FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Gelderman, MP Vostal, JG AF Gelderman, Monique P. Vostal, Jaroslav G. TI Current and Future Cellular Transfusion Products SO CLINICS IN LABORATORY MEDICINE LA English DT Article DE Red cells; Platelets; Transfusion; Novel transfusion products ID RED-BLOOD-CELLS; EMBRYONIC STEM-CELLS; RANDOMIZED CONTROLLED-TRIAL; PATHOGEN INACTIVATION; BACTERIAL-CONTAMINATION; THERAPEUTIC-EFFICACY; ANAEROBIC STORAGE; CARDIAC-SURGERY; IN-VITRO; PLATELETS AB Novel red blood cell and platelet transfusion products may be synthetic or may result from modifications to approved collection, processing, and storage procedures for existing cellular products. They must be reviewed and evaluated by the Food and Drug Administration before being legally marketed in the United States to ensure they are safe, pure, and potent. This article reviews the literature and discusses the current and future state of cellular transfusion products. C1 [Gelderman, Monique P.; Vostal, Jaroslav G.] US FDA, Lab Cellular Hematol, Div Hematol, Off Blood Res & Review,Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Gelderman, MP (reprint author), US FDA, Lab Cellular Hematol, Div Hematol, Off Blood Res & Review,Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 335, Rockville, MD 20852 USA. EM monique.gelderman-fuhrmann@fda.hhs.gov NR 53 TC 2 Z9 2 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 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD JUN PY 2010 VL 30 IS 2 BP 443 EP + DI 10.1016/j.cll.2010.02.005 PG 11 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 617BM UT WOS:000279255800008 PM 20513562 ER PT J AU Butler, PW Smith, SM Linderman, JD Brychta, RJ Alberobello, AT Dubaz, OM Luzon, JA Skarulis, MC Cochran, CS Wesley, RA Pucino, F Celi, FS AF Butler, P. W. Smith, S. M. Linderman, J. D. Brychta, R. J. Alberobello, A. T. Dubaz, O. M. Luzon, J. A. Skarulis, M. C. Cochran, C. S. Wesley, R. A. Pucino, F. Celi, F. S. TI Pharmacogenomic Response to Thyrotropin-Releasing Hormone Stimulation in Healthy Volunteers: The Influence of a Common Type 2 Deiodinase Gene Polymorphism on Serum T3 SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Butler, P. W.; Smith, S. M.; Linderman, J. D.; Brychta, R. J.; Alberobello, A. T.; Dubaz, O. M.; Luzon, J. A.; Skarulis, M. C.; Cochran, C. S.; Wesley, R. A.; Pucino, F.; Celi, F. S.] NIH, Bethesda, MD 20892 USA. [Pucino, F.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S22 EP S22 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400023 ER PT J AU Sood, M Benaviv-Meskin, D Heron-Chaturvedi, DC Lowy, N Narayan, NR Lesser, ML Escalon, LB Martocci, AS Levitt, HB Kleinberg, DL AF Sood, M. Benaviv-Meskin, D. Heron-Chaturvedi, D. C. Lowy, N. Narayan, N. R. Lesser, M. L. Escalon, L. B. Martocci, A. S. Levitt, H. B. Kleinberg, D. L. TI Development of an Acromegaly Registry To Follow Treatment. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Sood, M.; Benaviv-Meskin, D.; Heron-Chaturvedi, D. C.; Narayan, N. R.; Levitt, H. B.; Kleinberg, D. L.] NYU, Sch Med, New York, NY USA. [Lowy, N.] US FDA, Silver Spring, MD USA. [Lesser, M. L.] Feinstein Inst Med Res, Manhasset, NY USA. [Escalon, L. B.; Martocci, A. S.] NYU, Inst Canc, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989403256 ER PT J AU Tu, EY Joslin, CE Shoff, ME Lee, JA Fuerst, PE AF Tu, E. Y. Joslin, C. E. Shoff, M. E. Lee, J. A. Fuerst, P. E. TI Sequential corneal infection with two genotypically distinct Acanthamoebae associated with renewed contact lens wear SO EYE LA English DT Letter ID KERATITIS C1 [Tu, E. Y.; Joslin, C. E.; Lee, J. A.] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60607 USA. [Joslin, C. E.] Univ Illinois, Sch Publ Hlth, Div Epidemiol & Biostat, Chicago, IL USA. [Shoff, M. E.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Fuerst, P. E.] Ohio State Univ, Dept Ecol Evolut & Organismal Biol, Columbus, OH 43210 USA. RP Tu, EY (reprint author), Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60607 USA. EM etu@uic.edu FU PHS HHS [15689, 09073] NR 5 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X J9 EYE JI Eye PD JUN PY 2010 VL 24 IS 6 BP 1119 EP 1121 DI 10.1038/eye.2009.288 PG 4 WC Ophthalmology SC Ophthalmology GA 608YX UT WOS:000278623000044 PM 19942941 ER PT J AU Cokic, V Han, J Beleslin-Cokic, B Mirkovic, K Damjanovic, S Gotic, M Raj, P Noguchi, C Schechter, A AF Cokic, V. Han, J. Beleslin-Cokic, B. Mirkovic, K. Damjanovic, S. Gotic, M. Raj, P. Noguchi, C. Schechter, A. TI THERAPY RELATED GENE EXPRESSION OF HEMATOPOIETIC PROGENITOR CELLS IN CHRONIC MYELOPROLIFERATIVE NEOPLASMS SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the European-Hematology-Association CY JUN 10-13, 2010 CL Barcelona, SPAIN SP European Hematol Assoc C1 [Cokic, V.] Inst Med Res, Belgrade, Serbia. [Han, J.; Raj, P.] FDA, Ctr Biol Evaluation & Res, Bethesda, MD USA. [Beleslin-Cokic, B.; Mirkovic, K.; Damjanovic, S.] Inst Endocrinol, Belgrade, Serbia. [Gotic, M.] Univ Clin Ctr, Inst Hematol, Belgrade, Serbia. [Noguchi, C.; Schechter, A.] NID DK, Natl Inst Hlth, Mol Med Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2010 VL 95 SU 2 MA 0973 BP 403 EP 403 PG 1 WC Hematology SC Hematology GA 614IY UT WOS:000279051301294 ER PT J AU Iyer, JK Khurana, T Langer, M West, CM Ballard, JD Metcalf, JP Merkel, TJ Coggeshall, KM AF Iyer, Janaki K. Khurana, Taruna Langer, Marybeth West, Christopher M. Ballard, Jimmy D. Metcalf, Jordan P. Merkel, Tod J. Coggeshall, K. Mark TI Inflammatory Cytokine Response to Bacillus anthracis Peptidoglycan Requires Phagocytosis and Lysosomal Trafficking SO INFECTION AND IMMUNITY LA English DT Article ID DISSEMINATED INTRAVASCULAR COAGULATION; TOLL-LIKE RECEPTORS; STAPHYLOCOCCUS-AUREUS; LIPOTEICHOIC ACID; INHALATIONAL ANTHRAX; CELL-WALL; PLATELET-AGGREGATION; RECOGNITION PROTEIN; MURAMYL DIPEPTIDE; WHOLE-BLOOD AB During advanced stages of inhalation anthrax, Bacillus anthracis accumulates at high levels in the bloodstream of the infected host. This bacteremia leads to sepsis during late-stage anthrax; however, the mechanisms through which B. anthracis-derived factors contribute to the pathology of infected hosts are poorly defined. Peptidoglycan, a major component of the cell wall of Gram-positive bacteria, can provoke symptoms of sepsis in animal models. We have previously shown that peptidoglycan of B. anthracis can induce the production of proinflammatory cytokines by cells in human blood. Here, we show that biologically active peptidoglycan is shed from an active culture of encapsulated B. anthracis strain Ames in blood. Peptidoglycan is able to bind to surfaces of responding cells, and internalization of peptidoglycan is required for the production of inflammatory cytokines. We also show that the peptidoglycan traffics to lysosomes, and lysosomal function is required for cytokine production. We conclude that peptidoglycan of B. anthracis is initially bound by an unknown extracellular receptor, is phagocytosed, and traffics to lysosomes, where it is degraded to a product recognized by an intracellular receptor. Binding of the peptidoglycan product to the intracellular receptor causes a proinflammatory response. These findings provide new insight into the mechanism by which B. anthracis triggers sepsis during a critical stage of anthrax disease. C1 [Iyer, Janaki K.; Coggeshall, K. Mark] Oklahoma Med Res Fdn, Immunobiol & Canc Program, Oklahoma City, OK 73104 USA. [Khurana, Taruna; Merkel, Tod J.] US FDA, Lab Resp Pathogens, Div Bacterial Prod, CBER, Bethesda, MD 20892 USA. [Langer, Marybeth; Metcalf, Jordan P.] Univ Oklahoma, Hlth Sci Ctr, Div Pulm & Crit Care, Dept Med, Oklahoma City, OK 73104 USA. [West, Christopher M.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma Ctr Med Glycobiol, Dept Biochem & Mol Biol, Oklahoma City, OK 73104 USA. [Ballard, Jimmy D.] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA. RP Coggeshall, KM (reprint author), Oklahoma Med Res Fdn, Immunobiol & Canc Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM mark-coggeshall@omrf.org FU NIH [2U19 AI062629] FX This work was supported by NIH grant 2U19 AI062629. NR 53 TC 15 Z9 15 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 2010 VL 78 IS 6 BP 2418 EP 2428 DI 10.1128/IAI.00170-10 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 598ML UT WOS:000277841300007 PM 20308305 ER PT J AU Tryndyak, VP Beland, FA Pogribny, IP AF Tryndyak, Volodymyr P. Beland, Frederick A. Pogribny, Igor P. TI E-cadherin transcriptional down-regulation by epigenetic and microRNA-200 family alterations is related to mesenchymal and drug-resistant phenotypes in human breast cancer cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE breast cancer; E-cadherin; promoter methylation; histone; acetylation; microRNA miR-200 ID MIR-200 FAMILY; LUNG-CANCER; DNA METHYLATION; REPRESSORS ZEB1; PROMOTES EMT; TRANSITION; SIRT1; INHIBITION; LINES; EXPRESSION AB The conversion of early stage tumors into invasive malignancies with an aggressive phenotype has been associated with the irreversible loss of E-cadherin expression. The loss of E-cadherin expression in human tumors, including breast cancer, has been attributed to promoter CpG island hypermethylation and direct inhibition by transcriptional repressors. Recent evidence demonstrates that up-regulation of E-cadherin by microRNA-200b (miR-200b) and miR-200c through direct targeting of transcriptional repressors of E-cadherin, ZEB1, and ZEB2, inhibits epithelial-to-mesenchymal transition (EMT), a crucial process in the tumor progression. We demonstrate that microRNA miR-200 family-mediated transcriptional up-regulation of E-cadherin in mesenchymal MDA-MB-231 and BT-549 cells is associated directly with translational repression of ZEB1 and indirectly with increased acetylation of histone H3 at the E-cadherin promoter. The increase in histone H3 acetylation may be attributed to the disruption of repressive complexes between ZEB1 and histone deacetylases and to the inhibition of SIRT1, a class Ill histone deacetylase. These events inhibit EMT and reactivate a less aggressive epithelial phenotype in cancer cells. Additionally, disruption of ZEB1-histone deacetylase repressor complexes and down-regulation of SIRT1 histone deacetylase up-regulate proapoptotic genes in the p53 apoptotic pathway resulting in the increased sensitivity of cancer cells to the chemotherapeutic agent doxorubicin. C1 [Tryndyak, Volodymyr P.; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov NR 49 TC 123 Z9 142 U1 2 U2 22 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 1 PY 2010 VL 126 IS 11 BP 2575 EP 2583 DI 10.1002/ijc.24972 PG 9 WC Oncology SC Oncology GA 592AV UT WOS:000277347900007 PM 19839049 ER PT J AU Cartwright, EJ Prabhu, RM Zinderman, CE Schobert, WE Jensen, B Noble-Wang, J Church, K Welsh, C Kuehnert, M Burke, TL Srinivasan, A AF Cartwright, Emily J. Prabhu, Rajesh M. Zinderman, Craig E. Schobert, William E. Jensen, Bette Noble-Wang, Judith Church, Kelly Welsh, Cindi Kuehnert, Matthew Burke, Timothy L. Srinivasan, Arjun CA Food Drug Adm Tissue Safety Team TI Transmission of Elizabethkingia meningoseptica (Formerly Chryseobacterium meningosepticum) to Tissue-Allograft Recipients A Report of Two Cases SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article C1 [Cartwright, Emily J.; Jensen, Bette; Noble-Wang, Judith; Church, Kelly; Kuehnert, Matthew; Srinivasan, Arjun] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Atlanta, GA 30333 USA. [Prabhu, Rajesh M.; Welsh, Cindi] SMDC Hlth Syst, Dept Infect Dis, Duluth, MN 55805 USA. [Prabhu, Rajesh M.; Welsh, Cindi] SMDC Hlth Syst, Dept Infect Control, Duluth, MN 55805 USA. [Zinderman, Craig E.] US FDA, Off Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Cartwright, EJ (reprint author), Ctr Dis Control & Prevent, Div Healthcare Qual Promot, 1600 Clifton Rd,MS A35, Atlanta, GA 30333 USA. EM asrinivasan@cdc.gov NR 13 TC 12 Z9 12 U1 1 U2 4 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JUN PY 2010 VL 92A IS 6 BP 1501 EP 1506 DI 10.2106/JBJS.I.00502 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 603MC UT WOS:000278211700019 PM 20516326 ER PT J AU Newell, KA Asare, A Kirk, AD Gisler, TD Bourcier, K Suthanthiran, M Burlingham, WJ Marks, WH Sanz, I Lechler, RI Hernandez-Fuentes, MP Turka, LA Seyfert-Margolis, VL AF Newell, Kenneth A. Asare, Adam Kirk, Allan D. Gisler, Trang D. Bourcier, Kasia Suthanthiran, Manikkam Burlingham, William J. Marks, William H. Sanz, Ignacio Lechler, Robert I. Hernandez-Fuentes, Maria P. Turka, Laurence A. Seyfert-Margolis, Vicki L. CA Immune Tolerance Network ST507 TI Identification of a B cell signature associated with renal transplant tolerance in humans SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID DONOR LIVER-TRANSPLANTATION; GENE-EXPRESSION PROFILES; OPERATIONAL TOLERANCE; T-CELLS; ALLOGRAFT SURVIVAL; CUTTING EDGE; IMMUNOSUPPRESSION; RECIPIENTS; LYMPHOCYTES; WITHDRAWAL AB Establishing long-term allograft acceptance without the requirement for continuous immunosuppression, a condition known as allograft tolerance, is a highly desirable therapeutic goal in solid organ transplantation. Determining which recipients would benefit from withdrawal or minimization of immunosuppression would be greatly facilitated by biomarkers predictive of tolerance. In this study, we identified the largest reported cohort to our knowledge of tolerant renal transplant recipients, as defined by stable graft function and receiving no immunosuppression for more than 1 year, and compared their gene expression profiles and peripheral blood lymphocyte subsets with those of subjects with stable graft function who are receiving immunosuppressive drugs as well as healthy controls. In addition to being associated with clinical and phenotypic parameters, renal allograft tolerance was strongly associated with a B cell signature using several assays. Tolerant subjects showed increased expression of multiple B cell differentiation genes, and a set of just 3 of these genes distinguished tolerant from nontolerant recipients in a unique test set of samples. This B cell signature was associated with upregulation of CD20 mRNA in urine sediment cells and elevated numbers of peripheral blood naive and transitional B cells in tolerant participants compared with those receiving immunosuppression. These results point to a critical role for B cells in regulating alloimmunity and provide a candidate set of genes for wider-scale screening of renal transplant recipients. C1 [Newell, Kenneth A.; Kirk, Allan D.] Emory Univ, Atlanta, GA 30322 USA. [Asare, Adam; Gisler, Trang D.; Bourcier, Kasia] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Asare, Adam; Gisler, Trang D.; Bourcier, Kasia; Turka, Laurence A.; Seyfert-Margolis, Vicki L.] Immune Tolerance Network, Bethesda, MD USA. [Suthanthiran, Manikkam] Cornell Univ, Med Ctr, New York, NY 10021 USA. [Burlingham, William J.] Univ Wisconsin, Madison, WI USA. [Marks, William H.] Swedish Med Ctr, Seattle, WA USA. [Sanz, Ignacio] Univ Rochester, Rochester, NY USA. [Lechler, Robert I.; Hernandez-Fuentes, Maria P.] Kings Coll London, MRC Ctr Transplantat, London WC2R 2LS, England. [Turka, Laurence A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Turka, Laurence A.] Harvard Univ, Sch Med, Boston, MA USA. [Seyfert-Margolis, Vicki L.] US FDA, Silver Spring, MD USA. RP Newell, KA (reprint author), 101 Woodruff Circle,Suite 5105 WMB, Atlanta, GA 30322 USA. EM kanewell@emory.edu; lturka@bidmc.harvard.edu; Vicki.Seyfert-Margolis@fda.hhs.gov RI Kirk, Allan/B-6905-2012; Hernandez-Fuentes, Maria/B-5011-2010 OI Hernandez-Fuentes, Maria/0000-0002-7558-9441 FU National Institute of Allergy and Infectious Diseases; National Institute of Diabetes and Digestive and Kidney Disease; Juvenile Diabetes Research Foundation; EU [QLRT-2002-02127, ITN503ST, 512090 IP]; MRC [G0801537/ID: 88245]; Guy's & St. Thomas's Charity [080530]; Department of Health via NIHR FX This research was performed as a project of the ITN, a collaborative clinical research project headquartered at UCSF and funded by the National Institute of Allergy and Infectious Diseases, with support from the National Institute of Diabetes and Digestive and Kidney Disease and the Juvenile Diabetes Research Foundation. RI. Lechler and M.P. Hernandez-Fuentes acknowledge funding by EU FP5 (QLRT-2002-02127), ITN (ITN503ST), RISET consortium (512090 IP) of EU FP6, MRC (G0801537/ID: 88245), and Guy's & St. Thomas's Charity Grants (080530) and financial support from the Department of Health via NIHR comprehensive Biomedical Research Centre award to Guy's & St. Thomas's NHS Foundation Trust in partnership with KCL and King's College Hospital NHS Foundation Trust. K.A. Newell, A. Asare, L.A. Turka, and V.L. Seyfert-Margolis have filed a preliminary patent application based in part on these Findings. The authors are grateful to the following consortia members for their contributions to the study: Kristin Hilgert (trial management coordinator, ITN, Bethesda, Maryland, USA); Peter Sayre (clinical physician, ITN, UCSF, San Francisco, California, USA); Jeffrey B. Matthews (manuscript editing and recruitment, ITN, Vancouver, British Columbia, Canada); Pete Bianchine (medical monitor, NIAID, NIH, Bethesda, Maryland, USA); Richard Wang (biostatistician, ITN, Bethesda, Maryland, USA); David Schmeidler (programmer); Olga Livnat (programmer); and Nina Tatynina (data analyst). The views presented in this article do not necessarily reflect those of the Food and Drug Administration. ITN ST507 Study Group: L. Haynes (study coordinator, University of Wisconsin, Madison, Wisconsin, USA); A. Lewis (study coordinator, Emory University, Atlanta, Georgia, USA); J. Lieberman and C. Marks (study coordinators, Swedish Medical Center, Seattle, Washington, USA); E. Ford (study coordinator, NIH, Bethesda, Maryland, USA); Z. Gao (biostatistician, ITN, Bethesda, Maryland, USA); G. Chen (biostatistician, ITN, Bethesda, Maryland, USA); J.A. Bluestone (scientific advisor, UCSF, San Francisco, California, USA); P.A. Wallace (flow cytometry core director, University of Rochester, Rochester, New York, USA); J. Rogers (intracellular cytokine studies, University of Rochester, Rochester, New York, USA). NR 54 TC 316 Z9 334 U1 0 U2 15 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2010 VL 120 IS 6 BP 1836 EP 1847 DI 10.1172/JCI39933 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 605CH UT WOS:000278324400009 PM 20501946 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 SO JOURNAL OF FOOD PROTECTION LA English DT Article ID IDENTIFICATION SYSTEMS; CHROMOGENIC MEDIA; SURVIVAL AB Enterobacter sakazakii causes severe maladies and, in some cases, is fatal among infants. Powdered infant formula (PIF) contaminated with E. sakazakii has been documented as a potential cause of several outbreaks involving infants. This study describes the development of a method for the isolation and detection of E. sakazakii from PIP. It combines Taqman real-time PCR, Brilliance E. sakazakii and R&F chromogenic agars, and RAPID ID 32E biochemical tests. This method provides an expedient analysis within I to 2 clays depending on the amount and stress status of E. sakazakii organisms and competing microorganisms in PIF. The real-time PCR has bifunctional applications, including both screening and culture confirmation of E. sakazakii. 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. EM yi.chen@fda.hhs.gov RI Zhou, Tian/J-7175-2012 NR 17 TC 14 Z9 17 U1 0 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 JUN PY 2010 VL 73 IS 6 BP 1016 EP 1022 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 611CY UT WOS:000278789500001 PM 20537255 ER PT J AU Myers, MJ Farreli, DE Deaver, CM Mason, J Swaim, HL Yancy, HF AF Myers, Michael J. Farreli, Dorothy E. Deaver, Christine M. Mason, Jacquline Swaim, Heidi L. Yancy, Haile F. TI Detection of Rendered Meat and Bone Meals by PCR Is Dependent on Animal Species of Origin and DNA Extraction Method SO JOURNAL OF FOOD PROTECTION LA English DT Article ID FEEDSTUFFS; VALIDATION; PROTEINS; TESTS; FEED AB The capability of eight commercially available DNA extraction kits to extract bovine DNA originating in meat and bone meal from fortified feed was evaluated. Four different batches of bovine meat and bone meal (BMBM) were used for DNA extraction with the eight commercial DNA extraction kits. Within each kit, there were minimal differences in the batch-to-batch amounts of extracted DNA. There were differences between the kits in the amounts of DNA that could be extracted from the same amount of starting BMBM. These differences did not translate into differences in the amount of amplifiable DNA from BMBM-fortified dairy feed. Using a validated real-time PCR method, the kit yielding the highest amount extractable DNA was completely unable to yield a positive PCR result; one other kit was also unable to produce a positive PCR result from DNA extracted from BMBM-fortified feed. There was a complete lack of a correlation between the amount of bovine DNA isolated from BMBM by a given extraction kit compared with the relative amounts of DNA isolated from fortified animal feed as evidenced by the cycle threshold values generated using the real-time PCR method. These results demonstrate that extraction of DNA from processed animal protein is different for pure ingredients and fortified animal feeds. These results indicate that a method specifically developed using just animal-derived meat and bone meal may not yield a functional assay when used to detect animal tissues in complete animal feed. C1 [Myers, Michael J.; Farreli, Dorothy E.; Deaver, Christine M.; Mason, Jacquline; Swaim, Heidi L.; Yancy, Haile F.] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP Myers, MJ (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM michael.myers@fda.hhs.gov NR 9 TC 6 Z9 6 U1 0 U2 6 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JUN PY 2010 VL 73 IS 6 BP 1090 EP 1096 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 611CY UT WOS:000278789500011 PM 20537265 ER PT J AU Pope, TM Gagne, JJ Kesselheim, AS AF Pope, Thaddeus Mason Gagne, Joshua J. Kesselheim, Aaron S. TI Health Care Regulation in America: Complexity, Confrontation, and Compromise SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Book Review C1 [Pope, Thaddeus Mason] Widener Univ, Sch Law, Chester, PA 19013 USA. [Gagne, Joshua J.; Kesselheim, Aaron S.] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Gagne, Joshua J.] US FDA, Off Surveillance & Epidemiol, Rockville, MD 20857 USA. [Kesselheim, Aaron S.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Kesselheim, Aaron S.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Cambridge, MA 02138 USA. RP Pope, TM (reprint author), Widener Univ, Sch Law, Chester, PA 19013 USA. NR 32 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1073-1105 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD SUM PY 2010 VL 38 IS 2 BP 427 EP 432 PG 6 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 620XB UT WOS:000279534400025 ER PT J AU Volpe, DA Shaw, AB Chen, XH Zhou, L Chen, ML AF Volpe, Donna A. Shaw, Arthur B. Chen, Xiao-Hong Zhou, Liang Chen, Mei-Ling TI Effect of altered temperature storage on the in vitro cellular uptake of liposome drug products SO JOURNAL OF LIPOSOME RESEARCH LA English DT Article DE Liposomes; uptake; stress; temperature ID PHYSICAL STABILITY; DELIVERY-SYSTEMS; MACROPHAGES; DOXORUBICIN; PHARMACOKINETICS; FORMULATIONS; DAUNORUBICIN; CELLS AB The aim of this study was to evaluate whether temperature stress conditions affect the cellular uptake of liposomal doxorubicin, Doxil30 days and after hospital discharge. We used the National Death Index to identify cause of death information; in particular, those deaths that were likely caused by late rupture. We compared causes of late death and survival between EVAR and open repair using Wilcoxon log-rank and rank-sum tests. Results: Between 2001 and 2004, 13,971 patients underwent AAA repair (6119 EVAR, 7852 open repair). After a mean follow-up of 1.6 years in the EVAR cohort and 1.9 years in the open cohort, mortality rates were similar across repair type (15.4% EVAR, 15.9% open repair), with an adjusted odds ratio for death after open repair of 0.98 (95% confidence interval, 0.90-1.07). Of the 2194 documented deaths, 523 occurred before discharge or <= 30 days, and 1671 occurred >30 days and after hospital discharge. Cause of death information for the 1671 late deaths was available from the National Death Index for 1515 (91%). The 15 most common codes for causes of late death were dominated by cardiac disease (atherosclerotic heart disease, acute myocardial infarction) and pulmonary disease (lung cancer, respiratory failure). Causes of late death with specific mention of aneurysm were identified in 37 patients (2.4% of all deaths), but this event was not more common in EVAR or open repair (15 [0.3%] in the EVAR group, 22 [0.3%], in the open repair group; P = .71). Conclusions: Late deaths from aneurysm rupture after EVAR or open repair appear to be relatively infrequent and similarly distributed across procedure type. Our results emphasize that the effectiveness of EVAR is comparable to open AAA repair in preventing aneurysm-related death. (J Vase Surg 2010;51:1340-7.) C1 [Goodney, Philip P.] Dartmouth Hitchcock Med Ctr, Vasc Surg Sect, Dept Surg, Lebanon, NH 03765 USA. [Goodney, Philip P.; Fisher, Elliott S.; Finlayson, Samuel R. G.] Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH USA. [Tavris, Dale; Gross, Thomas] US FDA, Washington, DC 20204 USA. [Lucas, F. Lee] Maine Med Ctr, Ctr Outcomes Res & Effectiveness, Portland, ME 04102 USA. RP Goodney, PP (reprint author), Dartmouth Hitchcock Med Ctr, Vasc Surg Sect, Dept Surg, Lebanon, NH 03765 USA. EM philip.goodney@hitchcock.org FU NHLBI NIH HHS [K08 HL105676] NR 43 TC 15 Z9 16 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2010 VL 51 IS 6 BP 1340 EP 1347 DI 10.1016/j.jvs.2010.01.054 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 600GT UT WOS:000277974200002 PM 20385469 ER PT J AU Martinez, M Modric, S AF Martinez, M. Modric, S. TI Patient variation in veterinary medicine: part I. Influence of altered physiological states SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Review ID PASTEURELLA-HAEMOLYTICA INFECTION; SUBCLINICAL RENAL DYSFUNCTION; P450-MEDIATED DRUG-METABOLISM; SYNOVIAL-FLUID CONCENTRATIONS; PHARMACOKINETIC PARAMETERS; TISSUE CHAMBERS; LIVER-DISEASE; ACTINOBACILLUS-PLEUROPNEUMONIAE; TOLFENAMIC ACID; NEONATAL FOALS AB In veterinary medicine, the characterization of a drug's pharmacokinetic (PK) properties is generally based upon data that are derived from studies that employ small groups of young healthy animals, often of a single breed. These are also the data from which population predictions are often generated to forecast drug exposure characteristics in the target population under clinical conditions of use. In veterinary medicine, it is rare to find information on the covariates that can influence drug exposure characteristics. Therefore, it is important to recognize some of the factors that can alter the outcome of PK studies and therefore potentially alter the pharmacological response. Some of these factors are easily identified, such as breed, gender, age, and body weight. Others are less obvious, such as disease, heritable traits, and environmental factors. This manuscript provides an overview of the various stressors (such as disease, inflammation, pregnancy, and lactation) that can substantially alter drug PK. Part II of this series provides an overview of the potential impact of physiological variables such as age, weight, and heritable traits, on drug PK. Ultimately, failure to identify appropriate covariates can lead to substantial error when predicting the dose-exposure relationship within a population. C1 [Martinez, M.; Modric, S.] US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. RP Martinez, M (reprint author), US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. EM marilyn.martinez@fda.hhs.gov NR 188 TC 18 Z9 18 U1 1 U2 14 PU WILEY-BLACKWELL 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 JUN PY 2010 VL 33 IS 3 BP 213 EP 226 DI 10.1111/j.1365-2885.2009.01139.x PG 14 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 592YA UT WOS:000277416700001 PM 20557438 ER PT J AU Kaplan, S Smith, SRW Zuckerman, IH AF Kaplan, Sigal Smith, Sheila R. Weiss Zuckerman, Ilene H. TI Blood Pressure and Bone Mineral Density in Premenopausal and Postmenopausal Women SO JOURNAL OF WOMENS HEALTH LA English DT Article ID ESSENTIAL-HYPERTENSION; CALCIUM EXCRETION; CONTROLLED-TRIAL; NATIONAL-HEALTH; NHANES-III; HORMONE; HYDROCHLOROTHIAZIDE; PREVALENCE; THIAZIDE; THERAPY AB Introduction: Previous studies regarding the associations between blood pressure (BP) and bone mineral density (BMD) have shown conflicting results. However, menopausal status and pharmacotherapy may modify this relationship. The objective of this study was to explore the association between systolic BP (SBP) and diastolic BP (DBP) and BMD in pre- and postmenopausal women, and to assess the extent to which this association is mediated by menopausal status and pharmacotherapy. Methods: A cross-sectional study was conducted using a sample of 4,058 pre- and postmenopausal women aged 40 years or older (N = 991 and 3,067, respectively), who participated in NHANES III. BMD measurement of the femur neck was used as the primary outcome measure. Regression models were used to examine the association between SBP or DBP and BMD. Results: The unadjusted models for systolic and diastolic BP were positively and significantly associated with femoral BMD in premenopausal women (p = 0.0039 and p = 0.0065, respectively) as well as in postmenopausal women (p < 0.0001 for both SBP and DBP). After adjusting for covariates in the multivariate models, the association between BP and BMD in postmenopausal women no longer prevailed. In premenopausal women, the association between SBP or DBP and BMD was modified by hormone therapy (p = 0.0278 and p = 0.0025, respectively). Once the stratum-specific adjusted models by hormone therapy use were examined, the association between SBP or DBP and BMD was no longer significant. Conclusions: The study results suggest that there is no link between BP and BMD in pre- and postmenopausal C1 [Kaplan, Sigal] US FDA, Div Epidemiol, Off Surveillance & Epidemiol, CDER, Silver Spring, MD 20993 USA. [Smith, Sheila R. Weiss; Zuckerman, Ilene H.] Univ Maryland, Sch Pharm, Dept Pharmaceut Hlth Serv Res, Baltimore, MD 21201 USA. [Smith, Sheila R. Weiss] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. RP Kaplan, S (reprint author), US FDA, Div Epidemiol, Off Surveillance & Epidemiol, CDER, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM sigal.kaplan@fda.hhs.gov FU University of Maryland Women's Health Research Group FX This study was conducted as part of the doctoral dissertation of the author S. Kaplan at the University of Maryland. The study was supported by a research award granted to S. Kaplan by the University of Maryland Women's Health Research Group. No competing financial interests exist. The authors have no conflicts of interest to report. NR 35 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD JUN PY 2010 VL 19 IS 6 BP 1209 EP 1215 DI 10.1089/jwh.2009.1587 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 610YB UT WOS:000278775400020 PM 20545562 ER PT J AU Normand, SL Marinac-Dabic, D Sedrakyan, A Kaczmarek, R AF Normand, Sharon-Lise Marinac-Dabic, Danica Sedrakyan, Art Kaczmarek, Ronald TI Rethinking Analytical Strategies for Surveillance of Medical Devices The Case of Hip Arthroplasty SO MEDICAL CARE LA English DT Article; Proceedings Paper CT