weight management. Design: Experiment in which participants were randomly assigned 1 of 12 front-of-package claim conditions on bread or a frozen dinner. Seven of the 12 conditions also included Nutrition Facts (NF) information. Setting: Internet. Participants: 4,320 members of a national on-line consumer panel. Intervention: Exposure to images of a food package. Main Outcome Measures: Ratings on Likert scales about perceived healthfulness, helpfulness for weight management, and caloric content. Analysis: Mean ratings by outcome measure, condition, and product were calculated. Ratings were also used as the dependent measure in analysis of variance models. Results: Participants who saw front-of-package-only conditions rated products bearing low-carbohydrate claims as more helpful for weight management and lower in calories than the same products without a claim. Those who saw the bread with low-carbohydrate claims also rated it as more healthful than those who saw no claim. When the NF label was available and products had the same nutrition profile, participants rated products with low-carbohydrate claims the same as those with no claim. Conclusions and Implications: Consumers who do not use the NF panel may interpret low-carbohydrate claims to have meaning beyond the scope of the claim itself. C1 [Labiner-Wolfe, Judith] US Dept HHS, Off Womens Hlth, Washington, DC 20201 USA. [Labiner-Wolfe, Judith; Lin, Chung-Tung Jordan; Verrill, Linda] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Labiner-Wolfe, J (reprint author), US Dept HHS, Off Womens Hlth, 200 Independence Ave SW, Washington, DC 20201 USA. EM judith.labiner-wolfe@hhs.gov FU United States Food and Drug Administration FX This study was funded by the United States Food and Drug Administration. NR 20 TC 12 Z9 12 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1499-4046 J9 J NUTR EDUC BEHAV JI J. Nutr. Educ. Behav. PD SEP-OCT PY 2010 VL 42 IS 5 BP 315 EP 320 DI 10.1016/j.jneb.2009.08.002 PG 6 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA 648QW UT WOS:000281710000006 PM 20828665 ER PT J AU Townsend, RR Roman, MJ Najjar, SS Cockcroft, JR Feig, PU Stockbridge, NL AF Townsend, Raymond R. Roman, Mary J. Najjar, Samer S. Cockcroft, John R. Feig, Peter U. Stockbridge, Norman L. TI Central blood pressure measurements-an opportunity for efficacy and safety in drug development? SO JOURNAL OF THE AMERICAN SOCIETY OF HYPERTENSION LA English DT Editorial Material DE Blood pressure; central blood pressure; pharmacology; drug safety ID ARTERIAL STIFFNESS; CARDIOVASCULAR RISK; HEART; EVENTS; IMPACT AB Over a century of experience with brachial blood pressure has produced a substantial amount of information on the role of blood pressure as a factor in heart disease, stroke and kidney failure. Successful interventions lowering blood pressure and reducing damage to vital organs testify further to the importance of this vital sign. In recent years attempts to probe deeper into the value of knowledge of blood pressure levels closer to the heart (central blood pressures) suggest that noninvasive measurement of central aortic blood pressure may improve further efforts directed at both understanding drug benefit and uncovering potential drug safety issues. This commentary is a summary of a one-day meeting with the FDA in which the role of central blood pressure measurements as an adjunct to drug efficacy and safety were addressed. J Am Soc Hypertens 2010;4(5):211-214. (C) 2010 American Society of Hypertension. All rights reserved. C1 [Townsend, Raymond R.] Univ Penn, Philadelphia, PA 19104 USA. [Roman, Mary J.] Weill Cornell Med Coll, New York, NY USA. [Najjar, Samer S.] Washington Hosp Ctr, Washington, DC 20010 USA. [Cockcroft, John R.] Wales Heart Inst, Cardiff, S Glam, Wales. [Feig, Peter U.] Merck & Co Inc, Rahway, NJ 07065 USA. [Stockbridge, Norman L.] US FDA, Rockville, MD 20857 USA. RP Townsend, RR (reprint author), Univ Penn, 122 Founders Bldg,3400 Spruce St, Philadelphia, PA 19104 USA. EM townsend@mail.med.upenn.edu NR 20 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-1711 J9 J AM SOC HYPERTENS JI J. Am. Soc. Hypertens. PD SEP-OCT PY 2010 VL 4 IS 5 BP 211 EP 214 DI 10.1016/j.jash.2010.07.002 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 675ET UT WOS:000283809700002 PM 20729159 ER PT J AU Rossi, J AF Rossi, John TI Is Equal Moral Consideration Really Compatible with Unequal Moral Status? SO KENNEDY INSTITUTE OF ETHICS JOURNAL LA English DT Article AB The issue of moral considerability, or how much moral importance a being's interests deserve, is one of the most important in animal ethics. Some leading theorists-most notably David DeGrazia-have argued that a principle of "equal moral consideration" is compatible with "unequal moral status." Such a position would reconcile the egalitarian force of equal consideration with more stringent obligations to humans than animals. The article presents arguments that equal consideration is not compatible with unequal moral status, thereby forcing those who would justify significantly different moral protections for humans and animals to argue for unequal consideration. C1 US FDA, Off Pediat Therapeut, Silver Spring, MD USA. RP Rossi, J (reprint author), US FDA, Off Pediat Therapeut, Silver Spring, MD USA. NR 22 TC 0 Z9 0 U1 3 U2 3 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1054-6863 J9 KENNEDY INST ETHIC J JI Kennedy Inst. Ethics J. PD SEP PY 2010 VL 20 IS 3 BP 251 EP 276 PG 26 WC Ethics; Philosophy; Social Issues SC Social Sciences - Other Topics; Philosophy; Social Issues GA 672VW UT WOS:000283616100003 PM 21133335 ER PT J AU Van Dole, KB Williams, RE Brown, RS Gaynes, B DeVellis, R Funk, MJ AF Van Dole, Kristen B. Williams, Rachel E. Brown, Rebekkah S. Gaynes, Bradley DeVellis, Robert Funk, Michele Jonsson TI Longitudinal association of vasomotor symptoms and psychosocial outcomes among postmenopausal women in the United States: a population-based study SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Menopause; Postmenopausal; Vasomotor; Psychosocial; MENQOL; Epidemiology ID QUALITY-OF-LIFE; HOT FLASHES; MIDLIFE WOMEN; PERIMENOPAUSAL DEPRESSION; MENOPAUSAL TRANSITION; HEALTH; QUESTIONNAIRE; VENLAFAXINE; EXPERIENCE; FREQUENCY AB Objective: Vasomotor and psychosocial symptoms persist as common manifestations of menopause; their explicit association is unclear. We investigated this association among postmenopausal women over a 2-year period. Methods: The Menopause Epidemiology Study is a cross-sectional population-based study of women 40 to 65 years old in the United States. We followed participants who were postmenopausal at baseline and at 2-year follow-up (n = 1,506) in the analyses. The vasomotor and psychosocial domains of the Menopause-Specific Quality of Life Questionnaire were used to assess exposure and outcome. Change in symptoms was defined as the difference in the Menopause-Specific Quality of Life Questionnaire domain score from baseline to follow-up 2 years later. Demographic information, behavioral activities, reproductive history, and medication use were evaluated for effect modification and confounding. Covariate-adjusted linear regression was used to assess the relationship between the change in vasomotor symptoms and change in psychosocial symptoms. Results: One quarter (n = 375) of the women reported an increase in vasomotor symptoms over the 2-year study period. Twenty-two percent of the women reported an increase in both vasomotor and psychosocial symptoms. Current smoking status was found to be an effect modifier: a one-unit increase in the vasomotor domain was associated with a 0.21-unit (95% CI, 0.12-0.29) increase in the psychosocial domain among smokers; this was stronger (0.29, 95% CI, 0.20-0.39) among past or never smokers. Conclusions: This study provides further evidence of an association between vasomotor symptoms and psychosocial symptoms using a validated instrument in a population-based study. There is a small increase in psychosocial symptoms with increasing vasomotor symptoms. Clinicians may want to note this association when treating postmenopausal women with either condition. C1 [Van Dole, Kristen B.; Funk, Michele Jonsson] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Williams, Rachel E.] GlaxoSmithKline Inc, WorldWide Epidemiol, Upper Providence, PA USA. [Brown, Rebekkah S.] GlaxoSmithKline Inc, Dept Biostat, Res Triangle Pk, NC USA. [Gaynes, Bradley] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [DeVellis, Robert] Univ N Carolina, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC USA. RP Van Dole, KB (reprint author), US FDA, Div Epidemiol, Ctr Devices & Radiol Hlth, 10993 New Hampshire Ave,WO66-4107, Silver Spring, MD 20993 USA. EM kristen.vandole@fda.hhs.gov RI Jonsson Funk, Michele/F-6885-2011; OI Jonsson Funk, Michele/0000-0002-3756-7540; Gaynes, Bradley/0000-0002-8283-5030 FU GlaxoSmithKline; Merck Foundation; National Institute of Mental Health; M-3 Information; Bristol-Myers Squibb Company; Novartis; Agency for Healthcare Research and Quality FX This research was funded by GlaxoSmithKline.; K.B.V. received an unrestricted educational grant from GlaxoSmithKline and is a recipient of a Merck Foundation Predoctoral Fellowship in Pharmacoepidemiology. K.B.V. is now an employee of the US Food and Drug Administration; this research was completed during her doctoral program at the University of North Carolina at Chapel Hill. R.E.W. is an employee of GlaxoSmithKline and has equity interest in GlaxoSmithKline. R.S.B. is an employee of GlaxoSmithKline and has equity interest in GlaxoSmithKline. Within the past 12 months, B.G. has received grants and research support from the National Institute of Mental Health, Agency for Healthcare Research and Quality, the M-3 Information, Bristol-Myers Squibb Company, and Novartis. He has been as an advisor for Bristol-Myers Squibb Company. NR 34 TC 13 Z9 13 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD SEP-OCT PY 2010 VL 17 IS 5 BP 917 EP 923 DI 10.1097/gme.0b013e3181d824c8 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 647JL UT WOS:000281614700010 PM 20505546 ER PT J AU Knapton, AD Zhang, J Sistare, FD Hanig, JP AF Knapton, A. D. Zhang, J. Sistare, F. D. Hanig, J. P. TI THE USE OF IN SITU PERFUSION OF THE RAT MESENTERY AS A MODEL TO INVESTIGATE VASCULAR INJURY DIRECTLY INDUCED BY DRUGS SO METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY LA English DT Article ID FENOLDOPAM MESYLATE; MAST-CELLS; HISTAMINE; INHIBITOR; SEROTONIN; TOXICITY; LESIONS; PERMEABILITY; THEOPHYLLINE; PATHOGENESIS AB Exposure of the vasculature to vasodilators, pharmaceuticals and industrial chemicals may lead to injury of the blood vessel wall in animals. Vascular injury may begin with changes in the permeability of vascular endothelial cell and vessels, resulting in possible hemorrhage and edema leading subsequently to immune cell infiltration. The present study was undertaken to determine if the direct exposure of the Sprague Dawley rat mesenteric vasculature through the perfusion of aminophylline, fenoldopam, compound 48/80, histamine or serotonin has any such effects on the blood vessels, and if the two vital dyes Monastral blue B and Evans blue can be used to enhance the visualization of the vascular damage. Microscopic visualization was enhanced by the use of dyes and a variety of alterations of the perfused mesenteric vessels were detected, including varying degrees of most cell degranulation, micro vascular vasodilatation and increased vascular permeability. Macroscopic evidence of vascular damage was minimal. This study demonstrates that in situ perfusion of the rat mesentery is a simple and useful method to eliminate the influence of a variety of physiologic influences or homeostatic responses and can be used to further investigate drug-induced vascular damage. C1 [Knapton, A. D.; Zhang, J.; Sistare, F. D.; Hanig, J. P.] US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, Silver Spring, MD 20993 USA. RP Hanig, JP (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res HFD 910, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM joseph.hanig@fda.hhs.gov NR 29 TC 5 Z9 6 U1 0 U2 1 PU PROUS SCIENCE, SA-THOMSON REUTERS PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0379-0355 J9 METHOD FIND EXP CLIN JI Methods Find. Exp. Clin. Pharmacol. PD SEP PY 2010 VL 32 IS 7 BP 489 EP 497 DI 10.1358/mf.2010.32.7.1507854 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 754RB UT WOS:000289873300004 PM 21069100 ER PT J AU Chen, Q Decker, KB Boucher, PE Hinton, D Stibitz, S AF Chen, Qing Decker, Kimberly Baxter Boucher, Philip E. Hinton, Deborah Stibitz, Scott TI Novel architectural features of Bordetella pertussis fimbrial subunit promoters and their activation by the global virulence regulator BvgA SO MOLECULAR MICROBIOLOGY LA English DT Article ID COLI RNA-POLYMERASE; MUTATIONAL ANALYSIS; FHA PROMOTER; TRANSCRIPTIONAL ACTIVATION; SEQUENCE SIMILARITIES; RESPONSE REGULATOR; ACCESSORY GENES; BACTERIOPHAGE-T4; DNA; MOTA AB P>A prominent feature of the promoters of Bordetella pertussis fimbrial subunit genes fim2, fim3 and fimX is the presence of a 'C-stretch', a monotonic run of C residues. The C-stretch renders these genes capable of phase variation, through spontaneous variations in its length. For each of these we determined the length of the C-stretch that gave maximal transcriptional activity, and found that the three optimized promoters align perfectly, with identical distances between conserved upstream sequences and the downstream -10 elements and transcriptional start sites. We also demonstrated, for Pfim3, that the conserved sequence corresponds to BvgA binding sites. The more upstream of the two binding sites is predicted to be high affinity, by comparison to a functionally derived consensus BvgA-binding sequence. The other binding site is a fairly poor match to this consensus, with 10 of 14 bp belonging to the C-stretch. Interestingly, the centre of this downstream site of BvgA binding coincides exactly with the centre of the expected typical location of a -35 sequence. However, the lack of a recognizable -35 element (CCCCCC versus TTGACA), and the occupation of this site by BvgA similar to P suggest that activation of the fim promoters involves unusual interactions among BvgA, RNA polymerase and promoter DNA. C1 [Chen, Qing; Boucher, Philip E.; Stibitz, Scott] US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Decker, Kimberly Baxter; Hinton, Deborah] NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Chen, Q (reprint author), US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM qing.chen@fda.hhs.gov FU National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases FX The authors would like to thank M. Schmitt, C. Jones, R. Bonocora, L. Knipling, T. James and M. Hsieh for helpful discussions. K. Decker is a graduate student in the Graduate Partnership Program, Johns Hopkins University-National Institutes of Health. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. NR 46 TC 17 Z9 17 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD SEP PY 2010 VL 77 IS 5 BP 1326 EP 1340 DI 10.1111/j.1365-2958.2010.07293.x PG 15 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 643HW UT WOS:000281287200020 PM 20662776 ER PT J AU Cook, JA Davit, BM Polli, JE AF Cook, Jack A. Davit, Barbara M. Polli, James E. TI Impact of Biopharmaceutics Classification System-Based Biowaivers SO MOLECULAR PHARMACEUTICS LA English DT Article DE Biopharmaceutics Classification System; biowaiver; bioequivalence; highly variable drugs; cost ID DRUG DISPOSITION CLASSIFICATION; BIOEQUIVALENCE; PRODUCTS AB The Biopharmaceutics Classification System (BCS) is employed to waive in vivo bioequivalence testing (i.e. provide "biowaivers") for new and generic drugs that are BCS class I. Granting biowaivers under systems such as the BCS eliminates unnecessary drug exposures to healthy subjects and provides economic relief, while maintaining the high public health standard for therapeutic equivalence. International scientific consensus suggests class III drugs are also eligible for biowaivers. The objective of this study was to estimate the economic impact of class I BCS-based biowaivers, along with the economic impact of a potential expansion to BCS class III. Methods consider the distribution of drugs across the four BCS classes, numbers of in vivo bioequivalence studies performed from a five year period, and effects of highly variable drugs (HVDs). Results indicate that 26% of all drugs are class I non-HVDs, 7% are class I HVDs, 27% are class III non-HVDs, and 3% are class III HVDs. An estimated 66 to 76 million dollars can be saved each year in clinical study costs if all class I compounds were granted biowaivers. Between 21 and 24 million dollars of this savings is from HVDs. If BCS class III compounds were also granted waivers, an additional direct savings of 62 to 71 million dollars would be realized, with 9 to 10 million dollars coming from HVDs. C1 [Polli, James E.] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. [Cook, Jack A.] Pfizer Inc, Specialty Care Business Unit, Dept Clin Pharmacol, New London, CT USA. [Davit, Barbara M.] US FDA, Off Genet Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Polli, JE (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, HSF2,Room 623,20 Penn St, Baltimore, MD 21201 USA. EM jpolli@rx.umaryland.edu NR 25 TC 20 Z9 21 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD SEP-OCT PY 2010 VL 7 IS 5 BP 1539 EP 1544 DI 10.1021/mp1001747 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 656CS UT WOS:000282304200019 PM 20735084 ER PT J AU Dahan, A Miller, JM Hilfinger, JM Yamashita, S Yu, LX Lennernas, H Amidon, GL AF Dahan, Arik Miller, Jonathan M. Hilfinger, John M. Yamashita, Shinji Yu, Lawrence X. Lennernas, Hans Amidon, Gordon L. TI High-Permeability Criterion for BCS Classification: Segmental/pH Dependent Permeability Considerations SO MOLECULAR PHARMACEUTICS LA English DT Article DE Biopharmaceutics classification system; biowaiver; fraction dose absorbed; high-permeability criterion; intestinal permeability; oral drug absorption ID PREDICTING DRUG DISPOSITION; BIOPHARMACEUTICS CLASSIFICATION; INTESTINAL PERMEABILITY; CAPILLARY-ELECTROPHORESIS; GASTROINTESTINAL-TRACT; MEMBRANE-PERMEABILITY; P-GLYCOPROTEIN; BETA-BLOCKERS; D-SOTALOL; IN-VIVO AB The FDA classifies a drug substance as high-permeability when the fraction of dose absorbed (F(abs)) in humans is 90% or higher. This direct correlation between human permeability and Fab, has been recently controversial, since the beta-blocker sotalol showed high F(abs) (90%) and low Caco-2 permeability. The purpose of this study was to investigate the scientific basis for this disparity between permeability and F(abs). The effective permeabilities (P(eff)) of sotalol and metoprolol, a FDA standard for the low/high P(off) class boundary, were investigated in the rat perfusion model, in three different intestinal segments with pHs corresponding to the physiological pH in each region: (1) proximal jejunum, pH 6.5; (2) mid small intestine, pH 7.0; and (3) distal ileum, pH 7.5. Both metoprolol and sotalol showed pH-dependent permeability, with higher P(eff) at higher pH. At any given pH, sotalol showed lower permeability than metoprolol; however, the permeability of sotalol determined at pH 7.5 exceeded/matched metoprolol's at pH 6.5 and 7.0, respectively. Physicochemical analysis based on ionization, pK(a) and partitioning of these drugs predicted the same trend and clarified the mechanism behind these observed results. Experimental octanol buffer partitioning experiments confirmed the theoretical curves. An oral dose of metoprolol has been reported to be completely absorbed in the upper small intestine; it follows, hence, that metoprolol's P(eff), value at pH 7.5 is not likely physiologically relevant for an immediate release dosage form, and the permeability at pH 6.5 represents the actual relevant value for the low/high permeability class boundary. Although sotalol's permeability is low at pH 6,5 and 7.0, at pH 7.5 it exceeds/matches the threshold of metoprolol at pH 6.5 and 7.0, most likely responsible for its high Faros, In conclusion, we have shown that, in fact, there is no discrepancy between P(eff) and F(abs), in sotalol's absorption; the data emphasize that, if a compound has high fraction of dose absorbed, it will have high-permeability, not necessarily in the jejunum, but at some point along the relevant intestinal regions. C1 [Lennernas, Hans] Uppsala Univ, Dept Pharm, Biopharmaceut Res Grp, S-75123 Uppsala, Sweden. [Yu, Lawrence X.] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Yamashita, Shinji] Setsunan Univ, Fac Pharmaceut Sci, Osaka, Japan. [Dahan, Arik] Ben Gurion Univ Negev, Dept Clin Pharmacol, Sch Pharm, Fac Hlth Sci, IL-84105 Beer Sheva, Israel. [Hilfinger, John M.] TSRL Inc, Ann Arbor, MI 48108 USA. [Miller, Jonathan M.; Amidon, Gordon L.] Univ Michigan, Dept Pharmaceut Sci, Coll Pharm, Ann Arbor, MI 48109 USA. RP Dahan, A (reprint author), POB 653, IL-84105 Beer Sheva, Israel. EM arikd@bgu.ac.il NR 46 TC 57 Z9 57 U1 3 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD SEP-OCT PY 2010 VL 7 IS 5 BP 1827 EP 1834 DI 10.1021/mp100175a PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 656CS UT WOS:000282304200044 PM 20701326 ER PT J AU Graham, BS Kines, RC Corbett, KS Nicewonger, J Johnson, TR Chen, M LaVigne, D Roberts, JN Cuburu, N Schiller, JT Buck, CB AF Graham, B. S. Kines, R. C. Corbett, K. S. Nicewonger, J. Johnson, T. R. Chen, M. LaVigne, D. Roberts, J. N. Cuburu, N. Schiller, J. T. Buck, C. B. TI Mucosal delivery of human papillomavirus pseudovirus-encapsidated plasmids improves the potency of DNA vaccination SO MUCOSAL IMMUNOLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; T-LYMPHOCYTE RESPONSES; IN-VITRO; DENDRITIC CELLS; NEUTRALIZING ANTIBODIES; ORAL IMMUNIZATION; PARTICLE VACCINE; HEPARAN-SULFATE; CHIMERIC VIRUS; YOUNG-WOMEN AB Mucosal immunization may be important for protection against pathogens whose transmission and pathogenesis target the mucosal tissue. The capsid proteins of human papillomavirus (HPV) confer tropism for the basal epithelium and can encapsidate DNA during self-assembly to form pseudovirions (PsVs). Therefore, we produced mucosal vaccine vectors by HPV PsV encapsidation of DNA plasmids expressing an experimental antigen derived from the M and M2 proteins of respiratory syncytial virus (RSV). Intravaginal (IVag) delivery elicited local and systemic M/M2-specific CD8 + T-cell and antibody responses in mice that were comparable to an similar to 10,000-fold higher dose of naked DNA. A single HPV PsV IVag immunization primed for M/M2-specific-IgA in nasal and vaginal secretions. Based on light emission and immunofluorescent microscopy, immunization with HPV PsV-encapsidated luciferase-and red fluorescent protein (RFP)-expressing plasmids resulted in transient antigen expression (< 5 days), which was restricted to the vaginal epithelium. HPV PsV encapsidation of plasmid DNA is a novel strategy for mucosal immunization that could provide new vaccine options for selected mucosal pathogens. C1 [Graham, B. S.; Corbett, K. S.; Nicewonger, J.; Johnson, T. R.; Chen, M.; LaVigne, D.] NIAID, Viral Pathogenesis Lab, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Kines, R. C.; Cuburu, N.; Schiller, J. T.; Buck, C. B.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. [Roberts, J. N.] US FDA, Bethesda, MD 20014 USA. RP Graham, BS (reprint author), NIAID, Viral Pathogenesis Lab, Vaccine Res Ctr, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM bgraham@nih.gov OI Buck, Christopher/0000-0003-3165-8094 FU National Institute of Allergy and Infectious Diseases; National Cancer Institute FX This work was supported by intramural funding from the National Institute of Allergy and Infectious Diseases and the National Cancer Institute. NR 50 TC 18 Z9 21 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD SEP PY 2010 VL 3 IS 5 BP 475 EP 486 DI 10.1038/mi.2010.31 PG 12 WC Immunology SC Immunology GA 641HM UT WOS:000281115400007 PM 20555315 ER PT J AU Butts, CL Candando, KM Warfel, J Belyavskaya, E D'Agnillo, F Sternberg, EM AF Butts, C. L. Candando, K. M. Warfel, J. Belyavskaya, E. D'Agnillo, F. Sternberg, E. M. TI Progesterone regulation of uterine dendritic cell function in rodents is dependent on the stage of estrous cycle SO MUCOSAL IMMUNOLOGY LA English DT Article ID HOST-PATHOGEN INTERFACE; FEMALE GENITAL-TRACT; HUMAN ENDOMETRIUM; IMMUNE-RESPONSES; HORMONAL CONTRACEPTION; REPRODUCTIVE-TRACT; STEROID-HORMONES; EPITHELIAL-CELLS; CUTTING EDGE; SEX-HORMONES AB Steroid hormones, such as progesterone, are able to modify immunity and influence disease outcome. Dendritic cells (DCs) drive potent immune responses, express receptors for steroid hormones, and may be a primary target of steroid hormone actions during infection of the genital tract, including uterine tissue. Here, we report that progesterone limited DC-associated activation marker expression and inhibited cytokine secretion by uterine DCs, which was associated with changes in signal transducer and activator of transcription 1 (STAT1) activity. We also found that DCs from mice at stages with higher progesterone concentrations (diestrus, metaestrus) were more sensitive to progesterone than those in stages with lower progesterone concentrations (proestrus, estrus), both in vitro and in vivo. This difference correlated with the levels of progesterone receptor expressed by DCs. These data suggest that progesterone regulates DC function and could contribute to the susceptibility of females to uterine and other genital tract infections at selected time periods throughout the life cycle. C1 [Butts, C. L.; Candando, K. M.; Belyavskaya, E.; Sternberg, E. M.] NIMH, Sect Neuroendocrine Immunol, Bethesda, MD 20892 USA. [Warfel, J.; D'Agnillo, F.] US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Sternberg, EM (reprint author), NIMH, Sect Neuroendocrine Immunol, Bethesda, MD 20892 USA. EM sternbee@mail.nih.gov RI Warfel, Jason/D-2557-2011 FU National Institute of Mental Health (NIMH)/NIH; National Institute of Allergy & Infectious Diseases (NIAID)/NIH FX This work was supported by the Intramural Research Program of the National Institute of Mental Health (NIMH)/NIH and by a biodefense grant from the National Institute of Allergy & Infectious Diseases (NIAID)/NIH Intramural Research Program. We thank Dr Cecilia Tami for careful manuscript review and technical assistance. NR 68 TC 8 Z9 10 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD SEP PY 2010 VL 3 IS 5 BP 496 EP 505 DI 10.1038/mi.2010.28 PG 10 WC Immunology SC Immunology GA 641HM UT WOS:000281115400009 PM 20505661 ER PT J AU Demir, E Cary, MP Paley, S Fukuda, K Lemer, C Vastrik, I Wu, GN D'Eustachio, P Schaefer, C Luciano, J Schacherer, F Martinez-Flores, I Hu, ZJ Jimenez-Jacinto, V Joshi-Tope, G Kandasamy, K Lopez-Fuentes, AC Mi, HY Pichler, E Rodchenkov, I Splendiani, A Tkachev, S Zucker, J Gopinath, G Rajasimha, H Ramakrishnan, R Shah, I Syed, M Anwar, N Babur, O Blinov, M Brauner, E Corwin, D Donaldson, S Gibbons, F Goldberg, R Hornbeck, P Luna, A Murray-Rust, P Neumann, E Reubenacker, O Samwald, M van Iersel, M Wimalaratne, S Allen, K Braun, B Whirl-Carrillo, M Cheung, KH Dahlquist, K Finney, A Gillespie, M Glass, E Gong, L Haw, R Honig, M Hubaut, O Kane, D Krupa, S Kutmon, M Leonard, J Marks, D Merberg, D Petri, V Pico, A Ravenscroft, D Ren, LY Shah, N Sunshine, M Tang, R Whaley, R Letovksy, S Buetow, KH Rzhetsky, A Schachter, V Sobral, BS Dogrusoz, U McWeeney, S Aladjem, M Birney, E Collado-Vides, J Goto, S Hucka, M Le Novere, N Maltsev, N Pandey, A Thomas, P Wingender, E Karp, PD Sander, C Bader, GD AF Demir, Emek Cary, Michael P. Paley, Suzanne Fukuda, Ken Lemer, Christian Vastrik, Imre Wu, Guanming D'Eustachio, Peter Schaefer, Carl Luciano, Joanne Schacherer, Frank Martinez-Flores, Irma Hu, Zhenjun Jimenez-Jacinto, Veronica Joshi-Tope, Geeta Kandasamy, Kumaran Lopez-Fuentes, Alejandra C. Mi, Huaiyu Pichler, Elgar Rodchenkov, Igor Splendiani, Andrea Tkachev, Sasha Zucker, Jeremy Gopinath, Gopal Rajasimha, Harsha Ramakrishnan, Ranjani Shah, Imran Syed, Mustafa Anwar, Nadia Babur, Oezguen Blinov, Michael Brauner, Erik Corwin, Dan Donaldson, Sylva Gibbons, Frank Goldberg, Robert Hornbeck, Peter Luna, Augustin Murray-Rust, Peter Neumann, Eric Reubenacker, Oliver Samwald, Matthias van Iersel, Martijn Wimalaratne, Sarala Allen, Keith Braun, Burk Whirl-Carrillo, Michelle Cheung, Kei-Hoi Dahlquist, Kam Finney, Andrew Gillespie, Marc Glass, Elizabeth Gong, Li Haw, Robin Honig, Michael Hubaut, Olivier Kane, David Krupa, Shiva Kutmon, Martina Leonard, Julie Marks, Debbie Merberg, David Petri, Victoria Pico, Alex Ravenscroft, Dean Ren, Liya Shah, Nigam Sunshine, Margot Tang, Rebecca Whaley, Ryan Letovksy, Stan Buetow, Kenneth H. Rzhetsky, Andrey Schachter, Vincent Sobral, Bruno S. Dogrusoz, Ugur McWeeney, Shannon Aladjem, Mirit Birney, Ewan Collado-Vides, Julio Goto, Susumu Hucka, Michael Le Novere, Nicolas Maltsev, Natalia Pandey, Akhilesh Thomas, Paul Wingender, Edgar Karp, Peter D. Sander, Chris Bader, Gary D. TI The BioPAX community standard for pathway data sharing SO NATURE BIOTECHNOLOGY LA English DT Article ID SYSTEMS BIOLOGY; COLLABORATIVE CONSTRUCTION; SOFTWARE ENVIRONMENT; INTERACTION NETWORK; CELLULAR PATHWAYS; REPRESENTATION; ONTOLOGY; INFORMATION; CANCER; KNOWLEDGEBASE AB Biological Pathway Exchange (BioPAX) is a standard language to represent biological pathways at the molecular and cellular level and to facilitate the exchange of pathway data. The rapid growth of the volume of pathway data has spurred the development of databases and computational tools to aid interpretation; however, use of these data is hampered by the current fragmentation of pathway information across many databases with incompatible formats. BioPAX, which was created through a community process, solves this problem by making pathway data substantially easier to collect, index, interpret and share. BioPAX can represent metabolic and signaling pathways, molecular and genetic interactions and gene regulation networks. Using BioPAX, millions of interactions, organized into thousands of pathways, from many organisms are available from a growing number of databases. This large amount of pathway data in a computable form will support visualization, analysis and biological discovery. (C) 2010 Nature America, Inc. All rights reserved. C1 [Rodchenkov, Igor; Donaldson, Sylva; Bader, Gary D.] Univ Toronto, Banting & Best Dept Med Res, Donnelly Ctr Cellular & Biomol Res, Toronto, ON, Canada. [Demir, Emek; Cary, Michael P.; Anwar, Nadia; Babur, Oezguen; Sander, Chris] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Demir, Emek; Babur, Oezguen; Dogrusoz, Ugur] Bilkent Univ, Ctr Bioinformat, Ankara, Turkey. [Demir, Emek; Babur, Oezguen; Dogrusoz, Ugur] Bilkent Univ, Dept Comp Engn, Ankara, Turkey. [Mi, Huaiyu; Thomas, Paul] SRI Int, Ctr Artificial Intelligence, Menlo Pk, CA 94025 USA. [Fukuda, Ken] Japan Sci & Technol Agcy, Inst Bioinformat Res & Dev, Tokyo, Japan. [Lemer, Christian; Hubaut, Olivier] Univ Libre Bruxelles, Brussels, Belgium. [Vastrik, Imre; Birney, Ewan; Le Novere, Nicolas] European Bioinformat Inst, Cambridge, England. [Wu, Guanming; Haw, Robin] Ontario Inst Canc Res, Toronto, ON, Canada. [D'Eustachio, Peter] NYU, Sch Med, New York, NY USA. [Schaefer, Carl] NCI, Ctr Biomed Informat & Informat Technol, Rockville, MD USA. [Luciano, Joanne] Predict Med, Belmont, MA USA. [Schacherer, Frank; Braun, Burk] BIOBASE Corp, Beverly, MA USA. [Martinez-Flores, Irma; Jimenez-Jacinto, Veronica; Collado-Vides, Julio] Univ Nacl Autonoma Mexico, Ctr Ciencias Genom, Cuernavaca 62191, Morelos, Mexico. [Hu, Zhenjun] Boston Univ, Biomol Syst Lab, Boston, MA 02215 USA. [Joshi-Tope, Geeta; Ren, Liya] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Kandasamy, Kumaran; Pandey, Akhilesh] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Kandasamy, Kumaran; Pandey, Akhilesh] Johns Hopkins Univ, Dept Biol Chem, Baltimore, MD USA. [Kandasamy, Kumaran; Pandey, Akhilesh] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Kandasamy, Kumaran; Pandey, Akhilesh] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA. [Splendiani, Andrea] Univ Rennes 1, Fac Med, Rennes, France. [Splendiani, Andrea] Rothamsted Res, Harpenden, Herts, England. [Tkachev, Sasha; Hornbeck, Peter] Cell Signaling Technol Inc, Danvers, MA USA. [Zucker, Jeremy] Broad Inst, Cambridge, MA USA. [Gopinath, Gopal] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD USA. [Rajasimha, Harsha; Sobral, Bruno S.] Virginia Polytech Inst & State Univ, Virginia Bioinformat Inst, Blacksburg, VA 24061 USA. [Rajasimha, Harsha] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA. [Ramakrishnan, Ranjani; McWeeney, Shannon] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Shah, Imran] US Environm Protect Agcy Durham, Durham, NC USA. [Syed, Mustafa; Glass, Elizabeth; Maltsev, Natalia] Argonne Natl Lab, Math & Comp Sci Div, Argonne, IL 60439 USA. [Blinov, Michael] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Brauner, Erik; Gibbons, Frank] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Corwin, Dan] Lexikos Corp, Boston, MA USA. [Goldberg, Robert] Natl Inst Stand & Technol, Div Biotechnol, Gaithersburg, MD 20899 USA. [Luna, Augustin; Sunshine, Margot; Aladjem, Mirit] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Murray-Rust, Peter] Univ Cambridge, Dept Chem, Unilever Ctr Mol Sci Informat, Cambridge CB2 1EW, England. [Neumann, Eric] Clin Semant Grp, Lexington, MA USA. [Reubenacker, Oliver] Univ Connecticut, Ctr Hlth, Ctr Cell Anal & Modeling, Storrs, CT USA. [Samwald, Matthias] Natl Univ Ireland, Digital Enterprise Res Inst, Galway, Ireland. [Samwald, Matthias] Konrad Lorenz Inst Evolut & Cognit Res, Altenberg, Austria. [van Iersel, Martijn] Maastricht Univ, Dept Bioinformat, Maastricht, Netherlands. [Wimalaratne, Sarala] Univ Auckland, Auckland 1, New Zealand. [Allen, Keith; Leonard, Julie] Syngenta Biotech Inc, Res Triangle Pk, NC USA. [Whirl-Carrillo, Michelle; Gong, Li; Tang, Rebecca; Whaley, Ryan] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Cheung, Kei-Hoi] Yale Univ, Yale Ctr Med Informat, New Haven, CT USA. [Dahlquist, Kam] Loyola Marymount Univ, Los Angeles, CA 90045 USA. [Finney, Andrew] Physiomics PLC, Magdalen Ctr, Oxford, England. [Gillespie, Marc] St Johns Univ, Jamaica, NY 11439 USA. [Honig, Michael] Columbia Univ, New York, NY USA. [Kane, David] SRA Int, Fairfax, VA USA. [Krupa, Shiva] Novartis Knowledge Ctr, Cambridge, MA USA. [Kutmon, Martina] Univ Ottawa, Ottawa, ON, Canada. [Marks, Debbie] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Merberg, David] Vertex Pharmaceut, Cambridge, MA USA. [Petri, Victoria] Med Coll Wisconsin, Human & Mol Genet Ctr, Milwaukee, WI 53226 USA. [Pico, Alex] Gladstone Inst Cardiovasc Dis, San Francisco, CA USA. [Ravenscroft, Dean] Cornell Univ, Dept Genet & Plant Breeding, Ithaca, NY USA. [Shah, Nigam] Stanford Univ, Sch Med, Ctr Biomed Informat, Stanford, CA 94305 USA. [Letovksy, Stan] Millennium Pharmaceut Inc, Computat Sci Informat, Cambridge, MA USA. [Buetow, Kenneth H.] NCI, Ctr Biomed Informat & Informat Technol, Bethesda, MD 20892 USA. [Rzhetsky, Andrey] Univ Chicago, Inst Genom & Syst Biol, Chicago, IL 60637 USA. [Rzhetsky, Andrey] Argonne Natl Lab, Chicago, IL USA. [Schachter, Vincent] Total Gas & Power, Paris, France. [Goto, Susumu] Kyoto Univ, Inst Chem Res, Bioinformat Ctr, Kyoto 606, Japan. [Hucka, Michael] CALTECH, Biol Network Modeling Ctr, Pasadena, CA 91125 USA. [Wingender, Edgar] Dept Bioinformat, Gottingen, Germany. RP Bader, GD (reprint author), Univ Toronto, Banting & Best Dept Med Res, Donnelly Ctr Cellular & Biomol Res, Toronto, ON, Canada. EM biopax-paper@biopax.org RI van Iersel, Martijn/E-9105-2010; Syed, Mustafa/A-5252-2011; Bader, Gary/C-1176-2009; Le Novere, Nicolas/F-9973-2010; sander, chris/H-1452-2011; Hucka, Michael/B-1896-2012; rzhetsky, andrey/B-6118-2012; Pandey, Akhilesh/B-4127-2009; Vastrik, Imre/C-2690-2009; Zucker, Jeremy/M-3643-2016; Haw, Robin/D-1393-2009; OI van Iersel, Martijn/0000-0002-5877-4338; Bader, Gary/0000-0003-0185-8861; Le Novere, Nicolas/0000-0002-6309-7327; Pandey, Akhilesh/0000-0001-9943-6127; Zucker, Jeremy/0000-0002-7276-9009; Murray-Rust, Peter/0000-0003-3386-3972; McWeeney, Shannon/0000-0001-8333-6607; BABUR, OZGUN/0000-0002-0239-5259; Demir, Emek/0000-0002-3663-7113; D'Eustachio, Peter/0000-0002-5494-626X; Wingender, Edgar/0000-0002-7729-8453; Pico, Alexander/0000-0001-5706-2163; Gillespie, Marc/0000-0002-5766-1702; Haw, Robin/0000-0002-2013-7835; Kutmon, Martina/0000-0002-7699-8191; Wimalaratne, Sarala/0000-0002-5355-2576; Karp, Peter/0000-0002-5876-6418; Birney, Ewan/0000-0001-8314-8497; Fukuda, Ken/0000-0001-7366-1094 FU US Department of Energy [DE-FG02-04ER63931]; caBIG program; US National Institute of General Medical Sciences workshop [1R13GM076939, P41HG004118]; US National Human Genome Research Institute and Genome Canada through the Ontario Genomics Institute [2007-OGI-TD-05]; US National Institutes of Health [R01GM071962-07] FX Funded by the US Department of Energy workshop grant DE-FG02-04ER63931, the caBIG program, the US National Institute of General Medical Sciences workshop grant 1R13GM076939, grant P41HG004118 from the US National Human Genome Research Institute and Genome Canada through the Ontario Genomics Institute (2007-OGI-TD-05) and US National Institutes of Health grant R01GM071962-07. Thanks to many people who contributed to discussions on BioPAX mailing lists, at conferences and at BioPAX workshops, especially A. Ruttenberg and J. Rees. NR 65 TC 251 Z9 253 U1 5 U2 27 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD SEP PY 2010 VL 28 IS 9 BP 935 EP 942 DI 10.1038/nbt.1666 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 648UF UT WOS:000281719100019 PM 20829833 ER PT J AU Vance, JM Ali, S Bradley, WG Singer, C Di Monte, DA AF Vance, Jeffery M. Ali, Syed Bradley, Walter G. Singer, Carlos Di Monte, Donato A. TI Gene-environment interactions in Parkinson's disease and other forms of parkinsonism SO NEUROTOXICOLOGY LA English DT Article DE Parkinson; Neurotoxicant; MPTP; Synuclein; Cyanobacteria; Genome ID METHYLAMINO-L-ALANINE; ALPHA-SYNUCLEIN; MN9D CELLS; CYANOBACTERIAL NEUROTOXINS; NEURODEGENERATIVE DISEASE; SELECTIVE ALTERATIONS; PESTICIDE EXPOSURE; SUBSTANTIA-NIGRA; PC12 CELLS; GUAM AB It is widely recognized that both genetic and environmental factors are likely to contribute to the pathogenesis of human parkinsonism. While the identification of specific predisposing conditions and mechanisms of disease development remain elusive, new discoveries coupled with technological advances over the past decade have provided important clues. From the genetic standpoint, both causal and susceptibility genes have been identified, with some of these genes pointing to gene-environment interactions. The application of emerging genomic technologies, such as Genome Wide Association Studies (GWAS), will certainly further our knowledge of Parkinson's disease (PD)-related genes. From the environmental perspective, toxicant-induced models of parkinsonian syndromes, such as those associated with exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or beta-N-methylamino-L-alanine (BMAA), have revealed potential mechanisms of increased susceptibility based on genetic predisposition. Finally, new hypotheses on mechanisms of disease development include the possibility that exposure to neurotoxicants triggers an upregulation and pathological modifications of alpha-synuclein. Mutations in the alpha-synuclein gene are responsible for rare familial cases of parkinsonism, and polymorphisms in the promoter region of this gene confer a higher susceptibility to idiopathic PD. Thus, toxicant-alpha-synuclein interactions could have deleterious consequences and play a role in pathogenetic processes in human parkinsonism. (C) 2010 Elsevier Inc. All rights reserved. C1 [Di Monte, Donato A.] SRI Int, Ctr Hlth Sci, Menlo Pk, CA 94025 USA. [Vance, Jeffery M.; Bradley, Walter G.; Singer, Carlos] Univ Miami, Miami, FL 33101 USA. [Ali, Syed] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Di Monte, DA (reprint author), SRI Int, Ctr Hlth Sci, 333 Ravenswood Ave, Menlo Pk, CA 94025 USA. EM donato.dimonte@sri.com NR 45 TC 35 Z9 36 U1 0 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SEP PY 2010 VL 31 IS 5 BP 598 EP 602 DI 10.1016/j.neuro.2010.04.007 PG 5 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 651PI UT WOS:000281939200025 PM 20430055 ER PT J AU Ferguson, SA Berry, KJ AF Ferguson, Sherry A. Berry, Kimberly J. TI Chronic oral treatment with isotretinoin alters measures of activity but not anxiety in male and female rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Isotretinoin; 13-cis-retinoic acid; Accutane; Anxiety; Activity; Rat ID SPRAGUE-DAWLEY RATS; TRANS-RETINOIC ACID; PLUS-MAZE BEHAVIOR; 13-CIS-RETINOIC ACID; WISTAR-KYOTO; DEPRESSION; INCREASE; ACNE; ADOLESCENCE; ACCUTANE(R) AB Use of the anti-acne drug, Accutane (R) (ACC) (isotretinoin, 13-cis-retinoic acid), has been associated with neuropsychiatric events ranging from depression in animal models to depression and suicide ideation in humans. Our studies, however, have consistently indicated few effects on measures of depression in male and female rats. Still, the comorbidity of depression and anxiety suggests that anxiety assessments in ACC-treated rats could be informative. Such assessments must be balanced with measures of activity since drug-induced activity alterations may impact the expression of anxiety-like behaviors. Here, Sprague-Dawley rats (n = 15/sex/dose) were gavaged daily with 0 (soy oil), 7.5, or 30 mg/kg/day ACC beginning on postnatal day (PND) 59. Blood ACC levels similar to humans taking recommended ACC doses are produced by 7.5 mg/kg/day. Short-term activity was assessed in open fields prior to ACC treatment (PND 51) and again at PNDs 129 and 164 and in a complex environment at PNDs 66 and PND 184. Long-term residential activity was measured in running wheels (PNDs 85-92) and figure 8 mazes (PNDs 99-106). Anxiety-like behavior was assessed via elevated plus maze (EPM) activity on PND 98 and in a black/white apparatus on PND 125. The typical sex differences in most behaviors were exhibited (i.e., increased EPM open arm entries and overall activity in most measures in females); however, there were no significant effects of ACC treatment on open field activity, complex environment activity, residential running wheel activity, or EPM activity. Residential figure 8 maze activity indicated that male and female rats treated with 30 mg/kg/day were less active on all nights (p<0.05) and females treated with 7.5 or 30 mg/kg/day were less active than same-sex controls on most days (p<0.05). Similarly, rats of both sexes treated with 30 mg/kg/day were significantly less active in the black/white apparatus (p<0.05), entering the darkened area less frequently (p<0.05), although duration in the darkened area did not differ. These data indicate that at blood levels typically achieved by humans (i.e., the 7.5 mg/kg group), there are no significant anxiogenic effects associated with ACC treatment. At higher ACC levels, there are mild effects on activity but these appear to be apparatus- and/or age-specific. Published by Elsevier Inc. C1 [Ferguson, Sherry A.; Berry, Kimberly J.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Ferguson, SA (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM Sherry.Ferguson@fda.hhs.gov NR 40 TC 2 Z9 3 U1 2 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 EI 1872-9738 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD SEP-OCT PY 2010 VL 32 IS 5 BP 573 EP 578 DI 10.1016/j.ntt.2010.03.009 PG 6 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 651PT UT WOS:000281940300008 PM 20381607 ER PT J AU Tezak, Z Kondratovich, MV Mansfield, E AF Tezak, Zivana Kondratovich, Marina V. Mansfield, Elizabeth TI US FDA and personalized medicine: in vitro diagnostic regulatory perspective SO PERSONALIZED MEDICINE LA English DT Review DE companion diagnostics; device regulation; FDA; in vitro diagnostics; laboratory tests; personalized medicine; predictive markers; prognostic markers; regulatory challenges ID CLINICAL-TRIAL DESIGNS; PREDICTIVE BIOMARKERS; CANCER; DRUG; CHALLENGES; VALIDATION; SPECIMENS; OPINION; BIAS AB Personalized medicine has captured the attention of the public, including patients, healthcare providers, scientists, medical product manufacturers and many others. The US FDA will evaluate many of the products that will allow personalized medicine to be successfully implemented in the USA. This article addresses the FDA's approach to regulation of one component of personalized medicine, in vitro diagnostic devices. It also describes the FDA's efforts to integrate the various medical product regulatory authorities provided by Congress in the Federal Food, Drug and Cosmetic Act to develop effective mechanisms for oversight of medical products used to personalize treatment. Finally, it presents some of the current challenges in in vitro diagnostics oversight that may be of interest for personalized medicine. C1 [Tezak, Zivana; Kondratovich, Marina V.; Mansfield, Elizabeth] US FDA, Off Vitro Diagnost Device Evaluat & Safety, Ctr Devices & Radiol Hlth, Silver Spring, MD 20903 USA. RP Tezak, Z (reprint author), US FDA, Off Vitro Diagnost Device Evaluat & Safety, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20903 USA. EM zivana.tezak@fda.hhs.gov NR 32 TC 16 Z9 16 U1 1 U2 14 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 J9 PERS MED JI Pers. Med. PD SEP PY 2010 VL 7 IS 5 BP 517 EP 530 DI 10.2217/PME.10.53 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 666HZ UT WOS:000283106800011 ER PT J AU McMahon, AW Pratt, RG Hammad, TA Kozlowski, S Zhou, E Lu, S Kulick, CG Mallick, T Dal Pan, G AF McMahon, Ann W. Pratt, Robert G. Hammad, Tarek A. Kozlowski, Steven Zhou, Esther Lu, Susan Kulick, Corrinne G. Mallick, Tarun Dal Pan, Gerald TI Description of hypersensitivity adverse events following administration of heparin that was potentially contaminated with oversulfated chondroitin sulfate in early 2008 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE heparin; adverse events; contamination ID SYSTEM; SAFETY AB Purpose To characterize the nature of a heparin contaminant's clinical effects in cases reported to the Adverse Event Reporting System (AERS). The FDA received reports of heparin-associated adverse events (AEs) starting in late 2007-early 2008 during a national investigation of allergic-type events. The investigation identified Baxter Healthcare-brand heparin product due to its strongest association with the events. Later, oversulfated chondroitin sulfate (OSCS), a heparin-like contaminant, was discovered. Methods This study was a case series of heparin reports in AERS received 1 January 2008 to 31 March 2008. Variables considered were frequency of treatment settings, AEs, mortality; as well as heparin dose and OSCS contamination. Results Five hundred seventy-four AERS cases (unduplicated reports) were identified and included. Of 94 cases with a fatal outcome, 68 reported at least one AE term from the list used to identify an allergic-type event. Nearly 75% of AEs in cases of IVadministration (n = 170/233) reportedly occurred within 10 minutes, whereas over half of subcutaneous administration cases (n = 13/23) resulted in times-to-event of greater than 24 hours. Although cases with a time-to-event of less than 10 minutes appeared to correlate with higher levels of OSCS contamination, no clear differences were noted between high-and low-to-absent OSCS concentration lots with respect to AEs observed. Conclusions Intravenous administration and a higher OSCS concentration appeared to correlate with a more rapid onset of event. The FDA continues to monitor AEs associated with heparin use and has taken appropriate regulatory action to ensure a safe heparin drug supply. Published in 2010 by John Wiley & Sons, Ltd. C1 [McMahon, Ann W.; Pratt, Robert G.; Hammad, Tarek A.; Zhou, Esther; Lu, Susan; Kulick, Corrinne G.; Dal Pan, Gerald] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Kozlowski, Steven] US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Mallick, Tarun] US FDA, Off Biostat & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP McMahon, AW (reprint author), US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Room 3474, Silver Spring, MD 20993 USA. EM ann.mcmahon@fda.hhs.gov FU United States Food and Drug Administration (USFDA) FX This study was sponsored by the United States Food and Drug Administration (USFDA), and included analysis of some spontaneous reports provided by companies with a vested interest in the product being studied. The companies supply the data to the USFDA because they have a regulatory obligation to do so. All authors of this manuscript worked for the USFDA when this study was performed, and do not have any financial conflicts of interest to disclose. The views expressed in this manuscript represent the opinions of the authors, and do not necessarily represent the views of the USFDA. NR 14 TC 27 Z9 28 U1 1 U2 1 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 SEP PY 2010 VL 19 IS 9 BP 921 EP 933 DI 10.1002/pds.1991 PG 13 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 653IA UT WOS:000282081500006 PM 20661880 ER PT J AU Ryabinin, VA Kostina, EV Neverov, AA Maksakova, GA Sinyakov, AN AF Ryabinin, V. A. Kostina, E. V. Neverov, A. A. Maksakova, G. A. Sinyakov, A. N. TI Oligonucleotide microarray for the subtyping of influenza virus a neuraminidase SO RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY LA English DT Article DE influenza virus A; neuraminidase; microarray; typing; diagnostics ID DNA MICROARRAYS; A VIRUSES; IDENTIFICATION; HYBRIDIZATION; ASSAY; PCR AB A microarray for the subtyping of influenza A neuraminidase is presented. The selection of oligoprobes proceeded in two steps. The first step included the selection of peptides specific for each subtype of neuraminidase. At the second step, the oligoprobes were calculated using the found peptide structures with the subsequent additional selection of the most specific and representative probes. From 19 to 24 probes were used for the determination of each neuraminidase subtype. The microarray testing for 19 samples with the most widespread types (N1 and N2) specifies in an unequivocal definition 18 of them and only 1 isolate has not been identified. C1 [Ryabinin, V. A.; Kostina, E. V.; Maksakova, G. A.; Sinyakov, A. N.] Russian Acad Sci, Siberian Branch, Inst Chem Biol & Fundamental Med, Novosibirsk, Russia. [Neverov, A. A.] US FDA, Lab Method Dev, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Ryabinin, VA (reprint author), Russian Acad Sci, Siberian Branch, Inst Chem Biol & Fundamental Med, Pr Lavrentieva 8, Novosibirsk, Russia. EM ryabinin@nioboch.nsc.ru RI Sinyakov, Aleksandr /H-1129-2013; OI zaraat, javad/0000-0001-5341-7481 FU ISTC [3803] FX The work was carried out with the financial support of the ISTC (project no. 3803). NR 24 TC 5 Z9 5 U1 0 U2 0 PU MAIK NAUKA/INTERPERIODICA/SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 1068-1620 J9 RUSS J BIOORG CHEM+ JI Russ. J. Bioorg. Chem. PD SEP PY 2010 VL 36 IS 5 BP 634 EP 644 DI 10.1134/S1068162010050122 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 657SJ UT WOS:000282432300012 ER PT J AU Goodsaid, FM Mendrick, DL AF Goodsaid, Federico M. Mendrick, Donna L. TI Translational Medicine and the Value of Biomarker Qualification SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID SAFETY BIOMARKERS; KIDNEY INJURY; TOXICITY AB The gap between development of exploratory biomarkers and their acceptance in drug development and regulatory review is a hurdle in the development of better therapies. The U. S. Food and Drug Administration has developed a regulatory process for biomarker qualification to accelerate the process by which new biomarkers are integrated in the development of therapies. C1 [Goodsaid, Federico M.] US FDA, Genom Grp, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. [Mendrick, Donna L.] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Goodsaid, FM (reprint author), US FDA, Genom Grp, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. EM federico.goodsaid@fda.hhs.gov NR 18 TC 24 Z9 24 U1 1 U2 9 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 SEP 1 PY 2010 VL 2 IS 47 AR 47ps44 DI 10.1126/scitranslmed.3001040 PG 3 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 735SA UT WOS:000288436200002 PM 20811041 ER PT J AU Shomron, N Hamasaki-Katagiri, N Hunt, R Hershko, K Pommier, E Geetha, S Blaisdell, A Marple, A Roma, I Newell, J Allen, C Friedman, S Kimchi-Sarfaty, C AF Shomron, Noam Hamasaki-Katagiri, Nobuko Hunt, Ryan Hershko, Klilah Pommier, Elie Geetha, S. Blaisdell, Adam Marple, Andrew Roma, Isabella Newell, Jordan Allen, Courtni Friedman, Scott Kimchi-Sarfaty, Chava TI A splice variant of ADAMTS13 is expressed in human hepatic stellate cells and cancerous tissues SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE ADAMTS13; alternative splicing; intron retention; TTP; CUB domain ID THROMBOTIC THROMBOCYTOPENIC PURPURA; VON-WILLEBRAND-FACTOR; FACTOR-CLEAVING PROTEASE; MESSENGER-RNA; METALLOPROTEASE; ASSOCIATION; MUTATION; COMPLEX AB Although ADAMTS13, the von Willebrand factor (VWF)-cleaving protease, is expressed in a range of tissues, the physiological significance of tissue-specific ADAMTS13 alternative splicing isoforms have yet to be clarified. Screening a panel of human tissues and cell lines revealed a spliced ADAMTS13 transcript in hepatic stellate cells and a hepatoma cell line that retains the 25(th) intron.A nonsense codon within the intron truncates the protease, which gains 64 novel amino acids in lieu of both CUB domains. This isoform, while retaining VWF-cleaving capability, accumulates intracellularly and its biological inaccessibility may prevent its participation in regulating haemostasis and other physiologic functions. C1 [Shomron, Noam] Tel Aviv Univ, Sackler Fac Med, Dept Cell & Dev Biol, IL-69978 Tel Aviv, Israel. [Hamasaki-Katagiri, Nobuko; Hunt, Ryan; Hershko, Klilah; Pommier, Elie; Geetha, S.; Blaisdell, Adam; Newell, Jordan; Allen, Courtni; Kimchi-Sarfaty, Chava] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Marple, Andrew; Roma, Isabella] Natl Canc Inst, Cell Biol Lab, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD USA. [Friedman, Scott] Mt Sinai Sch Med, Div Liver Dis, New York, NY USA. RP Kimchi-Sarfaty, C (reprint author), 29 Lincoln Dr, Bethesda, MD 20982 USA. EM Chava.kimchi-sarfaty@fda.hhs.gov FU Intramural NIH HHS [Z01 BC005598-18] NR 18 TC 6 Z9 6 U1 0 U2 3 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD SEP PY 2010 VL 104 IS 3 BP 531 EP 535 DI 10.1160/TH09-12-0860 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 651ZV UT WOS:000281969900014 PM 20664912 ER PT J AU Wang, RS McDaniel, LP Manjanatha, MG Shelton, SD Doerge, DR Mei, N AF Wang, Rui-Sheng McDaniel, Lea P. Manjanatha, Mugimane G. Shelton, Sharon D. Doerge, Daniel R. Mei, Nan TI Mutagenicity of Acrylamide and Glycidamide in the Testes of Big Blue Mice SO TOXICOLOGICAL SCIENCES LA English DT Article DE acrylamide; glycidamide; Big Blue mice; testes; mutation frequency; mutation spectrum ID GERM-CELL MUTAGENICITY; DNA ADDUCT FORMATION; HERITABLE TRANSLOCATIONS; MUTATIONAL SPECTRA; TRANSGENIC MICE; DRINKING-WATER; RATS; GENOTOXICITY; MOUSE; CARCINOGENICITY AB Acrylamide (AA) is an industrial chemical, a by-product of fried starchy foods, and a mutagen and rodent carcinogen. It can also cause damage during spermatogenesis. In this study, we investigated whether AA and its metabolite glycidamide (GA) induce mutagenic effects in the germ cells of male mice. Male Big Blue transgenic mice were administered 1.4 or 7.0mM of AA or GA in the drinking water for up to 4 weeks. Testicular cII mutant frequency (MF) was determined 3 weeks after the last treatment, and the types of the mutations in the cII gene were analyzed by DNA sequencing. The testes cII MFs in mice treated with either the low or high exposure concentrations of AA and GA were increased significantly. There was no significant difference in the cII MFs between AA and GA at the low exposure concentration. The mutation spectra in mice treated with AA (1.4mM) or GA (both 1.4 and 7.0mM) differed significantly from those of controls, but there were no significant differences in mutation patterns between AA and GA treatments. Comparison of the mutation spectra between testes and livers showed that the spectra differed significantly between the two tissues following treatment with AA or GA, whereas the mutation spectra in the two tissues from control mice were similar. These results suggest that AA possesses mutagenic effects on testes by virtue of its metabolism to GA, possibly targeting spermatogonial stem cells, but possibly via different pathways when compared mutations in liver. C1 [Wang, Rui-Sheng; McDaniel, Lea P.; Manjanatha, Mugimane G.; Shelton, Sharon D.; Mei, Nan] Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Wang, Rui-Sheng] Japan Natl Inst Occupat Safety & Hlth, Div Hlth Effects Res, Kawasaki Ku, Kanagawa 2148585, Japan. [Doerge, Daniel R.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Mei, N (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM nan.mei@fda.hhs.gov RI mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 FU National Center for Toxicological Research (NCTR)/U.S. Food and Drug Administration [224-07-0007]; National Institute for Environmental Health Sciences; NCTR; U.S. Department of Energy; U.S. Food and Drug Administration FX This research was supported in part by Interagency Agreement 224-07-0007 between National Center for Toxicological Research (NCTR)/U.S. Food and Drug Administration and the National Institute for Environmental Health Sciences/National Toxicology Program. This research was partly supported by appointments (R.-S.W.) to the Research Program at the NCTR administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 43 TC 21 Z9 21 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 EI 1096-0929 J9 TOXICOL SCI JI Toxicol. Sci. PD SEP PY 2010 VL 117 IS 1 BP 72 EP 80 DI 10.1093/toxsci/kfq190 PG 9 WC Toxicology SC Toxicology GA 642FC UT WOS:000281188400009 PM 20581126 ER PT J AU Doerge, DR Twaddle, NC Vanlandingham, M Fisher, JW AF Doerge, Daniel R. Twaddle, Nathan C. Vanlandingham, Michelle Fisher, Jeffrey W. TI Pharmacokinetics of bisphenol A in neonatal and adult Sprague-Dawley rats SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Bisphenol A; Estrogen receptors; Mass spectrometry; Pharmacokinetics ID REPRODUCTIVE TOXICITY; EXPOSURE; MICE; GLUCURONIDATION; BIOAVAILABILITY; DISPOSITION; METABOLISM; INCREASES; EXCRETION; PROSTATE AB Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA in urine of >90% of Americans aged 660 suggests ubiquitous and frequent exposure. The current study used LC/MS/MS to measure serum pharmacokinetics of aglycone (active) and conjugated (inactive) BPA in adult and neonatal Sprague-Dawley rats by oral and injection routes. Deuterated BPA was used to avoid issues of background contamination. Linear pharmacokinetics were observed in adult rats treated orally in the range of 0-200 mu g/kg bw. Evidence for enterohepatic recirculation of conjugated, but not aglycone. BPA was observed in adult rats. Significant inverse relationships were observed between postnatal age and measures of internal exposures to aglycone BPA and its elimination. In neonatal rats treated orally, internal exposures to aglycone BPA were substantially lower than from subcutaneous injection. The results reinforce the critical role for first-pass Phase II metabolism of BPA in gut and liver after oral exposure that attenuates internal exposure to the aglycone form in rats of all ages. The internal exposures to aglycone BPA observed in adult and neonatal rats following a single oral dose of 100 mu g/kg bw are inconsistent with effects mediated by classical estrogen receptors based on binding affinities. However, an impact on alternative estrogen signaling pathways that have higher receptor affinity cannot be excluded in neonatal rats. These findings emphasize the importance of matching aglycone BPA internal dosimetry with receptor affinities in experimental animal studies reporting toxicity. Published by Elsevier Inc. C1 [Doerge, Daniel R.; Twaddle, Nathan C.; Vanlandingham, Michelle] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Fisher, Jeffrey W.] Univ Georgia, Coll Publ Hlth, Dept Environm Hlth Sci, Athens, GA 30602 USA. RP Doerge, DR (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM daniel.doerge@fda.hhs.gov FU NCTR/FDA [224-07-0007]; National Institute for Environmental Health Sciences [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. The authors are grateful to Dr. John F. Young for helpful discussions. The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration. NR 38 TC 64 Z9 65 U1 1 U2 17 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD SEP 1 PY 2010 VL 247 IS 2 BP 158 EP 165 DI 10.1016/j.taap.2010.06.008 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 638OA UT WOS:000280903000011 PM 20600215 ER PT J AU Tang, S Zhao, J Viswanath, R Nyambi, PN Vermeulen, M Redd, AD Dastyar, A Wang, X Gaddam, D Hewlett, IK AF Tang, S. Zhao, J. Viswanath, R. Nyambi, P. N. Vermeulen, M. Redd, A. D. Dastyar, A. Wang, X. Gaddam, D. Hewlett, I. K. TI Absence of Detectable Xenotropic Murine Leukemia Virus-Related Virus in Plasma or Peripheral Blood Mononuclear Cells of Human Immunodeficiency Virus Type One (HIV-1) Infected Individuals in Cameroon, South Africa, and Uganda SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting 2010 CY OCT 09-12, 2010 CL Baltimore, MD SP AABB C1 [Tang, S.; Zhao, J.; Viswanath, R.; Dastyar, A.; Wang, X.; Gaddam, D.; Hewlett, I. K.] US FDA, LMV DETTD OBRR CBER, Bethesda, MD 20014 USA. [Nyambi, P. N.] NYU, Sch Med, Dept Pathol, New York, NY USA. [Vermeulen, M.] S African Natl Blood Serv, ZA-1715 Weltevreden Pk, South Africa. [Redd, A. D.] NIAID, Div Intramural Res, Bethesda, MD 20892 USA. EM shixing.tang@fda.hhs.gov 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 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2010 VL 50 SU 2 BP 5A EP 6A PG 2 WC Hematology SC Hematology GA 649JM UT WOS:000281764900011 ER PT J AU Grinev, A Lu, Z Chancey, C Daniel, S Caglioti, S Winkelman, V Land, KJ Stramer, SL Rios, M AF Grinev, A. Lu, Z. Chancey, C. Daniel, S. Caglioti, S. Winkelman, V. Land, K. J. Stramer, S. L. Rios, M. TI Genetic Variability of West Nile Virus in the US, 2002-2009 SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting 2010 CY OCT 09-12, 2010 CL Baltimore, MD SP AABB C1 [Grinev, A.; Lu, Z.; Chancey, C.; Daniel, S.; Rios, M.] CBER FDA, Bethesda, MD USA. [Caglioti, S.; Winkelman, V.] Blood Syst Lab, Tempe, AZ USA. [Land, K. J.] Bonfils Blood Ctr, Denver, CO USA. [Stramer, S. L.] Amer Red Cross, Gaithersburg, MD USA. EM andriyan.grinev@fda.hhs.gov 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 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2010 VL 50 SU 2 BP 19A EP 19A PG 1 WC Hematology SC Hematology GA 649JM UT WOS:000281764900041 ER PT J AU Wang, X Zhao, J Ye, Z Stramer, SL Krysztol, D Winton, C Hewlett, IK AF Wang, X. Zhao, J. Ye, Z. Stramer, S. L. Krysztol, D. Winton, C. Hewlett, I. K. TI Absence of Detectable H1N1 Viremia in Blood Donor Samples Collected During the 2009-2010 Pandemic Period SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting 2010 CY OCT 09-12, 2010 CL Baltimore, MD SP AABB C1 [Wang, X.; Zhao, J.; Ye, Z.; Winton, C.; Hewlett, I. K.] FDA, CBER OBRR LMV, Bethesda, MD USA. [Stramer, S. L.; Krysztol, D.] Amer Red Cross, Rockville, MD USA. EM xue.wang@fda.hhs.gov 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 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2010 VL 50 SU 2 BP 20A EP 20A PG 1 WC Hematology SC Hematology GA 649JM UT WOS:000281764900044 ER PT J AU Menis, M Burwen, DR Izurieta, H Anderson, SA Sholley, C Erten, T Holness, LG MaCurdy, T Kelman, J Ball, R AF Menis, M. Burwen, D. R. Izurieta, H. Anderson, S. A. Sholley, C. Erten, T. Holness, L. G. MaCurdy, T. Kelman, J. Ball, R. TI Outpatient Transfusions and Occurrence of Transfusion-Related Acute Lung Injury (TRALI) Among US Elderly, 2007-2008 SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting 2010 CY OCT 09-12, 2010 CL Baltimore, MD SP AABB C1 [Menis, M.; Burwen, D. R.; Izurieta, H.; Anderson, S. A.; Ball, R.] US FDA, CBER OBE, Rockville, MD 20857 USA. [Sholley, C.; Erten, T.; MaCurdy, T.] Acumen LLC, Burlingame, CA USA. [Holness, L. G.] US FDA, CBER OBRR, Rockville, MD 20857 USA. [Kelman, J.] Ctr Medicare, Baltimore, MD USA. [Kelman, J.] Ctr Medicaid Serv, Baltimore, MD USA. EM mikhail.menis@fda.hhs.gov 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 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2010 VL 50 SU 2 BP 135A EP 135A PG 1 WC Hematology SC Hematology GA 649JM UT WOS:000281764900336 ER PT J AU Struble, E Duan, H Zhong, L Harman, C Virata-Theimer, M Yu, MW Feinstone, S Alter, HJ Zhang, P AF Struble, E. Duan, H. Zhong, L. Harman, C. Virata-Theimer, M. Yu, M. W. Feinstone, S. Alter, H. J. Zhang, P. TI Presence of Neutralizing Antibodies in the Plasma of Chronic Hepatitis C Patients SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting 2010 CY OCT 09-12, 2010 CL Baltimore, MD SP AABB C1 [Struble, E.; Zhong, L.; Harman, C.; Virata-Theimer, M.; Yu, M. W.; Zhang, P.] US FDA, OBRR, DH, CBER, Bethesda, MD 20014 USA. [Duan, H.; Feinstone, S.] US FDA, OVRR, CBER, Bethesda, MD 20014 USA. [Alter, H. J.] NIH, Ctr Clin, Bethesda, MD 20892 USA. EM evi.struble@fda.hhs.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2010 VL 50 SU 2 BP 204A EP 204A PG 1 WC Hematology SC Hematology GA 649JM UT WOS:000281764900523 ER PT J AU Anez, G Chancey, C Grinev, A Morales-Betoulle, M Rios, M AF Anez, G. Chancey, C. Grinev, A. Morales-Betoulle, M. Rios, M. TI Detection of Dengue Virus in an Infected Human Specimen Suggests Viral Attachment to Red Blood Cells (RBC) SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting 2010 CY OCT 09-12, 2010 CL Baltimore, MD SP AABB C1 [Anez, G.; Chancey, C.; Grinev, A.; Rios, M.] US FDA, Div Emerging & Transfus Transmitted Dis, CBER, Bethesda, MD 20014 USA. [Morales-Betoulle, M.] Univ Valle Guatemala, Lab Ecol Arbovirus & Virus Zoonot, Guatemala City, Guatemala. EM German.Anez@fda.hhs.gov 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 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2010 VL 50 SU 2 BP 208A EP 209A PG 2 WC Hematology SC Hematology GA 649JM UT WOS:000281764900535 ER PT J AU Chancey, C Stroka-Lee, AH Rios, M AF Chancey, C. Stroka-Lee, A. H. Rios, M. TI Investigation of Potential Ligands for West Nile Virus on Human RBC SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting 2010 CY OCT 09-12, 2010 CL Baltimore, MD SP AABB C1 [Chancey, C.; Rios, M.] US FDA, DETTD, CBER, Bethesda, MD 20014 USA. [Stroka-Lee, A. H.] NIH, DTM, Bethesda, MD 20892 USA. EM caren.chancey@fda.hhs.gov 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 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2010 VL 50 SU 2 BP 209A EP 209A PG 1 WC Hematology SC Hematology GA 649JM UT WOS:000281764900536 ER PT J AU Snoy, PJ AF Snoy, P. J. TI Establishing Efficacy of Human Products Using Animals: The US Food and Drug Administration's ''Animal Rule'' SO VETERINARY PATHOLOGY LA English DT Article DE efficacy testing; animal rule ID PATHOLOGY; ANTHRAX; INHALATION; INFECTION; PLAGUE AB In 2002, the US Food and Drug Administration issued regulations to allow the approval of human drugs and biological products based on animal efficacy studies when human efficacy studies would be unethical or not feasible. These regulations are intended to assist in the approval process for products aimed at preventing or treating human diseases caused by nuclear, radiological, biological, and chemical agents that have the potential to harm a significant percentage of the US population. This article discusses the criteria that must be met to use the Animal Rule to demonstrate efficacy in place of human clinical trials. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Snoy, PJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM philip.snoy@fda.hhs.gov NR 10 TC 39 Z9 39 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD SEP PY 2010 VL 47 IS 5 BP 774 EP 778 DI 10.1177/0300985810372506 PG 5 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA 675BN UT WOS:000283798900003 PM 20551476 ER PT J AU Schrand, AM Rahman, MF Hussain, SM Schlager, JJ Smith, DA Ali, SF AF Schrand, Amanda M. Rahman, Mohammad F. Hussain, Saber M. Schlager, John J. Smith, David A. Ali, Syed F. TI Metal-based nanoparticles and their toxicity assessment SO WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY LA English DT Review ID IN-VITRO CYTOTOXICITY; FUNCTIONALIZED CARBON NANOTUBES; TITANIUM-DIOXIDE PARTICLES; CERIUM OXIDE NANOPARTICLES; HUMAN DERMAL FIBROBLASTS; INDUCE OXIDATIVE DAMAGE; LUNG EPITHELIAL-CELLS; SPRAGUE-DAWLEY RATS; SILVER NANOPARTICLES; GOLD NANOPARTICLES AB Nanoparticles (NPs) can potentially cause adverse effects on organ, tissue, cellular, subcellular, and protein levels due to their unusual physicochemical properties (e.g., small size, high surface area to volume ratio, chemical composition, crystallinity, electronic properties, surface structure reactivity and functional groups, inorganic or organic coatings, solubility, shape, and aggregation behavior). Metal NPs, in particular, have received increasing interest due to their widespread medical, consumer, industrial, and military applications. However, as particle size decreases, some metal-based NPs are showing increased toxicity, even if the same material is relatively inert in its, bulk form (e.g., Ag, Au, and Cu). NPs also interact with proteins and enzymes within mammalian cells and they can interfere with the antioxidant defense mechanism leading to reactive oxygen species generation, the initiation of an inflammatory response and perturbation and destruction of the mitochondria causing apoptosis or necrosis. As a result, there are many challenges to overcome before we can determine if the benefits outweigh the risks associated with NPs. (C) 2010 John Wiley & Sons, Inc. WIREs Nanomed Nanobiotechnol 2010 2 544-568 C1 [Rahman, Mohammad F.; Ali, Syed F.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Schrand, Amanda M.; Hussain, Saber M.; Schlager, John J.; Smith, David A.] Wright Patterson AFB, Dayton, OH 45433 USA. RP Ali, SF (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM syed.ali@fda.hhs.gov FU Joint Science and Technology Office for Chemical and Biological Defense; United States Air Force Research Laboratory, Dayton, Ohio, USA FX AMS received support from the National Research Council Fellowship program funded by the Joint Science and Technology Office for Chemical and Biological Defense, a program administered by the Defense Threat Reduction Agency. MFR 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 of Science and Education (Oak Ridge, TN, USA) sponsored by the United States Air Force Research Laboratory, Dayton, Ohio, USA. NR 201 TC 193 Z9 195 U1 14 U2 147 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1939-5116 J9 WIRES NANOMED NANOBI JI Wiley Interdiscip. Rev.-Nanomed. Nanobiotechnol. PD SEP-OCT PY 2010 VL 2 IS 5 BP 544 EP 568 DI 10.1002/wnan.103 PG 25 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 645KU UT WOS:000281456300008 PM 20681021 ER PT J AU Arcidiacono, JA Evdokimov, E Lee, MH Jones, J Rudenko, L Schneider, B Snoy, PJ Wei, CH Wensky, AK Wonnacott, K AF Arcidiacono, Judith A. Evdokimov, Evgenij Lee, Mark H. Jones, Jeff Rudenko, Larisa Schneider, Bruce Snoy, Phillip J. Wei, Cheng-Hong Wensky, Allen K. Wonnacott, Keith TI Regulation of xenogeneic porcine pancreatic islets SO XENOTRANSPLANTATION LA English DT Review DE diabetes; FDA; pancreatic islets; porcine; regulation ID CYNOMOLGUS MONKEYS; XENOTRANSPLANTATION; TRANSPLANTATION; PRODUCTS AB The use of xenogeneic porcine pancreatic islets has been shown to be a potentially promising alternative to using human allogeneic islets to treat insulin-dependent type 1 diabetes (T1D). This article provides an overview of the existing FDA regulatory framework that would be applied to the regulation of clinical trials utilizing xenogeneic porcine pancreatic islets to treat T1D. C1 [Arcidiacono, Judith A.; Lee, Mark H.; Schneider, Bruce; Wei, Cheng-Hong; Wensky, Allen K.; Wonnacott, Keith] US FDA, Ctr Biol Evaluat & Res CBER, Off Cellular Tissue & Gene Therapies, Rockville, MD 20852 USA. [Evdokimov, Evgenij; Jones, Jeff; Rudenko, Larisa] US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20857 USA. [Snoy, Phillip J.] US FDA, CBER, Off Management, Div Vet Serv, Bethesda, MD 20014 USA. RP Arcidiacono, JA (reprint author), US FDA, Ctr Biol Evaluat & Res CBER, Off Cellular Tissue & Gene Therapies, 1401 Rockville Pike, Rockville, MD 20852 USA. EM keith.wonnacott@fda.hhs.gov NR 19 TC 11 Z9 11 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2010 VL 17 IS 5 BP 329 EP 337 DI 10.1111/j.1399-3089.2010.00592.x PG 9 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 667CL UT WOS:000283170100001 PM 20955290 ER PT J AU Spragg, DD Dong, J Fetics, BJ Helm, R Marine, JE Cheng, A Henrikson, CA Kass, DA Berger, RD AF Spragg, David D. Dong, Jun Fetics, Barry J. Helm, Robert Marine, Joseph E. Cheng, Alan Henrikson, Charles A. Kass, David A. Berger, Ronald D. TI Optimal Left Ventricular Endocardial Pacing Sites for Cardiac Resynchronization Therapy in Patients With Ischemic Cardiomyopathy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE cardiac resynchronization therapy; heart failure; pacing ID NONISCHEMIC DILATED CARDIOMYOPATHY; HEART-FAILURE PATIENTS; BUNDLE-BRANCH BLOCK; CORONARY-SINUS; CONDUCTION; EXPRESSION; MORTALITY; LEAD AB Objectives We sought to investigate the impact of left ventricular (LV) pacing site on mechanical response to cardiac resynchronization therapy (CRT) in patients with ischemic cardiomyopathy (ICM). Background CRT reduces morbidity and mortality in patients with dyssynchronous LV failure; however, variability in response, particularly in ICM patients, poses ongoing challenges. Endocardial biventricular (BiV) stimulation may provide more flexibility in LV site selection and yield more natural transmural activation patterns. Whether this applies to ICM and whether optimal LV endocardial pacing locations vary among ICM patients remain unknown. Methods Peak rate of LV pressure increase (dP/dtmax) was measured at baseline, during VDD pacing at the right ventricular apex, and during BiV pacing from the right ventricular apex and 51 +/- 14 different LV endocardial sites in patients with ICM (n = 11). Seven patients already had an epicardial LV lead (CRT) in place, allowing comparison of epicardial BiV stimulation with that using an endocardial site directly transmural to the CRT-coronary sinus lead tip. Electroanatomic 3-dimensional maps with color-coded dP/dtmax response defined optimal pacing regions delivering >= 85% of maximal increase in dP/dt(max). Results Endocardial BiV pacing improved dP/dtmax over right ventricular apex pacing in all patients (mean increase 241 +/- 38 mm Hg/s; p < 0.0001). In patients with pre-existing CRT leads, LV endocardial versus epicardial pacing at transmural sites yielded equivalent dP/dtmax values. However, dP/dtmax at the best endocardial site exceeded that achieved with the pre-implanted CRT device (mean increase 111 +/- 25 mm Hg/s; p = 0.004). An average of similar to 2 optimal endocardial sites were identified for each patient, located at the extreme basal lateral wall (8 of 11 patients) and other regions (9 of 11). Standard mid-LV free wall pacing yielded suboptimal LV function in 73% of patients. Optimal pacing sites were typically located in LV territories remote (9.3 +/- 3.6 cm) from the infarct zone. Conclusions CRT delivered at best LV endocardial sites is more effective than via pre-implanted coronary sinus lead pacing. The location of optimal LV endocardial pacing varies among patients with ICM, and individual tailoring may improve CRT efficacy in such patients. (J Am Coll Cardiol 2010;56:774-81) c 2010 by the American College of Cardiology Foundation C1 [Spragg, David D.; Fetics, Barry J.; Helm, Robert; Marine, Joseph E.; Cheng, Alan; Henrikson, Charles A.; Kass, David A.; Berger, Ronald D.] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Dong, Jun] US FDA, Div Cardiovasc Dis, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Spragg, DD (reprint author), Johns Hopkins Univ Hosp, 4940 Eastern Ave, Baltimore, MD 21224 USA. EM dspragg1@jhmi.edu NR 23 TC 95 Z9 98 U1 0 U2 3 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 AUG 31 PY 2010 VL 56 IS 10 BP 774 EP 781 DI 10.1016/j.jacc.2010.06.014 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 642JH UT WOS:000281207700005 PM 20797490 ER PT J AU Kordzakhia, G Siddiqui, O Huque, MF AF Kordzakhia, George Siddiqui, Ohidul Huque, Mohammad F. TI Method of balanced adjustment in testing co-primary endpoints SO STATISTICS IN MEDICINE LA English DT Article DE co-primary endpoints; clinical trials; multiplicity AB In a clinical trial, if there are three or more co-primary endpoints, the type II error could increase depending on the correlation among the endpoints and their treatment effect sizes. To keep the type H error under control one may have to consider larger sample sizes. However, in cases where treatment effect size of at least one of the endpoints is likely to be small, the required sample size estimates can exceed reasonable bounds. Patel (1991) proposed an approach that adjusts the significance level for testing each primary endpoint based on the idea of restricting the null space. In Chuang-Stein et al. (2007), the upward adjustment to the significance levels is based on controlling an average type I error rate. In the scenario that statistical significance of each individual hypothesis is not required, we introduce a compromise testing approach in which the significance level for a co-primary endpoint is adjusted upward only if the treatment shows high significance in one (or more than one) of the remaining co-primary endpoints. The adjustment depends on the correlation among the endpoints: larger adjustment is needed for cases of smaller correlation. The method is applicable for the scenario where the null space is restricted. Our testing approach controls maximum joint false positive rate over the restricted null space. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Kordzakhia, George; Siddiqui, Ohidul] US FDA, Div Biometr 1, Off Biostat, CDER, Silver Spring, MD 20993 USA. [Huque, Mohammad F.] US FDA, Div Biometr 4, Off Biostat, CDER, Silver Spring, MD 20993 USA. [Huque, Mohammad F.] Georgia So Univ, Jiann Ping Hsu Coll Publ Hlth, Adjunct Fac, Statesboro, GA 30460 USA. RP Kordzakhia, G (reprint author), US FDA, Div Biometr 1, Off Biostat, CDER, Silver Spring, MD 20993 USA. EM George.Kordzakhia@fda.hhs.gov NR 4 TC 10 Z9 10 U1 0 U2 1 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 AUG 30 PY 2010 VL 29 IS 19 BP 2055 EP 2066 DI 10.1002/sim.3950 PG 12 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 642EB UT WOS:000281185500012 PM 20683896 ER PT J AU Jensen, V Rappaport, BA AF Jensen, Valerie Rappaport, Bob A. TI The Reality of Drug Shortages - The Case of the Injectable Agent Propofol SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Jensen, Valerie] Ctr Drug Evaluat & Res, Drug Shortage Program, FDA, Silver Spring, MD USA. [Rappaport, Bob A.] Ctr Drug Evaluat & Res, Div Anesthesia & Analgesia Prod, FDA, Silver Spring, MD USA. RP Jensen, V (reprint author), Ctr Drug Evaluat & Res, Drug Shortage Program, FDA, Silver Spring, MD USA. NR 5 TC 45 Z9 46 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 26 PY 2010 VL 363 IS 9 BP 806 EP 807 DI 10.1056/NEJMp1005849 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 642HG UT WOS:000281196600003 PM 20554977 ER PT J AU Gunsolly, C Nicholson, JD Listwak, SJ Ledee, D Zelenka, P Verthelyi, D Chapoval, S Keegan, A Tonelli, LH AF Gunsolly, Chad Nicholson, James D. Listwak, Samuel J. Ledee, Dolena Zelenka, Peggy Verthelyi, Daniela Chapoval, Svetlana Keegan, Achsah Tonelli, Leonardo H. TI Expression and regulation in the brain of the chemokine CCL27 gene locus SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE CTACK; PESKY; Alternative splicing; In situ hybridization; Neuroimmune; RT-PCR ID CENTRAL-NERVOUS-SYSTEM; SKIN-ASSOCIATED CHEMOKINE; ALLERGIC RHINITIS; MESSENGER-RNA; CUTTING EDGE; CC-CHEMOKINE; MOUSE MODEL; T-CELLS; RECEPTOR; INFLAMMATION AB The chemokine CCL27 has chemoattractant properties for memory T cells and has been implicated in skin allergic reactions. The present study reports the expression in the brain of two CCL27 splice variants localized in the cerebral cortex and limbic regions. CCL27-like immunoreactivity was identified mainly in neurons. Variant 1 was found elevated in the olfactory bulbs during allergic inflammation induced by intranasal challenge with allergen. This was accompanied by the presence of T cells in the olfactory bulbs. Intranasal administration of neutralizing antibodies against CCL27 reduced the presence of T cells in the olfactory bulbs suggesting a function in T cell activity in the brain. (C) 2010 Elsevier B.V. All rights reserved. C1 [Gunsolly, Chad; Nicholson, James D.; Tonelli, Leonardo H.] Univ Maryland, Sch Med, Dept Psychiat, Lab Behav Neuroimmunol,Mood & Anxiety Program, Baltimore, MD 21201 USA. [Listwak, Samuel J.] NIMH, NIH, Bethesda, MD 20892 USA. [Ledee, Dolena; Zelenka, Peggy] NEI, Cell Differentiat Sect, NIH, Bethesda, MD 20892 USA. [Verthelyi, Daniela] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Review, Bethesda, MD 20014 USA. [Chapoval, Svetlana; Keegan, Achsah] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA. [Chapoval, Svetlana; Keegan, Achsah] Univ Maryland, Sch Med, Program Oncol, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. RP Tonelli, LH (reprint author), 685 W Baltimore St,MSTF Bldg,Room 934 C, Baltimore, MD 21201 USA. EM Ltonelli@psych.umaryland.edu FU NIH; Department of Psychiatry, University of Maryland School of Medicine FX The authors wish to thank Dr. Esther M. Sternberg from the National Institute of Mental Health for her logistic support and Dr. Steven Bernstein from the University of Maryland for his help with antibodies used in this study. This study was supported by an Intramural Award from the Integrative Neural Immune Program, NIH, to PZ and LHT and by research seed funding from the Department of Psychiatry, University of Maryland School of Medicine. NR 45 TC 4 Z9 4 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 AUG 25 PY 2010 VL 225 IS 1-2 BP 82 EP 90 DI 10.1016/j.jneuroim.2010.04.019 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 651LA UT WOS:000281928000011 PM 20605223 ER PT J AU Fitzgerald, T Graham, L Fazio, M AF Fitzgerald, Timothy Graham, LeRae Fazio, Michael TI Detection of nitrofuran metabolites in imported shrimp: An internship experience at the Food and Drug Administration SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 CUNY Queensborough Community Coll, Dept Chem, Bayside, NY USA. Food & Drug Adm Reg Off, Jamaica, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 2010 VL 240 MA 222-CHED PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V20UK UT WOS:000208164701240 ER PT J AU Forrey, C Yager, KG AF Forrey, Christopher Yager, Kevin G. TI Molecular dynamics study of block copolymer thin film morphology: Effect of substrate and free surface SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Ctr Devices & Radiol Hlth, Food & Drug Adm, Div Chem & Mat Sci, Silver Spring, MD USA. Brookhaven Natl Lab, Ctr Funct Nanomat, Upton, NY 11973 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 2010 VL 240 MA 234-PMSE PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V20UK UT WOS:000208164706426 ER PT J AU Keene, AM Tyner, KM AF Keene, Athena M. Tyner, Katherine M. TI Gold nanoparticles can reduce cell proliferation by altering plating surfaces SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Keene, Athena M.; Tyner, Katherine M.] US FDA, Off Testing & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 2010 VL 240 MA 2-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V20UK UT WOS:000208164707269 ER PT J AU Keene, AM Tyner, KM AF Keene, Athena M. Tyner, Katherine M. TI Analytical characterization of gold nanoparticle primary particles, aggregates, agglomerates, and agglomerated aggregates SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Keene, Athena M.; Tyner, Katherine M.] US FDA, Off Testing & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 2010 VL 240 MA 160-COLL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V20UK UT WOS:000208164701643 ER PT J AU Khan, SA Sung, KD Nawaz, MS Cerniglia, CE Tamplin, ML Phillips, RW Kelley, LC AF Khan, Saeed A. Sung, Kidon Nawaz, Mohamed S. Cerniglia, Carl E. Tamplin, Mark L. Phillips, Robert W. Kelley, Lynda C. TI Survivability of Bacillus anthracis (Sterne strain) in processed liquid eggs SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. USDA, RRC, Athens, GA USA. Univ Tasmania, Australian Food Safety Ctr Excellence, Hobart, Tas, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 2010 VL 240 MA 62-IEC PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V20UK UT WOS:000208164703205 ER PT J AU Marques, M Godinho, ALA Oliveira, C Pereira, SA Monteiro, EC Beland, FA Antunes, AMM AF Marques, Matilde Godinho, Ana L. A. Oliveira, Conceicao Pereira, Sofia A. Monteiro, Emilia C. Beland, Frederick A. Antunes, Alexandra M. M. TI Mass spectrometric detection of hemoglobin adducts from the anti-HIV drug nevirapine and its metabolite 12-hydroxy-nevirapine in rats SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Tecn Lisboa, Inst Super Tecn, Ctr Quim Estrutural, P-1096 Lisbon, Portugal. Univ Nova Lisboa, Dept Farmacol, Fac Ciencias Med, P-1200 Lisbon, Portugal. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RI PTMS, RNEM/C-1589-2014; Antunes, Alexandra/B-7871-2009; Faculdade de Ciencias Medicas, Nova Medical School/K-6209-2013 OI Antunes, Alexandra/0000-0003-1827-7369; NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 2010 VL 240 MA 78-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V20UK UT WOS:000208164707319 ER PT J AU McCrane, MP Ad, O Weinert, EE Ling, Y Mazzola, EP Lam, YF Rokita, SE AF McCrane, Michael P. Ad, Omer Weinert, Emily E. Ling, Ying Mazzola, Eugene P. Lam, Yiu-Fai Rokita, Steven E. TI Trapping reversible ortho-quinone methide - nucleoside adducts SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. UMD FDA Joint Inst, Dept Chem & Biochem, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 2010 VL 240 MA 100-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V20UK UT WOS:000208164707231 ER PT J AU Shi, F Wong, JW Zhang, K Hayward, DG Begley, TH AF Shi, Feng Wong, Jon W. Zhang, Kai Hayward, Douglas G. Begley, Timothy H. TI Multiresidue pesticide analysis of botanical dietary supplements by GC-MS/MS and LC-MS/MS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Shi, Feng; Wong, Jon W.; Zhang, Kai; Hayward, Douglas G.; Begley, Timothy H.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 2010 VL 240 MA 46-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V20UK UT WOS:000208164700210 ER PT J AU Volarath, P Little, S Yang, C Martin, M Reif, D Richard, A AF Volarath, Patra Little, Stephen Yang, Chihae Martin, Matt Reif, David Richard, Ann TI Feature analysis of ToxCast (TM) compounds SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US EPA, Natl Ctr Computat Toxicol, Res Triangle Pk, NC 27711 USA. US FDA, Ctr Food Safety & Nutr, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 2010 VL 240 MA 85-CINF PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V20UK UT WOS:000208164701576 ER PT J AU Wyzgoski, FJ Reese, RN Paudel, L Rinaldi, PL Ozgen, M Giusti, MM Johnson, J Tulio, AZ Bomser, JA Hardy, JK Chanon, AM Scheerens, JC Miller, AR AF Wyzgoski, Faith J. Reese, R. Neil Paudel, Liladhar Rinaldi, Peter L. Ozgen, Mustafa Giusti, M. Monica Johnson, Jodee Tulio, Artemio Z., Jr. Bomser, Joshua A. Hardy, James K. Chanon, Ann M. Scheerens, Joseph C. Miller, A. Raymond TI Correlating component variability of black raspberry (Rubus occidentalis L.) fruit extracts with chemical and biological responses using NMR data and multivariate statistical analysis SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Ohio State Univ, Dept Chem, Mansfield, OH USA. S Dakota State Univ, Dept Biol & Microbiol, Brookings, SD 57007 USA. Univ Akron, Dept Chem, Akron, OH 44325 USA. Dept Hort, Tasliciftlik, Tokat, Turkey. Ohio State Univ, Dept Food Sci & Technol, Columbus, OH 43210 USA. Ohio State Univ, Dept Human Nutr, Columbus, OH 43210 USA. US FDA, Summit Argo, IL USA. Ohio State Univ, Ohio Agr & Res & Dev Ctr, Dept Hort & Crop Sci, Wooster, OH USA. RI Giusti, Maria/B-3367-2012; Miller, Ray Miller/E-2999-2017 NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 2010 VL 240 MA 10-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V20UK UT WOS:000208164700067 ER PT J AU Xiao, GD Li, GW Chen, LA Zhang, ZJ Yin, JJ Wu, T Cheng, ZH Wei, XH Wang, ZT AF Xiao, Guodong Li, Guowen Chen, Liang Zhang, Zijia Yin, Jun-Jie Wu, Tao Cheng, Zhihong Wei, Xiaohui Wang, Zhengtao TI Isolation of antioxidants from Psoralea corylifolia fruits using high-speed counter-current chromatography guided by thin layer chromatography-antioxidant autographic assay SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE High-speed counter-current chromatography; Psoralea corylifolia; Antioxidant; TLC bioautography; Electron spin resonance ID BIOACTIVE CONSTITUENTS; PREPARATIVE ISOLATION; TLC-BIOAUTOGRAPHY; NITRIC-OXIDE; SEEDS; COMPONENTS; INHIBITORS; PURIFICATION; MEDICINES; PRODUCTS AB A combinative method using high-speed counter-current chromatography (HSCCC) and thin layer chromatography (TLC) as an antioxidant autographic assay was developed to separate antioxidant components from the fruits of Psoralea corylifolia. Under the guidance of TLC bioautography, eight compounds including five flavonoids and three coumarins were successfully separated from the fruits of P. corylifolia by HSCCC with an optimized two-phase solvent system, n-hexane-ethyl acetate-methanol-water (1:1.1:1.3:1, v/v/v/v). The separation produced 5.91 mg psoralen, 6.26 mg isopsoralen, 3.19 mg psoralidin, 0.92 mg corylifol A. and 2.43 mg bavachinin with corresponding purities of 99.5, 99.8, 99.4, 96.4, and 99.0%, as well as three sub-fractions, in a single run from 250 mg ethyl acetate fraction of P. corylifolia extract. Following an additional clean-up step by preparative TLC, 0.4 mg 8-prenyldaidzein (purity 91.7%), 4.18 mg neobavaisoflavone (purity 97.4%) and 4.36 mg isobavachalcone (purity 96.8%) were separated from the three individual sub-fractions. The structures of the isolated compounds were identified by (1)H NMR and (13)C NMR. The results of antioxidant activity estimation by electron spin resonance (ESR) method showed that psoralidin was the most active antioxidant with an IC(50) value of 44.7 mu M. This is the first report on simultaneous separation of eight compounds from P. corylifolia by HSCCC. (C) 2010 Elsevier B.V. All rights reserved. C1 [Cheng, Zhihong] Fudan Univ, Dept Pharmacognosy, Shanghai 201203, Peoples R China. [Xiao, Guodong; Chen, Liang; Zhang, Zijia; Wu, Tao; Cheng, Zhihong; Wei, Xiaohui; Wang, Zhengtao] Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, SATCM Key Lab New Resources & Qual Evaluat Chines, MOE Key Lab Standardizat Chinese Med, Shanghai 201210, Peoples R China. [Xiao, Guodong; Chen, Liang; Zhang, Zijia; Wu, Tao; Cheng, Zhihong; Wei, Xiaohui; Wang, Zhengtao] Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, Shanghai Key Lab Compound Chinese Med, Shanghai 201210, Peoples R China. [Li, Guowen] Shanghai Univ Tradit Chinese Med, Inst Digest Dis, Shanghai 200032, Peoples R China. [Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Cheng, ZH (reprint author), Fudan Univ, Dept Pharmacognosy, 826 Zhangheng Rd, Shanghai 201203, Peoples R China. EM laurawu2000@hotmail.com; chengzhh@fudan.edu.cn RI Yin, Jun Jie /E-5619-2014 FU Shanghai Municipal Education Commission [09SG42]; Ministry of Science and Technology of China [2009ZX09502-021]; Ministry of Education [706025]; Shanghai Leading Academic Discipline Project [J50305]; Shanghai Key Laboratory of Complex Prescription (Shanghai University of Traditional Chinese Medicine) [09DZ2270900] FX This study was supported by an Innovation Research Team grant and "Dawn" program (09SG42) (awarded to Dr. T. Wu) from Shanghai Municipal Education Commission, a grant from Ministry of Science and Technology of China-Major Project (2009ZX09502-021), a grant from Ministry of Education (706025) (awarded to Dr. Z.T. Wang), grants from Shanghai Leading Academic Discipline Project (J50305), and a grant from the Opening Project of Shanghai Key Laboratory of Complex Prescription (Shanghai University of Traditional Chinese Medicine) (09DZ2270900). NR 30 TC 44 Z9 47 U1 4 U2 34 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 AUG 20 PY 2010 VL 1217 IS 34 BP 5470 EP 5476 DI 10.1016/j.chroma.2010.06.041 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 643JG UT WOS:000281291000003 PM 20663508 ER PT J AU Binienda, ZK Beaudoin, MA Gough, B Ali, SF Virmani, A AF Binienda, Zbigniew K. Beaudoin, Micheal A. Gough, Bobby Ali, Syed F. Virmani, Ashraf TI Assessment of 3-nitropropionic acid-evoked peripheral neuropathy in rats: Neuroprotective effects of acetyl-L-carnitine and resveratrol SO NEUROSCIENCE LETTERS LA English DT Article DE 3-Nitropropionic acid; Neuropathy; Acetyl-L-carnitine; Resveratrol ID OXIDATIVE STRESS; INDUCED NEUROTOXICITY; DAMAGE; BRAIN; ANTIOXIDANT; MECHANISMS; TOXICITY; DISEASE; INJURY; TOXIN AB Oxidative stress and secondary excitotoxicity, due to cellular energy deficit, are major factors playing roles in 3-nitropropionic acid (3-NPA) induced mitochondrial dysfunction. Acute or chronic exposure to 3-NPA also leads to neuronal degeneration in different brain regions. The present study quantitatively assessed peripheral neuropathy induced by chronic exposure to 3-NPA in rats. The neuroprotective abilities of two antioxidants, acetyl-L-carnitine and resveratrol, were investigated as well. Rats were exposed for up to four weeks to 3-NPA alone or 3-NPA combined with acetyl-L-carnitine or resveratrol, administered peripherally. The experimental outcome was evaluated by neurophysiological, histological, and morphometric analyses. Rats exposed to 3-NPA developed hind limb paresis. Furthermore, a significant decrease in motor nerve conduction velocity (MCV) was detected in tail nerves and axonal degeneration in sciatic nerves (p < 0.05). Treatment with resveratrol prevented the functional effects of 3-NPA exposure, whereas treatment with acetyl-L-carnitine, preventing paresis, was not effective to MCV and morphological changes. These data suggest that resveratrol is a good candidate for treatment of metabolic neuropathy. The experimental outcome of this study shows that chronic treatment with 3-NPA in rats is relevant in development of an experimental model of toxic neuropathy. Published by Elsevier Ireland Ltd. C1 [Binienda, Zbigniew K.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT 132, Jefferson, AR 72079 USA. [Beaudoin, Micheal A.] Z Tech Co, Jefferson, AR 72079 USA. [Virmani, Ashraf] Sigma Tau Hlth Sci SpA, I-00040 Monte Porzio Catone, Italy. RP Binienda, ZK (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT 132, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM zbigniew.binienda@fda.hhs.gov FU NCTR/FDA [E-07110.31]; Toxicologic Pathology Associates FX This research was supported by the NCTR/FDA protocol E-07110.31. The authors thank Drs. Kelly Davis and Alan Warbritton (Toxicologic Pathology Associates) for their support in this study. NR 27 TC 14 Z9 14 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD AUG 16 PY 2010 VL 480 IS 2 BP 117 EP 121 DI 10.1016/j.neulet.2010.06.020 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 635LM UT WOS:000280657100006 PM 20542088 ER PT J AU Misplon, JA Lo, CY Gabbard, JD Tompkins, SM Epstein, SL AF Misplon, Julia A. Lo, Chia-Yun Gabbard, Jon D. Tompkins, S. Mark Epstein, Suzanne L. TI Genetic control of immune responses to influenza A matrix 2 protein (M2) SO VACCINE LA English DT Article DE Matrix 2; Influenza; Genetics ID INTEGRAL MEMBRANE-PROTEIN; EXTRACELLULAR DOMAIN; MONOCLONAL-ANTIBODY; VIRUS-INFECTION; PROTECTIVE IMMUNITY; CROSS-PROTECTION; VACCINE; MICE; EPITOPE; HEMAGGLUTININ AB Vaccines should protect genetically diverse populations. Therefore we tested the candidate "universal" influenza A matrix protein 2 (M2) vaccine in multiple mouse strains. Mice were primed with M2 DNA and boosted with M2 recombinant adenovirus (rAd). C57BL/6 (B6) mice developed no antibody or T-cell response to M2, while BALB/c responded strongly. CBA responses were intermediate. Both MHC and background genes influenced responsiveness. To improve low responses we immunized with adjuvanted peptide-carrier conjugates, or co-immunized with nucleoprotein (NP), which can augment T-cell help. The conjugate vaccine enhanced some outcomes but not others. Co-immunizing with NP improved outcomes over either NP or M2 immunizations alone. These results have implications for vaccination of genetically diverse populations. Published by Elsevier Ltd. C1 [Misplon, Julia A.; Lo, Chia-Yun; Epstein, Suzanne L.] Food & Drug Adm, Ctr Biol & Res, Rockville, MD 20852 USA. [Gabbard, Jon D.; Tompkins, S. Mark] Univ Georgia, Dept Infect Dis, Athens, GA 30602 USA. RP Epstein, SL (reprint author), Food & Drug Adm, Ctr Biol & Res, 1401 Rockville Pike,HFM 730, Rockville, MD 20852 USA. EM Suzanne.Epstein@FDA.HHS.GOV RI Tompkins, Stephen/A-3317-2008 OI Tompkins, Stephen/0000-0002-1523-5588 NR 53 TC 16 Z9 16 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 16 PY 2010 VL 28 IS 36 BP 5817 EP 5827 DI 10.1016/j.vaccine.2010.06.069 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 645IW UT WOS:000281449000009 PM 20600476 ER PT J AU Yang, MH Sun, S Bruck, HA Kostov, Y Rasooly, A AF Yang, Minghui Sun, Steven Bruck, Hugh Alan Kostov, Yordan Rasooly, Avraham TI Electrical percolation-based biosensor for real-time direct detection of staphylococcal enterotoxin B (SEB) SO BIOSENSORS & BIOELECTRONICS LA English DT Article DE Biosensor; Semiconductor; Carbon nanotubes; Electrical percolation; Antibody; Point of care; Personalized medicine ID CARBON NANOTUBES; ATOPIC-DERMATITIS; RHEUMATOID-ARTHRITIS; FOOD; SUPERANTIGENS; FUNCTIONALIZATION; PREVALENCE; CHILDREN; TOXINS; ELISA AB Electrical percolation-based biosensing is a new technology. This is the first report of an electrical percolation-based biosensor for real-time detection. The label-free biosensor is based on electrical percolation through a single-walled carbon nanotubes (SWNTs)-antibody complex that forms a network functioning as a "Biological Semiconductor (BSC). The conductivity of a BSC is directly related to the number of contacts facilitated by the antibody-antigen "connectors" within the SWNT network. BSCs are fabricated by immobilizing a pre-functionalized SWNTs-antibody complex directly on a poly(methyl methacrylate) (PMMA) and polycarbonate (PC) surface. Each BSC is connected via silver electrodes to a computerized ohmmeter, thereby enabling a continuous electronic measurement of molecular interactions (e.g. antibody-antigen binding) via the change in resistance. Using anti-staphylococcal enterotoxin B (SEB) IgG to functionalize the BSC, we demonstrate that the biosensor was able to detect SEB at concentrations as low as 5 ng/mL at a signal to baseline (S/B) ratio of 2. Such measurements were performed on the chip in wet conditions. The actuation of the chip by SEB is immediate, permitting real-time signal measurements. In addition to this "direct" label-free detection mode, a secondary antibody can be used to "label" the target molecule bound to the BSC in a manner analogous to an immunological sandwich "indirect" detection-type assay. Although a secondary antibody is not needed for direct detection, the indirect mode of detection may be useful as an additional measurement to verify or amplify signals from direct detection in clinical, food safety and other critical assays. The BSC was used to measure SEB both in buffer and in milk, a complex matrix, demonstrating the potential of electrical percolation-based biosensors for real-time label-free multi-analyte detection in clinical and complex samples. Assembly of BSCs is simple enough that multiple sensors can be fabricated on the same chip, thereby creating "Biological Central Processing Units (BCPUs)" capable of parallel processing and sorting out information on multiple analytes simultaneously which may be used for complex analysis and for point of care diagnostics. Published by Elsevier B.V. C1 [Yang, Minghui; Sun, Steven; Kostov, Yordan] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Bruck, Hugh Alan] Univ Maryland, College Pk, MD 20742 USA. [Sun, Steven; Rasooly, Avraham] US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. [Rasooly, Avraham] NCI, Bethesda, MD 20892 USA. [Yang, Minghui] Univ Jinan, Sch Chem & Chem Engn, Jinan 250022, Peoples R China. RP Rasooly, A (reprint author), NCI, NIH, 6130 Execut Blvd,EPN,Room 6035A, Rockville, MD 20852 USA. EM rasoolya@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 40 TC 14 Z9 16 U1 0 U2 19 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 AUG 15 PY 2010 VL 25 IS 12 BP 2573 EP 2578 DI 10.1016/j.bios.2010.04.019 PG 6 WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical; Electrochemistry; Nanoscience & Nanotechnology SC Biophysics; Biotechnology & Applied Microbiology; Chemistry; Electrochemistry; Science & Technology - Other Topics GA 620YI UT WOS:000279538700004 PM 20447819 ER PT J AU Kim, PW Wu, YT Cooper, C Rochester, G Valappil, T Wang, Y Kornegay, C Nambiar, S AF Kim, Peter W. Wu, Yu-te Cooper, Charles Rochester, George Valappil, Thamban Wang, Yan Kornegay, Cynthia Nambiar, Sumathi TI Meta-Analysis of a Possible Signal of Increased Mortality Associated with Cefepime Use SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID NEUTROPENIC PATIENTS; BACTERIAL-INFECTIONS; FEBRILE NEUTROPENIA; THERAPY; CEFTAZIDIME; EFFICACY; SAFETY; CANCER AB Background. On the basis of meta-analyses, concern has been raised regarding a possible signal of increased mortality associated with the use of cefepime versus other beta-lactam antibiotics. To further investigate this possible signal, we accessed findings and data from published and unpublished cefepime clinical trials. Methods. We performed meta-analyses using trial-and patient-level data from comparative trials. Trial-level analyses were performed using summary data from all patients in the trials, and patient-level analyses were performed on trials for which patient-level data were available. Thirty-day, all-cause mortality was analyzed using the Mantel-Haenszel adjusted risk difference (ARD) method. Results. The trial-level meta-analysis was based on 88 trials (9467 cefepime patients and 8288 comparator patients). The 30-day, all-cause mortality rates were 6.21% (588/9467) for the cefepime patients and 6.00% (497/8288) for comparator patients (ARD per 1000 population, 5.38; 95% confidence interval [CI], -1.53 to 12.28). In the patient-level analysis (35 trials, 5058 cefepime patients, and 3976 comparator patients), 30-day, all-cause mortality rates were 5.63% (285/5058) for cefepime patients and 5.68% (226/3976) for comparator patients (ARD per 1000 population, 4.83; 95% CI, -4.72 to 14.38). A sensitivity analysis based solely on the 24 febrile neutropenia trials did not show a statistically significant increase in mortality with cefepime use (ARD per 1000 population, 9.67; 95% CI, -2.87 to 22.21). Conclusions. In both trial-level and patient-level meta-analyses, we did not identify a statistically significant increase in mortality among cefepime-treated patients, compared with those treated with other antibacterials. C1 [Kim, Peter W.; Nambiar, Sumathi] US FDA, Off Antimicrobial Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Wu, Yu-te; Cooper, Charles; Rochester, George; Valappil, Thamban; Wang, Yan] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Kornegay, Cynthia] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Kim, PW (reprint author), US FDA, Off Antimicrobial Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM peter.kim@fda.hhs.gov NR 27 TC 31 Z9 32 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG 15 PY 2010 VL 51 IS 4 BP 381 EP 389 DI 10.1086/655131 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 626WJ UT WOS:000279998300007 PM 20624065 ER PT J AU Konduru, K Kaplan, GG AF Konduru, Krishnamurthy Kaplan, Gerardo G. TI Determinants in 3D(pol) Modulate the Rate of Growth of Hepatitis A Virus SO JOURNAL OF VIROLOGY LA English DT Article ID DEPENDENT RNA-POLYMERASE; COMPLETE NUCLEOTIDE-SEQUENCE; CELL-CULTURE; REPLICATION; HAV; POLYPROTEIN; RESISTANCE; IDENTIFICATION; ADAPTATION; PARTICLES AB Hepatitis A virus (HAV), an atypical member of the Picornaviridae, grows poorly in cell culture. To define determinants of HAV growth, we introduced a blasticidin (Bsd) resistance gene into the virus genome and selected variants that grew at high concentrations of Bsd. The mutants grew fast and had increased rates of RNA replication and translation but did not produce significantly higher virus yields. Nucleotide sequence analysis and reverse genetic studies revealed that a T6069G change resulting in a F42L amino acid substitution in the viral polymerase (3D(pol)) was required for growth at high Bsd concentrations whereas a silent C7027T mutation enhanced the growth rate. Here, we identified a novel determinant(s) in 3D(pol) that controls the kinetics of HAV growth. C1 [Konduru, Krishnamurthy; Kaplan, Gerardo G.] US FDA, Lab Hepatitis & Related Emerging Agents, DETTD OBRR, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Kaplan, GG (reprint author), US FDA, Lab Hepatitis & Related Emerging Agents, DETTD OBRR, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM gk@helix.nih.gov FU Food and Drug Administration (FDA) FX This work was supported by intramural research funds from the Food and Drug Administration (FDA) to G.G.K. NR 29 TC 4 Z9 4 U1 0 U2 1 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 AUG 15 PY 2010 VL 84 IS 16 BP 8342 EP 8347 DI 10.1128/JVI.01470-09 PG 6 WC Virology SC Virology GA 626QZ UT WOS:000279983200042 PM 20534860 ER PT J AU Sakamoto, K Huang, BW Iwasaki, K Hailemariam, K Ninomiya-Tsuji, J Tsuji, Y AF Sakamoto, Kensuke Huang, Bo-Wen Iwasaki, Kenta Hailemariam, Kiros Ninomiya-Tsuji, Jun Tsuji, Yoshiaki TI Regulation of Genotoxic Stress Response by Homeodomain-interacting Protein Kinase 2 through Phosphorylation of Cyclic AMP Response Element-binding Protein at Serine 271 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID CREB TRANSCRIPTIONAL ACTIVITY; FERRITIN-H GENE; MEDIATED TRANSCRIPTION; DNA-DAMAGE; HIPK2; FAMILY; P53; APOPTOSIS; MULTIPLE; SURVIVAL AB CREB (cyclic AMP response element-binding protein) is a stimulus-induced transcription factor that plays pivotal roles in cell survival and proliferation. The transactivation function of CREB is primarily regulated through Ser-133 phosphorylation by cAMP-dependent protein kinase A (PKA) and related kinases. Here we found that homeodomain-interacting protein kinase 2 (HIPK2), a DNA-damage responsive nuclear kinase, is a new CREB kinase for phosphorylation at Ser-271 but not Ser-133, and activates CREB transactivation function including brain-derived neurotrophic factor (BDNF) mRNA expression. Ser-271 to Glu-271 substitution potentiated the CREB transactivation function. ChIP assays in SH-SY5Y neuroblastoma cells demonstrated that CREB Ser-271 phosphorylation by HIPK2 increased recruitment of a transcriptional coactivator CBP (CREB binding protein) without modulation of CREB binding to the BDNF CRE sequence. HIPK2-/- MEF cells were more susceptible to apoptosis induced by etoposide, a DNA-damaging agent, than HIPK2+/+ cells. Etoposide activated CRE-dependent transcription in HIPK2+/+ MEF cells but not in HIPK2-/- cells. HIPK2 knockdown in SH-SY5Y cells decreased etoposide-induced BDNF mRNA expression. These results demonstrate that HIPK2 is a new CREB kinase that regulates CREB-dependent transcription in genotoxic stress. C1 [Sakamoto, Kensuke; Huang, Bo-Wen; Iwasaki, Kenta; Hailemariam, Kiros; Ninomiya-Tsuji, Jun; Tsuji, Yoshiaki] N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. [Iwasaki, Kenta] Nagoya Univ, Sch Med, Dept Appl Immunol, Showa Ku, Nagoya, Aichi 4668550, Japan. [Hailemariam, Kiros] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Tsuji, Y (reprint author), N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. EM yoshiaki_tsuji@ncsu.edu FU National Institutes of Health (NIH) [DK-60007, GM068812, DK-60007S]; National Institute of Environmental Health Sciences, National Institutes of Health [ES-007046]; North Carolina State University FX We thank Dr. Huang at University of California San Francisco for kindly providing us with the HIPK2 wt and knockout MEF cells. We thank Dr. Schmitz at Justus-Liebig University, Germany, for HIPK2 plasmids. We also thank Drs. Goodman and Eckner for CBP and p300 plasmids. This work was supported in part by National Institutes of Health (NIH) research grant DK-60007 to Y.T., GM068812 to J.N.-T., NIH Supplement Grant DK-60007S and National Institute of Environmental Health Sciences, National Institutes of Health Training Grant ES-007046 to K.H., and North Carolina State University Research Assistant Fellowship to B.-W.H. NR 37 TC 12 Z9 15 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD AUG 15 PY 2010 VL 21 IS 16 BP 2966 EP 2974 DI 10.1091/mbc.E10-01-0015 PG 9 WC Cell Biology SC Cell Biology GA 638EK UT WOS:000280875200014 PM 20573984 ER PT J AU Clegg, LX Hankey, BF Tiwari, R Feuer, EJ Edwards, BK AF Clegg, Limin X. Hankey, Benjamin F. Tiwari, Ram Feuer, Eric J. Edwards, Brenda K. TI Comment on 'Estimating average annual per cent change in trend analysis' Reply SO STATISTICS IN MEDICINE LA English DT Letter C1 [Clegg, Limin X.] US Dept Vet Affairs, Washington, DC 20001 USA. [Tiwari, Ram] US FDA, Silver Spring, MD 20993 USA. [Feuer, Eric J.; Edwards, Brenda K.] NCI, Bethesda, MD 20892 USA. RP Clegg, LX (reprint author), US Dept Vet Affairs, 801 1 St NW,Room 1018, Washington, DC 20001 USA. EM ram.tiwari@fda.hhs.gov; edwardsb@mail.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 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 AUG 15 PY 2010 VL 29 IS 18 BP 1961 EP 1961 DI 10.1002/sim.3983 PG 1 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 640XR UT WOS:000281088000010 ER PT J AU Etheridge, SM AF Etheridge, Stacey M. TI Paralytic shellfish poisoning: Seafood safety and human health perspectives SO TOXICON LA English DT Article DE Paralytic shellfish poisoning; Saxitoxin; Dinoflagellates; Seafood; Shellfish; Puffer fish; Lobster; Detection methods; Monitoring; Management; Urine; Serum ID DINOFLAGELLATE GYMNODINIUM-CATENATUM; RECEPTOR-BINDING ASSAY; CYANOBACTERIUM ANABAENA-CIRCINALIS; HYDROXYBENZOATE SAXITOXIN ANALOGS; HARMFUL ALGAL BLOOMS; SODIUM CHANNEL-II; PSP TOXINS; ALEXANDRIUM-FUNDYENSE; PUFFER FISH; ENZYMATIC TRANSFORMATION AB Paralytic shellfish poisoning (PSP) is the foodborne illness associated with the consumption of seafood products contaminated with the neurotoxins known collectively as saxitoxins (STXs). This family of neurotoxins binds to voltage-gated sodium channels, thereby attenuating action potentials by preventing the passage of sodium ions across the membrane. Symptoms include tingling, numbness, headaches, weakness and difficulty breathing. Medical treatment is to provide respiratory support, without which the prognosis can be fatal. To protect human health, seafood harvesting bans are in effect when toxins exceed a safe action level (typically 80 mu g STX eq 100 g(-1) tissue). Though worldwide fatalities have occurred, successful management and monitoring programs have minimized PSP cases and associated deaths. Much is known about the toxin sources, primarily certain dinoflagellate species, and there is extensive information on toxin transfer to traditional vectors - filter-feeding molluscan bivalves. Non-traditional vectors, such as puffer fish and lobster, may also pose a risk. Rapid and reliable detection methods are critical for toxin monitoring in a wide range of matrices, and these methods must be appropriately validated for regulatory purposes. This paper highlights PSP seafood safety concerns, documented human cases, applied detection methods as well as monitoring and management strategies for preventing PSP-contaminated seafood products from entering the food supply. Published by Elsevier Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, Div Analyt Chem, College Pk, MD 20740 USA. RP Etheridge, SM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, Div Analyt Chem, 5100 Paint Branch Pkwy,HFS 707, College Pk, MD 20740 USA. EM Stacey.etheridge@fda.hhs.gov OI DeGrasse, Stacey/0000-0001-7808-4193 NR 152 TC 85 Z9 96 U1 11 U2 78 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 AUG 15 PY 2010 VL 56 IS 2 SI SI BP 108 EP 122 DI 10.1016/j.toxicon.2009.12.013 PG 15 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 614NC UT WOS:000279065100002 PM 20035780 ER PT J AU Dickey, RW Plakas, SM AF Dickey, Robert W. Plakas, Steven M. TI Ciguatera: A public health perspective SO TOXICON LA English DT Article DE Ciguatera; Ciguatoxins ID SENSITIVE SODIUM-CHANNELS; DINOFLAGELLATE GAMBIERDISCUS-TOXICUS; CHRONIC-FATIGUE-SYNDROME; GUINEA-PIG ATRIA; RAT PARASYMPATHETIC NEURONS; STATES VIRGIN ISLANDS; CHRONIC PHASE LIPIDS; FISH POISONING CCFP; JACK CARANX-LATUS; CARIBBEAN CIGUATOXINS AB Ciguatera fish poisoning is a seafood-borne illness caused by consumption of fish that have accumulated lipid-soluble ciguatoxins. In the United States, ciguatera is responsible for the highest reported incidence of food-borne illness outbreaks attributed to finfish, and it is reported to hold this distinction globally. Ciguatoxins traverse the marine food web from primary producers, Gambierdiscus spp., to commonly consumed fish in tropical and subtropical regions of the world. Ciguatoxins comprise 12 known congeners among Caribbean and tropical Atlantic fish and 29 reported congeners among Pacific fish. Expanding trade in fisheries from ciguatera-endemic regions contributes to wider distribution and increasing frequency of disease among seafood consumers in non-endemic regions. Ciguatoxins produce a complex array of gastrointestinal, neurological and cardiological symptoms. Treatment options are very limited and supportive in nature. Information derived from the study of ciguatera outbreaks has improved clinical recognition, confirmation, and timely treatment. Such studies are equally important for the differentiation of ciguatoxin profiles in fish from one region to the next, the determination of toxicity thresholds in humans, and the formulation of safety limits. Analytical information from case and outbreak investigations was used to derive Pacific and Caribbean ciguatoxin threshold contamination rates for adverse effects in seafood consumers. To these threshold estimates 10-fold safety factors were applied to address individual human risk factors; uncertainty in the amount of fish consumed; and analytical accuracy. The studies may serve as the basis for industry and consumer advisory levels of 0.10 ppb C-CTX-1 equivalent toxicity in fish from the tropical Atlantic, Gulf of Mexico, Caribbean, and 0.01 ppb P-CTX-1 equivalent toxicity in fish from Pacific regions. Published by Elsevier Ltd. C1 [Dickey, Robert W.; Plakas, Steven M.] US FDA, Ctr Food Safety & Appl Nutr, Off Food Safety, Div Seafood Sci & Technol,Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Dickey, RW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Food Safety, Div Seafood Sci & Technol,Gulf Coast Seafood Lab, 1 Iberville Dr, Dauphin Isl, AL 36528 USA. EM robert.dickey@fda.hhs.gov NR 222 TC 94 Z9 97 U1 6 U2 52 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 AUG 15 PY 2010 VL 56 IS 2 SI SI BP 123 EP 136 DI 10.1016/j.toxicon.2009.09.008 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 614NC UT WOS:000279065100003 PM 19782098 ER PT J AU Plakas, SM Dickey, RW AF Plakas, Steven M. Dickey, Robert W. TI Advances in monitoring and toxicity assessment of brevetoxins in molluscan shellfish SO TOXICON LA English DT Review DE Brevetoxins; Neurotoxic shellfish poisoning; Monitoring; Shellfish ID OYSTER CRASSOSTREA-VIRGINICA; TANDEM MASS-SPECTROMETRY; KARENIA-BREVIS CULTURES; NEW-ZEALAND; RED TIDE; AUSTROVENUS-STUTCHBURYI; PERNA-CANALICULUS; PTYCHODISCUS-BREVIS; GREENSHELL MUSSEL; GYMNODINIUM-BREVE AB Herein, we describe advancements in monitoring of brevetoxins in molluscan shellfish, with respect to exposure management and control of neurotoxic shellfish poisoning (NSP). Current knowledge of the fate of brevetoxins in molluscan shellfish, and the toxic potency of brevetoxin metabolites, is presented. We review rapid assays for measuring composite brevetoxins, and methodology for measuring constituent brevetoxins, in contaminated shellfish. The applicability of in vitro methods for estimating brevetoxin burden and composite toxicity in shellfish is assessed. Specific and measurable biomarkers of brevetoxin exposure and toxicity in shellfish, and of human intoxication, are described. Their utility in regulatory monitoring of toxic shellfish and in clinical diagnosis of NSP is evaluated. Published by Elsevier Ltd. C1 [Plakas, Steven M.; Dickey, Robert W.] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Plakas, SM (reprint author), US FDA, Gulf Coast Seafood Lab, 1 Iberville Dr, Dauphin Isl, AL 36528 USA. EM Steven.Plakas@fda.hhs.gov NR 52 TC 27 Z9 29 U1 0 U2 16 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 AUG 15 PY 2010 VL 56 IS 2 SI SI BP 137 EP 149 DI 10.1016/j.toxicon.2009.11.007 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 614NC UT WOS:000279065100004 PM 19925816 ER PT J AU Deeds, JR Schwartz, MD AF Deeds, Jonathan R. Schwartz, Michael D. TI Human risk associated with palytoxin exposure SO TOXICON LA English DT Article DE Palytoxin; Seafood poisoning; Exposure risks; Marine aerosols; Aquarium zoanthids ID DINOFLAGELLATE OSTREOPSIS-SIAMENSIS; PUTATIVE PALYTOXIN; MOLECULAR EVIDENCE; CORAL-REEF; TOXIN; HEXACORALLIA; PALYTHOA; CRAB; IDENTIFICATION; SEQUESTRATION AB Palytoxin (PTX) was first isolated from the zoanthid Palythoa toxica. Evaluation of PTX toxicity using various animal models determined that PTX was extremely potent through intravenous, intraperitoneal, and intratracheal exposure. PTX was less potent by direct intragastric exposure. PTX also caused significant, non-lethal effects through dermal and ocular exposure. PTX and PTX-like compounds have now been found in additional zoanthid species, red alga, a sea anemone, and several dinoflagellates. PTXs are found throughout certain reef associated food webs, including in fish and crabs responsible for human illness and death. Many of the organisms found to contain PTXs in the environment are also sold in the home aquarium trade, and recent evidence suggests poisonings have occurred through exposure to these organisms. Due to co-occurrence with other seafood toxins, such as ciguatoxins, saxitoxins, and tetrodotoxin, it has been difficult to assess the true risk of PTX poisoning through seafood consumption in humans, but limited cases have been well documented, some involving human fatalities. Recent evidence also suggests that humans are negatively impacted through PTX exposure by inhalation and dermal routes. Continued research into the distribution and occurrence of PTX and PTX-like compounds both in seafood and marine organisms sold in the aquarium trade appears warranted. Published by Elsevier Ltd. C1 [Deeds, Jonathan R.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Schwartz, Michael D.] Georgia Poison Ctr, Atlanta, GA 30303 USA. RP Deeds, JR (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 707, College Pk, MD 20740 USA. EM jonathan.deeds@fda.hhs.gov NR 60 TC 88 Z9 89 U1 4 U2 22 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 AUG 15 PY 2010 VL 56 IS 2 SI SI BP 150 EP 162 DI 10.1016/j.toxicon.2009.05.035 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 614NC UT WOS:000279065100005 PM 19505494 ER PT J AU Hungerford, JM AF Hungerford, James M. TI Scombroid poisoning: A review SO TOXICON LA English DT Article DE Scombroid poisoning; Histamine; Scombrotoxin; Seafood safety; Test kits; Dockside testing ID LACTIC-ACID BACTERIUM; FREE AMINO-ACIDS; LIQUID-CHROMATOGRAPHIC DETERMINATION; HISTIDINE-DECARBOXYLASE ACTIVITY; CAPILLARY-ZONE-ELECTROPHORESIS; HISTAMINE N-METHYLTRANSFERASE; MAHIMAHI CORYPHAENA-HIPPURUS; TEMPERATURE-ABUSED ALBACORE; INTESTINAL DIAMINE OXIDASE; FLOW-INJECTION ANALYSIS AB Scombroid poisoning, also called histamine fish poisoning, is an allergy-like form of food poisoning that continues to be a major problem in seafood safety. The exact role of histamine in scombroid poisoning is not straightforward. Deviations from the expected dose-response have led to the advancement of various possible mechanisms of toxicity, none of them proven. Histamine action levels are used in regulation until more is known about the mechanism of scombroid poisoning. Scombroid poisoning and histamine are correlated but complicated. Victims of scombroid poisoning respond well to antihistamines, and chemical analyses of fish implicated in scombroid poisoning generally reveal elevated levels of histamine. Scombroid poisoning is unique among the seafood toxins since it results from product mishandling rather than contamination from other trophic levels. Inadequate cooling following harvest promotes bacterial histamine production, and can result in outbreaks of scombroid poisoning. Fish with high levels of free histidine, the enzyme substrate converted to histamine by bacterial histidine decarboxylase, are those most often implicated in scombroid poisoning. Laboratory methods and screening methods for detecting histamine are available in abundance, but need to be compared and validated to harmonize testing. Successful field testing, including dockside or on-board testing needed to augment HACCP efforts will have to integrate rapid and simplified detection methods with simplified and rapid sampling and extraction. Otherwise, time-consuming sample preparation reduces the impact of gains in detection speed on the overall analysis time. Published by Elsevier Ltd. C1 USFDA, ATC, PRL NW, Bothell, WA 98021 USA. RP Hungerford, JM (reprint author), USFDA, ATC, PRL NW, 22201 23rd Dr SE, Bothell, WA 98021 USA. EM James.Hungerford@fda.hhs.fda.gov NR 190 TC 111 Z9 113 U1 3 U2 51 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 AUG 15 PY 2010 VL 56 IS 2 SI SI BP 231 EP 243 DI 10.1016/j.toxicon.2010.02.006 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 614NC UT WOS:000279065100010 PM 20152850 ER PT J AU Wang, X Zhao, JP Tang, SX Ye, ZP Hewlett, I AF Wang, Xue Zhao, Jiangqin Tang, Shixing Ye, Zhiping Hewlett, Indira TI Viremia Associated with Fatal Outcomes in Ferrets Infected with Avian H5N1 Influenza Virus SO PLOS ONE LA English DT Article ID HUMANS; PATHOGENESIS; PATHOLOGY AB Avian H5N1 influenza viruses cause severe disease and high mortality in infected humans. However, tissue tropism and underlying pathogenesis of H5N1 virus infection in humans needs further investigation. The objective of this work was to study viremia, tissue tropism and disease pathogenesis of H5N1 virus infection in the susceptible ferret animal model. To evaluate the relationship of morbidity and mortality with virus loads, we performed studies in ferrets infected with the H5N1 strain A/VN/1203/04 to assess clinical signs after infection and virus load in lung, brain, ileum, nasal turbinate, nasal wash, and blood. We observed that H5N1 infection in ferrets is characterized by high virus load in the brain and and low levels in the ileum using real-time PCR. In addition, viral RNA was frequently detected in blood one or two days before death and associated with symptoms of diarrhea. Our observations further substantiate pathogenicity of H5N1 and further indicate that viremia may be a bio-marker for fatal outcomes in H5N1 infection. C1 [Wang, Xue; Zhao, Jiangqin; Tang, Shixing; Hewlett, Indira] US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20014 USA. [Ye, Zhiping] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Wang, X (reprint author), US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20014 USA. EM xue.wang@fda.hhs.gov; indira.hewlett@fda.hhs.gov NR 16 TC 10 Z9 11 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 12 PY 2010 VL 5 IS 8 AR e12099 DI 10.1371/journal.pone.0012099 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 637ZU UT WOS:000280859700005 PM 20730085 ER PT J AU Winterstein, AG Linden, S Lee, AE Fernandez, EM Kimberlin, CL AF Winterstein, Almut G. Linden, Stephan Lee, Abigail E. Fernandez, Erica M. Kimberlin, Carole L. TI Evaluation of Consumer Medication Information Dispensed in Retail Pharmacies SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID DRUG BENEFITS AB Background: United States retail pharmacies are key sources of written consumer medication information (CMI) through leaflets dispensed with prescription drugs. The content and format of this CMI are unregulated. Public Law 104-180 stipulates that by 2006, 95% of prescriptions be accompanied by "useful" CMI. Methods: Professional shoppers filled prescriptions for lisinopril and metformin in a national sample of 365 pharmacies. Dispensed CMI was evaluated according to explicit criteria (77 for lisinopril and 78 for metformin) adapted from Food and Drug Administration guidelines. Results: Six percent of pharmacies did not provide any written CMI. A mean (SD) of 60.2% (20.7%) and 57.7% (20.1%) of the criteria for useful CMI were met for lisinopril and metformin prescriptions, respectively. Shortcomings concerned especially "directions about use" with means of 53.4% (95% confidence interval [CI], 51.4%-56.5%) and 45.6% (43.7%-47.6%), and "comprehensibility/legibility,"with means of 43.8% (42.6%-44.9%) and 42.6% (41.1%-43.7%) for lisinopril and metformin, respectively. The CMI leaflets ranged from 33 to 2482 words, with more than 1000-word differences among those meeting higher than 80% of the content criteria, suggesting large variations in conciseness. Chain pharmacies had better adherence to content criteria than did independent stores, with mean differences of 22.1% (95% CI, 15.8%-28.4%) for lisinopril and 21.1% (95% CI, 14.9%-27.3%) for metformin. Conclusions: Although distribution through pharmacies seems effective, the content, format, reading level, and excessive length of CMI are disconcerting. Private sector initiatives to provide useful CMI have failed. Research is needed on effective information selection and presentation in terms of effects on comprehension, retention, and appropriate patient actions to derive optimal drug benefit. C1 [Winterstein, Almut G.] Univ Florida, Coll Pharm, Coll Publ Hlth & Hlth Profess, Gainesville, FL 32610 USA. [Winterstein, Almut G.] Univ Florida, Coll Pharm Epidemiol & Biostat, Coll Publ Hlth & Hlth Profess, Gainesville, FL 32610 USA. [Winterstein, Almut G.] Univ Florida, US FDA, Ctr Drug Evaluat & Res, Grad Program Pharmaceut Outcomes & Policy Res, Gainesville, FL 32610 USA. RP Winterstein, AG (reprint author), Univ Florida, Coll Pharm, Coll Publ Hlth & Hlth Profess, Box 100496, Gainesville, FL 32610 USA. EM almut@cop.ufl.edu RI winterstein, Almut/A-3017-2014 OI winterstein, Almut/0000-0002-6518-5961 NR 14 TC 18 Z9 18 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD AUG 9 PY 2010 VL 170 IS 15 BP 1317 EP 1324 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 635JN UT WOS:000280651500005 PM 20696955 ER PT J AU Summers, RM Liu, JM Rehani, B Stafford, P Brown, L Louie, A Barlow, DS Jensen, DW Cash, B Choi, JR Pickhardt, PJ Petrick, N AF Summers, Ronald M. Liu, Jiamin Rehani, Bhavya Stafford, Phillip Brown, Linda Louie, Adeline Barlow, Duncan S. Jensen, Donald W. Cash, Brooks Choi, J. Richard Pickhardt, Perry J. Petrick, Nicholas TI CT Colonography Computer-Aided Polyp Detection: Effect on Radiologist Observers of Polyp Identification by CAD on Both the Supine and Prone Scans SO ACADEMIC RADIOLOGY LA English DT Article DE CT; colon; CT; virtual imaging; colon cancer; image processing; automated detection; observer performance ID TOMOGRAPHIC VIRTUAL COLONOSCOPY; MAMMOGRAPHIC VIEWS; READER PARADIGM; 2ND READER; PERFORMANCE; SENSITIVITY; SCHEME AB Rationale and Objectives: To determine whether the display of computer-aided detection (CAD) marks on individual polyps on both the supine and prone scans leads to improved polyp detection by radiologists compared to the display of CAD marks on individual polyps on either the supine or the prone scan, but not both. Materials and Methods: The acquisition of patient data for this study was approved by the Institutional Review Board and was Health Insurance Portability and Accountability Act-compliant. Subsequently, the use of the data was declared exempt from further institutional review board review. Four radiologists interpreted 33 computed tomography colonography cases, 21 of which had one adenoma 6-9 mm in size, with the assistance of a CAD system in the first reader mode (ie, the radiologists reviewed only the CAD marks). The radiologists were shown each case twice, with different sets of CAD marks for each of the two readings. In one reading, a true-positive CAD mark for the same polyp was displayed on both the supine and prone scans (a double-mark reading). In the other reading, a true-positive CAD mark was displayed either on the supine or prone scan, but not both (a single-mark reading). True-positive marks were randomized between readings and there was at least a 1-month delay between readings to minimize recall bias. Sensitivity and specificity were determined and receiver operating characteristic (ROC) and multiple-reader multiple-case analyses were performed. Results: The average per polyp sensitivities were 60% (38%-81%) versus 71% (52%-91%) (P = .03) for single-mark and double-mark readings, respectively. The areas (95% confidence intervals) under the ROC curves were 0.76 (0.62-0.88) and 0.79 (0.58-0.96), respectively (P = NS). Specificities were similar for the single-mark compared with the double-mark readings. Conclusion: The display of CAD marks on a polyp on both the supine and prone scans led to more frequent detection of polyps by radiologists without adversely affecting specificity for detecting 6-9 mm adenomas. C1 [Summers, Ronald M.; Liu, Jiamin; Rehani, Bhavya; Stafford, Phillip; Brown, Linda; Louie, Adeline] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. [Barlow, Duncan S.; Jensen, Donald W.; Cash, Brooks] Natl Naval Med Ctr, Colon Hlth Initiat, Bethesda, MD USA. [Choi, J. Richard] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Pickhardt, Perry J.] Univ Wisconsin, Sch Med, Dept Radiol, Madison, WI USA. [Petrick, Nicholas] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Summers, RM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10,Room 1C368X MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov FU National Institutes of Health (NIH); National Institute of Biomedical Imaging and Bioengineering FX From the Imaging Biomarkers and Computer-Aided Diagnosis Laboratory, Radiology and Imaging Sciences, National Institutes of Health Clinical Center, Bldg. 10, Room 1C368X MSC 1182, Bethesda, MD 20892-1182 (R.M.S., J.L., B.R., P.S., LB., A.L.); Colon Health Initiative, National Naval Medical Center, Bethesda, MD (D.S.B., D.W.J., B.C.); Walter Reed Army Medical Center, Washington, DC (J.R.C.); Department of Radiology, University of Wisconsin Medical School, Madison, WI (P.J.P); Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD (NP.) Received February 15, 2010; accepted March 26, 2010. Presented in part at the 2008 meeting of CARS, Barcelona, Spain. Supported in part by the Intramural Research Program of the National Institutes of Health (NIH) Clinical Center and the National Institute of Biomedical Imaging and Bioengineering (NP.). R.M.S. has pending and/or awarded patents for the subject matter described in the manuscript and receives royalty income for a patent license from iCAD. His lab is supported in part by a Cooperative Research and Development Agreement with iCAD. Viatronix supplied the V3D Colon software to NIH free of charge. P.J.P. is on the medical advisory boards of Viatronix, Inc, and Medicsight, Inc, a consultant to Covidien and co-founder of VirtuoCTC. J.R.C. is on the medical advisory boards of Viatronix, Inc, and QI and has received research support from E-Z-EM. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government and no official endorsement of any equipment or product of any company mentioned in the publication should be inferred. Address correspondence to: R.M.S. e-mail: rms@nih.gov NR 31 TC 9 Z9 9 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 2010 VL 17 IS 8 BP 948 EP 959 DI 10.1016/j.acra.2010.03.024 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 627IO UT WOS:000280032900002 PM 20542452 ER PT J AU Wang, SY Phillippy, AM Deng, KP Rui, XQ Li, ZX Tortorello, ML Zhang, W AF Wang, Siyun Phillippy, Adam M. Deng, Kaiping Rui, Xiaoqian Li, Zengxin Tortorello, Mary Lou Zhang, Wei TI Transcriptomic Responses of Salmonella enterica Serovars Enteritidis and Typhimurium to Chlorine-Based Oxidative Stress SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID PROTEIN SECRETION SYSTEM; ESCHERICHIA-COLI K-12; BIOFILM FORMATION; III SECRETION; EGG-ALBUMIN; GENOME; IDENTIFICATION; EXPRESSION; GENES; MICROARRAY AB Salmonella enterica serovars Enteritidis and Typhimurium are the leading causative agents of salmonellosis in the United States. S. Enteritidis is predominantly associated with contamination of shell eggs and egg products, whereas S. Typhimurium is frequently linked to tainted poultry meats, fresh produce, and recently, peanut-based products. Chlorine is an oxidative disinfectant commonly used in the food industry to sanitize the surfaces of foods and food processing facilities (e.g., shell eggs and poultry meats). However, chlorine disinfection is not always effective, as some S. enterica strains may resist and survive the disinfection process. To date, little is known about the underlying mechanisms of how S. enterica responds to chlorine-based oxidative stress. In this study, we designed a custom bigenome microarray that consists of 385,000 60-mer oligonucleotide probes and targets 4,793 unique gene features in the genomes of S. Enteritidis strain PT4 and S. Typhimurium strain LT2. We explored the transcriptomic responses of both strains to two different chlorine treatments (130 ppm of chlorine for 30 min and 390 ppm of chlorine for 10 min) in brain heart infusion broth. We identified 209 S. enterica core genes associated with Fe-S cluster assembly, cysteine biosynthesis, stress response, ribosome formation, biofilm formation, and energy metabolism that were differentially expressed (> 1.5-fold; P < 0.05). In addition, we found that serovars Enteriditis and Typhimurium differed in the responses of 33 stress-related genes and 19 virulence-associated genes to the chlorine stress. Findings from this study suggest that the oxidative-stress response may render S. enterica resistant or susceptible to certain types of environmental stresses, which in turn promotes the development of more effective hurdle interventions to reduce the risk of S. enterica contamination in the food supply. C1 [Wang, Siyun; Rui, Xiaoqian; Li, Zengxin; Zhang, Wei] IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. [Phillippy, Adam M.] Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA. [Deng, Kaiping; Tortorello, Mary Lou] US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Zhang, W (reprint author), IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. EM zhangw@iit.edu FU USDA Agriculture and Food Research Initiative [2010-65201-20593]; FDA FX This study was supported in part by USDA Agriculture and Food Research Initiative grant no. 2010-65201-20593 to W.Z. and an FDA cooperative agreement research fund to the National Center for Food Safety and Technology of the Illinois Institute of Technology. NR 68 TC 21 Z9 23 U1 1 U2 14 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 AUG PY 2010 VL 76 IS 15 BP 5013 EP 5024 DI 10.1128/AEM.00823-10 PG 12 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 630II UT WOS:000280266200012 PM 20562293 ER PT J AU Rump, LV Beutin, L Fischer, M Feng, PCH AF Rump, Lydia V. Beutin, Lothar Fischer, Markus Feng, Peter C. H. TI Characterization of a gne::IS629 O Rough: H7 Escherichia coli Strain from a Hemorrhagic Colitis Patient SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID MULTIPLEX PCR; O157 ANTIGEN; IDENTIFICATION AB Shiga-toxigenic Escherichia coli strains that are O rough:H7 due to gne::IS629 were thought to be rare and to have unknown pathogenic potential. Recently, an O rough: H7 strain caused by gne:: IS629 was isolated from a hemorrhagic colitis patient, suggesting that these strains are pathogenic and may not be as rare as anticipated. C1 [Rump, Lydia V.; Feng, Peter C. H.] US FDA, HFS 711, Div Microbiol, College Pk, MD 20740 USA. [Rump, Lydia V.; Fischer, Markus] Univ Hamburg, Inst Food Chem, Hamburg, Germany. [Beutin, Lothar] Fed Inst Risk Assessment, Natl Reference Lab Escherichia coli, Berlin, Germany. RP Feng, PCH (reprint author), US FDA, HFS 711, Div Microbiol, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM peter.feng@fda.hhs.gov RI Fischer, Markus/G-9477-2012 FU Center for Food Safety and Applied Nutrition through FDA FX This project was supported by an appointment to the Research Fellowship Program for the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Associated Universities through a contract with the FDA. NR 8 TC 6 Z9 8 U1 0 U2 1 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 AUG PY 2010 VL 76 IS 15 BP 5290 EP 5291 DI 10.1128/AEM.00740-10 PG 2 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 630II UT WOS:000280266200045 PM 20543034 ER PT J AU Yildirim, S Elhanafi, D Lin, W Hitchins, AD Siletzky, RM Kathariou, S AF Yildirim, Suleyman Elhanafi, Driss Lin, Wen Hitchins, Anthony D. Siletzky, Robin M. Kathariou, S. TI Conservation of Genomic Localization and Sequence Content of Sau3AI-Like Restriction-Modification Gene Cassettes among Listeria monocytogenes Epidemic Clone I and Selected Strains of Serotype 1/2a SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID TURKEY-PROCESSING PLANTS; FOOD-BORNE PATHOGEN; MODIFICATION SYSTEMS; HORIZONTAL TRANSFER; MOLECULAR CHARACTERIZATION; STREPTOCOCCUS-SUIS; DNA; EXPRESSION; ENVIRONMENT; EVOLUTION AB Listeria monocytogenes is a food-borne pathogen with a clonal population structure and apparently limited gene flow between strains of different lineages. Strains of epidemic clone I (ECI) have been responsible for numerous outbreaks and invariably have DNA that is resistant to digestion by Sau3AI, suggesting methylation of cytosine at GATC sites. A putative restriction-modification (RM) gene cassette has been identified in the genome of the ECI strain F2365 and all other tested ECI strains but is absent from other strains of the same serotype (4b). Homologous RM cassettes have not been reported among L. monocytogenes isolates of other serotypes. Furthermore, conclusive evidence for the involvement of this RM cassette in the Sau3AI resistance phenotype of ECI strains has been lacking. In this study, we describe a highly conserved RM cassette in certain strains of serotypes 1/2a and 4a that have Sau3AI-resistant DNA. In these strains the RM cassette was in the same genomic location as in the ECI reference strain F2365. The cassette included a gene encoding a putative recombinase, suggesting insertion via site-specific recombination. Deletion of the RM cassette in the ECI strain F2365 and the serotype 1/2a strain A7 rendered the DNA of both strains susceptible to Sau3AI digestion, providing conclusive evidence that the cassette includes a gene required for methylation of cytosine at GATC sites in both strains. The findings suggest that, in addition to its presence in ECI strains, this RM cassette and the accompanying genomic DNA methylation is also encountered among selected strains of other lineages. C1 [Yildirim, Suleyman; Elhanafi, Driss; Siletzky, Robin M.; Kathariou, S.] N Carolina State Univ, Dept Food Sci, Raleigh, NC 27695 USA. [Lin, Wen] US FDA, Irvine, CA USA. [Hitchins, Anthony D.] US FDA, College Pk, MD USA. RP Kathariou, S (reprint author), N Carolina State Univ, Dept Food Sci, Box 7624, Raleigh, NC 27695 USA. EM skathar@unity.ncsu.edu FU USDA-National Alliance for Food Safety and Security; North Carolina State University; Cornell University; USDA-ARS; USDA [2006-35201-17377] FX Partial funding for this project was obtained from the USDA-National Alliance for Food Safety and Security through a project that involved collaboration between S. Kathariou and L.-A. Jaykus (North Carolina State University), K. Boor (Cornell University), and I. Wesley (USDA-ARS). The project was also partially funded by USDA grant 2006-35201-17377. NR 43 TC 9 Z9 9 U1 0 U2 4 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 AUG PY 2010 VL 76 IS 16 BP 5577 EP 5584 DI 10.1128/AEM.00648-10 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 635CO UT WOS:000280633400030 PM 20581194 ER PT J AU Diak, P Siegel, J La Grenade, L Choi, L Lemery, S McMahon, A AF Diak, Peter Siegel, Jeffrey La Grenade, Lois Choi, Lauren Lemery, Steven McMahon, Ann TI Tumor Necrosis Factor alpha Blockers and Malignancy in Children Forty-Eight Cases Reported to the Food and Drug Administration SO ARTHRITIS AND RHEUMATISM LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; EPSTEIN-BARR-VIRUS; RHEUMATOID-ARTHRITIS; INFLIXIMAB USE; LYMPHOMA; IMMUNOSURVEILLANCE; IMMUNOTHERAPY; FRANCE; RISK; TNF AB Objective. Malignancies reported in children using tumor necrosis factor alpha (TNF alpha) blockers have raised concerns of a potential increased risk. This study was undertaken to investigate postmarketing reports of malignancy in children treated with TNF blockers. Methods. The FDA's Adverse Event Reporting System was searched to identify malignancies associated with the use of infliximab, etanercept, and adalimumab in children in whom therapy was initiated between the ages of 0 and 18 years. The reporting rates for infliximab and etanercept were compared with the background rate of malignancy in the general pediatric population. Results. Forty-eight reports of malignancy in children were identified: 31 following infliximab use, 15 following etanercept use, and 2 following adalimumab use. Half of the malignancies reported were lymphomas and included both Hodgkin's and non-Hodgkin's lymphoma. The remaining reported cases involved a variety of different malignancies including leukemia, melanoma, and solid organ cancers. The majority of the reported cases (88%) involved the concomitant use of other immunosuppressants. Reporting rates for malignancy showed that infliximab had a consistently higher reporting rate when compared with background rates in the general pediatric population for lymphomas and all malignancies. The reporting rates for etanercept were elevated above background for lymphomas and were on par with background for all malignancies. Conclusion. There is evidence that treatment with TNF blockers in children may increase the risk of malignancy. However, the cases were confounded by the potential risk of malignancy associated with underlying illnesses and the use of concomitant immunosuppressants; therefore, a clear causal relationship could not be established. C1 [Diak, Peter; Siegel, Jeffrey; La Grenade, Lois; Choi, Lauren; Lemery, Steven; McMahon, Ann] US FDA, Silver Spring, MD 20993 USA. RP Diak, P (reprint author), US FDA, 10903 New Hampshire Ave,WO 22 Room 3408, Silver Spring, MD 20993 USA. EM peter.diak@fda.hhs.gov NR 30 TC 110 Z9 116 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD AUG PY 2010 VL 62 IS 8 BP 2517 EP 2524 DI 10.1002/art.27511 PG 8 WC Rheumatology SC Rheumatology GA 661WA UT WOS:000282762100037 PM 20506368 ER PT J AU Booth, B Hill, H AF Booth, Brian Hill, Howard TI Bioanalysis: the best of 2009 SO BIOANALYSIS LA English DT Editorial Material ID LC C1 [Booth, Brian] US FDA, Div Clin Pharmacol 5, Off Clin Pharmacol, Ctr Drug Res & Evaluat Res, Silver Spring, MD 20993 USA. [Hill, Howard] Huntingdon Life Sci, Huntingdon PE16 5HS, Cambs, England. RP Booth, B (reprint author), US FDA, Div Clin Pharmacol 5, Off Clin Pharmacol, Ctr Drug Res & Evaluat Res, Silver Spring, MD 20993 USA. EM brian.booth@fda.hhs.gov; hillh@ukorg.huntingdon.com NR 13 TC 0 Z9 0 U1 0 U2 0 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 J9 BIOANALYSIS JI Bioanalysis PD AUG PY 2010 VL 2 IS 8 SI SI BP 1345 EP 1347 DI 10.4155/BIO.10.95 PG 3 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 648PC UT WOS:000281705400002 PM 21083331 ER PT J AU Alyea, EP DeAngelo, DJ Moldrem, J Pagel, JM Przepiorka, D Sadelin, M Young, JW Giralt, S Bishop, M Riddell, S AF Alyea, Edwin P. DeAngelo, Daniel J. Moldrem, Jeffrey Pagel, John M. Przepiorka, Donna Sadelin, Michel Young, James W. Giralt, Sergio Bishop, Michael Riddell, Stan TI NCI First International Workshop on the Biology, Prevention and Treatment of Relapse after Allogeneic Hematopoietic Cell Transplantation: Report from the Committee on Prevention of Relapse Following Allogeneic Cell Transplantation for Hematologic Malignancies SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Allogeneic hematopoietic cell transplantation; Relapse prevention; Acute graft-versus-host disease; Immunotherapy; Resistant leukemia ID CHRONIC MYELOID-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; CHRONIC LYMPHOCYTIC-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; HUMAN T-CELLS; ANTIGEN-PRESENTING CELLS; ACUTE LYMPHOBLASTIC-LEUKEMIA; TOTAL-BODY IRRADIATION; REDUCED-INTENSITY TRANSPLANTATION AB Prevention of relapse after allogeneic hematopoietic stem cell transplantation is the most likely approach to improve survival of patients treated for hematologic malignancies. Herein we review the limits of currently available transplant therapies and the innovative strategies being developed to overcome resistance to therapy or to fill therapeutic modalities not currently available. These novel strategies include nonimmunologic therapies, such as targeted preparative regimens and posttransplant drug therapy, as well as immunologic interventions, including graft engineering, donor lymphocyte infusions, T cell engineering, vaccination, and dendritic cell-based approaches. Several aspects of the biology of the malignant cells as well as the host have been identified that obviate success of even these newer strategies. To maximize the potential for success, we recommend pursuing research to develop additional targeted therapies to be used in the preparative regimen or as maintenance posttransplant, better characterize the T cell and dendritic cells subsets involved in graft-versus-host disease and the graft-versus-leukemia/tumor effect, identify strategies for timing immunologic or nonimmunologic therapies to eliminate the noncycling cancer stem cell, identify more targets for immunotherapies, develop new vaccines that will not be limited by HLA, and develop methods to identify populations at very high risk for relapse to accelerate clinical development and avoid toxicity in patients not at risk for relapse. Biol Blood Marrow Transplant 16: 1037-1069 (2010) (C) 2010 American Society for Blood and Marrow Transplantation C1 [Alyea, Edwin P.; DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Moldrem, Jeffrey; Giralt, Sergio] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Pagel, John M.; Riddell, Stan] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Pagel, John M.; Riddell, Stan] Univ Washington, Seattle, WA 98195 USA. [Przepiorka, Donna] US FDA, Rockville, MD 20857 USA. [Sadelin, Michel; Young, James W.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Bishop, Michael] NCI, Bethesda, MD 20892 USA. RP Alyea, EP (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM edwin_alyea@dfci.harvard.edu FU NCI NIH HHS [P01 CA018029, P01 CA018029-36] NR 280 TC 23 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD AUG PY 2010 VL 16 IS 8 BP 1037 EP 1069 DI 10.1016/j.bbmt.2010.05.005 PG 33 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 628RH UT WOS:000280137800002 PM 20580849 ER PT J AU Adam, A Montpas, N Keire, D Desormeaux, A Brown, NJ Marceau, F Westenberger, B AF Adam, Albert Montpas, Nicolas Keire, David Desormeaux, Anik Brown, Nancy J. Marceau, Francois Westenberger, Benjamin TI Bradykinin forming capacity of oversulfated chondroitin sulfate contaminated heparin in vitro SO BIOMATERIALS LA English DT Article DE Heparin; Oversulfated chondroitin sulfate; Bradykinin; Anaphylactoid reaction ID TISSUE-PLASMINOGEN ACTIVATOR; ADVERSE CLINICAL EVENTS; ANAPHYLACTOID REACTIONS; PHARMACOLOGICAL PROFILE; DEXTRAN SULFATE; CONTACT SYSTEM; HUMAN-PLASMA; HEMODIALYSIS; INHIBITORS; ACE AB Oversulfated chondroitin sulfate (OSCS) contaminated heparin has been associated with severe anaphylactoid reaction (AR), mainly in dialysed patients. Although attributed to bradykinin (BK) released during contact system activation by OSCS, no definitive evidence exists until now for a BK release during incubation of contaminated heparin with human plasma. In this study, we investigated the kinin forming capacity of OSCS and OSCS contaminated heparin when incubated in vitro with a pool of human plasma. At 100 mu g/mL, OSCS liberates BK in a profile similar but not identical to dextran sulfate, a well known activator of the plasma contact system. The results have highlighted that the quantity of BK accumulated during contact system activation depends not only on the concentration of OSCS but also on the plasma dilution and the presence of an angiotensin converting enzyme inhibitor. We demonstrate a highly significant correlation between the concentration of OSCS present in the contaminated heparin and BK released concentration. In conclusion, for the first time, we show that OSCS contaminated heparin incubated with human plasma has the capacity to liberate BK at a concentration that could explain the role of this inflammatory peptide in the pathophysiology of AR associated with OSCS contaminated heparin. Disclaimer: The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Adam, Albert; Montpas, Nicolas; Desormeaux, Anik] Univ Montreal, Fac Pharm, Montreal, PQ H3T 1J4, Canada. [Keire, David; Westenberger, Benjamin] US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. [Brown, Nancy J.] Vanderbilt Univ, Med Ctr, Nashville, TN 37232 USA. [Marceau, Francois] CHUL CHUQ, Rheumathol & Immunol Res Ctr, Quebec City, PQ G1V 4G2, Canada. RP Adam, A (reprint author), Univ Montreal, Fac Pharm, 2900 Blvd E Montpetit, Montreal, PQ H3T 1J4, Canada. EM albert.adam@umontreal.ca RI Marceau, Francois/C-7471-2011 OI Marceau, Francois/0000-0003-1691-6083 FU Canadian Institutes of Health Research [MOP-93773]; National Institutes of Health (NIH) [1-R01-HL079184] FX The work of AA is funded by the Canadian Institutes of Health Research (Grant MOP-93773; in collaboration with FM) and the National Institutes of Health (NIH Grant 1-R01-HL079184; in collaboration with NJB). NR 38 TC 10 Z9 11 U1 0 U2 2 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 AUG PY 2010 VL 31 IS 22 BP 5741 EP 5748 DI 10.1016/j.biomaterials.2010.03.074 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 614XK UT WOS:000279092900003 PM 20427081 ER PT J AU Stratmeyer, ME Goering, PL Hitchins, VM Umbreit, TH AF Stratmeyer, Mel E. Goering, Peter L. Hitchins, Victoria M. Umbreit, Thomas H. TI What we know and don't know about the bioeffects of nanoparticles: developing experimental approaches for safety assessment SO BIOMEDICAL MICRODEVICES LA English DT Article DE In vitro; In vivo; Medical products; Nanoparticles ID IN-VITRO; CYTOTOXICITY; PARTICLES; EXPOSURE; SIZE AB The Center for Devices and Radiological Health (CDRH) of the US Food and Drug Administration (FDA) regulates nano-based medical products and therefore is required to address the safety and biological effects of nano-scale materials used in these products. Both in vitro and in vivo toxicological research studies are being conducted at the FDA to help determine the risks versus benefits of these new products. This article will briefly summarize some of the initial research findings from FDA-CDRH studies using TiO(2), polystyrene, and silicon nanoparticles. C1 [Stratmeyer, Mel E.; Goering, Peter L.; Hitchins, Victoria M.; Umbreit, Thomas H.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Stratmeyer, ME (reprint author), US FDA, Ctr Devices & Radiol Hlth, WO64-4078,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM melvin.stratmeyer@fda.hhs.gov; peter.goering@fda.hhs.gov; victoria.hitchins@fda.hhs.gov; thomas.umbreit@fda.hhs.gov FU Center for Devices and Radiological Health, Food and Drug Administration FX Center for Devices and Radiological Health, Food and Drug Administration NR 19 TC 6 Z9 6 U1 1 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1387-2176 J9 BIOMED MICRODEVICES JI Biomed. Microdevices PD AUG PY 2010 VL 12 IS 4 BP 569 EP 573 DI 10.1007/s10544-008-9261-9 PG 5 WC Engineering, Biomedical; Nanoscience & Nanotechnology SC Engineering; Science & Technology - Other Topics GA 620LA UT WOS:000279500200001 PM 19052876 ER PT J AU Aubin, Y Jones, C Freedberg, DI AF Aubin, Yves Jones, Christopher Freedberg, Daron I. TI Using NMR Spectroscopy to Obtain the Higher Order Structure of Biopharmaceutical Products SO BIOPHARM INTERNATIONAL LA English DT Article AB The higher order structure of complex biological therapeutics such as polysaccharide-containing vaccines, recombinant proteins, and monoclonal antibodies is an important quality attribute of biopharmaceutical products. The relationship between higher order structure and product efficacy is a crucial issue in comparability studies, be they assessments of manufacturing changes or follow-on biologics. Several biophysical methods, such as circular dichroism, fluorescence, and bioassays, are typical for assessing structure but none provide information at high resolution. Nuclear magnetic resonance (NMR) spectroscopy is a well-established technique for biomolecular structure determination, albeit underused in characterizing biotherapeutics. NMR is misperceived as too expensive or complicated and therefore is excluded from the methods toolbox to assess higher order structure. In this paper, we show simple applications of NMR that provide detailed information on higher order structure. We also address the complexity and cost of including NMR in the process and quality control environments. C1 [Aubin, Yves] Hlth Canada, BGTD, Prot Struct & Anal Labs, NMR Lab, Ottawa, ON K1A 0L2, Canada. [Jones, Christopher] Natl Inst Biol Stand & Controls, Mol Struct Lab, Potters Bar, Herts, England. [Freedberg, Daron I.] US FDA, NMR Lab, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Aubin, Y (reprint author), Hlth Canada, BGTD, Prot Struct & Anal Labs, NMR Lab, Ottawa, ON K1A 0L2, Canada. NR 10 TC 7 Z9 7 U1 0 U2 8 PU ADVANSTAR COMMUNICATIONS INC PI DULUTH PA 131 W 1ST STREET, DULUTH, MN 55802 USA SN 1542-166X J9 BIOPHARM INT JI Biopharm. Int. PD AUG PY 2010 SU S BP 28 EP 34 PG 7 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 640KP UT WOS:000281050400005 ER PT J AU Huang, L Johnson, KA Mariotto, AB Dignam, JJ Feuer, EJ AF Huang, Lan Johnson, Karen A. Mariotto, Angela B. Dignam, James J. Feuer, Eric J. TI Population-based survival-cure analysis of ER-negative breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Survival; Cure fraction; Breast cancer; ER-; Chemotherapy ID ANNUAL HAZARD RATES; RANDOMIZED-TRIALS; RECURRENCE; CHEMOTHERAPY; THERAPY; MODELS; TIME AB This study investigated the trends over time in age and stage specific population-based survival of estrogen receptor negative (ER-) breast cancer patients by examining the fraction of cured patients and the median survival time for uncured patients. Cause-specific survival data from the Surveillance, Epidemiology, and End Results program for cases diagnosed during 1992-1998 were used in mixed survival cure models to evaluate the cure fraction and the extension in survival for uncured patients. Survival trends were compared with adjuvant chemotherapy data available from an overlapping patterns-of-care study. For stage II N+ disease, the largest increase in cure fraction was 44-60% (P = 0.0257) for women aged a parts per thousand yen70 in contrast to a 7-8% point increase for women aged < 50 or 50-69 (P = 0.056 and 0.038, respectively). For women with stage III disease, the increases in the cure fraction were not statistically significant, although women aged 50-69 had a 10% point increase (P = 0.103). Increases in cure fraction correspond with increases in the use of adjuvant chemotherapy, particularly for the oldest age group. In this article, for the first time, we estimate the cure fraction for ER- patients. We notice that at age a parts per thousand yen70, the accelerated increase in cure fraction from 1992 to 1998 for women with stage II N+ compared with stage III suggests a selective benefit for chemotherapy in the lower stage group. C1 [Huang, Lan] US FDA, CDER OB DBV, Silver Spring, MD 20993 USA. [Johnson, Karen A.] NCI, BGCRG, DCP, Bethesda, MD 20892 USA. [Mariotto, Angela B.; Feuer, Eric J.] NCI, SRAB, DCCPS, Bethesda, MD 20892 USA. [Dignam, James J.