Symposium on Clinical and Comparative Effectiveness Research Methods II CY JUN 01-02, 2009 CL Rockville, MD SP Agcy Healthcare Res & Qual DE crossdesign synthesis; network meta-analysis; Bayesian hierarchical models; posterior distributions ID METAANALYSIS AB Background: Randomized trials that sometimes serve as the basis for device approval are small, short term, and generalizable to an increasingly smaller percentage of patients. Some of the most common and challenging devices are those used in hip replacement. Artificial hips are implanted in thousands to alleviate pain caused by noninflammatory joint disease and to restore patient mobility. During 2004 in the United States, although 68% of hospital stays for partial or total hip replacements were for those aged 65 years and older, younger patients will account for 52% by 2030. Methods: Using hierarchical modeling, we propose a framework for combining information from premarket and postmarket settings. Our key assumption is that device performance characteristics and outcomes obtained from 1 cohort are related to device characteristics and outcomes of the same or similar devices observed in other cohorts. We illustrate methods by jointly modeling Harris Hip Scores (HHSs) and revision-success data from 1851 subjects who participated in 3 pivotal randomized or observational studies of artificial hips. Results and Conclusions: Subjects participating in randomized studies had better 2-year HHS than those in observational studies ( posterior mean increase in HHS = 4.1, posterior standard deviation = 0.6). Patients implanted with ceramic-on-polyethylene hip used in 1 study had higher 2-year HHS than those implanted with a different ceramic-on-polyethylene hip in another study ( mean difference = 4.2, standard deviation = 0.6). Our approach is feasible and will advance regulatory science using a transparent and dynamic new paradigm for knowledge management throughout the total product life cycle. C1 [Normand, Sharon-Lise] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Marinac-Dabic, Danica; Sedrakyan, Art; Kaczmarek, Ronald] US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Rockville, MD 20857 USA. RP Normand, SL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM sharon@hcp.med.harvard.edu NR 18 TC 5 Z9 5 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUN PY 2010 VL 48 IS 6 SU 1 BP S58 EP S67 DI 10.1097/MLR.0b013e3181de9cfa PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 603SG UT WOS:000278227800011 PM 20473192 ER PT J AU Sedrakyan, A Marinac-Dabic, D Normand, SLT Mushlin, A Gross, T AF Sedrakyan, Art Marinac-Dabic, Danica Normand, Sharon-Lise T. Mushlin, Alvin Gross, Tom TI A Framework for Evidence Evaluation and Methodological Issues in Implantable Device Studies SO MEDICAL CARE LA English DT Article; Proceedings Paper CT Symposium on Clinical and Comparative Effectiveness Research Methods II CY JUN 01-02, 2009 CL Rockville, MD SP Agcy Healthcare Res & Qual DE comparative studies; medical devices; methodology ID RANDOMIZED CONTROLLED-TRIALS; ADVERSE EVENTS; INSTRUMENTAL VARIABLES; MEDICAL DEVICE; HEALTH-CARE; VOLUME; SURGERY; IDENTIFICATION AB Implantable medical devices (IMD) are frequently used in interventional medicine. There are a host of complex methodological issues to consider in conducting device studies. A general conceptual framework for evidence evaluation is needed to help investigators conduct comparative studies in this setting. It is known that clinical trials of implants require study design planning and creative execution that are quite different from those in pharmaceutical setting. Important study design issues such as randomization, masking and allocation concealment require unique approaches for each device. In addition, device comparative studies must cope with sources of variability different from pharmaceutical studies. These include operator learning curve effects, hospital-operator-patient interactions, and issues related to device technical characteristics. Observational studies of IMDs are particularly challenging. Selection of comparison groups, adjusting for confounding and addressing learning curve issues needs careful planning. We propose a general framework for IMD evaluation and provide an outline of the methodological issues that require further discussion. We hope this article will inspire and help to inform those interested in advancing comparative safety and effectiveness of IMDs and to plan and pursue future methodological work in this area. C1 [Sedrakyan, Art; Marinac-Dabic, Danica; Gross, Tom] US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Mushlin, Alvin] Cornell Univ, Weill Med Coll, Dept Publ Hlth, New York, NY 10021 USA. RP Sedrakyan, A (reprint author), US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, WO Bldg 66,Room 3115,10903 New Hampshire Av, Silver Spring, MD 20993 USA. EM art.sedrakyan@fda.hhs.gov NR 34 TC 25 Z9 27 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUN PY 2010 VL 48 IS 6 SU 1 BP S121 EP S128 DI 10.1097/MLR.0b013e3181d991c4 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 603SG UT WOS:000278227800019 PM 20421824 ER PT J AU Freed, M Park, S Badano, A AF Freed, Melanie Park, Subok Badano, Aldo TI A fast, angle-dependent, analytical model of CsI detector response for optimization of 3D x-ray breast imaging systems SO MEDICAL PHYSICS LA English DT Article DE cesium iodide; scintillator blur; x-ray; analytical model ID TOMOSYNTHESIS; PERFORMANCE; ALGORITHMS; RADIATION; ELECTRON; MANTIS; NOISE AB Purpose: Accurate models of detector blur are crucial for performing meaningful optimizations of three-dimensional (3D) x-ray breast imaging systems as well as for developing reconstruction algorithms that faithfully reproduce the imaged object anatomy. So far, x-ray detector blur has either been ignored or modeled as a shift-invariant symmetric function for these applications. The recent development of a Monte Carlo simulation package called MANTIS has allowed detailed modeling of these detector blur functions and demonstrated the magnitude of the anisotropy for both tomosynthesis and breast CT imaging systems. Despite the detailed results that MANTIS produces, the long simulation times required make inclusion of these results impractical in rigorous optimization and reconstruction algorithms. As a result, there is a need for detector blur models that can be rapidly generated. Methods: In this study, the authors have derived an analytical model for deterministic detector blur functions, referred to here as point response functions (PRFs), of columnar CsI phosphor screens. The analytical model is x-ray energy and incidence angle dependent and draws on results from MANTIS to indirectly include complicated interactions that are not explicitly included in the mathematical model. Once the mathematical expression is derived, values of the coefficients are determined by a two-dimensional (2D) fit to MANTIS-generated results based on a figure-of-merit (FOM) that measures the normalized differences between the MANTIS and analytical model results averaged over a region of interest. A smaller FOM indicates a better fit. This analysis was performed for a monochromatic x-ray energy of 25 keV, a CsI scintillator thickness of 150 mu m, and four incidence angles (0 degrees, 15 degrees, 30 degrees, and 45 degrees). Results: The FOMs comparing the analytical model to MANTIS for these parameters were 0.1951 +/- 0.0011, 0.1915 +/- 0.0014, 0.2266 +/- 0.0021, and 0.2416 +/- 0.0074 for 0 degrees, 15 degrees, 30 degrees, and 45 degrees, respectively. As a comparison, the same FOMs comparing MANTIS to 2D symmetric Gaussian fits to the zero-angle PRF were 0.6234 +/- 0.0020, 0.9058 +/- 0.0029, 1.491 +/- 0.012, and 2.757 +/- 0.039 for the same set of incidence angles. Therefore, the analytical model matches MANTIS results much better than a 2D symmetric Gaussian function. A comparison was also made against experimental data for a 170 mu m thick CsI screen and an x-ray energy of 25.6 keV. The corresponding FOMs were 0.3457 +/- 0.0036, 0.3281 +/- 0.0057, 0.3422 +/- 0.0023, and 0.3677 +/- 0.0041 for 0 degrees, 15 degrees, 30 degrees, and 45 degrees, respectively. In a previous study, FOMs comparing the same experimental data to MANTIS PRFs were found to be 0.2944 +/- 0.0027, 0.2387 +/- 0.0039, 0.2816 +/- 0.0025, and 0.2665 +/- 0.0032 for the same set of incidence angles. Conclusions: The two sets of derived FOMs, comparing MANTIS-generated PRFs and experimental data to the analytical model, demonstrate that the analytical model is able to reproduce experimental data with a FOM of less than two times that comparing MANTIS and experimental data. This performance is achieved in less than one millionth the computation time required to generate a comparable PRF with MANTIS. Such small computation times will allow for the inclusion of detailed detector physics in rigorous optimization and reconstruction algorithms for 3D x-ray breast imaging systems. [DOI: 10.1118/1.3397462] C1 [Freed, Melanie; Park, Subok; Badano, Aldo] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Freed, Melanie] Univ Maryland, Dept Bioengn, College Pk, MD 20742 USA. RP Freed, M (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM melanie.freed@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 FU FDA's Office of Women's Health; U.S. Department of Energy and the U.S. Food and Drug Administration FX The authors wish to thank Frank W. Samuelson and Jonathan S. Boswell for help with programming on the cluster and Kyle J. Myers, Robert J. Jennings, and Brandon D. Gallas (all from DIAM/OSEL/CDRH/FDA) for helpful discussions. The authors also acknowledge funding from the FDA's Office of Women's Health. This project was supported in part by an appointment to the Research Participation Program at the Center for Devices and Radiological Health administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 16 TC 24 Z9 24 U1 0 U2 7 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2010 VL 37 IS 6 BP 2593 EP 2605 DI 10.1118/1.3397462 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 608HC UT WOS:000278573100023 PM 20632571 ER PT J AU Li, G Liu, JH Abu-Asab, M Masabumi, S Maru, Y AF Li, Guang Liu, Juhong Abu-Asab, Mones Masabumi, Shibuya Maru, Yoshiro TI XPB Induces C1D Expression to Counteract UV-Induced Apoptosis SO MOLECULAR CANCER RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR TFIIH; RIBOSOMAL-PROTEIN S3; C-MYC EXPRESSION; XERODERMA-PIGMENTOSUM; DNA-REPAIR; EXCISION-REPAIR; COCKAYNE-SYNDROME; REPAIR/TRANSCRIPTION FACTOR; HELICASE; PROMOTER AB Although C1D has been shown to be involved in DNA double-strand break repair, how C1D expression was induced and the mechanism(s) by which C1D facilitates DNA repair in mammalian cells remain poorly understood. We and others have previously shown that expression of xeroderma pigmentosum B (XPB) protein efficiently compensated the UV irradiation-sensitive phenotype of 27-1 cells, which lack functional XPB. To further explore XPB-regulated genes that could be involved in UV-induced DNA repair, differential display analysis of mRNA levels from CHO-9, 27-1, and 27-1 complemented with wild-type XPB was done and C1D gene was identified as one of the major genes whose expression was significantly upregulated by restoring XPB function. We found that XPB is essential to induce C1D transcription after UV irradiation. The increase in C1D expression effectively compensates for the UV-induced proteolysis of C1D and thus maintains cellular C1D level to cope with DNA damage inflicted by UV irradiation. We further showed that although insufficient to rescue 27-1 cells from UV-induced apoptosis by itself, C1D facilitates XPB DNA repair through direct interaction with XPB. Our findings provided direct evidence that C1D is associated with DNA repair complex and may promote repair of UV-induced DNA damage. Mol Cancer Res; 8(6); 885-95. (C) 2010 AACR. C1 [Li, Guang] NCI, Pediat Tumor Biol & Ultra Struct Pathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Liu, Juhong] US FDA, Chem Lab, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. [Masabumi, Shibuya] Tokyo Med & Dent Univ, Dept Mol Oncol, Tokyo, Japan. [Maru, Yoshiro] Tokyo Womens Med Univ, Dept Pharmacol, Tokyo, Japan. RP Li, G (reprint author), NCI, Pediat Tumor Biol & Ultra Struct Pathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM liguan1@mail.nih.gov OI Abu-Asab, Mones/0000-0002-4047-1232 FU Intramural NIH HHS [Z99 CA999999] NR 36 TC 4 Z9 5 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD JUN PY 2010 VL 8 IS 6 BP 885 EP 895 DI 10.1158/1541-7786.MCR-09-0467 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 611TH UT WOS:000278845400008 PM 20530579 ER PT J AU Yoshida, T Zhang, YQ Rosado, LAR Chen, JJ Khan, T Moon, SY Zhang, BL AF Yoshida, Tatsushi Zhang, Yaqin Rosado, Leslie A. Rivera Chen, Junjie Khan, Tahira Moon, Sun Young Zhang, Baolin TI Blockade of Rac1 Activity Induces G(1) Cell Cycle Arrest or Apoptosis in Breast Cancer Cells through Downregulation of Cyclin D1, Survivin, and X-Linked Inhibitor of Apoptosis Protein SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID GUANOSINE TRIPHOSPHATASES REPRESENT; DRUG-INDUCED APOPTOSIS; HUMAN LYMPHOMA-CELLS; FACTOR-KAPPA-B; RHO-GTPASES; SIGNALING PATHWAYS; NIH3T3 CELLS; ACTIVATION; CDC42; EXPRESSION AB Rac1 GTPase regulates a variety of signaling pathways that are implicated in malignant phenotypes. Here, we show that selective inhibition of Rac1 activity by the pharmacologic inhibitor NSC23766 suppressed cell growth in a panel of human breast cancer cell lines, whereas it had little toxicity to normal mammary epithelial cells. NSC23766 elicits its cytotoxicity via two distinct mechanisms in a cell line-dependent manner: induction of G(1) cell cycle arrest in cell lines (MDA-MB-231, MCF7, and T47D) that express retinoblastoma (Rb) protein or apoptosis in Rb-deficient MDA-MB-468 cells. In MDA-MB-231 cells, Rac1 inhibition induced G(1) cell cycle arrest through downregulation of cyclin D1 and subsequent dephosphorylation/inactivation of Rb. By contrast, MDA-MB-468 cells underwent substantial apoptosis that was associated with loss of antiapoptotic proteins survivin and X-linked inhibitor of apoptosis protein (XIAP). Rac1 knockdown by RNAi interference confirmed the specificity of NSC23766 and requirement for Rac1 in the regulation of cyclin D1, survivin, and XIAP in breast cancer cells. Further, NF-kappa B, but not c-Jun NH2-terminal kinase or p38 pathways, mediates the survival signal from Rac1. Overall, our results indicate that Rac1 plays a central role in breast cancer cell survival through regulation of NF-kappa B-dependent gene products. Mol Cancer Ther; 9(6); 1657-68. (C)2010 AACR. C1 [Yoshida, Tatsushi; Zhang, Yaqin; Rosado, Leslie A. Rivera; Chen, Junjie; Khan, Tahira; Moon, Sun Young; Zhang, Baolin] US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Zhang, BL (reprint author), US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, 29 Lincoln Dr,Bldg 29A,Room 2A01,HFD-122, Bethesda, MD 20892 USA. EM Baolin.zhang@fda.hhs.gov RI Chen, Jun-Jie/E-1894-2012 NR 66 TC 34 Z9 35 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUN PY 2010 VL 9 IS 6 BP 1657 EP 1668 DI 10.1158/1535-7163.MCT-09-0906 PG 12 WC Oncology SC Oncology GA 608FS UT WOS:000278569200018 PM 20515940 ER PT J AU McNeil, DE Davis, C Jillapalli, D Targum, S Durmowicz, A Cote, TR AF McNeil, D. Elizabeth Davis, Carole Jillapalli, Devanand Targum, Shari Durmowicz, Anthony Cote, Timothy R. TI DUCHENNE MUSCULAR DYSTROPHY: DRUG DEVELOPMENT AND REGULATORY CONSIDERATIONS SO MUSCLE & NERVE LA English DT Article DE Duchenne muscular dystrophy; Food and Drug Administration; clinical trial design; corticosteroids; gene modification therapies ID FRIEDREICHS-ATAXIA; SKELETAL-MUSCLE; NONSENSE MUTATIONS; MDX MICE; EXPRESSION; CARDIOMYOPATHY; IDEBENONE; PATIENT; MODEL; FLOW AB Duchenne muscular dystrophy (DMD) is one of the most commonly recognized dystrophinopathies. There are no approved therapeutic options available for this disease but recent discoveries have led to hope that effective therapies might be forthcoming. With funding from patient advocacy groups, private investors, and governmental bodies such as the Food and Drug Administration Office of Orphan Product Development (FDA/OOPD), gene modification and other molecular therapies are being actively investigated. However, since DMD patients are few in number and disease manifestations vary considerably in early and late stages of disease, obtaining the data needed for full evaluation of putative therapies may prove challenging. Should ambulation remain the focus of Phase 2/3 studies or should consideration be given to the primary causes of late-stage morbidity and mortality, e.g., cardiac and respiratory dysfunction related to reduced or absent dystrophin production? It seems reasonable to argue that clinical trials planned for DMD should consider the entire population. Muscle Nerve 41: 740-745, 2010 C1 [McNeil, D. Elizabeth; Cote, Timothy R.] US FDA, OOPD, US Dept HHS, Rockville, MD 20857 USA. [Davis, Carole; Jillapalli, Devanand; Targum, Shari; Durmowicz, Anthony] US FDA, OND, US Dept HHS, Rockville, MD 20857 USA. RP McNeil, DE (reprint author), US FDA, OOPD, US Dept HHS, 5600 Fishers Lane HF-35, Rockville, MD 20857 USA. EM dawn.mcneil@fda.hhs.gov NR 25 TC 8 Z9 8 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD JUN PY 2010 VL 41 IS 6 BP 740 EP 745 DI 10.1002/mus.21623 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 604NI UT WOS:000278285300002 PM 20373504 ER PT J AU Prabhu, BM Ali, SF Murdock, RC Hussain, SM Srivatsan, M AF Prabhu, Badanavalu M. Ali, Syed F. Murdock, Richard C. Hussain, Saber M. Srivatsan, Malathi TI Copper nanoparticles exert size and concentration dependent toxicity on somatosensory neurons of rat SO NANOTOXICOLOGY LA English DT Article DE Copper nanoparticles; cytotoxicity; cell death; DRG neurons; histochemistry; neurotoxicity ID OXIDATIVE STRESS; IN-VITRO; METAL-IONS; CELLS; LIVER; HOMEOSTASIS; PARTICLES; CADMIUM; MITOCHONDRIA; GLUTATHIONE AB Metal nanoparticles, due to their unique properties and important applications in optical, magnetic, thermal, electrical, sensor devices and cosmetics, are beginning to be widely manufactured and used. This new and rapidly growing field of technology warrants a thorough examination of the material's bio-compatibility and safety. Ultra-small particles may adversely affect living cells and organisms since they can easily penetrate the body through skin contact, inhalation and ingestion. Retrograde transport of copper nanoparticles from nerve endings on the skin can reach the somatosensory neurons in dorsal root ganglion (DRG). Since copper nanoparticles have industrial and healthcare applications, we determined the concentration and size-dependant effects of their exposure on survival of DRG neurons of rat in cell culture. The neurons were exposed to copper nanoparticles of increasing concentrations (10-100 mu M) and sizes (40, 60 and 80 nm) for 24 h. Light microscopy, histochemical staining for copper, lactate dehydrogenase (LDH) assay for cell death, and MTS [3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide] assay for cell viability were performed to measure the resultant toxicity and cell survival. DRG neurons exposed to copper nanoparticles displayed vacuoles and detachment of some neurons from the substratum. Neurons also exhibited disrupted neurite network. LDH and MTS assays revealed that exposure to copper nanoparticles had significant toxic effect with all the sizes tested when compared to unexposed control cultures. Further analysis of the results showed that copper nanoparticles of smaller size and higher concentration exerted the maximum toxic effects. Rubeanic acid staining showed intracellular deposition of copper. These results demonstrate that copper nanoparticles are toxic in a size-and concentration-dependent manner to DRG neurons. C1 [Prabhu, Badanavalu M.; Srivatsan, Malathi] Arkansas State Univ, Dept Biol Sci, Jonesboro, AR USA. [Ali, Syed F.] Natl Ctr Toxicol Res FDA, Neurochem Lab, Div Neurotoxicol, Jefferson, AR USA. [Murdock, Richard C.; Hussain, Saber M.] USAF, Human Effectiveness Directorate, Res Lab, Dayton, OH USA. RP Srivatsan, M (reprint author), Arkansas State Univ, Dept Biol Sci, State Univ, AR 72467 USA. EM msrivatsan@astate.edu FU NIH/NIDA [1R15 DA19971]; NIH/NCRR, IDeA Networks of Biomedical Research Excellence (INBRE) [P20 RR-16460]; Arkansas Bioscience Institute FX For this study we used items of equipment supported by NIH/NIDA grant # 1R15 DA19971; by NIH/NCRR grant # P20 RR-16460 from the IDeA Networks of Biomedical Research Excellence (INBRE) Program; and by Arkansas Bioscience Institute to M. Srivatsan. We thank Jonathan Treece and Justin Yancey for their help with culture set-up. NR 43 TC 55 Z9 58 U1 0 U2 21 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1743-5390 J9 NANOTOXICOLOGY JI Nanotoxicology PD JUN PY 2010 VL 4 IS 2 BP 150 EP 160 DI 10.3109/17435390903337693 PG 11 WC Nanoscience & Nanotechnology; Toxicology SC Science & Technology - Other Topics; Toxicology GA 672AE UT WOS:000283554600002 PM 20543894 ER PT J AU Goodsaid, FM Amur, S Aubrecht, J Burczynski, ME Carl, K Catalano, J Charlab, R Close, S Cornu-Artis, C Essioux, L Fornace, AJ Hinman, L Hong, HX Hunt, I Jacobson-Kram, D Jawaid, A Laurie, D Lesko, L Li, HH Lindpaintner, K Mayne, J Morrow, P Papaluca-Amati, M Robison, TW Roth, J Schuppe-Koistinen, I Shi, LM Spleiss, O Tong, WD Truter, SL Vonderscher, J Westelinck, A Zhang, L Zineh, I AF Goodsaid, Federico M. Amur, Shashi Aubrecht, Jiri Burczynski, Michael E. Carl, Kevin Catalano, Jennifer Charlab, Rosane Close, Sandra Cornu-Artis, Catherine Essioux, Laurent Fornace, Albert J., Jr. Hinman, Lois Hong, Huixiao Hunt, Ian Jacobson-Kram, David Jawaid, Ansar Laurie, David Lesko, Lawrence Li, Heng-Hong Lindpaintner, Klaus Mayne, James Morrow, Peter Papaluca-Amati, Marisa Robison, Timothy W. Roth, John Schuppe-Koistinen, Ina Shi, Leming Spleiss, Olivia Tong, Weida Truter, Sharada L. Vonderscher, Jacky Westelinck, Agnes Zhang, Li Zineh, Issam TI Voluntary exploratory data submissions to the US FDA and the EMA: experience and impact SO NATURE REVIEWS DRUG DISCOVERY LA English DT Article ID RENAL-CELL CARCINOMA; BLOOD MONONUCLEAR-CELLS; DIHYDROPYRIMIDINE DEHYDROGENASE; CLINICAL-OUTCOMES; PROTOCOL BIOPSIES; DRUG DEVELOPMENT; XIMELAGATRAN; GENOTOXICITY; TRANSPLANTATION; CLOPIDOGREL AB Heterogeneity in the underlying mechanisms of disease processes and inter-patient variability in drug responses are major challenges in drug development. To address these challenges, biomarker strategies based on a range of platforms, such as microarray gene-expression technologies, are increasingly being applied to elucidate these sources of variability and thereby potentially increase drug development success rates. With the aim of enhancing understanding of the regulatory significance of such biomarker data by regulators and sponsors, the US Food and Drug Administration initiated a programme in 2004 to allow sponsors to submit exploratory genomic data voluntarily, without immediate regulatory impact. In this article, a selection of case studies from the first 5 years of this programme - which is now known as the voluntary exploratory data submission programme, and also involves collaboration with the European Medicines Agency - are discussed, and general lessons are highlighted. C1 [Goodsaid, Federico M.; Amur, Shashi; Charlab, Rosane; Zhang, Li; Zineh, Issam] US FDA, Genom Grp, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. [Mayne, James] Pfizer Global R&D, Worldwide Regulatory Strategy & Policy, Groton, CT 06340 USA. [Burczynski, Michael E.; Roth, John; Vonderscher, Jacky] F Hoffmann La Roche, Nutley, NJ 07110 USA. [Catalano, Jennifer] US FDA, Div Cell & Gene Therapies, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Carl, Kevin; Hinman, Lois] Novartis Pharmaceut, E Hanover, NJ 07936 USA. [Close, Sandra; Morrow, Peter] Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. [Cornu-Artis, Catherine; Laurie, David] Novartis Pharmaceut, CH-4133 Basel, Switzerland. [Essioux, Laurent; Spleiss, Olivia] F Hoffmann La Roche, CH-4070 Basel, Switzerland. [Fornace, Albert J., Jr.; Li, Heng-Hong] Georgetown Univ, Dept Biochem & Mol & Cellular Biol, Washington, DC 20007 USA. [Fornace, Albert J., Jr.; Li, Heng-Hong] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Hong, Huixiao; Shi, Leming; Tong, Weida] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Robison, Timothy W.] US FDA, Div Pulm & Allergy Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. [Lindpaintner, Klaus] Strateg Diagnost Inc, St Petersburg 197022, Russia. [Papaluca-Amati, Marisa] European Med Agcy, Preauthorisat Unit, Sector Safety & Efficacy Med, London E14 4HB, England. [Westelinck, Agnes] GlaxoSmithKline Inc, Collegeville, PA 19426 USA. RP Goodsaid, FM (reprint author), US FDA, Genom Grp, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Bldg 51,10903 New Hampshire Ave, Silver Spring, MD 20903 USA. EM Federico.Goodsaid@fda.hhs.gov RI Zhang, Jinny/C-4794-2012; OI Fornace, Albert/0000-0001-9695-085X NR 52 TC 48 Z9 51 U1 1 U2 7 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 JUN PY 2010 VL 9 IS 6 BP 435 EP U44 DI 10.1038/nrd3116 PG 16 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 603KQ UT WOS:000278207900021 PM 20514070 ER PT J AU Debisette, AT Martinelli, AM Couig, MP Braun, M AF Debisette, Annette Tyree Martinelli, Angela M. Couig, Mary Pat Braun, Michelle TI US Public Health Service Commissioned Corps Nurses: Responding in Times of National Need SO NURSING CLINICS OF NORTH AMERICA LA English DT Article DE US Public Health Service; Emergency preparedness; Disaster response; Public health service nursing; Commissioned Corps AB The US Public Health Service (PHS) is one of 7 uniformed services operating for the nation. Nurses form the largest category of personnel in the PHS and are integral members of teams identified to deploy in times of national need. PHS nurses serve "in harm's way" to protect and defend the public health of the nation during national emergencies and disasters of great magnitude, such as 9/11, Hurricane Katrina, the H1N1 virus outbreak, and so forth. In this article, the authors discuss how active-duty Commissioned Corps nurses in the US PHS respond during times of national need. Military nurses may be asked to serve in war zones, participate in humanitarian missions, and care for military beneficiaries. By contrast, the role of nurses in the Commissioned Corps is to protect, defend, and advance the public health of the nation. PHS nurses are critical members of interdisciplinary health care teams organized to provide health care to diverse populations in the United States and abroad. C1 [Debisette, Annette Tyree] US PHS, US FDA, Off Regulatory Affairs, Div Human Resource Dev, Rockville, MD 20852 USA. [Martinelli, Angela M.] NIAAA, Div Treatment & Recovery Res, Rockville, MD 20852 USA. [Couig, Mary Pat] US PHS, Bethesda, MD 20815 USA. [Braun, Michelle] NIH, US Publ Hlth Serv, Kidney Dis Sect, Ctr Clin, Bethesda, MD 20892 USA. RP Debisette, AT (reprint author), US PHS, US FDA, Off Regulatory Affairs, Div Human Resource Dev, 11919 Rockville Pike, Rockville, MD 20852 USA. EM Annette.debisette@fda.hhs.gov NR 7 TC 3 Z9 3 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 0029-6465 J9 NURS CLIN N AM JI Nurs. Clin. North Am. PD JUN PY 2010 VL 45 IS 2 BP 123 EP + DI 10.1016/j.cnur.2010.02.003 PG 15 WC Nursing SC Nursing GA 618FT UT WOS:000279337600004 PM 20510699 ER PT J AU Knebel, AR Martinelli, AM Orsega, S Doss, TL Balingit-Wines, AM Konchan, CL AF Knebel, Ann R. Martinelli, Angela M. Orsega, Susan Doss, Thomas L. Balingit-Wines, Ana Marie Konchan, Carol L. TI Ground Zero Recollections of US Public Health Service Nurses Deployed to New York City in September 2001 SO NURSING CLINICS OF NORTH AMERICA LA English DT Article DE US Public Health Service; Emergency preparedness; September 11; World Trade Center; Disaster response; Public health service nursing ID TRADE-CENTER DISASTER; RECOVERY; WORKERS; RESCUE AB The events of September 11, 2001, set in motion the broadest emergency response ever conducted by the US Department of Health and Human Services. In this article, some of the nurses who deployed to New York City in the aftermath of that horrific attack on the United States offer their recollections of the events. Although Public Health Service Commissioned Corps (PHS CC) officers participated in deployments before 9/11, this particular deployment accelerated the transformation of the PHS CC, because people came to realize the tremendous potential of a uniformed service of 6,000 health care professionals. When not responding to emergencies, PHS CC nurses daily serve the mission of the PHS to protect, promote, and advance the health and safety of the nation. In times of crisis, the PHS CC nurses stand ready to deploy in support of those in need of medical assistance. C1 [Knebel, Ann R.] US Dept Hlth & Human Serv, Off Assistant Secretary Preparedness & Response, Washington, DC 20201 USA. [Knebel, Ann R.; Martinelli, Angela M.; Orsega, Susan; Doss, Thomas L.; Balingit-Wines, Ana Marie; Konchan, Carol L.] US Publ Hlth Serv Commissioned Corps PHS CC, Off Publ Hlth & Sci, US Dept Hlth & Human Serv, Washington, DC 20201 USA. [Martinelli, Angela M.] NIAAA, Div Treatment & Recovery, Rockville, MD 20852 USA. [Orsega, Susan] NIAID, Div Clin Res, Collaborat Clin Res Branch, Bethesda, MD 20892 USA. [Doss, Thomas L.] Dept Def TRICARE Management Act, Falls Church, VA 22041 USA. [Balingit-Wines, Ana Marie] US Dept Hlth & Human Serv, FDA Ctr Devices & Radiol Hlth, US FDA, Off Compliance, Silver Spring, MD 20993 USA. [Konchan, Carol L.] NINDS, US Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Knebel, AR (reprint author), US Dept Hlth & Human Serv, Off Assistant Secretary Preparedness & Response, 200 Independence Ave SW,Room 638 G, Washington, DC 20201 USA. EM ann.knebel@hhs.gov NR 21 TC 2 Z9 2 U1 3 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 0029-6465 J9 NURS CLIN N AM JI Nurs. Clin. North Am. PD JUN PY 2010 VL 45 IS 2 BP 137 EP + DI 10.1016/j.cnur.2010.02.010 PG 17 WC Nursing SC Nursing GA 618FT UT WOS:000279337600005 PM 20510700 ER PT J AU Sharma, P Gurumurthy, S Duncan, R Nakhasi, HL Salotra, P AF Sharma, Paresh Gurumurthy, Srividya Duncan, Robert Nakhasi, Hira L. Salotra, Poonam TI Comparative in vivo expression of amastigote up regulated Leishmania genes in three different forms of Leishmaniasis SO PARASITOLOGY INTERNATIONAL LA English DT Article DE Leishmania; VL; PKDL; CL; Gene expression; Real time PCR ID DONOVANI; IDENTIFICATION; INFECTION; PROTEIN; A2 AB In Old World Leishmania infections in India, Leishmania donovani is responsible for visceral leishmaniasis (VL) and post kala-azar dermal leishmaniasis (PKDL) while L tropica is responsible for cutaneous leishmaniasis (CL) in humans. The molecular differences between the two species of Leishmania and within the same species causing distinct pathologies that govern the outcome of infection and pathogenesis in the human host are unknown. Quantitative expression of selected genes was evaluated directly in lesion tissues of VL, PKDL and CL patients. Assessment of in vivo mRNA level highlighted substantial differences in gene expression patterns, providing an indication of the genes involved in pathogenesis in the three different forms of Leishmaniasis. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Sharma, Paresh; Gurumurthy, Srividya; Salotra, Poonam] Safdarjung Hosp Campus, Inst Pathol ICMR, New Delhi 110029, India. [Duncan, Robert; Nakhasi, Hira L.] FDA, CBER, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20892 USA. RP Salotra, P (reprint author), Safdarjung Hosp Campus, Inst Pathol ICMR, New Delhi 110029, India. EM salotra@vsnl.com RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 FU DBT, India FX Financial support for the study, provided by the Indo-US VAP funded by DBT, India is gratefully acknowledged. NR 16 TC 6 Z9 7 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1383-5769 J9 PARASITOL INT JI Parasitol. Int. PD JUN PY 2010 VL 59 IS 2 BP 262 EP 264 DI 10.1016/j.parint.2009.11.003 PG 3 WC Parasitology SC Parasitology GA 663EW UT WOS:000282866800024 PM 19963076 ER PT J AU Li, RW Fein, SB Grummer-Strawn, LM AF Li, Ruowei Fein, Sara B. Grummer-Strawn, Laurence M. TI Do Infants Fed From Bottles Lack Self-regulation of Milk Intake Compared With Directly Breastfed Infants? SO PEDIATRICS LA English DT Article DE self-regulation; bottle-feeding; direct breastfeeding; childhood obesity ID FORMULA-FED INFANTS; BODY-MASS INDEX; CHILDHOOD OBESITY; FEEDING PRACTICES; ENERGY-INTAKE; EARLY GROWTH; US CHILDREN; WEIGHT-GAIN; OVERWEIGHT; ADOLESCENTS AB OBJECTIVE: How breastfeeding reduces the risk of childhood obesity is unclear, and 1 hypothesis pertains to the ability of breastfed infants to self-regulate. We studied whether infants' self-regulation of milk intake is affected by feeding mode (bottle versus breast) and the type of milk in the bottle (formula versus expressed breast milk). PATIENTS AND METHODS: Participants in the 2005-2007 Infant Feeding Practices Study II received monthly questionnaires during their infant's first year, and compete data were available for 1250 infants. We tested the impact of feeding mode and type of milk during early infancy on self-regulation during late infancy. RESULTS: Although only 27% of infants fed exclusively at the breast in early infancy emptied the bottle or cup in late infancy, 54% of infants who were fed both at the breast and by bottle did so, and 68% of those who were fed only by bottle did so. Multivariate regression analysis indicated that infants who were bottle-fed more intensively early in life were similar to 71% or 2 times more likely to empty the bottle or cup later in life than those who were bottle-fed less intensively (1/3-2/3 or 2/3 of milk feeds given by bottle versus <1/3 of milk feeds). When feeding formula and expressed milk were considered separately, similar dose-response relationships were observed. CONCLUSIONS: Infants who are bottle-fed in early infancy are more likely to empty the bottle or cup in late infancy than those who are fed directly at the breast. Bottle-feeding, regardless of the type of milk, is distinct from feeding at the breast in its effect on infants' self-regulation of milk intake. Pediatrics 2010; 125: e1386-e1393 C1 [Li, Ruowei; Grummer-Strawn, Laurence M.] Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Nutr Phys Act & Obes, Atlanta, GA 30341 USA. [Fein, Sara B.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Li, RW (reprint author), Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Nutr Phys Act & Obes, 4770 Buford Highway,MS K25, Atlanta, GA 30341 USA. EM rli1@cdc.gov FU Food and Drug Administration; Centers for Disease Control and Prevention; Office of Women's Health; National Institutes of Health; Maternal and Child Health Bureau in the US Department of Health and Human Services FX This study was supported by the Food and Drug Administration, Centers for Disease Control and Prevention, Office of Women's Health, National Institutes of Health, and Maternal and Child Health Bureau in the US Department of Health and Human Services. NR 43 TC 103 Z9 103 U1 2 U2 26 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 JUN PY 2010 VL 125 IS 6 BP E1386 EP E1393 DI 10.1542/peds.2009-2549 PG 8 WC Pediatrics SC Pediatrics GA 604GX UT WOS:000278268600043 PM 20457676 ER PT J AU Skelton, LL AF Skelton, L. L. TI Collaboration, cooperation, and engagement across agencies SO PHYTOPATHOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Phytopathological-Society (APS) CY AUG 07-11, 2010 CL Charlotte, NC SP Amer Phytopathol Soc C1 [Skelton, L. L.] US FDA, CFSAN, Off Food Safety, Produce Safety Staff, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER PHYTOPATHOLOGICAL SOC PI ST PAUL PA 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 USA SN 0031-949X J9 PHYTOPATHOLOGY JI Phytopathology PD JUN PY 2010 VL 100 IS 6 SU S BP S155 EP S155 PG 1 WC Plant Sciences SC Plant Sciences GA 822JU UT WOS:000295042001044 ER PT J AU Piper, BJ Ali, SF Daniels, LG Meyer, JS AF Piper, Brian J. Ali, Syed F. Daniels, Lauren G. Meyer, Jerrold S. TI Repeated Intermittent Methylenedioxymethamphetamine Exposure Protects Against the Behavioral and Neurotoxic, but Not Hyperthermic, Effects of an MDMA Binge in Adult Rats SO SYNAPSE LA English DT Article DE ecstasy; SERT; ejaculation; body weight; behavior; preconditioning ID CONDITIONED PLACE PREFERENCE; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; SEROTONIN SYNDROME; ECSTASY EXPOSURE; BRAIN; METHAMPHETAMINE; MICE; EJACULATION; TOXICITY; CHLOROAMPHETAMINE AB We have recently shown that chronic intermittent exposure of adolescent rats to 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) completely blocks the reduction in serotonin transporter (SERT) binding and the hypoactivity seen following a subsequent MDMA binge treatment. The present study determined whether a similar neuroprotective effect also occurs in rats given the same intermittent MDMA exposure in adulthood. Adult male Sprague Dawley rats were given either MDMA (10 mg/kg x 2) or saline, every fifth day, from postnatal day (PD) 60 to PD 85. The MDMA-induced latency until seminal plug production was reduced over the course of intermittent treatments. After a 1-week wash-out period, animals received either a low- or high-dose MDMA binge (2.5 or 5.0 mg/kg x 4). Core body temperature was measured during and after the binge to determine the effects of MDMA pretreatment on MDMA-induced hyperthermia. Spontaneous motor activity was determined the next day, and cortical and hippocampal samples were collected at 1 week postbinge to measure serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations as well as [(3)H]citalopram binding to SERT. Hyperthermia occurred more rapidly and seminal discharge was more common in the MDMA-pretreated group compared to the MDMA-naive group in animals given the low-dose binge. MDMA preexposure protected animals from the reductions in cortical 5-HT levels and SERT binding produced by the high-dose binge and blocked the postbinge hypoactivity. These findings indicate that chronic, intermittent MDMA exposure in adulthood induces neuroprotective effects similar to those seen with adolescent treatment. However, there was also evidence for drug-induced sensitization in adults that was not observed in adolescents. Thus, altered drug sensitivity in chronic Ecstasy users may depend not only on the frequency and pattern of use but also on the age of the user. Synapse 64:421-431, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Meyer, Jerrold S.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Daniels, Lauren G.] Univ Massachusetts, Dept Biochem & Mol Biol, Amherst, MA 01003 USA. [Ali, Syed F.] Natl Ctr Toxicol Res, Neurochem Lab, Jefferson, AR 72079 USA. [Piper, Brian J.; Meyer, Jerrold S.] Univ Massachusetts, Neurosci & Behav Program, Amherst, MA 01003 USA. RP Meyer, JS (reprint author), Univ Massachusetts, Dept Psychol, Tobin Hall,135 Hicks Way, Amherst, MA 01003 USA. EM jmeyer@psych.umass.edu OI Meyer, Jerrold/0000-0002-8382-7075 NR 49 TC 9 Z9 9 U1 0 U2 2 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 JUN PY 2010 VL 64 IS 6 BP 421 EP 431 DI 10.1002/syn.20744 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 586UE UT WOS:000276938200002 PM 20169574 ER PT J AU Mei, N McDaniel, LP Dobrovolsky, VN Guo, XQ Shaddock, JG Mittelstaedt, RA Azuma, M Shelton, SD McGarrity, LJ Doerge, DR Heflich, RH AF Mei, Nan McDaniel, Lea P. Dobrovolsky, Vasily N. Guo, Xiaoqing Shaddock, Joseph G. Mittelstaedt, Roberta A. Azuma, Mizuo Shelton, Sharon D. McGarrity, Lynda J. Doerge, Daniel R. Heflich, Robert H. TI The Genotoxicity of Acrylamide and Glycidamide in Big Blue Rats SO TOXICOLOGICAL SCIENCES LA English DT Article DE acrylamide; glycidamide; Big Blue rat; Hprt mutant assay; cII mutant assay ID IN-VIVO MUTATION; FISCHER-344 RATS; DIETARY ACRYLAMIDE; HEMOGLOBIN ADDUCTS; N-METHYLOLACRYLAMIDE; DRINKING-WATER; DOSE-RESPONSE; HPRT GENE; MICE; DNA AB Acrylamide (AA), a mutagen and rodent carcinogen, recently has been detected in fried and baked starchy foods, a finding that has prompted renewed interest in its potential for toxicity in humans. In the present study, we exposed Big Blue rats to the equivalent of similar to 5 and 10 mg/kg body weight/day of AA or its epoxide metabolite glycidamide (GA) via the drinking water, an AA treatment regimen comparable to those used to produce cancer in rats. After 2 months of dosing, the rats were euthanized and blood was taken for the micronucleus assay; spleens for the lymphocyte Hprt mutant assay; and liver, thyroid, bone marrow, testis (from males), and mammary gland (females) for the cII mutant assay. Neither AA nor GA increased the frequency of micronucleated reticulocytes. In contrast, both compounds produced small (approximately twofold to threefold above background) but significant increases in lymphocyte Hprt mutant frequency (MF, p < 0.05), with the increases having dose-related linear trends (p < 0.05 to p < 0.001). Neither compound increased the cII MF in testis, mammary gland (tumor target tissues), or liver (nontarget tissue), while both compounds induced weak positive increases in bone marrow (nontarget tissue) and thyroid (target tissue). Although the genotoxicity in tumor target tissue was weak, in combination with the responses in surrogate tissues, the results are consistent with AA being a gene mutagen in the rat via metabolism to GA. C1 [Mei, Nan; McDaniel, Lea P.; Dobrovolsky, Vasily N.; Guo, Xiaoqing; Shaddock, Joseph G.; Mittelstaedt, Roberta A.; Azuma, Mizuo; Shelton, Sharon D.; McGarrity, Lynda J.; Heflich, Robert H.] Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [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 U.S. Food and Drug Administration/National Center for Toxicological Research (NCTR [224-07-0007]; National Institute for Environmental Health Sciences [224-07-0007] FX Interagency Agreement # 224-07-0007 between the U.S. Food and Drug Administration/National Center for Toxicological Research (NCTR) and the National Institute for Environmental Health Sciences/National Toxicology Program. This research was partly supported by appointments (M. A. and X. G.) to the Postgraduate Research Program at the NCTR administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 50 TC 28 Z9 31 U1 3 U2 19 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUN PY 2010 VL 115 IS 2 BP 412 EP 421 DI 10.1093/toxsci/kfq069 PG 10 WC Toxicology SC Toxicology GA 600OR UT WOS:000277997100011 PM 20200216 ER PT J AU Deeds, JR Wiles, K Heideman, GB White, KD Abraham, A AF Deeds, Jonathan R. Wiles, Kirk Heideman, Gary B. White, Kevin D. Abraham, Ann TI First US report of shellfish harvesting closures due to confirmed okadaic acid in Texas Gulf coast oysters SO TOXICON LA English DT Article DE Diarrheic Shellfish Poisoning; Shellfish harvesting closures; Dinophysis sp.; Okadaic acid; Phycotoxins; Harmful algae; Seafood safety ID DINOPHYSIS-FORTII; TOXIN; IDENTIFICATION; DINOFLAGELLATE; PECTENOTOXIN-2 AB Between March 7 and April 12, 2008, several bay systems on the east (Gulf of Mexico) coast of Texas, USA were closed to the harvesting of oysters (Crassostrea virginica) due to the presence of the DSP (Diarrheic Shellfish Poisoning) toxin okadaic acid in excess of the 20 mu g/100 g tissue FDA regulatory guidance level. This was the first shellfish harvesting closure due to the confirmed presence of DSP toxins in US history. Light microscopic cell counts were performed on water samples collected from numerous sampling sites along the Texas Gulf coast where shellfish harvesting occurs. Ultra performance liquid chromatography, electrospray ionization, selected reaction monitoring, mass spectrometry (UPLC/ESI/SRM/MS) was used to detect DSP toxins in oysters. The closures were associated with an extensive bloom of the dinoflagellate Dinophysis cf. ovum. Only okadaic acid (OA) and OA acyl esters were found in shellfish tissues (max. OA eq. levels 47 mu g/100 g tissue). OA was also confirmed in a bloom water sample. No illnesses were reported associated with this event. DSP toxins now add to a growing list of phycotoxins, which include those responsible for PSP (paralytic shellfish poisoning), NSP (neurotoxic shellfish poisoning), and ASP (amnesic shellfish poisoning) which must now be monitored for in US coastal waters where shellfish are harvested. (C) Published by Elsevier Ltd. C1 [Deeds, Jonathan R.; White, Kevin D.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Wiles, Kirk; Heideman, Gary B.] Texas Dept State Hlth Serv, Seafood & Aquat Life Grp, Austin, TX USA. [Abraham, Ann] US FDA, Ctr Food Safety & Appl Nutr, Dauphin Isl, AL USA. RP Deeds, JR (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM jonathan.deeds@fda.hhs.gov NR 24 TC 26 Z9 26 U1 0 U2 19 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD JUN 1 PY 2010 VL 55 IS 6 BP 1138 EP 1146 DI 10.1016/j.toxicon.2010.01.003 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 580GS UT WOS:000276436600012 PM 20060850 ER PT J AU Roback, JD Caldwell, S Carson, J Davenport, R Drew, MJ Eder, A Fung, M Hamilton, M Hess, JR Luban, N Perkins, JG Sachais, BS Shander, A Silverman, T Snyder, E Tormey, C Waters, J Djulbegovic, B AF Roback, John D. Caldwell, Stephen Carson, Jeff Davenport, Robertson Drew, Mary Jo Eder, Anne Fung, Mark Hamilton, Marilyn Hess, John R. Luban, Naomi Perkins, Jeremy G. Sachais, Bruce S. Shander, Aryeh Silverman, Toby Snyder, Ed Tormey, Christopher Waters, John Djulbegovic, Ben TI Evidence-based practice guidelines for plasma transfusion SO TRANSFUSION LA English DT Article ID FRESH-FROZEN PLASMA; I TRAUMA CENTER; LIFE-THREATENING COAGULOPATHY; DAMAGE CONTROL HEMATOLOGY; BLOOD-PRODUCT UTILIZATION; LAST 60 YEARS; EXSANGUINATION PROTOCOL; RETROSPECTIVE ANALYSIS; LIVER-TRANSPLANTATION; MASSIVE TRANSFUSION AB BACKGROUND: There is little systematically derived evidence-based guidance to inform plasma transfusion decisions. To address this issue, the AABB commissioned the development of clinical practice guidelines to help direct appropriate transfusion of plasma. STUDY DESIGN AND METHODS: A systematic review (SR) and meta-analysis of randomized and observational studies was performed to quantify known benefits and harms of plasma transfusion in common clinical scenarios (see accompanying article). A multidisciplinary guidelines panel then used the SR and the GRADE methodology to develop evidence-based plasma transfusion guidelines as well as identify areas for future investigation. RESULTS: Based on evidence ranging primarily from moderate to very low in quality, the panel developed the following guidelines: 1) The panel suggested that plasma be transfused to patients requiring massive transfusion. However, 2) the panel could not recommend for or against transfusion of plasma at a plasma : red blood cell ratio of 1:3 or more during massive transfusion, 3) nor could the panel recommend for or against transfusion of plasma to patients undergoing surgery in the absence of massive transfusion. 4) The panel suggested that plasma be transfused in patients with warfarin therapy-related intracranial hemorrhage, 5) but could not recommend for or against transfusion of plasma to reverse warfarin anticoagulation in patients without intracranial hemorrhage. 