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. RP Huang, L (reprint author), US FDA, CDER OB DBV, 10903 New Hampshire Ave,Bldg 21,Rm 3629, Silver Spring, MD 20993 USA. EM lan.huang@fda.hhs.gov FU Susan G. Komen for the Cure Foundation; U.S. National Cancer Institute [NCI-U10-CA-69651, NCI-U10-CA-12027] FX The authors wish to thank the editors, and the referees for comments and suggestions. Work (JJD) was supported in part by a research grant from the Susan G. Komen for the Cure Foundation. The clinical trials data for Fig. 1 generation was obtained under Public Health Service grants NCI-U10-CA-69651 and NCI-U10-CA-12027 from the U.S. National Cancer Institute. NR 15 TC 3 Z9 3 U1 1 U2 6 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 AUG PY 2010 VL 123 IS 1 BP 257 EP 264 DI 10.1007/s10549-010-0752-z PG 8 WC Oncology SC Oncology GA 627SP UT WOS:000280063200030 PM 20130982 ER PT J AU Castro, MAA Dal-Pizzol, F Zdanov, S Soares, M Muller, CB Lopes, FM Zanotto, A Fernandes, MD Moreira, JCF Shacter, E Klamt, F AF Alves Castro, Mauro Antonio Dal-Pizzol, Felipe Zdanov, Stephanie Soares, Marcio Mueller, Carolina Beatriz Lopes, Fernanda Martins Zanotto-Filho, Alfeu Fernandes, Marilda da Cruz Fonseca Moreira, Jose Claudio Shacter, Emily Klamt, Fabio TI CFL1 Expression Levels as a Prognostic and Drug Resistance Marker in Nonsmall Cell Lung Cancer SO CANCER LA English DT Article DE prognosis; biomarker; lung cancer; nonsmall cell lung cancer; cofilin; CFL1 expression; drug resistance ID CARCINOMA-CELLS; MAMMARY-TUMORS; SOLID TUMORS; COFILIN; SURVIVAL; BREAST; CHEMOTHERAPY; METASTASIS; PREDICTION; INHIBITORS AB BACKGROUND: Nonsmall cell lung cancer (NSCLC) is the major determinant of overall cancer mortality worldwide. Despite progress in molecular research, current treatments offer limited benefits. Because NSCLC generates early metastasis, and this behavior requires great cell motility, herein the authors assessed the potential value of CFL1 gene (main member of the invasion/metastasis pathway) as a prognostic and predictive NSCLC biomarker. METHODS: Metadata analysis of tumor tissue microarray was applied to examine expression of CFL1 in archival lung cancer samples from 111 patients, and its clinicopathologic significance was investigated. The robustness of the finding was validated using another independent data set. Finally, the authors assayed in vitro the role of CFL1 levels in tumor invasiveness and drug resistance using 6 human NSCLC cell lines with different basal degrees of CFL1 gene expression. RESULTS: CFL1 levels in biopsies discriminate between good and bad prognosis at early tumor stages (IA, IB, and IIA/B), where high CFL1 levels are correlated with lower overall survival rate (P < .0001). Biomarker performance was further analyzed by immunohistochemistry, hazard ratio (P < .001), and receiver-operating characteristic curve (area = 0.787; P < .001). High CFL1 mRNA levels and protein content are positively correlated with cellular invasiveness (determined by Matrigel Invasion Chamber System) and resistance (2-fold increase in drug 50% growth inhibition dose) against a list of 22 alkylating agents. Hierarchical clustering analysis of the CFL1 gene network had the same robustness for stratified NSCLC patients. CONCLUSIONS: This study indicates that the CFL1 gene and its functional gene network can be used as prognostic biomarkers for NSCLC and could also guide chemotherapeutic interventions. Cancer 2010;116;3645-55. (C) 2070 American Cancer Society C1 [Alves Castro, Mauro Antonio; Mueller, Carolina Beatriz; Lopes, Fernanda Martins; Zanotto-Filho, Alfeu; Fonseca Moreira, Jose Claudio; Klamt, Fabio] Univ Fed Rio Grande do Sul, ICBS, Dept Biochem, BR-90035003 Porto Alegre, RS, Brazil. [Dal-Pizzol, Felipe] Univ Extremo Sul Catarinense, Lab Expt Physiopathol, Criciuma, Brazil. [Zdanov, Stephanie; Shacter, Emily] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. [Soares, Marcio] Natl Canc Inst, Intens Care Unit, Rio De Janeiro, Brazil. [Fernandes, Marilda da Cruz] UFCSPA, Lab Pathol Res, Porto Alegre, RS, Brazil. RP Klamt, F (reprint author), Univ Fed Rio Grande do Sul, ICBS, Dept Biochem, 2600 Ramiro Barcelos St, BR-90035003 Porto Alegre, RS, Brazil. EM 00025267@ufrgs.br RI Zdanov, Stephanie/G-2524-2012; Soares, Marcio/B-3083-2013; Castro, Mauro/A-5467-2008; Dal-Pizzol, Felipe/F-2756-2015; ZANOTTO-FILHO, ALFEU/A-8172-2016; Fernandes, Marilda/L-2819-2016 OI Soares, Marcio/0000-0003-2503-6088; Castro, Mauro/0000-0003-4942-8131; Dal-Pizzol, Felipe/0000-0003-3003-8977; ZANOTTO-FILHO, ALFEU/0000-0002-4188-3095; Fernandes, Marilda/0000-0003-4234-797X FU Brazilian Science and Technology Ministry/National Counsel of Technological and Scientific Development (MCT/CNPq) [479860]; MCT/CNPq National Institutes for Translational Medicine (INCT-TM) [573671]; National Cancer Institute, National Institutes of Health [NO1-CO-12, 400] FX Supported by Brazilian Science and Technology Ministry/National Counsel of Technological and Scientific Development (MCT/CNPq) Universal funds (479860 of 2006-8) and MCT/CNPq National Institutes for Translational Medicine (INCT-TM) funds (573671 of 2008-7), and US federal funds from the National Cancer Institute, National Institutes of Health (NO1-CO-12,400). NR 37 TC 25 Z9 27 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD AUG 1 PY 2010 VL 116 IS 15 BP 3645 EP 3655 DI 10.1002/cncr.25125 PG 11 WC Oncology SC Oncology GA 629TS UT WOS:000280223200017 PM 20564088 ER PT J AU Cramer, DW Vitonis, AF Pinheiro, SP McKolanis, JR Fichorova, RN Brown, KE Hatchette, TF Finn, OJ AF Cramer, Daniel W. Vitonis, Allison F. Pinheiro, Simone P. McKolanis, John R. Fichorova, Raina N. Brown, Kevin E. Hatchette, Todd F. Finn, Olivera J. TI Mumps and ovarian cancer: modern interpretation of an historic association SO CANCER CAUSES & CONTROL LA English DT Article DE Ovarian cancer; Mumps parotitis; MUC1; CA125 ID ANTIGEN MUC1; VIRUS; RISK; ANTIBODIES; CARCINOMAS; EXPRESSION; MUCINS AB Epidemiologic studies found childhood mumps might protect against ovarian cancer. To explain this association, we investigated whether mumps might engender immunity to ovarian cancer through antibodies against the cancer-associated antigen MUC1 abnormally expressed in the inflamed parotid gland. Through various health agencies, we obtained sera from 161 cases with mumps parotitis. Sera were obtained from 194 healthy controls. We used an ELISA to measure anti-MUC1 antibodies and electro-chemiluminescence assays to measure MUC1 and CA 125. Log-transformed measurements were analyzed by t-tests, generalized linear models, and Pearson or Spearman correlations. We also conducted a meta-analysis of all published studies regarding mumps and ovarian cancer. Adjusting for assay batch, age, and sex, the level of anti-MUC1 antibodies was significantly higher in mumps cases compared to controls (p = 0.002). Free circulating levels of CA 125, but not MUC1, were also higher in cases (p = 0.02). From the meta-analysis, the pooled odds ratio estimate (and 95% CI) for the mumps and ovarian cancer association was 0.81 (0.68-0.96) (p = 0.01). Mumps parotitis may lead to expression and immune recognition of a tumor-associated form of MUC1 and create effective immune surveillance of ovarian cancer cells that express this form of MUC1. C1 [Cramer, Daniel W.; Vitonis, Allison F.] Harvard Univ, Brigham & Womens Hosp, Dept Obstet & Gynecol, Obstet & Gynecol Epidemiol Ctr,Epidemiol Ctr,Med, Boston, MA 02115 USA. [Pinheiro, Simone P.] US FDA, Silver Spring, MD USA. [McKolanis, John R.; Finn, Olivera J.] Univ Pittsburgh, Sch Med, Dept Immunol, Pittsburgh, PA USA. [Fichorova, Raina N.] Harvard Univ, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Lab Genital Tract Biol,Med Sch, Boston, MA 02115 USA. [Brown, Kevin E.] Hlth Protect Agcy, Ctr Infect, London, England. [Hatchette, Todd F.] Queen Elizabeth 2 Hlth Sci Ctr, Dept Pathol & Lab Med, Div Microbiol, Halifax, NS, Canada. [Hatchette, Todd F.] Dalhousie Univ, Dept Pathol, Halifax, NS, Canada. RP Cramer, DW (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Obstet & Gynecol, Obstet & Gynecol Epidemiol Ctr,Epidemiol Ctr,Med, 221 Longwood Ave,RFB 366, Boston, MA 02115 USA. EM dwcramer@partners.org RI Fichorova, Raina/G-9969-2014 FU US Department of Defense [W81XWH-07-1-0292]; NIH [R01CA123170] FX ;We thank Claudia Krause, Bernard Johnson, and Michael Trythall for helping us assemble the specimen sets and for their thoughtful comments on the manuscript and Huaiping Yan and Vanessa Tang-Fernandez for laboratory assistance. Grants: US Department of Defense #W81XWH-07-1-0292 and NIH Grant R01CA123170. NR 25 TC 14 Z9 14 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD AUG PY 2010 VL 21 IS 8 BP 1193 EP 1201 DI 10.1007/s10552-010-9546-1 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 627TI UT WOS:000280065400005 PM 20559706 ER PT J AU Tang, SX Zhao, JQ Wang, AF Viswanath, R Harma, H Little, RF Yarchoan, R Stramer, SL Nyambi, PN Lee, S Wood, O Wong, EY Wang, X Hewlett, IK AF Tang, Shixing Zhao, Jiangqin Wang, Aifeng Viswanath, Ragupathy Harma, Harri Little, Richard F. Yarchoan, Robert Stramer, Susan L. Nyambi, Phillipe N. Lee, Sherwin Wood, Owen Wong, Eric Y. Wang, Xue Hewlett, Indira K. TI Characterization of Immune Responses to Capsid Protein p24 of Human Immunodeficiency Virus Type 1 and Implications for Detection SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; HIV-1 P24; SIGNAL AMPLIFICATION; GENETIC DIVERSITY; CORE PROTEIN; ANTIGEN; INFECTION; ASSAY; IMMUNOASSAYS; EPITOPES AB To further refine our current nanoparticle-based HIV-1 p24 antigen assay, we investigated immune responses to p24 to identify diagnostically significant immune dominant epitopes (IDEs) in HIV-infected human sera, to address cross-reactivity of anti-p24 antibodies to different subtypes, and to identify new biomarkers that distinguish acute from chronic HIV infection for more accurate incidence estimation. We identified two major linear epitope regions, located in the CypA binding loop and adjacent helices and at the end of the C-terminal domain. Most sera (86%) from acutely HIV-1-infected individuals reacted with multiple peptides, while 60% and 30% of AIDS patient samples reacted with multiple and single peptides, respectively. In contrast, 46% and 43% of chronically HIV-1-infected individuals reacted with one and none of the peptides, respectively, and only 11% reacted with multiple p24 peptides, indicating a progression of immune responses from polyclone-like during acute infection to monoclone-like or a nonresponse to linear epitopes during chronic infection. Anti-p24 antibodies (subtype B) show broad cross-reactivity to different HIV-1 subtypes, and the synergistic action of different combinations of anti-HIV antibodies improves capture and detection of divergent HIV-1 subtypes. Our results indicate that the modified peptide immunoassay is sensitive and specific for the rapid identification of HIV-1 p24 IDEs and for investigation of immune responses to p24 during natural HIV-1 infection. The data provide the foundation for development and refinement of new assays for improved p24 antigen testing as future tools for rapid and accurate diagnosis as part of early intervention strategies and estimations of incidence. C1 [Tang, Shixing; Zhao, Jiangqin; Wang, Aifeng; Viswanath, Ragupathy; Lee, Sherwin; Wood, Owen; Wong, Eric Y.; Wang, Xue; Hewlett, Indira K.] US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Harma, Harri] Univ Turku, Biophys Lab, FIN-20520 Turku, Finland. [Little, Richard F.; Yarchoan, Robert] NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. [Stramer, Susan L.] Amer Red Cross, Biomed Serv Sci Support Off, Gaithersburg, MD 20877 USA. [Nyambi, Phillipe N.] NYU, Sch Med, New York, NY 10010 USA. RP Tang, SX (reprint author), US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bldg 29B,Room 4NN16,8800 Rockville Pike, Bethesda, MD 20892 USA. EM shixing.tang@fda.hhs.gov; indira.hewlett@fda.hhs.gov FU National Heart, Lung and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID), NIH; National Cancer Institute (NCI), NIH FX This study was funded by an interagency agreement with the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID), NIH, and was supported in part by the Intramural Research Program of the National Cancer Institute (NCI), NIH. NR 38 TC 9 Z9 9 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD AUG PY 2010 VL 17 IS 8 BP 1244 EP 1251 DI 10.1128/CVI.00066-10 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 633XG UT WOS:000280539900012 PM 20534793 ER PT J AU Kleppinger, CF Ball, LK AF Kleppinger, Cynthia F. Ball, Leslie K. TI Building Quality in Clinical Trials With Use of a Quality Systems Approach SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ASSURANCE AB There is an increasing focus on having quality systems in place during the planning stages of clinical trials. Such systems require the development and implementation of standards for each step. Although this is not imposing something totally new on clinical research, a systematic approach will produce a more reliable and useful end product-high-quality data obtained without compromising the protection of human subjects' rights and welfare. A suggested quality system with standards for each step is addressed in this article. C1 [Kleppinger, Cynthia F.] US FDA, Div Sci Invest, Off Compliance, Ctr Drug Evaluat & Res,Fed Res Ctr, Silver Spring, MD 20993 USA. RP Kleppinger, CF (reprint author), US FDA, Div Sci Invest, Off Compliance, Ctr Drug Evaluat & Res,Fed Res Ctr, Bldg 51,Rm 5352,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Cynthia.Kleppinger@fda.hhs.gov FU US Food and Drug Administration; Infectious Diseases Society of America; American College of Chest Physicians; American Thoracic Society; Society of Critical Care Medicine; Pharmaceutical Research and Manufacturers of America; AstraZeneca Pharmaceuticals; Forest Pharmaceuticals FX This article was published as part of a supplement entitled "Workshop on Issues in the Design of Clinical Trials for Antibacterial Drugs for Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia," sponsored by the US Food and Drug Administration, Infectious Diseases Society of America, American College of Chest Physicians, American Thoracic Society, and the Society of Critical Care Medicine, with financial support from the Pharmaceutical Research and Manufacturers of America, AstraZeneca Pharmaceuticals, and Forest Pharmaceuticals. NR 26 TC 5 Z9 6 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG PY 2010 VL 51 SU 1 BP S111 EP S116 DI 10.1086/653058 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 619RO UT WOS:000279448000018 PM 20597658 ER PT J AU Laessig, KA AF Laessig, Katherine A. TI End Points in Hospital-Acquired Pneumonia and/or Ventilator-Associated Pneumonia Clinical Trials: Food and Drug Administration Perspective SO CLINICAL INFECTIOUS DISEASES LA English DT Article AB Identification of reliable, reproducible, and precise end points for future studies of hospital-acquired and ventilator-associated pneumonia is of paramount importance for approval of new therapeutic agents. As required by the Code of Federal Regulations 21 CFR 314.126, the methods of assessment of a subject's response (ie, end points) must be well defined and reliable. The study protocol and results should explain the variables measured, the methods of observation, and criteria used to assess response. Meeting these requirements has proven to be problematic in clinical trials for the evaluation of new products for the treatment of hospital-acquired and ventilator-associated pneumonia because of the subjectivity of assessing a clinical response end point. There are multiple issues and caveats to consider when selecting appropriate end points for these trials. C1 US FDA, Silver Spring, MD 20993 USA. RP Laessig, KA (reprint author), US FDA, 10903 New Hampshire Ave,Bldg 22,Rm 6380, Silver Spring, MD 20993 USA. EM katherine.laessig@fda.hhs.gov FU US Food and Drug Administration; Infectious Diseases Society of America; American College of Chest Physicians; American Thoracic Society; Society of Critical Care Medicine; Pharmaceutical Research and Manufacturers of America; AstraZeneca Pharmaceuticals; Forest Pharmaceuticals FX This article was published as part of a supplement entitled "Workshop on Issues in the Design of Clinical Trials for Antibacterial Drugs for Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia," sponsored by the US Food and Drug Administration, Infectious Diseases Society of America, American College of Chest Physicians, American Thoracic Society, and the Society of Critical Care Medicine, with financial support from the Pharmaceutical Research and Manufacturers of America, AstraZeneca Pharmaceuticals, and Forest Pharmaceuticals. NR 8 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG PY 2010 VL 51 SU 1 BP S117 EP S119 DI 10.1086/653059 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 619RO UT WOS:000279448000019 PM 20597659 ER PT J AU Sorbello, A Komo, S Valappil, T Nambiar, S AF Sorbello, Alfred Komo, Scott Valappil, Thamban Nambiar, Sumati TI Registration Trials of Antibacterial Drugs for the Treatment of Nosocomial Pneumonia SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CARE-ASSOCIATED INFECTIONS AB Since 1989, 12 registration trials have been submitted to the US Food and Drug Administration to support the clinical efficacy of 8 antibacterial drugs for the treatment of nosocomial pneumonia. Six trials used noninferiority designs, whereas the others were equivalence trials or lacked a prespecified hypothesis. Patients with nosocomial pneumonia and ventilator-associated pneumonia were frequently enrolled in the same clinical trials. Enrolled patients were predominantly male and had mean Acute Physiology and Chronic Health Evaluation II scores of 12-18. The investigator's assessment of clinical response was the primary end point, which was usually measured 7-14 days after study drug completion. Clinical cure rates among the intent-to-treat population for nosocomial pneumonia and ventilator-associated pneumonia ranged from 37% to 69% and 25% to 58%, respectively. All-cause mortality ranged from 8% to 28%. Pseudomonas aeruginosa, Acinetobacter species, and methicillin-resistant Staphylococcus aureus were common bacterial pathogens. The design, implementation, and limitations of the clinical trials and implications for future clinical research are discussed. C1 [Sorbello, Alfred; Nambiar, Sumati] US FDA, Off Antimicrobial Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Komo, Scott; Valappil, Thamban] US FDA, Div Biometr 4, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Sorbello, A (reprint author), US FDA, Off Antimicrobial Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM alfred.sorbello@fda.hhs.gov FU US Food and Drug Administration; Infectious Diseases Society of America; American College of Chest Physicians; American Thoracic Society; Society of Critical Care Medicine; Pharmaceutical Research and Manufacturers of America; AstraZeneca Pharmaceuticals; Forest Pharmaceuticals FX This article was published as part of a supplement entitled "Workshop on Issues in the Design of Clinical Trials for Antibacterial Drugs for Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia," sponsored by the US Food and Drug Administration, Infectious Diseases Society of America, American College of Chest Physicians, American Thoracic Society, and the Society of Critical Care Medicine, with financial support from the Pharmaceutical Research and Manufacturers of America, AstraZeneca Pharmaceuticals, and Forest Pharmaceuticals. NR 15 TC 12 Z9 12 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG PY 2010 VL 51 SU 1 BP S36 EP S41 DI 10.1086/653038 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 619RO UT WOS:000279448000007 PM 20597669 ER PT J AU Goldberger, MJ Singh, N Allerheiligan, S Gobburu, JVS Lalonde, R Smith, B Ryder, S Yozviak, A AF Goldberger, M. J. Singh, N. Allerheiligan, S. Gobburu, J. V. S. Lalonde, R. Smith, B. Ryder, S. Yozviak, A. TI ASCPT Task Force for Advancing Pharmacometrics and Integration into Drug Development SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID LABELING DECISIONS; IMPACT; PHARMACOLOGY; EXPERIENCE; APPROVAL AB Traditionally, medical and biostatistical experts have played a central role in ensuring validity of pharmaceutical testing. The science of pharmacometrics provides powerful approaches for supporting important drug development and regulatory decisions. Numerous case studies published by academic, industry, and US Food and Drug Administration scientists attest to the significant contribution of pharmacometrics to decision making. The economic and public health benefits of applying this discipline to clinical trials far outweigh the cost associated with its implementation. The purpose of the American Society for Clinical Pharmacology and Therapeutics (ASCPT) Task Force is to build on the momentum and accelerate dissemination of its impact and adoption into drug development. We describe briefly the contributions of pharmacometrics and the specific goals of the Task Force. C1 [Gobburu, J. V. S.] US FDA, Div Pharmacometr, Off Clin Pharmacol, Silver Spring, MD USA. [Goldberger, M. J.] Abbott, Rockville, MD USA. [Singh, N.; Yozviak, A.] McKinsey & Co Inc, New York, NY USA. [Allerheiligan, S.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Lalonde, R.] Pfizer Global Res & Dev, New London, CT USA. [Smith, B.] Amgen Inc, Thousand Oaks, CA 91320 USA. [Ryder, S.] Astellas Pharma Global Dev, Deerfield, IL USA. RP Gobburu, JVS (reprint author), US FDA, Div Pharmacometr, Off Clin Pharmacol, Silver Spring, MD USA. EM jogarao.gobburu@fda.hhs.gov NR 15 TC 3 Z9 3 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD AUG PY 2010 VL 88 IS 2 BP 158 EP 161 DI 10.1038/clpt.2010.141 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 628UH UT WOS:000280147500010 PM 20648032 ER PT J AU Grandinetti, CA Osborne, SF AF Grandinetti, C. A. Osborne, S. F. TI The Food and Drug Administration's Drug Safety Oversight Board: An Evolving Paradigm for Clinical Input on Drug Safety Topics SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID STIMULANT-DRUGS AB In 2005, the US Food and Drug Administration (FDA) formed the Drug Safety Oversight Board (DSB or Board) to evaluate and improve communication of controversial, complex, and emerging drug safety issues. The Board's membership includes members from three FDA centers and six other federal agencies. They provide critical feedback on the impact and effectiveness of the FDA's actions and communications. The Board plays an important role in promoting and protecting public health by ensuring that drugs are safe and effective. C1 [Grandinetti, C. A.; Osborne, S. F.] US FDA, Drug Safety Oversight Board, Off Ctr Director, CDER, Silver Spring, MD USA. RP Grandinetti, CA (reprint author), US FDA, Drug Safety Oversight Board, Off Ctr Director, CDER, Silver Spring, MD USA. EM cheryl.grandinetti@fda.hhs.gov NR 21 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD AUG PY 2010 VL 88 IS 2 BP 269 EP 274 DI 10.1038/clpt.2010.82 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 628UH UT WOS:000280147500028 PM 20531466 ER PT J AU Huang, JP Fang, H Fan, XH AF Huang, Jianping Fang, Hong Fan, Xiaohui TI Decision forest for classification of gene expression data SO COMPUTERS IN BIOLOGY AND MEDICINE LA English DT Article DE Decision forest; Gene expression data; Classification; Microarray; Ensemble ID MICROARRAY DATA; TUMOR CLASSIFICATION; CANCER; PREDICTION; SELECTION; DIAGNOSIS AB This study attempts to propose an improved decision forest (IDF) with an integrated graphical user interface. Based on four gene expression data sets, the IDF not only outperforms the original decision forest, but also is superior or comparable to other state-of-the-art machine learning methods, especially in dealing with high dimensional data. With an integrated built-in feature selection (FS) mechanism and fewer parameters to tune, it can be trained more efficiently than methods such as support vector machine, and can be built with much fewer trees than other popular tree-based ensemble methods. Moreover, it suffers less from the curse of dimensionality. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Huang, Jianping; Fan, Xiaohui] Zhejiang Univ, Coll Pharmaceut Sci, Pharmaceut Informat Inst, Hangzhou 310058, Zhejiang, Peoples R China. [Huang, Jianping] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Fang, Hong] NCTR FDA, ICF Int Co, Z Tech Corp, Jefferson, AR 72079 USA. RP Fan, XH (reprint author), Zhejiang Univ, Coll Pharmaceut Sci, Pharmaceut Informat Inst, 388 YuHangTang Rd, Hangzhou 310058, Zhejiang, Peoples R China. EM fanxh@zju.edu.cn FU National Natural Science Foundation of China [30801556, 30830121]; Science Foundation of Chinese University [2009QNA7031]; Research Fund for the Doctoral Program of Higher Education of China [20090101110126]; Zhejiang Provincial Natural Science Foundation of China [R2080693] FX Funding: This work was supported by the National Natural Science Foundation of China (nos. 30801556 and 30830121); Science Foundation of Chinese University (no. 2009QNA7031); Research Fund for the Doctoral Program of Higher Education of China (no. 20090101110126) and the Zhejiang Provincial Natural Science Foundation of China (no. R2080693). Dr. Huang's contribution to this work was performed while a postdoctoral fellow at FDA, working under the supervision of Dr. Weida Tong. NR 33 TC 10 Z9 11 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0010-4825 J9 COMPUT BIOL MED JI Comput. Biol. Med. PD AUG PY 2010 VL 40 IS 8 BP 698 EP 704 DI 10.1016/j.compbiomed.2010.06.004 PG 7 WC Biology; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Computer Science; Engineering; Mathematical & Computational Biology GA 657CC UT WOS:000282388000003 PM 20591424 ER PT J AU Sarkar, S Schmued, L AF Sarkar, Sumit Schmued, Larry TI Neurotoxicity of Ecstasy (MDMA): An Overview SO CURRENT PHARMACEUTICAL BIOTECHNOLOGY LA English DT Review DE MDMA; neurodegeneration; hyperthermia; neurotoxicity; serotonin; Fluoro-Jade B ID SUBSTITUTED AMPHETAMINES 3,4-METHYLENEDIOXYMETHAMPHETAMINE; ORALLY-ADMINISTERED MDMA; 5-HT NERVE-TERMINALS; SPRAGUE-DAWLEY RATS; BLOOD-BRAIN-BARRIER; DOPAMINE RELEASE; NEURONAL DEGENERATION; NUCLEUS-ACCUMBENS; IN-VIVO; METHYLENEDIOXYMETHAMPHETAMINE MDMA AB "Ecstasy" (MDMA) is a powerful hallucinogenic drug which has raised concern worldwide because of its high abuse liability. A plethora of studies have demonstrated that MDMA has the potential to induce neurotoxicity both in human and laboratory animals. Although research on MDMA has been carried out by many different laboratories, the mechanism underlying MDMA induced toxicity has not been fully elucidated. MDMA has the ability to reduce serotonin levels in terminals of axons in the cortex of rats and mice. Recently we have shown that it also has the potential to produce degenerate neurons in discrete areas of the brain such as insular and parietal cortex, thalamus, tenia tecta and bed nucleus of stria terminalis (BST). Acute effects of MDMA can result in a constellation of changes including arrthymias, hypertension, hyperthermia, serotonin (5-HT) syndrome, liver problems, seizures and also long lasting neurocognitive impairments including mood disturbances. In human MDMA abusers, there is evidence for reduction of serotonergic biochemical markers. Several factors may contribute to the MDMA-induced neurotoxicity, especially hyperthermia. Other factors potentially influencing MDMA toxicity include monoamine oxidase metabolism of dopamine and serotonin, nitric oxide generation, glutamate excitotoxicity, serotonin 2A receptor agonism and the formation of MDMA neurotoxic metabolites. In this review we will cover the following topics: pharmacological mechanisms, metabolic pathways and acute effects in laboratory animals, as well as in humans, with special attention on the mechanism and pathology of MDMA induced neurotoxicity. C1 [Sarkar, Sumit; Schmued, Larry] US FDA, Natl Ctr Toxicol Res, Dept Neurotoxicol, Jefferson, AR 72079 USA. RP Schmued, L (reprint author), US FDA, Natl Ctr Toxicol Res, Dept Neurotoxicol, Jefferson, AR 72079 USA. EM Larry.Schmued@fda.hhs.gov FU FDA FX We would like to acknowledge Elsevier publishers for allowing us to use the previously published photomicrographs. This work was supported in part by FDA protocol E7312. NR 109 TC 14 Z9 14 U1 3 U2 28 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2010 J9 CURR PHARM BIOTECHNO JI Curr. Pharm. Biotechnol. PD AUG PY 2010 VL 11 IS 5 BP 460 EP 469 PG 10 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 633BF UT WOS:000280473800007 PM 20420572 ER PT J AU Shaikh, B Rummel, NG Gieseker, C Reimschuessel, R Kawalek, J AF Shaikh, Badar Rummel, Nathan G. Gieseker, Charles Reimschuessel, Renate Kawalek, Joseph TI Comarative metabolism of albendazole in finfish species SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 9th International Meeting of the International-Society-for-the-Study-of-Xenobiotics(ISSX) CY SEP 04-08, 2010 CL Istanbul, TURKEY SP Int Soc Study Xenobiot C1 [Shaikh, Badar; Rummel, Nathan G.; Gieseker, Charles; Reimschuessel, Renate; Kawalek, Joseph] US FDA, Res Off, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PD AUG PY 2010 VL 42 SU 1 BP 88 EP 88 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 641RP UT WOS:000281147700157 ER PT J AU Lin, G Li, N Li, M Chan, WY Fu, PP Xu, HX AF Lin, Ge Li, Na Li, Mi Chan, Wood-Yee Fu, Peter P. Xu, Hong-Xi TI Potential biomarker for the assessment of hepatotoxicity induced by metabolic activation of pyrrolizidine alkaloids SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 9th International Meeting of the International-Society-for-the-Study-of-Xenobiotics(ISSX) CY SEP 04-08, 2010 CL Istanbul, TURKEY SP Int Soc Study Xenobiot C1 [Lin, Ge; Li, Na; Li, Mi; Chan, Wood-Yee] Chinese Univ Hong Kong, Sch Biomed Sci, Shatin, Hong Kong 72079, Peoples R China. [Fu, Peter P.] Natl Ctr Toxicol Res, Jefferson, AR USA. [Xu, Hong-Xi] Hong Kong Jockey Club Inst Chinese Med, Hong Kong, Hong Kong, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PD AUG PY 2010 VL 42 SU 1 BP 207 EP 207 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 641RP UT WOS:000281147700367 ER PT J AU Tryndyak, V Jeannot, E Rusyn, I Pogribny, I AF Tryndyak, V Jeannot, E. Rusyn, I Pogribny, I TI MicroRNA Expression during Aflatoxin B-1-Induced Hepatocarcinogenesis in HCV Transgenic and C57BL/6J Mice SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Tryndyak, V; Pogribny, I] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Jeannot, E.; Rusyn, I] Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 692 EP 692 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600034 ER PT J AU Scherhag, A Sorrentino, J Pogribny, I Rusyn, I Koturbash, I AF Scherhag, A. Sorrentino, J. Pogribny, I Rusyn, I Koturbash, I TI Epigenetic Changes in C57BL/6J Mice Induced by Short-Term Exposure to 1,3-Butadiene by Inhalation SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Scherhag, A.; Pogribny, I; Koturbash, I] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Scherhag, A.] Univ Kaiserslautern, Kaiserslautern, Rheinland Pfalz, Germany. [Sorrentino, J.; Rusyn, I] Univ N Carolina, Chapel Hill, NC USA. RI Rusyn, Ivan/S-2426-2016 NR 0 TC 0 Z9 0 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 693 EP 693 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600035 ER PT J AU Pereira, SA Tryndyak, VP Pogribny, IP Beland, FA AF Pereira, S. A. Tryndyak, V. P. Pogribny, I. P. Beland, F. A. TI Epigenetic Markers of Hepatotoxicity center dot A Nevirapine Story SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Pereira, S. A.] Univ Nova Lisboa, Fac Med Sci, Dept Pharmacol, Lisbon, Portugal. [Pereira, S. A.] Univ Nova Lisboa, CEDOC, Lisbon, Portugal. [Pereira, S. A.; Tryndyak, V. P.; Pogribny, I. P.; Beland, F. A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 0 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 699 EP 699 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600061 ER PT J AU Wang, Y Meng, F Arlt, VM Mei, N Chen, T Parsons, BL AF Wang, Y. Meng, F. Arlt, V. M. Mei, N. Chen, T. Parsons, B. L. TI Insight into Mechanisms of Aristolochic Acid-Induced Carcinogenesis Derived through ACB-PCR Analyses of H- and K-Ras Mutant Fractions in Rat Liver and Kidney SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Wang, Y.; Meng, F.; Mei, N.; Chen, T.; Parsons, B. L.] Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Arlt, V. M.] Inst Canc Res, Sect Mol Carcinogenesis, Sutton, Surrey, England. NR 0 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 710 EP 710 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600105 ER PT J AU Sarfaraz, S Tryndyak, VP Pognbny, IP Beland, FA AF Sarfaraz, S. Tryndyak, V. P. Pognbny, I. P. Beland, F. A. TI Role of Genetic and Epigenetic Changes in Acrylamide-Induced Lung Carcinogenesis in Mice SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Sarfaraz, S.; Tryndyak, V. P.; Pognbny, I. P.; Beland, F. A.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 712 EP 712 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600111 ER PT J AU Myers, MB McKinzie, PB Meng, F Wang, Y Parsons, BL AF Myers, M. B. McKinzie, P. B. Meng, F. Wang, Y. Parsons, B. L. TI Towards Developing Specific Oncomutations As Biomarkers of Cancer Risk SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Myers, M. B.; McKinzie, P. B.; Meng, F.; Wang, Y.; Parsons, B. L.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 714 EP 714 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600119 ER PT J AU John, K Churchwell, MI Beland, FA Pratt, MM McMullen, G Poiner, MC AF John, K. Churchwell, M., I Beland, F. A. Pratt, M. M. McMullen, G. Poiner, M. C. TI Chlorophyllin (CHL) Differentially Modulates Benzo(a)pyrene-DNA (BP-DNA) Adduct Formation in C57BL16 Mice Chronically Fed BP and CHL in the Diet SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [John, K.; Pratt, M. M.; McMullen, G.; Poiner, M. C.] NCI, NIH, Bethesda, MD 20892 USA. [Churchwell, M., I; Beland, F. A.] NCTR, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 720 EP 720 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600143 ER PT J AU Bhalli, JA Dobrovolsky, VN Heflich, RH AF Bhalli, J. A. Dobrovolsky, V. N. Heflich, R. H. TI Pig-a Mutation Manifestation in Mice Following Single and Split Doses of N-Ethyl-N-nitrosourea SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Bhalli, J. A.; Dobrovolsky, V. N.; Heflich, R. H.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 722 EP 722 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600153 ER PT J AU Dobrovolsky, VN Shaddock, JG Pearce, MG Heflich, RH AF Dobrovolsky, V. N. Shaddock, J. G. Pearce, M. G. Heflich, R. H. TI Differential Induction of Pig-a and Hprt Mutation following Exposure of Rats to Ionizing Radiation SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Dobrovolsky, V. N.; Shaddock, J. G.; Pearce, M. G.; Heflich, R. H.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 724 EP 724 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600159 ER PT J AU Ali, R Mittelstaedt, RA Shaddock, JG Bhalli, JA Heflich, RH AF Ali, R. Mittelstaedt, R. A. Shaddock, J. G. Bhalli, J. A. Heflich, R. H. TI Micronucleus Induction by Ochratoxin A in CHO and TK6 Cells SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Ali, R.; Mittelstaedt, R. A.; Shaddock, J. G.; Bhalli, J. A.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR USA. [Ali, R.] NIBGE, Faisalabad, Pakistan. NR 0 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 728 EP 728 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600176 ER PT J AU McDaniel, LP Mittelstaedt, RA Dobrovolsky, VN Doerge, DR Ding, W Heflich, RH AF McDaniel, L. P. Mittelstaedt, R. A. Dobrovolsky, V. N. Doerge, D. R. Ding, W. Heflich, R. H. TI Genotoxicity of Furan in Big Blue Rats SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [McDaniel, L. P.; Mittelstaedt, R. A.; Dobrovolsky, V. N.; Doerge, D. R.; Ding, W.; Heflich, R. H.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RI Ding, Wei/L-1503-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 728 EP 728 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600175 ER PT J AU Dertinger, SD Phonethepswath, S Weller, P Stankowski, LF Roberts, DJ Shi, J Krsmanovic, L Vohr, HW Custer, L Gleason, C Henwood, A Sweder, K Giddings, A Lynch, AM Gunther, WC Thiffeault, CJ Shutsky, TJ Fiedler, RD Bhalli, JA Heflich, RH AF Dertinger, S. D. Phonethepswath, S. Weller, P. Stankowski, L. F., Jr. Roberts, D. J. Shi, J. Krsmanovic, L. Vohr, H-W Custer, L. Gleason, C. Henwood, A. Sweder, K. Giddings, A. Lynch, A. M. Gunther, W. C. Thiffeault, C. J. Shutsky, T. J. Fiedler, R. D. Bhalli, J. A. Heflich, R. H. TI Pig-a Mutation Assay: Evaluation of Inter-Laboratory Transferability and Reproducibility SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Dertinger, S. D.; Phonethepswath, S.; Weller, P.] Litron Labs, Rochester, NY USA. [Stankowski, L. F., Jr.; Roberts, D. J.] Covance Labs, Vienna, VA USA. [Krsmanovic, L.] BioReliance, Rockville, MD USA. [Vohr, H-W] Bayer Schering Pharma AG, Wuppertal, Germany. [Custer, L.; Gleason, C.; Henwood, A.; Sweder, K.] Bristol Myers Squibb Co, Syracuse, NY USA. [Giddings, A.; Lynch, A. M.] GlaxoSmithKline Inc, Ware, Herts, England. [Gunther, W. C.; Thiffeault, C. J.; Shutsky, T. J.; Fiedler, R. D.] Pfizer Global R&D, Groton, CT USA. [Bhalli, J. A.; Heflich, R. H.] US FDA NCTR, Jefferson, AR USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 MA P86 BP 730 EP 730 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600184 ER PT J AU Levy, DD McDaniel, LP Witt, KL AF Levy, D. D. McDaniel, L. P. Witt, K. L. TI Sensitivity and Specificity of the In Vivo Rodent Micronucleus Assay towards the Detection of Rodent Carcinogens. An Updated Analysis of National Toxicology Program Data. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Levy, D. D.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [McDaniel, L. P.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Witt, K. L.] US NIH Natl Toxicol Program, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 731 EP 731 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600188 ER PT J AU Schisler, MR Gollapudi, BB Moore, MM AF Schisler, M. R. Gollapudi, B. B. Moore, M. M. TI Evaluation of the Mouse Lymphoma Mutation Assay (MLA) Data of the U. S. National Toxicology Program (NTP) Using International Workshop on Genotoxicity,Tests (IWGT) Criteria. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Schisler, M. R.; Gollapudi, B. B.] Dow Chem Co USA, Midland, MI 48674 USA. [Moore, M. M.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 7 Z9 7 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 732 EP 732 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600194 ER PT J AU Desai, VG Lee, T Moland, CL Branham, WS Fuscoe, JC Ali, AA Collins, JB Shelton, SD Manjanatha, MG AF Desai, V. G. Lee, T. Moland, C. L. Branham, W. S. Fuscoe, J. C. Ali, A. A. Collins, J. B. Shelton, S. D. Manjanatha, M. G. TI Altered Expression Levels of Mitochondria-Related Genes In Acrylamide- and Glycidamide-Treated Transgenic Big Blue Mice SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Desai, V. G.; Moland, C. L.; Branham, W. S.; Fuscoe, J. C.] US FDA, Ctr Funct Genom, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Lee, T.] Korea Univ, Dept Math & Informat, Jochiwon, Chungnam, South Korea. [Collins, J. B.] US FDA, Off Sci Coordinat, NCTR, Jefferson, AR USA. [Shelton, S. D.; Manjanatha, M. G.] US FDA, Div Genet Toxicol, NCTR, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 734 EP 734 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600202 ER PT J AU Mittelstaedt, RA Shaddock, JG Heflich, RH AF Mittelstaedt, R. A. Shaddock, J. G. Heflich, R. H. TI Comparison of Responses in the In Vitro Flow Cytometric Micronucleus Assay Using CHO and TK6 Cells SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Mittelstaedt, R. A.; Shaddock, J. G.; Heflich, R. H.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 734 EP 734 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600199 ER PT J AU Ding, W Bishop, ME Lyn-Cook, LE Kulkarni, R Levy, DD Aidoo, AL Manjanatha, MG AF Ding, W. Bishop, M. E. Lyn-Cook, L. E. Kulkarni, R. Levy, D. D. Aidoo, A. L. Manjanatha, M. G. TI Evaluation of Genotoxicity of Methyleugenol (MEG) Using Comet Assay and Pathway-Focused Gene Expression Profiling in the Liver of F344 Rats SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Ding, W.; Bishop, M. E.; Lyn-Cook, L. E.; Kulkarni, R.; Aidoo, A. L.; Manjanatha, M. G.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Levy, D. D.] US FDA, Ctr Food Safety & Nutr, College Pk, MD USA. RI Ding, Wei/L-1503-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 735 EP 735 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600205 ER PT J AU Reddy, NR Tetzloff, RC Skinner, GE AF Reddy, N. R. Tetzloff, R. C. Skinner, G. E. TI Effect of media, additives, and incubation conditions on the recovery of high pressure and heat-injured Clostridium botulinum spores SO FOOD MICROBIOLOGY LA English DT Article DE Clostridium botulinum; High pressure processing; Recovery of spores ID HIGH HYDROSTATIC-PRESSURE; INACTIVATION; RESISTANCE; PRESERVATION; FOODS; STERILIZATION; TEMPERATURES; LYSOZYME AB The effect of additives and post-treatment incubation conditions on the recovery of high pressure and heat-injured (i.e., processed at 620 MPa and 95 and 100 degrees C for 5 min) spores of Clostridium botulinum strains, 62-A (proteolytic type A) and 17-B (nonproteolytic type B) was studied. High pressure and heat-injured spores were inoculated into TPGY (Trypticase-Peptone-Glucose-Yeast extract) anaerobic broth media containing additives (lysozyme, L-alanine, L-aspartic acid, dipicolonic acid, sodium bicarbonate, and sodium lactate) at various concentrations (0-10 mu g/ml) individually or in combination. The spore counts of high pressure and heat-injured 62-A and 17-B recovered from TPGY broth containing lysozyme (10 mu g/ml) incubated for 4 months versus that recovered from peptone-yeast extract-glucose starch (PYGS) plating agar containing lysozyme (10 mu g/ml) incubated under anaerobic conditions for 5 days were also compared. None of the additives either individually or in combination in TPGY broth improved recovery of injured spore enumeration compared to processed controls without additives. Addition of lysozyme at concentrations of 5 and 10 mu g/ml in TPGY broth improved initial recovery of injured spores of 17-B during the first 4 days of incubation but did not result in additional recovery at the end of the 4 month incubation compared to the processed control without lysozyme. Adding lysozyme at a concentration of 10 mu g/ml to PYGS plating agar resulted in no effect on the recovery of high pressure and heat-injured 62-A and 17-B spores. The recovery counts of high pressure and heat-injured spores of 62-A and 17-B were lower (i.e., <1.0 log units) with PYGS plating agar compared to the MPN method using TPGY broth as the growth medium. Published by Elsevier Ltd. C1 [Reddy, N. R.; Skinner, G. E.] US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. [Tetzloff, R. C.] IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Reddy, NR (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM rukma.reddy@fda.hhs.gov NR 35 TC 17 Z9 17 U1 2 U2 19 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD AUG PY 2010 VL 27 IS 5 BP 613 EP 617 DI 10.1016/j.fm.2010.02.004 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 614LK UT WOS:000279060100009 PM 20510779 ER PT J AU Martinez-Urtaza, J Bowers, JC Trinanes, J DePaola, A AF Martinez-Urtaza, Jaime Bowers, John C. Trinanes, Joaquin DePaola, Angelo TI Climate anomalies and the increasing risk of Vibrio parahaemolyticus and Vibrio vulnificus illnesses SO FOOD RESEARCH INTERNATIONAL LA English DT Article DE V. parahaemolyticus; V. vulnificus; Climate anomalies; Outbreaks ID OYSTERS CRASSOSTREA-VIRGINICA; 1997-98 EL-NINO; UNITED-STATES; GULF-COAST; EPIDEMIC CHOLERA; CHESAPEAKE BAY; SEROVARS O3-K6; NORTHERN GULF; EMERGENCE; TEMPERATURE AB We examined the potential influence of climate anomalies in expanding the geographical and seasonal range of seafood-borne illnesses from Vibrio parahaemolyticus and Vibrio vulnificus. Archived climate data from areas of implicated seafood production were obtained from various sources, including in situ monitoring devices and satellite imagery. The geographical expansion of V. parahaemolyticus outbreaks into Peru and Alaska corresponded closely with climate anomalies such as El Nino, which brought large masses of abnormally warm water into these regions. Seasonal expansion of V. vulnificus illnesses associated with oysters harvested from the Gulf of Mexico in April and November correspond with warmer water temperatures (> 20 degrees C) recorded during these months since 1998. This retrospective review indicates that climate anomalies have already greatly expanded the risk area and season for vibrio illnesses and suggest that these events can be forecasted. Certainly, when similar circumstances occur in the future, adjustments in industry practices and regulatory policy should be considered, especially for seafood that is consumed raw, such as bivalve mollusks. Published by Elsevier Ltd. C1 [DePaola, Angelo] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. [Martinez-Urtaza, Jaime] Univ Santiago de Compostela, Inst Acuicultura, Santiago De Compostela 15782, Spain. [Bowers, John C.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Trinanes, Joaquin] Univ Santiago de Compostela, Inst Invest Tecnol, Santiago De Compostela 15782, Spain. RP DePaola, A (reprint author), US FDA, Gulf Coast Seafood Lab, POB 158, Dauphin Isl, AL 36528 USA. EM angelo.depaola@fda.hhs.gov RI Martinez-Urtaza, Jaime/A-5528-2015 NR 96 TC 65 Z9 67 U1 1 U2 32 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0963-9969 J9 FOOD RES INT JI Food Res. Int. PD AUG PY 2010 VL 43 IS 7 SI SI BP 1780 EP 1790 DI 10.1016/j.foodres.2010.04.001 PG 11 WC Food Science & Technology SC Food Science & Technology GA 663CN UT WOS:000282860700005 ER PT J AU M'ikanatha, NM Sandt, CH Localio, AR Tewari, D Rankin, SC Whichard, JM Altekruse, SF Lautenbach, E Folster, JP Russo, A Chiller, TM Reynolds, SM McDermott, PF AF M'ikanatha, Nkuchia M. Sandt, Carol H. Localio, A. Russell Tewari, Deepanker Rankin, Shelley C. Whichard, Jean M. Altekruse, Sean F. Lautenbach, Ebbing Folster, Jason P. Russo, Anthony Chiller, Tom M. Reynolds, Stanley M. McDermott, Patrick F. TI Multidrug-Resistant Salmonella Isolates from Retail Chicken Meat Compared with Human Clinical Isolates SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID UNITED-STATES; NONTYPHOIDAL SALMONELLA; ESCHERICHIA-COLI; FOOD ANIMALS; BETA-LACTAMASE; INFECTIONS; PLASMIDS; MEXICO; CMY-2 AB Aim: To examine the prevalence of antimicrobial-resistant Salmonella in chicken meat and correlate with isolates from ill humans. Methods: We isolated Salmonella from raw chicken purchased from a randomly selected sample of retail outlets in central Pennsylvania during 2006-2007. Salmonella isolates from meat were compared, using pulsed-field gel electrophoresis, to isolates in the PulseNet database of Salmonella recovered from humans. Results: Of 378 chicken meat samples, 84 (22%) contained Salmonella. Twenty-six (31%) of the Salmonella isolates were resistant to >= 3 antimicrobials and 18 (21%) were resistant to ceftiofur. All ceftiofur-resistant isolates exhibited reduced susceptibility (minimum inhibitory concentration >2 mg/mu L) to ceftriaxone and carried a blaCMY gene, as detected by polymerase chain reaction. Among the 28 Salmonella serovar Typhimurium isolates, 20 (71.4%) were resistant to >= 3 antimicrobials and 12 (42.9%) were resistant to ceftiofur. One ceftiofur-resistant Salmonella serovar Typhimurium poultry isolate exhibited a rare pulsed-field gel electrophoresis pattern indistinguishable from a human isolate in PulseNet; both isolates carried the bla(CMY-2) gene. Conclusions: These data demonstrate the presence of multidrug-resistant Salmonella in poultry meat, including blaCMY plasmid-mediated genes that confer resistance to both ceftiofur, used in poultry, and ceftriaxone, used for treating salmonellosis in humans. This study illustrates the potential for molecular subtyping databases to identify related Salmonella isolates from meat and ill humans, and suggests that chicken could be a source for multidrug-resistant salmonellosis in humans. C1 [M'ikanatha, Nkuchia M.] Penn Dept Hlth, Div Infect Dis Epidemiol, Harrisburg, PA 17120 USA. [M'ikanatha, Nkuchia M.; Localio, A. Russell; Rankin, Shelley C.; Lautenbach, Ebbing] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Sandt, Carol H.; Reynolds, Stanley M.] Penn Dept Hlth Bur Labs, Exton, PA USA. [Tewari, Deepanker; Russo, Anthony] Penn Dept Agr, Harrisburg, PA USA. [Whichard, Jean M.; Folster, Jason P.; Chiller, Tom M.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Altekruse, Sean F.] NIH, Bethesda, MD 20892 USA. [Folster, Jason P.] Atlanta Res & Educ Fdn, Atlanta, GA USA. [McDermott, Patrick F.] US FDA, Ctr Vet Med, Laurel, MD USA. RP M'ikanatha, NM (reprint author), Penn Dept Hlth, Div Infect Dis Epidemiol, Harrisburg, PA 17120 USA. EM nmikanatha@state.pa.us FU Agency for Healthcare Research and Quality Centers for Education and Research on Therapeutics [U18-HS10399]; Pennsylvania Department of Health through Centers for Disease Control and Prevention [ELC-04040] FX This study was supported in part by the Agency for Healthcare Research and Quality Centers for Education and Research on Therapeutics cooperative agreement (U18-HS10399) and by the Pennsylvania Department of Health through Centers for Disease Control and Prevention grant (ELC-04040) for National Antimicrobial Resistance Monitoring. NR 27 TC 23 Z9 24 U1 0 U2 3 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 AUG PY 2010 VL 7 IS 8 BP 929 EP 934 DI 10.1089/fpd.2009.0499 PG 6 WC Food Science & Technology SC Food Science & Technology GA 631UK UT WOS:000280374900009 PM 20443729 ER PT J AU Doi, SQ Chilakamarri, GC Mendonca, MC Araujo, M Nguyen, N Zuhl, I List, EO Kopchick, JJ Hirata, MH Sellitti, DF AF Doi, Sonia Q. Chilakamarri, Geetha C. Mendonca, Maria C. Araujo, Magali Nguyen, Nga Zuhl, Irina List, Edward O. Kopchick, John J. Hirata, Mario H. Sellitti, Donald F. TI Increased class A scavenger receptor and glomerular lipid precede mesangial matrix expansion in the bGH mouse model SO GROWTH HORMONE & IGF RESEARCH LA English DT Article DE Glomerulosclerosis; Macrophage; Mesangial cells; Kidney; Mouse ID LOW-DENSITY-LIPOPROTEIN; BOVINE GROWTH-HORMONE; TRANSGENIC MICE; RENAL-DISEASE; I COLLAGEN; EXPRESSION; CELLS; RAT; GLOMERULOSCLEROSIS; METABOLISM AB Objective: Elevated neutral lipid content and mRNA expression of class A scavenger receptor (SRA) have been found in the renal cortex of the bovine growth hormone (bGH) mouse model of progressive glomerulosclerosis (GS). We hypothesize that the increased expression of SRA precedes glomerular scarring in this model. Design: Real time RT-PCR and immunofluorescence were employed to measure SRA and collagen types I and IV in the bGH transgenic and control mice at 5 and 12 weeks (wk) of age to determine the chronology of change in SRA expression in relation to glomerular scarring. Alternative mechanisms for increasing glomerular lipid were assessed by measuring mRNA expression levels of low-density lipoprotein receptor (LDL-r), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), and ATP-binding cassette transporter A1 (ABCA1). In addition, the involvement of macrophages in early GS was assessed by CD68 mRNA expression in kidney cortex. Results: Both mRNA and protein levels of SRA were significantly increased in 5-wk bGH compared with control mice, whereas the expression of collagen I and IV was unaltered. Unchanged levels of LDL-r and HMGR mRNA indicate that neither regulated cholesterol uptake via LDL-r nor the cholesterol synthetic pathway played a role in the early lipid increase. The finding of increased ABCA1 expression was an indicator of excess intracellular lipid in the renal cortex of bGH mice at 5 wk. CD68 expression in bGH did not differ significantly from that of controls at 5 wk suggesting that cortical macrophage infiltration was not increased in bGH mice at this time point. Conclusion: An early increase in SRA mRNA and protein expression in the bGH kidney precedes glomerular scarring and is independent of macrophage influx. Published by Elsevier Ltd. on behalf of Growth Hormone Research Society. C1 [Doi, Sonia Q.; Chilakamarri, Geetha C.; Mendonca, Maria C.; Araujo, Magali; Sellitti, Donald F.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Chilakamarri, Geetha C.] Michigan State Univ, Lansing, MI USA. [Nguyen, Nga; Zuhl, Irina] US FDA, CBER, Bethesda, MD 20014 USA. [List, Edward O.; Kopchick, John J.] Ohio Univ, Edison Biotechnol Inst, Athens, OH 45701 USA. [Hirata, Mario H.] Univ Sao Paulo, Sch Pharmaceut Sci, Sao Paulo, Brazil. RP Doi, SQ (reprint author), Uniformed Serv Univ Hlth Sci, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM sdoi@usuhs.mil RI Hirata, Mario/D-3593-2012; Hirata, Mario/C-9718-2013 FU Uniformed Services University [C083ST] FX This work was funded by a Uniformed Services University grant #C083ST. NR 33 TC 4 Z9 4 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1096-6374 J9 GROWTH HORM IGF RES JI Growth Horm. IGF Res. PD AUG PY 2010 VL 20 IS 4 BP 326 EP 332 DI 10.1016/j.ghir.2010.05.002 PG 7 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 643AT UT WOS:000281265300009 PM 20576456 ER PT J AU Wang, SY Chen, CT Yin, JJ AF Wang, Shiow Ying Chen, Chi-Tsun Yin, Jun-Jie TI Allyl Isothiocyanate Reduces Fruit Decay of Blueberries by Paradoxically Generating Reactive Oxygen Species SO HORTSCIENCE LA English DT Meeting Abstract C1 [Wang, Shiow Ying; Chen, Chi-Tsun] ARS, USDA, Beltsville, MD USA. [Yin, Jun-Jie] US FDA, College Pk, MD USA. EM shiow.wang@ars.usda.gov; wangcysy@gmail.com; junjie.yin@fda.hhs.gov RI Yin, Jun Jie /E-5619-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HORTICULTURAL SCIENCE PI ALEXANDRIA PA 113 S WEST ST, STE 200, ALEXANDRIA, VA 22314-2851 USA SN 0018-5345 J9 HORTSCIENCE JI Hortscience PD AUG PY 2010 VL 45 IS 8 SU S BP S214 EP S214 PG 1 WC Horticulture SC Agriculture GA 822OZ UT WOS:000295060800505 ER PT J AU Johansson, A Celli, J Conlan, W Elkins, KL Forsman, M Keim, PS Larsson, P Manoil, C Nano, FE Petersen, JM Sjostedt, A AF Johansson, Anders Celli, Jean Conlan, Wayne Elkins, Karen L. Forsman, Mats Keim, Paul S. Larsson, Par Manoil, Colin Nano, Francis E. Petersen, Jeannine M. Sjostedt, Anders TI Objections to the transfer of Francisella novicida to the subspecies rank of Francisella tularensis SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Letter ID DIVERSITY; NAMES C1 [Johansson, Anders; Sjostedt, Anders] Umea Univ, Dept Clin Microbiol, S-90185 Umea, Sweden. [Celli, Jean] NIAID, Tularemia Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. [Conlan, Wayne] Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1C 2M7, Canada. [Elkins, Karen L.] US FDA, Lab Mycobacterial Dis & Cellular Immunol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Forsman, Mats; Larsson, Par] Swedish Def Res Agcy, Div CBRN Def & Secur, SE-90182 Umea, Sweden. [Keim, Paul S.] No Arizona Univ, Dept Biol Sci, Flagstaff, AZ 86011 USA. [Manoil, Colin] Univ Washington, Seattle, WA 98195 USA. [Nano, Francis E.] Univ Victoria, Dept Biochem & Microbiol, Victoria, BC V8W 3P6, Canada. [Petersen, Jeannine M.] Ctr Dis Control, Div Vector Borne Infect Dis, Bacterial Dis Branch, Ft Collins, CO 80521 USA. [Petersen, Jeannine M.] Ctr Dis Prevent, Div Vector Borne Infect Dis, Bacterial Dis Branch, Ft Collins, CO 80521 USA. RP Johansson, A (reprint author), Umea Univ, Dept Clin Microbiol, S-90185 Umea, Sweden. EM anders.johansson@climi.umu.se RI Keim, Paul/A-2269-2010; Forsman, Mats/A-1426-2016; Johansson, Anders/D-2928-2012; OI Forsman, Mats/0000-0002-4466-5325; Johansson, Anders/0000-0003-0548-5943; Sjostedt, Anders/0000-0002-0768-8405 NR 11 TC 31 Z9 31 U1 1 U2 5 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD AUG PY 2010 VL 60 BP 1717 EP 1718 DI 10.1099/ijs.0.022830-0 PN 8 PG 2 WC Microbiology SC Microbiology GA 642AS UT WOS:000281175700001 PM 20688748 ER PT J AU Sahu, SC O'Donnell, MW Wiesenfeld, PL AF Sahu, Saura C. O'Donnell, Michael W., Jr. Wiesenfeld, Paddy L. TI Comparative hepatotoxicity of deoxynivalenol in rat, mouse and human liver cells in culture SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE deoxynivalenol, mycotoxin, hepatotoxicity; liver toxicity, hepatocytes, rat Clone9 cells, mouse BNL CL2 cells; human HepG2 cells, human WRL68 cells ID FUSARIUM-TOXIN DEOXYNIVALENOL; IN-VITRO; LIPID-PEROXIDATION; OXIDATIVE STRESS; CEREAL-GRAINS; DNA-DAMAGE; T-2 TOXIN; TOXICITY; CYTOTOXICITY; HEPATOCYTES AB The present study was undertaken to assess, in vitro, the hepatotoxic potential of the food-borne mycotoxin, deoxynivalenol (DON), using rat (Clone9 and MH1C1), mouse (NBL CL2) and human (WRL68 and HepG2) liver cells in culture. The cells were treated with DON for 24 h at 37 degrees C in 5% CO(2) at concentrations of 0-25 mu g ml(-1). Following the treatment period, the cells were assayed for biochemical markers of hepatotoxicity that included three independent cytotoxicity assays, oxidative stress and mitochondria! dysfunction. Concentration-dependent cytotoxicity of DON was observed in each of the five different liver cells derived from three different species (rat, mouse and human) over the entire concentration range studied, beginning at 0.1 mu g ml(-1). At these concentrations DON did not induce a biologically significant increase in oxidative stress in these liver cells, and showed a significant decrease in the mitochondrial function only in the rat liver MH1C1 cells compared with the control. The results of this in vitro study suggest that DON is a potential hepatotoxin for the rat, mouse and human liver cells in the concentration range tested in this study. The liver cells used in this study showed distinct endpoint-sensitivity to DON related to the species. Published in 2010 by John Wiley and Sons, Ltd. C1 [Sahu, Saura C.; Wiesenfeld, Paddy L.] US FDA, Div Toxicol, Off Appl Res & Safety Assessment, Off Food Def Commun & Emergency Response,Ctr Food, Laurel, MD 20708 USA. [O'Donnell, Michael W., Jr.] US FDA, Div Publ Hlth & Biostat, Off Food Def Communic & Emergency Response, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Sahu, SC (reprint author), US FDA, Div Toxicol, Off Appl Res & Safety Assessment, Off Food Def Commun & Emergency Response,Ctr Food, Laurel, MD 20708 USA. NR 45 TC 13 Z9 13 U1 0 U2 25 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD AUG PY 2010 VL 30 IS 6 BP 566 EP 573 DI 10.1002/jat.1527 PG 8 WC Toxicology SC Toxicology GA 647KG UT WOS:000281616800008 PM 20809545 ER PT J AU Dasgupta, S Wansapura, J Hariharan, P Pratt, R Witte, D Myers, MR Banerjee, RK AF Dasgupta, Subhashish Wansapura, Janaka Hariharan, Prasanna Pratt, Ron Witte, David Myers, Matthew R. Banerjee, Rupak K. TI HIFU Lesion Volume as a Function of Sonication Time, as Determined by MRI, Histology, and Computations SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article DE HIFU; MRI; lesion size; sonication time; histology ID INTENSITY-FOCUSED ULTRASOUND; SOFT-TISSUE; CANCER; SURGERY; SIZE AB Characterization of high-intensity focused ultrasound (HIFU) systems using ex vivo tissues is an important part of the preclinical testing for new HIFU devices. In ex vivo characterization, the lesion volume produced by the absorption of HIFU energy is quantified as operational parameters are varied. This paper examines the three methods used for lesion-volume quantification: histology, magnetic resonance (MR) imaging, and numerical calculations. The methods were studied in the context of a clinically relevant problem for HIFU procedures-that of quantifying the change in the lesion volume with changing sonication time. The lesion volumes of sonicated samples of porcine liver were determined using the three methods, at focal intensities ranging from 800 W/cm(2) to 1700 W/cm(2) and sonication times between 20 s and 40 s. It was found that histology consistently yielded lower lesion volumes than the other two methods, and the calculated values were below magnetic resonance imaging (MRI) at high applied energies. Still, the three methods agreed with each other to within a +/- 10% difference for all of the experiments. Increasing the sonication time produced much larger changes in the lesion volume than increasing the acoustic intensity, for the same total energy expenditure, at lower energy (less than 1000 J) levels. At higher energy levels, (around 1500 J), increasing the sonication time and increasing the intensity produced roughly the same change in the lesion volume for the same total energy expenditure. [DOI: 10.1115/1.4001739] C1 [Dasgupta, Subhashish; Hariharan, Prasanna; Banerjee, Rupak K.] Univ Cincinnati, Dept Mech Engn, Cincinnati, OH 45221 USA. [Wansapura, Janaka; Pratt, Ron] Childrens Hosp, Med Ctr, Dept Xray Radiol, Cincinnati, OH 45229 USA. [Hariharan, Prasanna; Myers, Matthew R.] US FDA, Div Solid & Fluid Mech, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Witte, David] Childrens Hosp, Med Ctr, Dept Histopathol, Cincinnati, OH 45229 USA. [Banerjee, Rupak K.] Univ Cincinnati, Dept Biomed Engn, Cincinnati, OH 45221 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 gratefully acknowledged. NR 22 TC 3 Z9 3 U1 0 U2 2 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD AUG PY 2010 VL 132 IS 8 AR 081005 DI 10.1115/1.4001739 PG 7 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 633HP UT WOS:000280492800005 PM 20670054 ER PT J AU Singh, R Arlt, VM Henderson, CJ Phillips, DH Farmer, PB da Costa, GG AF Singh, Rajinder Arlt, Volker M. Henderson, Colin J. Phillips, David H. Farmer, Peter B. da Costa, Goncalo Gamboa TI Detection and quantitation of N-(deoxyguanosin-8-yl)-2-amino-1-methyl-6-Phenylimidazo[4,5-b]pyridine adducts in DNA using online column-switching liquid chromatography tandem mass spectrometry SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine(PhIP); DNA adducts; LC-MS/MS; Chemical carcinogen ID HETEROCYCLIC AMINES; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; IN-VITRO; FOOD; CARCINOGEN; METABOLISM; LIVER; MEAT; 2'-DEOXYGUANOSINE; QUANTIFICATION AB The heterocyclic aromatic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is formed by the grilled cooking of certain foods such as meats, poultry and fish. PhIP has been shown to induce tumours in the colon, prostate and mammary glands of rats and is regarded as a potential human dietary carcinogen. PhIP is metabolically activated via cytochrome P450 mediated oxidation to an N-hydroxylamino-PhIP intermediate that is subsequently converted to an ester by N-acetyltransferases or sulfotransferases and undergoes heterolytic cleavage to produce a PhIP-nitrenium ion, which reacts with DNA to form the N-(deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine ( PhIP-C8-dG) adduct. Thus far, the detection and quantification of PhIP-DNA adducts has relied to a large extent on (32)P-postlabelling methodologies. In order to expand the array of available techniques for the detection and improved quantification of PhIP-C8-dG adducts in DNA we have developed an online column-switching liquid chromatography (LC)-electrospray ionization (ESI)-tandem mass spectrometry (MS/MS) selected reaction monitoring (SRM) method incorporating an isotopically [(13)C(10)]-labelled PhIP-C8-dG internal standard for the analysis of DNA enzymatically hydrolysed to 2'-deoxynucleosides. A dose-dependent increase was observed for PhIP-C8-dG adducts when salmon testis DNA was reacted with N-acetoxy-PhIP. Analysis of DNA samples isolated from colon tissue of mice treated by oral gavage daily for 5 days with 50 mg/kg body weight of PhIP resulted in the detection of an average level of 14.8 +/- 3.7 PhIP-C8-dG adducts per 10(6) 2'-deoxynucleosides. The method required 50 mu g of hydrolysed animal DNA on column and the limit of detection for PhIP-C8-dG was 2.5 fmol (1.5 PhIP-C8-dG adducts per 10(8) 2'-cleoxynucleosides). In summary, the LC-ESI-MS/MS SRM method provides for the rapid automation of the sample clean up and a reduction in matrix components that would otherwise interfere with the mass spectrometric analysis, with sufficient sensitivity and precision to analyse DNA adducts in animals exposed to PhIP. (C) 2010 Elsevier B.V. All rights reserved. C1 [Singh, Rajinder; Farmer, Peter B.] Univ Leicester, Canc Biomarkers & Prevent Grp, Bioctr, Dept Canc Studies & Mol Med, Leicester LE1 7RH, Leics, England. [da Costa, Goncalo Gamboa] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Arlt, Volker M.; Phillips, David H.] Inst Canc Res, Sect Mol Carcinogenesis, Surrey SM2 5NG, England. [Henderson, Colin J.] Biomed Res Ctr, Canc Res UK Mol Pharmacol Unit, Dundee DD1 9SY, Scotland. RP Singh, R (reprint author), Univ Leicester, Canc Biomarkers & Prevent Grp, Bioctr, Dept Canc Studies & Mol Med, Univ Rd, Leicester LE1 7RH, Leics, England. EM rs25@le.ac.uk RI Singh, Raj/A-5398-2011; OI Henderson, Colin/0000-0002-4764-639X; Phillips, David/0000-0001-8509-3485; Arlt, Volker Manfred/0000-0003-4314-9318 FU European Union [FOOD-CT-2005-513943]; Cancer Research, UK [C6048/A10896]; Fundacao para a Ciencia e a Tecnologia (FCT), Portugal; FEDER [PPCDT/QUI/57110/2004] FX The authors acknowledge financial support from the European Union Network of Excellence ECNIS, Type B project (Environmental Cancer Risk, Nutrition and Individual Susceptibility, www.ecnis.org, Contract No. FOOD-CT-2005-513943) and from Cancer Research, UK (CRUK project grant C6048/A10896). This work was supported in part by a research grant from Fundacao para a Ciencia e a Tecnologia (FCT), Portugal and FEDER (PPCDT/QUI/57110/2004). The views presented in this article do not necessarily reflect those of the US Food and Drug Administration. NR 37 TC 15 Z9 15 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD AUG 1 PY 2010 VL 878 IS 23 BP 2155 EP 2162 DI 10.1016/j.jchromb.2010.06.008 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 634WU UT WOS:000280617400019 PM 20598652 ER PT J AU Steinsland, H Lacher, DW Sommerfelt, H Whittam, TS AF Steinsland, Hans Lacher, David W. Sommerfelt, Halvor Whittam, Thomas S. TI Ancestral Lineages of Human Enterotoxigenic Escherichia coli SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID PUTATIVE COLONIZATION FACTOR; HEAT-LABILE ENTEROTOXIN; YOUNG-CHILDREN; POPULATION-STRUCTURE; FACTOR ANTIGENS; GUINEA-BISSAU; DIARRHEA; STRAINS; EVOLUTIONARY; SEQUENCE AB Enterotoxigenic Escherichia coli (ETEC) is a common cause of diarrhea among children living in and among travelers visiting developing countries. Human ETEC strains represent an epidemiologically and phenotypically diverse group of pathogens, and there is a need to identify natural groupings of these organisms that may help to explain this diversity. Here, we sought to identify most of the important human ETEC lineages that exist in the E. coli population, because strains that originate from the same lineage may also have inherited many of the same epidemiological and phenotypic traits. We performed multilocus sequence typing (MLST) on 1,019 ETEC isolates obtained from humans in different countries and analyzed the data against a backdrop of MLST data from 1,250 non-ETEC E. coli and eight ETEC isolates from pigs. A total of 42 different lineages were identified, 15 of which, representing 792 (78%) of the strains, were estimated to have emerged > 900 years ago. Twenty of the lineages were represented in more than one country. There was evidence of extensive exchange of enterotoxin and colonization factor genes between different lineages. Human and porcine ETEC have probably emerged from the same ancestral ETEC lineage on at least three occasions. Our findings suggest that most ETEC strains circulating in the human population today originate from well-established, globally widespread ETEC lineages. Some of the more important lineages identified here may represent a smaller and more manageable target for the ongoing efforts to develop effective ETEC vaccines. C1 [Steinsland, Hans; Sommerfelt, Halvor] Univ Bergen, Ctr Int Hlth, N-5020 Bergen, Norway. [Steinsland, Hans] Univ Bergen, Dept Biomed, N-5020 Bergen, Norway. [Steinsland, Hans; Lacher, David W.; Whittam, Thomas S.] Michigan State Univ, Natl Food Safety & Toxicol Ctr, E Lansing, MI 48824 USA. [Lacher, David W.] US FDA, Div Mol Biol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD USA. [Sommerfelt, Halvor] Norwegian Inst Publ Hlth, Oslo, Norway. RP Steinsland, H (reprint author), Univ Bergen, Ctr Int Hlth, POB 7804, N-5020 Bergen, Norway. EM hans.steinsland@bio.uib.no FU Food and Waterborne Integrated Research Network Microbiology Research Unit under National Institutes of Health [N01-AI-30058]; Research Council of Norway [185872/S50]; Faculty of Medicine and Dentistry; University of Bergen, Bergen, Norway; Kaia and Arne Naevdals Fund, Bergen, Norway [470940] FX This study was supported in part by the Food and Waterborne Integrated Research Network Microbiology Research Unit under National Institutes of Health (www.nih.gov) research contract N01-AI-30058 (to T. S. Whittam); the Global Health and Vaccination (GLOBVAC) Research Programme under Research Council of Norway (www.rcn.no) contract 185872/S50 (salary to H. Steinsland); the Faculty of Medicine and Dentistry (www.uib.no/mofa/), University of Bergen, Bergen, Norway (salary to H. Steinsland); and Kaia and Arne Naevdals Fund, Bergen, Norway, research grant 470940 (to H. Steinsland). NR 60 TC 24 Z9 24 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD AUG PY 2010 VL 48 IS 8 BP 2916 EP 2924 DI 10.1128/JCM.02432-09 PG 9 WC Microbiology SC Microbiology GA 634AQ UT WOS:000280550500040 PM 20534806 ER PT J AU Zhang, GD Lampel, KA AF Zhang, Guodong Lampel, Keith A. TI Comparison of Chromogenic Biolog Rainbow Agar Shigella/Aeromonas with Xylose Lysine Desoxycholate Agar for Isolation and Detection of Shigella spp. from Foods SO JOURNAL OF FOOD PROTECTION LA English DT Article ID RURAL WESTERN KENYA; ANTIMICROBIAL RESISTANCE; BACTERIAL DIARRHEA; TOMATO SURFACES; UNITED-STATES; SONNEI; MEDIA; CULTURE; SALMONELLA; INFECTION AB Shigella outbreaks are widely reported throughout the world. However, it remains a challenge to isolate Shigella spp from foods by using conventional microbiological media. The main objective of this study was to determine the effectiveness of a novel chromogenic medium. Rainbow agar Shigella/Aeromonas (Rainbow agar), for the isolation and detection of Shigella spp in foods All four Shigella species, S sonnei, S flexneri, S dysenteriae, and S boydu, were studied Rainbow agar was compared with tryptic soy agar, xylose lysine desoxycholate agar (XLD), and Salmonella Shigella agar (SSA) for enumeration of Shigella spp in pure culture This chromogenic agar and XLD were also used to isolate Shigella spp in artificially contaminated foods (4 8 log CFU/g of food), including lettuce, parsley, cilantro, spinach, potato salad, and shrimp The inhibitory effect on Shigella growth by Rainbow agar was between that of XLD and SSA. All vegetables studied showed a moderately high background microflora on XLD and Rainbow agar. With artificially inoculated produce, Rainbow agar recovered about I to 2 log CFU more S sonnet S dysenteriae, and S boydu per g of food than did XLD For potato salad and shrimp, which had low background microflora on Rainbow agar, Rainbow agar was slightly better in recovering Shigella spp than XLD was in most cases However, we found that the addition of streptomycin (6 25 mg/liter) to Rainbow agar could facilitate the isolation of Shigella in vegetables tested In conclusion, Rainbow agar was a much more effective medium than was XLD for the isolation of Shingella spp from foods C1 [Zhang, Guodong; Lampel, Keith A.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Lampel, KA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS 712,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 23 TC 3 Z9 3 U1 1 U2 2 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 AUG PY 2010 VL 73 IS 8 BP 1458 EP 1465 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 641XV UT WOS:000281166900007 PM 20819355 ER PT J AU Timbo, BB Keys, C Klontz, K AF Timbo, Babgaleh B. Keys, Christine Klontz, Karl TI Characterization of Listeria monocytogenes Recovered from Imported Cheese Contributed to the National PulseNet Database by the US Food and Drug Administration from 2001 to 2008 SO JOURNAL OF FOOD PROTECTION LA English DT Article ID FIELD GEL-ELECTROPHORESIS; MEXICAN-STYLE CHEESE; PROTOCOL; OUTBREAK AB Imported foods must meet the same U S Food and Drug Administration (FDA) standards as domestic foods The FDA determines whether an imported food is in compliance with the Federal Food, Drug, and Cosmetic Act. Pursuant to its regulatory activities, the FDA conducts compliance surveillance on imported foods offered for entry into the U S commerce. The National PulseNet Database is the molecular surveillance network for foodborne infections and is widely used to provide real-time subtyping support to epidemiologic investigations of foodborne diseases FDA laboratories use pulsed-field gel electrophoresis to subtype foodborne pathogens recovered from imported foods and submit the molecular patterns to the National PulseNet Database at the Centers for Disease Control and Prevention There were 60 isolates of Listeria monocytogenes in the FDA Field Accomplishment and Compliance Tracking System from 2001 to 2008 due to cheese imported from the following countries. Mexico (n = 21 isolates), Italy (19), Israel (9), Portugal (5), Colombia (3), Greece (2), and Spain (1). We observed genetic diversity of L monocytogenes isolates and genetic relatedness among strains recovered from imported cheese products coming to the United States from different countries. Consistent characterization of L monocytogenes isolates recovered from imported cheeses, accompanied by epidemiologic investigations to ascertain human illness associated with these strains, could be helpful in the control of listeriosis acquired from imported cheeses. C1 [Timbo, Babgaleh B.; Klontz, Karl] US FDA, Off Food Def Commun & Emergency Response, College Pk, MD 20740 USA. [Keys, Christine] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Timbo, BB (reprint author), US FDA, Off Food Def Commun & Emergency Response, College Pk, MD 20740 USA. NR 13 TC 2 Z9 2 U1 1 U2 4 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 AUG PY 2010 VL 73 IS 8 BP 1511 EP 1514 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 641XV UT WOS:000281166900015 PM 20819363 ER PT J AU Donnelly, RP Kotenko, SV AF Donnelly, Raymond P. Kotenko, Sergei V. TI Interferon-Lambda: A New Addition to an Old Family SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Editorial Material ID POTENT ANTIVIRAL ACTIVITY; C VIRUS-REPLICATION; IFN-LAMBDA; I INTERFERON; RECEPTOR COMPLEX; EPITHELIAL-CELLS; III INTERFERONS; GENE-EXPRESSION; DENDRITIC CELLS; GAMMA RECEPTOR AB The discovery and initial description of the interferon-lambda (IFN-lambda) family in early 2003 opened an exciting new chapter in the field of IFN research. There are 3 IFN-lambda genes that encode 3 distinct but highly related proteins denoted IFN-lambda, -lambda 2, and -lambda 3. These proteins are also known as interleukin-29 (IL-29), IL-28A, and IL-28B, respectively. Collectively, these 3 cytokines comprise the type III subset of IFNs. They are distinct from both type I and type II IFNs for a number of reasons, including the fact that they signal through a heterodimeric receptor complex that is different from the receptors used by type I or type II IFNs. Although type I IFNs (IFN-alpha/beta) and type III IFNs (IFN-lambda) signal via distinct receptor complexes, they activate the same intracellular signaling pathway and many of the same biological activities, including antiviral activity, in a wide variety of target cells. Consistent with their antiviral activity, expression of the IFN-lambda genes and their corresponding proteins is inducible by infection with many types of viruses. Therefore, expression of the type III IFNs (IFN-lambda s) and their primary biological activity are very similar to the type I IFNs. However, unlike IFN-alpha receptors which are broadly expressed on most cell types, including leukocytes, IFN-lambda receptors are largely restricted to cells of epithelial origin. The potential clinical importance of IFN-lambda as a novel antiviral therapeutic agent is already apparent. In addition, preclinical studies by several groups indicate that IFN-lambda may also be useful as a potential therapeutic agent for other clinical indications, including certain types of cancer. C1 [Donnelly, Raymond P.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Kotenko, Sergei V.] Univ Med & Dent New Jersey, Univ Hosp Canc Ctr, Dept Biochem & Mol Biol, Newark, NJ 07103 USA. RP Donnelly, RP (reprint author), US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bldg 29A,Room 3B15 29 Lincoln Dr, Bethesda, MD 20892 USA. EM raymond.donnelly@fda.hhs.gov; kotenkse@umdnj.edu FU NIAID NIH HHS [R01 AI057468, AI057468, R21 AI076937, AI076937] NR 76 TC 167 Z9 185 U1 1 U2 15 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2010 VL 30 IS 8 BP 555 EP 564 DI 10.1089/jir.2010.0078 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 639IG UT WOS:000280967900001 PM 20712453 ER PT J AU Van Wagoner, RM Deeds, JR Tatters, AO Place, AR Tomas, CR Wright, JLC AF Van Wagoner, Ryan M. Deeds, Jonathan R. Tatters, Avery O. Place, Allen R. Tomas, Carmelo R. Wright, Jeffrey L. C. TI Structure and Relative Potency of Several Karlotoxins from Karlodinium veneficum SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID MEMBRANE-PERMEABILIZING ACTIVITIES; TRUNCATED POLYHYDROXYL CHAIN; ALGA PRYMNESIUM-PARVUM; MARINE DINOFLAGELLATE; AMPHIDINIUM-KLEBSII; TOXIN; ANTIFUNGAL; MICRUM; DINOPHYCEAE; PROFILES AB The karlotoxins are a family of amphidinol-like compounds that play roles in avoiding predation and in prey capture for the toxic dinoflagellate Karlodinium veneficum. The first member of the toxin group to be reported was KmTx 1 (1), and here we report an additional five new members of this family (3-7) from the same strain. Of these additional compounds, KmTx 3 (3) differs from KmTx 1 (1) in having one less methylene group in the saturated portion of its lipophilic arm. In addition, 64-E-chloro-KmTx 3 (4) and 10-O-sullo-KmTx 3 (5) were identified. Likewise, 65-E-chloro-KmTx 1 (6) and 10-O-sulfo-KmTx 1 (7) were also isolated. Comparison of the hemolytic activities of the newly isolated compounds to that of KmTx 1 shows that potency correlates positively with the length of the lipophilic arm and is disrupted by sulfonation of the polyol arm. C1 [Van Wagoner, Ryan M.; Tatters, Avery O.; Tomas, Carmelo R.; Wright, Jeffrey L. C.] Univ N Carolina, Ctr Marine Sci, Wilmington, NC 28409 USA. [Deeds, Jonathan R.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Place, Allen R.] Univ Maryland, Inst Marine & Environm Technol, Ctr Environm Sci, Baltimore, MD 21202 USA. RP Wright, JLC (reprint author), Univ N Carolina, Ctr Marine Sci, 5600 Marvin Moss Lane, Wilmington, NC 28409 USA. EM wrightj@uncw.edu RI Place, Allen/F-9267-2013 FU NIH [5P41GM076300-01]; MARBIONC; NSF, Division of Biological Infrastructure [DBI-0100085] FX J.L.C.W. gratefully acknowledges funding support from NIH (5P41GM076300-01). This work was supported in part by MARBIONC (J.L.C.W. and C.T.). We thank Mr. F. Sun (University of Illinois at Urbana-Champaign) for collecting high-resolution mass spectrometric data. The Q-Tof Ultima mass spectrometer (UIUC) was purchased in part with a grant from the NSF, Division of Biological Infrastructure (DBI-0100085). This is contribution #4398 from the UMCES Institute of Marine and Environmental Sciences and #329 from the Ecology and Oceanography of Harmful Algal Blooms (ECOHAB) program. NR 36 TC 21 Z9 21 U1 0 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD AUG PY 2010 VL 73 IS 8 BP 1360 EP 1365 DI 10.1021/np100158r PG 6 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 642CO UT WOS:000281181200008 PM 20795740 ER PT J AU Sampson, JH Archer, G Pedain, C Wembacher-Schroder, E Westphal, M Kunwar, S Vogelbaum, MA Coan, A Herndon, JE Raghavan, R Brady, ML Reardon, DA Friedman, AH Friedman, HS Rodriguez-Ponce, MI Chang, SM Mittermeyer, S Croteau, D Puri, RK AF Sampson, John H. Archer, Gary Pedain, Christoph Wembacher-Schroeder, Eva Westphal, Manfred Kunwar, Sandeep Vogelbaum, Michael A. Coan, April Herndon, James E., II Raghavan, Raghu Brady, Martin L. Reardon, David A. Friedman, Allan H. Friedman, Henry S. Rodriguez-Ponce, M. Inmaculada Chang, Susan M. Mittermeyer, Stephan Croteau, David Puri, Raj K. CA PRECISE Trial Investigators TI Poor drug distribution as a possible explanation for the results of the PRECISE trial Clinical article SO JOURNAL OF NEUROSURGERY LA English DT Article DE brain neoplasm; drug delivery system; interleukin-13; planning software; convection-enhanced delivery ID CONVECTION-ENHANCED DELIVERY; RECURRENT MALIGNANT GLIOMA; IL4-PSEUDOMONAS EXOTOXIN NBI-3001; NEUROTROPHIC FACTOR; GLIOBLASTOMA-MULTIFORME; PSEUDOMONAS EXOTOXIN; BRAIN-TUMORS; INFUSION; IL13-PE38QQR; SAFETY AB Object. Convection-enhanced delivery (CED) is a novel intracerebral drug delivery technique with considerable promise for delivering therapeutic agents throughout the CNS. Despite this promise, Phase III clinical trials employing CED have failed to meet clinical end points. Although this may be due to inactive agents or a failure to rigorously validate drug targets, the authors have previously demonstrated that catheter positioning plays a major role in drug distribution using this technique. The purpose of the present work was to retrospectively analyze the expected drug distribution based on catheter positioning data available from the CED arm of the PRECISE trial. Methods. Data on catheter positioning from all patients randomized to the CED arm of the PRECISE trial were available for analyses. BrainLAB iPlan Flow software was used to estimate the expected drug distribution. Results. Only 49.8% of catheters met all positioning criteria. Still, catheter positioning score (hazard ratio 0.93, p = 0.043) and the number of optimally positioned catheters (hazard ratio 0.72, p = 0.038) had a significant effect on progression-free survival. Estimated coverage of relevant target volumes was low, however, with only 20.1% of the 2-cm penumbra surrounding the resection cavity covered on average. Although tumor location and resection cavity volume had no effect on coverage volume, estimations of drug delivery to relevant target volumes did correlate well with catheter score (p < 0.003), and optimally positioned catheters had larger coverage volumes (p < 0.002). Only overall survival (p = 0.006) was higher for investigators considered experienced after adjusting for patient age and Karnofsky Performance Scale score. Conclusions. The potential efficacy of drugs delivered by CED may be severely constrained by ineffective delivery in many patients. Routine use of software algorithms and alternative catheter designs and infusion parameters may improve the efficacy of drugs delivered by CED. (DOI: 10.3171/2009.11.JNS091052) C1 [Sampson, John H.] Duke Univ, Med Ctr, Div Neurosurg, Dept Surg, Durham, NC 27710 USA. [Sampson, John H.] Duke Univ, Dept Pathol, Durham, NC 27710 USA. [Coan, April; Herndon, James E., II] Duke Univ, Canc Ctr Biostat Unit, Durham, NC 27710 USA. [Sampson, John H.; Archer, Gary; Coan, April; Herndon, James E., II; Friedman, Allan H.; Friedman, Henry S.] Duke Univ, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA. [Pedain, Christoph; Wembacher-Schroeder, Eva; Rodriguez-Ponce, M. Inmaculada; Mittermeyer, Stephan] BrainLAB AG, Feldkirchen, Germany. [Westphal, Manfred] Klin & Poliklin Neurochirurgie, Hamburg, Germany. [Kunwar, Sandeep] Univ Calif San Francisco, Calif Ctr Pituitary Disorders, San Francisco, CA 94143 USA. [Croteau, David] Neopharm Inc, Lake Bluff, IL USA. [Puri, Raj K.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Vogelbaum, Michael A.] Cleveland Clin, Cleveland, OH 44106 USA. RP Sampson, JH (reprint author), Duke Univ, Med Ctr, Div Neurosurg, Dept Surg, Box 3050, Durham, NC 27710 USA. EM john.sampson@duke.edu FU NeoPharm, Inc. FX The authors acknowledge NeoPharm, Inc., for financial support of the PRECISE trial. They also acknowledge Sharon McGehee, Denise Lally-Goss. and Beth Perry. NR 20 TC 91 Z9 93 U1 1 U2 8 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD AUG PY 2010 VL 113 IS 2 BP 301 EP 309 DI 10.3171/2009.11.JNS091052 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 632FH UT WOS:000280405900027 PM 20020841 ER PT J AU Martinez, MN Lindquist, D Modric, S AF Martinez, Marilyn N. Lindquist, Danielle Modric, Sanja TI Terminology Challenges: Defining Modified Release Dosage Forms in Veterinary Medicine SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE bioavailability; controlled release; formulation; pharamcokinetics; preclinical pharmacokinetics ID SUSTAINED-RELEASE; PHARMACOKINETIC MODEL; PROTEIN-BINDING; BEAGLE DOGS; HALF-LIFE; IN-VITRO; CATTLE; SULFAMETHAZINE; DISPOSITION; IVERMECTIN AB Terminologies for describing dosage form release characteristics for human pharmaceuticals have been addressed by bodies such as the US Food and Drug Administration (FDA), the international Conference on Harmonization (ICH), and the US Pharmacopeia (USP). While the definition for terms such as "immediate release," "modified release," "extended release," and "delayed release" are now well accepted for human pharmaceuticals, confusion still exists within the veterinary community. In part, this confusion is attributable to differences between human and veterinary dosage forms (such as the preponderance of parenteral vs. oral extended release products for use in animals vs. the focus on oral extended release formulations for human use) which reflect interspecies differences in physiology and conditions of use. It also simply reflects a lack of attention to existing definitions. In an effort to remedy this problem, this manuscript reflects an initial effort to suggest definitions that may be appropriate for describing formulation effects in veterinary medicine. (C) 2010 Wiley-Liss, Inc and the American Pharmacists Association J Pharm Sci 99.3281-3290, 2010 C1 [Martinez, Marilyn N.; Lindquist, Danielle; Modric, Sanja] US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. RP Martinez, MN (reprint author), US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. NR 42 TC 0 Z9 0 U1 1 U2 9 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD AUG PY 2010 VL 99 IS 8 BP 3281 EP 3290 DI 10.1002/jps.22095 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 632PC UT WOS:000280435700002 PM 20213837 ER PT J AU Guo, CN Doub, WH Kauffman, JF AF Guo, Changning Doub, William H. Kauffman, John F. TI Propagation of Uncertainty in Nasal Spray In Vitro Performance Models Using Monte Carlo Simulation: Part II. Error Propagation During Product Performance Modeling SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE factorial design; in vitro models; mathematical model; Monte Carlo; nasal drug delivery; drug design AB Monte Carlo simulations were applied to investigate the propagation of uncertainty in both input variables and response measurements on model prediction for nasal spray product performance design of experiment (DOE) models in the first part of this study, with an initial assumption that the models perfectly represent the relationship between input variables and the measured responses. In this article, we discard the initial assumption, and extended the Monte Carlo simulation study to examine the influence of both input variable variation and product performance measurement variation on the uncertainty in DOE model coefficients. The Monte Carlo simulations presented in this article illustrate the importance of careful error propagation during product performance modeling. Our results show that the error estimates based on Monte Carlo simulation result in smaller model coefficient standard deviations than those from regression methods. This suggests that the estimated standard deviations from regression may overestimate the uncertainties in the model coefficients Monte Carlo simulations provide a simple software solution to understand the propagation of uncertainty in complex DOE models so that design space can be specified with statistically meaningful confidence levels. (C) 2010 Wiley-Liss, Inc and the American Pharmacists Association J Pharm Sci 99 3572-3578, 2010 C1 [Guo, Changning; Doub, William H.; Kauffman, John F.] US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Guo, CN (reprint author), US FDA, Div Pharmaceut Anal, 1114 Market St,Room 1002, St Louis, MO 63101 USA. NR 9 TC 1 Z9 1 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD AUG PY 2010 VL 99 IS 8 BP 3572 EP 3578 DI 10.1002/jps.22094 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 632PC UT WOS:000280435700027 PM 20564385 ER PT J AU Pimenova, T Pereira, CP Gehrig, P Buehler, PW Schaer, DJ Zenobi, R AF Pimenova, Tatiana Pereira, Claudia P. Gehrig, Peter Buehler, Paul W. Schaer, Dominik J. Zenobi, Renato TI Quantitative Mass Spectrometry Defines an Oxidative Hotspot in Hemoglobin that is Specifically Protected by Haptoglobin SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE hemoglobin oxidation; haptoglobin; quantification; iTRAQ; mass spectrometry ID CARDIOVASCULAR INJURY; SCAVENGER PATHWAYS; ALZHEIMERS-DISEASE; HYDROGEN-PEROXIDE; STRESS; PROTEOMICS; COMPLEX; CD163; IDENTIFICATION; MECHANISMS AB The reaction of hemoglobin (Hb) with hydrogen peroxide (H(2)O(2)) results in free radicals generated at the heme iron, followed by radical transfer to the porphyrin/globin. In the present work, we employed isobaric tagging for relative and absolute quantification (iTRAQ) and a LC MALDI-MS/MS-based proteomic approach to identify the extent of oxidative changes within tetrameric Hb and dimeric Hb haptoglobin (Hb Hp) complexes. Extensive oxidative modifications were found to be restricted to peptides containing alpha Tyr42, beta Tyr145, and beta Cys93. The protein region composed of these peptides appears to define an area of oxidative activity within the Hb tetramer that extends across the critical alpha 1 beta 2/alpha 2 beta 1 interface. Extensive oxidative modifications occurring at beta Cys93 indicate that this surface amino acid is an important end point for free radical induced protein oxidation within Hb. Conversely when Hp 1-1 or 2-2 was complexed with dissociable Hb, oxidative changes in Hp complexed dimeric Hb were prevented. This protection was not observed in a stabilized tetrameric Hb, which displays a weak binding affinity for Hp. Therefore, dimerization of Hb and Hp binding may interfere with free radical translocation and play an important role in the overall antioxidant mechanism of Hp. Interestingly, the prevention of peroxide induced Hb amino acid oxidation in purified Hb-Hp1-1 and Hb-Hp2-2 was found to be equal, indicating a phenotype independent specificity in the process of oxidative protection. Taken together, these data suggest differences in oxidative modifications resulting from peroxide induced heme emanated free radical distribution in tetrameric compared to Hp1-1/Hp2-2 stabilized dimeric Hb. C1 [Pimenova, Tatiana; Zenobi, Renato] ETH, Dept Chem & Appl Biosci, CH-8093 Zurich, Switzerland. [Buehler, Paul W.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Gehrig, Peter] UZH ETH Zurich, Funct Genom Ctr Zurich, Zurich, Switzerland. [Pereira, Claudia P.; Schaer, Dominik J.] Univ Zurich, CH-8006 Zurich, Switzerland. RP Zenobi, R (reprint author), ETH, Dept Chem & Appl Biosci, CH-8093 Zurich, Switzerland. EM dominik.schaer@usz.ch; zenobi@org.chem.ethz.ch FU Swiss National Science Foundation [31-120658] FX We acknowledge Abdu Alayash, CBER, FDA, Bethesda for providing the purified alpha alpha-crosslinked Hb. This work was supported by the Swiss National Science Foundation grant 31-120658 (D.J.S.). The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy. NR 32 TC 31 Z9 31 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD AUG PY 2010 VL 9 IS 8 BP 4061 EP 4070 DI 10.1021/pr100252e PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 634LT UT WOS:000280583700028 PM 20568812 ER PT J AU Shabalina, SA Ogurtsov, AY Spiridonov, AN Novichkov, PS Spiridonov, NA Koonin, EV AF Shabalina, Svetlana A. Ogurtsov, Aleksey Y. Spiridonov, Alexey N. Novichkov, Pavel S. Spiridonov, Nikolay A. Koonin, Eugene V. TI Distinct Patterns of Expression and Evolution of Intronless and Intron-Containing Mammalian Genes SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE alternative splicing; intronless genes; monomorphic genes; polymorphic genes; mammalian gene evolution ID NETWORK; GENOME; EXPORT; CELLS; RATES AB Comparison of expression levels and breadth and evolutionary rates of intronless and intron-containing mammalian genes shows that intronless genes are expressed at lower levels, tend to be tissue specific, and evolve significantly faster than spliced genes. By contrast, monomorphic spliced genes that are not subject to detectable alternative splicing and polymorphic alternatively spliced genes show similar statistically indistinguishable patterns of expression and evolution. Alternative splicing is most common in ancient genes, whereas intronless genes appear to have relatively recent origins. These results imply tight coupling between different stages of gene expression, in particular, transcription, splicing, and nucleocytosolic transport of transcripts, and suggest that formation of intronless genes is an important route of evolution of novel tissue-specific functions in animals. C1 [Shabalina, Svetlana A.; Ogurtsov, Aleksey Y.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Spiridonov, Alexey N.] MIT, Dept Math, Cambridge, MA 02139 USA. [Novichkov, Pavel S.] Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA. [Spiridonov, Nikolay A.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Shabalina, SA (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM shabalin@ncbi.nlm.nih.gov; koonin@ncbi.nlm.nih.gov RI Shabalina, Svetlana/N-8939-2013; Spiridonov, Nikolay/B-6287-2014 OI Shabalina, Svetlana/0000-0003-2272-7473; FU Department of Health and Human Services (National Library of Medicine, National Institutes of Health) FX The authors' research is supported by the intramural funds of the Department of Health and Human Services (National Library of Medicine, National Institutes of Health). NR 29 TC 34 Z9 36 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD AUG PY 2010 VL 27 IS 8 BP 1745 EP 1749 DI 10.1093/molbev/msq086 PG 5 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 630TI UT WOS:000280296700002 PM 20360214 ER PT J AU Whiting, SJ Calvo, MS AF Whiting, Susan J. Calvo, Mona S. TI Correcting poor vitamin D status: Do older adults need higher repletion doses of vitamin D-3 than younger adults? SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Review DE 25-Hydroxyvitannin D; Cholecalciferol; Elderly; Repletion ID NURSING-HOME RESIDENTS; D SUPPLEMENTATION; ERGOCALCIFEROL VITAMIN-D-2; D DEFICIENCY; 25-HYDROXYVITAMIN-D; ULTRAVIOLET; EFFICACY; FRACTURE; SINGLE; CANCER AB We conducted an examination of recent studies to determine whether older adults (>= 65 years) need higher levels of supplementary vitamin D than young adults when attempting to replete vitamin D status in deficient subjects, i.e. those with levels of 25-hydroxyvitamin D less than 75 nmol/L. As data on repletion with vitamin D-2 have recently been published, we restricted our discussion to the use of vitamin D-3 from dietary supplements, prescriptions for large oral doses, and bolus dosing or injections. Most published dosing regimens failed to achieve 75 nmol/L in most all subjects, whether young adults (<65 years) or older adults (>= 65 years). Whether as daily or bolus oral supplementation, elderly subjects appeared to need more vitamin D3 compared with younger adults, however, baseline levels, endpoints, study duration, compliance, and other factors were different among studies. To ensure most subjects are replete in vitamin D, a daily dose of more than 50 mu g (2000 IU) in younger and 125 mu g (5000IU) is required. Other strategies including bolus and loading doses are described. No study reported adverse effects of using oral intakes about the current upper level of 50 mu g (2000IU). C1 [Whiting, Susan J.] Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK S7N 5C9, Canada. [Calvo, Mona S.] US Food & Drug Adm Laurel, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD USA. RP Whiting, SJ (reprint author), Univ Saskatchewan, Coll Pharm & Nutr, 110 Sci Pl, Saskatoon, SK S7N 5C9, Canada. EM susan.whiting@usask.ca NR 37 TC 17 Z9 17 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1613-4125 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD AUG PY 2010 VL 54 IS 8 BP 1077 EP 1084 DI 10.1002/mnfr.200900536 PG 8 WC Food Science & Technology SC Food Science & Technology GA 646DA UT WOS:000281515000005 PM 20440693 ER PT J AU Babu, US Calvo, MS AF Babu, Uma S. Calvo, Mona S. TI Modern India and the vitamin D dilemma: Evidence for the need of a national food fortification program SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Review DE Fortification; India; Sun exposure; Skin Pigmentation; Vitamin D deficiency ID BREAST-FED INFANTS; BONE-MINERAL DENSITY; 25-HYDROXYVITAMIN D CONCENTRATIONS; HEALTHY SOUTH INDIANS; LOW DIETARY CALCIUM; D-DEFICIENCY; SERUM 25-HYDROXYVITAMIN-D; NUTRITIONAL RICKETS; D SUPPLEMENTATION; HIGH PREVALENCE AB India is located between 8.4 and 37.6 degrees N latitude with the majority of its population living in regions experiencing ample sunlight throughout the year. Historically, Indians obtained most of their vitamin D through adequate sun exposure; however, darker skin pigmentation and the changes which have accompanied India's modernization, including increased hours spent working indoors and pollution, limit sun exposure for many. Inadequate sun exposure results in reduced vitamin D synthesis and ultimately poor vitamin D status if not compensated by dietary intake. Dietary vitamin D intake is very low in India because of low consumption of vitamin D rich foods, absence of fortification and low use of supplements. All these factors contribute to poor vitamin D status as measured by low circulating levels of 25-hydroxy vitamin D. Our review searches the published literature specific to India for evidence that would confirm the need to fortify food staples with vitamin D or stimulate public health policies for vitamin D supplementation and dietary guidelines tailored to the Indian diet. This review documents findings of widespread vitamin D deficiency in Indian populations in higher and lower socioeconomic strata, in all age groups, in both genders and people in various professions. Moreover, poor vitamin D status in India is accompanied by increased bone disorders including osteoporosis, osteomalacia in adults and rickets and other bone deformities in children. Without a concerted national effort to screen for vitamin D status, to implement policies or guidelines for vitamin D fortification and/or supplementation and to re-assess recommended dietary intake guidelines, dramatic increase in the number of bone disorders and other diseases may lie ahead. C1 [Babu, Uma S.; Calvo, Mona S.] US FDA, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Babu, US (reprint author), US FDA, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, HFS-025,MOD 1,8301 Muirkirk Rd, Laurel, MD 20708 USA. EM uma.babu@fda.hhs.gov NR 108 TC 32 Z9 33 U1 0 U2 11 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1613-4125 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD AUG PY 2010 VL 54 IS 8 BP 1134 EP 1147 DI 10.1002/mnfr.200900480 PG 14 WC Food Science & Technology SC Food Science & Technology GA 646DA UT WOS:000281515000011 PM 20440690 ER PT J AU Katz, R AF Katz, Russell TI Risk management: an FDA perspective SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the Americas-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis CY JUN, 2010 CL San Antonio, TX SP Americas Comm Treatment & Res Multiple Sclerosis C1 [Katz, Russell] US Dept HHS, Neurol Prod Div, US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER J JI Mult. Scler. J. PD AUG PY 2010 VL 16 IS 8 BP 998 EP 999 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 634TO UT WOS:000280608600023 ER PT J AU Shi, LM Campbell, G Jones, WD Campagne, F Wen, ZN Walker, SJ Su, ZQ Chu, TM Goodsaid, FM Pusztai, L Shaughnessy, JD Oberthuer, A Thomas, RS Paules, RS Fielden, M Barlogie, B Chen, WJ Du, P Fischer, M Furlanello, C Gallas, BD Ge, XJ Megherbi, DB Symmans, WF Wang, MD Zhang, J Bitter, H Brors, B Bushel, PR Bylesjo, M Chen, MJ Cheng, J Cheng, J Chou, J Davison, TS Delorenzi, M Deng, YP Devanarayan, V Dix, DJ Dopazo, J Dorff, KC Elloumi, F Fan, JQ Fan, SC Fan, XH Fang, H Gonzaludo, N Hess, KR Hong, H Huan, J Irizarry, RA Judson, R Juraeva, D Lababidi, S Lambert, CG Li, L Li, Y Li, Z Lin, SM Liu, GZ Lobenhofer, EK Luo, J Luo, W McCall, MN Nikolsky, Y Pennello, GA Perkins, RG Philip, R Popovici, V Price, ND Qian, F Scherer, A Shi, TL Shi, WW Sung, JY Thierry-Mieg, D Thierry-Mieg, J Thodima, V Trygg, J Vishnuvajjala, L Wang, SJ Wu, JP Wu, YC Xie, Q Yousef, WA Zhang, L Zhang, XG Zhong, S Zhou, YM Zhu, S Arasappan, D Bao, WJ Lucas, AB Berthold, F Brennan, RJ Buness, A Catalano, JG Chang, C Chen, R Cheng, YY Cui, J Czika, W Demichelis, F Deng, XT Dosymbekov, D Eils, R Feng, Y Fostel, J Fulmer-Smentek, S Fuscoe, JC Gatto, L Ge, WG Goldstein, DR Guo, L Halbert, DN Han, J Harris, SC Hatzis, C Herman, D Huang, JP Jensen, RV Jiang, R Johnson, CD Jurman, G Kahlert, Y Khuder, SA Kohl, M Li, JY Li, L Li, ML Li, QZ Li, S Li, ZG Liu, J Liu, Y Liu, ZC Meng, L Madera, M Martinez-Murillo, F Medina, I Meehan, J Miclaus, K Moffitt, RA Montaner, D Mukherjee, P Mulligan, GJ Neville, P Nikolskaya, T Ning, BT Page, GP Parker, J Parry, RM Peng, XJ Peterson, RL Phan, JH Quanz, B Ren, Y Riccadonna, S Roter, AH Samuelson, FW Schumacher, MM Shambaugh, JD Shi, QA Shippy, R Si, SZ Smalter, A Sotiriou, C Soukup, M Staedtler, F Steiner, G Stokes, TH Sun, QL Tan, PY Tang, R Tezak, Z Thorn, B Tsyganova, M Turpaz, Y Vega, SC Visintainer, R von Frese, J Wang, C Wang, E Wang, JW Wang, W Westermann, F Willey, JC Woods, M Wu, SJ Xiao, NQ Xu, J Xu, L Yang, L Zeng, X Zhang, JL Zhang, L Zhang, M Zhao, C Puri, RK Scherf, U Tong, W Wolfinger, RD AF Shi, Leming Campbell, Gregory Jones, Wendell D. Campagne, Fabien Wen, Zhining Walker, Stephen J. Su, Zhenqiang Chu, Tzu-Ming Goodsaid, Federico M. Pusztai, Lajos Shaughnessy, John D., Jr. Oberthuer, Andre Thomas, Russell S. Paules, Richard S. Fielden, Mark Barlogie, Bart Chen, Weijie Du, Pan Fischer, Matthias Furlanello, Cesare Gallas, Brandon D. Ge, Xijin Megherbi, Dalila B. Symmans, W. Fraser Wang, May D. Zhang, John Bitter, Hans Brors, Benedikt Bushel, Pierre R. Bylesjo, Max Chen, Minjun Cheng, Jie Cheng, Jing Chou, Jeff Davison, Timothy S. Delorenzi, Mauro Deng, Youping Devanarayan, Viswanath Dix, David J. Dopazo, Joaquin Dorff, Kevin C. Elloumi, Fathi Fan, Jianqing Fan, Shicai Fan, Xiaohui Fang, Hong Gonzaludo, Nina Hess, Kenneth R. Hong, Huixiao Huan, Jun Irizarry, Rafael A. Judson, Richard Juraeva, Dilafruz Lababidi, Samir Lambert, Christophe G. Li, Li Li, Yanen Li, Zhen Lin, Simon M. Liu, Guozhen Lobenhofer, Edward K. Luo, Jun Luo, Wen McCall, Matthew N. Nikolsky, Yuri Pennello, Gene A. Perkins, Roger G. Philip, Reena Popovici, Vlad Price, Nathan D. Qian, Feng Scherer, Andreas Shi, Tieliu Shi, Weiwei Sung, Jaeyun Thierry-Mieg, Danielle Thierry-Mieg, Jean Thodima, Venkata Trygg, Johan Vishnuvajjala, Lakshmi Wang, Sue Jane Wu, Jianping Wu, Yichao Xie, Qian Yousef, Waleed A. Zhang, Liang Zhang, Xuegong Zhong, Sheng Zhou, Yiming Zhu, Sheng Arasappan, Dhivya Bao, Wenjun Lucas, Anne Bergstrom Berthold, Frank Brennan, Richard J. Buness, Andreas Catalano, Jennifer G. Chang, Chang Chen, Rong Cheng, Yiyu Cui, Jian Czika, Wendy Demichelis, Francesca Deng, Xutao Dosymbekov, Damir Eils, Roland Feng, Yang Fostel, Jennifer Fulmer-Smentek, Stephanie Fuscoe, James C. Gatto, Laurent Ge, Weigong Goldstein, Darlene R. Guo, Li Halbert, Donald N. Han, Jing Harris, Stephen C. Hatzis, Christos Herman, Damir Huang, Jianping Jensen, Roderick V. Jiang, Rui Johnson, Charles D. Jurman, Giuseppe Kahlert, Yvonne Khuder, Sadik A. Kohl, Matthias Li, Jianying Li, Li Li, Menglong Li, Quan-Zhen Li, Shao Li, Zhiguang Liu, Jie Liu, Ying Liu, Zhichao Meng, Lu Madera, Manuel Martinez-Murillo, Francisco Medina, Ignacio Meehan, Joseph Miclaus, Kelci Moffitt, Richard A. Montaner, David Mukherjee, Piali Mulligan, George J. Neville, Padraic Nikolskaya, Tatiana Ning, Baitang Page, Grier P. Parker, Joel Parry, R. Mitchell Peng, Xuejun Peterson, Ron L. Phan, John H. Quanz, Brian Ren, Yi Riccadonna, Samantha Roter, Alan H. Samuelson, Frank W. Schumacher, Martin M. Shambaugh, Joseph D. Shi, Qiang Shippy, Richard Si, Shengzhu Smalter, Aaron Sotiriou, Christos Soukup, Mat Staedtler, Frank Steiner, Guido Stokes, Todd H. Sun, Qinglan Tan, Pei-Yi Tang, Rong Tezak, Zivana Thorn, Brett Tsyganova, Marina Turpaz, Yaron Vega, Silvia C. Visintainer, Roberto von Frese, Juergen Wang, Charles Wang, Eric Wang, Junwei Wang, Wei Westermann, Frank Willey, James C. Woods, Matthew Wu, Shujian Xiao, Nianqing Xu, Joshua Xu, Lei Yang, Lun Zeng, Xiao Zhang, Jialu Zhang, Li Zhang, Min Zhao, Chen Puri, Raj K. Scherf, Uwe Tong, Weida Wolfinger, Russell D. CA MAQC Consortium TI The MicroArray Quality Control (MAQC)-IIII study of common practices for the development and validation of microarray-based predictive models SO NATURE BIOTECHNOLOGY LA English DT Article ID GENE-EXPRESSION DATA; CONTROL MAQC PROJECT; MULTIPLE-MYELOMA; BREAST-CANCER; PUBLISHED MICROARRAY; FOLLICULAR LYMPHOMA; RISK-STRATIFICATION; DNA MICROARRAYS; CLASSIFICATION; PERFORMANCE AB Gene expression data from microarrays are being applied to predict preclinical and clinical endpoints, but the reliability of these predictions has not been established. In the MAQC-II project, 36 independent teams analyzed six microarray data sets to generate predictive models for classifying a sample with respect to one of 13 endpoints indicative of lung or liver toxicity in rodents, or of breast cancer, multiple myeloma or neuroblastoma in humans. In total, >30,000 models were built using many combinations of analytical methods. The teams generated predictive models without knowing the biological meaning of some of the endpoints and, to mimic clinical reality, tested the models on data that had not been used for training. We found that model performance depended largely on the endpoint and team proficiency and that different approaches generated models of similar performance. The conclusions and recommendations from MAQC-II should be useful for regulatory agencies, study committees and independent investigators that evaluate methods for global gene expression analysis. C1 [Shi, Leming; Wen, Zhining; Chen, Minjun; Hong, Huixiao; Perkins, Roger G.; Fuscoe, James C.; Ge, Weigong; Harris, Stephen C.; Li, Zhiguang; Liu, Jie; Liu, Zhichao; Ning, Baitang; Shi, Qiang; Thorn, Brett; Xu, Lei; Yang, Lun; Zhang, Min; Tong, Weida] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Campbell, Gregory; Chen, Weijie; Gallas, Brandon D.; Pennello, Gene A.; Philip, Reena; Vishnuvajjala, Lakshmi; Martinez-Murillo, Francisco; Samuelson, Frank W.; Tang, Rong; Tezak, Zivana; Scherf, Uwe] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Jones, Wendell D.; Parker, Joel] Express Anal Inc, Durham, NC USA. [Campagne, Fabien] Cornell Univ, Dept Physiol & Biophys, Weill Med Coll, New York, NY 10021 USA. [Walker, Stephen J.] Wake Forest Univ, Wake Forest Inst Regenerat Med, Winston Salem, NC 27109 USA. [Su, Zhenqiang; Fang, Hong; Qian, Feng; Arasappan, Dhivya; Meehan, Joseph; Xu, Joshua] Z Tech, Jefferson, AR USA. [Chu, Tzu-Ming; Li, Li; Bao, Wenjun; Czika, Wendy; Miclaus, Kelci; Neville, Padraic; Tan, Pei-Yi; Wolfinger, Russell D.] SAS Inst Inc, Cary, NC USA. [Goodsaid, Federico M.; Wang, Sue Jane; Soukup, Mat; Zhang, Jialu; Zhang, Li] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Pusztai, Lajos] Univ Texas MD Anderson Canc Ctr, Breast Med Oncol Dept, Houston, TX 77030 USA. [Shaughnessy, John D., Jr.; Barlogie, Bart; Zhou, Yiming] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. [Oberthuer, Andre; Fischer, Matthias; Berthold, Frank; Kahlert, Yvonne] Univ Cologne, Dept Pediat Oncol & Hematol, Cologne, Germany. [Oberthuer, Andre; Fischer, Matthias; Berthold, Frank; Kahlert, Yvonne] Univ Cologne, Ctr Mol Med CMMC, Cologne, Germany. [Thomas, Russell S.] Hamner Inst Hlth Sci, Res Triangle Pk, NC USA. [Paules, Richard S.; Bushel, Pierre R.; Chou, Jeff; Fostel, Jennifer] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA. [Fielden, Mark] Roche Palo Alto LLC, San Francisco, CA USA. [Du, Pan; Lin, Simon M.] Northwestern Univ, Biomed Informat Ctr, Chicago, IL 60611 USA. [Furlanello, Cesare; Jurman, Giuseppe; Riccadonna, Samantha; Visintainer, Roberto] Fdn Bruno Kessler, Povo, Italy. [Ge, Xijin] S Dakota State Univ, Dept Math & Stat, Brookings, SD 57007 USA. [Megherbi, Dalila B.; Madera, Manuel] Univ Massachusetts Lowell, CMINDS Res Ctr, Dept Elect & Comp Engn, Lowell, MA USA. [Symmans, W. Fraser] UI MD Anderson Canc Ctr, Dept Pathol, Houston, TX USA. [Wang, May D.; Moffitt, Richard A.; Parry, R. Mitchell; Phan, John H.; Stokes, Todd H.] Georgia Inst Technol, Dept Biomed Engn, Atlanta, GA 30332 USA. [Wang, May D.; Moffitt, Richard A.; Parry, R. Mitchell; Phan, John H.; Stokes, Todd H.] Emory Univ, Atlanta, GA 30322 USA. [Zhang, John; Luo, Jun; Wang, Eric; Woods, Matthew] Syst Analyt Inc, Waltham, MA USA. [Bitter, Hans] Hoffmann LaRoche, Nutley, NJ USA. [Brors, Benedikt; Juraeva, Dilafruz; Eils, Roland; Westermann, Frank] German Canc Res Ctr, Dept Theoret Bioinformat, Heidelberg, Germany. [Bylesjo, Max; Trygg, Johan] Umea Univ, Computat Life Sci Cluster CLiC, Chem Biol Ctr KBC, Umea, Sweden. [Cheng, Jie] GlaxoSmithKline Inc, Collegeville, PA USA. [Cheng, Jing] Tsinghua Univ, Sch Med, Med Syst Biol Res Ctr, Beijing 100084, Peoples R China. [Davison, Timothy S.] Almac Diagnost Ltd, Craigavon, North Ireland. [Delorenzi, Mauro; Popovici, Vlad] Swiss Inst Bioinformat, Lausanne, Switzerland. [Deng, Youping] Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA. [Devanarayan, Viswanath] Global Pharmaceut R&D, Abbott Labs, Souderton, PA USA. [Dix, David J.; Elloumi, Fathi; Judson, Richard; Li, Zhen] US EPA, Natl Ctr Computat Toxicol, Res Triangle Pk, NC 27711 USA. [Dopazo, Joaquin] CIPF, Dept Bioinformat & Genom, Valencia, Spain. [Fan, Jianqing; Feng, Yang] Princeton Univ, Dept Operat Res & Financial Engn, Princeton, NJ 08544 USA. [Fan, Shicai; Zhang, Xuegong; Jiang, Rui; Liu, Ying; Meng, Lu] Tsinghua Univ, MOE Key Lab Bioinformat, TNLIST, Dept Automat, Beijing 100084, Peoples R China. [Fan, Xiaohui; Cheng, Yiyu; Huang, Jianping; Li, Shao] Zhejiang Univ, Coll Pharmaceut Sci, Inst Pharmaceut Informat, Hangzhou 310003, Zhejiang, Peoples R China. [Gonzaludo, Nina] Roche Palo Alto LLC, Palo Alto, CA USA. [Hess, Kenneth R.] UT MD Anderson Canc Ctr, Dept Biostat, Houston, TX USA. [Huan, Jun; Quanz, Brian; Smalter, Aaron] Univ Kansas, Dept Elect Engn & Comp Sci, Lawrence, KS 66045 USA. [Irizarry, Rafael A.; McCall, Matthew N.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. [Lababidi, Samir; Catalano, Jennifer G.; Han, Jing; Puri, Raj K.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Lambert, Christophe G.] Golden Helix Inc, Bozeman, MT USA. [Li, Yanen] Univ Illinois, Dept Comp Sci, Urbana, IL 61801 USA. [Liu, Guozhen; Zeng, Xiao] SABiosciences Corp, Frederick, MD USA. [Lobenhofer, Edward K.] Cogenics, Morrisville, NC USA. [Luo, Wen] Ligand Pharmaceut Inc, La Jolla, CA 92037 USA. [Nikolsky, Yuri; Shi, Weiwei; Brennan, Richard J.; Nikolskaya, Tatiana] GeneGo Inc, Encinitas, CA USA. [Price, Nathan D.; Sung, Jaeyun] Univ Illinois, Dept Chem & Biomol Engn, Urbana, IL 61801 USA. [Scherer, Andreas] Spheromics, Kontiolahti, Finland. [Shi, Tieliu; Chang, Chang; Cui, Jian; Wang, Junwei; Zhao, Chen] E China Normal Univ, Ctr Bioinformat, Shanghai 200062, Peoples R China. [Shi, Tieliu; Chang, Chang; Cui, Jian; Wang, Junwei; Zhao, Chen] E China Normal Univ, Inst Biomed Sci, Sch Life Sci, Shanghai 200062, Peoples R China. [Thierry-Mieg, Danielle; Thierry-Mieg, Jean] Natl Ctr Biotechnol Informat, NIH, Bethesda, MD USA. [Thodima, Venkata] Mem Sloan Kettering Canc Ctr, Rockefeller Res Labs, New York, NY 10021 USA. [Wu, Jianping; Zhang, Liang; Zhu, Sheng; Sun, Qinglan] CapitalBio Corp, Beijing, Peoples R China. [Wu, Yichao] N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. [Xie, Qian] SRA Int FMMFS, Rockville, MD USA. [Yousef, Waleed A.] Helwan Univ, Helwan, Egypt. [Zhong, Sheng] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA. [Lucas, Anne Bergstrom; Fulmer-Smentek, Stephanie] Agilent Technol, Santa Clara, CA USA. [Buness, Andreas] F Hoffmann La Roche Ltd, Basel, Switzerland. [Chen, Rong] Stanford Univ, Stanford Ctr Biomed Informat Res, Stanford, CA 94305 USA. [Demichelis, Francesca] Cornell Univ, Weill Med Coll, Dept Pathol, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY 10021 USA. [Demichelis, Francesca] Cornell Univ, Weill Med Coll, Lab Med, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY 10021 USA. [Deng, Xutao; Wang, Charles] Univ Calif Los Angeles, Cedars Sinai Med Ctr, David Geffen Sch Med, Los Angeles, CA 90048 USA. [Dosymbekov, Damir; Tsyganova, Marina] Russian Acad Sci, Vavilov Inst Gen Genet, Moscow, Russia. [Gatto, Laurent] DNAVision SA, Gosselies, Belgium. [Goldstein, Darlene R.] Ecole Polytech Fed Lausanne, Lausanne, Switzerland. [Guo, Li] Chinese Acad Sci, Inst Proc Engn, State Key Lab Multiphase Complex Syst, Beijing, Peoples R China. [Halbert, Donald N.] Abbott Labs, Abbott Pk, IL 60064 USA. [Hatzis, Christos] Nuvera Biosci Inc, Woburn, MA USA. [Herman, Damir] Univ Arkansas Med Sci, Winthrop P Rockefeller Canc Inst, Little Rock, AR 72205 USA. [Jensen, Roderick V.] VirginiaTech, Blacksburg, VA USA. [Johnson, Charles D.] BioMath Solut LLC, Austin, TX USA. [Khuder, Sadik A.] Univ Toledo, Bioinformat Program, Toledo, OH 43606 USA. [Kohl, Matthias] Univ Bayreuth, Dept Math, Bayreuth, Germany. [Li, Jianying] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Li, Li] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. [Li, Menglong] Sichuan Univ, Coll Chem, Chengdu 610064, Sichuan, Peoples R China. [Li, Quan-Zhen] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Medina, Ignacio; Montaner, David] CIPF, Valencia, Spain. [Mulligan, George J.] Millennium Pharmaceut Inc, Cambridge, MA USA. [Page, Grier P.] RTI Int, Atlanta, GA USA. [Peng, Xuejun] Takeda Global R&D Ctr Inc, Deerfield, IL USA. [Peterson, Ron L.] Novartis Inst Biomed Res, Cambridge, MA USA. [Ren, Yi] Rutgers State Univ, WM Keck Ctr Collaborat Neurosci, Piscataway, NJ USA. [Roter, Alan H.] Entelos Inc, Foster City, CA USA. [Schumacher, Martin M.; Staedtler, Frank] Novartis Pharma AG, Biomarker Dev, Novartis Inst BioMed Res, Basel, Switzerland. [Shambaugh, Joseph D.] Genedata Inc, Lexington, MA USA. [Shippy, Richard] Affymetrix Inc, Santa Clara, CA USA. [Si, Shengzhu] Hefei Teachers Coll, Dept Chem & Chem Engn, Hefei, Anhui, Peoples R China. [Sotiriou, Christos] Inst Jules Bordet, B-1000 Brussels, Belgium. [Steiner, Guido] F Hoffmann La Roche Ltd, Biostat, Basel, Switzerland. [Turpaz, Yaron] Lilly Singapore, Ctr Drug Discovery, Immunos, Singapore, Singapore. [Vega, Silvia C.] Microsoft Corp, US Hlth Solut Grp, Redmond, WA 98052 USA. [von Frese, Juergen] Data Anal Solut DA SOL GmbH, Greifenberg, Germany. [Wang, Wei] Cornell Univ, Ithaca, NY USA. [Willey, James C.] Univ Toledo Hlth Sci Campus, Dept Med, Div Pulm & Crit Care Med, Toledo, OH USA. [Wu, Shujian] Bristol Myers Squibb, Pennington, NJ USA. [Xiao, Nianqing] OpGen Inc, Gaithersburg, MD USA. Tsinghua Univ, TNLIST, Dept Automat, Bioinformat Div, Beijing 100084, Peoples R China. RP Shi, LM (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM leming.shi@fda.hhs.gov RI Popovici, Vlad/C-2039-2008; Campagne, Fabien/F-5158-2010; Yang, Lun/B-4859-2012; Zhang, Jinny/C-4794-2012; Chen, Weijie/A-3712-2012; Dopazo, Joaquin/A-9270-2014; Liu, Zhichao/C-4035-2011; Huan, Jun/A-1007-2015; Su, Zhenqiang/H-3914-2012; Su, Zhiguo/G-2422-2011; Jiang, Rui/B-1345-2012; Brors, Benedikt/E-5620-2013; Qiang, Shi/E-6266-2012; Nikolskaya, Tatiana/M-5008-2013; Feng, Yang/D-3329-2015; Hatzis, Christos/M-3867-2015; Eils, Roland/B-6121-2009; THIERRY-MIEG, Jean/F-1975-2017 OI Popovici, Vlad/0000-0002-1311-9188; Dopazo, Joaquin/0000-0003-3318-120X; Huan, Jun/0000-0003-4929-2617; Jiang, Rui/0000-0002-7533-3753; Brors, Benedikt/0000-0001-5940-3101; Feng, Yang/0000-0001-7746-7598; Hatzis, Christos/0000-0002-8120-2290; Eils, Roland/0000-0002-0034-4036; THIERRY-MIEG, Jean/0000-0002-0396-6789 FU National Institutes of Health (NIH) [1R01GM083084-01, 1R01RR021967-01A2, T32GM074906]; National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina [HHSN273200700046U]; Biomedical Informatics Core of the Institutional Clinical and Translational Science [RFA-RM-07002] FX The MAQC-II project was funded in part by the FDA's Office of Critical Path Programs (to L. S.). Participants from the National Institutes of Health (NIH) were supported by the Intramural Research Program of NIH, Bethesda, Maryland or the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina. J.F. was supported by the Division of Intramural Research of the NIEHS under contract HHSN273200700046U. Participants from the Johns Hopkins University were supported by grants from the NIH (1R01GM083084-01 and 1R01RR021967-01A2 to R.A.I. and T32GM074906 to M.M.). Participants from the Weill Medical College of Cornell University were partially supported by the Biomedical Informatics Core of the Institutional Clinical and Translational Science Award RFA-RM-07002. F. C. acknowledges resources from The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine and from the David A. Cofrin Center for Biomedical Information at Weill Cornell. The data set from The Hamner Institutes for Health Sciences was supported by a grant from the American Chemistry Council's Long Range Research Initiative. The breast cancer data set was generated with support of grants from NIH (R-01 to L.P.), The Breast Cancer Research Foundation (to L.P. and W.F.S.) and the Faculty Incentive Funds of the University of Texas MD Anderson Cancer Center (to W.F.S.). The data set from the University of Arkansas for Medical Sciences was supported by National Cancer Institute (NCI) PO1 grant CA55819-01A1, NCI R33 Grant CA97513-01, Donna D. and Donald M. Lambert Lebow Fund to Cure Myeloma and Nancy and Steven Grand Foundation. We are grateful to the individuals whose gene expression data were used in this study. All MAQC-II participants freely donated their time and reagents for the completion and analyses of the MAQC-II project. The MAQC-II consortium also thanks R. O'Neill for his encouragement and coordination among FDA Centers on the formation of the RBWG. The MAQC-II consortium gratefully dedicates this work in memory of R.F. Wagner who enthusiastically worked on the MAQC-II project and inspired many of us until he unexpectedly passed away in June 2008. NR 65 TC 325 Z9 333 U1 10 U2 112 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD AUG PY 2010 VL 28 IS 8 BP 827 EP U109 DI 10.1038/nbt.1665 PG 15 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 636RM UT WOS:000280757500023 PM 20676074 ER PT J AU Conde, L Halperin, E Akers, NK Brown, KM Smedby, KE Rothman, N Nieters, A Slager, SL Brooks-Wilson, A Agana, L Riby, J Liu, JJ Adami, HO Darabi, H Hjalgrim, H Low, HQ Humphreys, K Melbye, M Chang, ET Glimelius, B Cozen, W Davis, S Hartge, P Morton, LM Schenk, M Wang, SS Armstrong, B Kricker, A Milliken, S Purdue, MP Vajdic, CM Boyle, P Lan, Q Zahm, SH Zhang, YW Zheng, TZ Becker, N Benavente, Y Boffetta, P Brennan, P Butterbach, K Cocco, P Foretova, L Maynadie, M de Sanjose, S Staines, A Spinelli, JJ Achenbach, SJ Call, TG Camp, NJ Glenn, M Caporaso, NE Cerhan, JR Cunningham, JM Goldin, LR Hanson, CA Kay, NE Lanasa, MC Leis, JF Marti, GE Rabe, KG Rassenti, LZ Spector, LG Strom, SS Vachon, CM Weinberg, JB Holly, EA Chanock, S Smith, MT Bracci, PM Skibola, CF AF Conde, Lucia Halperin, Eran Akers, Nicholas K. Brown, Kevin M. Smedby, Karin E. Rothman, Nathaniel Nieters, Alexandra Slager, Susan L. Brooks-Wilson, Angela Agana, Luz Riby, Jacques Liu, Jianjun Adami, Hans-Olov Darabi, Hatef Hjalgrim, Henrik Low, Hui-Qi Humphreys, Keith Melbye, Mads Chang, Ellen T. Glimelius, Bengt Cozen, Wendy Davis, Scott Hartge, Patricia Morton, Lindsay M. Schenk, Maryjean Wang, Sophia S. Armstrong, Bruce Kricker, Anne Milliken, Sam Purdue, Mark P. Vajdic, Claire M. Boyle, Peter Lan, Qing Zahm, Shelia H. Zhang, Yawei Zheng, Tongzhang Becker, Nikolaus Benavente, Yolanda Boffetta, Paolo Brennan, Paul Butterbach, Katja Cocco, Pierluigi Foretova, Lenka Maynadie, Marc de Sanjose, Silvia Staines, Anthony Spinelli, John J. Achenbach, Sara J. Call, Timothy G. Camp, Nicola J. Glenn, Martha Caporaso, Neil E. Cerhan, James R. Cunningham, Julie M. Goldin, Lynn R. Hanson, Curtis A. Kay, Neil E. Lanasa, Mark C. Leis, Jose F. Marti, Gerald E. Rabe, Kari G. Rassenti, Laura Z. Spector, Logan G. Strom, Sara S. Vachon, Celine M. Weinberg, J. Brice Holly, Elizabeth A. Chanock, Stephen Smith, Martyn T. Bracci, Paige M. Skibola, Christine F. TI Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32 SO NATURE GENETICS LA English DT Article ID NON-HODGKIN-LYMPHOMA; NECROSIS-FACTOR TNF; HIGH-RESOLUTION; HLA; SUSCEPTIBILITY; HAPLOTYPE; POLYMORPHISMS AB To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 x 10(-29) and rs7755224, combined P = 2.00 x 10(-19); r(2) = 1.0), supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility. We also found confirmatory evidence of a previously reported association between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined P = 4.24 x 10(-9)). C1 [Conde, Lucia; Akers, Nicholas K.; Agana, Luz; Riby, Jacques; Smith, Martyn T.; Skibola, Christine F.] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA. [Halperin, Eran] Tel Aviv Univ, Mol Microbiol & Biotechnol Dept, IL-69978 Tel Aviv, Israel. [Halperin, Eran] Int Comp Sci Inst, Berkeley, CA 94704 USA. [Brown, Kevin M.] Translat Genom Res Inst TGen, Integrat Canc Genom Div, Phoenix, AZ USA. [Smedby, Karin E.] Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden. [Rothman, Nathaniel; Hartge, Patricia; Morton, Lindsay M.; Wang, Sophia S.; Purdue, Mark P.; Lan, Qing; Zahm, Shelia H.; Caporaso, Neil E.; Goldin, Lynn R.; Chanock, Stephen] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Nieters, Alexandra; Becker, Nikolaus; Butterbach, Katja] German Canc Res Ctr, D-6900 Heidelberg, Germany. [Nieters, Alexandra] Univ Freiburg, Med Ctr, Ctr Chron Immunodeficiency, D-7800 Freiburg, Germany. [Slager, Susan L.; Achenbach, Sara J.; Call, Timothy G.; Cerhan, James R.; Cunningham, Julie M.; Hanson, Curtis A.; Kay, Neil E.; Leis, Jose F.; Rabe, Kari G.; Vachon, Celine M.] Mayo Clin, Coll Med, Rochester, MN USA. [Brooks-Wilson, Angela; Spinelli, John J.] British Columbia Canc Agcy, British Columbia Canc Res Ctr, Vancouver, BC V5Z 4E6, Canada. [Brooks-Wilson, Angela] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Vancouver, BC, Canada. [Liu, Jianjun; Low, Hui-Qi] ASTAR, Genome Inst Singapore, Singapore, Singapore. [Adami, Hans-Olov; Darabi, Hatef; Humphreys, Keith] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Adami, Hans-Olov] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hjalgrim, Henrik; Melbye, Mads] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. [Chang, Ellen T.] Canc Prevent Inst Calif, Fremont, CA USA. [Chang, Ellen T.] Stanford Univ, Sch Med, Div Epidemiol, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Glimelius, Bengt] Karolinska Univ Hosp, Karolinska Inst, Dept Oncol & Pathol, Stockholm, Sweden. [Glimelius, Bengt] Uppsala Univ, Akademiska Hosp, Dept Oncol Radiol & Clin Immunol, Uppsala, Sweden. [Cozen, Wendy] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Davis, Scott] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Schenk, Maryjean] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI USA. [Wang, Sophia S.] City Hope Natl Med Ctr, Beckman Res Inst, Div Etiol, Duarte, CA 91010 USA. [Wang, Sophia S.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Armstrong, Bruce; Kricker, Anne] Univ Sydney, Sydney Sch Publ Hlth, Sydney, NSW 2006, Australia. [Milliken, Sam] St Vincents Hosp, Dept Haematol, Sydney, NSW 2010, Australia. [Vajdic, Claire M.] Univ New S Wales, Res Ctr, Prince Wales Clin Sch, Sydney, NSW, Australia. [Boyle, Peter; Boffetta, Paolo] Int Prevent Res Inst, Lyon, France. [Zhang, Yawei; Zheng, Tongzhang] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Benavente, Yolanda; de Sanjose, Silvia] Catalan Inst Oncol, Unit Infect & Canc UNIC, Canc Epidemiol Res Programme, Barcelona, Spain. [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France. [Cocco, Pierluigi] Univ Cagliari, Dept Publ Hlth, Occupat Hlth Sect, Cagliari, Italy. [Foretova, Lenka] Masaryk Mem Canc Inst, Brno, Czech Republic. [Maynadie, Marc] Univ Burgundy, Univ Hosp Dijon, Registry Hematol Malignancies, EA4184, Dijon, France. [Staines, Anthony] Univ Coll Dublin, Sch Publ Hlth & Populat Sci, Dublin 2, Ireland. [Spinelli, John J.] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V5Z 1M9, Canada. [Camp, Nicola J.; Glenn, Martha] Univ Utah, Sch Med, Dept Biomed Informat, Salt Lake City, UT USA. [Lanasa, Mark C.; Weinberg, J. Brice] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Marti, Gerald E.] US Natl Inst Hlth, Div Cell & Gene Therapies, Off Cellular Tissues & Gene Therapies, US FDA, Bethesda, MD USA. [Rassenti, Laura Z.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Spector, Logan G.] Univ Minnesota, Prevent & Etiol Res Program, Masonic Canc Ctr, Minneapolis, MN USA. [Strom, Sara S.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Holly, Elizabeth A.; Bracci, Paige M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Skibola, CF (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA. EM chrisfs@berkeley.edu RI Benavente, Yolanda/H-9810-2014; Chang, Ellen/G-5700-2010; Conde, Lucia/D-9295-2011; Spinelli, John/B-6210-2013; Boyle, Peter/A-4380-2014; Tang, Macy/B-9798-2014; Brooks-Wilson, Angela/E-9399-2012; de Sanjose Llongueras, Silvia/H-6339-2014; Morton, Lindsay/B-5234-2015; Armstrong, Bruce/K-9464-2015; Purdue, Mark/C-9228-2016; OI Vajdic, Claire/0000-0002-3612-8298; Cerhan, James/0000-0002-7482-178X; Boyle, Peter/0000-0001-6251-0610; Brooks-Wilson, Angela/0000-0003-1009-6408; Morton, Lindsay/0000-0001-9767-2310; Armstrong, Bruce/0000-0001-8940-7525; Purdue, Mark/0000-0003-1177-3108; Staines, Anthony/0000-0001-9161-1357; Spector, Logan/0000-0003-2516-0222 FU National Cancer Institute (NCI), US National Institutes of Health (NIH) [CA122663, CA104682, CA45614, CA89745]; American Cancer Society [IRG-07-06401]; Agency for Science and Technology and Research of Singapore (A*STAR); NCI [R01 CA91253, R01 CA118444, CA62006]; Swedish Cancer Society; Swedish Research Council; Danish Medical Research Council; Information Management Services, Inc.; NIH (NCI); US Public Health Service (PHS) [N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010, N02-PC-71105]; National Health and Medical Research Council of Australia; Cancer Council NSW; University of Sydney Medical Foundation; Canadian Cancer Society; Canadian Institutes of Health Research; German Jose Carreras Leukemia Foundation [DJCLS_R04/08, R07/26f]; EC [QLK4-CT-2000-00422]; Federal Office for Radiation Protection (Germany) [StSch4261, StSch4420]; Spanish Ministry of Health [06/02/0073]; FIS [08-1555]; Marato TV3 (Spain) [051210]; La Fondation de France [1999 0084 71]; Compagnia di San Paolo di Torino; Health Research Board, Ireland; Ministry of Health of the Czech Republic [MZ0 MOU 2005] FX This work was supported by grants CA122663 and CA104682 from the National Cancer Institute (NCI), US National Institutes of Health (NIH) (C. F. S.); grants CA45614 and CA89745 from the NCI, NIH (E. A. H.); the American Cancer Society (IRG-07-06401) and a charitable donation by S. Chase (K. B.). E. H. is a faculty fellow of the Edmond J. Safra Bioinformatics program at Tel-Aviv University. SCALE study: We thank X.Y. Chen, H. B. Toh, K. K. Heng and W.Y. Meah from Genome Institute of Singapore for their support in genotyping analyses. We are also grateful to L. Klareskog, Center for Molecular Medicine, and L. Alfredsson, Institute of Environmental Medicine at the Karolinska Institute, Stockholm, Sweden, for sharing DNA from their EIRA study control population and to E. Rehnberg for help with imputing genotypes in the SCALE study. The following agencies contributed funding to SCALE that facilitated the present project: Agency for Science and Technology and Research of Singapore (A*STAR), NCI, the Swedish Cancer Society, the Swedish Research Council and the Danish Medical Research Council. GEC-Mayo Study: This study is supported by grants R01 CA91253 and R01 CA118444 from the NCI. NCI-SEER study: We thank P. Hui of the Information Management Services, Inc. for programming support, and we acknowledge the contributions of the staff and scientists at the SEER centers of Iowa, Los Angeles, Detroit and Seattle for conducting the study's field effort. We especially acknowledge the contributions of study site principal investigator L. Bernstein (Los Angeles). The NCI-SEER study was supported by the Intramural Research Program of the NIH (NCI) and by US Public Health Service (PHS) contracts N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010 and N02-PC-71105. Yale study: This study is supported by grant CA62006 from the NCI and the Intramural Research Program of the NIH (NCI). NSW study: The NSW study was supported by a National Health and Medical Research Council of Australia project grant, Cancer Council NSW, a University of Sydney Medical Foundation Program Grant and the Intramural Research Program of the NIH (NCI). BC study: Funding for the British Columbia study was from the Canadian Cancer Society and the Canadian Institutes of Health Research. A.B.-W. is a Senior Scholar of the Michael Smith Foundation for Health Research. EpiLymph study: Funding was available from the German Jose Carreras Leukemia Foundation (DJCLS_R04/08 and R07/26f) (A.N.), the EC 5th Framework Program Quality of Life grant No. QLK4-CT-2000-00422 (P. Boffetta, P. Brennan), the Federal Office for Radiation Protection grants No. StSch4261 and StSch4420 (Germany), the Spanish Ministry of Health grants Centro de Investigacion Biomedica en Red de Epidemiologia y Salud Publica (CIBERESP) (06/02/0073), FIS 08-1555 and Marato TV3 (051210) (Spain), La Fondation de France, no. 1999 0084 71 (M. Maynadie), Compagnia di San Paolo di Torino, Programma Oncologia 2001 (P. C.), the Health Research Board, Ireland, and the Ministry of Health of the Czech Republic, MZ0 MOU 2005 (L. F.). NR 13 TC 86 Z9 88 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 2010 VL 42 IS 8 BP 661 EP 664 DI 10.1038/ng.626 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 633RZ UT WOS:000280524000008 PM 20639881 ER PT J AU Kunwar, S Chang, S Westphal, M Vogelbaum, M Sampson, J Barnett, G Shaffrey, M Ram, Z Piepmeier, J Prados, M Croteau, D Pedain, C Leland, P Husain, SR Joshi, BH Puri, RK AF Kunwar, Sandeep Chang, Susan Westphal, Manfred Vogelbaum, Michael Sampson, John Barnett, Gene Shaffrey, Mark Ram, Zvi Piepmeier, Joseph Prados, Michael Croteau, David Pedain, Christoph Leland, Pamela Husain, Syed R. Joshi, Bharat H. Puri, Raj K. CA PRECISE Study Grp TI Phase II trial of pazopanib (GW786034), an oral multi-targeted angiogenesis inhibitor, for adults with recurrent glioblastoma SO NEURO-ONCOLOGY LA English DT Article DE antiangiogenesis; clinical therapy trials; giloblastoma ID CONVECTION-ENHANCED DELIVERY; HUMAN GLIOMA-CELLS; MALIGNANT GLIOMA; INTERLEUKIN-13 RECEPTOR; PSEUDOMONAS EXOTOXIN; TARGETED CYTOTOXIN; BRAIN-TUMORS; INFUSION; THERAPY; PROTEIN AB The objective of this phase II single-arm study was to evaluate the efficacy and safety of pazopanib, a multi-targeted tyrosine kinase inhibitor, against vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3, platelet-derived growth factor receptor-alpha and -beta, and c-Kit, in recurrent glioblastoma. Patients with < 2 relapses and no prior anti-VEGF/VEGFR therapy were treated with pazopanib 800 mg daily on 4-week cycles without planned interruptions. Brain magnetic resonance imaging and clinical reassessment were made every 8 weeks. The primary endpoint was efficacy as measured by 6-month progression-free survival (PFS6). Thirty-five GBM patients with a median age of 53 years and median Karnofsky performance scale of 90 were accrued. Grade 3/4 toxicities included leukopenia (n = 1), lymphopenia (n = 2), thrombocytopenia (n = 1), ALT elevation (n = 3), AST elevation (n = 1), CNS hemorrhage (n = 1), fatigue (n = 1), and thrombotic/embolic events (n = 3); 8 patients required dose reduction. Two patients had a partial radiographic response by standard bidimensional measurements, whereas 9 patients (6 at the 8-week point and 3 only within the first month of treatment) had decreased contrast enhancement, vasogenic edema, and mass effect but < 50% reduction in tumor. The median PFS was 12 weeks (95% confidence interval [CI]: 8-14 weeks) and only 1 patient had a PFS time >= 6 months (PFS6 = 3%). Thirty patients (86%) had died and median survival was 35 weeks (95% CI: 24-47 weeks). Pazopanib was reasonably well tolerated with a spectrum of toxicities similar to other anti-VEGF/VEGFR agents. Single-agent pazopanib did not prolong PFS in this patient population but showed in situ biological activity as demonstrated by radiographic responses. ClinicalTrials.gov identifier: NCT00459381. C1 [Chang, Susan] Univ Calif San Francisco, Dept Neurol Surg, Div Neurooncol, San Francisco, CA 94143 USA. [Westphal, Manfred] Univ Hosp Eppendorf, Dept Neurosurg, Hamburg, Germany. [Vogelbaum, Michael; Barnett, Gene] Cleveland Clin, Brain Tumor & Neurooncol Ctr, Cleveland, OH 44106 USA. [Sampson, John] Duke Univ, Div Neurooncol, Durham, NC USA. [Shaffrey, Mark] Univ Virginia, Dept Neurosurg, Charlottesville, VA USA. [Ram, Zvi] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Neurosurg, IL-69978 Tel Aviv, Israel. [Piepmeier, Joseph] Yale Univ, Dept Neurosurg, New Haven, CT USA. [Croteau, David] NeoPharm Inc, Lake Bluff, IL USA. [Pedain, Christoph] BrainLAB, Feldkirchen, Germany. [Leland, Pamela; Husain, Syed R.; Joshi, Bharat H.; Puri, Raj K.] US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD USA. RP Chang, S (reprint author), Univ Calif San Francisco, Dept Neurol Surg, Div Neurooncol, 400 Parnassus Ave,A-808, San Francisco, CA 94143 USA. EM changs@neurosurg.ucsf.edu FU NeoPharm, Inc. FX Funding for this study was provided by NeoPharm, Inc. NR 40 TC 152 Z9 156 U1 0 U2 13 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD AUG PY 2010 VL 12 IS 8 BP 871 EP 881 DI 10.1093/neuonc/noq054 PG 11 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 636CM UT WOS:000280705800013 PM 20511192 ER PT J AU Huang, A Li, JA Summers, RM Petrick, N Hara, AK AF Huang, Adam Li, Jiang Summers, Ronald M. Petrick, Nicholas Hara, Amy K. TI Improving polyp detection algorithms for CT colonography: Pareto front approach SO PATTERN RECOGNITION LETTERS LA English DT Article DE Pareto front; Computer-aided detection; Polyp detection; CT colonography; Virtual colonoscopy ID COMPUTER-AIDED DIAGNOSIS; TOMOGRAPHIC VIRTUAL COLONOSCOPY; SUPPORT VECTOR MACHINES; FINITE-SAMPLE SIZE; COLONIC POLYPS; COLORECTAL NEOPLASIA; FEATURE-SELECTION; NEURAL-NETWORKS; CLASSIFICATION; SEGMENTATION AB We investigated a Pareto front approach to improve polyp detection algorithms for CT colonography (CTC). A dataset of 56 CTC colon surfaces with 87 proven positive detections of 53 polyps sized 4-60 mm was used to evaluate the performance of a one-step and a two-step curvature-based region growing algorithm. The algorithmic performance was statistically evaluated and compared based on the Pareto optimal solutions from 20 experiments by evolutionary algorithms. The false positive rate was lower (p < 0.05) by the two-step algorithm than by the one-step for 63% of all possible operating points. While operating at a suitable sensitivity level such as 90.8% (79/87) or 88.5% (77/87), the false positive rate was reduced by 24.4% (95% confidence intervals 17.9-31.0%) or 45.8% (95% confidence intervals 40.1-51.0%), respectively. We demonstrated that, with a proper experimental design, the Pareto optimization process can effectively help in fine-tuning and redesigning polyp detection algorithms. (C) 2010 Elsevier B.V. All rights reserved. C1 [Huang, Adam; Li, Jiang; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. [Huang, Adam] Natl Cent Univ, Res Ctr Adapt Data Anal, Jhongli, Taiwan. [Li, Jiang] Old Dominion Univ, Dept Elect & Comp Engn, Virginia Modeling Anal & Simulat Ctr, Norfolk, VA 23529 USA. [Petrick, Nicholas] US FDA, NIBIB, Ctr Devices & Radiol Hlth Lab Assessment, Silver Spring, MD 20993 USA. [Hara, Amy K.] Mayo Clin, Scottsdale, AZ 85259 USA. RP Summers, RM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10,Room 1C368X MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov FU iCAD; National Institutes of Health (NIH) Clinical Center; National Institute of Biomedical Imaging and Bioengineering at NIH (NP); National Science Council of Republic of China (Taiwan) [NSC 98-2314-B-008-001, 97-2627-B-008-007] FX Authors A. Huang, J. Li, and R.M. Summers have pending and/or awarded patents for the subject matter described in the manuscript. Authors A. Huang and R.M. Summers receive patent royalties from iCAD. Author Summers' lab is supported in part by a Cooperative Research and Development Agreement with iCAD and received free research software from Viatronix.; We thank the anonymous reviewer who suggests adding the FN example in Fig. 8. This additional figure adds clarity to our discussion and leads us to correct an error in the operating parameter NB value given in (Huang et al., 2007). This research was conducted while the first and second authors were post-doctoral fellows supported by the intramural programs of the National Institutes of Health (NIH) Clinical Center. Support was also provided by the intramural program of the National Institute of Biomedical Imaging and Bioengineering at NIH (NP). This study utilized the high-performance computational capabilities of the NIH Biowulf PC/Linux cluster. The first author was partially supported by the National Science Council of Republic of China (Taiwan), NSC 98-2314-B-008-001 and 97-2627-B-008-007. NR 50 TC 0 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8655 EI 1872-7344 J9 PATTERN RECOGN LETT JI Pattern Recognit. Lett. PD AUG 1 PY 2010 VL 31 IS 11 BP 1461 EP 1469 DI 10.1016/j.patrec.2010.03.013 PG 9 WC Computer Science, Artificial Intelligence SC Computer Science GA 624QO UT WOS:000279834800028 PM 20548966 ER PT J AU Wang, CL Hefflin, B Cope, JU Gross, TP Ritchie, MB Qi, YL Chu, JX AF Wang, Cunlin Hefflin, Brock Cope, Judith U. Gross, Thomas P. Ritchie, Mary Beth Qi, Youlin Chu, Jianxiong TI Emergency Department Visits for Medical Device-Associated Adverse Events Among Children SO PEDIATRICS LA English DT Article DE medical device; adverse events; emergency department ID INJURY SURVEILLANCE SYSTEM; EPIDEMIOLOGY; SAFETY AB OBJECTIVES: The purposes of this study were to provide national estimates of emergency department (ED) visits for medical device-associated adverse events (MDAEs) in the pediatric population and to characterize these events further. METHODS: ED medical record reports from the National Electronic Injury Surveillance System All Injury Program database from January 1, 2004, through December 21, 2005, were reviewed. MDAEs among pediatric patients were identified, and data were abstracted. National estimates for pediatric MDAEs were determined according to medical specialty, device category and class, injury diagnosis, and patient characteristics and outcome. RESULTS: The total estimated number of pediatric MDAEs during the 24-month period was 144 799 (95% confidence interval: 113 051183 903), involving devices from 13 medical specialties. Contact lenses accounted for most MDAEs (23%), followed by hypodermic needles (8%). The distribution of MDAEs according to medical specialty varied according to age subgroup. The most-prevalent types of injuries included contusions/abrasions, foreign-body intrusions, punctures, lacerations, and infections. The most-frequently affected body parts were the eyeball, pubic region, finger, face, and ear. The majority of pediatric MDAEs involved class II (moderate-risk) devices. The incidence of pediatric MDAEs decreased with increasing age from early to late childhood and then spiked after 10 years of age. More girls than boys were affected at older ages (16-21 years) and more boys than girls at younger ages (<= 10 years). Hospitalizations were more likely to involve invasive or implanted devices. CONCLUSIONS: This study provides national estimates of pediatric MDAEs resulting in ED visits and highlights the need to develop interventions to prevent pediatric device-related injuries. Pediatrics 2010;126:247-259 C1 [Wang, Cunlin; Hefflin, Brock; Gross, Thomas P.; Ritchie, Mary Beth; Qi, Youlin; Chu, Jianxiong] US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Silver Spring, MD 20993 USA. [Wang, Cunlin] US FDA, Off Pediat Therapeut, Off Commissioner, Silver Spring, MD 20993 USA. [Cope, Judith U.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Wang, CL (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, White Oak Bldg 66,Room 4104,10903 New Hampshire A, Silver Spring, MD 20993 USA. EM cunlin.wang@fda.hhs.gov NR 26 TC 13 Z9 13 U1 0 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD AUG PY 2010 VL 126 IS 2 BP 247 EP 259 DI 10.1542/peds.2010-0528 PG 13 WC Pediatrics SC Pediatrics GA 634FO UT WOS:000280565700008 PM 20660543 ER PT J AU Tompkins, L Lynch, C Haidar, S Polli, J Wang, HB AF Tompkins, Leslie Lynch, Caitlin Haidar, Sam Polli, James Wang, Hongbing TI Effects of Commonly Used Excipients on the Expression of CYP3A4 in Colon and Liver Cells SO PHARMACEUTICAL RESEARCH LA English DT Article DE excipients; CYP3A4; PXR; induction; repression ID BIOPHARMACEUTICS CLASSIFICATION-SYSTEM; PREGNANE-X-RECEPTOR; CONSTITUTIVE ANDROSTANE RECEPTOR; CANCER RESISTANCE PROTEIN; GENE-EXPRESSION; DRUG-INTERACTIONS; HUMAN HEPATOCYTES; MEDIATED EFFLUX; WORKSHOP REPORT; P-GLYCOPROTEIN AB The objective of this investigation was to assess whether common pharmaceutical excipients regulate the expression of drug-metabolizing enzymes in human colon and liver cells. Nineteen commonly used excipients were evaluated using a panel of experiments including cell-based human PXR activation assays, real-time RT-PCR assays for CYP3A4 mRNA expression, and immunoblot analysis of CYP3A4 protein expression in immortalized human liver cells (HepG2 and Fa2N4), human primary hepatocytes, and the intestinal LS174T cell models. No excipient activated human PXR or practically induced CYP3A4. However, three excipients (polysorbate 80, pregelatinized starch, and hydroxypropyl methylcellulose) tended to decrease mRNA and protein expression across experimental models. This study represents the first investigation of the potential role of excipients in the expression of drug-metabolizing enzymes. Findings imply that some excipients may hold potential for excipient-drug interactions by repression of CYP3A4 expression. C1 [Tompkins, Leslie; Lynch, Caitlin; Polli, James; Wang, Hongbing] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. [Haidar, Sam] US FDA, Rockville, MD 20855 USA. RP Wang, HB (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, 20 Penn St, Baltimore, MD 21201 USA. EM hwang@rx.umaryland.edu FU National Institute of Health [R01, DK061652] FX The authors thank Dr. Steve Kliewer (University of Texas, Southwestern Medical Center, Dallas, TX) for providing the pSG5-hPXR expression vector. Human liver tissues were procured with the assistance of Jennifer Fuhrman from the University of Maryland Medical Center (Baltimore, MD). This research was partly supported by National Institute of Health Grant (R01, DK061652). NR 42 TC 11 Z9 12 U1 1 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORDR JI Pharm. Res. PD AUG PY 2010 VL 27 IS 8 BP 1703 EP 1712 DI 10.1007/s11095-010-0170-2 PG 10 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 620NH UT WOS:000279506100019 PM 20503067 ER PT J AU Mu, L Sprando, RL AF Mu, Li Sprando, Robert L. TI Application of Nanotechnology in Cosmetics SO PHARMACEUTICAL RESEARCH LA English DT Editorial Material ID LIPID NANOPARTICLES C1 [Mu, Li; Sprando, Robert L.] US FDA, Div Toxicol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Mu, L (reprint author), US FDA, Div Toxicol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM Li.Mu@fda.hhs.gov NR 15 TC 49 Z9 49 U1 1 U2 45 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORDR JI Pharm. Res. PD AUG PY 2010 VL 27 IS 8 BP 1746 EP 1749 DI 10.1007/s11095-010-0139-1 PG 4 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 620NH UT WOS:000279506100024 PM 20407919 ER PT J AU Wu, YT Makuch, RW AF Wu, Yu-te Makuch, Robert W. TI Sample size for post-marketing safety studies based on historical controls SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE two-group cohort studies; drug safety; exact method; sample size; external control ID 2 POISSON MEANS; POWER AB Purpose As part of a drug's entire life cycle, post-marketing studies are an important part in the identification of rare, serious adverse events. Recently, the US Food and Drug Administration (FDA) has begun to implement new post-marketing safety mandates as a consequence of increased emphasis on safety. The purpose of this research is to provide exact sample size formula for the proposed hybrid design, based on a two-group cohort study with incorporation of historical external data. Methods Exact sample size formula based on the Poisson distribution is developed, because the detection of rare events is our outcome of interest. Performance of exact method is compared to its approximate large-sample theory counterpart. Results The proposed hybrid design requires a smaller sample size compared to the standard, two-group prospective study design. In addition, the exact method reduces the number of subjects required in the treatment group by up to 30% compared to the approximate method for the study scenarios examined. Conclusions The proposed hybrid design satisfies the advantages and rationale of the two-group design with smaller sample sizes generally required. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Wu, Yu-te] US FDA, Div Biometr 7, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Makuch, Robert W.] Yale Univ, Div Biostat, Sch Publ Hlth, New Haven, CT USA. RP Wu, YT (reprint author), US FDA, Div Biometr 7, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,BLDG 21,Rm 4669, Silver Spring, MD 20993 USA. EM yutewu@yahoo.com RI Research Datalink, Clinical Practice/H-2477-2013 NR 12 TC 1 Z9 1 U1 0 U2 1 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 IS 8 BP 869 EP 875 DI 10.1002/pds.1990 PG 7 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 638MA UT WOS:000280897800016 PM 20572025 ER PT J AU Ahmad, SR Elixhauser, A AF Ahmad, Syed Rizwanuddin Elixhauser, Anne TI Hospitalizations Associated with Acetaminophen Poisoning in the United States SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract CT 26th International Conference on Pharmacoepidemiology and Therapeutic Risk Management CY AUG 19-22, 2010 CL Brighton, ENGLAND C1 [Ahmad, Syed Rizwanuddin] US FDA, Div Epidemiol, Off Surveillance & Epidemiol, CDER, Silver Spring, MD USA. [Elixhauser, Anne] Agcy Healthcare Res & Qual, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 641 BP S271 EP S272 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200615 ER PT J AU Ahmad, SR Raine, J Hawton, K Dal Pan, G AF Ahmad, Syed Rizwanuddin Raine, June Hawton, Keith Dal Pan, Gerald TI The Public Health Burden of Acetaminophen Poisonings: Risk Management Efforts To Mitigate it SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract CT 26th International Conference on Pharmacoepidemiology and Therapeutic Risk Management CY AUG 19-22, 2010 CL Brighton, ENGLAND C1 [Ahmad, Syed Rizwanuddin; Dal Pan, Gerald] US FDA, Off Surveillance & Epidemiol, CDER, Silver Spring, MD USA. [Raine, June] MHRA, London, England. [Hawton, Keith] Univ Oxford, Ctr Suicide Res, Oxford, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 575 BP S244 EP S244 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200552 ER PT J AU Andrade, S Scott, P Cheetham, C Cooper, W Davis, R Li, DK Dublin, S Pawloski, P Raebel, M Toh, D AF Andrade, Susan Scott, Pamela Cheetham, Craig Cooper, William Davis, Robert Li, De-Kun Dublin, Sascha Pawloski, Pamala Raebel, Marsha Toh, Darren TI Medication Exposure in Pregnancy Risk Evaluation Program SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Andrade, Susan] Meyers Primary Care Inst, Worcester, MA USA. [Scott, Pamela] US FDA, Silver Spring, MD USA. [Cheetham, Craig] Kaiser Permanente S Calif, Los Angeles, CA USA. [Cooper, William] Vanderbilt Univ, Nashville, TN 37235 USA. [Davis, Robert] Kaiser Permanente GA, Atlanta, GA USA. [Li, De-Kun] Kaiser Permanente N Calif, Oakland, CA USA. [Dublin, Sascha] Grp Hlth, Seattle, WA USA. [Pawloski, Pamala] HealthPartners, Minneapolis, MN USA. [Raebel, Marsha] Kaiser Permanente CO, Denver, CO USA. [Toh, Darren] Harvard Pilgrim Hlth Care, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 706 BP S298 EP S299 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200677 ER PT J AU Bonhoeffer, J Sturkenboom, M Kurz, X Kramarz, P Zuber, P Izurieta, H AF Bonhoeffer, Jan Sturkenboom, Miriam Kurz, Xavier Kramarz, Piotr Zuber, Patrick Izurieta, Hector TI Optimizing Global Vaccine Safety Monitoring: Lessons Learned from H1N1 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract CT 26th International Conference on Pharmacoepidemiology and Therapeutic Risk Management CY AUG 19-22, 2010 CL Brighton, ENGLAND C1 [Bonhoeffer, Jan] Brighton Collaborat, Basel, Switzerland. [Sturkenboom, Miriam] Erasmus Univ, Med Ctr, Rotterdam, Netherlands. [Kurz, Xavier] European Med Agcy, London, England. [Kramarz, Piotr] European Ctr Dis Prevent & Control, Stockholm, Sweden. [Zuber, Patrick] WHO, Washington, DC USA. [Izurieta, Hector] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 310 BP S133 EP S133 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200302 ER PT J AU Buckler, A Jain, N Golding, B Barash, F Wise, R AF Buckler, Aileen Jain, Nisha Golding, Basil Barash, Faith Wise, Robert TI Acute Hemolysis Consistent with Intravascular Hemolysis in Patients Receiving WinRho To Treat ITP SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract CT 26th International Conference on Pharmacoepidemiology and Therapeutic Risk Management CY AUG 19-22, 2010 CL Brighton, ENGLAND C1 [Buckler, Aileen; Jain, Nisha; Golding, Basil; Barash, Faith; Wise, Robert] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 441 BP S187 EP S187 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200423 ER PT J AU Burwen, D Sandhu, S MaCurdy, T Kelman, J Gibbs, J Garcia, B Markatou, M Forshee, R Gullet, R Izurieta, H Worrall, C Ball, R AF Burwen, D. Sandhu, S. MaCurdy, T. Kelman, J. Gibbs, J. Garcia, B. Markatou, M. Forshee, R. Gullet, R. Izurieta, H. Worrall, C. Ball, R. TI Surveillance for Guillain-Barre Syndrome after Influenza Vaccination among the Medicare Population, 2009-2010 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Burwen, D.; Sandhu, S.; Markatou, M.; Forshee, R.; Izurieta, H.; Ball, R.] US FDA, Rockville, MD 20857 USA. [MaCurdy, T.; Gibbs, J.; Garcia, B.; Gullet, R.] Acumen LLC, Burlingame, CA USA. [Kelman, J.; Worrall, C.] Ctr Medicare & Medicaid Serv CMS, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 34 BP S15 EP S15 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200034 ER PT J AU Chai, GP Mehta, H Governale, L AF Chai, Grace P. Mehta, Hina Governale, Laura TI Pediatric Atypical Antipsychotic Outpatient Drug Utilization in the US: Y2002-Y2009 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract CT 26th International Conference on Pharmacoepidemiology and Therapeutic Risk Management CY AUG 19-22, 2010 CL Brighton, ENGLAND C1 [Chai, Grace P.] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 668 BP S282 EP S283 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200641 ER PT J AU Dixon, WG Richards, M Askling, J Petri, H Ahmad, SR AF Dixon, William G. Richards, Margaret Askling, Johan Petri, Hans Ahmad, Syed R. TI Lessons Learned from Collaboration among EU Biologics Registries in Rheumatology SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract CT 26th International Conference on Pharmacoepidemiology and Therapeutic Risk Management CY AUG 19-22, 2010 CL Brighton, ENGLAND C1 [Dixon, William G.] Univ Manchester, Manchester, Lancs, England. [Richards, Margaret] Genzyme Corp, Cambridge, MA USA. [Askling, Johan] Karolinska Inst, Stockholm, Sweden. [Petri, Hans] Roche Prod Ltd, Welwyn Garden City, Herts, England. [Ahmad, Syed R.] US FDA, CDER, OSE, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 572 BP S242 EP S243 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200549 ER PT J AU Gold, S Xie, SJ Taylor, L Szarfman, A Coster, T AF Gold, Sigfried Xie, Suji Taylor, Lockwood Szarfman, Ana Coster, Trinka TI A Sorting and Classification Method for Interactive Visualization of Drug/Event Patterns across Many Patient Timelines SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Gold, Sigfried] Phase Forward Inc, Lincoln Safety Grp, Waltham, MA USA. [Xie, Suji; Taylor, Lockwood; Coster, Trinka] US Army Off Surgeon Gen, Pharmacovigilance Ctr, Silver Spring, MD USA. [Szarfman, Ana] FDA, CDER, White Oak, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 726 BP S307 EP S307 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200696 ER PT J AU Hammad, T Pinheiro, SP Irvine, D Kesten, S AF Hammad, Tarek Pinheiro, Simone P. Irvine, David Kesten, Steven TI Role of Meta-Analysis in Drug Safety: Methodological Considerations and Regulatory Implications SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract CT 26th International Conference on Pharmacoepidemiology and Therapeutic Risk Management CY AUG 19-22, 2010 CL Brighton, ENGLAND C1 [Hammad, Tarek; Pinheiro, Simone P.] US FDA, Silver Spring, MD USA. [Irvine, David] Med & Healthcare Prod Regulatory Agcy, London, England. [Kesten, Steven] Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 313 BP S134 EP S135 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200305 ER PT J AU Hartzema, A Ryan, P Stang, P Racoosin, J Overhage, M AF Hartzema, Abraham Ryan, Patrick Stang, Paul Racoosin, Judy Overhage, Marc TI Establishing Drug-Era Persistence Window for Active Surveillance SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Hartzema, Abraham] Univ Florida, Coll Pharm, Gainesville, FL USA. [Ryan, Patrick] GlaxoSmithKline, Stat & Quantitat Sci, Res Triangle Pk, NC USA. [Stang, Paul] Johnson & Johnson, Res & Dev, Titusville, NJ USA. [Racoosin, Judy] FDA, Sentinel Initiat, Silver Spring, MD USA. [Overhage, Marc] Regenstrief Inst Hlth Care, Med Informat, Indianapolis, IN USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 724 BP S306 EP S306 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200694 ER PT J AU Hartzema, AG MaCurdy, TE Gibbs, JM Racoosin, JA Worrall, C Kelman, JA AF Hartzema, Abraham G. MaCurdy, Thomas E. Gibbs, Jonathan M. Racoosin, Judith A. Worrall, Chris Kelman, Jeffrey A. TI Impact of Medicare Claim Resubmissions on Drug and Health Identifiers SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Hartzema, Abraham G.] Univ Florida, Pharmaceut Outcomes & Policy, Gainesville, FL USA. [MaCurdy, Thomas E.; Gibbs, Jonathan M.] Acumen LLC, Burlingame, CA USA. [Racoosin, Judith A.] US FDA, Sentinel Initiat, CDER, Silver Spring, MD USA. [Worrall, Chris; Kelman, Jeffrey A.] CMS, Ctr Beneficiary Choices, Baltimore, MD USA. [MaCurdy, Thomas E.] Stanford Univ, Econ, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 18 BP S8 EP S8 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200019 ER PT J AU Hua, W Tiernan, R Steffey, A Martin, D Wise, R AF Hua, Wei Tiernan, Rosemary Steffey, Amy Martin, David Wise, Robert TI Postmarketing Safety Review for Rotarix (R): Data from the Vaccine Adverse Event Reporting System (VAERS), April 2008-October 2009 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Hua, Wei; Tiernan, Rosemary; Steffey, Amy; Martin, David; Wise, Robert] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 770 BP S326 EP S327 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200740 ER PT J AU Kaplan, S Zhou, E AF Kaplan, Sigal Zhou, Esther TI Persistency and Concurrency Analysis of Leflunomide Therapy SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Kaplan, Sigal; Zhou, Esther] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 212 BP S91 EP S91 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200207 ER PT J AU Kaplan, S Ding, YL AF Kaplan, Sigal Ding, Yulan TI Characterization of Salmeterol Utilization and Concurrent Asthma Therapy SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Kaplan, Sigal; Ding, Yulan] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 148 BP S63 EP S63 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200143 ER PT J AU Kulldorff, M Dashevsky, I Avery, T Chan, AK Davis, RL Graham, D Andrade, SE Boudreau, D Gunter, MJ Herrinton, L Pawloski, P Raebel, MA Roblin, D Platt, R Brown, JS AF Kulldorff, Martin Dashevsky, Inna Avery, Taliser Chan, Arnold K. Davis, Robert L. Graham, David Andrade, Susan E. Boudreau, Denise Gunter, Margaret J. Herrinton, Lisa Pawloski, Pam Raebel, Marsha A. Roblin, Douglas Platt, Richard Brown, Jeffrey S. TI Drug Safety Data Mining with a Tree-Based Scan Statistic SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract CT 26th International Conference on Pharmacoepidemiology and Therapeutic Risk Management CY AUG 19-22, 2010 CL Brighton, ENGLAND C1 [Kulldorff, Martin; Dashevsky, Inna; Avery, Taliser; Platt, Richard; Brown, Jeffrey S.] Harvard Med Sch, Boston, MA USA. [Kulldorff, Martin; Dashevsky, Inna; Avery, Taliser; Platt, Richard; Brown, Jeffrey S.] Harvard Pilgrim Hlth Care, Boston, MA USA. [Chan, Arnold K.] I3 Drug Safety, Waltham, MA USA. [Davis, Robert L.; Roblin, Douglas] Kaiser Permanente Georgia, Atlanta, GA USA. [Graham, David] FDA, Rockville, MD USA. [Andrade, Susan E.] Univ Massachusetts, Worcester, MA 01605 USA. [Andrade, Susan E.] Fallon Fdn, Worcester, MA USA. [Boudreau, Denise] Grp Hlth Cooperat Puget Sound, Seattle, WA USA. [Gunter, Margaret J.] Lovelace Clin Fdn, Albuquerque, NM USA. [Herrinton, Lisa] Kaiser Permanente Northern Calif, Oakland, CA USA. [Pawloski, Pam] HealthPartners, Minneapolis, MN USA. [Raebel, Marsha A.] Kaiser Permanente Colorado, Denver, CO USA. Kaiser Permanente Northwest, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 406 BP S172 EP S173 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200391 ER PT J AU Kuyateh, F Mehta, H Ouellet-Hellstrom, R Ali, F Singer, E MaCurdy, TE Graham, DJ AF Kuyateh, Fatmatta Mehta, Hina Ouellet-Hellstrom, Rita Ali, Farzana Singer, Emily MaCurdy, Thomas E. Graham, David J. TI Comparison of Opioid Use Patterns in Medicare, Medicaid, and a National Prescription Tracker Service SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Kuyateh, Fatmatta; Mehta, Hina; Ouellet-Hellstrom, Rita; Graham, David J.] US FDA, Silver Spring, MD USA. [Ali, Farzana; Singer, Emily; MaCurdy, Thomas E.] Acumen LLC, Burlingame, CA USA. [MaCurdy, Thomas E.] Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 103 BP S44 EP S44 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200100 ER PT J AU Manthripragada, A Zhou, E Budnitz, D Lovegrove, M Willy, M AF Manthripragada, Angelika Zhou, Esther Budnitz, Daniel Lovegrove, Maribeth Willy, Mary TI Characterization of Acetaminophen Overdose-Related Emergency Department Visits and Hospitalizations in the United States SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract CT 26th International Conference on Pharmacoepidemiology and Therapeutic Risk Management CY AUG 19-22, 2010 CL Brighton, ENGLAND C1 [Manthripragada, Angelika; Zhou, Esther; Willy, Mary] FDA, Silver Spring, MD USA. [Budnitz, Daniel; Lovegrove, Maribeth] CDC, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 591 BP S251 EP S251 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200568 ER PT J AU Marinac-Dabic, D Sedrakyan, A Ritchey, ME Normand, SL Resnic, F AF Marinac-Dabic, Danica Sedrakyan, Art Ritchey, Mary E. Normand, Sharon-Lise Resnic, Frederic TI Challenges and Opportunities in Shaping Medical Device Epidemiology SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Marinac-Dabic, Danica; Sedrakyan, Art; Ritchey, Mary E.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Normand, Sharon-Lise; Resnic, Frederic] Harvard Univ, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 781 BP S331 EP S332 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200751 ER PT J AU Mol, P Bahri, P Avorn, J Benkimoun, P Arias, A Morrato, E del Pan, G Haaijer-Ruskamp, F Straus, S AF Mol, P. Bahri, P. Avorn, J. Benkimoun, P. Arias, A. Morrato, E. del Pan, G. Haaijer-Ruskamp, F. Straus, S. TI Regulatory Risk Communication Are We Getting Ahead? SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract CT 26th International Conference on Pharmacoepidemiology and Therapeutic Risk Management CY AUG 19-22, 2010 CL Brighton, ENGLAND C1 [Mol, P.; Haaijer-Ruskamp, F.] Univ Med Ctr Groningen, Groningen, Netherlands. [Mol, P.; Straus, S.] Dutch Med Evaluat Board, The Hague, Netherlands. [Bahri, P.] European Med Agcy, London, England. [Avorn, J.] Harvard Med Sch, Boston, MA USA. [Benkimoun, P.] Univ Victor Segalen Bordeaux 2, Bordeaux, France. [Arias, A.] Hlth Canada, Ottawa, ON, Canada. [Morrato, E.] Univ Colorado, Denver, CO 80202 USA. [del Pan, G.] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 312 BP S134 EP S134 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200304 ER PT J AU Ou, AC Jain, N Maplethorpe, CW Wise, RP AF Ou, Alan C. Jain, Nisha Maplethorpe, Charles W. Wise, Robert P. TI Updated Post-Licensure Safety Surveillance for Recombinant Human Coagulation Factor VIIa SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract CT 26th International Conference on Pharmacoepidemiology and Therapeutic Risk Management CY AUG 19-22, 2010 CL Brighton, ENGLAND C1 [Ou, Alan C.; Jain, Nisha; Maplethorpe, Charles W.; Wise, Robert P.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 443 BP S187 EP S188 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200425 ER PT J AU Ouellet-Hellstrom, R Kuyateh, F Ali, F Singer, E MaCurdy, TE Graham, DJ AF Ouellet-Hellstrom, Rita Kuyateh, Fatmatta Ali, Farzana Singer, Emily MaCurdy, Thomas E. Graham, David J. TI Selected Opioid Use in Medicare Part D and Medicaid Elderly SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract CT 26th International Conference on Pharmacoepidemiology and Therapeutic Risk Management CY AUG 19-22, 2010 CL Brighton, ENGLAND C1 [Ouellet-Hellstrom, Rita; Kuyateh, Fatmatta; Graham, David J.] FDA, Silver Spring, MD USA. [Ali, Farzana; Singer, Emily; MaCurdy, Thomas E.] Acumen LLC, Burlingame, CA USA. [MaCurdy, Thomas E.] Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 675 BP S285 EP S286 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200648 ER PT J AU Pinnow, E Ritchey, ME Tilley, A Marinac-Dabic, D AF Pinnow, Ellen Ritchey, Mary E. Tilley, Andrea Marinac-Dabic, Danica TI Effectiveness of Recruiting and Retention Strategies for Clinical Studies of Drugs, Medical Devices, and Biologics SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract CT 26th International Conference on Pharmacoepidemiology and Therapeutic Risk Management CY AUG 19-22, 2010 CL Brighton, ENGLAND C1 [Pinnow, Ellen; Ritchey, Mary E.; Marinac-Dabic, Danica] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Tilley, Andrea] Assoc Clin Res Professionals, Alexandria, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 440 BP S186 EP S187 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200422 ER PT J AU Qiang, Y Niu, M Martin, D Izurieta, H AF Qiang, Yandong Niu, Manette Martin, David Izurieta, Hector TI Adverse Events Following Varicella-Zoster Virus Vaccination (Zostavax): Reports to the Vaccine Adverse Event Reporting System, 2006-2009 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Qiang, Yandong; Niu, Manette; Martin, David; Izurieta, Hector] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 772 BP S327 EP S328 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200742 ER PT J AU Qiang, Y Groom, A Redd, J Haberling, D Holman, R Jim, C Izurieta, H Sutherland, A Layne, L Cullen, T Cheek, J AF Qiang, Yandong Groom, Amy Redd, John Haberling, Dana Holman, Robert Jim, Cheyenne Izurieta, Hector Sutherland, Andrea Layne, Larry Cullen, Theresa Cheek, James TI Safety of the Influenza A (H1N1) 2009 Monovalent Vaccine among the Indian Health Service User Population SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Qiang, Yandong; Haberling, Dana; Holman, Robert; Izurieta, Hector; Sutherland, Andrea] US FDA, Rockville, MD 20857 USA. [Groom, Amy; Jim, Cheyenne] Ctr Dis Control & Prevent, Atlanta, GA USA. [Redd, John; Layne, Larry; Cullen, Theresa; Cheek, James] Indian Hlth Serv, Albuquerque, NM USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 775 BP S329 EP S329 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200745 ER PT J AU Steffey, A Lizewski, R Sutherland, A Roberts, J Miller, N Wise, RP AF Steffey, Amy Lizewski, Rhonda Sutherland, Andrea Roberts, Jeff Miller, Nancy Wise, Robert P. TI Acute Pancreatitis after Quadrivalent Human Papillomavirus Vaccination: Reports to a Post-Marketing Passive Surveillance System, 2006-2009 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract CT 26th International Conference on Pharmacoepidemiology and Therapeutic Risk Management CY AUG 19-22, 2010 CL Brighton, ENGLAND C1 [Steffey, Amy; Lizewski, Rhonda; Sutherland, Andrea; Roberts, Jeff; Miller, Nancy; Wise, Robert P.] US FDA, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 439 BP S186 EP S186 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200421 ER PT J AU Walker, AM Daniel, GW Smoyer-Tomic, K Puenpatom, T Gu, T Izurieta, H AF Walker, Alexander M. Daniel, Gregory W. Smoyer-Tomic, Karen Puenpatom, Tosmai Gu, Tao Izurieta, Hector TI Identification of Novel Post-Vaccine Syndromes Using Information Theory SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Walker, Alexander M.] WHISCON, Newton, MA USA. [Daniel, Gregory W.; Smoyer-Tomic, Karen; Puenpatom, Tosmai; Gu, Tao] HealthCore, Wilmington, DE USA. [Izurieta, Hector] US FDA, CBER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 16 BP S7 EP S8 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200017 ER PT J AU Zhang, H Hammad, TA Giovannuci, E Kang, E Christiani, DC AF Zhang, Hui Hammad, Tarek A. Giovannuci, Edward Kang, Elizabeth Christiani, David C. TI Validation of Cancer Diagnoses Recorded in the General Practice Research Database SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Zhang, Hui; Hammad, Tarek A.; Giovannuci, Edward; Christiani, David C.] Harvard Univ, Dept Epidemiol, Boston, MA 02115 USA. [Zhang, Hui; Kang, Elizabeth] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 25 BP S11 EP S12 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200026 ER PT J AU Zhang, H Tarek, HA Christiani, DC Giovannuci, E AF Zhang, Hui Tarek, Hammad A. Christiani, David C. Giovannuci, Edward TI Hypoglycemic Agents and the Risk of Cancer SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Zhang, Hui; Christiani, David C.; Giovannuci, Edward] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Zhang, Hui; Tarek, Hammad A.] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 3 BP S1 EP S2 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200004 ER PT J AU Slikker, W AF Slikker, W., Jr. TI Of genomics and bioinformatics SO PHARMACOGENOMICS JOURNAL LA English DT Editorial Material C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Slikker, W (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM william.slikker@fda.hhs.gov NR 2 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD AUG PY 2010 VL 10 IS 4 BP 245 EP 246 DI 10.1038/tpj.2010.59 PG 2 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 636DT UT WOS:000280709100001 PM 20676063 ER PT J AU Fan, X Lobenhofer, EK Chen, M Shi, W Huang, J Luo, J Zhang, J Walker, SJ Chu, TM Li, L Wolfinger, R Bao, W Paules, RS Bushel, PR Li, J Shi, T Nikolskaya, T Nikolsky, Y Hong, H Deng, Y Cheng, Y Fang, H Shi, L Tong, W AF Fan, X. Lobenhofer, E. K. Chen, M. Shi, W. Huang, J. Luo, J. Zhang, J. Walker, S. J. Chu, T-M Li, L. Wolfinger, R. Bao, W. Paules, R. S. Bushel, P. R. Li, J. Shi, T. Nikolskaya, T. Nikolsky, Y. Hong, H. Deng, Y. Cheng, Y. Fang, H. Shi, L. Tong, W. TI Consistency of predictive signature genes and classifiers generated using different microarray platforms SO PHARMACOGENOMICS JOURNAL LA English DT Article DE microarray; cross-platform; gene signature; classifier; MAQC; hepatotoxicity ID CONTROL MAQC PROJECT; CROSS-PLATFORM; DNA MICROARRAY; EXPRESSION MEASUREMENTS; DECISION FOREST; PERFORMANCE; TECHNOLOGIES; REPRODUCIBILITY; NORMALIZATION; VISUALIZATION AB Microarray-based classifiers and associated signature genes generated from various platforms are abundantly reported in the literature; however, the utility of the classifiers and signature genes in cross-platform prediction applications remains largely uncertain. As part of the MicroArray Quality Control Phase II (MAQC-II) project, we show in this study 80-90% cross-platform prediction consistency using a large toxicogenomics data set by illustrating that: (1) the signature genes of a classifier generated from one platform can be directly applied to another platform to develop a predictive classifier; (2) a classifier developed using data generated from one platform can accurately predict samples that were profiled using a different platform. The results suggest the potential utility of using published signature genes in cross-platform applications and the possible adoption of the published classifiers for a variety of applications. The study reveals an opportunity for possible translation of biomarkers identified using microarrays to clinically validated non-array gene expression assays. The Pharmacogenomics Journal (2010) 10, 247-257; doi: 10.1038/tpj.2010.34 C1 [Fan, X.; Huang, J.; Cheng, Y.] Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310003, Zhejiang, Peoples R China. [Lobenhofer, E. K.] Cogenics, Morrisville, NC USA. [Chen, M.; Huang, J.; Hong, H.; Shi, L.; Tong, W.] US FDA, Ctr Toxicoinformat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Shi, W.; Nikolskaya, T.; Nikolsky, Y.] GeneGo Inc, St Joseph, MI USA. [Luo, J.; Zhang, J.] Syst Analyt Inc, Waltham, MA USA. [Walker, S. J.] Wake Forest Inst Regenerat Med, Winston Salem, NC USA. [Chu, T-M; Li, L.; Wolfinger, R.; Bao, W.] SAS Inst Inc, Cary, NC USA. [Paules, R. S.; Bushel, P. R.; Li, J.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Shi, T.] Chinese Acad Sci, Shanghai Informat Ctr Sci, Shanghai, Peoples R China. [Nikolskaya, T.] Russian Acad Sci, NI Vavilov Gen Genet Res Inst, Moscow, Russia. [Deng, Y.] Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA. [Fang, H.] US FDA, Z Tech, NCTR, Tempe, AR USA. RP Tong, W (reprint author), US FDA, Ctr Toxicoinformat, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM weida.tong@fda.hhs.gov FU Chinese Key Technologies RD Program [2005CB23402]; National Science Foundation of China [30801556]; Research Fund for the Doctoral Program of Higher Education of China [20090101110126] FX Dr Xiaohui Fan thanks the support by Chinese Key Technologies R&D Program (No. 2005CB23402), the National Science Foundation of China (No. 30801556) and Research Fund for the Doctoral Program of Higher Education of China (No. 20090101110126) for participating in the MAQC project at National Center for Toxicological Research of the US Food and Drug Administration. The views presented in this article do not necessarily reflect those of the US Food and Drug Administration. NR 32 TC 27 Z9 30 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD AUG PY 2010 VL 10 IS 4 BP 247 EP 257 DI 10.1038/tpj.2010.34 PG 11 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 636DT UT WOS:000280709100002 PM 20676064 ER PT J AU Oberthuer, A Juraeva, D Li, L Kahlert, Y Westermann, F Eils, R Berthold, F Shi, L Wolfinger, RD Fischer, M Brors, B AF Oberthuer, A. Juraeva, D. Li, L. Kahlert, Y. Westermann, F. Eils, R. Berthold, F. Shi, L. Wolfinger, R. D. Fischer, M. Brors, B. TI Comparison of performance of one-color and two-color gene-expression analyses in predicting clinical endpoints of neuroblastoma patients SO PHARMACOGENOMICS JOURNAL LA English DT Article DE MAQC-II; microarray; one-color; two-color; neuroblastoma; classification of clinical endpoints ID CDNA MICROARRAYS; ROC CURVE; CLASSIFICATION; CANCER; PLATFORMS; AREA AB Microarray-based prediction of clinical endpoints may be performed using either a one-color approach reflecting mRNA abundance in absolute intensity values or a two-color approach yielding ratios of fluorescent intensities. In this study, as part of the MAQC-II project, we systematically compared the classification performance resulting from one-and two-color gene-expression profiles of 478 neuroblastoma samples. In total, 196 classification models were applied to these measurements to predict four clinical endpoints, and classification performances were compared in terms of accuracy, area under the curve, Matthews correlation coefficient and root mean-squared error. Whereas prediction performance varied with distinct clinical endpoints and classification models, equivalent performance metrics were observed for one-and two-color measurements in both internal and external validation. Furthermore, overlap of selected signature genes correlated inversely with endpoint prediction difficulty. In summary, our data strongly substantiate that the choice of platform is not a primary factor for successful gene expression based-prediction of clinical endpoints. The Pharmacogenomics Journal (2010) 10, 258-266; doi: 10.1038/tpj.2010.53 C1 [Juraeva, D.; Eils, R.; Brors, B.] German Canc Res Ctr, Div Theoret Bioinformat, D-69120 Heidelberg, Germany. [Oberthuer, A.; Kahlert, Y.; Berthold, F.; Fischer, M.] Childrens Hosp, Dept Pediat Oncol & Hematol, Cologne, Germany. [Oberthuer, A.; Kahlert, Y.; Berthold, F.; Fischer, M.] Univ Cologne, Ctr Mol Med Cologne ZMMK, Cologne, Germany. [Li, L.; Wolfinger, R. D.] SAS Inst, Cary, NC USA. [Westermann, F.] German Canc Res Ctr, Div Tumor Genet, D-69120 Heidelberg, Germany. [Eils, R.] Univ Heidelberg, Inst Pharm & Mol Biotechnol, Div Bioinformat & Funct Genom, Heidelberg, Germany. [Eils, R.] Univ Heidelberg, Bioquant Ctr, Heidelberg, Germany. [Shi, L.] US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Brors, B (reprint author), German Canc Res Ctr, Div Theoret Bioinformat, Neuenheimer Feld 280, D-69120 Heidelberg, Germany. EM b.brors@dkfz.de RI Brors, Benedikt/E-5620-2013; Eils, Roland/B-6121-2009 OI Brors, Benedikt/0000-0001-5940-3101; Eils, Roland/0000-0002-0034-4036 FU German Federal Ministry of Research and Education (BMBF) through the National Genome Research Network [01GS0895, 01GS0896]; European Commission [LSHC-CT-2006-037260]; Deutsche Krebshilfe [50-2719-Fi1]; Auerbach Stiftung FX This study was supported by grants 01GS0895 (MF) and 01GS0896 (BB) from the German Federal Ministry of Research and Education (BMBF) through the National Genome Research Network. BB was further supported by a grant from the European Commission (LSHC-CT-2006-037260). Furthermore, this study was supported by the Deutsche Krebshilfe (grant 50-2719-Fi1 to MF) and by the Auerbach Stiftung. NR 18 TC 35 Z9 38 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD AUG PY 2010 VL 10 IS 4 BP 258 EP 266 DI 10.1038/tpj.2010.53 PG 9 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 636DT UT WOS:000280709100003 PM 20676065 ER PT J AU Huang, J Shi, W Zhang, J Chou, JW Paules, RS Gerrish, K Li, J Luo, J Wolfinger, RD Bao, W Chu, TM Nikolsky, Y Nikolskaya, T Dosymbekov, D Tsyganova, MO Shi, L Fan, X Corton, JC Chen, M Cheng, Y Tong, W Fang, H Bushel, PR AF Huang, J. Shi, W. Zhang, J. Chou, J. W. Paules, R. S. Gerrish, K. Li, J. Luo, J. Wolfinger, R. D. Bao, W. Chu, T-M Nikolsky, Y. Nikolskaya, T. Dosymbekov, D. Tsyganova, M. O. Shi, L. Fan, X. Corton, J. C. Chen, M. Cheng, Y. Tong, W. Fang, H. Bushel, P. R. TI Genomic indicators in the blood predict drug-induced liver injury SO PHARMACOGENOMICS JOURNAL LA English DT Article DE prediction; acetaminophen; blood; cross-tissue; liver injury; microarray gene expression ID GENE-EXPRESSION PROFILES; COEXPRESSED GENES; SERUM BIOMARKERS; HEPATOTOXICITY; MICROARRAY; TOXICITY; MECHANISMS; RATS; NEUTROPHILS; PHENOTYPE AB Genomic biomarkers for the detection of drug-induced liver injury (DILI) from blood are urgently needed for monitoring drug safety. We used a unique data set as part of the Food and Drug Administration led MicroArray Quality Control Phase-II (MAQC-II) project consisting of gene expression data from the two tissues (blood and liver) to test cross-tissue predictability of genomic indicators to a form of chemically induced liver injury. We then use the genomic indicators from the blood as biomarkers for prediction of acetaminophen-induced liver injury and show that the cross-tissue predictability of a response to the pharmaceutical agent (accuracy as high as 92.1%) is better than, or at least comparable to, that of non-therapeutic compounds. We provide a database of gene expression for the highly informative predictors, which brings biological context to the possible mechanisms involved in DILI. Pathway-based predictors were associated with inflammation, angiogenesis, Toll-like receptor signaling, apoptosis, and mitochondrial damage. The results show for the first time and support the hypothesis that genomic indicators in the blood can serve as potential diagnostic biomarkers predictive of DILI. The Pharmacogenomics Journal (2010) 10, 267-277; doi: 10.1038/tpj.2010.33 C1 [Chou, J. W.; Li, J.; Bushel, P. R.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Huang, J.; Fan, X.; Cheng, Y.] Zhejiang Univ, Coll Pharmaceut Sci, Pharmaceut Informat Inst, Hangzhou 310003, Zhejiang, Peoples R China. [Shi, W.; Nikolsky, Y.; Nikolskaya, T.] GeneGO, St Joseph, MI USA. [Zhang, J.; Luo, J.] Syst Analyt, Dept Bioinformat, Waltham, MA USA. [Paules, R. S.; Gerrish, K.] NIEHS, Microarray Grp, Res Triangle Pk, NC 27709 USA. [Wolfinger, R. D.; Bao, W.; Chu, T-M] SAS, Genom Div, Cary, NC USA. [Dosymbekov, D.; Tsyganova, M. O.] Russian Acad Sci, NI Vavilov Gen Genet Res Inst, Moscow, Russia. [Huang, J.; Shi, L.; Fan, X.; Chen, M.; Tong, W.] US FDA, Ctr Toxicoinformat, Natl Ctr Toxicol Res, Jefferson, AR USA. [Corton, J. C.] US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. [Fang, H.] US FDA, Div Bioinformat, Z Tech Corp, NCTR, Jefferson, AR USA. [Nikolskaya, T.] Russian Acad Sci, Inst Gen Genet, Syst Biol Lab, Moscow V71, Russia. RP Bushel, PR (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. EM bushel@niehs.nih.gov FU Oak Ridge Institute for Science and Education (ORISE) at the National Center for Toxicological Research (NCTR), US Food and Drug Administration (FDA); China State; Chinese Key Technologies RD Program [2005CB23402]; National Science Foundation of China at the NCTR/FDA [30801556]; Intramural Research Program of the NIH; NIEHS [Z01 ES102345-03] FX We thank the National Center for Toxicogenomics at the National Institute of Environmental Health Sciences (NIEHS) for the hepatotoxicant compendium data. In addition, we thank the participants of MAQC-II for comments, feedback, and discussions on the topic of this paper during teleconferences and face-to-face project meetings. We also thank K Shockley, A Merrick, S Hester, B Ward, and D Mendrick for their critical review of the manuscript. JH acknowledge the support of the Oak Ridge Institute for Science and Education (ORISE) for the Post-graduate Research Program at the National Center for Toxicological Research (NCTR), US Food and Drug Administration (FDA). JH also acknowledges the support of the China State-funded Study Abroad Program that is organized by the China Scholarship Council (CSC). JH and XF both acknowledge the Chinese Key Technologies R&D Program (No. 2005CB23402) and the National Science Foundation of China (No. 30801556) for support to participate in the MAQC-II project at the NCTR/FDA. This research was supported, in part by, the Intramural Research Program of the NIH and NIEHS (Z01 ES102345-03). This document has been reviewed in accordance with the US FDA and Environmental Protection Agency (EPA) policies and is approved for publication. Approval does not signify that the contents necessarily reflect the position or opinions of the FDA or EPA nor does mention of trade names or commercial products constitute endorsement or recommendation for use. The findings, views, and conclusions in this report are those of the authors and do not necessarily represent or reflect the views of the FDA or EPA. NR 42 TC 31 Z9 38 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD AUG PY 2010 VL 10 IS 4 BP 267 EP 277 DI 10.1038/tpj.2010.33 PG 11 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 636DT UT WOS:000280709100004 PM 20676066 ER PT J AU Luo, J Schumacher, M Scherer, A Sanoudou, D Megherbi, D Davison, T Shi, T Tong, W Shi, L Hong, H Zhao, C Elloumi, F Shi, W Thomas, R Lin, S Tillinghast, G Liu, G Zhou, Y Herman, D Li, Y Deng, Y Fang, H Bushel, P Woods, M Zhang, J AF Luo, J. Schumacher, M. Scherer, A. Sanoudou, D. Megherbi, D. Davison, T. Shi, T. Tong, W. Shi, L. Hong, H. Zhao, C. Elloumi, F. Shi, W. Thomas, R. Lin, S. Tillinghast, G. Liu, G. Zhou, Y. Herman, D. Li, Y. Deng, Y. Fang, H. Bushel, P. Woods, M. Zhang, J. TI A comparison of batch effect removal methods for enhancement of prediction performance using MAQC-II microarray gene expression data SO PHARMACOGENOMICS JOURNAL LA English DT Article DE batch effect; batch effect removal; cross-batch prediction; microarray; gene expression; MAQC-II ID NORMALIZATION; CANCER; BLOOD AB Batch effects are the systematic non-biological differences between batches (groups) of samples in microarray experiments due to various causes such as differences in sample preparation and hybridization protocols. Previous work focused mainly on the development of methods for effective batch effects removal. However, their impact on cross-batch prediction performance, which is one of the most important goals in microarray-based applications, has not been addressed. This paper uses a broad selection of data sets from the Microarray Quality Control Phase II (MAQC-II) effort, generated on three microarray platforms with different causes of batch effects to assess the efficacy of their removal. Two data sets from cross-tissue and cross-platform experiments are also included. Of the 120 cases studied using Support vector machines (SVM) and K nearest neighbors (KNN) as classifiers and Matthews correlation coefficient (MCC) as performance metric, we find that Ratio-G, Ratio-A, EJLR, mean-centering and standardization methods perform better or equivalent to no batch effect removal in 89, 85, 83, 79 and 75% of the cases, respectively, suggesting that the application of these methods is generally advisable and ratio-based methods are preferred. The Pharmacogenomics Journal (2010) 10, 278-291; doi: 10.1038/tpj.2010.57 C1 [Zhang, J.] Syst Analyt Inc, Dept Bioinformat, Waltham, MA 02453 USA. [Schumacher, M.] Novartis Pharma AG, NIBR, Biomarker Dev Dept, Basel, Switzerland. [Scherer, A.] Spheromics, Kontiolahti, Finland. [Sanoudou, D.] Acad Athens, Biomed Res Fdn, Dept Mol Biol, Athens, Greece. [Sanoudou, D.] Univ Athens, Sch Med, Dept Pharmacol, Athens 11528, Greece. [Megherbi, D.] Univ Massachusetts, Dept Elect & Comp Engn, CMINDS Res Ctr, Lowell, MA USA. [Davison, T.] Almac Diagnost, Craigavon, North Ireland. [Shi, T.] Chinese Acad Sci, Shanghai Informat Ctr Life Sci, Shanghai, Peoples R China. [Tong, W.; Shi, L.; Hong, H.] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Zhao, C.] NE Forestry Univ, Coll Life Sci, Harbin, Heilongjiang, Peoples R China. [Elloumi, F.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Shi, W.] GeneGo Inc, St Joseph, MI USA. [Thomas, R.] Hamner Inst Hlth Sci, Res Triangle Pk, NC USA. [Lin, S.] Northwestern Univ, Clin & Translat Sci Inst, Chicago, IL 60611 USA. [Tillinghast, G.] Riverside Canc Care Ctr, Dept Clin Res, Newport News, VA USA. [Liu, G.] SABiosci Corp, R&D Div, Frederick, MD USA. [Zhou, Y.; Herman, D.] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. [Li, Y.] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA. [Deng, Y.] Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA. [Fang, H.] US FDA, Z Tech, Natl Ctr Toxicol Res, Jefferson, AR USA. [Bushel, P.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Zhang, J (reprint author), Syst Analyt Inc, Dept Bioinformat, 55 Moody St,Suite 21, Waltham, MA 02453 USA. EM johnz@SystemsAnalytics.com OI Thomas, Russell/0000-0002-2340-0301; Sanoudou, Despina/0000-0003-3704-1941 NR 17 TC 71 Z9 75 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X EI 1473-1150 J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD AUG PY 2010 VL 10 IS 4 BP 278 EP 291 DI 10.1038/tpj.2010.57 PG 14 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 636DT UT WOS:000280709100005 PM 20676067 ER PT J AU Parry, RM Jones, W Stokes, TH Phan, JH Moffitt, RA Fang, H Shi, L Oberthuer, A Fischer, M Tong, W Wang, MD AF Parry, R. M. Jones, W. Stokes, T. H. Phan, J. H. Moffitt, R. A. Fang, H. Shi, L. Oberthuer, A. Fischer, M. Tong, W. Wang, M. D. TI k-Nearest neighbor models for microarray gene expression analysis and clinical outcome prediction SO PHARMACOGENOMICS JOURNAL LA English DT Article DE MAQC-II; k-nearest neighbor (KNN) models; data analysis protocol; predictable good performance; cancer prediction; parameter selection ID HUMAN NEUROBLASTOMA-CELLS; NEURONAL DIFFERENTIATION; PROSTATE-CANCER; CLASSIFICATION; SURVIVAL; TUMORS; CARCINOMA; ADENOCARCINOMA; PROTEIN; SYSTEM AB In the clinical application of genomic data analysis and modeling, a number of factors contribute to the performance of disease classification and clinical outcome prediction. This study focuses on the k-nearest neighbor (KNN) modeling strategy and its clinical use. Although KNN is simple and clinically appealing, large performance variations were found among experienced data analysis teams in the MicroArray Quality Control Phase II (MAQC-II) project. For clinical end points and controls from breast cancer, neuroblastoma and multiple myeloma, we systematically generated 463 320 KNN models by varying feature ranking method, number of features, distance metric, number of neighbors, vote weighting and decision threshold. We identified factors that contribute to the MAQC-II project performance variation, and validated a KNN data analysis protocol using a newly generated clinical data set with 478 neuroblastoma patients. We interpreted the biological and practical significance of the derived KNN models, and compared their performance with existing clinical factors. The Pharmacogenomics Journal (2010) 10, 292-309; doi: 10.1038/tpj.2010.56 C1 [Parry, R. M.; Phan, J. H.; Moffitt, R. A.; Wang, M. D.] Georgia Inst Technol, Dept Biomed Engn, Atlanta, GA 30332 USA. [Parry, R. M.; Phan, J. H.; Moffitt, R. A.; Wang, M. D.] Emory Univ, Atlanta, GA 30332 USA. [Jones, W.] Express Anal Inc, Durham, NC USA. [Stokes, T. H.] Georgia Inst Technol, Dept Elect & Comp Engn, Atlanta, GA 30332 USA. [Fang, H.] US FDA, Z Tech, Natl Ctr Toxicol Res, Jefferson, AR USA. [Shi, L.; Tong, W.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Oberthuer, A.; Fischer, M.] Univ Cologne, Childrens Hosp, Dept Pediat Oncol & Hematol, Cologne, Germany. [Oberthuer, A.; Fischer, M.] Univ Cologne, Ctr Mol Med Cologne ZMMK, Cologne, Germany. RP Wang, MD (reprint author), Georgia Inst Technol, Dept Biomed Engn, 313 Ferst Dr,UA Whitaker Bldg Suite 4106, Atlanta, GA 30332 USA. EM Weida.Tong@fda.hhs.gov; maywang@bme.gatech.edu FU Emory-Georgia Tech NCI Center for Cancer Nanotechnology Excellence [U54CA119338]; NCI Bioengineering Research Partnership [R01CA108468]; Georgia Cancer Coalition; National Science Foundation; Microsoft Research; Hewlett-Packard FX This research was supported by Emory-Georgia Tech NCI Center for Cancer Nanotechnology Excellence (U54CA119338), NCI Bioengineering Research Partnership (R01CA108468), Georgia Cancer Coalition (Distinguished Cancer Scholar Award to MDW), National Science Foundation (Graduate Student Research Fellowship to RM), Microsoft Research and Hewlett-Packard. NR 50 TC 37 Z9 40 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD AUG PY 2010 VL 10 IS 4 BP 292 EP 309 DI 10.1038/tpj.2010.56 PG 18 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 636DT UT WOS:000280709100006 PM 20676068 ER PT J AU Shi, W Bessarabova, M Dosymbekov, D Dezso, Z Nikolskaya, T Dudoladova, M Serebryiskaya, T Bugrim, A Guryanov, A Brennan, RJ Shah, R Dopazo, J Chen, M Deng, Y Shi, T Jurman, G Furlanello, C Thomas, RS Corton, JC Tong, W Shi, L Nikolsky, Y AF Shi, W. Bessarabova, M. Dosymbekov, D. Dezso, Z. Nikolskaya, T. Dudoladova, M. Serebryiskaya, T. Bugrim, A. Guryanov, A. Brennan, R. J. Shah, R. Dopazo, J. Chen, M. Deng, Y. Shi, T. Jurman, G. Furlanello, C. Thomas, R. S. Corton, J. C. Tong, W. Shi, L. Nikolsky, Y. TI Functional analysis of multiple genomic signatures demonstrates that classification algorithms choose phenotype-related genes SO PHARMACOGENOMICS JOURNAL LA English DT Article DE genomic signatures; enrichment analysis; network reconstruction; biological pathways; interactome; MAQCII ID BREAST-CANCER; EXPRESSION PROFILES; BIOLOGY; DISEASE; INTERACTOME; INTEGRATION; PREDICTION; BIOMARKERS; NETWORKS; PATHWAYS AB Gene expression signatures of toxicity and clinical response benefit both safety assessment and clinical practice; however, difficulties in connecting signature genes with the predicted end points have limited their application. The Microarray Quality Control Consortium II (MAQCII) project generated 262 signatures for ten clinical and three toxicological end points from six gene expression data sets, an unprecedented collection of diverse signatures that has permitted a wide-ranging analysis on the nature of such predictive models. A comprehensive analysis of the genes of these signatures and their nonredundant unions using ontology enrichment, biological network building and interactome connectivity analyses demonstrated the link between gene signatures and the biological basis of their predictive power. Different signatures for a given end point were more similar at the level of biological properties and transcriptional control than at the gene level. Signatures tended to be enriched in function and pathway in an end point and model-specific manner, and showed a topological bias for incoming interactions. Importantly, the level of biological similarity between different signatures for a given end point correlated positively with the accuracy of the signature predictions. These findings will aid the understanding, and application of predictive genomic signatures, and support their broader application in predictive medicine. The Pharmacogenomics Journal (2010) 10, 310-323; doi: 10.1038/tpj.2010.35 C1 [Shi, W.; Dezso, Z.; Nikolskaya, T.; Bugrim, A.; Guryanov, A.; Brennan, R. J.; Nikolsky, Y.] GeneGo Inc, St Joseph, MI 49085 USA. [Bessarabova, M.; Dosymbekov, D.; Nikolskaya, T.; Dudoladova, M.; Serebryiskaya, T.; Guryanov, A.] Russian Acad Sci, NI Vavilov Gen Genet Res Inst, Moscow, Russia. [Shah, R.] SRA Int Inc, Durham, NC USA. [Dopazo, J.] Ctr Invest Principe Felipe, Valencia, Spain. [Chen, M.; Tong, W.; Shi, L.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Deng, Y.] Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA. [Shi, T.] E China Normal Univ, Coll Life Sci, Ctr Bioinformat, Shanghai 200062, Peoples R China. [Shi, T.] E China Normal Univ, Coll Life Sci, Inst Biomed Sci, Shanghai 200062, Peoples R China. [Jurman, G.; Furlanello, C.] Fondaz Bruno Kessler, Trento, Italy. [Thomas, R. S.] Hamner Inst Hlth Sci, Durham, NC USA. [Corton, J. C.] US EPA, Div Environm Carcinogenesis, NHEERL, Durham, NC USA. RP Nikolsky, Y (reprint author), GeneGo Inc, 500 Renaissance Dr 106, St Joseph, MI 49085 USA. EM yuri@genego.com OI Thomas, Russell/0000-0002-2340-0301; Furlanello, Cesare/0000-0002-5384-3605; Dopazo, Joaquin/0000-0003-3318-120X; Jurman, Giuseppe/0000-0002-2705-5728 FU American Chemistry Council's Long-Range Research Initiative; Honeywell Inc. FX Dr Russell Thomas' research was supported by the American Chemistry Council's Long-Range Research Initiative and a contract by Honeywell Inc. All other authors declare no conflict of interest. NR 46 TC 22 Z9 25 U1 2 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X EI 1473-1150 J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD AUG PY 2010 VL 10 IS 4 BP 310 EP 323 DI 10.1038/tpj.2010.35 PG 14 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 636DT UT WOS:000280709100007 PM 20676069 ER PT J AU Miclaus, K Chierici, M Lambert, C Zhang, L Vega, S Hong, H Yin, S Furlanello, C Wolfinger, R Goodsaid, F AF Miclaus, K. Chierici, M. Lambert, C. Zhang, L. Vega, S. Hong, H. Yin, S. Furlanello, C. Wolfinger, R. Goodsaid, F. TI Variability in GWAS analysis: the impact of genotype calling algorithm inconsistencies SO PHARMACOGENOMICS JOURNAL LA English DT Article DE genotype calling algorithms; BRLMM; CRLMM; CHIAMO; batch effects; GWAS; association studies ID GENOME-WIDE ASSOCIATION AB The Genome-Wide Association Working Group (GWAWG) is part of a large-scale effort by the MicroArray Quality Consortium (MAQC) to assess the quality of genomic experiments, technologies and analyses for genome-wide association studies (GWASs). One of the aims of the working group is to assess the variability of genotype calls within and between different genotype calling algorithms using data for coronary artery disease from the Wellcome Trust Case Control Consortium (WTCCC) and the University of Ottawa Heart Institute. Our results show that the choice of genotyping algorithm (for example, Bayesian robust linear model with Mahalanobis distance classifier (BRLMM), the corrected robust linear model with maximum-likelihood-based distances (CRLMM) and CHIAMO (developed and implemented by the WTCCC)) can introduce marked variability in the results of downstream case-control association analysis for the Affymetrix 500K array. The amount of discordance between results is influenced by how samples are combined and processed through the respective genotype calling algorithm, indicating that systematic genotype errors due to computational batch effects are propagated to the list of single-nucleotide polymorphisms found to be significantly associated with the trait of interest. Further work using HapMap samples shows that inconsistencies between Affymetrix arrays and calling algorithms can lead to genotyping errors that influence downstream analysis. The Pharmacogenomics Journal (2010) 10, 324-335; doi: 10.1038/tpj.2010.46 C1 [Miclaus, K.] SAS Inst, JMP Genom, Cary, NC 27513 USA. [Chierici, M.; Furlanello, C.] Fondaz Bruno Kessler, Trento, Italy. [Lambert, C.] Golden Helix, Bozeman, MT USA. [Zhang, L.; Yin, S.; Goodsaid, F.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Vega, S.] Microsoft Corp, Hlth Solut Grp, Redmond, WA 98052 USA. [Hong, H.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Miclaus, K (reprint author), SAS Inst, JMP Genom, 100 SAS Campus Dr, Cary, NC 27513 USA. EM Kelci.Miclaus@sas.com RI Zhang, Jinny/C-4794-2012; OI Chierici, Marco/0000-0001-9791-9301; Furlanello, Cesare/0000-0002-5384-3605 NR 16 TC 9 Z9 9 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD AUG PY 2010 VL 10 IS 4 BP 324 EP 335 DI 10.1038/tpj.2010.46 PG 12 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 636DT UT WOS:000280709100008 PM 20676070 ER PT J AU Miclaus, K Wolfinger, R Vega, S Chierici, M Furlanello, C Lambert, C Hong, H Zhang, L Yin, S Goodsaid, F AF Miclaus, K. Wolfinger, R. Vega, S. Chierici, M. Furlanello, C. Lambert, C. Hong, H. Zhang, Li Yin, S. Goodsaid, F. TI Batch effects in the BRLMM genotype calling algorithm influence GWAS results for the Affymetrix 500K array SO PHARMACOGENOMICS JOURNAL LA English DT Article DE genotype calling error; BRLMM calling algorithm; WTCCC; GWAS; association studies ID GENOME-WIDE ASSOCIATION; DIFFERENTIAL BIAS; LARGE-SCALE; MICROARRAYS; PROGRESS AB The Affymetrix GeneChip Human Mapping 500K array is common for genome-wide association studies (GWASs). Recent findings highlight the importance of accurate genotype calling algorithms to reduce the inflation in Type I and Type II error rates. Differential results due to genotype calling errors can introduce severe bias in case-control association study results. Using data from the Wellcome Trust Case Control Consortium, 1991 individuals with coronary artery disease (CAD) and 1500 controls from the UK Blood Services (NBS) were genotyped on the Affymetrix 500K array. Different batch sizes and compositions were used in the Bayesian Robust Linear Model with Mahalanobis distance classifier (BRLMM) genotype calling algorithm to assess the batch effect on downstream association analysis. Results show that composition (cases and controls genotyped simultaneously or separate) and size (number of individuals processed by BRLMM at a time) can create 2-3% discordance in the results for quality control and statistical analysis and may contribute to the lack of reproducibility between GWASs. The changes in batch size are largely responsible for differential single-nucleotide polymorphism results, yet we observe evidence of an interactive effect of batch size and composition that contributes to discordant results in the list of significantly associated loci. The Pharmacogenomics Journal (2010) 10, 336-346; doi: 10.1038/tpj.2010.36 C1 [Miclaus, K.] JMP Genom, SAS Inst, Cary, NC 27513 USA. [Vega, S.] Microsoft Corp, Hlth Solut Grp, Redmond, WA 98052 USA. [Chierici, M.; Furlanello, C.] Fondaz Bruno Kessler, Trento, Italy. [Lambert, C.] Golden Helix, Bozeman, MT USA. [Hong, H.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Zhang, Li; Yin, S.; Goodsaid, F.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Miclaus, K (reprint author), JMP Genom, SAS Inst, 100 SAS Campus Dr, Cary, NC 27513 USA. EM Kelci.Miclaus@jmp.com RI Zhang, Jinny/C-4794-2012; OI Chierici, Marco/0000-0001-9791-9301; Furlanello, Cesare/0000-0002-5384-3605 NR 17 TC 6 Z9 6 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD AUG PY 2010 VL 10 IS 4 BP 336 EP 346 DI 10.1038/tpj.2010.36 PG 11 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 636DT UT WOS:000280709100009 PM 20676071 ER PT J AU Zhang, L Yin, S Miclaus, K Chierici, M Vega, S Lambert, C Hong, H Wolfinger, RD Furlanello, C Goodsaid, F AF Zhang, L. Yin, S. Miclaus, K. Chierici, M. Vega, S. Lambert, C. Hong, H. Wolfinger, R. D. Furlanello, C. Goodsaid, F. TI Assessment of variability in GWAS with CRLMM genotyping algorithm on WTCCC coronary artery disease SO PHARMACOGENOMICS JOURNAL LA English DT Article DE CRLMM; GWAS; WTCCC; CAD; robustness; accuracy ID GENOME-WIDE ASSOCIATION; CALLING ALGORITHM; MICROARRAYS; NORMALIZATION; EXPLORATION; VALIDATION; ARRAYS; TESTS AB The robustness of genome-wide association study (GWAS) results depends on the genotyping algorithms used to establish the association. This paper initiated the assessment of the impact of the Corrected Robust Linear Model with Maximum Likelihood Classification (CRLMM) genotyping quality on identifying real significant genes in a GWAS with large sample sizes. With microarray image data from the Wellcome Trust Case-Control Consortium (WTCCC), 1991 individuals with coronary artery disease (CAD) and 1500 controls, genetic associations were evaluated under various batch sizes and compositions. Experimental designs included different batch sizes of 250, 350, 500, 2000 samples with different distributions of cases and controls in each batch with either randomized or simply combined (4: 3 case-control ratios) or separate case-control samples as well as whole 3491 samples. The separate composition could create 2-3% discordance in the single nucleotide polymorphism (SNP) results for quality control/statistical analysis and might contribute to the lack of reproducibility between GWAS. CRLMM shows high genotyping accuracy and stability to batch effects. According to the genotypic and allelic tests (P<5.0 x 10(-7)), nine significant signals on chromosome 9 were found consistently in all batch sizes with combined design. Our findings are critical to optimize the reproducibility of GWAS and confirm the genetic role in the pathophysiology of CAD. The Pharmacogenomics Journal (2010) 10, 347-354; doi: 10.1038/tpj.2010.27 C1 [Zhang, L.; Yin, S.; Goodsaid, F.] US FDA, Genom Grp, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. [Miclaus, K.; Wolfinger, R. D.] SAS Inst, Cary, NC USA. [Chierici, M.; Furlanello, C.] Fondaz Bruno Kessler, Trento, Italy. [Vega, S.] Microsoft Corp, Hlth Solut Grp, Redmond, WA 98052 USA. [Lambert, C.] Golden Helix, Bozeman, MT USA. [Hong, H.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Goodsaid, F (reprint author), US FDA, Genom Grp, Off Clin Pharmacol, Ctr Drug Evaluat & Res, WO51 Rm2148 HFD 870,10903 New Hampshire, Silver Spring, MD 20903 USA. EM li.zhang@fda.hhs.gov; federico.goodsaid@fda.hhs.gov RI Zhang, Jinny/C-4794-2012; OI Furlanello, Cesare/0000-0002-5384-3605; Chierici, Marco/0000-0001-9791-9301 NR 15 TC 7 Z9 7 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD AUG PY 2010 VL 10 IS 4 BP 347 EP 354 DI 10.1038/tpj.2010.27 PG 8 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 636DT UT WOS:000280709100010 PM 20676072 ER PT J AU Hong, H Shi, L Su, Z Ge, W Jones, WD Czika, W Miclaus, K Lambert, CG Vega, SC Zhang, J Ning, B Liu, J Green, B Xu, L Fang, H Perkins, R Lin, SM Jafari, N Park, K Ahn, T Chierici, M Furlanello, C Zhang, L Wolfinger, RD Goodsaid, F Tong, W AF Hong, H. Shi, L. Su, Z. Ge, W. Jones, W. D. Czika, W. Miclaus, K. Lambert, C. G. Vega, S. C. Zhang, J. Ning, B. Liu, J. Green, B. Xu, L. Fang, H. Perkins, R. Lin, S. M. Jafari, N. Park, K. Ahn, T. Chierici, M. Furlanello, C. Zhang, L. Wolfinger, R. D. Goodsaid, F. Tong, W. TI Assessing sources of inconsistencies in genotypes and their effects on genome-wide association studies with HapMap samples SO PHARMACOGENOMICS JOURNAL LA English DT Article DE repeatability; association; genotype; calling algorithm; intensity; copy number ID POPULATION STRATIFICATION; BREAST-CANCER; SUSCEPTIBILITY VARIANT; MACULAR DEGENERATION; COLORECTAL-CANCER; CROHN-DISEASE; RISK LOCUS; SNPS; SCAN; GENE AB The discordance in results of independent genome-wide association studies (GWAS) indicates the potential for Type I and Type II errors. We assessed the repeatibility of current Affymetrix technologies that support GWAS. Reasonable reproducibility was observed for both raw intensity and the genotypes/copy number variants. We also assessed consistencies between different SNP arrays and between genotype calling algorithms. We observed that the inconsistency in genotypes was generally small at the specimen level. To further examine whether the differences from genotyping and genotype calling are possible sources of variation in GWAS results, an association analysis was applied to compare the associated SNPs. We observed that the inconsistency in genotypes not only propagated to the association analysis, but was amplified in the associated SNPs. Our studies show that inconsistencies between SNP arrays and between genotype calling algorithms are potential sources for the lack of reproducibility in GWAS results. The Pharmacogenomics Journal (2010) 10, 364-374; doi: 10.1038/tpj.2010.24; published online 6 April 2010 C1 [Hong, H.; Shi, L.; Su, Z.; Ge, W.; Xu, L.; Perkins, R.; Tong, W.] US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Jones, W. D.] Express Anal, Suite, NC USA. [Czika, W.; Miclaus, K.; Wolfinger, R. D.] SAS Inst, Cary, NC USA. [Lambert, C. G.] Golden Helix, Bozeman, MT USA. [Vega, S. C.] Microsoft Corp, Hlth Solut Grp, Seattle, WA USA. [Zhang, J.] Syst Analyt, Waltham, MA USA. [Ning, B.; Liu, J.; Green, B.] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR USA. [Fang, H.] US FDA, Z Tech Corp, Natl Ctr Toxicol Res, Jefferson, AR USA. [Lin, S. M.] Northwestern Univ, Biomed Informat Ctr, Chicago, IL 60611 USA. [Jafari, N.] Northwestern Univ, Ctr Genet Med, Chicago, IL 60611 USA. [Park, K.; Ahn, T.] Samsung Adv Inst Technol, Yongin, Gyeonggi Do, South Korea. [Chierici, M.; Furlanello, C.] Fondaz Bruno Kessler, Trento, Italy. [Zhang, L.; Goodsaid, F.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Hong, H (reprint author), US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM huixiao.hong@fda.hhs.gov RI Zhang, Jinny/C-4794-2012; OI Chierici, Marco/0000-0001-9791-9301; Furlanello, Cesare/0000-0002-5384-3605 FU NCTR-US FDA FX HH thanks Dr Williams Slikker for his support on this research project. LX thanks NCTR-US FDA for providing the ORISE postdoctoral research fellowship to participate in the project. NR 46 TC 11 Z9 13 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD AUG PY 2010 VL 10 IS 4 BP 364 EP 374 DI 10.1038/tpj.2010.24 PG 11 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 636DT UT WOS:000280709100012 PM 20368714 ER PT J AU Dowling, TC Matzke, GR Murphy, JE Burckart, GJ AF Dowling, Thomas C. Matzke, Gary R. Murphy, John E. Burckart, Gilbert J. TI Evaluation of Renal Drug Dosing: Prescribing Information and Clinical Pharmacist Approaches SO PHARMACOTHERAPY LA English DT Article DE new molecular entity; NME; drug dosing; drug safety; glomerular filtration rate; GFR; kidney function ID GLOMERULAR-FILTRATION-RATE; COCKCROFT-GAULT EQUATIONS; CREATININE CLEARANCE; SERUM CREATININE; KIDNEY-FUNCTION; OBESE-PATIENTS; DISEASE; DIET; DOSAGE; RECOMMENDATIONS AB Study Objective. To characterize renal function parameters reported in United States Food and Drug Administration-approved prescribing information (package inserts), to compare dosage recommendations for patients with impaired renal function between prescribing information and tertiary drug dosing references, and to evaluate renal function quantification methods most commonly used by clinical pharmacists to develop dosage regimens. Design. Retrospective analysis and Web-based survey. Data Sources. Prescribing information for all new molecular entities (NMEs) approved from 1998-2007 in which dosing recommendations were proposed for patients with impaired renal function, drug monographs from four tertiary drug dosing references (Micromedex, Lexi-Comp, Epocrates Rx, and American Hospital Formulary Service [AHFS] Drug Information) for all identified NMEs, and a Web-based survey of 204 nephrology and critical care pharmacy practitioners. Measurements and Main Results. A total of 44 NMEs included renal dosing recommendations in their prescribing information. For all 44 NMEs, prescribing information was reviewed to determine methods to quantify renal function, units of measure reported, and use of chronic kidney disease terminology. The most common index of renal function was creatinine clearance; the Cockcroft-Gault equation was specified in the prescribing information of 11 NMEs. Standardization for body weight was inconsistent, with prescribing information for four NMEs reporting renal function in ml/minute/1.73 m(2). The prescribing information or tertiary sources did not mention use of estimated glomerular filtration rate (eGFR) or the Modification of Diet in Renal Disease Study (MDRD) equation. Epocrates Rx provided the most abbreviated renal dosing information, whereas AHFS Drug Information was the most comprehensive, and Lexi-Comp includes a renal function calculator. Nearly all (86%) clinical pharmacists indicated that automated eGFR is reported at their institutions, although they do not use these predictions for dosing in patients with impaired renal function, and their approaches to renal function estimation varied widely. Conclusion. Reporting of renal function methods and dosing recommendations for patients with impaired renal function requires standardization in order to ensure optimal dosing. Pharmacy clinicians do not substitute eGFR in place of creatinine clearance for renal dosing, which is consistent with current prescribing information. Studies are needed that will evaluate the validity of using eGFR to predict drug clearance and thereby generate dosage recommendations. C1 [Dowling, Thomas C.] Univ Maryland, Sch Pharm, Dept Pharm Practice & Sci, Baltimore, MD 21201 USA. [Matzke, Gary R.] Virginia Commonwealth Univ, Sch Pharm, Richmond, VA USA. [Matzke, Gary R.] Virginia Commonwealth Univ, Sch Med, Richmond, VA USA. [Murphy, John E.] Univ Arizona, Coll Pharm, Dept Pharm Practice & Sci, Tucson, AZ 85721 USA. [Murphy, John E.] Univ Arizona, Coll Med, Dept Pharm Practice & Sci, Tucson, AZ USA. [Burckart, Gilbert J.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Dowling, TC (reprint author), Univ Maryland, Sch Pharm, Dept Pharm Practice & Sci, 100 N Penn St,AHB Room 540, Baltimore, MD 21201 USA. EM tdowling@rx.umaryland.edu RI Dowling, Thomas/D-2147-2013 OI Dowling, Thomas/0000-0003-3214-9283 NR 57 TC 28 Z9 28 U1 0 U2 5 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD AUG PY 2010 VL 30 IS 8 BP 776 EP 786 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 632QA UT WOS:000280439300005 PM 20653353 ER PT J AU Penzak, SR Robertson, SM Hunt, JD Chairez, C Malati, CY Alfaro, RM Stevenson, JM Kovacs, JA AF Penzak, Scott R. Robertson, Sarah M. Hunt, Jennifer D. Chairez, Cheryl Malati, Christine Y. Alfaro, Raul M. Stevenson, James M. Kovacs, Joseph A. TI Echinacea purpurea Significantly Induces Cytochrome P450 3A Activity but Does Not Alter Lopinavir-Ritonavir Exposure in Healthy Subjects SO PHARMACOTHERAPY LA English DT Article DE human immunodeficiency virus; HIV; protease inhibitors; lopinavir; ritonavir; Echinacea purpurea; herb; cytochrome P450; CYP; P-glycoprotein; P-gp; drug interaction ID HIV-INFECTED PATIENTS; ST-JOHNS WORT; DRUG-INTERACTIONS; GINKGO-BILOBA; IN-VIVO; PHARMACOKINETICS; COMPLEMENTARY; LOPINAVIR/RITONAVIR; SAQUINAVIR; INDINAVIR AB Study Objective. To determine the influence of Echinacea purpurea on the pharmacokinetics of lopinavir-ritonavir and on cytochrome P450 (CYP) 3A and P-glycoprotein activity by using the probe substrates midazolam and fexofenadine, respectively. Design. Open-label, single-sequence pharmacokinetic study. Setting. Outpatient clinic in a federal government research center. Subjects. Thirteen healthy volunteers (eight men, five women). Intervention. Subjects received lopinavir 400 mg-ritonavir 100 mg twice/day with meals for 29.5 days. On day 16, subjects received E. purpurea 500 mg 3 times/day for 28 days: 14 days in combination with lopinavir-ritonavir and 14 days of E. purpurea alone. In order to assess CYP3A and P-glycoprotein activity subjects received single oral doses of midazolam 8 mg and fexofenadine 120 mg, respectively, before and after the 28 days of E. purpurea. Measurements and Main Results. On days 15 and 30 of lopinavir-ritonavir administration (before and after E. puipurea administration, respectively), serial blood samples were collected over 12 hours to determine lopinavir and ritonavir concentrations and subsequent pharmacokinetic parameters by using noncompartmental methods. Neither lopinavir nor ritonavir pharmacokinetics were significantly altered by 14 days of E. purpurea coadministration. The post-echinacea:pre-echinacea geometric mean ratios (GMRs) for lopinavir area under the concentration-time curve (AUC) from 0-12 hours and for maximum concentration were 0.96 (90% confidence interval [CI] 0.83-1.10, p=0.82) and 1.00 (90% CI 0.88-1.12, p=0.72), respectively. Conversely, GMRs for midazolam AUC from time zero extrapolated to infinity and oral clearance were 0.73 (90% CI 0.61-0.85, p=0.008) and 1.37 (90% CI 1.10-1.63, p=0.02), respectively. Fexofenadine pharmacokinetics did not significantly differ before and after E. purpurea administration (p>0.05). Conclusion. Echinacea purpurea induced CYP3A activity but did not alter lopinavir concentrations, most likely due to the presence of the potent CYP3A inhibitor, ritonavir. Echinacea purpurea is unlikely to alter the pharmacokinetics of ritonavir-boosted protease inhibitors but may cause modest decreases in plasma concentrations of other CYP3A substrates. C1 [Penzak, Scott R.; Malati, Christine Y.; Alfaro, Raul M.] NIH, Clin Res Ctr, Dept Pharm, Clin Pharmacokinet Res Lab, Bethesda, MD 20892 USA. [Hunt, Jennifer D.; Kovacs, Joseph A.] NIH, Dept Crit Care Med, Clin Res Ctr, Bethesda, MD 20892 USA. [Chairez, Cheryl] NIAID, NIH, Bethesda, MD 20892 USA. [Robertson, Sarah M.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Dept Hlth & Human Serv, Silver Spring, MD USA. [Stevenson, James M.] Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. RP Penzak, SR (reprint author), NIH, Clin Res Ctr, Dept Pharm, Clin Pharmacokinet Res Lab, Bldg 10,1N 257, Bethesda, MD 20892 USA. EM spenzak@mail.cc.nih.gov FU National Institutes of Health Clinical Center; National Institute of Allergy and Infectious Diseases FX Supported by the Intramural Research Programs of the National Institutes of Health Clinical Center and the National Institute of Allergy and Infectious Diseases. NR 28 TC 28 Z9 29 U1 0 U2 3 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD AUG PY 2010 VL 30 IS 8 BP 797 EP 805 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 632QA UT WOS:000280439300007 PM 20653355 ER PT J AU Shin, YJ Tata, DB Waynant, RE Gehlbach, PL Chuck, RS AF Shin, Young Joo Tata, Darrell B. Waynant, Ronald E. Gehlbach, Peter L. Chuck, Roy S. TI Fluorometric Determination of the Redox State and Distribution of Mitochondria in Human Malignant Glioblastoma Cells Grown on Different Culturing Substrates SO PHOTOMEDICINE AND LASER SURGERY LA English DT Article ID FLUORESCENCE SPECTROSCOPY; FIBROBLAST PROLIFERATION; EPITHELIAL-CELLS; CANCER-THERAPY; FREE-RADICALS; FLAVOPROTEIN; NAD(P)H; INHIBITION; MICROSCOPY; MECHANISM AB Objectives: To evaluate the redox state and the spatial distribution of mitochondria in malignant human brain cancer cells grown on different substrates. Methods: Cellular autofluorescence images were obtained through an inverted fluorescence microscope and the redox fluorometric ratio was evaluated (after the subtraction of background) as the net fluorescence signal through the DAPI filter divided by the net fluorescence signal through the FITC filter. Spatial mitochondria distribution patterns were evaluated by division of the cell area at the midpoint between the nuclear and cell membranes. The average fluorescence in the central area (CF) was divided by the average fluorescence from the peripheral area (PF). The CF/PF ratios were compared between cells cultured on either poly-D-lysine or collagen I substrates. Results: Glioblastoma cells seeded on the collagen-coated plates were observed to proliferate similar to 33-50% faster than the cells seeded on the poly-D-lysine-coated plates. Consistent with the proliferation findings, the redox ratios were lower for the cells seeded on the collagen-coated plates compared with poly-D-lysine. However, cell size and the percentage of cells with perinuclear mitochondrial distribution were not observed to be different in the cells seeded on the two surfaces. Conclusions: Redox ratio computation by using redox fluorometry is a useful predictor of cellular proliferation. C1 [Chuck, Roy S.] Yeshiva Univ, Albert Einstein Coll Med, Bronx, NY 10467 USA. [Chuck, Roy S.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Shin, Young Joo] Hallym Univ, Dept Ophthalmol, Gangnam Sacred Heart Hosp, Seoul, South Korea. [Tata, Darrell B.; Waynant, Ronald E.] US FDA, OSEL, Div Phys, Silver Spring, MD USA. [Gehlbach, Peter L.] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA. RP Chuck, RS (reprint author), Yeshiva Univ, Albert Einstein Coll Med, 3332 Rochambeau Ave,Centennial Bldg, Bronx, NY 10467 USA. EM rchuck@montefiore.org NR 27 TC 0 Z9 0 U1 1 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1549-5418 J9 PHOTOMED LASER SURG JI Photomed. Laser Surg. PD AUG PY 2010 VL 28 SU 1 BP S105 EP S110 DI 10.1089/pho.2009.2600 PG 6 WC Surgery SC Surgery GA 635PE UT WOS:000280667300011 PM 20666574 ER PT J AU Thomas, M George, NI Saini, UT Patterson, TA Hanig, JP Bowyer, JF AF Thomas, Monzy George, Nysia I. Saini, Upasana T. Patterson, Tucker A. Hanig, Joseph P. Bowyer, John F. TI Endoplasmic Reticulum Stress Responses Differ in Meninges and Associated Vasculature, Striatum, and Parietal Cortex After a Neurotoxic Amphetamine Exposure SO SYNAPSE LA English DT Article DE amphetamines; vasculature; hyperthermia; meninges; blood-brain barrier; gene expression; endoplasmic reticulum stress; unfolded protein response ID UNFOLDED PROTEIN RESPONSE; BLOOD-BRAIN-BARRIER; NF-KAPPA-B; GLUTAMINE ANDROGEN RECEPTOR; CELL-DEATH; ER STRESS; METHAMPHETAMINE NEUROTOXICITY; SUBSTITUTED AMPHETAMINES; INTRACEREBRAL HEMORRHAGE; NEURONAL DEGENERATION AB Amphetamine (AMPH) is used to treat attention deficit and hyperactivity disorders, but it can produce neurotoxicity and adverse vascular effects at high doses. The endoplasmic reticulum (ER) stress response (ERSR) entails the unfolded protein response, which helps to avoid or minimize ER dysfunction. ERSR is often associated with toxicities resulting from the accumulation of unfolded or misfolded proteins and has been associated with methamphetamine toxicity in the striatum. The present study evaluates the effect of AMPH on several ERSR elements in meninges and associated vasculature (MAV), parietal cortex, and striatum Adult, male Sprague Dawley rats were exposed to saline, environmentally induced hyperthermia (EIH) or four consecutive doses of AMPH that produce hyperthermia Expression changes (mRNA and protein levels) of key ERSR-related genes in MAV, striatu n, and parietal cortex at 3 h or 1 day postdosing were monitored AMPH increased the expression of some ERSR-related genes in all tissues Atf4 (activating transcription factor 4, an indicator of Perk pathway activation), Hspa5/Grp78 (Glucose regulated protein 78, master regulator of ERSR), Pdia4 (protein disulfide isomerase, protein-folding enzyme), and Nfkb1. (nuclear factor of kappa b, ERSR sensor) mRNA increased significantly in MAV and parietal cortex 3 h after AMPH. In striatum, Atf4 and Hspa5/Grp78 mRNA significantly increased 3 h after AMPH, but Pdia4 and Nfkb11 did not Thus, AMPH caused a robust activation of the Perk pathway in all tissues, but significant Ire1 pathway activation occurred only after AMPH treatment in the parietal cortex and striatum. Ddit3/Chop, a downstream effector of the ERSR pathway related to the neurotoxicity, was only increased in striatum aid parietal cortex Conversely. Pdia4, an enzyme protective in the ERSR, was only increased in MAV. The overall ERSR manifestation varied significantly between MAV, striatum, and parietal cortex after a neurotoxic exposure to AMPH Synapse 64:579 593, 2010. Published 2010 Wiley-Liss Inc C1 [Thomas, Monzy; Saini, Upasana T.; Patterson, Tucker A.; Bowyer, John F.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [George, Nysia I.] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Hanig, Joseph P.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Bowyer, JF (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, HFT 132, Jefferson, AR 72079 USA. NR 97 TC 8 Z9 9 U1 4 U2 10 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD AUG PY 2010 VL 64 IS 8 BP 579 EP 593 DI 10.1002/syn.20763 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 621AI UT WOS:000279545100001 PM 20340164 ER PT J AU Weaver, JL Zhang, J Knapton, A Miller, T Espandiari, P Smith, R Gu, YZ Snyder, RD AF Weaver, James L. Zhang, Jun Knapton, Alan Miller, Terry Espandiari, Parvaneh Smith, Roger Gu, Yi-Zhong Snyder, Ronald D. TI Early Events in Vascular Injury in the Rat Induced by the Phosphodiesterase IV Inhibitor SCH 351591 SO TOXICOLOGIC PATHOLOGY LA English DT Article DE vascular injury; phosphodiesterase inhibitor; biomarkers ID SPRAGUE-DAWLEY RATS; NITRIC-OXIDE; FENOLDOPAM MESYLATE; III INHIBITORS; MAST-CELLS; TOXICITY; RECEPTOR; LESIONS; HISTAMINE; THEOPHYLLINE AB Treatment with drugs from multiple classes induces vascular injury with medial necrosis, hemorrhage, endothelial damage, and inflammation. Previous research has suggested early events might be occurring well in advance of the full lesions that appear forty-eight to seventy-two hours after dosing with SCH 351591, a PDE IV inhibitor. This study was performed to study early events in detail. Rats were dosed with 20 mg/kg of drug by gavage and sacrificed at times between fifteen and 240 minutes after dosing. Tissues were collected for histopathological analysis and gene expression studies. Serum was collected for biomarker analysis. The data from biomarker analysis showed a three-part response with an early phase that was maximal at fifteen to thirty minutes, a second phase from forty-five to 180 minutes, and the third phase that was starting to rise at four hours. The first phase included increases in lymphocytes, serum histamine, and serum nitrite. The second phase shows continued elevation of serum nitrite. The third phase was marked by an increase in serum GRO/CINC-1. At fifteen minutes, histopathology showed activation of mast cells, but not degranulation. Increases in endothelial activation and perivascular inflammatory cells were first apparent at thirty minutes and increased through 240 minutes. C1 [Weaver, James L.; Zhang, Jun; Knapton, Alan; Miller, Terry; Espandiari, Parvaneh] US FDA, DAPR, CDER, Silver Spring, MD 20093 USA. [Smith, Roger; Gu, Yi-Zhong; Snyder, Ronald D.] Schering Plough Res Inst, Summit, NJ USA. RP Weaver, JL (reprint author), US FDA, DAPR, CDER, 10903 New Hampshire Ave, Silver Spring, MD 20093 USA. EM James.Weaver@fda.hhs.gov NR 33 TC 11 Z9 11 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 AUG PY 2010 VL 38 IS 5 BP 738 EP 744 DI 10.1177/0192623310374331 PG 7 WC Pathology; Toxicology SC Pathology; Toxicology GA 707UT UT WOS:000286314800007 PM 20585143 ER PT J AU Botts, S Ennulat, D Francke-Carroll, S Graham, M Maronpot, RR Mohutsky, M AF Botts, Suzanne Ennulat, Daniela Francke-Carroll, Sabine Graham, Mark Maronpot, Robert R. Mohutsky, Michael CA Initiative Working Grp Chairs TI Introduction to Hepatic Drug Metabolizing Enzyme Induction in Drug Safety Evaluation Studies SO TOXICOLOGIC PATHOLOGY LA English DT Article DE hepatic drug metabolizing enzyme induction ID NUCLEAR RECEPTORS; GENES; MONKEY; MOUSE; CAR; RAT; PXR; DOG AB The following three articles represent the output of a combined effort initiated by the Scientific Regulatory Policy Committee of the Society of Toxicologic Pathology to provide a unified review of current scientific practices and relevant literature and provide suggestions regarding the recognition, interpretation, and risk assessment of hepatic drug metabolizing enzyme (DME) induction studies. The core objective was to provide a review that the scientific community including pathologists, regulatory scientists, toxicologists, investigative scientists, and others would find valuable for managing, designing, and interpreting toxicity studies supporting regulatory filings. Three working groups composed of scientists from industry, academia, and regulatory agencies were convened to review the available literature on important aspects of the interpretation and risk assessment of hepatic microsomal DME enzyme induction in three publications. The three reviews are as follows: "Effects of Hepatic Drug Metabolizing Enzyme Induction on Clinical Pathology Parameters in Animals and Man," Toxicol Pathol "Hepatic Drug Metabolizing Enzyme Induction: Microscopic and Ultrastructural Appearance," Toxicol Pathol "Hepatic Drug Metabolizing Enzyme Induction and Implications for Preclinical and Clinical Risk Assessment," Toxicol Pathol The purpose of this introduction is not to summarize the articles but rather to frame the series and to provide a common mechanistic introduction. C1 [Botts, Suzanne] Hoffmann La Roche Inc, Toxicol & Pathol, SRPC Initiat, Nutley, NJ 07110 USA. [Ennulat, Daniela] GlaxoSmithKline Inc, Clin Pathol Working Grp, King Of Prussia, PA USA. [Francke-Carroll, Sabine] US FDA, CFSAN, Risk Assessment Working Grp, College Pk, MD USA. [Maronpot, Robert R.] Maronpot Consulting LLC, Anat & Ultrastruct Pathol Working Grp, Raleigh, NC USA. RP Botts, S (reprint author), Hoffmann La Roche Inc, Toxicol & Pathol, SRPC Initiat, 340 Kingsland St, Nutley, NJ 07110 USA. EM suzanne.botts@roche.com NR 16 TC 3 Z9 3 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 EI 1533-1601 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD AUG PY 2010 VL 38 IS 5 BP 796 EP 798 DI 10.1177/0192623310374330 PG 3 WC Pathology; Toxicology SC Pathology; Toxicology GA 707UT UT WOS:000286314800012 PM 20622194 ER PT J AU Mohutsky, MA Romeike, A Meador, V Lee, WM Fowler, J Francke-Carroll, S AF Mohutsky, Michael A. Romeike, Annette Meador, Vince Lee, William M. Fowler, John Francke-Carroll, Sabine TI Hepatic Drug-Metabolizing Enzyme Induction and Implications for Preclinical and Clinical Risk Assessment SO TOXICOLOGIC PATHOLOGY LA English DT Article DE metabolism; induction; hepatic; drug-metabolizing enzymes; enzyme induction; risk assessment ID PREGNANE-X-RECEPTOR; CONSTITUTIVE ANDROSTANE RECEPTOR; HUMAN CYTOCHROME-P450 ENZYMES; BIOACTIVATION IN-VITRO; REPORTER GENE ASSAY; HUMAN HEPATOCYTES; HUMAN-LIVER; CYP3A4 INDUCTION; CARBON-TETRACHLORIDE; ANTIANGIOGENIC AGENT AB Hepatic drug metabolizing enzyme (DME) induction complicates the development of new drugs owing to altered efficacy of concomitant treatments, reduction in exposure resulting from autoinduction, and potential generation of toxic metabolites. Risk assessment of DME induction during clinical evaluation is confounded by several uncertainties pertaining to hazard identification and dose response analysis. Hepatic DME induction rarely leads to clinical evidence of altered metabolism and toxicity in the patient, which typically occur only if the DME induction is relatively severe. High drug doses are associated with a greater likelihood of hepatic DME induction and downstream effects; therefore, drugs of low potency requiring higher dosing tend to lead to a greater risk of drug-drug interactions. Vigilance in clinical trials for increased or diminished drug effect and, specifically, pharmacokinetic studies in the presence of other drugs and concomitant diseases are necessary for a drug risk assessment profile. Efforts to remove hepatic DME-inducing drugs from development can be facilitated with current in vitro and in vivo assessments and will improve with the development of newer technologies. A carefully tailored case-by-case approach will lead to the development of efficacious drugs with an acceptable risk/benefit profile available to patients. C1 [Francke-Carroll, Sabine] US FDA, CFSAN, College Pk, MD 20740 USA. [Mohutsky, Michael A.] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. [Romeike, Annette] IPSAR Consultancy, St Cyr Sur Loire, France. [Meador, Vince] Covance Inc, Madison, WI USA. [Lee, William M.] UT SW Med Ctr Dallas, Dept Internal Med, Dallas, TX USA. RP Francke-Carroll, S (reprint author), US FDA, CFSAN, 5100 Paint Branch Pkwy,HFS-205, College Pk, MD 20740 USA. EM sabine.francke@fda.hhs.gov NR 105 TC 11 Z9 11 U1 0 U2 2 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 AUG PY 2010 VL 38 IS 5 BP 799 EP 809 DI 10.1177/0192623310375099 PG 11 WC Pathology; Toxicology SC Pathology; Toxicology GA 707UT UT WOS:000286314800013 PM 20616377 ER PT J AU Yu, MYW Alter, HJ Virata-Theimer, MLA Geng, YS Ma, L Schechterly, CA Colvin, CA Luban, NLC AF Yu, Mei-ying W. Alter, Harvey J. Virata-Theimer, Maria Luisa A. Geng, Yansheng Ma, Li Schechterly, Cathy A. Colvin, Camilla A. Luban, Naomi L. C. TI Parvovirus B19 infection transmitted by transfusion of red blood cells confirmed by molecular analysis of linked donor and recipient samples SO TRANSFUSION LA English DT Article ID FACTOR-VIII CONCENTRATE; INTERNATIONAL STANDARD; DNA; TRANSMISSION; PLASMA; PREVALENCE; PATIENT; IDENTIFICATION; FRACTIONATION; ORGANIZATION AB BACKGROUND: Extremely high viremic levels of parvovirus B19 (B19V) can be found in acutely infected, but asymptomatic donors. However, reports of transmission by single-donor blood components are rare. In this prospective study, paired donor-recipient samples were used to investigate the transfusion risk. STUDY DESIGN AND METHODS: Posttransfusion plasma or blood samples from recipients were tested for B19V DNA by polymerase chain reaction, generally at 4 and 8 weeks, and for anti-B19V immunoglobulin (Ig)G by enzyme immunoassay, at 12 and 24 weeks. To rule out infection unrelated to transfusion, pretransfusion samples and linked donor's samples for each B19V DNA positive recipient were assayed for B19V DNA and anti-B19V IgG and IgM. To confirm transmission, sequencing and phylogenetic analysis were performed. RESULTS: A total of 14 of 869 (1.6%) recipients were B19V DNA positive, but only 1 of 869 (0.12%; 95% confidence interval, 0.0029%-0.6409%) was negative for B19V DNA and anti-B19V IgG before transfusion and seroconverted posttransfusion. This newly infected patient received 5 x 10(10) IU B19V DNA in one red blood cell (RBC) unit from an acutely infected anti-B19V negative donor in addition to RBCs from three other donors that cumulatively contained 1320 IU of anti-B19V IgG. DNA sequencing and phylogenetic analysis showed that sequences from the linked donor and recipient were identical (Genotype 1), thus establishing transfusion transmission. CONCLUSIONS: The 0.12% transmission rate documented here, although low, could nonetheless result in hundreds or thousands of infections annually in the United States based on calculated confidence limits. Although most would be asymptomatic, some could have severe clinical outcomes, especially in neonates and those with immunocompromised or hemolytic states. C1 [Yu, Mei-ying W.] US FDA, Ctr Biol Evaluat & Res, Div Hematol, HFM 345, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. George Washington Univ, Sch Med & Hlth Sci, Dept Pediat, Div Lab Med,Childrens Natl Med Ctr, Washington, DC 20052 USA. RP Yu, MYW (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, HFM 345, Room 303,29 Lincoln Dr, Bethesda, MD 20892 USA. EM mei-ying.yu@fda.hhs.gov FU National Institutes of Health (NIH) [R01 HL67229]; NIH Clinical Center; CBER, FDA FX The study was funded in part by a grant from the NIH and in part by the Intramural Research Program of the NIH Clinical Center and that of CBER, FDA.; The study was supported in part by a grant (R01 HL67229) from the National Institutes of Health (NLCL and HJA). YG and LM were supported by the Research Participation Program at the CBER administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the FDA. We thank Dr J.S. Finlayson for critical review of the manuscript, Ms Hailing Yan for performing some of the anti-B19V assays, and Dr Jessica Kim for statistical consultation, all of them from CBER/FDA. NR 51 TC 19 Z9 22 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD AUG PY 2010 VL 50 IS 8 BP 1712 EP 1721 DI 10.1111/j.1537-2995.2010.02591.x PG 10 WC Hematology SC Hematology GA 634PZ UT WOS:000280596700013 PM 20158689 ER PT J AU Phillips, RA Stratmeyer, ME Harris, GR AF Phillips, Robert A. Stratmeyer, Mel E. Harris, Gerald R. TI SAFETY AND US REGULATORY CONSIDERATIONS IN THE NONCLINICAL USE OF MEDICAL ULTRASOUND DEVICES SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Review DE Fetal keepsake videos; Over-the-counter (OTC) devices; Low intensity biologic effects ID INTENSITY PULSED ULTRASOUND; DIAGNOSTIC ULTRASOUND; ACCELERATION; CELLS AB Ultrasound imaging has been used for medical purposes for over 50 years and has an excellent safety record. Ultrasonic fetal scanning is generally considered safe and is properly used when medical information on a pregnancy is needed. However, ultrasound energy delivered to the fetus cannot be regarded as completely innocuous. Even though there are no demonstrated risks from ultrasound imaging, it can produce effects on the body. Laboratory studies have demonstrated that diagnostic levels of ultrasound can produce physical effects in tissue, such as mechanical vibrations, rise in temperature and cavitation. A number of in vitro and in vivo ( animal and human) biologic effects have been reported following exposure to diagnostic ultrasound devices and low intensity ultrasound used for therapeutic purposes. Most public health experts, clinicians and industry agree that exposure of the fetus to ultrasound for nonmedical purposes should be avoided. The U. S. Food and Drug Administration (FDA) supports this position. (E-mail: gerald.harris@fda.hhs.gov) Published by Elsevier Inc. on behalf of World Federation for Ultrasound in Medicine & Biology. C1 [Phillips, Robert A.; Stratmeyer, Mel E.; Harris, Gerald R.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Harris, GR (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Room WO62-2104, Silver Spring, MD 20993 USA. EM gerald.harris@fda.hhs.gov NR 19 TC 4 Z9 4 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD AUG PY 2010 VL 36 IS 8 BP 1224 EP 1228 DI 10.1016/j.ultrasmedbio.2010.03.020 PG 5 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 643VR UT WOS:000281328200004 PM 20447750 ER PT J AU Ali, SF Bondy, SC AF Ali, Syed F. Bondy, S. C. TI Red wine but not ethanol at low doses can protect against the toxicity of methamphetamine SO BRAIN RESEARCH LA English DT Article DE Methamphetamine; Parkinson's disease; Dopamineric systems; Red wine; Striatum; Neurotoxicity ID INDUCED OXIDATIVE STRESS; DOPAMINERGIC-NEURONS; FRENCH PARADOX; RAT-LIVER; RESVERATROL; NEUROTOXICITY; MICE; POLYPHENOL; DEPENDENCE; DISEASE AB The goal of this study was twofold (a) to search for possible interactive effects between two common drugs of abuse, ethanol and methamphetamine b) To inquire whether any effects of ethanol could be replicated using an equivalent amount of ethanol in the form of red wine Adult male C57/6 N mice received 2% ethanol for 8 weeks in drinking water or red wine diluted to yield the same ethanol content On the 9th week animals received multiple injections of methamphetamine (4 x 10 mg/kg, ip, every 2 h) They were then sacrificed 72 h after treatment Methamphetamine produced a significant depletion of dopamine and DOPAC in the striatum Treatment with both ethanol and methamphetamine led to a reduction of striatal dopamine and DOPAC that were both non-significantly greater than that observed with methamphetamine alone Alcohol alone produced no changes in the striatal content of dopamine or its metabolite, DOPAC These data suggest that low doses of alcohol potentiate methamphetamine-induced neurotoxicity in mice and that this combination may be especially detrimental to the brain However, an equivalent dose of ethanol in the form of red wine actually partially protected against methamphetamine-induced depletion of dopamine and DOPAC in red wine treated mice. This implies the presence of other agents in red wine, which may mitigate the toxicity of methamphetamine (C) 2010 Elsevier B V All rights reserved C1 [Bondy, S. C.] Univ Calif Irvine, Dept Med, Div Occupat Med, Environm Toxicol Program, Irvine, CA 92697 USA. [Ali, Syed F.] Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Bondy, SC (reprint author), Univ Calif Irvine, Dept Med, Div Occupat Med, Environm Toxicol Program, Irvine, CA 92697 USA. FU National Institutes of Health [AG 17694] FX This work was supported in part by a grant from the National Institutes of Health (AG 17694) to SCE NR 23 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 30 PY 2010 VL 1346 BP 247 EP 250 DI 10.1016/j.brainres.2010.05.058 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 636PB UT WOS:000280749200025 PM 20510887 ER PT J AU Graham, DJ Ouellet-Hellstrom, R MaCurdy, TE Ali, F Sholley, C Worrall, C Kelman, JA AF Graham, David J. Ouellet-Hellstrom, Rita MaCurdy, Thomas E. Ali, Farzana Sholley, Christopher Worrall, Christopher Kelman, Jeffrey A. TI Risk of Acute Myocardial Infarction, Stroke, Heart Failure, and Death in Elderly Medicare Patients Treated With Rosiglitazone or Pioglitazone SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID POSITIVE PREDICTIVE-VALUE; CARDIOVASCULAR OUTCOMES; ADMINISTRATIVE DATA; CODING ACCURACY; UNITED-STATES; DATABASE; DISEASE; EVENTS; COHORT; THIAZOLIDINEDIONES AB Context Studies have suggested that the use of rosiglitazone may be associated with an increased risk of serious cardiovascular events compared with other treatments for type 2 diabetes. Objective To determine if the risk of serious cardiovascular harm is increased by rosiglitazone compared with pioglitazone, the other thiazolidinedione marketed in the United States. Design, Setting, and Patients Nationwide, observational, retrospective, inception cohort of 227 571 Medicare beneficiaries aged 65 years or older (mean age, 74.4 years) who initiated treatment with rosiglitazone or pioglitazone through a Medicare Part D prescription drug plan from July 2006-June 2009 and who underwent follow-up for up to 3 years after thiazolidinedione initiation. Main Outcome Measures Individual end points of acute myocardial infarction (AMI), stroke, heart failure, and all-cause mortality (death), and composite end point of AMI, stroke, heart failure, or death, assessed using incidence rates by thiazolidinedione, attributable risk, number needed to harm, Kaplan-Meier plots of time to event, and Cox proportional hazard ratios for time to event, adjusted for potential confounding factors, with pioglitazone as reference. Results A total of 8667 end points were observed during the study period. The adjusted hazard ratio for rosiglitazone compared with pioglitazone was 1.06 (95% confidence interval [CI], 0.96-1.18) for AMI; 1.27 (95% CI, 1.12-1.45) for stroke; 1.25 (95% CI, 1.16-1.34) for heart failure; 1.14 (95% CI, 1.05-1.24) for death; and 1.18 (95% CI, 1.12-1.23) for the composite of AMI, stroke, heart failure, or death. The attributable risk for this composite end point was 1.68 (95% CI, 1.27-2.08) excess events per 100 person-years of treatment with rosiglitazone compared with pioglitazone. The corresponding number needed to harm was 60 (95% CI, 48-79) treated for 1 year. Conclusion Compared with prescription of pioglitazone, prescription of rosiglitazone was associated with an increased risk of stroke, heart failure, and all-cause mortality and an increased risk of the composite of AMI, stroke, heart failure, or all-cause mortality in patients 65 years or older. JAMA. 2010;304(4):411-418 www.jama.com C1 [Graham, David J.; Ouellet-Hellstrom, Rita] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [MaCurdy, Thomas E.] Stanford Univ, Stanford, CA 94305 USA. [MaCurdy, Thomas E.; Ali, Farzana; Sholley, Christopher] Acumen LLC, Burlingame, CA USA. [Worrall, Christopher; Kelman, Jeffrey A.] Ctr Medicare Serv, Washington, DC USA. [Worrall, Christopher; Kelman, Jeffrey A.] Ctr Medicaid Serv, Washington, DC USA. RP Graham, DJ (reprint author), US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Room 4314, Silver Spring, MD 20993 USA. EM david.graham1@fda.hhs.gov FU Office of the Assistant Secretary for Planning and Evaluation (ASPE); Centers for Medicare & Medicaid Services (CMS); US Food and Drug Administration (FDA); Office of the Assistant Secretary for Planning and Evaluation in the Department of Health and Human Services FX This study was funded by the Office of the Assistant Secretary for Planning and Evaluation (ASPE), the Centers for Medicare & Medicaid Services (CMS), and the US Food and Drug Administration (FDA).; We thank the Office of the Assistant Secretary for Planning and Evaluation in the Department of Health and Human Services for scientific contributions and financial support of this study and the SafeRx Project. We also extend special thanks to Mark Levenson, PhD, and Stephine Keeton, PhD (both with the FDA Office of Biostatistics), for providing statistical advice and to Pallavi Mukherji, MSc, Richard Domurat, BS, Jonathan Gibbs, BA, and Konrad Turski, MSc ( all with Acumen LLC), for assistance with programming and data analysis. These individuals are salaried employees of their respective organizations and received no additional compensation related to their contributions to this study. NR 39 TC 271 Z9 286 U1 0 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 28 PY 2010 VL 304 IS 4 BP 411 EP 418 DI 10.1001/jama.2010.920 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 631MA UT WOS:000280350100024 PM 20584880 ER PT J AU Calhoun, JV AF Calhoun, John V. TI AFFIRMATION OF THE NAME PAPILIO HYLLUS CRAMER (LYCAENIDAE) FOR A NEARCTIC BUTTERFLY, WITH THE DESIGNATION OF A NEOTYPE SO JOURNAL OF THE LEPIDOPTERISTS SOCIETY LA English DT Article DE Dru Drury; Thomas James; William Jones; Hans Willem Rengers; Papilio thersamon; Polyommatus thoe AB Since its description Papilio hyllus Cramer, 1775 has been linked to at least five lycaenine and thecline species of butterflies. Although most authors now consider P. hyllus to represent the same Nearctic species subsequently described as Polyommatus time Guerin-Meneville, [1832], some consider it to represent the Palearctic species described as Papilio thersamon Esper, 1784. For over three decades the name Lycaena hyllus has been employed for the Nearctic species, but the identity of Papilio hyllus remains contentious. The original water-color drawings of Cramer's illustrated type specimen indicate that P hyllus is a senior subjective synonym of P. thoe. A connection between the English entomologist Dru Drury (1725-1804) and the Dutch naturalist Hans Willem (Baron) Rengers (1722-1786) suggests that the illustrated type specimen of P hyllus was collected by Thomas James in New York. A neotype is designated to objectively define the nominal species Papilio hyllus. C1 [Calhoun, John V.] Univ Florida, Florida Museum Nat Hist, McGuire Ctr Lepidoptera & Biodivers, Gainesville, FL 32611 USA. [Calhoun, John V.] FDACS, DPI, Gainesville, FL USA. RP Calhoun, JV (reprint author), 977 Wicks Dr, Palm Harbor, FL 34684 USA. NR 97 TC 0 Z9 0 U1 0 U2 0 PU LEPIDOPTERISTS SOC PI LOS ANGELES PA 900 EXPOSITION BLVD, LOS ANGELES, CA 90007-4057 USA SN 0024-0966 J9 J LEPID SOC JI J. Lepid. Soc. PD JUL 27 PY 2010 VL 64 IS 2 BP 79 EP 90 PG 12 WC Entomology SC Entomology GA 633JI UT WOS:000280497600003 ER PT J AU Brown, CR Hung, GC Dunton, D Chiang, HL AF Brown, C. Randell Hung, Guo-Chiuan Dunton, Danielle Chiang, Hui-Ling TI The TOR Complex 1 Is Distributed in Endosomes and in Retrograde Vesicles That Form from the Vacuole Membrane and Plays an Important Role in the Vacuole Import and Degradation Pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID YEAST SACCHAROMYCES-CEREVISIAE; CATABOLITE INACTIVATION; MOLECULAR MACHINERY; PROTEIN-TRANSPORT; PICHIA-PASTORIS; VID VESICLES; BETA-COP; FRUCTOSE-1,6-BISPHOSPHATASE; AUTOPHAGY; BIOGENESIS AB The key gluconeogenic enzyme fructose-1,6-bisphosphatase (FBPase) is induced when Saccharomyces cerevisiae are starved of glucose. However, when glucose is added to cells that have been starved for 3 days, FBPase is degraded in the vacuole. FBPase is first imported to Vid (vacuole import and degradation) vesicles, and these vesicles then merge with the endocytic pathway. In this report we show that two additional gluconeogenic enzymes, isocitrate lyase and phosphoenolpyruvate carboxykinase, were also degraded in the vacuole via the Vid pathway. These new cargo proteins and FBPase interacted with the TORC1 complex during glucose starvation. However, Tor1p was dissociated from FBPase after the addition of glucose. FBPase degradation was inhibited in cells overexpressing TOR1, suggesting that excessive Tor1p is inhibitory. Both Tco89p and Tor1p were found in endosomes coming from the plasma membrane as well as in retrograde vesicles forming from the vacuole membrane. When TORC1 was inactivated by rapamycin, FBPase degradation was inhibited. We suggest that TORC1 interacts with multiple cargo proteins destined for the Vid pathway and plays an important role in the degradation of FBPase in the vacuole. C1 [Brown, C. Randell; Chiang, Hui-Ling] Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA. [Hung, Guo-Chiuan] US FDA, Div Cellular & Gene Therapy, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Chiang, HL (reprint author), Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, 500 Univ Dr, Hershey, PA 17033 USA. EM hxc32@psu.edu FU National Institutes of Health [R01GM 59480]; Pennsylvania Tobacco Settlement Fund FX This work was supported, in whole or in part, by National Institutes of Health Grant R01GM 59480. This work was also supported by a grant from the Pennsylvania Tobacco Settlement Fund (to H.-L. C.). NR 49 TC 12 Z9 12 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 23 PY 2010 VL 285 IS 30 BP 23357 EP 23368 DI 10.1074/jbc.M109.075143 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 626WX UT WOS:000279999900069 PM 20457600 ER PT J AU Hamburg, MA Collins, FS AF Hamburg, Margaret A. Collins, Francis S. TI The Path to Personalized Medicine SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Hamburg, Margaret A.] US FDA, Silver Spring, MD USA. [Collins, Francis S.] NIH, Bethesda, MD 20892 USA. RP Hamburg, MA (reprint author), US FDA, Silver Spring, MD USA. NR 5 TC 593 Z9 608 U1 20 U2 197 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 22 PY 2010 VL 363 IS 4 BP 301 EP 304 DI 10.1056/NEJMp1006304 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 628RU UT WOS:000280139300001 PM 20551152 ER PT J AU Butryee, C Intaraluk, P Mao, G AF Butryee, C. Intaraluk, P. Mao, G. TI Risk assessment model for establishing heavy metal limits in health supplements SO TOXICOLOGY LETTERS LA English DT Meeting Abstract C1 [Butryee, C.] Mahidol Univ, Inst Nutr, Bangkok 10700, Thailand. [Intaraluk, P.] US FDA, Food Control Div, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD JUL 17 PY 2010 VL 196 SU S BP S94 EP S94 DI 10.1016/j.toxlet.2010.03.341 PG 1 WC Toxicology SC Toxicology GA V25II UT WOS:000208471300287 ER PT J AU Chen, T Li, Z Su, Z Shi, L AF Chen, T. Li, Z. Su, Z. Shi, L. TI Transcriptome analysis identifies the carcinogenic effects of aristolochic acid in rat kidney SO TOXICOLOGY LETTERS LA English DT Meeting Abstract C1 [Chen, T.; Li, Z.; Su, Z.; Shi, L.] US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD JUL 17 PY 2010 VL 196 SU S BP S178 EP S178 DI 10.1016/j.toxlet.2010.03.607 PG 1 WC Toxicology SC Toxicology GA V25II UT WOS:000208471301082 ER PT J AU Valerio, L AF Valerio, L., Jr. TI In silico toxicology: Predictive methods and applied regulatory research at the US FDA Center for Drug Evaluation and Research SO TOXICOLOGY LETTERS LA English DT Meeting Abstract C1 [Valerio, L., Jr.] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD JUL 17 PY 2010 VL 196 SU S BP S26 EP S26 DI 10.1016/j.toxlet.2010.03.119 PG 1 WC Toxicology SC Toxicology GA V25II UT WOS:000208471300079 ER PT J AU Hirsch, DS Shen, Y Dokmanovic, M Wu, WJ AF Hirsch, Dianne S. Shen, Yi Dokmanovic, Milos Wu, Wen Jin TI pp60(c-Src) Phosphorylates and Activates Vacuolar Protein Sorting 34 to Mediate Cellular Transformation SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; PHOSPHATIDYLINOSITOL 3'-KINASES; DISTINCT ROLES; BREAST-CANCER; LIPID KINASE; C-SRC; V-SRC; 3-KINASE; VPS34; RAS AB Vacuolar protein sorting 34 (VPS34) contributes to the regulation of the mammalian target of rapamycin complex 1/S6 kinase 1 pathway downstream of nutrient signaling. However, intracellular mechanisms leading to VPS34 activation remain unclear. Here, we report that Src directly phosphorylates VPS34, and that this phosphorylation activates VPS34 lipid kinase activity, leading to Src-Y527F-mediated cellular transformation. Silencing endogenous VPS34 specifically inhibits Src-Y527F-induced colony formation in soft agar, but not Ras-G12V-induced colony formation. We have identified two novel hVPS34 mutations, which either eliminate lipid kinase activity (kinase-dead mutant) or reduce tyrosine phosphorylation by Src-Y527F. When kinase-dead mutant of hVPS34 is stably expressed in Src-Y527F-transformed cells, transformation activities are blocked, indicating that the lipid kinase activity of hVPS34 is essential for Src-mediated cellular transformation. Furthermore, stable expression of this hVPS34 kinase-dead mutant causes an increased number of binucleate and multinucleate cells, suggesting that the kinase activity of hVPS34 is also required for cytokinesis. Moreover, when the hVPS34 mutant that has reduced tyrosine phosphorylation by Src is stably expressed in SrcY527F- transformed cells, Src-Y527F-stimulated colony formation is also reduced. Data presented here provide important evidence that VPS34 lipid kinase activity could be positively regulated by Src-mediated tyrosine phosphorylation in mammalian cells. This finding highlights a previously unappreciated relationship between VPS34, a class III phosphatidylinositol-3-kinase, and Src non-receptor tyrosine kinase. Additionally, we find that the levels of VPS34 expression and tyrosine phosphorylation are correlated with the tumorigenic activity of human breast cancer cells, indicating that Src to VPS34 signaling warrants further investigation as a pathway contributing to the development and progression of human cancers. Cancer Res; 70(14); 5974-83. (C) 2010 AACR. C1 [Hirsch, Dianne S.; Shen, Yi; Dokmanovic, Milos; Wu, Wen Jin] US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Wu, WJ (reprint author), US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, HFD-123,29B Lincoln Dr,Room 3NN-15, Bethesda, MD 20892 USA. EM wen.wu@fda.hhs.gov NR 36 TC 9 Z9 9 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 2010 VL 70 IS 14 BP 5974 EP 5983 DI 10.1158/0008-5472.CAN-09-2682 PG 10 WC Oncology SC Oncology GA 626GV UT WOS:000279955300033 PM 20551057 ER PT J AU Stone, JH Merkel, PA Spiera, R Seo, P Langford, CA Hoffman, GS Kallenberg, CGM Clair, EWS Turkiewicz, A Tchao, NK Webber, L Ding, L Sejismundo, LP Mieras, K Weitzenkamp, D Ikle, D Seyfert-Margolis, V Mueller, M Brunetta, P Allen, NB Fervenza, FC Geetha, D Keogh, KA Kissin, EY Monach, PA Peikert, T Stegeman, C Ytterberg, SR Specks, U AF Stone, John H. Merkel, Peter A. Spiera, Robert Seo, Philip Langford, Carol A. Hoffman, Gary S. Kallenberg, Cees G. M. Clair, E. William St. Turkiewicz, Anthony Tchao, Nadia K. Webber, Lisa Ding, Linna Sejismundo, Lourdes P. Mieras, Kathleen Weitzenkamp, David Ikle, David Seyfert-Margolis, Vicki Mueller, Mark Brunetta, Paul Allen, Nancy B. Fervenza, Fernando C. Geetha, Duvuru Keogh, Karina A. Kissin, Eugene Y. Monach, Paul A. Peikert, Tobias Stegeman, Coen Ytterberg, Steven R. Specks, Ulrich CA RAVE-ITN Res Grp TI Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ANTIBODY-ASSOCIATED VASCULITIS; GRANULOMATOSIS ETANERCEPT TRIAL; WEGENERS-GRANULOMATOSIS; RANDOMIZED-TRIAL; SYSTEMIC VASCULITIDES; CELL-ACTIVATION; B-CELLS; THERAPY; INDUCTION; REMISSION AB Background: Cyclophosphamide and glucocorticoids have been the cornerstone of remission-induction therapy for severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis for 40 years. Uncontrolled studies suggest that rituximab is effective and may be safer than a cyclophosphamide-based regimen. Methods: We conducted a multicenter, randomized, double-blind, double-dummy, noninferiority trial of rituximab (375 mg per square meter of body-surface area per week for 4 weeks) as compared with cyclophosphamide (2 mg per kilogram of body weight per day) for remission induction. Glucocorticoids were tapered off; the primary end point was remission of disease without the use of prednisone at 6 months. Results: Nine centers enrolled 197 ANCA-positive patients with either Wegener's granulomatosis or microscopic polyangiitis. Baseline disease activity, organ involvement, and the proportion of patients with relapsing disease were similar in the two treatment groups. Sixty-three patients in the rituximab group (64%) reached the primary end point, as compared with 52 patients in the control group (53%), a result that met the criterion for noninferiority (P<0.001). The rituximab-based regimen was more efficacious than the cyclophosphamide-based regimen for inducing remission of relapsing disease; 34 of 51 patients in the rituximab group (67%) as compared with 21 of 50 patients in the control group (42%) reached the primary end point (P=0.01). Rituximab was also as effective as cyclophosphamide in the treatment of patients with major renal disease or alveolar hemorrhage. There were no significant differences between the treatment groups with respect to rates of adverse events. Conclusions: Rituximab therapy was not inferior to daily cyclophosphamide treatment for induction of remission in severe ANCA-associated vasculitis and may be superior in relapsing disease. (Funded by the National Institutes of Allergy and Infectious Diseases, Genentech, and Biogen; ClinicalTrials.gov number, NCT00104299.) N Engl J Med 2010;363:221-32. C1 [Specks, Ulrich] Mayo Clin & Mayo Fdn, Div Pulm & Crit Care Med, Rochester, MN 55905 USA. [Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Merkel, Peter A.; Kissin, Eugene Y.; Monach, Paul A.] Boston Univ, Med Ctr, Boston, MA USA. [Spiera, Robert] Hosp Special Surg, New York, NY 10021 USA. [Seo, Philip; Sejismundo, Lourdes P.; Geetha, Duvuru] Johns Hopkins Univ, Baltimore, MD USA. [Langford, Carol A.; Hoffman, Gary S.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Kallenberg, Cees G. M.; Stegeman, Coen] Univ Groningen, Groningen, Netherlands. [Clair, E. William St.; Allen, Nancy B.] Duke Univ, Durham, NC USA. [Turkiewicz, Anthony] Univ Alabama, Birmingham, AL USA. [Tchao, Nadia K.; Seyfert-Margolis, Vicki; Mueller, Mark] Immune Tolerance Network, Bethesda, MD USA. [Webber, Lisa; Ding, Linna] NIAID, Bethesda, MD 20892 USA. [Seyfert-Margolis, Vicki] US FDA, Rockville, MD 20857 USA. [Brunetta, Paul] Genentech Inc, San Francisco, CA 94080 USA. [Weitzenkamp, David; Ikle, David] Rho, Raleigh, NC USA. RP Specks, U (reprint author), Mayo Clin & Mayo Fdn, Div Pulm & Crit Care Med, Rochester, MN 55905 USA. EM specks.ulrich@mayo.edu OI Carey, John/0000-0001-7292-2328 FU National Institute of Allergy and Infectious Diseases [N01-AI-15416, ITN021AI]; Mayo Clinic and Foundation; National Center for Research Resources (NCRR) [RR024150-01, RR025005, K24 AR049185, K23 AR052820]; Boston University; National Institutes of Health [RR 025771, M01 RR00533, K24 AR02224]; Arthritis Foundation FX Supported by a grant from the National Institute of Allergy and Infectious Diseases to the Immune Tolerance Network (N01-AI-15416; protocol no. ITN021AI). Genentech and Biogen provided the study medications and partial funding. At the Mayo Clinic and Foundation, the trial was supported by a Clinical and Translational Science Award from the National Center for Research Resources (NCRR) (RR024150-01); at Johns Hopkins University, by grants from the NCRR (RR025005) and career development awards (K24 AR049185, to Dr. Stone, and K23 AR052820, to Dr. Seo); and at Boston University, by a Clinical and Translational Science Award (RR 025771), grants from the National Institutes of Health (M01 RR00533) and a career development award (K24 AR02224, to Dr. Merkel), and an Arthritis Foundation Investigator Award (to Dr. Monach). Enzyme-linked immunosorbent assay kits for antineutrophil cytoplasmic antibody were provided by Euroimmun (Lubeck, Germany). NR 35 TC 748 Z9 784 U1 1 U2 31 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 15 PY 2010 VL 363 IS 3 BP 221 EP 232 DI 10.1056/NEJMoa0909905 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 625AR UT WOS:000279864200005 PM 20647199 ER PT J AU Cinar, HN Kothary, M Datta, AR Tall, BD Sprando, R Bilecen, K Yildiz, F McCardell, B AF Cinar, Hediye Nese Kothary, Mahendra Datta, Atin R. Tall, Ben D. Sprando, Robert Bilecen, Kivanc Yildiz, Fitnat McCardell, Barbara TI Vibrio cholerae Hemolysin Is Required for Lethality, Developmental Delay, and Intestinal Vacuolation in Caenorhabditis elegans SO PLOS ONE LA English DT Article ID PORE-FORMING TOXINS; HOST-PATHOGEN INTERACTIONS; LIVE ORAL VACCINE; EL-TOR HEMOLYSIN; CELL VACUOLATION; BACTERIAL PATHOGENESIS; VIRULENCE FACTORS; CYTOLYSIN; O1; PROTEASE AB Background: Cholera toxin (CT) and toxin-co-regulated pili (TCP) are the major virulence factors of Vibrio cholerae O1 and O139 strains that contribute to the pathogenesis of disease during devastating cholera pandemics. However, CT and TCP negative V. cholerae strains are still able to cause severe diarrheal disease in humans through mechanisms that are not well understood. Methodology/Principal Findings: To determine the role of other virulence factors in V. cholerae pathogenesis, we used a CT and TCP independent infection model in the nematode Caenorhabditis elegans and identified the hemolysin A (hlyA) gene as a factor responsible for animal death and developmental delay. We demonstrated a correlation between the severity of infection in the nematode and the level of hemolytic activity in the V. cholerae biotypes. At the cellular level, V. cholerae infection induces formation of vacuoles in the intestinal cells in a hlyA dependent manner, consistent with the previous in vitro observations. Conclusions/Significance: Our data strongly suggest that HlyA is a virulence factor in C. elegans infection leading to lethality and developmental delay presumably through intestinal cytopathic changes. C1 [Cinar, Hediye Nese; Kothary, Mahendra; Datta, Atin R.; Tall, Ben D.; McCardell, Barbara] US FDA, Div Virulence Assessment, Laurel, MD USA. [Bilecen, Kivanc; Yildiz, Fitnat] Univ Calif Santa Cruz, Dept Environm Toxicol, Santa Cruz, CA 95064 USA. [Sprando, Robert] US FDA, Div Toxicol, Laurel, MD USA. RP Cinar, HN (reprint author), US FDA, Div Virulence Assessment, Laurel, MD USA. EM hediye.cinar@fda.hhs.gov OI Bilecen, Kivanc/0000-0002-6254-3516; Tall, Ben/0000-0003-0399-3629 FU Food and Drug Administration FX This study was funded by Food and Drug Administration intramural funding. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 16 Z9 16 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 JUL 13 PY 2010 VL 5 IS 7 AR e11558 DI 10.1371/journal.pone.0011558 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 624MG UT WOS:000279822300012 PM 20644623 ER PT J AU Desai, S Brinker, A Swann, J Iyasu, S AF Desai, Shrey Brinker, Allen Swann, Joslyn Iyasu, Solomon TI Sitagliptin-Associated Drug Allergy: Review of Spontaneous Adverse Event Reports SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter C1 [Desai, Shrey] SEWA Rural, Community Hlth Project, Jhagadia 393110, Gujarat, India. [Brinker, Allen; Swann, Joslyn; Iyasu, Solomon] US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Div Drug Risk Evaluat, Rockville, MD 20857 USA. RP Desai, S (reprint author), SEWA Rural, Community Hlth Project, Jhagadia 393110, Gujarat, India. EM sdesai1977@yahoo.com NR 5 TC 14 Z9 15 U1 0 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 JUL 12 PY 2010 VL 170 IS 13 BP 1169 EP 1171 DI 10.1001/archinternmed.2010.188 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 624DY UT WOS:000279797700016 PM 20625027 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 Properly Folded Bacterially Expressed H1N1 Hemagglutinin Globular Head and Ectodomain Vaccines Protect Ferrets against H1N1 Pandemic Influenza Virus SO PLOS ONE LA English DT Article ID ELDERLY ADULTS; INSECT CELLS; H5N1 VIRUS; TRANSPORT; RESPONSES; EFFICACY; BINDING; SITES AB Background: In the face of impending influenza pandemic, a rapid vaccine production and mass vaccination is the most effective approach to prevent the large scale mortality and morbidity that was associated with the 1918 "Spanish Flu''. The traditional process of influenza vaccine production in eggs is time consuming and may not meet the demands of rapid global vaccination required to curtail influenza pandemic. Methodology/Principal Findings: Recombinant technology can be used to express the hemagglutinin (HA) of the emerging new influenza strain in a variety of systems including mammalian, insect, and bacterial cells. In this study, two forms of HA proteins derived from the currently circulating novel H1N1 A/California/07/2009 virus, HA1 (1-330) and HA (1-480), were expressed and purified from E. coli under controlled redox refolding conditions that favoured proper protein folding. However, only the recombinant HA1 (1-330) protein formed oligomers, including functional trimers that bound receptor and caused agglutination of human red blood cells. These proteins were used to vaccinate ferrets prior to challenge with the A/California/07/2009 virus. Both proteins induced neutralizing antibodies, and reduced viral loads in nasal washes. However, the HA1 (1-330) protein that had higher content of multimeric forms provided better protection from fever and weight loss at a lower vaccine dose compared with HA (1-480). Protein yield for the HA1 (1-330) ranged around 40 mg/Liter, while the HA (1-480) yield was 0.4-0.8 mg/Liter. Conclusions/Significance: This is the first study that describes production in bacterial system of properly folded functional globular HA1 domain trimers, lacking the HA2 transmembrane protein, that elicit potent neutralizing antibody responses following vaccination and protect ferrets from in vivo challenge. The combination of bacterial expression system with established quality control methods could provide a mechanism for rapid large scale production of influenza vaccines in the face of influenza pandemic 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 20014 USA. [Crevar, Corey J.; Carter, Donald M.; Ross, Ted M.] Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA USA. RP Khurana, S (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM hana.golding@fda.hhs.gov FU American Recovery and Reinvestment Act supplement [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 TMR. This study was also partly supported by IAA 224-10-1006 from DMID, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 52 Z9 55 U1 2 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 JUL 12 PY 2010 VL 5 IS 7 AR e11548 DI 10.1371/journal.pone.0011548 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 623XV UT WOS:000279781600025 PM 20634959 ER PT J AU Alosh, M Huque, MF AF Alosh, Mohamed Huque, Mohammad F. TI A consistency-adjusted alpha-adaptive strategy for sequential testing SO STATISTICS IN MEDICINE LA English DT Article DE alpha-adaptive; multiplicity; consistency criterion; piecewise linear adaptive ID PIOGLITAZONE CLINICAL-TRIAL; SECONDARY END-POINTS; HEART-FAILURE; MACROVASCULAR EVENTS; RANDOMIZED-TRIAL; MILLENNIUM; CALCULUS; CARVEDILOL; CAPTOPRIL; MORTALITY AB In a clinical trial with two clinically important endpoints, each of which can fully characterize a treatment benefit to support an efficacy claim by itself, a minimum degree of consistency in the findings is expected; otherwise interpretation of study findings can be problematic. Clinical trial literature contains examples where lack of consistency in the findings of clinically relevant endpoints led to difficulties in interpreting study results. The aim of this paper is to introduce this consistency concept at the study design stage and investigate the consequences of its implementation in the statistical analysis plan. The proposed methodology allows testing of hierarchically ordered endpoints to proceed as long as a pre-specified consistency criterion is met. In addition, while an initial allocation of the alpha level is specified for the ordered endpoints at the design stage, the methodology allows the alpha level allocated to the second endpoint to be adaptive to the findings of the first endpoint. In addition, the methodology takes into account the correlation between the endpoints in calculating the significance level and the power of the test for the next endpoint. The proposed Consistency-Adjusted Alpha-Adaptive Strategy (CAAAS) is very general. Several of the well-known multiplicity adjustment approaches arise as special cases of this strategy by appropriate selection of the consistency level and the form of alpha-adaptation function. We discuss control of the Type I error rate as well as power of the proposed methodology and consider its application to clinical trial data. Published in 2010 by John Wiley & Sons, Ltd. C1 [Alosh, Mohamed] US FDA, Div Biometr 3, Off Biostat, OTS,CDER, Silver Spring, MD 20993 USA. [Huque, Mohammad F.] US FDA, Div Biometr 4, Off Biostat, OTS,CDER, Silver Spring, MD 20993 USA. [Huque, Mohammad F.] Georgia So Univ, Jiann Ping Hsu Coll Publ Hlth, Statesboro, GA 30460 USA. RP Alosh, M (reprint author), US FDA, Div Biometr 3, Off Biostat, OTS,CDER, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Mohamed.Alosh@fda.hhs.gov NR 20 TC 18 Z9 18 U1 0 U2 2 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 JUL 10 PY 2010 VL 29 IS 15 BP 1559 EP 1571 DI 10.1002/sim.3896 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 620MA UT WOS:000279502800001 PM 20552571 ER PT J AU Kretzer, RM Foreman, CL Shuren, J AF Kretzer, Ryan M. Foreman, Christy L. Shuren, Jeffrey TI Modernizing Device Regulation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID CARDIOVASCULAR DEVICES C1 [Kretzer, Ryan M.; Foreman, Christy L.; Shuren, Jeffrey] US FDA, Silver Spring, MD USA. RP Kretzer, RM (reprint author), US FDA, Silver Spring, MD USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 8 PY 2010 VL 363 IS 2 BP 196 EP 197 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 621JY UT WOS:000279574100025 PM 20653080 ER PT J AU Khare, S Alali, W Zhang, SP Hunter, D Pugh, R Fang, FC Libby, SJ Adams, LG AF Khare, Sangeeta Alali, Walid Zhang, Shuping Hunter, Doris Pugh, Roberta Fang, Ferric C. Libby, Stephen J. Adams, L. Garry TI Vaccination with attenuated Salmonella enterica Dublin expressing E coli O157:H7 outer membrane protein Intimin induces transient reduction of fecal shedding of E coli O157:H7 in cattle SO BMC VETERINARY RESEARCH LA English DT Article ID ADULT BEEF-CATTLE; ORAL IMMUNIZATION; INTESTINAL COLONIZATION; EXPERIMENTAL-INFECTION; FOODBORNE PATHOGENS; CROSS-CONTAMINATION; ANTIBODY-RESPONSES; IMMUNE-RESPONSES; GROUND-BEEF; O157-H7 AB Background: Escherichia coli serogroup O157:H7 has emerged as an important zoonotic bacterial pathogen, causing a range of symptoms from self-limiting bloody diarrhea to severe hemorrhagic colitis and hemolytic-uremic syndrome in humans. Beef and dairy cattle are considered the most important animal reservoirs for this pathogen. One of the important virulence characteristics of E. coli O157: H7 is the eaeA gene encoding the 97 kDa surface protein intimin. Intimin is required for attachment and effacement during the interaction of enterohemorrhagic E. coli with human and bovine neonatal enterocytes. The present study was undertaken to test the hypothesis that an adaptive mucosal immune response directed against intimin will reduce or prevent enteric colonization and fecal shedding of E. coli O157: H7 in cattle. Results: Cattle were orally inoculated with either milk (control), milk with live attenuated Salmonella enterica serovar Dublin (vector), or milk with live attenuated recombinant S. Dublin expressing intimin (vaccinated) on days 0, 14 and 28. On day 98, all calves were challenged orally with E. coli O157: H7 to evaluate whether vaccination with the recombinant S. Dublin expressing intimin would reduce the level of E. coli O157: H7 fecal shedding. During the first 28 days, vaccinated calves shed both the vector strain and the intimin-expressing S. Dublin strain at a similar level. The vector strain was shed for a significantly longer period as compared to the level of recombinant vaccine strain. Calves that received the intimin-expressed vaccine ceased shedding S. Dublin from day 28 to day 63. All calves were challenged with E. coli O157: H7 on day 98 to determine the effect on fecal shedding of E. coli O157: H7. The amount of E. coli O157: H7 in feces was measured for 30 days post-challenge. We observed a transient clearance of E. coli O157: H7 from the feces in the vaccinated calves. The magnitude of fecal E. coli O157: H7 shedding did not correlate with the presence of intimin-specific fecal IgA. Conclusion: Oral vaccination with live attenuated recombinant S. Dublin expressing intimin reduced enteric colonization and fecal shedding of E. coli O157: H7. However, the transient clearance of E. coli O157: H7 was not associated with an enhanced IgA-mediated mucosal immune response. C1 [Khare, Sangeeta; Zhang, Shuping; Hunter, Doris; Pugh, Roberta; Adams, L. Garry] Texas A&M Univ, Dept Vet Pathobiol, Coll Vet Med & Biomed Sci, College Stn, TX 77843 USA. [Libby, Stephen J.] N Carolina State Univ, Dept Microbiol, Raleigh, NC 27695 USA. [Fang, Ferric C.; Libby, Stephen J.] Univ Washington, Sch Med, Dept Lab Med, Seattle, WA 98195 USA. [Fang, Ferric C.; Libby, Stephen J.] Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA. [Khare, Sangeeta; Adams, L. Garry] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Khare, S (reprint author), Texas A&M Univ, Dept Vet Pathobiol, Coll Vet Med & Biomed Sci, College Stn, TX 77843 USA. EM skhare@cvm.tamu.edu; gadams@cvm.tamu.edu OI Fang, Ferric/0000-0002-3243-110X FU USDA CSREES National Research Initiative [9800488, 1999-35201-8578] FX We acknowledge funding from USDA CSREES National Research Initiative number 9800488 and grant number 1999-35201-8578 to support the project. We are grateful for the active contribution of all student workers and the farm manager (Mr. Alan Patranella) who provided animal care. NR 53 TC 8 Z9 10 U1 2 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1746-6148 J9 BMC VET RES JI BMC Vet. Res. PD JUL 7 PY 2010 VL 6 AR 35 DI 10.1186/1746-6148-6-35 PG 9 WC Veterinary Sciences SC Veterinary Sciences GA 655PF UT WOS:000282261200001 PM 20609252 ER PT J AU Uber, P Summers, K Mehra, MR AF Uber, Patricia Summers, Kelly Mehra, Mandeep R. TI Clinicians and Nutraceutical Use in Cardiology Patients: Ignorance and Neglect SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 [Uber, Patricia; Mehra, Mandeep R.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Summers, Kelly] US FDA, Silver Spring, MD 20993 USA. RP Uber, P (reprint author), Univ Maryland, Sch Med, Baltimore, MD 21201 USA. OI Mehra, Mandeep/0000-0001-8683-7044 NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 6 PY 2010 VL 153 IS 1 BP 65 EP 66 DI 10.7326/0003-4819-153-1-201007060-00029 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 620GS UT WOS:000279487700026 PM 20621919 ER PT J AU Hong, JS Stavis, SM Lacerda, SHD Locascio, LE Raghavan, SR Gaitan, M AF Hong, Jennifer S. Stavis, Samuel M. Lacerda, Silvia H. DePaoli Locascio, Laurie E. Raghavan, Srinivasa R. Gaitan, Michael TI Microfluidic Directed Self-Assembly of Liposome-Hydrogel Hybrid Nanoparticles SO LANGMUIR LA English DT Article ID MULTIANGLE LIGHT-SCATTERING; DRUG-DELIVERY; IN-VITRO; NANOGELS; SIZE; DEVICE; POLY(N-ISOPROPYLACRYLAMIDE); FRACTIONATION; CYTOTOXICITY; MONODISPERSE AB We present a microfluidic method to direct the self-assembly of temperature-sensitive liposome-hydrogel hybrid nanoparticles. Our approach yields nanoparticles with structural properties and highly monodisperse size distributions precisely controlled across a broad range relevant to the targeted delivery and controlled release of encapsulated therapeutic agents. We used microfluidic hydrodynamic focusing to control the convective-diffusive mixing of two miscible nanoparticle precursor solutions (a DPPC:cholesterol:DCP phospholipid formulation in isopropanol and a photopolymerizable N-isopropylacrylamide mixture in aqueous butler) to form nanoscale lipid vesicles with encapsulated hydrogel precursors. These precursor nanoparticles were collected off-chip and were irradiated with ultraviolet (UV) light in bulk to polymerize the nanoparticle interiors into hydrogel cores. Multiangle laser light scattering in conjunction with asymmetric flow field-flow fractionation was used to characterize nanoparticle size distributions, which spanned the approximate to 150 to approximate to 300 nm diameter range as controlled by microfluidic mixing conditions, with a polydispersity of approximate to 3% to approximate to 5% (relative standard deviation). Transmission electron microscopy was then used to confirm the spherical shape and core-shell composition of the hybrid nanoparticles. This method may be extended to the directed self-assembly of other similar cross-linked hybrid nanoparticle systems with engineered size/structure-function relationships for practical use in healthcare and life science applications. C1 [Hong, Jennifer S.; Stavis, Samuel M.; Gaitan, Michael] NIST, Div Semicond Elect, Gaithersburg, MD 20899 USA. [Locascio, Laurie E.] NIST, Div Biochem Sci, Gaithersburg, MD 20899 USA. [Hong, Jennifer S.] Univ Maryland, Dept Bioengn, College Pk, MD 20742 USA. [Raghavan, Srinivasa R.] Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA. [Lacerda, Silvia H. DePaoli] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20817 USA. RP Hong, JS (reprint author), NIST, Div Semicond Elect, Gaithersburg, MD 20899 USA. EM Jennifer.hong@nist.gov FU National Institute of Standards and Technology (NIST); NSF FX This research was performed while SMS held a National Research Council Research Associateship Award at the National Institute of Standards and Technology (NIST). Device fabrication was performed in part at the Cornell Nanoscale Science and Technology Facility (CNF), a member of the National Nanotechnology Infrastructure Network supported by the NSF, and in part at the NisT Center for Nanoscale Science and Technology (CNST). The authors thank the CNF and CNST staff for assistance with device fabrication, Wyatt Vreeland from the NIST Biochemical Science Division for use of the AF4-MALLS instrumentation, and Jon Geist and Darwin Reyes from the NIST Semiconductor Electronics Division for helpful discussions. NR 43 TC 44 Z9 45 U1 9 U2 106 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD JUL 6 PY 2010 VL 26 IS 13 BP 11581 EP 11588 DI 10.1021/la100879p PG 8 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 616VX UT WOS:000279239900161 PM 20429539 ER PT J AU Gavrielides, MA Kinnard, LM Myers, KJ Peregoy, J Pritchard, WF Zeng, RP Esparza, J Karanian, J Petrick, N AF Gavrielides, Marios A. Kinnard, Lisa M. Myers, Kyle J. Peregoy, Jennifer Pritchard, William F. Zeng, Rongping Esparza, Juan Karanian, John Petrick, Nicholas TI A resource for the assessment of lung nodule size estimation methods: database of thoracic CT scans of an anthropomorphic phantom SO OPTICS EXPRESS LA English DT Article ID PULMONARY NODULES; SOLID TUMORS; TRUTH DATA; RECIST; ERROR AB A number of interrelated factors can affect the precision and accuracy of lung nodule size estimation. To quantify the effect of these factors, we have been conducting phantom CT studies using an anthropomorphic thoracic phantom containing a vasculature insert to which synthetic nodules were inserted or attached. Ten repeat scans were acquired on different multi-detector scanners, using several sets of acquisition and reconstruction protocols and various nodule characteristics (size, shape, density, location). This study design enables both bias and variance analysis for the nodule size estimation task. The resulting database is in the process of becoming publicly available as a resource to facilitate the assessment of lung nodule size estimation methodologies and to enable comparisons between different methods regarding measurement error. This resource complements public databases of clinical data and will contribute towards the development of procedures that will maximize the utility of CT imaging for lung cancer screening and tumor therapy evaluation. (C) 2010 Optical Society of America C1 [Gavrielides, Marios A.; Kinnard, Lisa M.; Myers, Kyle J.; Zeng, Rongping; Petrick, Nicholas] US FDA, Div Imaging & Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Peregoy, Jennifer; Pritchard, William F.; Esparza, Juan; Karanian, John] US FDA, Lab Cardiovasc & Intervent Therapeut, Div Biol, Ctr Devices & Radiol Hlth,Off Sci & Engn Labs, Silver Spring, MD USA. RP Gavrielides, MA (reprint author), US FDA, Div Imaging & Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. EM marios.gavrielides@fda.hhs.gov FU U.S. Food and Drug Administration; National Institute of Biomedical Imaging and Bioengineering; National Cancer Institute [224-07-6030]; Center for Interventional Oncology at the National Institutes of Health (NIH); NIH, United States Food and Drug Administration (FDA) FX This research was funded though a Critical Path grant from the U.S. Food and Drug Administration. The intramural research program of the National Institute of Biomedical Imaging and Bioengineering and the National Cancer Institute through IAG no. 224-07-6030 provided partial support for this work. Phantom scans on the Siemens Somatom Definition were conducted at the Center for Clinical Imaging Research in the Mallinckrodt Institute of Radiology (MIR) at the Washington University School of Medicine in St. Louis, MO. The authors would like to thank Bruce Whiting of MIR for his assistance. Phantom scans on the Philips IDT Mx8000 were supported in part by the Center for Interventional Oncology at the National Institutes of Health (NIH) and an Interagency Agreement between the NIH and the United States Food and Drug Administration (FDA). Finally, the authors would like to thank Wei-Chung Cheng for his assistance with photographs. The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services. NR 14 TC 23 Z9 25 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD JUL 5 PY 2010 VL 18 IS 14 BP 15244 EP 15255 DI 10.1364/OE.18.015244 PG 12 WC Optics SC Optics GA 622DN UT WOS:000279639900097 PM 20640011 ER PT J AU Buckler, AJ Schwartz, LH Petrick, N McNitt-Gray, M Zhao, B Fenimore, C Reeves, AP Mozley, PD Avila, RS AF Buckler, A. J. Schwartz, L. H. Petrick, N. McNitt-Gray, M. Zhao, B. Fenimore, C. Reeves, A. P. Mozley, P. D. Avila, R. S. TI Data sets for the qualification of volumetric CT as a quantitative imaging biomarker in lung cancer SO OPTICS EXPRESS LA English DT Article ID TUMOR RESPONSE; INTRAOBSERVER VARIABILITY; PULMONARY NODULES; TRUTH DATA; THERAPY; ERROR; INTEROBSERVER; CRITERIA; PHANTOM; TRIALS AB The drug development industry is faced with increasing costs and decreasing success rates. New ways to understand biology as well as the increasing interest in personalized treatments for smaller patient segments requires new capabilities for the rapid assessment of treatment responses. Deployment of qualified imaging biomarkers lags apparent technology capabilities. The lack of consensus methods and qualification evidence needed for large-scale multi-center trials, as well as the standardization that allows them, are widely acknowledged to be the limiting factors. The current fragmentation in imaging vendor offerings, coupled with the independent activities of individual biopharmaceutical companies and their contract research organizations (CROs), may stand in the way of the greater opportunity were these efforts to be drawn together. A preliminary report, "Volumetric CT: a potential biomarker of response," of the Quantitative Imaging Biomarkers Alliance (QIBA) activity was presented at the Medical Imaging Continuum: Path Forward for Advancing the Uses of Medical Imaging in the Development of New Biopharmaceutical Products meeting of the Extended Pharmaceutical Research and Manufacturers of America (PhRMA) Imaging Group sponsored by the Drug Information Agency (DIA) in October 2008. The clinical context in Lung Cancer and a methodology for approaching the qualification of volumetric CT as a biomarker has since been reported [Acad. Radiol. 17, 100-106, 107-115 (2010)]. This report reviews the effort to collect and utilize publicly available data sets to provide a transparent environment in which to pursue the qualification activities in such a way as to allow independent peer review and verification of results. This article focuses specifically on our role as stewards of image sets for developing new tools. (C) 2010 Optical Society of America C1 [Buckler, A. J.] Buckler Biomed LLC, Wenham, MA USA. [Schwartz, L. H.; Zhao, B.] Columbia Univ, New York, NY USA. [Petrick, N.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [McNitt-Gray, M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Fenimore, C.] Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. [Reeves, A. P.] Cornell Univ, Ithaca, NY USA. [Mozley, P. D.] Merck Res Labs, West Point, PA USA. [Avila, R. S.] Kitware Inc, Clifton Pk, NY USA. RP Buckler, AJ (reprint author), Buckler Biomed LLC, Wenham, MA USA. EM andrew@bucklerbiomedical.com OI Buckler, Andrew/0000-0002-0786-4835; McNItt-Gray, Michael/0000-0003-3004-4613 FU NCI; CDRH/NIBIB Laboratory for the Assessment of Medical Imaging Systems (LAMIS) FX Many members of our Technical Committee have made substantial contributions to the work described in this report. We would like to specifically acknowledge the following people in addition to the authors (alphabetically): Robert Ford (RadPharm), David Gustafson (Intio), Philip F. Judy (NLST), Matthias Thorn (Siemens Healthcare), James Mulshine (Rush), Daniel Nicolson (Definiens), Kevin O'Donnell (Toshiba), and Daniel C. Sullivan (Duke University and Scientific Advisor to RSNA). Linda Bresolin, Joseph Koudelik, and Fiona Miller of the RSNA organized each meeting, kept our records, and built the contents of our wiki. We would further like to acknowledge the support of the NCI Cancer Imaging Program, its RIDER Project (http://imaging.cancer.gov/reportsandpublications/ReportsandPresentation s/LungImaging/), and the CDRH/NIBIB Laboratory for the Assessment of Medical Imaging Systems (LAMIS) (http://www.nibib.nih.gov/Research/Intramural/LAMIS) NR 29 TC 9 Z9 9 U1 0 U2 4 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD JUL 5 PY 2010 VL 18 IS 14 BP 15267 EP 15282 DI 10.1364/OE.18.015267 PG 16 WC Optics SC Optics GA 622DN UT WOS:000279639900099 PM 20640013 ER PT J AU Behrman, RE Woodcock, J AF Behrman, Rachel E. Woodcock, Janet TI FDA Regulations for Drug Development SO SCIENCE LA English DT Letter C1 [Behrman, Rachel E.; Woodcock, Janet] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. RP Behrman, RE (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. EM rachel.behrman@fda.hhs.gov NR 0 TC 3 Z9 3 U1 0 U2 1 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 JUL 2 PY 2010 VL 329 IS 5987 BP 33 EP 33 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 619BL UT WOS:000279402700014 PM 20595600 ER PT J AU Fong, TL Klontz, KC Canas-Coto, A Casper, SJ Durazo, FA Davern, TJ Hayashi, P Lee, WM Seeff, LB AF Fong, Tse-Ling Klontz, Karl C. Canas-Coto, Alejandro Casper, Steven J. Durazo, Francisco A. Davern, Timothy J., II Hayashi, Paul Lee, William M. Seeff, Leonard B. TI Hepatotoxicity Due to Hydroxycut: A Case Series SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID WEIGHT-LOSS SUPPLEMENTS; GREEN TEA; LIVER-INJURY; AUTOIMMUNE-HEPATITIS; CAUSALITY ASSESSMENT AB OBJECTIVES: Muscletech Hydroxycut (Iovate Health Sciences Research, Oakville, Ontario, Canada) was a popular weight-loss supplement that was recalled by the manufacturer in May 2009 on the basis of reports of hepatotoxicity associated with this supplement. We sought to characterize the clinical presentation of Hydroxycut-associated liver injury and to adjudicate these cases for causal association with Hydroxycut. METHODS: We assessed the causality and grading of severity of liver injury using methodology developed by the Drug-Induced Liver Injury Network (DILIN) study. RESULTS: Eight patients who developed liver injury after taking Hydroxycut treated at different medical centers were identified. All were hospitalized, and three of eight patients required liver transplantation. Nine other cases with adequate clinical information were obtained from the FDA MedWatch database, including one fatal case of acute liver failure. Usual symptoms were jaundice, fatigue, nausea, vomiting, and abdominal pain. Most patients exhibited a hepatocellular pattern of injury. Adjudication for causality revealed eight cases as definite, five highly likely, two probable, and two were considered to be possible. CONCLUSIONS: Hydroxycut has been clearly implicated as a cause for severe liver injury that may lead to acute liver failure and death. Weight-loss supplements represent a class of dietary supplements that should be regarded as capable of causing severe hepatic toxicity when the usual causes of identified liver injury cannot be otherwise elucidated. C1 [Fong, Tse-Ling] Univ So Calif, Div Gastrointestinal & Liver Dis, Keck Sch Med, Los Angeles, CA 90033 USA. [Klontz, Karl C.; Casper, Steven J.] US FDA, Ctr Food Safety & Appl Nutr, Bethesda, MD 20014 USA. [Canas-Coto, Alejandro; Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. [Durazo, Francisco A.] Univ Calif Los Angeles, Div Digest & Liver Dis, Los Angeles, CA USA. [Davern, Timothy J., II] Univ Calif San Francisco, Div Gastroenterol, San Francisco, CA 94143 USA. [Hayashi, Paul] Univ N Carolina, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. [Seeff, Leonard B.] NIH, Liver Dis Res Branch, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. [Durazo, Francisco A.; Davern, Timothy J., II; Lee, William M.] NIDDK, Bethesda, MD 20892 USA. RP Fong, TL (reprint author), Univ So Calif, Div Gastrointestinal & Liver Dis, Keck Sch Med, 1510 San Pablo St ,2-F, Los Angeles, CA 90033 USA. EM tselingf@usc.edu FU NIDDK NIH HHS [U01 DK065238, U01 DK065184, U01 DK065176, U01 DK083027, U01 DK065201, U01 DK065211, U01 DK083023, U01 DK082992, U01 DK083020] NR 29 TC 47 Z9 47 U1 3 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUL PY 2010 VL 105 IS 7 BP 1561 EP 1566 DI 10.1038/ajg.2010.5 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 620ZD UT WOS:000279541200015 PM 20104221 ER PT J AU Hildebrandt, S AF Hildebrandt, Sabine TI Multiplexed identification of different fish species by detection of parvalbumin, a common fish allergen gene: a DNA application of multi-analyte profiling (xMAP(TM)) SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE Fish allergy; Parvalbumin; PCR; Universal primer; xMAP ID CROSS-REACTIVITY; ANTIBODY-BINDING; FROG PARVALBUMIN; CARP PARVALBUMIN; MAJOR ALLERGEN; FOOD; MUSCLE; HYPERSENSITIVITY; PURIFICATION; CHALLENGE AB Fish are a common cause of allergic reactions associated with food consumption, with parvalbumin being the major allergenic protein. Some fish-hypersensitive patients tolerate some fish species while being allergic to others. Reliable detection methods for allergenic fish species in foods are necessary to ensure compliance with food allergen labeling guidelines to protect fish-allergic consumers. The objective of this project was to develop a multi-analyte detection method for the presence of fish in food. Therefore, conserved parvalbumin exon sequences were utilized for the design of universal PCR primers amplifying intron DNA and small regions of exons flanking the enclosed intron from even very distantly related fish species. An assay for the identification of eight fish species was developed using xMAP(TM) technology with probes targeting species-specific parvalbumin intron regions. Additionally, a universal fish probe was designed targeting a highly conserved exon region located between the intron and the reverse primer region. The universal fish assay showed no cross-reactivity with other species, such as beef, pork, lamb, chicken, turkey, and shrimp. Importantly, with the exception of one notable case with fish in the same subfamily, species-specific detection showed no cross-reactivity with other fish species. Limits of detection for these eight species were experimentally estimated to range from 0.01% to 0.04%, with potential to increase the detection sensitivity. This report introduces a newly developed method for the multiplex identification of at least eight allergenic fish species in food, which could conceivably be extended to detect up to 100 species simultaneously in one sample. C1 [Hildebrandt, Sabine] US FDA, CFSAN, Off Regulatory Sci, Div Bioanalyt Chem, College Pk, MD 20740 USA. RP Hildebrandt, S (reprint author), US FDA, CFSAN, Off Regulatory Sci, Div Bioanalyt Chem, HFS 716,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM s-hildebrandt@gmx.net NR 34 TC 16 Z9 16 U1 0 U2 8 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD JUL PY 2010 VL 397 IS 5 BP 1787 EP 1796 DI 10.1007/s00216-010-3760-2 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 611IY UT WOS:000278810000021 PM 20467728 ER PT J AU Viswanathan, CT AF Viswanathan, C. T. TI Regulatory observations in bioanalytical determinations SO BIOANALYSIS LA English DT Article AB The concept of measuring analytes in biological media is a long-established area of the quantitative sciences that is employed in many sectors. While academic research and R&D units of private firms have been in the forefront of developing complex methodologies, it is the regulatory environment that has brought the focus and rigor to the quality control of the quantitative determination of drug concentration in biological samples. In this article, the author examines the regulatory findings discovered during the course of several years of auditing bioanalytical work. The outcomes of these findings underscore the importance of quality method validation to ensure the reliability of the data generated. The failure to ensure the reliability of these data can lead to potential risks in the health management of millions of people in the USA. C1 US FDA, Div Sci Invest, Off Compliance, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Viswanathan, CT (reprint author), US FDA, Div Sci Invest, Off Compliance, Ctr Drug Evaluat & Res, 7520 Standish Pl, Rockville, MD 20857 USA. EM ct.viswanathan@fda.hhs.gov NR 5 TC 4 Z9 4 U1 0 U2 0 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 J9 BIOANALYSIS JI Bioanalysis PD JUL PY 2010 VL 2 IS 7 BP 1325 EP 1329 DI 10.4155/BIO.10.85 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 644VV UT WOS:000281410700020 PM 21083243 ER PT J AU Cimafranca, MA Davila, J Ekman, GC Andrews, RN Neese, SL Peretz, J Woodling, KA Helferich, WG Sarkar, J Flaws, JA Schantz, SL Doerge, DR Cooke, PS AF Cimafranca, Melissa A. Davila, Juanmahel Ekman, Gail C. Andrews, Rachel N. Neese, Steven L. Peretz, Jackye Woodling, Kellie A. Helferich, William G. Sarkar, Jhimly Flaws, Jodi A. Schantz, Susan L. Doerge, Daniel R. Cooke, Paul S. TI Acute and Chronic Effects of Oral Genistein Administration in Neonatal Mice SO BIOLOGY OF REPRODUCTION LA English DT Article DE female reproductive tract; genistein; infant; soy formula; toxicology ID SOY-BASED FORMULAS; FEMALE REPRODUCTIVE-SYSTEM; EXPERT PANEL REPORT; PHYTOESTROGEN GENISTEIN; INFANT FORMULA; DEVELOPMENTAL TOXICITY; ESTROGENIC CHEMICALS; PHYTO-ESTROGENS; ESTROUS-CYCLE; IMMUNE STATUS AB Soy-based infant formulas are widely used in the United States and some other countries. These formulas contain high levels of the estrogenic isoflavone genistein, leading to concern that neonatal genistein exposure could cause acute and/or long-term adverse effects on reproductive and other organs. However, previous work to assess genistein effects in rodent models has not typically replicated the route of delivery and/or serum genistein concentrations reported for soy formula-fed human infants. Our objective was to develop a mouse model that more closely mimics the oral genistein exposure and total serum genistein concentrations observed in soy formula-fed infants. Mouse pups were dosed orally with genistein in a soy formula-corn oil emulsion from Postnatal Day (PND) 1 to PND 5, then effects on reproductive and nonreproductive organs were assessed after dosing and during subsequent development. Neonatal treatment resulted in changes both at the completion of dosing (PND 5) and in adult animals. At PND 5, neonatal genistein treatment caused increased relative uterine weight and down-regulation of progesterone receptor in uterine epithelia. Estrogenic effects of genistein were also seen in the neonatal ovary and thymus, which had an increase in the incidence of multioocyte follicles (MOFs) and a decrease in thymic weight relative to body weight, respectively. The increased incidence of MOFs persisted into adulthood for neonatally treated genistein females, and estrous cycle abnormalities were seen at 6 mo of age despite normal fertility in these mice. The immediate and long-term effects in this neonatal animal model raise concerns that high serum concentrations of genistein are estrogenic and could potentially impact the development of human infants fed soy formula. C1 [Cimafranca, Melissa A.; Davila, Juanmahel; Ekman, Gail C.; Andrews, Rachel N.; Neese, Steven L.; Peretz, Jackye; Sarkar, Jhimly; Flaws, Jodi A.; Schantz, Susan L.; Cooke, Paul S.] Univ Illinois, Dept Vet Biosci, Urbana, IL 61802 USA. [Helferich, William G.] Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61802 USA. [Helferich, William G.; Cooke, Paul S.] Univ Illinois, Div Nutr Sci, Urbana, IL 61802 USA. [Woodling, Kellie A.; Doerge, Daniel R.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Cooke, PS (reprint author), Univ Illinois, Dept Vet Biosci, 2001 S Lincoln Ave, Urbana, IL 61802 USA. EM p-cooke@illinois.edu FU NIH [P01 AG24387]; NIEHS [ES07326]; National Center for Research Resources, NIH [C06 RR16515] FX Supported by NIH grant P01 AG24387 (to S. L. S., D. R. D., W. G. H., and P. S. C.). M. A. C. and S.L.N. were supported by NIEHS grant ES07326 during conduct of this research. Work at the University of Illinois was conducted in a facility constructed with support from Research Facilities Improvement Program grant C06 RR16515 from the National Center for Research Resources, NIH. NR 53 TC 32 Z9 34 U1 0 U2 7 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUL PY 2010 VL 83 IS 1 BP 114 EP 121 DI 10.1095/biolreprod.109.080549 PG 8 WC Reproductive Biology SC Reproductive Biology GA 613RR UT WOS:000278998300014 PM 20357267 ER PT J AU Kondragunta, B Drew, JL Brorson, KA Moreira, AR Rao, G AF Kondragunta, Bhargavi Drew, Jessica L. Brorson, Kurt A. Moreira, Antonio R. Rao, Govind TI Advances in Clone Selection Using High-Throughput Bioreactors SO BIOTECHNOLOGY PROGRESS LA English DT Article DE high-throughput; mini-bioreactors; subcloning; noninvasive; optical; sensors ID MAMMALIAN-CELL CULTURE; MINIATURE BIOREACTOR; PROTEIN-PRODUCTION; OPTICAL SENSOR; SHAKE-FLASKS; SYSTEM; MICROBIOREACTOR; PH; PRODUCTIVITY; STABILITY AB Effective clone selection is a crucial step toward developing a robust mammalian cell culture production platform. Currently, clone selection is done by culturing cells in well plates and picking the highest producers. Ideally, clone selection should be done in a stirred tank bioreactor as this would best replicate the eventual production environment. The actual number of clones selected for future evaluation in bioreactors at bench-scale is limited by the scale-up and operational costs involved. This study describes the application of miniaturized stirred high-throughput bioreactors (35 mL working volume; HTBRs) with noninvasive optical sensors for clone screening and selection. We investigated a method for testing several subclones simultaneously in a stirred environment using our high throughput bioreactors (up to 12 clones per HTBR run) and compared it with a traditional well plate selection approach. Importantly, it was found that selecting clones solely based on results from stationary well plate cultures could result in the chance of missing higher producing clones. Our approach suggests that choosing a clone after analyzing its performance in a stirred bioreactor environment is an improved method for clone selection. (C) 2010 American Institute of Chemical Engineers Biotechnol. Prog., 26: 1095-1103, 2010 C1 [Kondragunta, Bhargavi; Drew, Jessica L.; Moreira, Antonio R.; Rao, Govind] Univ Maryland, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Kondragunta, Bhargavi; Drew, Jessica L.; Moreira, Antonio R.; Rao, Govind] Univ Maryland, Dept Chem & Biochem Engn, Baltimore, MD 21250 USA. [Kondragunta, Bhargavi; Brorson, Kurt A.] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. RP Rao, G (reprint author), Univ Maryland, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. EM grao@umbc.edu FU Sartorius-Stedim Biotechnology; Fluorometrix FX The authors acknowledge the support from Sartorius-Stedim Biotechnology and Fluorometrix. GR has an equity position in Fluorometrix. NR 27 TC 23 Z9 23 U1 0 U2 11 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD JUL-AUG PY 2010 VL 26 IS 4 BP 1095 EP 1103 DI 10.1002/btpr.392 PG 9 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 640IP UT WOS:000281045100023 PM 20205162 ER PT J AU Thompson, KL Rosenzweig, BA Zhang, J Knapton, AD Honchel, R Lipshultz, SE Retief, J Sistare, FD Herman, EH AF Thompson, Karol L. Rosenzweig, Barry A. Zhang, Jun Knapton, Alan D. Honchel, Ronald Lipshultz, Steven E. Retief, Jacques Sistare, Frank D. Herman, Eugene H. TI Early alterations in heart gene expression profiles associated with doxorubicin cardiotoxicity in rats SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Doxorubicin; Anthracycline; Cardiotoxicity; Microarray; Dexrazoxane; Cardioprotection ID CARDIOMYOCYTE APOPTOSIS; HYPERTENSIVE-RATS; OXIDATIVE STRESS; SKELETAL-MUSCLE; DEXRAZOXANE; PREVENTION; MITOCHONDRIA; SUPEROXIDE; MICROARRAY; ICRF-187 AB The antineoplastic anthracycline doxorubicin can induce a dose-dependent cardiomyopathy that limits the total cumulative dose prescribed to cancer patients. In both preclinical and clinical studies, pretreatment with dexrazoxane, an intracellular iron chelator, partially protects against anthracycline-induced cardiomyopathy. To identify potential additional cardioprotective treatment strategies, we investigated early doxorubicin-induced changes in cardiac gene expression. Spontaneously hypertensive male rats (n = 47) received weekly intravenous injections of doxorubicin (3 mg/kg) or saline 30 min after pretreatment with dexrazoxane (50 mg/kg) or saline by intraperitoneal injection. Cardiac samples were analyzed 24 h after the first (n = 20), second (n = 13), or third (n = 14) intravenous injection on days 1, 8, or 15 of the study, respectively. Rats receiving three doses of doxorubicin had minimal myocardial alterations that were attenuated by dexrazoxane. Cardiac expression levels of genes associated with the Nrf2-mediated stress response were increased after a single dose of doxorubicin, but not affected by cardioprotectant pretreatment. In contrast, an early repressive effect of doxorubicin on transcript levels of genes associated with mitochondrial function was attenuated by dexrazoxane pretreatment. Dexrazoxane had little effect on gene expression by itself. Genomic analysis provided further evidence that mitochondria are the primary target of doxorubicin-induced oxidative damage that leads to cardiomyopathy and the primary site of cardioprotective action by dexrazoxane. Additional strategies that prevent the formation of oxygen radicals by doxorubicin in mitochondria may provide increased cardioprotection. C1 [Thompson, Karol L.; Rosenzweig, Barry A.; Zhang, Jun; Knapton, Alan D.; Honchel, Ronald; Sistare, Frank D.; Herman, Eugene H.] Ctr Drug Evaluat & Res, US FDA, Silver Spring, MD 20993 USA. [Lipshultz, Steven E.] Univ Miami, Dept Pediat, Leonard M Miller Sch Med, Miami, FL 33152 USA. [Retief, Jacques] Affymetrix Inc, Santa Clara, CA USA. RP Thompson, KL (reprint author), Ctr Drug Evaluat & Res, US FDA, LSB64 Room 2036,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM karol.thompson@fda.hhs.gov NR 39 TC 31 Z9 35 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUL PY 2010 VL 66 IS 2 BP 303 EP 314 DI 10.1007/s00280-009-1164-9 PG 12 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 597TV UT WOS:000277785600012 PM 19915844 ER PT J AU Chen, K Tan, ZW He, MZ Li, JB Tang, SX Hewlett, I Yu, F Jin, YX Yang, M AF Chen, Kan Tan, Zhiwu He, Meizi Li, Jiebo Tang, Shixing Hewlett, Indira Yu, Fei Jin, Yinxue Yang, Ming TI Structure-Activity Relationships (SAR) Research of Thiourea Derivatives as Dual Inhibitors Targeting both HIV-1 Capsid and Human Cyclophilin A SO CHEMICAL BIOLOGY & DRUG DESIGN LA English DT Article DE capsid; HIV-1; human cyclophilin A; SAR; thiourea derivatives ID IMMUNODEFICIENCY-VIRUS TYPE-1; ASSEMBLY IN-VITRO; CHEMICAL INHIBITORS; PROTEIN; BIOASSAY; COMPLEX AB HIV-1 capsid (CA) and human cyclophilin A (CypA) play important roles in HIV-1 assembly and disassembly processes, which are critical in HIV-1 replication. Based on the discovery of thiourea derivatives targeting both of the two proteins and indicating effective inhibitory activities in our group, we designed and synthesized a new class of thiourea derivatives. Their abilities to bind to capsid and cyclophilin A were determined by ultraviolet spectroscopic analysis, fluorescence binding affinity, and PPIase inhibition assay. Furthermore, the newly synthesized compounds were tested for their antiviral activities and cytotoxicities using CEM cells. According to the biological evaluation and subsequent molecular docking analyses, we studied the structure-activity relationships of thiourea derivatives. Three optimal compounds (K17, K24, K25) based on the achieved structure-activity relationships would be the basis for future optimization. C1 [Chen, Kan; Tan, Zhiwu; He, Meizi; Li, Jiebo; Yu, Fei; Jin, Yinxue; Yang, Ming] Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China. [Tang, Shixing; Hewlett, Indira] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Yang, M (reprint author), Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China. EM yangm@bjmu.edu.cn RI Li, Jiebo/D-1516-2015 OI Li, Jiebo/0000-0001-8124-8769 FU National Natural Science Foundation of China [30670415] FX This project was supported by the National Natural Science Foundation of China (No. 30670415). NR 22 TC 9 Z9 11 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1747-0277 J9 CHEM BIOL DRUG DES JI Chem. Biol. Drug Des. PD JUL PY 2010 VL 76 IS 1 BP 25 EP 33 DI 10.1111/j.1747-0285.2010.00981.x PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 601QP UT WOS:000278078300004 PM 20456372 ER PT J AU Jang, SH Colangelo, PM Gobburu, JVS AF Jang, S. H. Colangelo, P. M. Gobburu, J. V. S. TI Exposure-Response of Posaconazole Used for Prophylaxis Against Invasive Fungal Infections: Evaluating the Need to Adjust Doses Based on Drug Concentrations in Plasma SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID CELL TRANSPLANT RECIPIENTS; VERSUS-HOST-DISEASE; ORAL POSACONAZOLE; CONTROLLED-TRIAL; PHARMACOKINETICS; FLUCONAZOLE; ASPERGILLOSIS; THERAPY; SAFETY AB The purpose of this article is to report the exposure-response (E-R) relationship of posaconazole oral suspension (POS) for prophylaxis against invasive fungal infections (IFIs), on the basis of the us Food and Drug administration (FDA) clinical pharmacology review of two randomized, active-controlled clinical studies. posaconazole average steady-state plasma concentrations (C(avg)) ranged from 22 to 3,650 ng/ml after administration of POS 200 mg three times daily (t.i.d.). in a double-blind, randomized clinical trial, the quartile ranges of C(avg) with midpoint values of 289, 736, 1,239, and 2,607 ng/ml had clinical failure rates of 44, 21, 18, and 18%, respectively, indicating an inverse association between C(avg) and clinical failure rate. There were no significant relationships between C(avg) and posaconazole-related major adverse events. Determining posaconazole concentrations in plasma will aid in assessing the need for either POS dose adjustment (e.g., increasing the POS dose) or switching to another systemic antifungal drug, thereby improving the effectiveness of prophylaxis against IFIs. C1 [Jang, S. H.; Colangelo, P. M.; Gobburu, J. V. S.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Jang, SH (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM seong.jang@fda.hhs.gov NR 18 TC 96 Z9 97 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 JUL PY 2010 VL 88 IS 1 BP 115 EP 119 DI 10.1038/clpt.2010.64 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 617IC UT WOS:000279273200019 PM 20505665 ER PT J AU Levis, S Strickman-Stein, N Doerge, DR Krischer, J AF Levis, Silvina Strickman-Stein, Nancy Doerge, Daniel R. Krischer, Jeffrey TI Design and baseline characteristics of the Soy Phytoestrogens As Replacement Estrogen (SPARE) study - A clinical trial of the effects of soy isoflavones in menopausal women SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Menopause; Bone health; Osteoporosis; Soy; Isoflavones ID BONE-MINERAL DENSITY; POSTMENOPAUSAL JAPANESE WOMEN; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; HORMONE-THERAPY; PROTEIN ISOLATE; METABOLISM; SUPPLEMENTATION; GENISTEIN AB Following the results of the Women's Health Initiative, many women now decline estrogen replacement at the time of menopause and seek natural remedies that would treat menopausal symptoms and prevent bone loss and other long-term consequences of estrogen deficiency, but without adverse effects on the breast, uterus, and cardiovascular system. The results of most soy studies in this population have had limitations because of poor design, small sample size, or short duration. This report describes the study rationale, design, and procedures of the Soy Phytoestrogens As Replacement Estrogen (SPARE) study, which was designed to determine the efficacy of soy isoflavones in preventing spinal bone loss and menopausal symptoms in the initial years of menopause. Women ages 45 to 60 without osteoporosis and within 5 years from menopause were randomized to receive soy isoflavones 200 mg daily or placebo for 2 years. Participants have yearly measurements of spine and hip bone density, urinary phytoestrogens, and serum lipids, thyroid stimulating hormone, and estradiol. Menopausal symptoms, mood changes, depression, and quality of life are assessed annually. The SPARE study recruited 283 women, 66.1% were Hispanic white. With a large cohort, long duration, and large isoflavone dose, this trial will provide important, relevant, and currently unavailable information on the benefits of purified soy isoflavones in the prevention of bone loss and menopausal symptoms in the first 5 years of menopause. Given the high proportion of Hispanics participating in the study, the results of this trial will also be applicable to this minority group. Published by Elsevier Inc. C1 [Levis, Silvina] Univ Miami, Miller Sch Med, Miami Vet Affairs Healthcare Syst, Ctr Geriatr Res Educ & Clin, Miami, FL 33125 USA. [Levis, Silvina] Univ Miami, Miller Sch Med, Geriatr Inst, Miami, FL 33136 USA. [Levis, Silvina] Univ Miami, Miller Sch Med, Div Gerontol & Geriatr Med, Miami, FL 33136 USA. [Strickman-Stein, Nancy] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. [Doerge, Daniel R.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Krischer, Jeffrey] Univ S Florida, Dept Pediat, Tampa, FL 33612 USA. RP Levis, S (reprint author), Univ Miami, Miller Sch Med, POB 016960 C-211, Miami, FL 33101 USA. EM slevis@med.miami.edu; nstein@med.miami.edu; DDoerge@nctr.fda.gov; jpkrischer@epi.usf.edu FU National Institute of Arthritis, Musculoskeletal, and Skin Diseases [R01 AR48932-01A1] FX This work is supported by a grant (R01 AR48932-01A1) from the National Institute of Arthritis, Musculoskeletal, and Skin Diseases. The views expressed do not necessarily reflect those of the U.S. Food and Drug Administration. The authors report no competing financial interests. NR 56 TC 15 Z9 18 U1 3 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JUL PY 2010 VL 31 IS 4 BP 293 EP 302 DI 10.1016/j.cct.2010.03.007 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 627HX UT WOS:000280031200006 PM 20230914 ER PT J AU Sen, A Stultz, BG Lee, H Hursh, DA AF Sen, Aditya Stultz, Brian G. Lee, Heuijung Hursh, Deborah A. TI Odd paired transcriptional activation of decapentaplegic in the Drosophila eye/antennal disc is cell autonomous but indirect SO DEVELOPMENTAL BIOLOGY LA English DT Article DE odd paired (opa); Cubitus interruptus (Ci); Zic; Gli; decapentaplegic (dpp); SELEX; DNA binding; sloppy paired 1 (slp1) ID ADULT HEAD DEVELOPMENT; CIS-REGULATORY REGION; DNA-BINDING PROTEINS; ZINC-FINGER PROTEIN; CUBITUS INTERRUPTUS; FOREBRAIN DEVELOPMENT; ZIC GENES; FAMILY; MORPHOGENESIS; EXPRESSION AB The gene odd paired (opa), a Drosophila homolog of the Zinc finger protein of the cerebellum (Zic) family of mammalian transcription factors, plays roles in embryonic segmentation and development of the adult head. We have determined the preferred DNA binding sequence of Opa by SELEX and shown that it is necessary and sufficient to activate transcription of reporter gene constructs under Opa control in transgenic flies. We have found a related sequence in the enhancer region of an opa-responsive gene, sloppy paired 1. This site also responds to Opa in reporter constructs in vivo. However, nucleotide alterations that abolish the ability of Opa to bind this site in vitro have no effect on the ability of Opa to activate expression from constructs bearing these mutations in vivo. These data suggest that while Opa can function in vivo as a sequence specific transcriptional regulator, it does not require DNA binding for transcriptional activation. Published by Elsevier Inc. C1 [Sen, Aditya; Stultz, Brian G.; Lee, Heuijung; Hursh, Deborah A.] US FDA, Cell & Tissue Therapy Branch, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Hursh, DA (reprint author), US FDA, Cell & Tissue Therapy Branch, Ctr Biol Evaluat & Res, HFM 740,Bldg 29B,Rm 1E16,8800 Rockville Pike, Bethesda, MD 20892 USA. EM deborah.hursh@fda.hhs.gov NR 47 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2010 VL 343 IS 1-2 BP 167 EP 177 DI 10.1016/j.ydbio.2010.04.003 PG 11 WC Developmental Biology SC Developmental Biology GA 612QE UT WOS:000278915300014 PM 20403347 ER PT J AU Nie, L Chu, HT Li, F Cole, SR AF Nie, Lei Chu, Haitao Li, Feng Cole, Stephen R. TI Relative Excess Risk Due to Interaction Resampling-based Confidence Intervals SO EPIDEMIOLOGY LA English DT Article ID LOGISTIC-REGRESSION AB Relative excess risk due to interaction (RERI) has been used to quantify the joint effects of 2 exposures in epidemiology. However, the construction of confidence intervals (CIs) for RERI is complicated by sparse cells. Assuming that the data contain no zero cells, here we propose constructing CIs for RERI using nonparametric and parametric bootstrap methods with a continuity correction, and compare these proposed methods to existing methods using 3 empirical examples and Monte Carlo simulations. Our results show that, when cell counts are not sparse, CIs resulting from the explored bootstrap methods are generally acceptable in terms of CI coverage and length, although computationally more demanding than existing methods. However, when cell counts are sparse, the proposed bootstrap methods using a continuity correction outperform existing methods and continue to provide acceptable CIs. The continuity correction is needed for the explored bootstrap methods to provide acceptable CIs because resampled data sets may contain zero cells even when the observed data do not. C1 [Nie, Lei] US FDA, Div Biometr 4, Off Biometr, OTS,CDER, Silver Spring, MD 20993 USA. [Chu, Haitao] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Chu, Haitao] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Li, Feng] US FDA, Div Biometr 2, Off Biometr, OTC,CDER, Silver Spring, MD 20993 USA. [Cole, Stephen R.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. RP Nie, L (reprint author), US FDA, Div Biometr 4, Off Biometr, OTS,CDER, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM lei.nie@fda.hhs.gov RI Li, Feng/B-8021-2011; Chu, Haitao /J-7576-2012; OI Chu, Haitao/0000-0003-0932-598X FU Lineberger Cancer Center [CA16086]; US National Cancer Institute [R03-AI-071763, R01-AA-01759, P30-AI-50410] FX Supported in part by the Lineberger Cancer Center Core Grant CA16086 from the US National Cancer Institute and by R03-AI-071763, R01-AA-01759,and P30-AI-50410. NR 14 TC 12 Z9 13 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2010 VL 21 IS 4 BP 552 EP 556 DI 10.1097/EDE.0b013e3181e09b0b PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 614EQ UT WOS:000279038600018 PM 20502336 ER PT J AU Nie, L Chu, HT Liu, CL Cole, SR Vexler, A Schisterman, EF AF Nie, Lei Chu, Haitao Liu, Chenglong Cole, Stephen R. Vexler, Albert Schisterman, Enrique F. TI Linear Regression With an Independent Variable Subject to a Detection Limit SO EPIDEMIOLOGY LA English DT Article ID MEASUREMENT ERROR; MODELS AB Background: Linear regression with a left-censored independent variable X due to limit of detection (LOD) was recently considered by 2 groups of researchers: Richardson and Ciampi (Am J Epidemiol. 2003; 157: 355-363), and Schisterman et al (Am J Epidemiol. 2006; 163: 374-383). Methods: Both groups obtained consistent estimators for the regression slopes by replacing left-censored X with a constant, that is, the expectation of X given X below LOD E(X vertical bar X60% of KA patients are unresponsive to sodium antimony gluconate (SAG) treatment. Determinants of resistance in laboratory strains are partly known, however the mechanism operating in field isolates is not well understood. In microarray-based expression profiling with RNA isolated from field isolates of drug-resistant and -sensitive L. donovani parasites, genes encoding histone 1 (H1), histone 2A (H2A), histone 4 (H4), mitogen-activated protein kinase 1 (MAPK1) and two hypothetical proteins showed significantly higher expression in antimony-resistant parasites, whilst genes encoding an amino acid transporter showed higher expression in sensitive parasites. The expression level of these genes was validated by semiquantitative polymerase chain reaction (PCR). Furthermore, the higher expression of H1, H2A and MAPK1 was confirmed at the protein level in resistant isolates. Overexpression of H2A in a drug-sensitive laboratory strain as well as a field isolate of L. donovani resulted in conversion of SAG-sensitive Leishmania parasites into a resistant phenotype. Moreover, H2A overexpression resulted in a significant decrease in susceptibility towards other antileishmanial drugs currently in use, i.e. amphotericin B and miltefosine, pointing to its role in drug resistance. (C) 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. C1 [Singh, Ruchi; Kumar, Dhiraj; Salotra, Poonam] Inst Pathol ICMR, New Delhi 110029, India. [Singh, Ruchi; Duncan, Robert C.; Nakhasi, Hira L.] FDA, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review, CBER, Bethesda, MD USA. RP Salotra, P (reprint author), Natl Inst Malaria Res ICMR, Delhi, India. EM salotra@vsnl.com RI Duncan, Robert/I-8168-2015; OI Duncan, Robert/0000-0001-8409-2501; Singh, Ruchi/0000-0001-8094-4703 FU Indian Council of Medical Research (ICMR, India); Council of Scientific and Industrial Research (CSIR) FX Funding: This work was supported by an Indian Council of Medical Research (ICMR, India) grant to PS and a UNESCO L'Oreal for Women in Science fellowship grant to RS. DK is grateful to the Council of Scientific and Industrial Research (CSIR) for financial support. NR 38 TC 22 Z9 22 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-8579 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD JUL PY 2010 VL 36 IS 1 BP 50 EP 57 DI 10.1016/j.ijantimicag.2010.03.012 PG 8 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 599RL UT WOS:000277930700009 PM 20427152 ER PT J AU Nelson, RM Lewis, LL Struble, K Wood, SF AF Nelson, Robert M. Lewis, Linda L. Struble, Kimberly Wood, Susan F. TI Ethical and Regulatory Considerations for the Inclusion of Adolescents in HIV Biomedical Prevention Research SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE adolescent; clinical trials; control group; ethics; HIV; informed consent; microbicides; placebo; pre-exposure prophylaxis; pregnancy; vaccines ID INFLUENZA IMMUNIZATION; VACCINE AB Adolescents should be enrolled in ethically appropriate and scientifically rigorous HIV biomedical prevention research involving vaccines, pre-exposure prophylaxis, or microbicides. There is general agreement that children should only be enrolled in a clinical trial if the scientific objectives cannot be met either through enrolling adult subjects who can provide informed consent personally or through conducting research using animal models. In addition, the risks to which children are exposed in a clinical trial without the possibility of direct therapeutic benefit must be low. Children also should not be placed at a disadvantage after being enrolled in a clinical trial by, for example, being exposed to an unnecessarily risky intervention or by failing to receive a comparable treatment that would prevent significant morbidity or mortality. In light of this shared framework, we discuss the timing of enrolling adolescents in HIV prevention trials; some general study design considerations that may be necessary for adequate labeling of products for an adolescent indication; the use of data obtained from international studies for licensure applications in the United States; the role of parental permission and adolescent assent to research participation; and the inclusion of pregnant adolescents in HIV biomedical prevention research. C1 [Nelson, Robert M.] US FDA, Off Pediat Therapeut, Off Commissioner, Silver Spring, MD 20993 USA. [Lewis, Linda L.; Struble, Kimberly] Ctr Drug Evaluat & Res, Div Antiviral Prod, Off New Drugs, US FDA, Silver Spring, MD USA. [Wood, Susan F.] George Washington Univ, Sch Publ Hlth & Hlth Serv, Jacobs Inst Womens Hlth, Washington, DC USA. RP Nelson, RM (reprint author), US FDA, Off Pediat Therapeut, Off Commissioner, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM robert.nelson@fda.hhs.gov NR 25 TC 20 Z9 20 U1 4 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JUL 1 PY 2010 VL 54 SU 1 BP S18 EP S24 DI 10.1097/QAI.0b013e3181e2012e PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 614LB UT WOS:000279059100005 PM 20571419 ER PT J AU Oles, CJ Trucksess, MW AF Oles, Carolyn J. Trucksess, Mary W. TI Determination of Fumonisin B-1 in Botanical Roots by Liquid Chromatography with Fluorescence Detection: Single-Laboratory Validation SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MEDICINAL-PLANTS; CORN; LEUKOENCEPHALOMALACIA; PERFORMANCE; MYCOTOXINS; AFRICA; TEA AB The accuracy, repeatability, and reproducibility characteristics of a published method for measuring levels of fumonisin B-1 (FB1) in botanical root products were determined by an AOAC single-laboratory validation procedure. Replicates of 10 test portions of each powdered root product (black cohosh, echinacea, ginger, ginseng, valerian, dong quai, and turmeric) at each spiking level (FB1 at 0, 50, 100, and 200 ng/g) were analyzed on 3 separate days. Test samples were extracted with methanol-acetonitrile-water (25 + 25 + 100, v/v/v). The extracts were centrifuged, the supernatants diluted with phosphate-buffered saline (PBS) containing 1% Tween 20 and filtered, and the filtrates applied to an immunoaffinity column containing antibodies specific for fumonisins. After the column was washed sequentially with PBS and water, the toxin was eluted from the column with 80% methanol, and the eluate dried by lyophilization. The residue was reconstituted with 50% acetonitrile. FB1 was derivatized with a mixture of o-phthaldialdehyde and mercaptoethanol by using an LC autoinjector. Separations were performed with an RP-LC column, and the FB1 derivative was quantified by fluorescence detection. All root products were found to contain FB1 at <10 ng/g. Average within- and between-day recoveries of FB1 from the botanical roots ranged from 67 to 95% and from 68 to 100%, respectively. Total RSD values for within- and between-day repeatability ranged from 5.5 to 26.4%. HorRat values were <1.3 for all of the matrixes examined. The method meets the AOAC method performance criteria at levels of >50 ng/g for the seven botanical roots tested. C1 [Oles, Carolyn J.; Trucksess, Mary W.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. RP Trucksess, MW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM mary.trucksess@fda.hhs.gov FU Office of Dietary Supplements, National Institutes of Health, Bethesda, MD FX This work was supported in part by the Office of Dietary Supplements, National Institutes of Health, Bethesda, MD. NR 20 TC 4 Z9 5 U1 0 U2 3 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 JUL-AUG PY 2010 VL 93 IS 4 BP 1155 EP 1160 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 645UQ UT WOS:000281492100014 PM 20922947 ER PT J AU Trucksess, MW Bao, L Weaver, CM White, KD AF Trucksess, Mary W. Bao, Lei Weaver, Carol M. White, Kevin D. TI Determination of Deoxynivalenol in Processed Foods SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID IMMUNOAFFINITY COLUMN CLEANUP; FUSARIUM HEAD BLIGHT; WHOLE WHEAT-FLOUR; LIQUID-CHROMATOGRAPHY; WHITE FLOUR; MYCOTOXINS; CEREALS; BRAN AB Deoxynivalenol (DON), commonly referred to as vomitoxin, belongs to a class of naturally occurring mycotoxins produced by Fusarium fungi. The presence of DON in foods is a human health concern. The frequency of occurrence of DON in wheat is high, although cleaning prior to milling can reduce DON concentration in final products, and food processing can partially degrade the toxin. This paper describes a method for the determination of DON in some major wheat food products, including bread, breakfast cereals, pasta, pretzels, and crackers. Test samples containing 5% polyethylene glycol were extracted with water. After blending and centrifuging, the supernatant was diluted with water and filtered through glass microfiber filter paper. The filtrate was then passed through an immunoaffinity column and the toxins eluted with methanol. The toxins were then subjected to RPLC separation and UV detection. The accuracy and repeatability characteristics of the method were determined. Recoveries of DON spiked at levels from 0.5 to 1.5 mu g/g in the five processed foods were >70%. SD and RSD values ranged from 2.0 to 23.5% and from 2.0 to 23.2%, respectively. HorRat values were <2 for all of the matrixes examined. The method was found to be acceptable for the matrixes examined. LC/MS/MS with multiple-reaction monitoring was used to confirm the identity of DON in naturally contaminated test samples. C1 [Trucksess, Mary W.; Weaver, Carol M.] US FDA, Ctr Food Safety & Appl Nutr, Div Bioanalyt Chem, College Pk, MD 20740 USA. [White, Kevin D.] US FDA, Ctr Food Safety & Appl Nutr, Div Analyt Chem, College Pk, MD 20740 USA. RP Trucksess, MW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Bioanalyt Chem, College Pk, MD 20740 USA. EM mary.trucksess@fda.hhs.gov FU U.S. Department of Energy; FDA FX This project was supported in part by an appointment of Lei Bao to the Research Participation Program at the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the FDA. We would like to thank Henry Kim (FDA, College Park, MD) for his guidance in selecting the processed foods, Jeanne I. Rader (FDA, College Park, MD) for her support and guidance, and Chelsea Sapp (FDA, College Park, MD) for her assistance in sample preparation. NR 17 TC 4 Z9 4 U1 3 U2 12 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 JUL-AUG PY 2010 VL 93 IS 4 BP 1236 EP 1242 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 645UQ UT WOS:000281492100024 PM 20922957 ER PT J AU Rivkees, SA Szarfman, A AF Rivkees, Scott A. Szarfman, Ana TI Dissimilar Hepatotoxicity Profiles of Propylthiouracil and Methimazole in Children SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INDUCED CHOLESTATIC JAUNDICE; GRAVES-DISEASE; LIVER-INJURY; HYPERTHYROID PATIENT; REMISSION; TRANSPLANTATION; PREDICTORS; VASCULITIS; ANTIBODY; FAILURE AB Background: The antithyroid drugs propylthiouracil and methimazole were introduced for clinical use about 60 yr ago and are estimated to be used in more than 6000 children and adolescents per year in the United States. Over the years that these medications have been used, reports of adverse events involving hepatotoxicity have appeared. To date, there has not been a systematic and comparative evaluation of the adverse events associated with antithyroid drug use. Objective: Our objective was to assess safety and hepatotoxicity profiles of propylthiouracil and methimazole by age in the U. S. Food and Drug Administration's Adverse Event Reporting System (AERS). Design: We used the multi-item gamma-Poisson shrinker (MGPS) data mining algorithm to analyze more than 40 yr of safety data in AERS. MGPS uses a Bayesian model to calculate adjusted observed to expected ratios [empiric Bayes geometric mean (EBGM) values] for every drug-adverse event combination in AERS, focusing on hepatotoxicity events. Results: MGPS identified higher-than-expected reporting of severe liver injury in pediatric patients treated with propylthiouracil but not with methimazole. Propylthiouracil had a high adjusted reporting ratio for severe liver injury (EBGM 17; 90% confidence interval = 11.5-24.1) in the group less than 17 yr old. The highest EBGM values for methimazole were with mild liver injury in the group 61 yr and older [EBGM 4.8 (3.3-6.8)], which consisted of cholestasis. Vasculitis was also observed for propylthiouracil in children and adolescents, reaching higher EBGM values than hepatotoxicity signals. Conclusions: MGPS detects higher-than-expected reporting of severe hepatotoxicity and vasculitis in children and adolescents with propylthiouracil but not with methimazole. (J Clin Endocrinol Metab 95: 3260-3267, 2010) C1 [Rivkees, Scott A.] Yale Univ, Yale Pediat Thyroid Ctr, Sect Dev Endocrinol & Biol, Sch Med, New Haven, CT 06520 USA. [Szarfman, Ana] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Rivkees, SA (reprint author), Yale Univ, Yale Pediat Thyroid Ctr, Sect Dev Endocrinol & Biol, Sch Med, 464 Congress Ave, New Haven, CT 06520 USA. EM scott.rivkees@yale.edu NR 32 TC 55 Z9 58 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2010 VL 95 IS 7 BP 3260 EP 3267 DI 10.1210/jc.2009-2546 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 621OS UT WOS:000279589600026 PM 20427502 ER PT J AU Rao, SS Mohan, KVK Atreya, CD AF Rao, Shilpakala Sainath Mohan, Ketha V. K. Atreya, Chintamani D. TI Detection technologies for Bacillus anthracis: Prospects and challenges SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Review DE Bacillus anthracis; Detection; Biological warfare agents; Biological agents; Antibodies; Aptamers ID POLYMERASE-CHAIN-REACTION; REAL-TIME PCR; BIOLOGICAL THREAT AGENTS; ACID-SOLUBLE PROTEINS; FRAGMENT LENGTH POLYMORPHISM; LINKED-IMMUNOSORBENT-ASSAY; CELL-WALL POLYSACCHARIDE; COLLAGEN-LIKE REGION; 16S RIBOSOMAL-RNA; CEREUS GROUP AB Bacillus anthracis is a Gram-positive, spore-forming bacterium representing the etiological agent of acute infectious disease anthrax, a lethal but rare disease of animals and humans in nature. With recent use of anthrax as a bioweapon, a number of techniques have been recently developed and evaluated to facilitate its rapid detection of B. anthracis in the environment as well as in point-of-care settings for humans suspected of exposure to the pathogen. Complex laboratory methods for B. anthracis identification are required since B. anthracis has similarities with other Bacillus species and its existence in both spore and vegetative forms. This review discusses current challenges and various improvements associated with anthrax agent detection. Published by Elsevier B.V. C1 [Rao, Shilpakala Sainath; Mohan, Ketha V. K.; Atreya, Chintamani D.] US FDA, Sect Cell Biol, Lab Cellular Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Atreya, CD (reprint author), Bldg 29A,Room 2C-11,NIH Campus,8800 Rockville Pik, Bethesda, MD 20892 USA. FU Biomedical Advanced Research Development Authority (BARDA); Center for Biologics Evaluation and Research (CBER) FX This work was partially supported by Biomedical Advanced Research Development Authority (BARDA) funds to CA. SS is a recipient of a postdoctoral fellowship at the Center for Biologics Evaluation and Research (CBER) administered by the Oak Ridge Institute for Science and Education (ORISE) through an intra agency agreement between the U. S. Department of Energy and the U.S. Food and Drug Administration. Authors wish to thank Dr. Jan Simak, DH, OBRR, CBER and Dr. Tahir Malik, DVP, CBER for their review of the manuscript. NR 162 TC 48 Z9 51 U1 4 U2 46 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD JUL PY 2010 VL 82 IS 1 BP 1 EP 10 DI 10.1016/j.mimet.2010.04.005 PG 10 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 621HV UT WOS:000279567700001 PM 20399814 ER PT J AU Davis, MA Lim, JY Soyer, Y Harbottle, H Chang, YF New, D Orfe, LH Besser, TE Call, DR AF Davis, Margaret A. Lim, Ji Youn Soyer, Yesim Harbottle, Heather Chang, Yung-Fu New, Daniel Orfe, Lisa H. Besser, Thomas E. Call, Douglas R. TI Development and validation of a resistance and virulence gene microarray targeting Escherichia coli and Salmonella enterica SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE Microarray; Validation; Resistance genes; Enterobacteriaceae ID DIFFERENTIALLY EXPRESSED GENES; MEDIATED QUINOLONE RESISTANCE; SPECTRUM BETA-LACTAMASES; ANTIMICROBIAL RESISTANCE; DNA MICROARRAY; OLIGONUCLEOTIDE MICROARRAY; MOLECULAR CHARACTERIZATION; PLATFORM COMPARABILITY; GENOME SEQUENCE; QUALITY-CONTROL AB A microarray was developed to simultaneously screen Escherichia coli and Salmonella enterica for multiple genetic traits. The final array included 203 60-mer oligonucleotide probes, including 117 for resistance genes, 16 for virulence genes, 25 for replicon markers, and 45 other markers. Validity of the array was tested by assessing inter-laboratory agreement among four collaborating groups using a blinded study design. Internal validation indicated that the assay was reliable (area under the receiver-operator characteristic curve = 0.97). Inter-laboratory agreement, however, was poor when estimated using the intraclass correlation coefficient, which ranged from 0.27 (95% confidence interval 0.24, 0.29) to 0.29 (0.23, 0.34). These findings suggest that extensive testing and procedure standardization will be needed before bacterial genotyping arrays can be readily shared between laboratories. (C) 2010 Elsevier B.V. All rights reserved. C1 [Davis, Margaret A.; New, Daniel; Orfe, Lisa H.; Besser, Thomas E.; Call, Douglas R.] Washington State Univ, Dept Vet Microbiol & Pathol, Coll Vet Med, Pullman, WA 99164 USA. [Lim, Ji Youn] Univ Idaho, Microbiol Mol Biol & Biochem Dept, Moscow, ID 83844 USA. [Soyer, Yesim] Cornell Univ, Dept Food Sci, Ithaca, NY 14853 USA. [Harbottle, Heather] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [Chang, Yung-Fu] Cornell Univ, Coll Vet Med, Dept Populat Med & Diagnost Sci, Ithaca, NY 14853 USA. RP Davis, MA (reprint author), Washington State Univ, Dept Vet Microbiol & Pathol, Coll Vet Med, POB 647040, Pullman, WA 99164 USA. EM madavis@vetmed.wsu.edu RI Soyer, Yesim/A-8584-2010; Besser, Thomas/A-4655-2011; OI Soyer, Yesim/0000-0001-9687-9715 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [N01-A1-30054, N01-A1-30055] FX We gratefully acknowledge the technical assistance of Stacey LaFrentz, Katherine N.K. Baker and Dennis M. Satterwhite. This project has been funded in whole with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract numbers N01-A1-30054 and N01-A1-30055. NR 60 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD JUL PY 2010 VL 82 IS 1 BP 36 EP 41 DI 10.1016/j.mimet.2010.03.017 PG 6 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 621HV UT WOS:000279567700005 PM 20362014 ER PT J AU Castelan-Vega, JA Jimenez-Alberto, A Ribas-Aparicio, RM AF Castelan-Vega, Juan A. Jimenez-Alberto, Alicia Ribas-Aparicio, Rosa M. TI Homology modeling and molecular dynamics simulations of HgiDII methyltransferase in complex with DNA and S-adenosyl-methionine: Catalytic mechanism and interactions with DNA SO JOURNAL OF MOLECULAR MODELING LA English DT Article DE DNA-methyltransferase; DNA recognition; Homology modeling; M.HgiDII; Molecular dynamics; S-adenosyl-methionine ID TARGET RECOGNITION DOMAIN; CYTOSINE METHYLTRANSFERASE; HHAL METHYLTRANSFERASE; SEQUENCE; BASE; RESTRICTION; PROTEINS; ENZYMES; BINDING; EVOLUTION AB M.HgiDII is a methyltransferase (MTase) from Herpetosiphon giganteus that recognizes the sequence GTCGAC. This enzyme belongs to a group of MTases that share a high degree of amino acid similarity, albeit none of them has been thoroughly characterized. To study the catalytic mechanism of M.HgiDII and its interactions with DNA, we performed molecular dynamics simulations with a homology model of M.HgiDII complexed with DNA and S-adenosyl-methionine. Our results indicate that M.HgiDII may not rely only on Glu119 to activate the cytosine ring, which is an early step in the catalysis of cytosine methylation; apparently, Arg160 and Arg162 may also participate in the activation by interacting with cytosine O2. Another residue from the catalytic site, Val118, also played a relevant role in the catalysis of M.HgiDII. Val118 interacted with the target cytosine and kept water molecules from accessing the region of the catalytic pocket where Cys79 interacts with cytosine, thus preventing water-mediated disruption of interactions in the catalytic site. Specific recognition of DNA was mediated mainly by amino acids of the target recognition domain, although some amino acids (loop 80-88) of the catalytic domain may also contribute to DNA recognition. These interactions involved direct contacts between M.HgiDII and DNA, as well as indirect contacts through water bridges. Additionally, analysis of sequence alignments with closely related MTases helped us to identify a motif in the TRD of M.HgiDII that may be relevant to specific DNA recognition. C1 [Jimenez-Alberto, Alicia; Ribas-Aparicio, Rosa M.] Inst Politecn Nacl, Escuela Nacl Ciencias Biol, Dept Microbiol, Mexico City 11340, DF, Mexico. [Castelan-Vega, Juan A.] US FDA, CBER, DBPAP, Rockville, MD 20852 USA. RP Ribas-Aparicio, RM (reprint author), Inst Politecn Nacl, Escuela Nacl Ciencias Biol, Dept Microbiol, Prolongac Carpio & Plan Ayala S-N, Mexico City 11340, DF, Mexico. EM rmrj@encb.ipn.mx FU Instituto Politecnico Nacional (IPN); SIP [20091190]; Consejo Nacional de Ciencia y Tecnolog a (CONACyT, Mexico); Comite Tecnico de Prestaciones a Becarios (COTEPABE, IPN); U.S. Department of Energy; U.S. Food and Drug Administration FX RMR-A is grateful for support to this work from the Instituto Politecnico Nacional (IPN), SIP grant number 20091190, and is recipient of COFAA and EDD fellowships, granted by the IPN. JAC gives thanks to the Consejo Nacional de Ciencia y Tecnolog a (CONACyT, Mexico) and the IPN for graduate study fellowships. JAC thanks support from the Comite Tecnico de Prestaciones a Becarios (COTEPABE, IPN). During the realization of this work, JAC received financial support from the Research Participation Program at the Center for Biologics Evaluation and Research, administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. The authors are greatly indebted to Juan L. Arciniega (Food and Drug Administration) and the NIH Helix Systems group for providing access to high-performance computational resources. NR 46 TC 1 Z9 1 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1610-2940 J9 J MOL MODEL JI J. Mol. Model. PD JUL PY 2010 VL 16 IS 7 BP 1213 EP 1222 DI 10.1007/s00894-009-0632-9 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Biophysics; Chemistry; Computer Science GA 600ZL UT WOS:000278027600005 PM 20033464 ER PT J AU Mahmood, I AF Mahmood, Iftekhar TI Theoretical Versus Empirical Allometry: Facts Behind Theories and Application to Pharmacokinetics SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Editorial Material DE clearance; pharamcokinetics; population pharmacokinetics; hepatic clearance; renal excretion ID UNIVERSAL METABOLIC ALLOMETRY; POPULATION PHARMACOKINETICS; DRUG CLEARANCE; BODY-SIZE; ENERGY-METABOLISM; CHILDREN; PREDICTION; EXPONENTS; MODEL; MASS AB Although, no credible data are available, it is widely believed that the pharmacokinetic parameters such as clearance, volume of distribution, and elimination half-life can be scaled with a fixed exponent of 0.75, 1.0, and 0.25, respectively. However, logically it is difficult to perceive that the exponents of allometry for a given parameter will revolve around a fixed number. Over the last 80 years, theoretical biologists and physiologists are entangled in an argument whether the exponent of basal metabolic rate against body weight is 0.67 or 0.75. There are evidence for and against these two exponents. However, in-depth investigative works suggest that there is not really any universal exponent for any allometrically related parameter and the exponent of allometry depends on several factors. The main focus of this report is to show the readers that there is enough evidence from experimental data that negate the notion of fixed exponents in biology, physiology, and pharmacokinetics. In short, the notion of a fixed exponent is theoretical and there is no evidence that the exponent of a physiological or pharmacokinetic parameter revolves around a fixed number. (C) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:2927-2933, 2010 C1 [Mahmood, Iftekhar] US FDA, Div Hematol, OBRR, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Mahmood, I (reprint author), US FDA, Div Hematol, OBRR, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM iftekhar.mahmood@fda.hhs.gov NR 46 TC 38 Z9 41 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD JUL PY 2010 VL 99 IS 7 BP 2927 EP 2933 DI 10.1002/jps.22073 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 617JL UT WOS:000279276800001 PM 20127826 ER PT J AU Wokovich, AM Shen, MY Doub, WH Machado, SG Buhse, LF AF Wokovich, Anna M. Shen, Meiyu Doub, William H. Machado, Stella G. Buhse, Lucinda F. TI Release Liner Removal Method For Transdermal Drug Delivery Systems (TDDS) SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE release liner; liner; adhesion; peel; transdermal system; patch ID 90-DEGREES PEEL ADHESION AB A release liner removal test is a valuable test for assessing the quality of a transdermal drug delivery system (i.e., TDDS, patch). This test measures the force required to remove the release liner from a patch. The objective of the present study was to establish sample preparation and instrument parameters for measuring release liner removal adhesion for TDDS. Ten TDDS were evaluated (six drugs for a total of 29 lots). Patches which had a rate-controlling membrane were run as-is, since they could not be cut to a precise width without sacrificing their structural integrity. Patches that were square or rectangular in shape were run as-is, and the width of these patches was determined using a digital caliper. Patches which were not square or rectangular in shape and did not have a rate-controlling membrane were cut to a precise width using a specimen cutter. Double-sided tape was used to adhere the liner side of the transdermal system to a clean stainless steel test panel. A release liner peel adhesion method for TDDS is proposed using a dwell time of approximately 3 min, a peel angle of 90 degrees, and a peel speed of 300 mm/min. (C) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3177-3187, 2010 C1 [Wokovich, Anna M.; Doub, William H.; Buhse, Lucinda F.] US FDA, Ctr Drug Evaluat & Res, St Louis, MO USA. [Shen, Meiyu; Machado, Stella G.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Wokovich, AM (reprint author), US FDA, Ctr Drug Evaluat & Res, St Louis, MO USA. EM anna.wokovich@fda.hhs.gov NR 26 TC 3 Z9 3 U1 1 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD JUL PY 2010 VL 99 IS 7 BP 3177 EP 3187 DI 10.1002/jps.22067 PG 11 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 617JL UT WOS:000279276800024 PM 20135693 ER PT J AU Liu, YB Maruvada, S Herman, BA Harris, GR AF Liu, Yunbo Maruvada, Subha Herman, Bruce A. Harris, Gerald R. TI Egg white as a blood coagulation surrogate SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article DE biomedical ultrasonics; coagulation; haemodynamics; ultrasonic measurement; viscosity ID INTENSITY FOCUSED ULTRASOUND; CONTRAST-ENHANCED ULTRASOUND; THERMAL ABLATION; MIMICKING FLUID; PHANTOM; TISSUE; PERFUSION; ATTENUATION; VALIDATION; HEMORRHAGE AB Egg white, a protein-containing solution, is characterized as a blood coagulation surrogate for the acoustical and thermal evaluation of therapeutic ultrasound, especially high intensity focused ultrasound (HIFU) devices. Physical properties, including coagulation temperature, frequency dependent attenuation, sound speed, viscosity, and thermal properties, were measured as a function of temperature (20-95 degrees C). Thermal coagulation and attenuation (5-12 and 1 MHz) of cow blood, pig blood, and human blood also were assessed and compared with egg white. For a 30 s thermal exposure, both egg white and blood samples (3 mm thickness) started to denature at 65 degrees C and coagulate into an elastic gel at 85 degrees C. The attenuation of egg white was found to be similar to that of the blood samples, having values of 0.23f(1.09), 1.58f(0.61), and 2.7f(0.5) dB/cm at 20, 75, and 95 degrees C, respectively. This significant attenuation increase with temperature was determined to be caused mainly by bubble cavity formation. The other temperature-dependent parameters are also similar to the reported values for blood. These properties make egg white a potentially useful bench testing tool for the safety and efficacy evaluation of therapeutic ultrasound devices. (C) 2010 Acoustical Society of America. [DOI: 10.1121/1.3442361] C1 [Liu, Yunbo; Maruvada, Subha; Herman, Bruce A.; Harris, Gerald R.] Food & Drug Adm, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Liu, YB (reprint author), Food & Drug Adm, Ctr Devices & Radiol Hlth, Bldg 62,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM yxl@cdrh.fda.gov FU Defense Advanced Research Projects Agency (DARPA) [224-05-6016] FX The authors are grateful to Dr. Luke Herbertson and Dr. Richard Malinauskas for supporting with the blood experiments. This research was supported by Defense Advanced Research Projects Agency (DARPA) through IAG Grant No. 224-05-6016. NR 35 TC 1 Z9 1 U1 1 U2 2 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JUL PY 2010 VL 128 IS 1 BP 480 EP 489 DI 10.1121/1.3442361 PG 10 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 626WV UT WOS:000279999700061 PM 20649242 ER PT J AU Mohammed, HP Ramos, MM Rivera, A Johansson, M Munoz-Jordan, JL Sun, W Tomashek, KM AF Mohammed, Hamish P. Ramos, Mary M. Rivera, Aidsa Johansson, Michael Munoz-Jordan, Jorge L. Sun, Wellington Tomashek, Kay M. TI Travel-Associated Dengue Infections in the United States, 1996 to 2005 - Response SO JOURNAL OF TRAVEL MEDICINE LA English DT Letter C1 [Mohammed, Hamish P.; Rivera, Aidsa; Johansson, Michael; Munoz-Jordan, Jorge L.; Tomashek, Kay M.] Ctr Dis Control & Prevent, Dengue Branch, Div Vector Borne Infect Dis, San Juan, Puerto Rico, Spain. [Ramos, Mary M.] Univ New Mexico, Dept Pediat, Albuquerque, NM 87131 USA. [Sun, Wellington] US FDA, Div Vaccine & Related Prod Applicat, Kensington, MD USA. RP Mohammed, HP (reprint author), Ctr Dis Control & Prevent, Dengue Branch, Div Vector Borne Infect Dis, San Juan, Puerto Rico, Spain. NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1195-1982 J9 J TRAVEL MED JI J. Travel Med. PD JUL-AUG PY 2010 VL 17 IS 4 BP 286 EP 286 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 619SE UT WOS:000279449800016 ER PT J AU Dey, R Meneses, C Salotra, P Kamhawi, S Nakhasi, HL Duncan, R AF Dey, Ranadhir Meneses, Claudio Salotra, Poonam Kamhawi, Shaden Nakhasi, Hira L. Duncan, Robert TI Characterization of a Leishmania stage-specific mitochondrial membrane protein that enhances the activity of cytochrome c oxidase and its role in virulence SO MOLECULAR MICROBIOLOGY LA English DT Article ID PROCYCLIC TRYPANOSOMA-BRUCEI; DIFFERENTIALLY EXPRESSED GENES; PHLEBOTOMINE SAND FLIES; ATTENUATED VIRULENCE; PROTECTIVE IMMUNITY; PARASITE SURVIVAL; RESPIRATORY-CHAIN; INFECTIVE STAGE; MAMMALIAN HOSTS; DOWN-REGULATION AB P>Leishmaniasis is caused by the dimorphic protozoan parasite Leishmania. Differentiation of the insect form, promastigotes, to the vertebrate form, amastigotes, and survival inside the vertebrate host accompanies a drastic metabolic shift. We describe a gene first identified in amastigotes that is essential for survival inside the host. Gene expression analysis identified a 27 kDa protein-encoding gene (Ldp27) that was more abundantly expressed in amastigotes and metacyclic promastigotes than in procyclic promastigotes. Immunofluorescence and biochemical analysis revealed that Ldp27 is a mitochondrial membrane protein. Co-immunoprecipitation using antibodies to the cytochrome c oxidase (COX) complex, present in the inner mitochondrial membrane, placed the p27 protein in the COX complex. Ldp27 gene-deleted parasites (Ldp27-/-) showed significantly less COX activity and ATP synthesis than wild type in intracellular amastigotes. Moreover, the Ldp27-/- parasites were less virulent both in human macrophages and in BALB/c mice. These results demonstrate that Ldp27 is an important component of an active COX complex enhancing oxidative phosphorylation specifically in infectious metacyclics and amastigotes and promoting parasite survival in the host. Thus, Ldp27 can be explored as a potential drug target and parasites devoid of the p27 gene could be considered as a live attenuated vaccine candidate against visceral leishmaniasis. C1 [Dey, Ranadhir; Nakhasi, Hira L.; Duncan, Robert] US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Meneses, Claudio; Kamhawi, Shaden] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. [Salotra, Poonam] Safdarjung Hosp Campus, Inst Pathol ICMR, New Delhi, India. RP Duncan, R (reprint author), US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM robert.duncan@fda.hhs.gov RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 FU Intramural NIH HHS [Z99 OD999999] NR 68 TC 28 Z9 29 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD JUL PY 2010 VL 77 IS 2 BP 399 EP 414 DI 10.1111/j.1365-2958.2010.07214.x PG 16 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 620YX UT WOS:000279540600010 PM 20497506 ER PT J AU Braun, MM Farag-El-Massah, S Xu, K Cote, TR AF Braun, M. Miles Farag-El-Massah, Sheiren Xu, Kui Cote, Timothy R. TI Emergence of orphan drugs in the United States: a quantitative assessment of the first 25 years SO NATURE REVIEWS DRUG DISCOVERY LA English DT Article ID RARE DISEASES AB The 1983 US Orphan Drug Act has stimulated the development of new therapies for rare diseases. To provide the first comprehensive overview of orphan-designated products and their indications, this article quantitatively analyses the characteristics and distribution of orphan designations and approvals by the US Food and Drug Administration from 1983 to August 2008. Of the 1,892 orphan-designated products, 326 received marketing approval, representing 247 different drugs and more than 200 different diseases. About half of the approvals had occurred by 4 years after designation was granted. The most common patient population size for orphan designations and approvals was fewer than 10,000 patients, and cancer was the most common disease area. The implications of such findings for future development and marketing of therapies for rare diseases are discussed. C1 [Braun, M. Miles; Farag-El-Massah, Sheiren; Xu, Kui; Cote, Timothy R.] US FDA, Off Orphan Prod Dev, Silverspring, MD 20993 USA. RP Cote, TR (reprint author), US FDA, Off Orphan Prod Dev, Silverspring, MD 20993 USA. EM timothy.cote@fda.hhs.gov NR 7 TC 68 Z9 70 U1 0 U2 15 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 JUL PY 2010 VL 9 IS 7 BP 519 EP 522 DI 10.1038/nrd3160 PG 4 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 628TF UT WOS:000280143900022 PM 20531273 ER PT J AU Hampel, H Frank, R Broich, K Teipel, SJ Katz, RG Hardy, J Herholz, K Bokde, ALW Jessen, F Hoessler, YC Sanhai, WR Zetterberg, H Woodcock, J Blennow, K AF Hampel, Harald Frank, Richard Broich, Karl Teipel, Stefan J. Katz, Russell G. Hardy, John Herholz, Karl Bokde, Arun L. W. Jessen, Frank Hoessler, Yvonne C. Sanhai, Wendy R. Zetterberg, Henrik Woodcock, Janet Blennow, Kaj TI Biomarkers for Alzheimer's disease: academic, industry and regulatory perspectives SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID MILD COGNITIVE IMPAIRMENT; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL GLUCOSE-METABOLISM; GAMMA-SECRETASE INHIBITOR; HUMAN CEREBROSPINAL-FLUID; LONGITUDINAL PET EVALUATION; AMYLOID PRECURSOR PROTEIN; BETA IMMUNIZATION AN1792; GENOME-WIDE ASSOCIATION; A-BETA AB Advances in therapeutic strategies for Alzheimer's disease that lead to even small delays in onset and progression of the condition would significantly reduce the global burden of the disease. To effectively test compounds for Alzheimer's disease and bring therapy to individuals as early as possible there is an urgent need for collaboration between academic institutions, industry and regulatory organizations for the establishment of standards and networks for the identification and qualification of biological marker candidates. Biomarkers are needed to monitor drug safety, to identify individuals who are most likely to respond to specific treatments, to stratify presymptomatic patients and to quantify the benefits of treatments. Biomarkers that achieve these characteristics should enable objective business decisions in portfolio management and facilitate regulatory approval of new therapies. C1 [Hampel, Harald] Goethe Univ Frankfurt, Dept Psychiat Psychosomat Med & Psychotherapy, D-60528 Frankfurt, Germany. [Frank, Richard] GE Healthcare, Global Med Affairs & Clin Strategy, Princeton, NJ 08540 USA. [Broich, Karl] Fed Inst Drugs & Med Devices BfArM, D-53175 Bonn, Germany. [Teipel, Stefan J.] Univ Rostock, Dept Psychiat, D-18147 Rostock, Germany. [Teipel, Stefan J.; Jessen, Frank] German Ctr Neurodegenerat Disorders, DZNE, D-18147 Rostock, Germany. [Katz, Russell G.] US FDA, Div Neurol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Hardy, John] Univ Coll, Inst Neurol, Dept Mol Neurosci, London WC1 3BG, England. [Hardy, John] Univ Coll, Inst Neurol, Reta Lila Weston Labs, London WC1 3BG, England. [Herholz, Karl] Univ Manchester, Wolfson Mol Imaging Ctr, Manchester M20 3LJ, Lancs, England. [Bokde, Arun L. W.] Natl Childrens Hosp, Adelaide & Meath Hosp Incorporating, Trin Ctr Hlth Sci, Trin Coll Dublin,Sch Med, Dublin 24, Ireland. [Bokde, Arun L. W.] Natl Childrens Hosp, Adelaide & Meath Hosp Incorporating, Trin Ctr Hlth Sci, Trin Coll Dublin,Trinity Coll Inst Neurosci, Dublin 24, Ireland. [Jessen, Frank] Univ Bonn, Dept Psychiat, D-53105 Bonn, Germany. [Hoessler, Yvonne C.] Univ Munich, Alzheimer Mem Ctr, Dept Psychiat, D-80336 Munich, Germany. [Sanhai, Wendy R.] US FDA, Off Commissioner, Silver Spring, MD 20993 USA. [Zetterberg, Henrik; Blennow, Kaj] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, S-43180 Motndal, Sweden. [Woodcock, Janet] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Hampel, H (reprint author), Goethe Univ Frankfurt, Dept Psychiat Psychosomat Med & Psychotherapy, Heinrich Hoffmann Str 10, D-60528 Frankfurt, Germany. EM harald.hampel@med.uni-frankfurt.de RI Hardy, John/C-2451-2009; Jessen, Frank/E-7655-2012; OI Hampel, Harald/0000-0003-0894-8982 FU Science Foundation Ireland [08/IN.1/B1846] FX The authors would like to thank K. Duggan for technical assistance. H.H. acknowledges support by the Science Foundation Ireland Investigator Neuroimaging Grant Programme (08/IN.1/B1846). NR 138 TC 300 Z9 312 U1 14 U2 91 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 JUL PY 2010 VL 9 IS 7 BP 560 EP 574 DI 10.1038/nrd3115 PG 15 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 628TF UT WOS:000280143900026 PM 20592748 ER PT J AU Ferguson, SA Boctor, SY AF Ferguson, Sherry A. Boctor, Sherin Y. TI Cocaine responsiveness or anhedonia in rats treated with methylphenidate during adolescence SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Methylphenidate; Adolescence; Rat; Conditioned place preference; Cocaine; Saccharin ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; CONDITIONED PLACE PREFERENCE; DEFICIT HYPERACTIVITY DISORDER; EARLY-LIFE EXPOSURE; SUBSTANCE-ABUSE; FEMALE RATS; ORAL METHYLPHENIDATE; BEHAVIORAL-RESPONSES; CROSS-SENSITIZATION; LOCOMOTOR-ACTIVITY AB Methylphenidate (MPH) treatment in boys diagnosed with ADHD is reported to decrease the risk of drug abuse in adulthood. Similarly, MPH treatment appears to decrease the cocaine preference of male rats during conditioned place preference (CPP) tests. However, the effects of MPH treatment on later drug use of girls/women or CPP in female rodents have not been fully examined, nor have a clinically-relevant MPH dose and/or administration route been thoroughly studied. Here, Sprague-Dawley rats (n = 34/sex/treatment) were treated orally 3x/day on postnatal days (PNDs) 29-50 with water or 3 mg MPH/kg, a dose producing serum levels within the human clinical range. CPP assessments to cocaine (10 mg/kg, ip) (PNDs 62-71) indicated MPH-treated rats were less active during pre- and postconditioning sessions (p<.04), but there were no significant MPH-related differences in conditioning strength. Baseline open field activity at PND 84 indicated that MPH-treated females were more active than same-sex controls (p<.05). A cocaine challenge (10 mg/kg, ip) elevated activity similarly in MPH-treated and controls of both sexes. As an anhedonia measure, saccharin solution intake on PNDs 87-90 indicated no significant MPH effects. Estrous cycle phase did not appear to affect cocaine response during CPP or open field assessments. Hormonal levels at PND 90 indicated 63% higher corticosterone levels in MPH-treated females relative to same-sex controls (p<.05), a finding that deserves further investigation. These results address some of the major issues surrounding animal models of MPH treatment and provide additional support for a lack of severe long-term behavioral effects of adolescent MPH. Published by Elsevier Inc. C1 [Ferguson, Sherry A.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Interdisciplinary Biomed Sci, Little Rock, AR 72205 USA. RP Ferguson, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM Sherry.Ferguson@fda.hhs.gov FU National Center for Toxicological Research/FDA FX Funding for this study was provided by the National Center for Toxicological Research/FDA. The authors are grateful for the technical expertise provided by Ms. Lee McVay and the animal care staff of the Bionetics Corporation. We appreciate the concentration assays provided by Mr. Paul Siitonen, Division of Biochemical Toxicology, NCTR for the MPH solutions. Mr. Richard Rasmussen of the Bionetics Corporation provided design and construction of the CPP apparatus and Ms. Jennifer Boyd-Cook expertly scored the CPP videorecordings. We are thankful to Mr. Ralph Patton for conducting the hormone assays and Mr. Andy Matson of the Bionetics Corporation for accurate MPH, vehicle and cocaine solutions. Dr. Natalya Sadovova conducted the estrous phase analyses. Finally, we acknowledge Dr. Suzanne Morris, Division of Genetic and Reproductive Toxicology, NCTR for her encouragement in the conduct of this study. All experiments reported here complied with the current laws of the United States. NR 61 TC 18 Z9 18 U1 3 U2 4 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 JUL-AUG PY 2010 VL 32 IS 4 BP 432 EP 442 DI 10.1016/j.ntt.2010.03.007 PG 11 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 620VF UT WOS:000279528000003 PM 20347964 ER PT J AU Chelonis, J Johnson, T Ferguson, S Kubacak, B Edwards, M Paule, M AF Chelonis, John Johnson, Teresa Ferguson, Sherry Kubacak, Brian Edwards, Mark Paule, Merle TI Effects of methylphenidate on motivation in children with attention-deficit/hyperactivity disorder SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 34th Annual Meeting of the Neurobehavioral-Teratology-Society/50th Annual Meeting of the Teratology-Society/23rd Annual Meeting of the Organization-of-Teratology-Information-Specialists CY JUN 26-30, 2010 CL Louisville, KY SP Neurobehav Teratol Soc, Teratol Soc, Org Teratol Informat Specialists C1 [Chelonis, John; Ferguson, Sherry; Paule, Merle] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Chelonis, John; Johnson, Teresa; Ferguson, Sherry; Kubacak, Brian; Edwards, Mark; Paule, Merle] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Little Rock, AR 72205 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-AUG PY 2010 VL 32 IS 4 MA NBTS30 BP 504 EP 504 DI 10.1016/j.ntt.2010.04.031 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 620VF UT WOS:000279528000039 ER PT J AU Garey, J Binienda, Z Paule, M AF Garey, Joan Binienda, Zbigniew Paule, Merle TI Effect of lifetime exposure to acrylamide on motor nerve conduction velocity in rats at one year of age SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 34th Annual Meeting of the Neurobehavioral-Teratology-Society/50th Annual Meeting of the Teratology-Society/23rd Annual Meeting of the Organization-of-Teratology-Information-Specialists CY JUN 26-30, 2010 CL Louisville, KY SP Neurobehav Teratol Soc, Teratol Soc, Org Teratol Informat Specialists C1 [Garey, Joan] SRC Inc, Arlington, VA USA. [Binienda, Zbigniew; Paule, Merle] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-AUG PY 2010 VL 32 IS 4 MA NBTS31 BP 504 EP 505 DI 10.1016/j.ntt.2010.04.032 PG 2 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 620VF UT WOS:000279528000040 ER PT J AU Kwitkowski, VE Prowell, TM Ibrahim, A Farrell, AT Justice, R Mitchell, SS Sridhara, R Pazdur, R AF Kwitkowski, Virginia E. Prowell, Tatiana M. Ibrahim, Amna Farrell, Ann T. Justice, Robert Mitchell, Shan Sun Sridhara, Rajeshwari Pazdur, Richard TI Temsirolimus: Is Improved Survival the Correct Expression of Drug Activity? Reply SO ONCOLOGIST LA English DT Letter C1 [Kwitkowski, Virginia E.; Prowell, Tatiana M.; Ibrahim, Amna; Farrell, Ann T.; Justice, Robert; Sridhara, Rajeshwari; Pazdur, Richard] US FDA, Div Drug Oncol Prod, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Mitchell, Shan Sun] Univ Texas Arlington, Dept Math, Arlington, TX 76019 USA. RP Kwitkowski, VE (reprint author), US FDA, Div Drug Oncol Prod, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Mailstop 2105, Silver Spring, MD 20993 USA. EM Virginia.Kwitkowski@fda.hhs.gov NR 0 TC 0 Z9 0 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 JUL PY 2010 VL 15 IS 7 BP 792 EP 792 DI 10.1634/theoncologist.2010-0144 PG 1 WC Oncology SC Oncology GA 633FH UT WOS:000280484600016 ER PT J AU Agrawal, A Pfefer, TJ Gilani, N Drezek, R AF Agrawal, Anant Pfefer, T. Joshua Gilani, Naureen Drezek, Rebekah TI Three-dimensional characterization of optical coherence tomography point spread functions with a nanoparticle-embedded phantom SO OPTICS LETTERS LA English DT Article ID MICROSCOPY; RESOLUTION AB We present a novel (to our knowledge) approach for measurement of the three-dimensional point spread function (PSF) of optical coherence tomography (OCT) systems using a nanoparticle-embedded phantom (NEP), toward development of standardized test methods for biophotonic imaging. The NEP comprises highly reflective plasmonic nanoparticles, homogeneously distributed in a transparent silicone matrix. OCT image volumes were analyzed to characterize PSFs in axial and lateral directions at a variety of locations in the NEP. Results indicate submicrometer agreement with conventional approaches to measure dimensions of the PSF. The NEP offers a robust approach for validating and comparing imaging performance of OCT devices. (C) 2010 Optical Society of America C1 [Agrawal, Anant; Pfefer, T. Joshua; Gilani, Naureen] US FDA, Opt Diagnost Devices Lab, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Drezek, Rebekah] Rice Univ, Dept Bioengn, Houston, TX 77005 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 RI Drezek, Rebekah/A-5101-2012; Pfefer, Josh/I-9055-2012 NR 11 TC 32 Z9 34 U1 1 U2 4 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD JUL 1 PY 2010 VL 35 IS 13 BP 2269 EP 2271 PG 3 WC Optics SC Optics GA 619NC UT WOS:000279435900051 PM 20596216 ER PT J AU Dworkin, RH Turk, DC Peirce-Sandner, S McDermott, MP Farrar, JT Hertz, S Katz, NP Raja, SN Rappaport, BA AF Dworkin, Robert H. Turk, Dennis C. Peirce-Sandner, Sarah McDermott, Michael P. Farrar, John T. Hertz, Sharon Katz, Nathaniel P. Raja, Srinivasa N. Rappaport, Bob A. TI Placebo and treatment group responses in postherpetic neuralgia vs. painful diabetic peripheral neuropathy clinical trials in the REPORT database SO PAIN LA English DT Review ID ACTIVE-CONTROL TRIALS; IMMPACT RECOMMENDATIONS; DOUBLE-BLIND; PHARMACOLOGICAL MANAGEMENT; OUTCOME MEASURES; ISSUES; LAMOTRIGINE; TOPIRAMATE C1 [Dworkin, Robert H.; Peirce-Sandner, Sarah] Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY 14642 USA. [Dworkin, Robert H.] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA. [Turk, Dennis C.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [McDermott, Michael P.] Univ Rochester, Sch Med & Dent, Dept Biostat & Computat Biol, Rochester, NY 14642 USA. [McDermott, Michael P.] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA. [Farrar, John T.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Hertz, Sharon; Rappaport, Bob A.] US FDA, Bethesda, MD 20014 USA. [Katz, Nathaniel P.] Tufts Univ, Boston, MA 02111 USA. [Katz, Nathaniel P.] Analges Res, Needham, MA USA. [Raja, Srinivasa N.] Johns Hopkins Univ, Dept Anesthesiol & Crit Care Med, Baltimore, MD USA. RP Dworkin, RH (reprint author), Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY 14642 USA. EM robert_dworkin@urmc.rochester.edu RI Farrar, John/A-1037-2007; OI Farrar, John/0000-0001-8656-5157; Yang, Shuman/0000-0002-9638-0890 FU US Food and Drug Administration FX The authors thank Ms. Amanda Kascic for her contributions to the preparation of the REPORT database. The views expressed in this article are those of the authors, none of whom have financial conflicts of interest related to the material presented in this manuscript. No official endorsement by the US Food and Drug Administration or the pharmaceutical companies that have provided unrestricted grants for the support of IMMPACT to the University of Rochester Office of Continuing Professional Education should be inferred. NR 37 TC 29 Z9 30 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUL PY 2010 VL 150 IS 1 BP 12 EP 16 DI 10.1016/j.pain.2010.02.002 PG 5 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 608AI UT WOS:000278549900007 PM 20202753 ER PT J AU Talele, SS Xu, K Pariser, AR Braun, MM Farag-El-Massah, S Phillips, MI Thompson, BH Cote, TR AF Talele, Sonali S. Xu, Kui Pariser, Anne R. Braun, M. Miles Farag-El-Massah, Sheiren Phillips, M. Ian Thompson, Barry H. Cote, Timothy R. TI Therapies for Inborn Errors of Metabolism: What Has the Orphan Drug Act Delivered? SO PEDIATRICS LA English DT Article DE inborn errors of metabolism; lysosomal storage diseases; mitochondrial diseases; orphan drug designation; investigational new drug application; clinical development time ID DISEASES AB OBJECTIVE: The 1983 US Orphan Drug Act established a process through which promising therapies are designated as orphan products and, later, with satisfactory safety and efficacy data, receive marketing approval and fiscal incentives. We examined accomplishments in drug development for inborn errors of metabolism (IEMs). METHODS: Food and Drug Administration data were used to identify orphan product designations and approvals for IEMs, and the trends for the past 26 years were summarized. Individual clinical development times (CDTs) from filing investigational new drug application to marketing approval were determined. RESULTS: We examined 1956 orphan product designations from 1983 through 2008 and found 93 (4.8%) for IEMs. Of those, 24 (25.8%) received marketing approval. This proportion of approval was significantly (P = .036) higher than that for non-IEM orphan products (17%). Among the IEM products, disorders of complex molecules received the most designations and approvals (61 and 11, respectively). Among the subgroups, lysosomal storage diseases received the most designations and approvals (43 and 9, respectively), whereas mitochondrial diseases (other than fatty acid oxidation disorders) received 7 designations with no approvals. We then examined the CDTs for the approved IEM products and found a median of 6.4 years (range: 2.6-25.1 years). Biological products had significantly shorter CDTs than drugs (mean: 4.6 vs 11.0 years; P = .003). CONCLUSION: For 26 years, the Orphan Drug Act has generated new therapies for IEMs. Why some IEMs have motivated successful drug development and others have not remains enigmatic; yet the needs of IEM patients without treatment are a certainty. Pediatrics 2010;126:101-106 C1 [Talele, Sonali S.; Xu, Kui; Braun, M. Miles; Farag-El-Massah, Sheiren; Cote, Timothy R.] US FDA, Off Orphan Prod Dev, Silver Spring, MD 20993 USA. [Pariser, Anne R.] US FDA, Div Gastroenterol Prod, Off New Drugs, Silver Spring, MD 20993 USA. [Talele, Sonali S.; Phillips, M. Ian] Keck Grad Inst, Ctr Rare Dis Therapies, Claremont, CA USA. [Farag-El-Massah, Sheiren] Univ Minnesota, Coll Pharm, Dept Social & Adm Pharm Program, Minneapolis, MN 55455 USA. [Thompson, Barry H.] Amer Coll Med Genet, Bethesda, MD USA. RP Cote, TR (reprint author), US FDA, Off Orphan Prod Dev, 10903 New Hampshire Ave,W032-5271, Silver Spring, MD 20993 USA. EM timothy.cote@fda.hhs.gov NR 8 TC 11 Z9 11 U1 0 U2 3 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 JUL PY 2010 VL 126 IS 1 BP 101 EP 106 DI 10.1542/peds.2009-3246 PG 6 WC Pediatrics SC Pediatrics GA 619LF UT WOS:000279431000014 PM 20566615 ER PT J AU Wang, SJ AF Wang, Sue-Jane TI Multi-Regional Clinical Trials - What are the Challenges? SO PHARMACEUTICAL STATISTICS LA English DT Editorial Material C1 [Wang, Sue-Jane] US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Wang, Sue-Jane] Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Wang, SJ (reprint author), US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 7 TC 3 Z9 4 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1539-1604 J9 PHARM STAT JI Pharm. Stat. PD JUL-SEP PY 2010 VL 9 IS 3 SI SI BP 171 EP 172 DI 10.1002/pst.457 PG 2 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 663VM UT WOS:000282918300001 PM 20821408 ER PT J AU Hung, HMJ Wang, SJ O'Neill, RT AF Hung, H. M. James Wang, Sue-Jane O'Neill, Robert T. TI Consideration of regional difference in design and analysis of multi-regional trials SO PHARMACEUTICAL STATISTICS LA English DT Article DE global trial; inconsistency; I(2) statistic; probability of reversal; random-effect AB Clinical trial strategy, particularly in developing pharmaceutical products, has recently expanded to a global level in the sense that multiple geographical regions participate in the trial simultaneously under the same study protocol. The possible benefits of this strategy are obvious, at least from the cost and efficiency considerations. The challenges with this strategy are many, ranging from trial or data quality assurance to statistical methods for design and analysis of such trials. In many regulatory submissions, the presence of regional differences in the estimated treatment effect, whether they are different only in magnitude or in direction, often presents great difficulty in interpretation of the global trial results, particularly for the acceptability by the local regulatory authorities. This article presents a number of useful statistical analysis tools for exploration of regional differences and a method that may be worth consideration in designing a multi-regional clinical trial. Published in 2010 by John Wiley & Sons, Ltd. C1 [Hung, H. M. James] US FDA, Div Biometr 1, OB, CDER, Silver Spring, MD 20993 USA. [Wang, Sue-Jane; O'Neill, Robert T.] US FDA, Off Biostat, CDER, Silver Spring, MD 20993 USA. RP Hung, HMJ (reprint author), US FDA, Div Biometr 1, OB, CDER, 10903 New Hampshire Ave,BLDG 21,Room 4616, Silver Spring, MD 20993 USA. EM hsienming.hung@fda.hhs.gov NR 13 TC 32 Z9 32 U1 1 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1539-1604 J9 PHARM STAT JI Pharm. Stat. PD JUL-SEP PY 2010 VL 9 IS 3 SI SI BP 173 EP 178 DI 10.1002/pst.440 PG 6 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 663VM UT WOS:000282918300002 PM 20872619 ER PT J AU Chen, YF Wang, SJ Khin, NA Hung, HMJ Laughren, TP AF Chen, Yeh-Fong Wang, Sue-Jane Khin, Ni A. Hung, H. M. James Laughren, Thomas P. TI Trial design issues and treatment effect modeling in multi-regional schizophrenia trials SO PHARMACEUTICAL STATISTICS LA English DT Article DE multi-regional schizophrenia trials; ANCOVA model; recursive partitioning ID NEGATIVE SYNDROME SCALE; CLINICAL-TRIALS; PLACEBO AB In recent years, we have seen an increasing trend of foreign data as part of clinical trial data submitted in new drug applications (NDA) to US Food and Drug Administration (FDA). To understand the design and analysis characteristics, we studied schizophrenia multi-regional clinical trials (MRCTs). The schizophrenia data set consisted of a total of 12 585 patients collected from 33 clinical trials with 63.8% patients from North America, the largest region. The data set constituted 10 schizophrenia drug programs in support of NDAs submitted to FDA from December 1993 to December 2005. Two main objectives were pursued. First, we investigated some study design issues including potential heterogeneity of treatment effect via meta analysis and placebo response pattern over time. Second, we performed empirical modeling in two ways, supervised and unsupervised, to explain potential impact of baseline covariates on treatment effect in MRCTs. Based on our analysis results, placebo response appeared to increase over time and primarily attributed to US region. On average, the observed treatment effect in the US was generally smaller than non-US region. Both supervised and unsupervised empirical modeling selected baseline Positive and Negative Syndrome Scale total score as one of the most important covariates explaining a treatment effect. Region also played a role in explaining potential treatment effect heterogeneity. When baseline body weight was considered as a covariate in an empiric model, our results indicated that it alone did not seem to be an important factor in explaining regional difference. Published in 2010 by John Wiley & Sons, Ltd. C1 [Chen, Yeh-Fong; Hung, H. M. James] US FDA, Div Biometr 1, HFD 710, Off Biostat,Off Translat Sci,CDER, Silver Spring, MD 20993 USA. [Khin, Ni A.; Laughren, Thomas P.] US FDA, Div Psychiat Prod, Off Drug Evaluat 1, Off New Drugs,CDER, Rockville, MD 20857 USA. RP Chen, YF (reprint author), US FDA, Div Biometr 1, HFD 710, Off Biostat,Off Translat Sci,CDER, 10903 New Hampshire Ave,Bldg 21,Room 4610, Silver Spring, MD 20993 USA. EM yehfong.chen@fda.hhs.gov NR 25 TC 24 Z9 24 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1539-1604 J9 PHARM STAT JI Pharm. Stat. PD JUL-SEP PY 2010 VL 9 IS 3 SI SI BP 217 EP 229 DI 10.1002/pst.439 PG 13 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 663VM UT WOS:000282918300007 PM 20872622 ER PT J AU Piccardo, P Cervenakova, L Vasilyeva, I Yakovleva, O Bacik, I Cervenak, J Gregori, L Pomeroy, K Kurillova, L McKenzie, C Asher, DM AF Piccardo, P. Cervenakova, L. Vasilyeva, I. Yakovleva, O. Bacik, I. Cervenak, J. Gregori, L. Pomeroy, K. Kurillova, L. McKenzie, C. Asher, D. M. TI Potential of Cell Substrates used for Production of Biologics to Propagate Transmissible Spongiform Encephalopathy (TSE) Agents: 5-year Update SO PRION LA English DT Meeting Abstract DE cell culture; animal models; biologics; prion; TSE-agent C1 [Piccardo, P.; Bacik, I.; Cervenak, J.; Gregori, L.; Pomeroy, K.; Kurillova, L.; Asher, D. M.] US FDA, Lab Bacterial & TSE Agents, CBER, Rockville, MD 20857 USA. [Cervenakova, L.; Vasilyeva, I.; Yakovleva, O.; McKenzie, C.] Amer Red Cross, Holland Lab, Washington, DC 20006 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 J9 PRION JI Prion PD JUL-SEP PY 2010 VL 4 IS 3 BP 146 EP 146 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 702CN UT WOS:000285872300093 ER PT J AU Yang, H Anderson, SA AF Yang, Hong Anderson, Steven A. TI Updated Risk Assessment of Variant Creutzfeldt-Jakob Disease (vCJD) Risks for US Blood Recipients SO PRION LA English DT Meeting Abstract DE risk assessment; transfusion-transmitted vCJD C1 [Yang, Hong; Anderson, Steven A.] US FDA, Off Biostat & Epidemiol, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 J9 PRION JI Prion PD JUL-SEP PY 2010 VL 4 IS 3 BP 166 EP 166 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 702CN UT WOS:000285872300143 ER PT J AU Gregori, L AF Gregori, Luisa TI Regulatory Challenges Posed by Variant Creutzfeldt-Jakob Disease for Blood Products and Biologics SO PRION LA English DT Meeting Abstract DE regulatory policies; FDA; blood; vCJD; macaque; reference panels C1 [Gregori, Luisa] Food & Drug Adm, CBER, OBRR, DETTD, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 J9 PRION JI Prion PD JUL-SEP PY 2010 VL 4 IS 3 BP 168 EP 168 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 702CN UT WOS:000285872300148 ER PT J AU Bradford, BM Marshall, AS Brown, DA Kisielewiski, DJ Tuzi, NL Piccardo, P Clarke, A Perry, VH Manson, JC AF Bradford, Barry M. Marshall, Alison S. Brown, Deborah A. Kisielewiski, Dorothy J. Tuzi, Nadia L. Piccardo, Pedro Clarke, Alan Perry, V. Hugh Manson, Jean C. TI Inducible Neuronal PrP Knockout Mice Reveal Potential Therapeutic Window for TSE Intervention SO PRION LA English DT Meeting Abstract DE neurodegeneration; tamoxifen inducible Cre/LoxP; PrP knockout C1 [Bradford, Barry M.; Marshall, Alison S.; Brown, Deborah A.; Kisielewiski, Dorothy J.; Manson, Jean C.] Univ Edinburgh, Roslin Inst, Neuropathogenesis Div, Bioctr, Roslin, Midlothian, Scotland. [Bradford, Barry M.; Marshall, Alison S.; Brown, Deborah A.; Kisielewiski, Dorothy J.; Manson, Jean C.] Univ Edinburgh, RDSVS, Neuropathogenesis Div, Bioctr, Roslin, Midlothian, Scotland. [Tuzi, Nadia L.] Univ Edinburgh, Biol Teaching Org, Edinburgh, Midlothian, Scotland. [Piccardo, Pedro] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Clarke, Alan] Cardiff Sch Biosci, Cardiff, S Glam, Wales. [Perry, V. Hugh] Univ Southampton, Sch Biol Sci, Southampton, Hants, England. RI Clarke, Alan/A-6256-2008; Bradford, Barry/B-3783-2013; clarke, alan/P-2820-2014 OI Bradford, Barry/0000-0002-4007-1685; NR 0 TC 0 Z9 0 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 J9 PRION JI Prion PD JUL-SEP PY 2010 VL 4 IS 3 BP 173 EP 173 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 702CN UT WOS:000285872300159 ER PT J AU Angelone, LM Bit-Babik, G Chou, CK AF Angelone, Leonardo M. Bit-Babik, Giorgi Chou, Chung-Kwang TI Computational Electromagnetic Analysis in a Human Head Model with EEG Electrodes and Leads Exposed to RF-Field Sources at 915 MHz and 1748 MHz SO RADIATION RESEARCH LA English DT Article ID METALLIC IMPLANTS; 7 TESLA; MRI; SAR; TEMPERATURE; SIMULATION; SAFETY; STIMULATOR; ELEVATION; COILS AB An electromagnetic analysis of a human head with EEC electrodes and leads exposed to RF-field sources was performed by means of Finite-Difference Time-Domain simulations on a 1-mm(3) MRI-based human head model. RF-field source models included a half-wave dipole, a patch antenna, and a realistic CAD-based mobile phone at 915 MHz and 1748 MHz. EEC electrodes/leads models included two configurations of EEG leads, both a standard 10-20 montage with 19 electrodes and a 32-electrode cap, and metallic and high resistive leads. Whole-head and peak 10-g average SAR showed less than 20% changes with and without leads. Peak 1-g and 10-g average SARs were below the ICNIRP and IEEE guideline limits. Conversely, a comprehensive volumetric assessment of changes in the RF field with and without metallic EEG leads showed an increase of two orders of magnitude in single-voxel power absorption in the epidermis and a 40-fold increase in the brain during exposure to the 915 MHz mobile phone. Results varied with the geometry and conductivity of EEG electrodes/leads. This enhancement confirms the validity of the question whether any observed effects in studies involving EEG recordings during RE-field exposure are directly related to the RE fields generated by the source or indirectly to the RF-field-induced currents due to the presence of conductive EEG leads. (C) 2010 by Radiation Research Society C1 [Angelone, Leonardo M.] US FDA, Div Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Angelone, Leonardo M.] Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Bit-Babik, Giorgi; Chou, Chung-Kwang] Motorola Inc, Enterprise Mobil Solut, Ft Lauderdale, FL USA. RP Angelone, LM (reprint author), 10903 New Hampshire Ave,WO62 Rm 1109, Silver Spring, MD 20993 USA. EM leonardo.angelone@fda.hhs.gov OI Angelone, Leonardo/0000-0002-1105-021X FU Mobile Manufacturer Forum; NCRR [P41RR14075]; MIND Institute; Athinoula A. Martinos Center for Biomedical Imaging FX This study was supported by the Mobile Manufacturer Forum, the NCRR (grant P41RR14075), the MIND Institute, and the Athinoula A. Martinos Center for Biomedical Imaging. Giorgi Bit-Babik and CK. Chou are employees of Motorola whose research focuses on the safe use of electromagnetic energy. They contributed their time on this project with the support of the company. The authors would like to thank Bruce Rosen, Giorgio Bonmassar, Christos Vasios, Nikos Makris, David Kennedy, Jonathan Kaiser, George Papadimitriou at the A.Martinos Center for Biomedical Imaging and Mark Cronin-Golomb and Sergio Fantini at Tufts University for the help and the useful insights during the completion of the study. The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services. NR 46 TC 8 Z9 8 U1 0 U2 6 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD JUL PY 2010 VL 174 IS 1 BP 91 EP 100 DI 10.1667/RR1933.1 PG 10 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 626SA UT WOS:000279986000011 PM 20681803 ER PT J AU Meng, FX Bermudez, E McKinzie, PB Andersen, ME Clewell, HJ Parsons, BL AF Meng, Fanxue Bermudez, Edilberto McKinzie, Page B. Andersen, Melvin E. Clewell, Harvey J., III Parsons, Barbara L. TI Measurement of tumor-associated mutations in the nasal mucosa of rats exposed to varying doses of formaldehyde SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE p53 mutation; K-Ras mutation; ACB-PCR; Dose response assessment; Risk assessment; Mode of action; Allele-specific amplification; Regenerative cell proliferation ID PROTEIN CROSS-LINKS; NATIONAL-CANCER-INSTITUTE; SQUAMOUS-CELL CARCINOMAS; RAS MUTANT FRACTION; ACB-PCR MEASUREMENT; P53 MUTATIONS; NASOPHARYNGEAL CANCER; RISK ASSESSMENT; INHALED FORMALDEHYDE; CYTOGENETIC ANALYSIS AB This study examined the potential induction of tumor-associated mutations in formaldehyde-exposed rat nasal mucosa using a sensitive method, allele-specific competitive blocker-PCR (ACB-PCR). Levels of p53 codon 271 CGT to CAT and K-Ras codon 12 GGT to GAT mutations were quantified in nasal mucosa of rats exposed to formaldehyde. In addition, nasal mucosa cell proliferation was monitored because regenerative cell proliferation is considered a key event in formaldehyde-induced carcinogenesis. Male F344 rats (6-7 weeks old, 5 rats/group) were exposed to 0, 0.7, 2, 6, 10, and 15 ppm formaldehyde for 13 weeks (6 h/day, 5 days/week). ACB-PCR was used to determine levels of p53 and K-Ras mutations. Although two of five untreated rats had measureable spontaneous p53 mutant fractions (MFs), most nasal mucosa samples had p53 MFs below 10(-5). All K-Ras MF measurements were below 10(-5). No dose-related increases in p53 or K-Ras MF were observed, even though significant increases in bromodeoxyuridine incorporation demonstrated induced cell proliferation in the 10 and 15 ppm formaldehyde-treatment groups. Therefore, induction of tumor-associated p53 mutation likely occurs after several other key events in formaldehyde-induced carcinogenesis. Published by Elsevier Inc. C1 [Meng, Fanxue; McKinzie, Page B.; Parsons, Barbara L.] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Bermudez, Edilberto] Hamner Inst Hlth Sci, Div Toxicol & Preclin Studies, Res Triangle Pk, NC 27709 USA. [Andersen, Melvin E.; Clewell, Harvey J., III] Hamner Inst Hlth Sci, Div Computat Biol, Res Triangle Pk, NC 27709 USA. RP Meng, FX (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM Fanxue.Meng@fda.hhs.gov OI Andersen, Melvin/0000-0002-3894-4811 NR 59 TC 16 Z9 17 U1 0 U2 5 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 JUL-AUG PY 2010 VL 57 IS 2-3 BP 274 EP 283 DI 10.1016/j.yrtph.2010.03.007 PG 10 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 610YP UT WOS:000278777300016 PM 20347909 ER PT J AU Gendel, SM AF Gendel, Steven M. TI Science, Policy and the Value-Free Ideal SO RISK ANALYSIS LA English DT Book Review C1 [Gendel, Steven M.] US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. RP Gendel, SM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. EM steven.gendel@fda.hhs.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD JUL PY 2010 VL 30 IS 7 BP 1176 EP 1177 PG 2 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 626BC UT WOS:000279939700017 ER PT J AU Scherf, U Becker, R Chan, M Hojvat, S AF Scherf, Uwe Becker, Robert Chan, Maria Hojvat, Sally TI Approval of novel biomarkers: FDA's perspective and major requests SO SCANDINAVIAN JOURNAL OF CLINICAL & LABORATORY INVESTIGATION LA English DT Article DE analytical; biomarker types; FDA/CDRH Device Classification; qualification; validation AB FDA has been regulating diagnostic tests (including biomarkers) since passage of the Medical Device Amendments of 1976. Although always of interest as diagnostic tools, biomarkers (particularly genetic/genomic) have become of increased interest because of their potential impact on the development and personalized use of drugs. Unfortunately, there seem to be uncertainties among translational researchers as to the specific analytical and clinical measurement criteria needed for the approval of these novel biomarkers. This meeting presentation describes the current FDA perspective and major requirements and data for the validation/approval of an in vitro diagnostic device (IVD) based on a biomarker. The approval process for an IVD based on a biomarker used in the identification of a disease or condition (diagnosing, screening, monitoring) is well established, and is essentially identical to the process to generate sufficient analytical and clinical data for the approval of regular diagnostic devices. On the contrary, approvals for IVDs based on biomarker which may be designed to evaluate the efficacy or answer safety questions for new drug entities are less streamlined. The clinical studies are more complex, resulting in higher ethical standards, increased costs and requiring complex statistical evaluation. There is a small but growing literature on new models for co-development of drugs and diagnostics which will be discussed. Regulators like the FDA develop and bring a flexible regulatory toolbox to the table and are committed to assuring that scientific and regulatory thresholds are tempered to assure rapid access to new technologies while protecting public health. C1 [Scherf, Uwe; Becker, Robert; Chan, Maria; Hojvat, Sally] US FDA, Off Vitro Diagnost Device Evaluat & Safety, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Scherf, U (reprint author), US FDA, Off Vitro Diagnost Device Evaluat & Safety, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. EM Uwe.Scherf@fda.hhs.go NR 8 TC 5 Z9 6 U1 0 U2 10 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 0036-5513 J9 SCAND J CLIN LAB INV JI Scand. J. Clin. Lab. Invest. PD JUL PY 2010 VL 70 SU 242 BP 96 EP 102 DI 10.3109/00365513.2010.493415 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 631GB UT WOS:000280333600020 ER PT J AU Schreider, J Barrow, C Birchfield, N Dearfield, K Devlin, D Henry, S Kramer, M Schappelle, S Solomon, K Weed, DL Embry, MR AF Schreider, Jay Barrow, Craig Birchfield, Norman Dearfield, Kerry Devlin, Dennis Henry, Sara Kramer, Melissa Schappelle, Seema Solomon, Keith Weed, Douglas L. Embry, Michelle R. TI Enhancing the Credibility of Decisions Based on Scientific Conclusions: Transparency Is Imperative SO TOXICOLOGICAL SCIENCES LA English DT Editorial Material DE transparency; credibility; risk assessment; scientific integrity; criteria AB Transparency and documentation of the decision process are at the core of a credible risk assessment and, in addition, are essential in the presentation of a weight of evidence (WoE) based approach. Lack of confidence in the risk assessment process (as the basis for a risk management decision), beginning with evaluation of raw data and continuing through the risk decision process, is largely because of issues surrounding transparency. There is a critical need to implement greater transparency throughout the risk assessment process, and although doing so will not guarantee the correctness of the risk assessment or that all risk assessors come up with the same conclusions, it will provide essential information on how a particular conclusion or decision was made, thereby increasing confidence in the conclusions. Recognizing this issue, the International Life Sciences Institute Health and Environmental Sciences Institute convened a multi-sector committee tasked with discussing this issue and examining existing guidance and recommendations related to transparency in risk assessment. The committee concluded that transparency is inextricably linked to credibility: credibility of the data, credibility of the risk assessment process, and credibility of the resulting decision making. To increase this credibility, existing guidance concerning criteria elements of transparency related to the risk assessment process must be more widely disseminated and applied, and raw data for studies used in human health and environmental risk assessment must be more widely available. Finally, the decision-making process in risk management must be better documented and a guidance framework established for both the process itself and its communication to the public. C1 [Schreider, Jay] Calif Environm Protect Agcy, Dept Pesticide Regulat, Sacramento, CA 95812 USA. [Barrow, Craig] Dow Chem Co USA, Toxicol Environm Res & Consulting, Washington, DC 20006 USA. [Birchfield, Norman; Kramer, Melissa; Schappelle, Seema] US EPA, Off Res & Dev, Washington, DC 20460 USA. [Dearfield, Kerry] US Food Safety & Inspect Serv, Off Publ Hlth Sci, USDA, Washington, DC 20250 USA. [Devlin, Dennis] ExxonMobil Biomed Sci Inc, Toxicol & Environm Sci, Annandale, NJ 08801 USA. [Henry, Sara] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Solomon, Keith] Univ Guelph, Ctr Toxicol, Guelph, ON N1G 2W1, Canada. [Weed, Douglas L.] DLW Consulting Serv LLC, Kensington, MD 20895 USA. [Embry, Michelle R.] ILSI Hlth & Environm Sci Inst, Washington, DC 20005 USA. RP Embry, MR (reprint author), ILSI Hlth & Environm Sci Inst, 1156 15th St NW, Washington, DC 20005 USA. EM membry@ilsi.org NR 9 TC 17 Z9 17 U1 0 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 JUL PY 2010 VL 116 IS 1 BP 5 EP 7 DI 10.1093/toxsci/kfq102 PG 3 WC Toxicology SC Toxicology GA 617XZ UT WOS:000279316500002 PM 20363830 ER PT J AU Epstein, JS Holmberg, JA AF Epstein, Jay S. Holmberg, Jerry A. TI Progress in monitoring blood safety SO TRANSFUSION LA English DT Editorial Material ID IMMUNODEFICIENCY-VIRUS TRANSMISSION; VIRAL-INFECTIONS; DONORS; RISK; DONATION C1 [Epstein, Jay S.] US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Holmberg, Jerry A.] US Dept HHS, Off Publ Hlth & Sci, Rockville, MD USA. RP Epstein, JS (reprint author), US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM jay.epstein@fda.hhs.gov NR 21 TC 14 Z9 15 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL PY 2010 VL 50 IS 7 BP 1408 EP 1412 PG 5 WC Hematology SC Hematology GA 619TO UT WOS:000279453400002 PM 20636529 ER PT J AU Kannan, M Atreya, C AF Kannan, Meganathan Atreya, Chintamani TI Differential profiling of human red blood cells during storage for 52 selected microRNAs SO TRANSFUSION LA English DT Article ID IN-VITRO; EXPRESSION; ERYTHROPOIESIS; PRESERVATION; TRANSFUSION; APOPTOSIS; PATHWAYS; PROTEIN AB BACKGROUND: MicroRNAs (miRNAs), the negative regulators of cellular mRNAs, are present in mature red blood cells (RBCs) in abundance relative to other blood cells. So far, there are no studies aimed at identifying large-scale miRNA profiles during storage of RBCs. STUDY DESIGN AND METHODS: RNA samples from each RBC bag stored at 4 degrees C were collected on Days 0, 20, and 40 and subjected to miRNA profiling by using a membrane-based array. Fifty-two selected miRNAs of cellular apoptotic pathway represent the array. Through bioinformatics analyses, we identified potential target genes for selected miRNAs. RESULTS: Differential profiling of RBCs for 52 miRNAs revealed two distinguishable patterns during storage: Forty-eight miRNAs demonstrated no trend at all, while four miRNAs, miR-96, miR-150, miR-196a, and miR-197, demonstrated an increase up to Day 20 and subsequently decreased during storage. We selected miR-96 and subjected it to standard bioinformatics analyses for target gene predictions, which identified several mRNAs including the RBC proapoptotic calpain small subunit-1 (CAPNS1) as potential targets of miR-96. To validate these predictions, we selected CAPNS1 mRNA as an example and confirmed its presence in the RBCs. Future experimental verification would help define miR-96-CAPNS1 interaction, if any, in the stored RBCs. CONCLUSIONS: This study for the first time provided a differential profile of stored RBCs for selected miRNAs related to cellular apoptotic pathway and opened new avenues toward identification of novel in vitro RBC biomarkers of storage lesions. Future studies focusing on target gene-miRNA interactions in stored RBCs would also unravel underlying mechanisms of storage lesions. C1 [Kannan, Meganathan; Atreya, Chintamani] US FDA, Sect Cell Biol, Lab Cellular Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Atreya, C (reprint author), Bldg 29A,Room 2C-11,NIH Campus,8800 Rockville Pik, Bethesda, MD 20892 USA. EM chintamani.atreya@fda.hhs.gov FU CBER; FDA; Critical Path Research Initiative; Oak Ridge Institute for Science and Engineering FX CDA is a recipient of CBER, FDA, Critical Path Research Initiative funds and MK is a recipient of Oak Ridge Institute for Science and Engineering fellowship. The authors thank Drs Krishna Ketha and Shilpakala Sainathrao, CBER, FDA, for the manuscript review; Ms Sandhya Kulkarni for providing positive RNA control samples for RT-PCR; and Dr Monique Gelderman-Fuhrmann, CBER, for helping with obtaining the RBC bags from the NIH blood bank, Department of Transfusion Medicine (DTM), Clinical Center (CC), NIH. NR 26 TC 22 Z9 22 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL PY 2010 VL 50 IS 7 BP 1581 EP 1588 DI 10.1111/j.1537-2995.2010.02585.x PG 8 WC Hematology SC Hematology GA 619TO UT WOS:000279453400024 PM 20158686 ER PT J AU Kulkarni, S Kannan, M Atreya, CD AF Kulkarni, Sandhya Kannan, Meganathan Atreya, Chintamani D. TI Omic Approaches to Quality Biomarkers for Stored Platelets: Are We There Yet? SO TRANSFUSION MEDICINE REVIEWS LA English DT Review ID ACTIVATED HUMAN PLATELETS; IN-VITRO; ADDITIVE SOLUTION; FLOW-CYTOMETRY; STORAGE; MICRORNAS; PLASMA; TRANSFUSION; EXPRESSION; APOPTOSIS AB At present, there is no single biomarker that serves as the "gold standard" predictive of the quality of stored platelets used for transfusion. Some of the measurable features of platelets such as morphology, biochemical status, physiologic response to osmotic stress and agonist-induced changes, and measurement of process-associated activation indicators of platelets are considered useful in assessing the in vitro quality of stored platelets. Such in vitro measurements combined with in vivo survival estimations using radiolabeled platelets in healthy volunteers provide reasonable estimates of in vivo platelet function after transfusion. Thus, the current practice of estimating the quality and functional aspects of ex vivo stored platelets involves utilization of a battery of tests that dates back to preomic era. On the other hand, during the last decade, seminal discoveries have been made in platelet molecular and cell biology by using "omic"-based approaches such as proteomics, genomics, and transcriptomics. Can we mobilize some of these discoveries toward developing reliable quality biomarkers for stored platelets? To address this topic, we briefly review current practices and provide insights into some of the omic approaches that could be helpful in identifying quality storage biomarkers of platelets in the near future. We also briefly discuss here some of the challenges in using proteomic approaches and advantages of using one of the transcriptomics approaches toward platelet biomarker development. Published by Elsevier Inc. C1 [Kulkarni, Sandhya; Kannan, Meganathan; Atreya, Chintamani D.] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Off Blood Res & Review, Rockville, MD 20852 USA. RP Atreya, CD (reprint author), US FDA, WOCI, Suit 400N,HFM-300 1401 Rockville Pike, Rockville, MD 20852 USA. EM chintamani.atreya@fda.hhs.gov FU FDA, CBER Critical Path Research Initiative; Oak Ridge Institute for Science and Engineering FX This work in part is supported by the FDA, CBER Critical Path Research Initiative funds to CDA. MK is a recipient of Oak Ridge Institute for Science and Engineering fellowship. NR 50 TC 5 Z9 5 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0887-7963 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD JUL PY 2010 VL 24 IS 3 BP 211 EP 217 DI 10.1016/j.tmrv.2010.03.003 PG 7 WC Hematology SC Hematology GA 633IM UT WOS:000280495300004 PM 20656188 ER PT J AU Wear, K AF Wear, Keith TI Robert F. Wagner 1938-2008 In memoriam SO ULTRASONIC IMAGING LA English DT Biographical-Item C1 US FDA, CDRH, Rockville, MD 20857 USA. RP Wear, K (reprint author), US FDA, CDRH, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DYNAMEDIA INC PI SILVER SPRING PA 2 FULHAM COURT, SILVER SPRING, MD 20902 USA SN 0161-7346 J9 ULTRASONIC IMAGING JI Ultrason. Imaging PD JUL PY 2010 VL 32 IS 3 BP 129 EP 130 PG 2 WC Acoustics; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 633IU UT WOS:000280496200001 ER PT J AU Rios, M Grinev, A Chancey, C Sylvester, D Caglioti, S Winkelman, V Land, KJ Stramer, SL AF Rios, M. Grinev, A. Chancey, C. Sylvester, D. Caglioti, S. Winkelman, V. Land, K. J. Stramer, S. L. TI GENETIC EVOLUTION OF WEST NILE VIRUS (WNV) CIRCULATING IN THE US FROM 2002-2009 ALLOWED INTENSIFIED VIRAL SPREAD SO VOX SANGUINIS LA English DT Meeting Abstract C1 [Grinev, A.] US FDA, CBER, OBRR, DETTD, Bethesda, MD 20014 USA. [Caglioti, S.; Winkelman, V.] Blood Syst Labs, Tempe, AZ USA. [Land, K. J.] Bonfils Blood Ctr, Denver, CO USA. [Stramer, S. L.] Amer Red Cross, Gaithersburg, 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 0042-9007 J9 VOX SANG JI Vox Sang. PD JUL PY 2010 VL 99 SU 1 BP 32 EP 33 PG 2 WC Hematology SC Hematology GA 625DE UT WOS:000279872500080 ER PT J AU Ferguson, M Yu, MW Heath, A AF Ferguson, M. Yu, M. W. Heath, A. TI Calibration of the second International Standard for hepatitis B immunoglobulin in an international collaborative study SO VOX SANGUINIS LA English DT Article DE anti-HBs; assay kits; hepatitis B immunization; hepatitis B vaccine; immunoglobulin; standard AB Background and Objectives The International Standard for hepatitis B immunoglobulin is used in the standardization of the anti-HBs content of immunoglobulins for prophylactic and therapeutic use and also in the standardization and calibration of quantitative diagnostic anti-HBs assay kits. A collaborative study was undertaken to assess the suitability of a candidate Second International Standard (2nd IS), and to calibrate it in International Units (IU). Materials and Methods The candidate 2nd IS was prepared from a bulk of 5% hepatitis B immunoglobulin (NIBSC code 07/164). Twenty-two participants from 12 countries assayed the first IS, the candidate 2nd IS, a freeze-dried pool of plasma containing anti-HBs and a plasma from a blood donor. These samples were assayed with 19 different assay kits. Results Data from 102 assays were received. The mean potencies of two coded samples of the candidate 2nd IS were 100 center dot 7 and 101 center dot 4 IU/ml (combined potency 101 center dot 0 IU/ml). The geometric coefficients of variation for these samples were both 13%. The predicted long-term stability of 07/164 was assessed by assaying samples stored at elevated temperatures for a period of 6 months. 07/164 was predicted to be stable at -20 degrees C with the estimated % loss per year of below 0 center dot 2%. Conclusion 07/164 was established as the 2nd IS for hepatitis B immunoglobulin with an assigned potency of 100 IU/ampoule by the WHO Expert Committee on Biological Standardisation. The United States Food and Drug Administration has adopted the same standard as the new Reference for Hepatitis B Immunoglobulin, Lot 3. C1 [Heath, A.] Natl Inst Biol Stand & Controls, Div Biostat, S Mimms EN6 3QG, Herts, England. [Ferguson, M.] Natl Inst Biol Stand & Controls, Div Virol, S Mimms EN6 3QG, Herts, England. [Yu, M. W.] US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Heath, A (reprint author), Natl Inst Biol Stand & Controls, Div Biostat, Blanche Lane, S Mimms EN6 3QG, Herts, England. EM alan.heath@nibsc.hpa.org.uk NR 5 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0042-9007 J9 VOX SANG JI Vox Sang. PD JUL PY 2010 VL 99 IS 1 BP 77 EP 84 DI 10.1111/j.1423-0410.2010.01314.x PG 8 WC Hematology SC Hematology GA 609UP UT WOS:000278683200009 PM 20202182 ER PT J AU Walderhaug, M Yang, H Kumar, S AF Walderhaug, M. Yang, H. Kumar, S. TI RISK-BENEFIT ANALYSIS FOR US TRAVELERS TO MALARIA-ENDEMIC AREAS OF MEXICO AND BLOOD DONATION DEFERRAL SO VOX SANGUINIS LA English DT Meeting Abstract C1 [Walderhaug, M.; Yang, H.; Kumar, S.] US FDA, Rockville, MD 20857 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 0042-9007 J9 VOX SANG JI Vox Sang. PD JUL PY 2010 VL 99 SU 1 BP 121 EP 122 PG 2 WC Hematology SC Hematology GA 625DE UT WOS:000279872500302 ER PT J AU Anderson, S Yang, H Forshee, R Walderhaug, M AF Anderson, S. Yang, H. Forshee, R. Walderhaug, M. TI UPDATED RISK ASSESSMENT OF VARIANT CREUTZFELDT-JAKOB DISEASE (VCJD) RISKS FOR RECIPIENTS OF BLOOD AND PLASMA-DERIVED PRODUCTS IN THE US SO VOX SANGUINIS LA English DT Meeting Abstract C1 [Anderson, S.; Yang, H.; Forshee, R.; Walderhaug, M.] US FDA, Washington, DC 20204 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 0042-9007 J9 VOX SANG JI Vox Sang. PD JUL PY 2010 VL 99 SU 1 BP 122 EP 122 PG 1 WC Hematology SC Hematology GA 625DE UT WOS:000279872500303 ER PT J AU StOrmer, M Brachert, J de Korte, D McDonald, C Wendel, S Wood, EM Arroyo, A Devine, D Epstein, JS Gabriel, C Cohava, C Goodrich, R Hanschmann, KM Heath, DG Jacobs, MR Keil, S Lambrecht, B Lee, CK Marcelis, J Marschner, S McGuane, S Mckee, M Muller, T Muthivhi, T Pettersson, A Radziwon, P Ramirez-Arcos, S Reesink, HW Rojo, J Rood, I Schmidt, M AF Stoermer, M. Brachert, J. de Korte, D. McDonald, C. Wendel, S. Wood, E. M. Arroyo, A. Devine, D. Epstein, J. S. Gabriel, C. Cohava, C. Goodrich, R. Hanschmann, K-M Heath, D. G. Jacobs, M. R. Keil, S. Lambrecht, B. Lee, C-K Marcelis, J. Marschner, S. McGuane, S. Mckee, M. Mueller, T. Muthivhi, T. Pettersson, A. Radziwon, P. Ramirez-Arcos, S. Reesink, H. W. Rojo, J. Rood, I Schmidt, M. TI ISBT INTERNATIONAL VALIDATION STUDY ON BLOOD-BACTERIA-STANDARDS (TRANSFUSION-RELEVANT BACTERIAL STRAIN PANEL) SO VOX SANGUINIS LA English DT Meeting Abstract C1 [Stoermer, M.; Brachert, J.; Hanschmann, K-M] Paul Ehrlich Inst, Fed Inst Vaccines & Biomed, D-6070 Langen, Germany. [de Korte, D.; Marcelis, J.; Rood, I] Sanquin Blood Supply Fdn, Amsterdam, Netherlands. [McDonald, C.; McGuane, S.] NHS Blood & Transplant, London, England. [Wendel, S.] Hosp Sirio Libanes, Sao Paulo, Brazil. [Wood, E. M.] Australian Red Cross Blood Serv, Melbourne, Vic, Australia. [Arroyo, A.; Rojo, J.] Ctr Nacl Transfus Sanguinea, Mexico City, DF, Mexico. [Devine, D.; Ramirez-Arcos, S.] Canadian Blood Serv, Ottawa, ON, Canada. [Epstein, J. S.] US FDA, Rockville, MD 20857 USA. [Gabriel, C.] Blutzent Linz, Austrian Red Cross, Linz, Austria. [Cohava, C.; Mckee, M.] Amer Type Culture Collect, Manassas, VA USA. [Goodrich, R.; Keil, S.; Marschner, S.] CaridianBCT Biotechnol, Lakewood, CO USA. [Heath, D. G.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Jacobs, M. R.] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. [Lambrecht, B.; Mueller, T.] NSTOB, German Red Cross, Springe, Germany. [Lee, C-K] Hong Kong Red Cross Blood Transfus Serv, Hong Kong, Hong Kong, Peoples R China. [Muthivhi, T.] South African Natl Blood Serv, Weltevreden Pk, South Africa. [Pettersson, A.] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [Radziwon, P.] Reg Ctr Transfus Med, Bialystok, Poland. [Reesink, H. W.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Schmidt, M.] German Red Cross, Frankfurt, Germany. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0042-9007 J9 VOX SANG JI Vox Sang. PD JUL PY 2010 VL 99 SU 1 BP 309 EP 310 PG 2 WC Hematology SC Hematology GA 625DE UT WOS:000279872501374 ER PT J AU Anez, G Chancey, C Grinev, A Morales-Betoulle, ME Rios, M AF Anez, G. Chancey, C. Grinev, A. Morales-Betoulle, M. E. Rios, M. TI STUDY OF A DENGUE IMPORTED CASE TO THE US SHOWS HIGHER LEVEL OF VIRUS ASSOCIATED TO RBC THAN IN PLASMA FROM THE SAME BLOOD SPECIMEN SO VOX SANGUINIS LA English DT Meeting Abstract C1 [Anez, G.; Chancey, C.; Grinev, A.; Rios, M.] US FDA, Bethesda, MD 20014 USA. [Morales-Betoulle, M. E.] Univ Valle Guatemala, Guatemala City, Guatemala. 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 0042-9007 J9 VOX SANG JI Vox Sang. PD JUL PY 2010 VL 99 SU 1 BP 321 EP 321 PG 1 WC Hematology SC Hematology GA 625DE UT WOS:000279872501406 ER PT J AU Kennett, SB Porter, CM Horvath-Arcidiacono, JA Bloom, ET AF Kennett, Sarah B. Porter, Cynthia M. Horvath-Arcidiacono, Judith A. Bloom, Eda T. TI Characterization of baboon NK cells and their xenogeneic activity SO XENOTRANSPLANTATION LA English DT Article DE baboon; natural killer cells; pig; xenotransplantation ID NATURAL-KILLER-CELLS; MESENCHYMAL STEM-CELLS; MEDIATED CYTOTOXICITY; RHESUS MACAQUES; TUMOR-CELLS; IN-VITRO; XENOTRANSPLANTATION; RECEPTORS; IDENTIFICATION; EXPRESSION AB Background: Baboons are commonly used as models for transplantation and preclinical testing of various types of therapeutic agents. For proper assessment of information gathered from these models, differences between the baboon and human immune systems need to be characterized. Natural killer (NK) cells are the first line of defense against many infectious agents and cancer and are important mediators of transplantation rejection reactions, particularly during xenotransplantation. In this study, we examined baboon NK cell function and developed methods for purifying and expanding these cells. Methods: Baboon NK cells were analyzed using a combination of extracellular and intracellular cell staining, cell sorting, interleukin (IL)-2 mediated stimulation and expansion, and 4 h cytotoxicity assays with human and pig target cell lines. Results: Baboon peripheral blood mononuclear cell (PBMC) exert very low but detectable cytolytic activity against both human (K562) and pig (PAEC, J2) target cells, and this activity is enhanced within 4 h of treatment with IL-2. Like human NK cells, many baboon PBMC express the lytic enzymes granzyme A, granzyme B, and perforin. Based on these markers, we identified a subpopulation of CD3- baboon lymphocytes that are CD8dim and CD16bright that likely represents the baboon NK cells. These cells also are characterized by expression of the natural cytotoxicity receptor NKp46. Baboon CD3-NKp46+ cells purified by flow cytometric cell sorting have high cytolytic capacity that can be further enhanced by IL-2 stimulation. These baboon NK cells can be expanded in vitro and retain extremely high cytolytic capacity. While fresh baboon lymphocytes express very little CD56, the expanded baboon NK cells are predominantly CD56+; approximately 10% of the expanded NK cells are CD56dim, and the remainder are CD56bright. Conclusions: Baboon NK cells that are IL-2 responsive can be identified on the basis of a CD3-NKp46+CD8dimCD16+/- or CD3-CD8dimCD16bright phenotype and can be isolated and expanded in culture. These results may allow for a more accurate representation of the human innate immune system in baboon models and more accurate analyses of the role of the baboon innate immune system cells in preclinical models. C1 [Kennett, Sarah B.] US FDA, Ctr Biol Evaluat & Res, Gene Transfer & Immunogenic Branch, Div Cellular & Gene Therapies, Bethesda, MD USA. [Kennett, Sarah B.] NCI FDA Interagency Oncol Task Force, Bethesda, MD 20892 USA. RP Horvath-Arcidiacono, JA (reprint author), US FDA, 1401 Rockville Pike,HFM 700, Rockville, MD 20852 USA. EM judith.arcidiacono@fda.hhs.gov NR 42 TC 8 Z9 8 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JUL-AUG PY 2010 VL 17 IS 4 BP 288 EP 299 DI 10.1111/j.1399-3089.2010.00591.x PG 12 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 640RQ UT WOS:000281070200005 PM 20723201 ER PT J AU Yang, BW Qu, D Zhang, XL Shen, JL Cui, SH Shi, Y Xi, ML Sheng, M Zhi, SA Meng, JH AF Yang, Baowei Qu, Dong Zhang, Xiuli Shen, Jinling Cui, Shenghui Shi, Ying Xi, Meili Sheng, Min Zhi, Shuai Meng, Jianghong TI Prevalence and characterization of Salmonella serovars in retail meats of marketplace in Shaanxi, China SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE Salmonella; Prevalence; Characterization; Retail meats ID ANTIMICROBIAL RESISTANCE; ANTIBIOTIC-RESISTANCE; CHICKEN CARCASSES; UNITED-STATES; POULTRY PRODUCTS; SEROTYPES; SURVEILLANCE; INTEGRONS; ANIMALS; TRENDS AB A total of 764 retail meat including 515 chicken, 91 pork, 78 beef and 80 lamb samples were collected in Shaanxi Province of China in 2007-2008 to determine the prevalence of Salmonella. The isolates were characterized using serotyping. antimicrobial susceptibility testing, and the presence of bla(CMY-2) and bla(TEM) and class I integrons. Selective serovars were further subtyped using PFGE. Approximately 54% (276) of chicken, 31% (28) of pork, 17% (13) of beef and 20% (16) of lamb samples were positive of Salmonella. Among 24 serovars identified, Enteritidis (31.5%) was most common, followed by Typhimurium (13.4%), Shubra (10.0%), Indiana (9.7%), Derby (9.5%) and Djugu (7.0%). Nearly 80% of the isolates (283) were resistant to at least one antimicrobial, and 53% (191) to more than three antimicrobials. Resistance was most frequently observed to sulfamethoxazole (67%), to trimethoprim/sulfamethoxazole (58%) and to tetracycline (56%). Furthermore, many isolates were resistant to nalidixic acid (35%), ciprofloxacin (21%) and ceftriaxone (16%). Most isolates of Shubra (89%) and Indiana (88%) were resistant to 9 antimicrobials, compared to only 11% of Enteritidis and 9% of Infantis that showed similar resistance. Class I integrons were detected in 10% of the isolates, and contained aadA, tetR, dhfr, bla(PSE-1), bla(DHA-1), and bla(VEB-1), gene cassettes alone or various combinations. Ceftriaxone- and/or cefoperazone-resistant isolates (n=62) carried bla(TEM) (51.6%) and/or bla(CMY-2) (56.5%). A total of 116 PFGE patterns were generated among 210 selected isolates. Our findings indicated that Salmonella contamination was common in retail meats, and that the Salmonella isolates were phenotypically and genetically diverse. Additionally, many Salmonella isolates were resistant to multiple antimicrobials. (C) 2010 Elsevier B.V. All rights reserved. C1 [Yang, Baowei; Qu, Dong; Shen, Jinling; Shi, Ying; Xi, Meili; Sheng, Min; Zhi, Shuai; Meng, Jianghong] NW A&F Univ, Coll Food Sci & Engn, Yangling 712100, Shaanxi, Peoples R China. [Cui, Shenghui] State Food & Drug Adm, Beijing 100050, Peoples R China. [Meng, Jianghong] Univ Maryland, Joint Inst Food Safety & Appl Nutr, Dept Nutr & Food Sci, College Pk, MD 20742 USA. RP Meng, JH (reprint author), NW A&F Univ, Coll Food Sci & Engn, 28 Xinong Rd, Yangling 712100, Shaanxi, Peoples R China. EM jmeng@umd.edu FU Chinese Ministry of Education; Northwest A&F University, Yangling, Shanxi, China FX The research work was supported in part by Chang Jiang Scholar Program of the Chinese Ministry of Education, and Northwest A&F University, Yangling, Shanxi, China. NR 43 TC 85 Z9 95 U1 2 U2 36 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD JUN 30 PY 2010 VL 141 IS 1-2 BP 63 EP 72 DI 10.1016/j.ijfoodmicro.2010.04.015 PG 10 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 622YS UT WOS:000279704000010 PM 20493570 ER PT J AU Lampel, KA Chen, Y AF Lampel, K. A. Chen, Y. TI Method for the isolation and detection of Enterobacter sakazakii (Cronobacter) from powdered infant formula (vol 136, pg 179, 2009) SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Correction C1 [Lampel, K. A.; Chen, Y.] US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Lampel, KA (reprint author), US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD USA. NR 1 TC 0 Z9 0 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD JUN 30 PY 2010 VL 141 IS 1-2 BP 136 EP 136 DI 10.1016/j.ijfoodmicro.2010.04.003 PG 1 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 622YS UT WOS:000279704000021 ER PT J AU Kang, SH Tsong, Y AF Kang, Seung-Ho Tsong, Yi TI Strength of evidence of non-inferiority trials-The adjustment of the type I error rate in non-inferiority trials with the synthesis method SO STATISTICS IN MEDICINE LA English DT Article DE across-trial type I error; multivariate central limit theorem; binary data; correlation ID STATISTICAL-METHODS; PLACEBO ARM; DESIGN; ISSUES; DEPENDENCY; UTILITY; CHOICE; MARGIN AB In non-inferiority trials that employ the synthesis method several types of dependencies among test statistics occur due to sharing of the same information from the historical trial. The conditions under which the dependencies appear may be divided into three categories. The first case is when a new drug is approved with single non-inferiority trial. The second case is when a new drug is approved if two independent non-inferiority trials show positive results. The third case is when two new different drugs are approved with the same active control. The problem of the dependencies is that they can make the type I error rate deviate from the nominal level. In order to study such deviations, we introduce the unconditional and conditional across-trial type I error rates when the non-inferiority margin is estimated from the historical trial, and investigate how the dependencies affect the type I error rates. We show that the unconditional across-trial type I error rate increases dramatically as does the correlation between two non-inferiority tests when a new drug is approved based on the positive results of two non-inferiority trials. We conclude that the conditional across-trial type I error rate involves the unknown treatment effect in the historical trial. The formulae of the conditional across-trial type I error rates provide us with a way of investigating the conditional across-trial type I error rates for various assumed values of the treatment effect in the historical trial. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Kang, Seung-Ho] Yonsei Univ, Dept Appl Stat, Seoul 120749, South Korea. [Tsong, Yi] US FDA, Ctr Drug Evaluat, Off Biostat, Div Biometr 6, Silver Spring, MD USA. RP Kang, SH (reprint author), 262 Seongsanno, Seoul 120749, South Korea. EM seungho@yonsei.ac.kr FU Korea Science & Engineering Foundation [R01-2007-000-20713-0] FX This work was supported by grant No. R01-2007-000-20713-0 from the Basic Research Program of the Korea Science & Engineering Foundation. NR 14 TC 6 Z9 6 U1 1 U2 8 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 JUN 30 PY 2010 VL 29 IS 14 BP 1477 EP 1487 DI 10.1002/sim.3903 PG 11 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 618SS UT WOS:000279376600002 PM 20535762 ER PT J AU Jackson, MC Huang, L Xie, QA Tiwari, RC AF Jackson, Monica C. Huang, Lan Xie, Qian Tiwari, Ram C. TI A modified version of Moran's I SO INTERNATIONAL JOURNAL OF HEALTH GEOGRAPHICS LA English DT Article ID POPULATION-DENSITY; CANCER MORTALITY; CLUSTERS; PATTERNS; DISEASE; TESTS; POWER AB Background: Investigation of global clustering patterns across regions is very important in spatial data analysis. Moran's I is a widely used spatial statistic for detecting global spatial patterns such as an east-west trend or an unusually large cluster. Here, we intend to improve Moran's I for evaluating global clustering patterns by including the weight function in the variance, introducing a population density (PD) weight function in the statistics, and conducting Monte Carlo simulation for testing. We compare our modified Moran's I with Oden's I*(pop) for simulated data with homogeneous populations. The proposed method is applied to a census tract data set. Methods: We present a modified version of Moran's I which includes information about the strength of the neighboring association when estimating the variance for the statistic. We provide a power analysis on Moran's I, a modified version of Moran's I, and I*(pop) in a simulation study. Data were simulated under two common spatial correlation scenarios of local and global clustering. Results: For simulated data with a large cluster pattern, the modified Moran's I has the highest power (43.4%) compared to Moran's I (39.9%) and I*(pop) (12.4%) when the adjacent weight function is used with 5%, 10%, 15%, 20%, or 30% of the total population as the geographic range for the cluster. For two global clustering patterns, the modified Moran's I (power > 25.3%) performed better than both Moran's I (> 24.6%) and I*(pop) (> 7.9%) with the adjacent weight function. With the population density weight function, all methods performed equally well. In the real data example, all statistics indicate the existence of a global clustering pattern in a leukemia data set. The modified Moran's I has the lowest p-value (. 0014) followed by Moran's I (. 0156) and I*(pop) (.011). Conclusions: Our power analysis and simulation study show that the modified Moran's I achieved higher power than Moran's I and I*(pop) for evaluating global and local clustering patterns on geographic data with homogeneous populations. The inclusion of the PD weight function which in turn redefines the neighbors seems to have a large impact on the power of detecting global clustering patterns. Our methods to improve the original version of Moran's I for homogeneous populations can also be extended to some alternative versions of Moran's I methods developed for heterogeneous populations. C1 [Jackson, Monica C.; Xie, Qian] American Univ, Dept Math & Stat, Washington, DC 20016 USA. [Huang, Lan; Tiwari, Ram C.] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Jackson, MC (reprint author), American Univ, Dept Math & Stat, 4400 Massachusetts Ave NW, Washington, DC 20016 USA. EM monica@american.edu NR 25 TC 5 Z9 6 U1 0 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-072X J9 INT J HEALTH GEOGR JI Int. J. Health Geogr. PD JUN 29 PY 2010 VL 9 AR 33 DI 10.1186/1476-072X-9-33 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 627JL UT WOS:000280035200001 PM 20587045 ER PT J AU Yakes, BJ Keller, DW Porter, MD AF Yakes, Betsy Jean Keller, David W. Porter, Marc D. TI Electrochemically modulated liquid chromatographic separation of triazines and the effect of pH on retention SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Electrochemically modulated liquid chromatography (EMLC); Applied potential (E(app)); Herbicide; Triazine; pH ID POROUS GRAPHITIC CARBON; POTENTIAL-CONTROLLED CHROMATOGRAPHY; TANDEM MASS-SPECTROMETRY; WATER MOBILE PHASES; STATIONARY-PHASE; DEGRADATION-PRODUCTS; IONIZABLE COMPOUNDS; GAS-CHROMATOGRAPHY; ENANTIOMERIC SEPARATIONS; ION-EXCHANGE AB Electrochemically modulated liquid chromatography (EMLC) manipulates analyte retention by changing the potential applied (E(app)) to a conductive stationary phase. This paper applies EMLC to the separation of a set of seven triazines which are commonly used but environmentally hazardous herbicides. Experiments herein examine the influence of E(app) and the pH of the mobile phase on triazine retention. The results are discussed in terms of: (1) retention of triazines of dissimilar acid strengths and by correlations with the pH of the mobile phase; (2) how changes in E(app) and acid-base equilibria modulate elution; (3) qualitative insights into EMLC-based retention; and (4) potential merits of EMLC in realizing the rapid separation of the seven-component triazine mixture. Published by Elsevier B.V. C1 Iowa State Univ, Dept Chem, Ames Lab USDOE, Ames, IA 50011 USA. Iowa State Univ, Dept Chem & Biol Engn, Ames Lab USDOE, Ames, IA 50011 USA. Iowa State Univ, Inst Combinatorial Discovery, Ames, IA 50011 USA. RP Yakes, BJ (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM betsy.yakes@fda.hhs.gov RI Yakes, Betsy/K-2646-2012 FU US Department of Energy-Ames Laboratory; Iowa State University [DE-AC02-07CH11358] FX The authors express their appreciation to Dr. Jennifer Granger for her insights and assistance in manuscript preparation. This work was supported by the US Department of Energy-Ames Laboratory. The Ames Laboratory is operated for the US Department of Energy by Iowa State University under Contract No. DE-AC02-07CH11358. NR 64 TC 6 Z9 6 U1 0 U2 11 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 JUN 25 PY 2010 VL 1217 IS 26 BP 4395 EP 4401 DI 10.1016/j.chroma.2010.04.031 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 612RT UT WOS:000278920900020 PM 20478562 ER PT J AU Asamoah, AK Sharfstein, JM AF Asamoah, Afia K. Sharfstein, Joshua M. TI Transparency at the Food and Drug Administration. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Asamoah, Afia K.] US FDA, Transparency Initiat, Silver Spring, MD USA. RP Asamoah, AK (reprint author), US FDA, Transparency Initiat, Silver Spring, MD USA. NR 0 TC 26 Z9 27 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 24 PY 2010 VL 362 IS 25 BP 2341 EP 2343 DI 10.1056/NEJMp1005202 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 614GO UT WOS:000279043800001 PM 20484392 ER PT J AU Katz, EJ Ilev, IK Krauthamer, V Kim, DH Weinreich, D AF Katz, Elizabeth J. Ilev, Ilko K. Krauthamer, Victor Kim, Do Hyun Weinreich, Daniel TI Excitation of primary afferent neurons by near-infrared light in vitro SO NEUROREPORT LA English DT Article DE dorsal root ganglion; laser; near-infrared light; nodose ganglion; optical stimulation ID ROOT GANGLION NEURONS; OPTICAL STIMULATION; RECEPTOR; TISSUE; NERVE; LASER; EXCITABILITY; EXPRESSION; CAPSAICIN; CHANNEL AB Near-infrared light therapy is an emerging neurostimulation technology, but its cellular mechanism of action remains unresolved. Using standard intracellular recording techniques, we observed that 5-10ms pulses of 1889 nm light depolarized the membrane potential for hundreds of milliseconds in more than 85% of dorsal root ganglion and nodose ganglion neurons tested. The laser-evoked depolarizations (LEDs) exhibited complex, multiphasic kinetics comprising fast and slow components. There was no discernable difference in the LEDs in intact ganglion neurons and in acutely isolated neurons. Thus, the LED sensor seems to reside within the neuronal membrane. The near-uniform distribution of responsive neurons increased membrane conductance, and the negative reversal potential value (-41 +/- 2.9 mV) suggests that LED is unrelated to the activation of heat-sensitive transient receptor potential cation channel subfamily V member 1 channels. The long duration of LEDs favors an involvement of second messengers. NeuroReport 21: 662-666 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [Katz, Elizabeth J.; Ilev, Ilko K.; Krauthamer, Victor; Kim, Do Hyun; Weinreich, Daniel] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Weinreich, Daniel] Sch Med, Dept Pharmacol, Baltimore, MD USA. RP Katz, EJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62, Silver Spring, MD 20993 USA. EM elizabeth.katz@fda.hhs.gov FU US Army Telemedicine & Advanced Technology Research Center [IAG 24-06-6066] FX The authors thank Drs N. Kramer, T. Moreira, and Kenneth C. Curley. This research has been supported in part by a grant from the US Army Telemedicine & Advanced Technology Research Center, IAG 24-06-6066. Disclaimer: the mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services. NR 24 TC 11 Z9 11 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUN 23 PY 2010 VL 21 IS 9 BP 662 EP 666 DI 10.1097/WNR.0b013e32833add3a PG 5 WC Neurosciences SC Neurosciences & Neurology GA 612DQ UT WOS:000278877400012 PM 20495496 ER PT J AU Eggert, D Thomas, C Spackman, E Pritchard, N Rojo, F Bublot, M Swayne, DE AF Eggert, Dawn Thomas, Colleen Spackman, Erica Pritchard, Nikki Rojo, Francisco Bublot, Michel Swayne, David E. TI Characterization and efficacy determination of commercially available Central American H5N2 avian influenza vaccines for poultry SO VACCINE LA English DT Article DE Chickens; Low pathogenicity avian influenza; H5N2; Vaccine ID NORTH-AMERICA; HONG-KONG; VIRUS; CHICKENS; HEMAGGLUTININ; EVOLUTION; MEXICO; INFECTION; IMMUNITY; UPDATE AB A poultry vaccination program was implemented in Central America beginning in January 1995 to control both H5N2 low (LPAI) and high pathogenicity avian influenza. This study was conducted to identify seed strain composition and the efficacy of 10 commercially available H5 vaccines against challenge with H5N2 LPAI viruses isolated from Latin America in 2003. The original 1994 vaccine seed virus in commercial inactivated vaccines did not significantly reduce challenge virus shed titers. However, two seed strains of inactivated vaccines, genetically more closely related to the challenge virus, did significantly reduce titers of challenge virus shed from respiratory tract. In addition, a live recombinant fowlpox virus vaccine containing a more distantly related Eurasian lineage H5 gene insert significantly reduced respiratory shedding as compared to sham vaccinates. These results demonstrate the feasibility of identifying vaccine seed strains in commercial finished products for regulatory verification and the need for periodic challenge testing against current field strains in order to select efficacious vaccine seed strains. Published by Elsevier Ltd. C1 [Eggert, Dawn; Thomas, Colleen; Spackman, Erica; Swayne, David E.] ARS, SE Poultry Res Lab, USDA, Athens, GA 30605 USA. [Thomas, Colleen] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Pritchard, Nikki] Merial Select Inc, R&D, Gainesville, GA 30501 USA. [Rojo, Francisco] Merial Mexico SA CV, Mexico City 76246, DF, Mexico. [Bublot, Michel] Merial SAS, R&D, F-69007 Lyon, France. RP Swayne, DE (reprint author), ARS, SE Poultry Res Lab, USDA, 934 Coll Stn Rd, Athens, GA 30605 USA. EM David.Swayne@ars.usda.gov FU USDA [6612-32000-048-00D]; Trust Agreement [58-6612-7-171] FX This research was supported by USDA CRIS project 6612-32000-048-00D and Trust Agreement 58-6612-7-171. Joan R. Beck, James Doster, Kira Moresco, and Scott Lee are thanked for providing excellent technical assistance. NR 30 TC 9 Z9 9 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUN 23 PY 2010 VL 28 IS 29 BP 4609 EP 4615 DI 10.1016/j.vaccine.2010.04.081 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 625AO UT WOS:000279863900012 PM 20470798 ER PT J AU Long-Croal, LM Wen, XB Ostlund, EN Hoshino, Y AF Long-Croal, LaShanda M. Wen, Xiaobo Ostlund, Eileen N. Hoshino, Yasutaka TI Concentration of acrylamide in a polyacrylamide gel affects VP4 gene coding assignment of group A equine rotavirus strains with P[12] specificity SO VIROLOGY JOURNAL LA English DT Article ID GENOMIC CHARACTERIZATION; G-SEROTYPE; ELECTROPHORESIS; DIARRHEA; BOVINE; IDENTIFICATION; NEUTRALIZATION; EPIDEMIOLOGY; INFECTION; ASSAY AB Background: It is universally acknowledged that genome segment 4 of group A rotavirus, the major etiologic agent of severe diarrhea in infants and neonatal farm animals, encodes outer capsid neutralization and protective antigen VP4. Results: To determine which genome segment of three group A equine rotavirus strains (H-2, FI-14 and FI-23) with P[12] specificity encodes the VP4, we analyzed dsRNAs of strains H-2, FI-14 and FI-23 as well as their reassortants by polyacrylamide gel electrophoresis (PAGE) at varying concentrations of acrylamide. The relative position of the VP4 gene of the three equine P[12] strains varied (either genome segment 3 or 4) depending upon the concentration of acrylamide. The VP4 gene bearing P[3], P[4], P[6], P[7], P[8] or P[18] specificity did not exhibit this phenomenon when the PAGE running conditions were varied. Conclusions: The concentration of acrylamide in a PAGE gel affected VP4 gene coding assignment of equine rotavirus strains bearing P[12] specificity. C1 [Long-Croal, LaShanda M.; Wen, Xiaobo; Hoshino, Yasutaka] NIAID, Rotavirus Vaccine Dev Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Ostlund, Eileen N.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20994 USA. [Ostlund, Eileen N.] Anim & Plant Hlth Inspect Serv, Diagnost Virol Lab, Natl Vet Serv Labs, USDA, Ames, IA 50010 USA. RP Hoshino, Y (reprint author), NIAID, Rotavirus Vaccine Dev Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM thoshino@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA FX We thank Dr. Albert Z. Kapikian for continuing support of the project and Ronald Jones for his excellent technical support. This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA. NR 33 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD JUN 23 PY 2010 VL 7 AR 136 DI 10.1186/1743-422X-7-136 PG 6 WC Virology SC Virology GA 630WX UT WOS:000280307300001 PM 20573245 ER PT J AU Goldkind, SF Sahin, L Gallauresi, B AF Goldkind, Sara F. Sahin, Leyla Gallauresi, Beverly TI Enrolling Pregnant Women in Research - Lessons from the H1N1 Influenza Pandemic SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Goldkind, Sara F.; Gallauresi, Beverly] US FDA, Off Commissioner, Silver Spring, MD USA. [Goldkind, Sara F.] US FDA, Off Good Clin Practice, Silver Spring, MD USA. [Sahin, Leyla] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Sahin, Leyla] US FDA, Maternal Hlth Team, Silver Spring, MD USA. [Gallauresi, Beverly] US FDA, Off Womens Hlth, Silver Spring, MD USA. RP Goldkind, SF (reprint author), US FDA, Off Commissioner, Silver Spring, MD USA. NR 5 TC 37 Z9 38 U1 0 U2 6 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 17 PY 2010 VL 362 IS 24 BP 2241 EP 2243 DI 10.1056/NEJMp1003462 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 611LJ UT WOS:000278816300001 PM 20554981 ER PT J AU Choudhuri, S Cui, Y Klaassen, CD AF Choudhuri, Supratim Cui, Yue Klaassen, Curtis D. TI Molecular targets of epigenetic regulation and effectors of environmental influences SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE DNA; Drug-metabolizing enzymes; Histone modifications; Methylation; Transporters ncRNA; miRNA ID DIETARY-PROTEIN RESTRICTION; EMBRYONIC STEM-CELLS; DNA METHYLATION; TRANSCRIPTIONAL REPRESSOR; GENE-EXPRESSION; PROMOTER HYPERMETHYLATION; TRANSGENERATIONAL ACTIONS; HISTONE MODIFICATIONS; ABERRANT EXPRESSION; TISSUE DISTRIBUTION AB The true understanding of what we currently define as epigenetics evolved over time as our knowledge on DNA methylation and chromatin modifications and their effects on gene expression increased. The current explosion of research on epigenetics and the increasing documentation of the effects of various environmental factors on DNA methylation, chromatin modification, as well as on the expression of small non-coding RNAs (ncRNAs) have expanded the scope of research on the etiology of various diseases including cancer. The current review briefly discusses the molecular mechanisms of epigenetic regulation and expands the discussion with examples on the role of environment, such as the immediate environment during development, in inducing epigenetic changes and modulating gene expression. Published by Elsevier Inc. C1 [Choudhuri, Supratim] US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, Div Biotechnol, College Pk, MD 20740 USA. [Choudhuri, Supratim] GRAS Notice Review, College Pk, MD USA. [Cui, Yue; Klaassen, Curtis D.] Univ Kansas, Med Ctr, Dept Pharmacol & Toxicol, Kansas City, KS 66103 USA. RP Choudhuri, S (reprint author), US FDA, Ctr Food Safety & Appl Nutr, OFAS DBGNR, HFS 255,5100 Paint Branch Rainbow Blvd, College Pk, MD 20740 USA. EM Supratim.Choudhuri@fda.hhs.gov; cklaasse@kumc.edu FU NCRR NIH HHS [P20 RR021940-045683, P20 RR021940-01, P20 RR021940-027767, P20 RR021940-03, P20 RR021940, P20 RR021940-02, P20 RR021940-036307, P20 RR021940-045675, P20 RR021940-036317, P20 RR021940-017636, P20 RR021940-04]; NIEHS NIH HHS [R01 ES009716, T32 ES007079-26A2, T32 ES007079-20, R01 ES009716-04, R01 ES013714-01A1, R01 ES009649-05A2, T32 ES007079-28, R01 ES009716-08, R01 ES013714-03, T32 ES007079-29, R01 ES009649-06, R01 ES009649-03, T32 ES007079-25, R01 ES009716-07, R01 ES009716-06A2, T32 ES007079, T32 ES007079-21, T32 ES007079-27, R01 ES009649-01A2, R01 ES009716-03, R01 ES009716-05, R01 ES009716-01A2, T32 ES007079-24, R01 ES009649, R01 ES009649-04, R01 ES009649-02, R01 ES013714-02, R01 ES013714-04, R01 ES013714, R01 ES013714-05, T32 ES007079-22, R01 ES009649-07, R01 ES009716-09, R01 ES009716-02, T32 ES007079-23] NR 115 TC 46 Z9 50 U1 0 U2 23 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JUN 15 PY 2010 VL 245 IS 3 BP 378 EP 393 DI 10.1016/j.taap.2010.03.022 PG 16 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 603JI UT WOS:000278204400011 PM 20381512 ER PT J AU Marshall, KM Bradshaw, M Johnson, EA AF Marshall, Kristin M. Bradshaw, Marite Johnson, Eric A. TI Conjugative Botulinum Neurotoxin-Encoding Plasmids in Clostridium botulinum SO PLOS ONE LA English DT Article ID INFANT BOTULISM; GENOME SEQUENCE; COMPLEX GENES; HALL-A; STRAINS; PERFRINGENS; IDENTIFICATION; EXPRESSION; DIVERSITY; SUBTYPES AB Background: Clostridium botulinum produces seven distinct serotypes of botulinum neurotoxins (BoNTs). The genes encoding different subtype neurotoxins of serotypes A, B, F and several dual neurotoxin-producing strains have been shown to reside on plasmids, suggesting that intra-and interspecies transfer of BoNT-encoding plasmids may occur. The objective of the present study was to determine whether these C. botulinum BoNT-encoding plasmids are conjugative. Methodology/Principal Findings: C. botulinum BoNT-encoding plasmids pBotCDC-A3 (strain CDC-A3), pCLJ (strain 657Ba) and pCLL (strain Eklund 17B) were tagged with the erythromycin resistance marker (Erm) using the ClosTron mutagenesis system by inserting a group II intron into the neurotoxin genes carried on these plasmids. Transfer of the tagged plasmids from the donor strains CDC-A3, 657Ba and Eklund 17B to tetracycline-resistant recipient C. botulinum strains was evaluated in mating experiments. Erythromycin and tetracycline resistant transconjugants were isolated from donor: recipient mating pairs tested. Transfer of the plasmids to the transconjugants was confirmed by pulsed-field gel electrophoresis (PFGE) and Southern hybridizations. Transfer required cell-to-cell contact and was DNase resistant. This indicates that transfer of these plasmids occurs via a conjugation mechanism. Conclusions/Significance: This is the first evidence supporting conjugal transfer of native botulinum neurotoxin-encoding plasmids in C. botulinum, and provides a probable mechanism for the lateral distribution of BoNT-encoding plasmids to other C. botulinum strains. The potential transfer of C. botulinum BoNT-encoding plasmids to other bacterial hosts in the environment or within the human intestine is of great concern for human pathogenicity and necessitates further characterization of these plasmids. C1 [Marshall, Kristin M.; Bradshaw, Marite; Johnson, Eric A.] Univ Wisconsin, Coll Agr & Life Sci, Dept Bacteriol, Madison, WI 53706 USA. RP Marshall, KM (reprint author), US FDA, Natl Ctr Food Safety & Technol, Summit, NJ USA. EM eajohnso@wisc.edu FU Food Research Institute of the University of Wisconsin-Madison; NIH/NIAID Regional Center of Excellence; NIH [1-U54-AI-057153] FX This work was sponsored by the Food Research Institute of the University of Wisconsin-Madison and by the NIH/NIAID Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research (RCE) Program. The authors wish to acknowledge membership and support from the Pacific Southwest Regional Center of Excellence grant U54 AI065359 and from the Region V "Great Lakes" Regional center of Excellence (NIH award 1-U54-AI-057153). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 24 Z9 24 U1 0 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 JUN 11 PY 2010 VL 5 IS 6 AR e11087 DI 10.1371/journal.pone.0011087 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 609NG UT WOS:000278662900024 PM 20552020 ER PT J AU Cederroth, CR Zimmermann, C Beny, JL Schaad, O Combepine, C Descombes, P Doerge, DR Pralong, FP Vassalli, JD Nefa, S AF Cederroth, Christopher R. Zimmermann, Celine Beny, Jean-Louis Schaad, Olivier Combepine, Chantal Descombes, Patrick Doerge, Daniel R. Pralong, Francois P. Vassalli, Jean-Dominique Nefa, Serge TI Potential detrimental effects of a phytoestrogen-rich diet on male fertility in mice SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE Dietary soy; Phytoestrogens; Isoflavones; Genistein; Endocrine disruptors; Reproduction; Spermatogenesis; Spermiogenesis; Androgen ID GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE-S; LACKING ANDROGEN RECEPTOR; SPRAGUE-DAWLEY RATS; SOY FORMULA MILK; SEMINAL-VESICLE; SERTOLI-CELL; REPRODUCTIVE DEVELOPMENT; TESTOSTERONE LEVELS; MARMOSET MONKEYS; SPERM MOTILITY AB Soy and soy-based products are widely consumed by infants and adult individuals. There has been speculation that the presence of isoflavone phytoestrogens in soybean cause adverse effects on the development and function of the male reproductive system The purpose of this study was to examine the influence of dietary soy and phytoestrogens on testicular and reproductive functions. Male mice were fed from conception to adulthood with either a high soy-containing diet or a soy-free diet. Although adult mice fed a soy-rich diet exhibited normal male behaviour and were fertile, we observed a reduced proportion of haploid germ cells in testes correlating with a 25% decrease in epididymal sperm counts and a 21% reduction in litter size LH and androgens levels were not affected but transcripts coding for androgen-response genes in Sertoli cells and Gapd-s, a germ cell-specific gene involved in sperm glycolysis and mobility were significantly reduced In addition, we found that dietary soy decreased the size of the seminal vesicle but without affecting its proteolytic activity. Taken together, these studies show that long-term exposure to dietary soy and phytoestrogens may affect male reproductive function resulting in a small decrease in sperm count and fertility (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Nefa, Serge] Univ Geneva, Dept Genet Med & Dev, Fac Med, Sch Med, CH-1211 Geneva 4, Switzerland. [Beny, Jean-Louis] Univ Geneva, Dept Zool, CH-1211 Geneva, Switzerland. [Schaad, Olivier; Descombes, Patrick] Univ Geneva, Natl Ctr Competence Res Frontiers Genet, CH-1211 Geneva 4, Switzerland. [Pralong, Francois P.] Univ Lausanne Hosp, Serv Endocrinol Diabetol & Metab, Lausanne, Switzerland. [Doerge, Daniel R.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Nefa, S (reprint author), Univ Geneva, Dept Genet Med & Dev, Fac Med, Sch Med, Rue Michel Servet 1, CH-1211 Geneva 4, Switzerland. RI Cederroth, Christopher/B-9932-2011; OI Cederroth, Christopher/0000-0001-7267-5136 FU Swiss National Science Foundation [NRP50, 4050-104375]; Foundation Gertrude von Meissner and The Sir Jules Thorn Charitable Overseas Trust Reg.; Ernst & Lucie Schmidheiny Foundation FX We thank Francoise Gribi, Olivier Schaad, Didier Cholet for assistance. Serge Nef has received Swiss National Science Foundation Grant no. NRP50, 4050-104375, and is also supported by the Foundation Gertrude von Meissner and The Sir Jules Thorn Charitable Overseas Trust Reg., Schaan Christopher R. Cederroth is supported by the Ernst & Lucie Schmidheiny Foundation. Serge Nef declares is a founder of Amazentis S.A. and a member of its scientific advisory board. NR 49 TC 24 Z9 28 U1 3 U2 31 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JUN 10 PY 2010 VL 321 IS 2 BP 152 EP 160 DI 10.1016/j.mce.2010.02.011 PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 599ND UT WOS:000277919000007 PM 20171261 ER PT J AU Shao, L Wu, LH Fang, H Tong, WD Fan, XH AF Shao, Li Wu, Leihong Fang, Hong Tong, Weida Fan, Xiaohui TI Does Applicability Domain Exist in Microarray-Based Genomic Research? SO PLOS ONE LA English DT Article ID GENE-EXPRESSION DATA; BREAST-CANCER; OLIGONUCLEOTIDE MICROARRAY; ESTROGEN-RECEPTOR; DNA MICROARRAYS; PREDICTION; CLASSIFICATION; MODELS; CHEMOTHERAPY; VALIDATION AB Constructing an accurate predictive model for clinical decision-making on the basis of a relatively small number of tumor samples with high-dimensional microarray data remains a very challenging problem. The validity of such models has been seriously questioned due to their failure in clinical validation using independent samples. Besides the statistical issues such as selection bias, some studies further implied the probable reason was improper sample selection that did not resemble the genomic space defined by the training population. Assuming that predictions would be more reliable for interpolation than extrapolation, we set to investigate the impact of applicability domain (AD) on model performance in microarray-based genomic research by evaluating and comparing model performance for samples with different extrapolation degrees. We found that the issue of applicability domain may not exist in microarray-based genomic research for clinical applications. Therefore, it is not practicable to improve model validity based on applicability domain. C1 [Shao, Li; Wu, Leihong; Fan, Xiaohui] Zhejiang Univ, Pharmaceut Informat Inst, Coll Pharmaceut Sci, Hangzhou 310003, Zhejiang, Peoples R China. [Fang, Hong] US FDA, Z Tech Corp, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Fan, XH (reprint author), Zhejiang Univ, Pharmaceut Informat Inst, Coll Pharmaceut Sci, Hangzhou 310003, Zhejiang, Peoples R China. EM fanxh@zju.edu.cn OI Wu, Leihong/0000-0002-4093-3708 FU National Science Foundation of China [30801556, 30830121]; Science Foundation of Chinese University [2009QNA7031]; Zhejiang Provincial Natural Science Foundation of China [R2080693] FX This work was supported by the National Science Foundation of China (No. 30801556 and 30830121), Science Foundation of Chinese University (No. 2009QNA7031) and the Zhejiang Provincial Natural Science Foundation of China (No. R2080693). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 5 Z9 5 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 10 PY 2010 VL 5 IS 6 AR e11055 DI 10.1371/journal.pone.0011055 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 608QA UT WOS:000278599600015 PM 20548774 ER PT J AU Garber, EAE Venkateswaran, KV O'Brien, TW AF Garber, Eric A. E. Venkateswaran, Kodumudi V. O'Brien, Thomas W. TI Simultaneous Multiplex Detection and Confirmation of the Proteinaceous Toxins Abrin, Ricin, Botulinum Toxins, and Staphylococcus Enterotoxins A, B, and C in Food SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Abrin; botulinum toxin; ricin; Staphylococcus enterotoxin; food; multiplex; Luminex ID LINKED-IMMUNOSORBENT-ASSAY; BIOTHREAT AGENTS; ANTIBODIES; IMMUNOASSAY; POWDER AB Detection of proteinaceous toxins in complex heterogeneous mixtures requires highly specific and sensitive methods. Multiplex technology employing multiple antibodies that recognize different epitopes on a toxin provides built-in confirmatory analysis as part of the initial screen and thereby increases the reliability associated with both presumptive positive and negative results. Polyclonal and monoclonal antibodies were obtained for abrin, botulinum toxins, ricin, and Staphylococcus enterotoxins A, B, and C (SEA, SEB, and SEC). Food samples were spiked with the toxins either individually or mixed and analyzed following 40-fold dilution. Abrin, botulinum toxin A complex, ricin, and SEB displayed limits of detection in the original food samples ranging from 0.03 to 1.3 mu g/mL, from 0.03 to 0.07 mu g/mL, from 0.01 to 0.1 mu g/mL, and from <0.01 to 0.03 mu g/mL, respectively. Redundancy, that is, multiple antibodies for each toxin, some recognizing different epitopes or displaying different binding affinities, provided a "fingerprint" for the presence of the toxins and built-in confirmation, thus reducing the likelihood of false-positive and false-negative results. Inclusion of internal controls, including a unique protein, helped control for variations in dilution. Paramagnetic microspheres facilitated the detection of analyte in foods containing particulate matter incompatible with the use of filter plates normally used in the wash steps of assays employing standard polystyrene microspheres. C1 [Garber, Eric A. E.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. [Venkateswaran, Kodumudi V.] Radix BioSolut, Georgetown, TX 78626 USA. [O'Brien, Thomas W.] Tetracore Inc, Rockville, MD 20850 USA. RP Garber, EAE (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Eric.Garber@fda.hhs.gov NR 26 TC 28 Z9 29 U1 0 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUN 9 PY 2010 VL 58 IS 11 BP 6600 EP 6607 DI 10.1021/jf100789n PG 8 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 602OU UT WOS:000278149500009 PM 20455521 ER PT J AU Duan, H Struble, E Zhong, LL Mihalik, K Major, M Zhang, P Feinstone, S Feigelstock, D AF Duan, Hongying Struble, Evi Zhong, Lilin Mihalik, Kathleen Major, Marian Zhang, Pei Feinstone, Stephen Feigelstock, Dino TI Hepatitis C virus with a naturally occurring single amino-acid substitution in the E2 envelope protein escapes neutralization by naturally-induced and vaccine-induced antibodies SO VACCINE LA English DT Article DE HCV; Vaccine; Escape mutations; Neutralization ID HYPERVARIABLE REGION-1; IMMUNE-RESPONSES; CHIMPANZEES; INFECTION; HCV; IMMUNIZATION; REPLICATION; PREVENTION; INDUCTION; EVOLUTION AB Mutations arising in neutralizing epitopes of hepatitis C virus may play a role in the ability of the virus to escape control by neutralizing antibodies and in the establishment of chronic infections. An amino-acid substitution, Q412H, within a major conserved neutralization epitope EP I (aa 412-426) in the E2 glycoprotein is observed in chronic HCV carriers. We found that naturally acquired polyclonal EPI-specific antibodies have an equivalent binding capacity toward either the wild type or the Q412H mutant peptide encompassing the EP I epitope. While EP I-specific antibodies neutralized J6/JFH1 virus in vitro, they did not neutralize J6/JFH1 virus containing the Q412H mutation. Furthermore, we found that plasma obtained from a chimpanzee that had anti-E1/E2 antibodies following experimental immunization, neutralized the wild type J6/JFH1 virus but failed to neutralize the mutant virus. Thus, mutation Q412H found in naturally occurring variants could represent an antibody escape mutation. These data may have important implications for vaccine design. Published by Elsevier Ltd. C1 [Feigelstock, Dino] US FDA, CBER OVRR, Lab Hepatitis Viruses, Div Viral Prod, Bethesda, MD 20892 USA. [Struble, Evi; Zhong, Lilin; Zhang, Pei] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. RP Feigelstock, D (reprint author), US FDA, CBER OVRR, Lab Hepatitis Viruses, Div Viral Prod, Bldg 29A,Room 1D02,HFM 448,29 Lincoln Dr, Bethesda, MD 20892 USA. EM Dino.feigelstock@fda.hhs.gov FU Food and Drug Administration FX This work was supported by internal funding from the Food and Drug Administration. NR 29 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUN 7 PY 2010 VL 28 IS 25 BP 4138 EP 4144 DI 10.1016/j.vaccine.2010.04.024 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 614EZ UT WOS:000279039500004 PM 20433800 ER PT J AU Palaima, E Leymarie, N Stroud, D Mizanur, RM Hodgkin, J Gravato-Nobre, MJ Costello, CE Cipollo, JF AF Palaima, Elizabeth Leymarie, Nancy Stroud, Dave Mizanur, Rahman M. Hodgkin, Jonathan Gravato-Nobre, Maria J. Costello, Catherine E. Cipollo, John F. TI The Caenorhabditis elegans bus-2 Mutant Reveals a New Class of O-Glycans Affecting Bacterial Resistance SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PATHOGEN MICROBACTERIUM-NEMATOPHILUM; BLOOD-GROUP ANTIGENS; C-ELEGANS; INFECTION; TOXIN; GLYCOSYLTRANSFERASES; ATTACHMENT; DIVERSITY; FEATURES; BINDING AB Microbacterium nematophilum causes a deleterious infection of the C. elegans hindgut initiated by adhesion to rectal and anal cuticle. C. elegans bus-2 mutants, which are resistant to M. nematophilum and also to the formation of surface biofilms by Yersinia sp., carry genetic lesions in a putative glycosyltransferase containing conserved domains of core-1 beta 1,3-galactosyltransferases. bus-2 is predicted to act in the synthesis of core-1 type O-glycans. This observation implies that the infection requires the presence of host core-1 O-glycoconjugates and is therefore carbohydrate-dependent. Chemical analysis reported here reveals that bus-2 is indeed deficient in core-1 O-glycans. These mutants also exhibit a new subclass of O-glycans whose structures were determined by high performance tandem mass spectrometry; these are highly fucosylated and have a novel core that contains internally linked GlcA. Lectin studies showed that core-1 glycans and this novel class of O-glycans are both expressed in the tissue that is infected in the wild type worms. In worms having the bus-2 genetic background, core-1 glycans are decreased, whereas the novel fucosyl O-glycans are increased in abundance in this region. Expression analysis using a red fluorescent protein marker showed that bus-2 is expressed in the posterior gut, cuticle seam cells, and spermatheca, the first two of which are likely to be involved in secreting the carbohydrate-rich surface coat of the cuticle. Therefore, in the bus-2 background of reduced core-1 O-glycans, the novel fucosyl glycans likely replace or mask remaining core-1 ligands, leading to the resistance phenotype. There are more than 35 Microbacterium species, some of which are pathogenic in man. This study is the first to analyze the biochemistry of adhesion to a host tissue by a Microbacterium species. C1 [Mizanur, Rahman M.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Palaima, Elizabeth; Leymarie, Nancy; Costello, Catherine E.; Cipollo, John F.] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. [Palaima, Elizabeth; Leymarie, Nancy; Costello, Catherine E.; Cipollo, John F.] Boston Univ, Sch Med, Dept Mol Med, Boston, MA 02118 USA. [Stroud, Dave; Hodgkin, Jonathan; Gravato-Nobre, Maria J.] Univ Oxford, Dept Biochem, Genet Unit, Oxford OX1 3QU, England. RP Cipollo, JF (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 29,Rm 126,8800 Rockville Pike, Bethesda, MD 20892 USA. EM john.cipollo@fda.hhs.gov OI Costello, Catherine/0000-0003-1594-5122 FU National Institutes of Health [P41RR010888, S10RR015942, S10RR020946]; Medical Research Council (United Kingdom) [G0600238] FX This work was supported, in whole or in part, by National Institutes of Health Grants P41RR010888 and S10RR015942 (to C. E. C.) and S10RR020946 (to J. Zaia). This work was also supported by Medical Research Council (United Kingdom) Grant G0600238 (to J. H.). NR 37 TC 13 Z9 15 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 4 PY 2010 VL 285 IS 23 BP 17662 EP 17672 DI 10.1074/jbc.M109.065433 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 602IT UT WOS:000278133400044 PM 20385555 ER PT J AU Matyas, B Cronquist, A Cartter, M Tobin-D'Angelo, M Blythe, D Smith, K Lathrop, S Morse, D Cieslak, P Dunn, J Holt, KG Henao, OL Fullerton, KE Mahon, BE Hoekstra, RM Griffin, PM Tauxe, RV Bhattarai, A AF Matyas, B. Cronquist, A. Cartter, M. Tobin-D'Angelo, M. Blythe, D. Smith, K. Lathrop, S. Morse, D. Cieslak, P. Dunn, J. Holt, K. G. Henao, O. L. Fullerton, K. E. Mahon, B. E. Hoekstra, R. M. Griffin, P. M. Tauxe, R. V. Bhattarai, Achuyt TI Preliminary FoodNet Data on the Incidence of Infection With Pathogens Transmitted Commonly Through Food-10 States, 2009 (Reprinted from MMWR, vol 59, pg 418-422, 2010) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint ID MULTISTATE OUTBREAK; UNITED-STATES C1 [Cartter, M.] Connecticut Dept Publ Hlth & Addict Serv, Hartford, CT 06106 USA. [Blythe, D.] Maryland Dept Hlth & Mental Hyg, Baltimore, MD 21201 USA. [Smith, K.] Minnesota Dept Hlth, Minneapolis, MN 55414 USA. [Morse, D.] New York State Dept Hlth, Albany, NY 12237 USA. [Holt, K. G.] US FDA, Ctr Food Safety & Appl Nutr, USDA, Food Safety & Inspect Svc, Rockville, MD 20857 USA. [Bhattarai, Achuyt] CDC, Atlanta, GA 30333 USA. RI Bhattarai, Achuyt/B-8760-2008 OI Bhattarai, Achuyt/0000-0002-0514-4850 NR 10 TC 2 Z9 3 U1 2 U2 6 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 JUN 2 PY 2010 VL 303 IS 21 BP 2130 EP 2132 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 603BE UT WOS:000278182100009 ER PT J AU Rahman, Z Zidan, AS Khan, MA AF Rahman, Ziyaur Zidan, Ahmed S. Khan, Mansoor A. TI Formulation and Evaluation of a Protein-loaded Solid Dispersions by Non-destructive Methods SO AAPS JOURNAL LA English DT Article DE cyclosporin; NIR; PEG-6000; PXRD; solid dispersion ID RAY-POWDER DIFFRACTION; NEAR-INFRARED SPECTROSCOPY; CYCLOSPORINE-A; IN-VITRO; REFLECTANCE SPECTRA; PARTICLE-SIZE; DRUG; BIOAVAILABILITY; DISSOLUTION; REGRESSION AB The purpose of this investigation was to develop solid dispersion (SD) formulation of cyclosporine (CyA) using polyethylene glycol (PEG-6000) to enhance its dissolution rate followed by nondestructive method for the prediction of both drug and carrier. SD formulations were prepared by varying the ratio of CyA and PEG-6000 by solvent evaporation technique and characterized by dissolution, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), powder X-ray diffraction (PXRD), near infrared (NIR) and near infrared chemical imaging (NIR-CI). Dissolution data revealed enhanced dissolution of CyA when compared with pure CyA. DSC results showed that the crystallinity of PEG-6000 has decreased as indicated by decrease in the enthalpy of fusion and melting peak in the formulations. FTIR data demonstrated no chemical interaction between drug and carrier. The surface morphology of SD formulations was similar to PEG-6000 particle. NIR-CI disclosed homogeneity of SD matrix as indicated by symmetrical histograms with smaller values of skewness. Similar to NIR, a multivariate peak evaluation with principal component analysis and partial least square (PLS) were carried out with PXRD spectral data. PLS models with both techniques showed good correlation coefficient and smaller value of root mean square of errors. The accuracy of model for predicting CyA and PEG-6000 in NIR and PXRD data were 5.22%, 5.35%, 5.27%, and 2.10%, respectively. In summary, chemometric applications of non-destructive method sensors provided a valuable means of characterization and estimation of drug and carrier in the novel formulations. C1 [Rahman, Ziyaur; Zidan, Ahmed S.; Khan, Mansoor A.] US FDA, Div Prod Qual & Res, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Zidan, Ahmed S.] Zagazig Univ, Fac Pharm, Zagazig, Egypt. [Khan, Mansoor A.] DPQR, FDA, CDER, Silver Spring, MD 20993 USA. RP Khan, MA (reprint author), US FDA, Div Prod Qual & Res, Ctr Drug Evaluat & Res, Silver Spring, MD 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. The views presented in this article do not necessarily reflect those of the US Food and Drug Administration. NR 47 TC 12 Z9 12 U1 2 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD JUN PY 2010 VL 12 IS 2 BP 158 EP 170 DI 10.1208/s12248-009-9171-7 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 574FX UT WOS:000275975700006 PM 20127529 ER PT J AU Zidan, AS Spinks, C Fortunak, J Habib, M Khan, MA AF Zidan, Ahmed S. Spinks, Crystal Fortunak, Joseph Habib, Muhammad Khan, Mansoor A. TI Near-Infrared Investigations of Novel Anti-HIV Tenofovir Liposomes SO AAPS JOURNAL LA English DT Article DE characterization; chemical imaging; liposomes; near infrared; tenofovir ID TRANSMEMBRANE-PH GRADIENTS; LARGE UNILAMELLAR VESICLES; DRUG-DELIVERY SYSTEMS; ANTIRETROVIRAL THERAPY; PART II; SPECTROSCOPY; STRATEGIES; REGRESSION; PHARMACOKINETICS; STEARYLAMINE AB Near-infrared (NIR) approaches is considered one of the most well-studied process analyzers evolving from the process analytical technology initiatives. The objective of this study was to evaluate NIR spectroscopy and imaging to assess individual components within a novel tenofovir liposomal formulation. By varying stearylamine, as a positive charge imparting agent, five batches were prepared by the thin film method. Each formulation was characterized in terms of drug entrapment efficiency, release characteristics, particle sizing, and zeta potential. Drug excipients compatibility was tested using Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction. The obtained results showed an increase in drug entrapment and a slower drug release by increasing the incorporated percentage of stearylamine. The compatibility testing revealed a significant interaction between the drug and some of the investigated excipients. The developed NIR calibration model was able to assess drug, phospholipid, and stearylamine levels along the batches. The calibration and prediction plots were linear with correlation coefficients of more than 0.9. The root square standard errors of calibration and prediction did not attain 5% of the measured values confirming the accuracy of the model. In contrast, NIR spectral imaging was capable of clearly distinguishing the different batches, both qualitatively and quantitatively. A linear relationship was obtained correlating the actual drug entrapped and the predicted values obtained from the partial least squares images. C1 [Zidan, Ahmed S.; Spinks, Crystal; Khan, Mansoor A.] US FDA, Div Prod Qual Res, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Spinks, Crystal; Fortunak, Joseph; Habib, Muhammad] Howard Univ, Sch Pharm, Dept Pharmaceut Sci, Washington, DC 20059 USA. [Zidan, Ahmed S.] Zagazig Univ, Fac Pharm, Dept Pharmaceut, Zagazig, Egypt. RP Khan, MA (reprint author), US FDA, Div Prod Qual Res, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM Mansoor.Khan@fda.hhs.gov RI Zidan, Ahmed/I-1147-2012 NR 40 TC 21 Z9 21 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD JUN PY 2010 VL 12 IS 2 BP 202 EP 214 DI 10.1208/s12248-010-9177-1 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 574FX UT WOS:000275975700011 PM 20195931 ER PT J AU Collier, JW Shah, RB Gupta, A Sayeed, V Habib, MJ Khan, MA AF Collier, Jarrod W. Shah, Rakhi B. Gupta, Abhay Sayeed, Vilayat Habib, Muhammad J. Khan, Mansoor A. TI Influence of Formulation and Processing Factors on Stability of Levothyroxine Sodium Pentahydrate SO AAPS PHARMSCITECH LA English DT Article DE excipients; formulation; levothyroxine sodium pentahydrate; moisture sorption; stability ID EXCIPIENT COMPATIBILITY; DEGRADATION PRODUCTS; TABLETS; IDENTIFICATION; GRANULATION AB Stability of formulations over shelf-life is critical for having a quality product. Choice of excipients, manufacturing process, storage conditions, and packaging can either mitigate or enhance the degradation of the active pharmaceutical ingredient (API), affecting potency and/or stability. The purpose was to investigate the influence of processing and formulation factors on stability of levothyroxine (API). The API was stored at long-term (25A degrees C/60%RH), accelerated (40A degrees C/75%RH), and low-humidity (25A degrees C/0%RH and 40A degrees C/0%RH) conditions for 28 days. Effect of moisture loss was evaluated by drying it (room temperature, N(2)) and placed at 25A degrees C/0%RH and 40A degrees C/0%RH. The API was incubated with various excipients (based on package insert of marketed tablets) in either 1:1, 1:10, or 1:100 ratios with 5% moisture at 60A degrees C. Commonly used ratios for excipients were used. The equilibrium sorption data was collected on the API and excipients. The API was stable in solid state for the study duration under all conditions for both forms (potency between 90% and 110%). Excipients effect on stability varied and crospovidone, povidone, and sodium laurel sulfate (SLS) caused significant API degradation where deiodination and deamination occurred. Moisture sorption values were different across excipients. Crospovidone and povidone were hygroscopic whereas SLS showed deliquescence at high RH. The transient formulation procedures where temperature might go up or humidity might go down would not have major impact on the API stability. Excipients influence stability and if possible, those three should either be avoided or used in minimum quantity which could provide more stable tablet formulations with minimum potency loss throughout its shelf-life. C1 [Collier, Jarrod W.; Shah, Rakhi B.; Gupta, Abhay; Khan, Mansoor A.] US FDA, Div Prod Qual Res, Off Testing & Res, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Collier, Jarrod W.; Habib, Muhammad J.] Howard Univ, Sch Pharm, Dept Pharmaceut Sci, Washington, DC 20059 USA. [Sayeed, Vilayat] US FDA, Div Chem 3, Off Gener Drugs, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Khan, MA (reprint author), US FDA, Div Prod Qual Res, Off Testing & Res, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Life Sci Bldg 64, Silver Spring, MD 20993 USA. EM Mansoor.khan@fda.hhs.gov NR 23 TC 14 Z9 14 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PD JUN PY 2010 VL 11 IS 2 BP 818 EP 825 DI 10.1208/s12249-010-9434-8 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 612RY UT WOS:000278921400037 PM 20454876 ER PT J AU Zhang, YB Ali, SF Dervishi, E Xu, Y Li, ZR Casciano, D Biris, AS AF Zhang, Yongbin Ali, Syed F. Dervishi, Enkeleda Xu, Yang Li, Zhongrui Casciano, Daniel Biris, Alexandru S. TI Cytotoxicity Effects of Graphene and Single-Wall Carbon Nanotubes in Neural Phaeochromocytoma-Derived PC12 Cells SO ACS NANO LA English DT Article DE graphene; single-wall carbon nanotubes; cytotoxicity; shape; PC12 cells; reactive oxidative species ID PULMONARY TOXICITY; DRUG-DELIVERY; RATS AB Graphitic nanomaterials such as graphene layers (G) and single-wall carbon nanotubes (SWCNT) are potential candidates in a large number of biomedical applications. However, little is known about the effects of these nanomaterials on biological systems. Here we show that the shape of these materials is directly related to their induced cellular toxicity. Both G and SWCNT induce cytotoxic effects, and these effects are concentration-and shape-dependent. Interestingly, at low concentrations, G induced stronger metabolic activity than SWCNT, a trend that reversed at higher concentrations. Lactate dehydrogenase levels were found to be significantly higher for SWCNT as compared to the G samples. Moreover, reactive oxygen species were generated in a concentration-and time-dependent manner after exposure to G, indicating an oxidative stress mechanism. Furthermore, time-dependent caspase 3 activation after exposure to G (10 mu g/mL) shows evidence of apoptosis. Altogether these studies suggest different biological activities of the graphitic nanomaterials, with the shape playing a primary role. C1 [Zhang, Yongbin; Ali, Syed F.] US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Dervishi, Enkeleda; Xu, Yang; Li, Zhongrui; Casciano, Daniel; Biris, Alexandru S.] Univ Arkansas, Nanotechnol Ctr, Dept Appl Sci, Little Rock, AR 72204 USA. RP Ali, SF (reprint author), US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM syed.ali@fda.hhs.gov; asbiris@ualr.edu RI Biris, Alexandru/A-8507-2010 FU National Center for Toxicological Research; Arkansas Science and Technology Authority [08-CAT-03] FX This research was supported in part by an appointment (Y.Z.) to the Research Participation Program at the National Center for Toxicological Research, administrated by the Oak Ridge Institute of Science and Education through an inter-agency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration. Financial assistance from the Arkansas Science and Technology Authority Grant No. 08-CAT-03 is highly appreciated. NR 31 TC 446 Z9 463 U1 28 U2 245 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 J9 ACS NANO JI ACS Nano PD JUN PY 2010 VL 4 IS 6 BP 3181 EP 3186 DI 10.1021/nn1007176 PG 6 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 612HU UT WOS:000278888600029 PM 20481456 ER PT J AU Krulewitch, CJ Ritchey, MB Cheng, H Marinac-Dabic, D Gross, T Ji, J Gibbs, J Turski, K AF Krulewitch, C. J. Ritchey, M. B. Cheng, H. Marinac-Dabic, D. Gross, T. Ji, J. Gibbs, J. Turski, K. TI A METHODOLOGY TO USE MEDICARE CLAIMS DATABASE TO EVALUATE DEVICE SAFETY: EVALUATION OF UROGYNECOLOGIC SURGICAL MESH SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Krulewitch, C. J.; Ritchey, M. B.; Cheng, H.; Marinac-Dabic, D.; Gross, T.; Ji, J.; Gibbs, J.; Turski, K.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S47 EP S47 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300187 ER PT J AU Marinac-Dabic, D Dole, KV AF Marinac-Dabic, D. Dole, K. V. TI APPLICATION OF METHODOLOGICAL ADVANCEMENTS AND CHALLENGES IN MEDICAL DEVICE RESEARCH: WHAT CAN WE DO, AND WHAT CAN WE DO BETTER? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Marinac-Dabic, D.; Dole, K. V.] US FDA, Div Epidemiol, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S47 EP S47 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300188 ER PT J AU Mohan, KVK Rao, SS Atreya, CD AF Mohan, Ketha V. K. Rao, Shilpakala Sainath Atreya, Chintamani D. TI Antiviral activity of selected antimicrobial peptides against vaccinia virus SO ANTIVIRAL RESEARCH LA English DT Article DE AMPs; RW peptides; Platelet-derived peptides; Microbicidal; pfu ID WEST-NILE-VIRUS; SARS-COV; INACTIVATION; PROTEIN; ENTRY; IDENTIFICATION; INFECTIONS; INHIBITION; MECHANISMS; PRODUCTS AB Antimicrobial peptides (AMPS) are gaining importance as effective therapeutic alternatives to conventional antibiotics. Recently we have shown that a set of nine synthetic antimicrobial peptides, four originating from thrombin-induced human platelet-derived antimicrobial proteins named PD1-PD4 and five synthetic repeats of arginine-tryptophan (RW) repeats (RW1-5) demonstrate antibacterial activity in plasma and platelets. Using WR strain of vaccinia virus (VV) as a model virus for enveloped virus in the present study, we tested the same nine synthetic peptides for their antiviral activity. A cell culture-based standard plaque reduction assay was utilized to estimate antiviral effectiveness of the peptides. Our analysis revealed that peptides PD3, PD4, and RW3 were virucidal against W with PD3 demonstrating the highest antiviral activity of 100-fold reduction in viral titers, whereas, PD4 and RW3 peptide treatments resulted in 10-30-fold reduction. The EC(50) values of PD3, PD4 and RW3 were found to be 40 mu g/ml, 50 mu g/ml and 6.5 mu M, respectively. In VV-spiked plasma samples, the virucidal activity of PD3, PD4 and RW3 was close to 100% (90-100-fold reduction). Overall, the present study constitutes a new proof-of-concept in developing peptide therapeutics for vaccinia virus infections in biothreat scenarios and as in vitro viral reduction agents. Published by Elsevier B.V. C1 [Mohan, Ketha V. K.; Rao, Shilpakala Sainath; Atreya, Chintamani D.] US FDA, Sect Cell Biol, Lab Cellular Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Mohan, KVK (reprint author), Bldg 29A,Room 2C-11,NIH Campus,8800 Rockville Pik, Bethesda, MD 20892 USA. EM krishna.ketha@fda.hhs.gov FU Center for Biologics Evaluation and Research (CBER) FX The authors wish to acknowledge Dr. Bernard Moss, NIH, Bethesda, for providing the WR virus strain. SSR is a recipient of a postdoctoral fellowship at the Center for Biologics Evaluation and Research (CBER) administered by the Oak Ridge Institute for Science and Education (ORISE) through an intra-agency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. Review of the manuscript by Drs. Tahir Malik and Zhiping Ye, CBER is gratefully acknowledged. NR 35 TC 17 Z9 17 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JUN PY 2010 VL 86 IS 3 BP 306 EP 311 DI 10.1016/j.antiviral.2010.03.012 PG 6 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 604VL UT WOS:000278306500010 PM 20347875 ER PT J AU Han, JH Ilev, IK Kim, DH Song, CG Kang, JU AF Han, J. -H. Ilev, I. K. Kim, D. -H. Song, C. G. Kang, J. U. TI Investigation of gold-coated bare fiber probe for in situ intra-vitreous coherence domain optical imaging and sensing SO APPLIED PHYSICS B-LASERS AND OPTICS LA English DT Article ID RETINAL VEIN OCCLUSION; FROG RETINA; TOMOGRAPHY; SURGERY; OCT AB We have investigated the usage of gold-plated bare fiber probes for in situ imaging of retinal layers and surrounding ocular tissues using time-domain common-path optical coherence tomography. The fabricated intra-vitreous gold-plated micro-fiber probe can be fully integrated with surgical tools working in close proximity to the tissue to provide subsurface images having a self-contained reference plane independent to the Fresnel reflection between the distal end of the probe and the following medium for achieving reference in typical common-path optical coherence tomography. We have fully characterized the probe in an aqueous medium equivalent to the vitreous humor in the eye and were able to differentiate various functional retinal tissue layers whose thickness is larger than the system's resolution. C1 [Han, J. -H.; Song, C. G.; Kang, J. U.] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. [Ilev, I. K.; Kim, D. -H.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Song, C. G.] Chonbuk Natl Univ, Sch Elect & Informat Engn, Ctr Adv Image & Informat Technol, Jeonju 561756, Jeonbuk, South Korea. RP Han, JH (reprint author), Johns Hopkins Univ, Dept Elect & Comp Engn, 3400 N Charles St, Baltimore, MD 21218 USA. EM jhan16@jhu.edu RI Kang, Jin/A-3228-2010 FU NIH [BRP 1R01 EB 007969-01] FX This work was supported in part by NIH grant BRP 1R01 EB 007969-01. NR 33 TC 6 Z9 6 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0946-2171 J9 APPL PHYS B-LASERS O JI Appl. Phys. B-Lasers Opt. PD JUN PY 2010 VL 99 IS 4 BP 741 EP 746 DI 10.1007/s00340-010-3910-4 PG 6 WC Optics; Physics, Applied SC Optics; Physics GA 607PZ UT WOS:000278519900018 PM 20567605 ER PT J AU Ananthaswamy, N Rutledge, R Sauna, ZE Ambudkar, SV Dine, E Nelson, E Xia, D Golin, J AF Ananthaswamy, Neeti Rutledge, Robert Sauna, Zuben E. Ambudkar, Suresh V. Dine, Elliot Nelson, Emily Xia, Di Golin, John TI The Signaling Interface of the Yeast Multidrug Transporter Pdr5 Adopts a Cis Conformation, and There Are Functional Overlap and Equivalence of the Deviant and Canonical Q-Loop Residues SO BIOCHEMISTRY LA English DT Article ID NUCLEOTIDE-BINDING DOMAIN; ABC TRANSPORTER; P-GLYCOPROTEIN; ATP HYDROLYSIS; EFFLUX; MECHANISM; ARCHITECTURE; MUTATIONS; CASSETTE; COMPLEX AB ABC transporters are polytopic proteins. ATP hydrolysis and substrate transport take place in separate domains, and these activities must he coordinated through a signal interface. We previously characterized a mutation (S558Y) in the yeast multidrug transporter Pdr5 that uncouples ATP hydrolysis and drug transport. To characterize the transmission interface, we used a genetic screen to isolate second-site mutations of S558Y that restore drug transport. We recovered suppressors that restore drug resistance; their locations provide functional evidence for an interface in the cis rather than the trans configuration indicated by structural and cross-linking studies of bacterial and eukaryotic efflux transporters. One mutation, E244G, defines the Q-loop of the deviant portion of NBD1, which is the hallmark of this group of fungal transporters. When moved to an otherwise wild-type background, this mutation and its counterpart in the canonical ATP-binding site Q951G show a similar reduction in drug resistance and in the very high basal-level ATP hydrolysis characteristic of Pdr5. A double E244G. Q951G mutant is considerably more drug sensitive than either of the single mutations. Surprisingly, then, the deviant and canonical Q-loop residues are functionally overlapping and equivalent in a strikingly asymmetric ABC transporter. C1 [Ananthaswamy, Neeti; Dine, Elliot; Nelson, Emily; Golin, John] Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA. [Rutledge, Robert; Ambudkar, Suresh V.; Xia, Di] NCI, Cell Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. [Sauna, Zuben E.] US FDA, Bethesda, MD 20892 USA. RP Golin, J (reprint author), Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA. EM golin@cua.edu FU NIH [GM07721]; NIH, National Cancer Institute, Center for Cancer Research; FDA FX This work was supported by NIH Grant GM07721 to J.G., the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (R.R., D.X., S.V.A.), and the FDA (Z.E.S.) NR 27 TC 19 Z9 19 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 1 PY 2010 VL 49 IS 21 BP 4440 EP 4449 DI 10.1021/bi100394j PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 599KX UT WOS:000277912100004 PM 20426485 ER PT J AU Miesegaes, G Lute, S Brorson, K AF Miesegaes, George Lute, Scott Brorson, Kurt TI Analysis of Viral Clearance Unit Operations for Monoclonal Antibodies SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE viral clearance; therapeutic monoclonal antibody; downstream processing ID ANION-EXCHANGE CHROMATOGRAPHY; VIRUS REMOVAL; CELLS; PARTICLES; SEQUENCES; CULTURE; MEDIA AB Demonstration of viral clearance is a critical step in assuring the safety of biotechnology products. We generated a viral clearance database that contains product information, unit operation process parameters, and viral clearance data from monoclonal antibody and antibody-related regulatory submissions to FDA. Here we present a broad overview of the database and resulting analyses. We report that the diversity of model viruses tested expands as products transition to late-phase. We also present averages and ranges of viral clearance results by Protein A and ion exchange chromatography steps, low pH chemical inactivation, and virus filtration, focusing on retro- and parvo-viruses. For most unit operations, an average log reduction value (LRV, a measure of clearance power) for retrovirus of >4 log(10) were measured. Cases where clearance data fell outside of the anticipated range (i.e., outliers) were rationally explained. Lastly, a historical analysis did not find evidence of any improvement trend in viral clearance over time. The data collectively suggest that many unit operations in general can reliably clear viruses. Biotechnol. Bioeng. 2010;106: 238-246. Published 2010 Wiley Periodicals, Inc. C1 [Miesegaes, George; Lute, Scott; Brorson, Kurt] US FDA, Off Biotechnol Prod, CDER, Silver Spring, MD 20903 USA. RP Miesegaes, G (reprint author), US FDA, Off Biotechnol Prod, CDER, 10903 New Hampshire Ave, Silver Spring, MD 20903 USA. EM george.miesegaes@fda.hhs.gov FU COCK/FDA; Eli Lilly Co. FX We thank Ruth Cordoda, Keith Webber, and Patrick Swann (COCK/FDA) as well as Mark Bailey and Adith Venkiteshwaran (Bioprocess R&D, Eli Lilly & Co.) for careful review of this manuscript. This work was funded in part by a cooperative research and development agreement (CICADA) between COCK/FDA and Eli Lilly & Co. NR 27 TC 31 Z9 32 U1 3 U2 22 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD JUN 1 PY 2010 VL 106 IS 2 BP 238 EP 246 DI 10.1002/bit.22662 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 594CI UT WOS:000277510400007 PM 20073086 ER PT J AU Altekruse, SF Huang, L Cucinelli, JE McNeel, TS Wells, KM Oliver, MN AF Altekruse, Sean F. Huang, Lan Cucinelli, James E. McNeel, Timothy S. Wells, Kristen M. Oliver, M. Norman TI Spatial Patterns of Localized-Stage Prostate Cancer Incidence Among White and Black Men in the Southeastern United States, 1999-2001 SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SOCIOECONOMIC-STATUS; DIAGNOSIS; RACE; MORTALITY; ILLINOIS; IMPACT AB Background: In the United States, prostate cancer incidence is higher among black than among white males, with a higher proportion of blacks diagnosed with advanced-stage cancer. Methods: Prostate cancer incidence (1999-2001) and census tract data were obtained for 66,468 cases in four states that account for 20% of U.S. blacks: Georgia, Florida, Alabama, and Tennessee. Spatial clusters of localized-stage prostate cancer incidence were detected by spatial scan. Clusters were examined by relative risk, population density, and socioeconomic and racial attributes. Results: Overall prostate cancer incidence rates were higher in black than in white men, and a lower proportion of black cases were diagnosed with localized-stage cancer. Strong associations were seen between urban residence and high relative risk of localized-stage cancer. The highest relative risks generally occurred in clusters with a lower percent black population than the national average. Conversely, of eight nonurban clusters with significantly elevated relative risk of localized-disease, seven had a higher proportion of blacks than the national average. Furthermore, positive correlations between percent black population and relative risk of localized-stage cancer were seen in Alabama and Georgia. Conclusion: Association between urban residence and high relative risk of localized-stage disease (favorable prognosis) persisted after spatial clusters were stratified by percent black population. Unexpectedly, seven of eight nonurban clusters with high relative risk of localized-stage disease had a higher percentage of blacks than the U. S. population. Impact: Although evidence of racial disparity in prostate cancer was found, there were some encouraging findings. Studies of community-level factors that might contribute to these findings are recommended. Cancer Epidemiol Biomarkers Prev; 19( 6); 1460-7. (C) 2010 AACR. C1 [Altekruse, Sean F.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. [Huang, Lan] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Cucinelli, James E.; McNeel, Timothy S.] Informat Management Serv Inc, Silver Spring, MD USA. [Wells, Kristen M.] Univ Virginia, Sch Med, Dept Family Med, Charlottesville, VA 22908 USA. [Oliver, M. Norman] Univ Virginia, Sch Med, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA. RP Altekruse, SF (reprint author), NCI, Div Canc Control & Populat Sci, 6116 Execut Blvd,Room 5003, Rockville, MD 20852 USA. EM altekrusesf@mail.nih.gov FU NCI NIH HHS [HHSN261200900022C]; PHS HHS [HHSN261200900022C] NR 22 TC 11 Z9 11 U1 2 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2010 VL 19 IS 6 BP 1460 EP 1467 DI 10.1158/1055-9965.EPI-09-1310 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607MD UT WOS:000278507300008 PM 20501756 ER PT J AU Filkowski, JN Ilnytskyy, Y Tamminga, J Koturbash, I Golubov, A Bagnyukova, T Pogribny, IP Kovalchuk, O AF Filkowski, Jody N. Ilnytskyy, Yaroslav Tamminga, Jan Koturbash, Igor Golubov, Andrey Bagnyukova, Tetyana Pogribny, Igor P. Kovalchuk, Olga TI Hypomethylation and genome instability in the germline of exposed parents and their progeny is associated with altered miRNA expression SO CARCINOGENESIS LA English DT Article ID DNA-DAMAGE; IN-VIVO; IONIZING-RADIATION; GENE-EXPRESSION; METHYLATION; MICRORNAS; LSH; MICE; MOUSE; ELEMENTS AB Recent studies suggest that transgenerational genome instability may be epigenetic in nature and mediated via altered DNA methylation and microRNAome. Here, we investigated the nature and mechanisms underlying the disruption of DNA methylation and microRNA expression status in the germline and progeny of exposed parents. We have found that paternal irradiation leads to upregulation of the miR-29 family in the exposed male germline, which causes decreased expression of de novo methyltransferase, DNA methyltransferase 3a, and profound hypomethylation of long interspersed nuclear elements 1 (LINE1) and short interspersed nuclear elements B2 (SINE B2). Epigenetic changes in the male germline further resulted in deleterious effects in the somatic thymus tissue from the progeny of exposed animals, including hypomethylation of LINE1 and SINE B2. Hypomethylation of LINE1 and SINE B2 in the thymus tissue from the progeny was associated with a significant decrease in the levels of lymphoid-specific helicase (LSH) that is crucial for the maintenance of methylation and silencing of repetitive elements. Furthermore, we noted a significant upregulation of miR-468 that targets LSH and leads to its decreased expression in thymus in the progeny of exposed parents. We suggest that miR-468-mediated suppression of LSH leads to aberrant methylation of LINE1 and SINE B2. In summary, altered microRNAome and hypomethylation of retroelements constitute deleterious effects that may significantly influence genome stability of the parental germline and consequently cause genome instability in the progeny. C1 [Filkowski, Jody N.; Ilnytskyy, Yaroslav; Tamminga, Jan; Koturbash, Igor; Golubov, Andrey; Kovalchuk, Olga] Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. [Bagnyukova, Tetyana; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Kovalchuk, O (reprint author), Univ Lethbridge, Dept Biol Sci, 4401 Univ Lethbridge, Lethbridge, AB T1K 3M4, Canada. EM olga.kovalchuk@uleth.ca FU Alberta Cancer Board [22180]; Alberta Heritage Foundation for Medical Research; National Science and Engineering Research Council Graduate Scholarships FX Alberta Cancer Board operating grant (22180) to O.K. J.F. was a recipient of the Alberta Heritage Foundation for Medical Research and the National Science and Engineering Research Council Graduate Scholarships. NR 58 TC 36 Z9 40 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2010 VL 31 IS 6 BP 1110 EP 1115 DI 10.1093/carcin/bgp300 PG 6 WC Oncology SC Oncology GA 603OS UT WOS:000278218500021 PM 19959559 ER PT J AU Ngundi, MM Meade, BD Lin, TL Tang, WJ Burns, DL AF Ngundi, Miriam M. Meade, Bruce D. Lin, Tsai-Lien Tang, Wei-Jen Burns, Drusilla L. TI Comparison of Three Anthrax Toxin Neutralization Assays SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID PROTECTIVE ANTIGEN; BACILLUS-ANTHRACIS; MONOCLONAL-ANTIBODY; INHALATION ANTHRAX; INTRANASAL CHALLENGE; RHESUS MACAQUES; LETHAL FACTOR; EDEMA FACTOR; GUINEA-PIGS; VACCINE AB Different types of anthrax toxin neutralization assays have been utilized to measure the antibody levels elicited by anthrax vaccines in both nonclinical and clinical studies. In the present study, we sought to determine whether three commonly used toxin neutralization assays-J774A.1 cell-, RAW 264.7 cell-, and CHO cell-based assays-yield comparable estimates of neutralization activities for sera obtained after vaccination with anthrax vaccines composed of recombinant protective antigen (rPA). In order to compare the assays, sera were assayed alongside a common reference serum sample and the neutralization titers were expressed relative to the titer for the reference sample in each assay. Analysis of sera from rabbits immunized with multiple doses of the rPA vaccine showed that for later bleeds, the quantitative agreement between the assays was good; however, for early bleeds, some heterogeneity in relative neutralization estimates was observed. Analysis of serum samples from rabbits, nonhuman primates, and humans immunized with the rPA vaccine showed that the relative neutralization estimates obtained in the different assays agreed to various extents, depending on the species of origin of the sera examined. We identified differences in the magnitudes of the Fc receptor-mediated neutralization associated with the J774A.1 cell-and RAW 264.7 cell-based assays, which may account for some of the species dependence of the assays. The differences in the relative neutralization estimates among the assays were relatively small and were always less than 2.5-fold. However, because toxin neutralization assays will likely be used to establish the efficacies of new anthrax vaccines, our findings should be considered when assay outputs are interpreted. C1 [Burns, Drusilla L.] US FDA, CBER, HFM 434, Bethesda, MD 20892 USA. [Meade, Bruce D.] Meade Biol, Hillsborough, NC 27278 USA. [Tang, Wei-Jen] Univ Chicago, Chicago, IL 60637 USA. RP Burns, DL (reprint author), US FDA, CBER, HFM 434, Bldg 29,Room 130,8800 Rockville Pike, Bethesda, MD 20892 USA. EM drusilla.burns@fda.hhs.gov OI Tang, Wei-Jen/0000-0002-8267-8995 FU National Institute of Allergy and Infectious Diseases, NIH [N01-AI-25461, N01-AI-30061]; Food and Drug Administration FX This work was supported in part by an interagency agreement between the National Institute of Allergy and Infectious Diseases, NIH, and the Food and Drug Administration.; The following reagents were obtained from the NIH Biodefense and Emerging Infections Research Resources Repository, NIAID, NIH: anthrax LF, recombinant from Bacillus anthracis, NR-142; anthrax PA, recombinant from Bacillus anthracis, NR-140; J774A.1 monocyte/macrophage (mouse) Working Cell Bank sample, NR-28; and rabbit anti-PA reference serum sample pool, NR-3839. Human serum samples were obtained through NIH/NIAID, DMID study 01-003 under contract number N01-AI-25461. NHP serum samples were obtained from Battelle Memorial Institute's Biomedical Research Center (with cooperation from PharmAthene, Inc.), where they were generated under NIH/NIAID contract number N01-AI-30061. NR 36 TC 8 Z9 8 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 JUN PY 2010 VL 17 IS 6 BP 895 EP 903 DI 10.1128/CVI.00513-09 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 603MG UT WOS:000278212100002 PM 20375243 ER PT J AU Baker-Smith, CM Benjamin, DK Califf, RM Murphy, MD Li, JS Smith, PB AF Baker-Smith, C. M. Benjamin, D. K., Jr. Califf, R. M. Murphy, M. D. Li, J. S. Smith, P. B. TI Cough in Pediatric Patients Receiving Angiotensin-Converting Enzyme Inhibitor Therapy or Angiotensin Receptor Blocker Therapy in Randomized Controlled Trials SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID HYPERTENSION AB The incidence of cough in children receiving antihypertension therapy with angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs) is unknown. We analyzed patient-level data from eight randomized trials for the treatment of pediatric hypertension, six of them involving ACEis and two involving ARBs. The incidence of cough in children receiving ACEis (reported cough, 3.2%) was similar to that in children receiving ARBs (reported cough, 1.8%) (P = 0.34). Reports of cough were lower in children than in adults. C1 [Baker-Smith, C. M.; Benjamin, D. K., Jr.; Califf, R. M.; Li, J. S.; Smith, P. B.] Duke Univ, Dept Pediat, Durham, NC 27706 USA. [Baker-Smith, C. M.; Benjamin, D. K., Jr.; Califf, R. M.; Li, J. S.; Smith, P. B.] Duke Univ, Dept Med, Durham, NC 27706 USA. [Baker-Smith, C. M.; Benjamin, D. K., Jr.; Califf, R. M.; Li, J. S.; Smith, P. B.] Duke Univ, Duke Clin Res Inst, Durham, NC 27706 USA. [Benjamin, D. K., Jr.; Murphy, M. D.; Li, J. S.; Smith, P. B.] US FDA, Rockville, MD 20857 USA. RP Smith, PB (reprint author), Duke Univ, Dept Pediat, Durham, NC 27706 USA. EM brian.smith@duke.edu RI Smith, Phillip/I-5565-2014 FU National Institute of Child Health and Human Development (NICHD) [1U10-HD45962-05, 1UL1RR024128-01, 1K23HD060040-01, 1K24HD058735-01]; Pfizer; Astellas; AstraZeneca; Johnson & Johnson Pharmaceutical Research Development; MedImmune; Medicines Company; Sanofi-Aventis; Bristol-Myers-Squibb; Genzyme; PTC Biotherapeutics; Astellas Pharma US; Cadence Pharmaceuticals Inc; Cubist Pharmaceuticals; Merck; Novartis Pharmaceuticals; Schering Plough; Johnson & Johnson Pharmaceuticals; Lilly; Scios Pharma FX We are grateful to Norman Stockbridge of the Division of Cardiovascular and Renal Products, Center for Drug Evaluation and Research, US Food and Drug Administration (FDA), for providing access to study data. D.K.B. and J.S.L. received support from National Institute of Child Health and Human Development (NICHD) 1U10-HD45962-05 and the FDA. D.K.B., J.S.L., P.B.S., and R.M.C. received support from NICHD 1UL1RR024128-01.P.B.S. received support from NICHD 1K23HD060040-01, and D.K.B. received support from 1K24HD058735-01.; D.K.B. reports receiving research support from Pfizer, Astellas, AstraZeneca, Johnson & Johnson Pharmaceutical Research & Development, MedImmune, and the Medicines Company and also reports consulting honoraria from Biosynexus, Pfizer, and GlaxoSmithKline.J.S.L. reports receiving research support from Sanofi-Aventis, Bristol-Myers-Squibb, Genzyme, PTC Biotherapeutics, and Pfizer. P.B.S. reports receiving research support from Astellas Pharma US, Cadence Pharmaceuticals Inc, Cubist Pharmaceuticals, and Pfizer. R.M.C. reports the following: receiving research support from Merck, Novartis Pharmaceuticals, Schering Plough, Johnson & Johnson Pharmaceuticals, Lilly, and Scios Pharma; receiving honoraria for educational activities from Heart.org, Kowa Research Institute, and Novartis Pharmaceuticals; and receiving consulting honoraria from Acumed, Amylin, Aterovax, Avalere Health, Bayer, Biogen, Boehringer Ingelheim, Boston Scientific, Brandeis University, NR 10 TC 10 Z9 10 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUN PY 2010 VL 87 IS 6 BP 668 EP 671 DI 10.1038/clpt.2009.231 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 604FX UT WOS:000278264000019 PM 20130570 ER PT J AU Alayash, AI AF Alayash, Abdu I. TI Setbacks in Blood Substitutes Research and Development: A Biochemical Perspective SO CLINICS IN LABORATORY MEDICINE LA English DT Article DE Blood substitutes; Hemoglobin toxicity; Oxygen transport ID ENDOTHELIAL-CELLS; NITRIC-OXIDE; HEMOGLOBIN; SCAVENGER; HIF-1-ALPHA; OXIDATION AB Recent setbacks in using Hb-based technology to develop oxygen carriers or blood substitutes may spur new and fundamentally different approaches for the development of a new generation of hemoglobin-based oxygen carriers (HBOCs). This article briefly details some underlying mechanisms that may have been responsible for the adverse-event profile associated with HBOCs, with a focus on the contribution of the author's laboratory toward identifying some of these biochemical pathways and some ways and means to control them. It is hoped that this will aid in the development of a safe and effective second generation of HBOCs. C1 NIH, Div Hematol, Lab Biochem & Vasc Biol, Bethesda, MD 20892 USA. [Alayash, Abdu I.] NIH, CBER, US FDA, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), NIH, Div Hematol, Lab Biochem & Vasc Biol, Bldg 29,Room 112,8800 Rickville Pike, Bethesda, MD 20892 USA. EM abdu.alayash@fda.hhs.gov NR 23 TC 15 Z9 16 U1 1 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD JUN PY 2010 VL 30 IS 2 BP 381 EP + DI 10.1016/j.cll.2010.02.009 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 617BM UT WOS:000279255800003 PM 20513557 ER EF