6) The panel suggested against plasma transfusion for other selected groups of patients. CONCLUSION: We have systematically developed evidence-based guidance to inform plasma transfusion decisions in common clinical scenarios. Data from additional randomized studies will be required to establish more comprehensive and definitive guidelines for plasma transfusion. C1 [Roback, John D.] Emory Univ, Sch Med, Dept Pathol & Lab Med, Ctr Transfus & Cellular Therapies, Atlanta, GA 30322 USA. Univ Virginia, GI Hepatol, Charlottesville, VA USA. UMDNJ Robert Wood Johnson Univ Hosp, New Brunswick, NJ USA. Univ Michigan, Sch Med, Dept Pathol, Blood Bank, Ann Arbor, MI USA. Univ Michigan, Sch Med, Dept Pathol, Transfus Serv, Ann Arbor, MI USA. Amer Red Cross, Pacific NW Blood Serv Reg, Portland, OR USA. Amer Red Cross, Biomed Serv, Washington, DC 20006 USA. Univ Vermont, Burlington, VT USA. Fletcher Allen Hlth Care, Dept Pathol, Burlington, VT USA. Childrens Mercy Hosp, Kansas City, MO 64108 USA. Univ Maryland, Dept Pathol, Med Ctr, Baltimore, MD 21201 USA. Childrens Hosp, Natl Med Ctr, Washington, DC 20010 USA. Walter Reed Army Inst Res, Dept Blood Res, Silver Spring, MD USA. Univ Penn, Dept Pathol & Lab Med, Div Transfus Med, Philadelphia, PA 19104 USA. Englewood Hosp, Mt Sinai Sch Med, Dept Anesthesiol, Englewood, NJ USA. Med Ctr, Englewood, NJ USA. Yale New Haven Med Ctr, New Haven, CT 06504 USA. US FDA, Rockville, MD 20857 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Univ S Florida, Ctr Evidence Based Med & Hlth Outcome Res, Clin Translat Sci Inst, Tampa, FL USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. RP Roback, JD (reprint author), Emory Univ, Sch Med, Dept Pathol & Lab Med, Ctr Transfus & Cellular Therapies, Atlanta, GA 30322 USA. EM jroback@emory.edu RI Djulbegovic, Benjamin/I-3661-2012; Hess, John/K-4001-2013 OI Djulbegovic, Benjamin/0000-0003-0671-1447; Hess, John/0000-0001-8596-4420 FU AABB FX This work was completely funded by the AABB. NR 53 TC 108 Z9 113 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 2010 VL 50 IS 6 BP 1227 EP 1239 DI 10.1111/j.1537-2995.2010.02632.x PG 13 WC Hematology SC Hematology GA 604ZH UT WOS:000278316500012 PM 20345562 ER PT J AU Laird, N Fitzmaurice, G Ding, XA AF Laird, Nan Fitzmaurice, Garrett Ding, Xiao TI Comments on 'Empirical vs natural weighting in random effects meta-analysis' SO STATISTICS IN MEDICINE LA English DT Editorial Material C1 [Laird, Nan; Fitzmaurice, Garrett] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Fitzmaurice, Garrett] McLean Hosp, Lab Psychiat Biostat, Belmont, MA 02478 USA. [Ding, Xiao] US FDA, Off Biostat, Silver Spring, MD 20993 USA. RP Laird, N (reprint author), 655 Huntington Ave,Bldg 2,Room 447, Boston, MA 02115 USA. EM laird@hsph.harvard.edu RI Rohlf, F/A-8710-2008 NR 6 TC 8 Z9 8 U1 0 U2 5 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 MAY 30 PY 2010 VL 29 IS 12 BP 1266 EP 1267 DI 10.1002/sim.3657 PG 2 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 606MD UT WOS:000278428200002 PM 20499329 ER PT J AU Fintschenko, Y Krynitsky, AJ Wong, JW AF Fintschenko, Yolanda Krynitsky, Alexander J. Wong, Jon W. TI Emerging Pesticide Residue Issues and Analytical Approaches SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Editorial Material DE Pesticide residues; organic residue analysis; instrumentation; bioassay; chromatography; mass spectrometry ID SOLID-PHASE EXTRACTION; CHROMATOGRAPHY-MASS SPECTROMETRY; GAS-CHROMATOGRAPHY; WATER; FOOD AB The 46th Annual Florida Pesticide Residue Workshop of 2009 (FPRW 2009) held in St. Pete Beach, FL, is the latest in an annual tradition drawing scientists from U.S. federal and state government laboratories, industry, and other laboratories worldwide. In 2009, selected FPRW presenters were invited to contribute to this special issue of the Journal of Agricultural and Food Chemistry with a section devoted to emerging pesticide residue issues and analytical approaches. What follows is the written record of what should become a scientific conversation launched at FPRW 2009. There are two distinct approaches to organic residue analysis: instrumental methods and assays. In much of the world, scientists primarily rely on laboratories equipped with instrumentation for analysis, usually gas chromatography and liquid chromatography with some type of selective detector. In the discussion of instrumental approaches, the focus is on chromatography with mass spectrometry as a detection method. Approaches such as biomonitoring and assays fall outside the traditional instrumental method approach to residue analysis. Assays that do not require laboratory equipment are of greater interest for screening and are well-suited to field use. Regardless of the analytical method, the success of multiresidue analysis relies on the appropriate choice of sample preparation and cleanup methodologies. Many new sample preparation and cleanup approaches used for pesticide and other small molecule contaminant residue analyses in a variety of complex sample matrices are discussed in this special issue. The goal of these approaches is to reduce overall analysis time and solvent consumption without compromising the analytical results. C1 [Fintschenko, Yolanda] LabSmith, Livermore, CA 94551 USA. [Fintschenko, Yolanda] Thermo Fisher Sci, San Jose, CA 95134 USA. [Krynitsky, Alexander J.; Wong, Jon W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Fintschenko, Y (reprint author), LabSmith, 4659 Las Positas Rd,Suite C, Livermore, CA 94551 USA. EM yfintschenko@labsmith.com NR 12 TC 6 Z9 9 U1 3 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAY 26 PY 2010 VL 58 IS 10 BP 5859 EP 5861 DI 10.1021/jf904599w PG 3 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 596YN UT WOS:000277721900001 PM 20441152 ER PT J AU Wong, JW Zhang, K Tech, K Hayward, DG Makovi, CM Krynitsky, AJ Schenck, FJ Banerjee, K Dasgupta, S Brown, D AF Wong, Jon W. Zhang, Kai Tech, Katherine Hayward, Douglas G. Makovi, Carolyn M. Krynitsky, Alexander J. Schenck, Frank J. Banerjee, Kaushik Dasgupta, Soma Brown, Don TI Multiresidue Pesticide Analysis in Fresh Produce by Capillary Gas Chromatography-Mass Spectrometry/Selective Ion Monitoring (GC-MS/SIM) and-Tandem Mass Spectrometry (GC-MS/MS) SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article; Proceedings Paper CT 46th Annual Florida Pesticide Residue Workshop (FPRW 2009) CY 2009 CL St Pete Beach, FL DE Multiresidue methods; GC-MS/SIM; GC-MS/MS; modified QuEChERS ID SOLID-PHASE EXTRACTION; FLAME PHOTOMETRIC DETECTION; LIQUID-CHROMATOGRAPHY; RESIDUE ANALYSIS; ETHYL-ACETATE; ORGANOPHOSPHORUS PESTICIDES; AGRICULTURAL PRODUCTS; SELECTIVE DETECTION; QUECHERS METHOD; COLUMN CLEANUP AB A multiresidue method for the analysis of pesticides in fresh produce has been developed using salt-out acetonitrile extraction, solid-phase dispersive cleanup with octadecyl-bonded silica (C-18), and graphitized carbon black/primary-secondary amine (GCB/PSA) sorbents and toluene, followed by capillary gas chromatography-mass spectrometry in selected ion monitoring mode (GC-MS/SIM) or tandem mass spectrometry (GC-MS/MS). Quantitation was determined from calibration curves using matrix-matched standards ranging from 3.3 to 6667 ng/mL with r(2) > 0.99, and geometric mean limits of quantitation were typically 8.4 and 3.4 mu g/kg for GC-MS/SIM and GC-MS/MS, respectively. Identification was determined by using target and qualifier ions and qualifier-to-target ratios for GC-MS/SIM and two ion transitions for GC-MS/MS. Fortification studies (10, 25, 100, and 500 mu g/kg) were performed on 167 organohalogen, organophosphorus, and pyrethroid pesticides in 10 different commodities (apple, broccoli, carrot, onion, orange, pea, peach, potato, spinach, and tomato). The mean percent recoveries were 90 +/- 14, 87 +/- 14, 89 +/- 14, and 92 +/- 14% for GC-MS/SIM and 95 +/- 22, 93 +/- 14, 93 +/- 13, and 97 +/- 13% for GC-MS/MS at 10, 25, 100, and 500 mu g/kg, respectively. GC-MS/MS was shown to be more effective than GC-MS/SIM due to its specificity and sensitivity in detecting pesticides in fresh produce samples. The method, based on concepts from the multiresidue procedure used by the Canadian Food Inspection Agency and QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe), was shown to be efficient in screening, identifying, and quantitating pesticides in fresh produce samples. C1 [Wong, Jon W.; Zhang, Kai; Hayward, Douglas G.; Makovi, Carolyn M.; Krynitsky, Alexander J.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. [Tech, Katherine] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. [Schenck, Frank J.] US FDA, Off Regulatory Affairs, SE Reg Lab, Atlanta, GA 30309 USA. [Banerjee, Kaushik; Dasgupta, Soma] Natl Res Ctr Grapes, Pune 412307, Maharashtra, India. [Brown, Don] Exova UK, Birmingham B44 9ET, W Midlands, England. RP Wong, JW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, HES-706,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM jon.wong@fda.hhs.gov NR 42 TC 45 Z9 50 U1 6 U2 84 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 EI 1520-5118 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAY 26 PY 2010 VL 58 IS 10 BP 5868 EP 5883 DI 10.1021/jf903854n PG 16 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 596YN UT WOS:000277721900003 PM 20199080 ER PT J AU Wong, JW Zhang, K Tech, K Hayward, DG Krynitsky, AJ Cassias, I Schenck, FJ Banerjee, K Dasgupta, S Brown, D AF Wong, Jon W. Zhang, Kai Tech, Katherine Hayward, Douglas G. Krynitsky, Alexander J. Cassias, Irene Schenck, Frank J. Banerjee, Kaushik Dasgupta, Soma Brown, Don TI Multiresidue Pesticide Analysis of Ginseng Powders Using Acetonitrile- or Acetone-Based Extraction, Solid-Phase Extraction Cleanup, and Gas Chromatography-Mass Spectrometry/Selective Ion Monitoring (GC-MS/SIM) or -Tandem Mass Spectrometry (GC-MS/MS) SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article; Proceedings Paper CT 46th Annual Florida Pesticide Residue Workshop (FPRW 2009) CY 2009 CL St Pete Beach, FL DE Multiresidue methods; organohalogen pesticides; GC-MS/SIM; GC-MS/MS; acetonitrile; acetone/cyclohexane/ethyl acetate; ginseng ID FLAME PHOTOMETRIC DETECTION; LIQUID-CHROMATOGRAPHY; ORGANOCHLORINE PESTICIDES; AGRICULTURAL PRODUCTS; MEDICINAL-PLANTS; RESIDUE METHOD; RAPID METHOD; VEGETABLES; FRUITS; ROOT AB A multiresidue method for the analysis of 168 pesticides in dried powdered ginseng has been developed using acetonitrile or acetone mixture (acetone/cyclohexane/ethyl acetate, 2:1:1 v/v/v) extraction, solid-phase extraction (SPE) cleanup with octyl-bonded silica (C-8), graphitized carbon black/primary secondary amine (GCB/PSA) sorbents and toluene, and capillary gas chromatography mass spectrometry/selective ion monitoring (GC-MS/SIM) or -tandem mass spectrometry (GC-MS/MS). The geometric mean limits of quantitation (LOQs) were 53 and 6 mu g/kg for the acetonitrile extraction and 48 and 7 mu g/kg for the acetone-based extraction for GC-MS/SIM and GC-MS/MS, respectively. Mean percent recoveries and standard deviations from the ginseng fortified at 25, 100, and 500 mu g/kg using GC-MS/SIM were 87 +/- 10, 88 +/- 8, and 86 +/- 10% from acetonitrile extracts and 88 +/- 13, 88 +/- 12, and 88 +/- 14% from acetone mixture extracts, respectively. The Mean percent recoveries from the ginseng at the 25, 100, and 500 mu g/kg levels using GC-MS/MS were 83 +/- 19, 90 +/- 13, and 89 +/- 11% from acetonitrile extracts and 98 +/- 20, 91 +/- 13, and 88 +/- 14% from acetone extracts, respectively. Twelve dried ginseng products were found to contain one or more of the following pesticides and their metabolites: BHCs (benzene hexachlorides, alpha-, beta-, gamma-, and delta-), chlorothalonil, chlorpyrifos, DDT (dichlorodiphenyl trichloroethane), dacthal, diazinon, iprodione, quintozene, and procymidone ranging from <1 to >4000 mu g/kg. No significant differences were found between the two extraction solvents, and GC-MS/MS was found to be more specific and sensitive than GC-MS/SIM. The procedures described were shown to be effective in screening, identifying, confirming, and quantitating pesticides in commercial ginseng products. C1 [Wong, Jon W.; Zhang, Kai; Hayward, Douglas G.; Krynitsky, Alexander J.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Tech, Katherine] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. [Cassias, Irene] US FDA, Off Regulatory Affairs, Pacific Reg Lab SW, Irvine, CA 92612 USA. [Schenck, Frank J.] US FDA, Off Regulatory Affairs, SE Reg Lab, Atlanta, GA 30309 USA. [Banerjee, Kaushik; Dasgupta, Soma] Natl Res Ctr Grapes, Pune 412307, Maharashtra, India. [Brown, Don] Exova UK, Birmingham B44 9ET, W Midlands, England. RP Wong, JW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-706,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM jon.wong@fda.hhs.gov NR 40 TC 37 Z9 44 U1 8 U2 62 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 EI 1520-5118 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAY 26 PY 2010 VL 58 IS 10 BP 5884 EP 5896 DI 10.1021/jf903851h PG 13 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 596YN UT WOS:000277721900004 PM 20225896 ER PT J AU Wong, J Hao, CY Zhang, K Yang, P Banerjee, K Hayward, D Iftakhar, I Schreiber, A Tech, K Sack, C Smoker, M Chen, XR Utture, SC Oulkar, DP AF Wong, Jon Hao, Chunyan Zhang, Kai Yang, Paul Banerjee, Kaushik Hayward, Douglas Iftakhar, Imran Schreiber, Andre Tech, Katherine Sack, Chris Smoker, Michael Chen, Xiangru Utture, Sagar C. Oulkar, Dasharath P. TI Development and Interlaboratory Validation of a QuEChERS-Based Liquid Chromatography-Tandem Mass Spectrometry Method for Multiresidue Pesticide Analysis SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article; Proceedings Paper CT 46th Annual Florida Pesticide Residue Workshop (FPRW 2009) CY 2009 CL St Pete Beach, FL DE Pesticides; liquid chromatograph-tandem mass spectrometer (LC-MS/MS); QuEChERS; principal component analysis ID EXTRACTION; RESIDUES; MS AB A high-throughput, QuEChERS (Quick, Easy, Cheap, Effective, Rugged, Safe) sample preparation and liquid chromatography tandem mass spectrometry (LC-MS/MS) analytical method has been developed and validated for the determination of 191 pesticides in vegetation and fruit samples. Using identical LC analytical column and MS/MS instrumentation and operation parameters, this method was evaluated at the U.S. Food and Drug Administration (FDA), National Research Centre for Grapes (NRCG), India, and Ontario Ministry of the Environment (MOE) laboratories. Method validation results showed that all but 1 of these 191 pesticides can be analyzed by LC-MS/MS with instrument detection limits (IDL) in the parts per trillion (ppt) range. Matrix-dependent IDL studies showed that due to either the low ionization efficiency or matrix effect exerted, 14 of these 191 pesticides could not be analyzed by this method. Method recovery (%R) and method detection limits (MDLs) were determined by the three laboratories using four sample matrices in replicates (N = 4). With >79% of %R data from the fortification studies in the range from 80 to 120%, MDLs were determined in the low parts per billion range with >94% of MDLs in the range from 0.5 to 5 ppb. Applying this method to the analysis of incurred samples showed that two multiple reaction monitoring (MRM) transitions may not be enough to provide 100% true positive identification of target pesticides; however, quantitative results obtained from the three laboratories had an excellent match with only a few discrepancies in the low parts per billion levels. The %R data from the fortification studies were subjected to principal component analysis and showed the majority of %R fell into the cluster of 80% < %R < 120%. Due to the matrix effect exerted by ginseng and peach, outliers were observed at the lowest spiking levels of 10 and 25 ppb. The study also showed that QuEChERS samples should be analyzed as soon as prepared or stored in a freezer to avoid any adverse affect on the analytes evaluated. C1 [Hao, Chunyan; Yang, Paul; Iftakhar, Imran; Chen, Xiangru] Ontario Minist Environm, Lab Serv Branch, Toronto, ON M9P 3V6, Canada. [Wong, Jon; Zhang, Kai; Hayward, Douglas] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Tech, Katherine; Sack, Chris; Smoker, Michael] US FDA, Kansas City, KS 66215 USA. [Banerjee, Kaushik; Utture, Sagar C.; Oulkar, Dasharath P.] Natl Res Ctr Grapes, Pune 412307, Maharashtra, India. [Schreiber, Andre] AB Sciex, Concord, ON L4K 4V8, Canada. RP Yang, P (reprint author), Ontario Minist Environm, Lab Serv Branch, Toronto, ON M9P 3V6, Canada. EM paul.yang@ontario.ca FU NIH HHS [Y1-OD-6412-01] NR 9 TC 39 Z9 45 U1 1 U2 24 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAY 26 PY 2010 VL 58 IS 10 BP 5897 EP 5903 DI 10.1021/jf903849n PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 596YN UT WOS:000277721900005 PM 20196606 ER PT J AU Basch, EM Reeve, BB Cleeland, CS Sloan, JA Mendoza, TR Abemethy, AP Bruner, D Minasian, LM Burke, LB Schrag, D AF Basch, E. M. Reeve, B. B. Cleeland, C. S. Sloan, J. A. Mendoza, T. R. Abemethy, A. P. Bruner, D. Minasian, L. M. Burke, L. B. Schrag, D. CA PRO-CTCAE Investigators TI Development of the patient-reported version of the common terminology criteria for adverse events (PRO-CTCAE) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, Bethesda, MD 20892 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Mayo Clin Rochester, Rochester, MN USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. US FDA, Silver Spring, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2010 VL 28 IS 15 SU S MA e19605 PG 1 WC Oncology SC Oncology GA V30YT UT WOS:000208852001668 ER PT J AU Cortazar, P Keegan, P Justice, RL Johnson, JR Pazdur, R AF Cortazar, P. Keegan, P. Justice, R. L. Johnson, J. R. Pazdur, R. TI Targeted cancer therapies; FDA approval overview. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Cortazar, P.; Keegan, P.; Justice, R. L.; Johnson, J. R.; Pazdur, R.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2010 VL 28 IS 15 SU S MA 2537 PG 1 WC Oncology SC Oncology GA V30YT UT WOS:000208852003128 ER PT J AU Fadiran, EO Nguyen, T Parekh, A AF Fadiran, E. O. Nguyen, T. Parekh, A. TI Oncology studies funded by the FDA Office of Women's Health: 1994-2009. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Fadiran, E. O.; Nguyen, T.; Parekh, A.] US FDA, Off Womens Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2010 VL 28 IS 15 SU S MA e13659 PG 1 WC Oncology SC Oncology GA V30YT UT WOS:000208852000506 ER PT J AU Grillo, JA Abraham, S Khandelwal, A Liu, Q Booth, B Rahman, NA AF Grillo, J. A. Abraham, S. Khandelwal, A. Liu, Q. Booth, B. Rahman, N. A. TI A comparison of the Cockroft-Gault (CG) and the modification of diet in renal disease (MDRD) equations for estimating renal function and guiding dose adjustment of oncology-related drugs SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Grillo, J. A.; Abraham, S.; Khandelwal, A.; Liu, Q.; Booth, B.; Rahman, N. A.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2010 VL 28 IS 15 SU S MA 2601 PG 1 WC Oncology SC Oncology GA V30YT UT WOS:000208852003192 ER PT J AU Gulley, JL Stein, WD Schlom, J Madan, RA Dahut, WL Figg, WD Ming, YM Price, D Bates, SE Fojo, AT AF Gulley, J. L. Stein, W. D. Schlom, J. Madan, R. A. Dahut, W. L. Figg, W. D. Ming, Y. M. Price, D. Bates, S. E. Fojo, A. T. TI A retrospective analysis of intramural NCI prostate cancer trials:Progress made and insights gleaned. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Med Oncol Branch, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NCI, Lab Tumor Immunol & Biol, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA. NCI, US FDA, Silver Spring, MD USA. RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2010 VL 28 IS 15 SU S MA 4657 PG 1 WC Oncology SC Oncology GA V30YT UT WOS:000208852004026 ER PT J AU Higgins, MJ Prowell, TM Blackford, A Slater, S Argani, P Green, H Khouri, N Blumenthal, R Garber, JE Stearns, V AF Higgins, M. J. Prowell, T. M. Blackford, A. Slater, S. Argani, P. Green, H. Khouri, N. Blumenthal, R. Garber, J. E. Stearns, V. TI A short-term biomarker modulation prevention study of simvastatin in women at increased risk for breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. US FDA, Silver Spring, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2010 VL 28 IS 15 SU S MA 1505 PG 1 WC Oncology SC Oncology GA V30YT UT WOS:000208852002678 ER PT J AU Malik, SM Ibrahim, A Sridhara, R Justice, RL Pazdur, R AF Malik, S. M. Ibrahim, A. Sridhara, R. Justice, R. L. Pazdur, R. TI Use of progression-free survival (PES) as an endpoint in advanced non-small cell lung cancer (NSCLC) trials: FDA perspective SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Malik, S. M.; Ibrahim, A.; Sridhara, R.; Justice, R. L.; Pazdur, R.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2010 VL 28 IS 15 SU S MA e18001 PG 1 WC Oncology SC Oncology GA V30YT UT WOS:000208852001347 ER PT J AU Ning, YM Johnson, JR Farrell, AT Maher, VE Justice, RL Pazdur, R AF Ning, Y. M. Johnson, J. R. Farrell, A. T. Maher, V. E. Justice, R. L. Pazdur, R. TI FDA accelerated approval of anticancer agents SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, US FDA, Silver Spring, MD USA. US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2010 VL 28 IS 15 SU S MA 6065 PG 1 WC Oncology SC Oncology GA V30YT UT WOS:000208852004344 ER PT J AU Cowley, SC Meierovics, AI Frelinger, JA Iwakura, Y Elkins, KL AF Cowley, Siobhan C. Meierovics, Anda I. Frelinger, Jeffrey A. Iwakura, Yoichiro Elkins, Karen L. TI Lung CD4(-)CD8(-) Double-Negative T Cells Are Prominent Producers of IL-17A and IFN-gamma during Primary Respiratory Murine Infection with Francisella tularensis Live Vaccine Strain SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYCOBACTERIUM-TUBERCULOSIS INFECTION; IN-VIVO; IMMUNE-RESPONSES; HOST-DEFENSE; INTRACELLULAR BACTERIUM; NEUTROPHIL RECRUITMENT; INTERFERON-GAMMA; EPITHELIAL-CELLS; LVS; CD4(+) AB For several intracellular infections, pulmonary vaccination provides measurably better protection against pulmonary challenge. The unique factors that contribute to pulmonary immune responses are not well characterized. In this study, we show that CD4(-) CD8(-) double negative (DN) T cells are a major responding T cell subset in the lungs of mice during pulmonary Francisella tularensis live vaccine strain (LVS) infection. DN T cells were a minor (<2%) subset in spleens and lungs of mice during sublethal intradermal infection with LVS. In contrast, they were a major responding T cell subset in lungs during pulmonary LVS infection, producing large quantities of IFN-gamma and IL-17A. The numbers of IL-17A(+) DN T cells in the lungs exceeded that of CD4(+) and CD8(+) T cells on day 7 postinfection; by day 14 postinfection, all three IL-17A producing T cell subsets were present in equivalent numbers. CD4(+), CD8(+), and DN T cell production of IL-17A was not observed in the spleens of pulmonary-infected mice or the lungs and spleens of intradermally infected mice. Correspondingly, IL-17A knockout mice were more susceptible to respiratory than intradermal LVS infection, with delayed clearance 1-3 wk postinfection. Finally, in vitro treatment of LVS-infected macrophages and alveolar type II epithelial cells with IFN-gamma and IL-17A affected significantly greater LVS growth control than treatment with either cytokine alone. The data presented in this study demonstrate that DN cells contribute to production of IL-17A and IFN-gamma in the lungs during inhalational Francisella infection and that these cytokines additively activate host cells to control LVS intracellular growth. The Journal of Immunology, 2010, 184: 5791-5801. C1 [Cowley, Siobhan C.; Meierovics, Anda I.; Elkins, Karen L.] US FDA, Div Bacterial Parasit & Allergen Prod, Lab Mycobacterial Dis & Cellular Immunol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Frelinger, Jeffrey A.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27514 USA. [Iwakura, Yoichiro] Univ Tokyo, Inst Med Sci, Ctr Med Expt, Minato Ku, Tokyo, Japan. RP Cowley, SC (reprint author), US FDA, Div Bacterial Parasit & Allergen Prod, Lab Mycobacterial Dis & Cellular Immunol, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 431, Rockville, MD 20852 USA. EM siobhan.cowley@fda.hhs.gov RI Iwakura, Yoichiro/E-5457-2011 OI Iwakura, Yoichiro/0000-0002-9934-5775 NR 36 TC 52 Z9 52 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2010 VL 184 IS 10 BP 5791 EP 5801 DI 10.4049/jimmunol.1000362 PG 11 WC Immunology SC Immunology GA 594IO UT WOS:000277530700042 PM 20393138 ER PT J AU Lees, KR Bluhmki, E von Kummer, R Brott, TG Toni, D Grotta, JC Albers, GW Kaste, M Marler, JR Hamilton, SA Tilley, BC Davis, SM Donnan, GA Hacke, W Ninds, EA AF Lees, Kennedy R. Bluhmki, Erich von Kummer, Ruediger Brott, Thomas G. Toni, Danilo Grotta, James C. Albers, Gregory W. Kaste, Markku Marler, John R. Hamilton, Scott A. Tilley, Barbara C. Davis, Stephen M. Donnan, Geoffrey A. Hacke, Werner Ninds, Ecass Atlantis CA ECASS Study Grp Investigator ATLANTIS Study Grp Investigator NINDS Study Grp Investigator EPITHET rt-PA Study Grp Investigat TI Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials SO LANCET LA English DT Article ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; COOPERATIVE ACUTE STROKE; RT-PA STROKE; RANDOMIZED-TRIAL; DOUBLE-BLIND; ADVANCED CT; THROMBOLYSIS; THERAPIES AB Background Early administration of intravenous recombinant tissue plasminogen activator (rt-PA) after ischaemic stroke improves outcome. Previous analysis of combined data from individual patients suggested potential benefit beyond 3 h from stroke onset. We re-examined the effect of time to treatment with intravenous rt-PA (alteplase) on therapeutic benefit and clinical risk by adding recent trial data to the analysis. Methods We added data from ECASS III (821 patients) and EPITHET (100 patients) to a pool of common data elements from six other trials of alteplase for acute stroke (2775 patients). We used multivariate logistic regression to assess the relation of stroke onset to start of treatment (on) with treatment on favourable 3-month outcome (defined as modified Rankin score 0-1), mortality, and occurrence and outcome of clinically relevant parenchymal haemorrhage. The presence of an arterial occlusion was inferred from the patient's symptoms and absence of haemorrhage or other causes of ischaemic stroke. Vascular imaging was not a requirement in the trials. All patients with confirmed OTT within 360 min were included in the analysis. Findings Treatment was started within 360 min of stroke onset in 3670 patients randomly allocated to alteplase (n=1850) or to placebo (n=1820). Odds of a favourable 3-month outcome increased as OTT decreased (p=0.0269) and no benefit of alteplase treatment was seen after around 270 min. Adjusted odds of a favourable 3-month outcome were 2.55 (95% CI 1.44-4.52) for 0-90 min, 1.64 (1.12-2.40) for 91-180 min, 1.34 (1.06-1.68) for 181-270 min, and 1.22 (0.92-1.61) for 271-360 min in favour of the alteplase group. Large parenchymal haemorrhage was seen in 96 (5.2%) of 1850 patients assigned to alteplase and 18 (1.0%) of 1820 controls, with no clear relation to OTT (p=0.4140). Adjusted odds of mortality increased with OTT (p=0.0444) and were 0.78 (0.41-1.48) for 0-90 min, 1.13 (0.70-1.82) for 91-180 min, 1.22 (0.87-1.71) for 181-270 min, and 1.49 (1.00-2.21) for 271-360 min. Interpretation Patients with ischaemic stroke selected by clinical symptoms and CT benefit from intravenous alteplase when treated up to 4.5 h. To increase benefit to a maximum, every effort should be taken to shorten delay in initiation of treatment. Beyond 4.5 h, risk might outweigh benefit. C1 [Lees, Kennedy R.] Univ Glasgow, Western Infirm, Dept Med & Therapeut, Glasgow FAC MED, Lanark, Scotland. [Bluhmki, Erich] Boehringer Ingelheim GmbH & Co KG, Dept Stat, Bieberach, Germany. [von Kummer, Ruediger] Univ Klinikum Carl Gustav Carus, Dresden Univ Stroke Ctr, Dept Neuroradiol, Dresden, Germany. [Brott, Thomas G.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Toni, Danilo] La Sapienza Univ Hosp, Emergency Dept Stroke Unit, Rome, Italy. [Grotta, James C.] Univ Texas Med Sch Houston, Dept Neurol, Houston, TX USA. [Albers, Gregory W.; Hamilton, Scott A.] Stanford Univ, Stanford Stroke Ctr, Palo Alto, CA 94304 USA. [Kaste, Markku] Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland. [Marler, John R.] US FDA, Silver Spring, MD USA. [Tilley, Barbara C.] Univ Texas Sch Publ Hlth, Div Biostat, Houston, TX USA. [Davis, Stephen M.] Univ Melbourne, Dept Neurol, Melbourne, Vic 3010, Australia. [Donnan, Geoffrey A.] Univ Melbourne, Florey Neurosci Inst, Melbourne, Vic 3010, Australia. [Hacke, Werner] Heidelberg Univ, Dept Neurol, Heidelberg, Germany. RP Lees, KR (reprint author), Western Infirm & Associated Hosp, Gardiner Inst, Univ Dept Med & Therapeut, Glasgow G11 6NT, Lanark, Scotland. EM k.r.lees@clinmed.gla.ac.uk RI Bastianello, Stefano/A-9001-2012; Buchan, Alastair/B-9095-2009; Vanhooren, Geert/H-4433-2011; LEYS, Didier/G-2955-2016; bladin, chris/B-9136-2013; D'ESTE, CATHERINE/G-7392-2013; Attia, John/F-5376-2013; Davis, Stephen/L-5260-2013; Parsons, Mark/G-3750-2014; Hankey, Graeme /H-4968-2014 OI Donnan, Geoffrey/0000-0001-6324-3403; Kaste, Markku/0000-0001-6557-6412; Buchan, Alastair/0000-0002-2918-5200; Vanhooren, Geert/0000-0001-6818-9346; LEYS, Didier/0000-0003-4408-4392; Attia, John/0000-0001-9800-1308; Davis, Stephen/0000-0003-0962-2300; Hankey, Graeme /0000-0002-6044-7328 FU Boehringer Ingelheim; Lundbeck; Thrombogenics; Novo-Nordisk; Pfizer; Sanofi-Aventis FX KRL, RvK, DT, MK, and WH report honoraria from Boehringer Ingelheim for their roles in conduct of the ECASS trials. KRL reports honoraria from Lundbeck and Thrombogenics. DT reports honoraria from Novo-Nordisk, Pfizer, Sanofi-Aventis, and Boehringer Ingelheim. EB is an employee of Boehringer Ingelheim. RvK and JCG report being consultants to Lundbeck. GWA reports being a consultant to Lundbeck and Boehringer Ingelheiin. SMD reports honoraria from Boehringer Ingelheim. TGB, JRM, SAFI, BCT, and GAD declare that they have no conflicts of interest. NR 29 TC 877 Z9 912 U1 14 U2 68 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD MAY 15 PY 2010 VL 375 IS 9727 BP 1695 EP 1703 DI 10.1016/S0140-6736(10)60491-6 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 599DK UT WOS:000277890200031 PM 20472172 ER PT J AU Deyton, L Sharfstein, J Hamburg, M AF Deyton, Lawrence Sharfstein, Joshua Hamburg, Margaret TI Tobacco Product Regulation - A Public Health Approach SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Deyton, Lawrence] Ctr Tobacco Prod, Silver Spring, MD USA. [Sharfstein, Joshua; Hamburg, Margaret] US FDA, Dept Hlth & Human Serv, Silver Spring, MD USA. RP Deyton, L (reprint author), Ctr Tobacco Prod, Silver Spring, MD USA. NR 5 TC 36 Z9 36 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 MAY 13 PY 2010 VL 362 IS 19 BP 1753 EP 1756 DI 10.1056/NEJMp1004152 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 594RQ UT WOS:000277555500001 PM 20410498 ER PT J AU Narayanan, S Silva, R Peruzzi, G Alvarez, Y Simhadri, VR Debell, K Coligan, JE Borrego, F AF Narayanan, Sriram Silva, Rodolfo Peruzzi, Giovanna Alvarez, Yelina Simhadri, Venkateswara R. Debell, Karen Coligan, John E. Borrego, Francisco TI Human Th1 Cells That Express CD300a Are Polyfunctional and After Stimulation Up-Regulate the T-Box Transcription Factor Eomesodermin SO PLOS ONE LA English DT Article ID RECEPTOR IRP60 CD300A; IFN-GAMMA PRODUCTION; INHIBITORY RECEPTOR; INTERFERON-GAMMA; HELPER LYMPHOCYTES; LEISHMANIA-MAJOR; DENDRITIC CELLS; BET; DIFFERENTIATION; EFFECTOR AB Human naive CD4 T cells express low levels of the immunomodulatory receptor CD300a, whereas effector/memory CD4 cells can be either CD300a(+) or CD300a(-). This suggested that CD300a expression could define a specific subset within the effector/memory CD4 T cell subpopulations. In fact, ex vivo analysis of the IFN-gamma producing CD4 T cells showed that they are enriched in the CD300a(+) subset. Moreover, stimulated CD4 T cells producing TNF-alpha and IL-2 besides IFN-gamma (polyfunctional) are predominantly CD300a(+). In addition to producing markedly higher levels of Th1-associated cytokines, the stimulated CD300a(+) CD4 T cells are distinguished by a striking up-regulation of the T-box transcription factor eomesodermin (Eomes), whereas T-bet is up-regulated in both CD300a+ and CD300a(-) activated CD4 T cells to similar levels. The pleiotropic cytokine TGF-beta 1 has a determinant role in dictating the development of this Th1 subset, as its presence inhibits the expression of CD300a and down-regulates the expression of Eomes and IFN-gamma. We conclude that CD300a+ human Th1 cells tend to be polyfunctional and after stimulation up-regulate Eomes. C1 [Narayanan, Sriram; Silva, Rodolfo; Peruzzi, Giovanna; Alvarez, Yelina; Coligan, John E.] NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Rockville, MD USA. [Simhadri, Venkateswara R.; Debell, Karen; Borrego, Francisco] US FDA, Ctr Biol Evaluat & Res, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, Bethesda, MD USA. RP Narayanan, S (reprint author), NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Rockville, MD USA. EM Francisco.Borrego@fda.hhs.gov OI Narayanan, Sriram/0000-0002-6484-2800; Peruzzi, Giovanna/0000-0002-6517-9107 FU Food and Drug Administration (FDA); National Institute of Allergy and Infectious Diseases (NIAID) FX This work was supported by the intramural programs of Food and Drug Administration (FDA) and the National Institute of Allergy and Infectious Diseases (NIAID). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 22 Z9 22 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 13 PY 2010 VL 5 IS 5 AR e10636 DI 10.1371/journal.pone.0010636 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 595SN UT WOS:000277633500020 PM 20498708 ER PT J AU Chen, ML Shah, VP Ganes, D Midha, KK Caro, 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 Winkle, H Yu, L AF Chen, Mei-Ling Shah, Vinod P. Ganes, Derek Midha, Kamal K. Caro, 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 Winkle, Helen Yu, Lawrence TI Challenges and opportunities in establishing scientific and regulatory standards for assuring therapeutic equivalence of modified-release products: Workshop summary report SO EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE Bioequivalence; Therapeutic equivalence; Pharmaceutical equivalence; Interchangeability; Modified release; Partial area-under-the-curve ID BUPROPION AB Modified-release products are complex dosage forms designed to release drug in a controlled manner to achieve desired efficacy and safety. Inappropriate control of drug release from such products may result in reduced efficacy or increased toxicity. This workshop provided an opportunity for pharmaceutical scientists from academia, industry and regulatory agencies to discuss current regulatory expectations and industry practices for demonstrating pharmaceutical equivalence and bioequivalence of MR products, further facilitating the establishment of regulatory standards for ensuring therapeutic equivalence of these products. Published by Elsevier B.V. C1 [Chen, Mei-Ling] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Shah, Vinod P.; Midha, Kamal K.] FIP, The Hague, Netherlands. [Midha, Kamal K.] Univ Saskatchewan, Saskatoon, SK S7N 0W0, Canada. [Nambiar, Prabu] Vertex Pharmaceut Inc, Cambridge, MA USA. [Thombre, Avinash G.] Pfizer Inc, New York, NY USA. [Preskorn, Sheldon H.] Univ Kansas, Lawrence, KS 66045 USA. [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,Rm 4108, Silver Spring, MD 20993 USA. EM Meiling.Chen@fda.hhs.gov RI Yu, Lawrence/L-6280-2016; Preskorn, Sheldon/L-9839-2016 NR 10 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-0987 J9 EUR J PHARM SCI JI Eur. J. Pharm. Sci. PD MAY 12 PY 2010 VL 40 IS 2 BP 148 EP 153 DI 10.1016/j.ejps.2010.03.017 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 602UY UT WOS:000278165600010 PM 20347972 ER PT J AU Hayward, DG Pisano, TS Wong, JW Scudder, RJ AF Hayward, Douglas G. Pisano, Tamani S. Wong, Jon W. Scudder, Richard J. TI Multiresidue Method for Pesticides and Persistent Organic Pollutants (POPs) in Milk and Cream Using Comprehensive Two-Dimensional Capillary Gas Chromatography-Time-of-Flight Mass Spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Multiresidue methods; fat determination; persistent organic pollutant; pesticides; gel permeation chromatography; SPE; GC x GC-TOFMS; two-dimensional GC ID SOLID-PHASE EXTRACTION; GEL-PERMEATION CHROMATOGRAPHY; ELECTRON-CAPTURE DETECTION; VIRGIN OLIVE OIL; RESIDUES; CLEANUP; ORGANOCHLORINE; MATRICES; VEGETABLES; FRUITS AB A method for the analysis of pesticides and their metabolites including most of the persistent organic pollutants (POPs) in milk and cream is described. The method was single-laboratory validated through milk fortification in quadruplicate with 34 pesticides, isomers, and metabolites including 12 of the insecticide POPs and their metabolites. Whole cow's milk was fortified at 0.2, 0.4, 1, 2, 10, or 50 mu g/kg wet weight and extracted with acetone/cyclohexane/ethyl acetate (2:1:1) with the addition of Mg2SO4 and NaCl. Fat recovered in the extract accurately reflected the fat content of the milk or cream. All test portions were purified on a gel permeation chromatograph (GPC) followed by solid phase extraction (SPE) cleanup on a mixed bed graphitized carbon black (GCB) and primary/secondary amine silica gel (PSA) column before determination using a comprehensive two-dimensional gas chromatograph interfaced to a time-of-flight mass spectrometer. Average recoveries were 77, 72, 73, 66, 77, and 84% for 0.2, 0.4, 1, 2, 10, and 50 mu g/kg wet weight whole milk, respectively. The average relative standard deviations for 0.2, 0.4, 1, 2, 10, and 50 mu g/kg were 10, 8, 7, 7, 3, and 3%, respectively. The limits of quantification (LOQs) for all pesticides were 0.2 or 0.4 mu g/kg wet weight. An archived cream sample collected in 1982 on Oahu, Hawaii, was found to contain only hepatachlor epoxide (HE) and DDE-p,p' at 380 +/- 24 and 69 +/- 17 mu g/kg fat, significantly elevated over the current action level of 50 mu g/kg fat for HE. C1 [Hayward, Douglas G.; Wong, Jon W.] US FDA, College Pk, MD 20740 USA. [Pisano, Tamani S.] Univ Maryland, College Pk, MD 20740 USA. [Scudder, Richard J.] Hawaii Heptachlor Res & Educ Fdn, Honolulu, HI 96813 USA. RP Hayward, DG (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. FU Hawaii Heptachlor Research and Education Foundation (HHR&EF.), Oahu, Hawaii FX We thank the Hawaii Heptachlor Research and Education Foundation (HHR&EF.), Oahu, Hawaii. We also thank the U.S. Environmental Protection Agency National Pesticide Standard Repository (Et. Meade, MD) and, especially. Theresa Cole for providing pesticide standards used in this study. NR 37 TC 8 Z9 9 U1 1 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 EI 1520-5118 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAY 12 PY 2010 VL 58 IS 9 BP 5248 EP 5256 DI 10.1021/jf100021p PG 9 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 590OW UT WOS:000277237500006 PM 20441225 ER PT J AU Lanthier, ML Sridhara, R Johnson, JR Farrell, A Keegan, P Justice, R Pazdur, R AF Lanthier, Michael L. Sridhara, Rajeshwari Johnson, John R. Farrell, Ann Keegan, Patricia Justice, Robert Pazdur, Richard TI Accelerated Approval and Oncology Drug Development Timelines SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 [Lanthier, Michael L.] US FDA, Off Planning, Off Commissioner, Rockville, MD 20857 USA. [Sridhara, Rajeshwari] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Johnson, John R.; Farrell, Ann; Keegan, Patricia; Justice, Robert; Pazdur, Richard] US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Lanthier, ML (reprint author), US FDA, Off Planning, Off Commissioner, Rockville, MD 20857 USA. NR 5 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 10 PY 2010 VL 28 IS 14 BP E226 EP E227 DI 10.1200/JCO.2009.26.2121 PG 2 WC Oncology SC Oncology GA 592OT UT WOS:000277389600031 PM 20194846 ER PT J AU Rubinstein, LV Steinberg, SM Kummar, S Kinders, R Parchment, RE Murgo, AJ Tomaszewski, JE Doroshow, JH AF Rubinstein, Larry V. Steinberg, Seth M. Kummar, Shivaani Kinders, Robert Parchment, Ralph E. Murgo, Anthony J. Tomaszewski, Joseph E. Doroshow, James H. TI The statistics of phase 0 trials SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Annual Conference on Statistical Issues in Clinical Trials-Early, Translational and Proof of Concept Studies - The Go/No Go Decisions CY APR 08, 2008 CL Philadelphia, PA DE first-in-man study; PD-driven phase 0 trial; pharmacodynamic assay; phase 1 clinical trial; phase 2 clinical trial ID CLINICAL-TRIALS; DRUG DEVELOPMENT; ADVANCED MALIGNANCIES; TUMOR SIZE; END-POINT; CANCER; INHIBITOR; ABT-888 AB The PD-driven phase 0 trial is a new form, designed to be a first-in-man study, often of a new agent, conducted to assess drug effect on a molecular target, by means of a pharmacodynamic (PD) assay, in a very small number (10-15) of patients. Such a study is meant to be a proof of principle trial to determine whether the agent yields the PD effect predicted by pre-clinical studies. The dosage is meant to be pharmacologically active, but is neither toxic nor likely to yield clinical benefit. Such a trial may be used to serve as a very early test of an agent's biologic effect, allowing for early weeding out of ineffective agents, or as an early means of determining the most promising of competing analogue agents. This manuscript will present designs for such PD-driven studies that are statistically efficient and rigorous, focusing on non-comparative trials. The phase 0 trial promises to become an increasingly important tool for facilitating and speeding the development of new therapeutic agents, particularly in oncology. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Rubinstein, Larry V.; Tomaszewski, Joseph E.; Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Steinberg, Seth M.; Kummar, Shivaani; Doroshow, James H.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Kinders, Robert; Parchment, Ralph E.] NCI, Lab Human Toxicol & Pharmacol, Appl Dev Res Support Directorate, SAIC Frederick Inc, Frederick, MD 21702 USA. [Murgo, Anthony J.] US FDA, Off Oncol Drug Prod, Silver Spring, MD USA. RP Rubinstein, LV (reprint author), NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. EM rubinsteinl@ctep.nci.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 10 TC 11 Z9 12 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAY 10 PY 2010 VL 29 IS 10 BP 1072 EP 1076 DI 10.1002/sim.3840 PG 5 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 597DI UT WOS:000277735900003 PM 20419759 ER PT J AU Nie, L Soon, G AF Nie, Lei Soon, Guoxing TI A covariate-adjustment regression model approach to noninferiority margin definition SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Annual Conference on Statistical Issues in Clinical Trials-Early, Translational and Proof of Concept Studies - The Go/No Go Decisions CY APR 08, 2008 CL Philadelphia, PA DE constancy assumption; fixed margin approach; generalized linear model; noninferiority margin; synthesis method ID NON-INFERIORITY TRIALS; ACTIVE-CONTROL TRIALS; PLACEBO-CONTROLLED TRIALS; CLINICAL-TRIALS; ISSUES; EQUIVALENCE; DESIGN; CHOICE; DELTA AB To maintain the interpretability of the effect of experimental treatment (EXP) obtained from a noninferiority trial, current statistical approaches often require the constancy assumption. This assumption typically requires that the control treatment effect in the population of the active control trial is the same as its effect presented in the population of the historical trial. To prevent constancy assumption violation, clinical trial sponsors were recommended to make sure that the design of the active control trial is as close to the design of the historical trial as possible. However, these rigorous requirements are rarely fulfilled in practice. The inevitable discrepancies between the historical trial and the active control trial have led to debates on many controversial issues. Without support from a well-developed quantitative method to determine the impact of the discrepancies on the constancy assumption violation, a correct judgment seems difficult. In this paper, we present a covariate-adjustment generalized linear regression model approach to achieve two goals: (1) to quantify the impact of population difference between the historical trial and the active control trial on the degree of constancy assumption violation and (2) to redefine the active control treatment effect in the active control trial population if the quantification suggests an unacceptable violation. Through achieving goal (1), we examine whether or not a population difference leads to an unacceptable violation. Through achieving goal (2), we redefine the noninferiority margin if the violation is unacceptable. This approach allows us to correctly determine the effect of EXP in the noninferiority trial population when constancy assumption is violated due to the population difference. We illustrate the covariate-adjustment approach through a case study. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Nie, Lei; Soon, Guoxing] US FDA, Div Biometr 4, Off Biometr, OTS,CDER, Silver Spring, MD 20993 USA. RP Soon, G (reprint author), 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM guoxing.soon@fda.hhs.gov FU PHS HHS [RSR-09-14] NR 27 TC 9 Z9 9 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAY 10 PY 2010 VL 29 IS 10 BP 1107 EP 1113 DI 10.1002/sim.3871 PG 7 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 597DI UT WOS:000277735900007 PM 20209669 ER PT J AU Unger, EF Thompson, AM Temple, R AF Unger, Ellis F. Thompson, Aliza M. Temple, Robert TI Reevaluating Erythropoiesis-Stimulating Agents REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID CHRONIC KIDNEY-DISEASE; EPOETIN; ALPHA C1 [Unger, Ellis F.; Thompson, Aliza M.; Temple, Robert] US FDA, Silver Spring, MD USA. RP Unger, EF (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 MAY 6 PY 2010 VL 362 IS 18 BP 1743 EP 1744 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 591OQ UT WOS:000277311200025 ER PT J AU Panteleev, MA Balandina, AN Lipets, EN Ovanesov, MV Ataullakhanov, FI AF Panteleev, Mikhail A. Balandina, Anna N. Lipets, Elena N. Ovanesov, Mikhail V. Ataullakhanov, Fazoil I. TI Task-Oriented Modular Decomposition of Biological Networks: Trigger Mechanism in Blood Coagulation SO BIOPHYSICAL JOURNAL LA English DT Article ID CIRCULATING TISSUE FACTOR; SPATIOTEMPORAL DYNAMICS; THROMBIN GENERATION; MATHEMATICAL-MODEL; CLOT STRUCTURE; HEAT-SHOCK; PROTEIN-C; INITIATION; SURFACE; PLASMA AB Analysis of complex time-dependent biological networks is an important challenge in the current postgenomic era. We propose a middle-out approach for decomposition and analysis of complex time-dependent biological networks based on: 1), creation of a detailed mechanism-driven mathematical model of the network; 2), network response decomposition into several physiologically relevant subtasks; and 3), subsequent decomposition of the model, with the help of task-oriented necessity and sensitivity analysis into several modules that each control a single specific subtask, which is followed by further simplification employing temporal hierarchy reduction. The technique is tested and illustrated by studying blood coagulation. Five subtasks (threshold, triggering, control by blood flow velocity, spatial propagation, and localization), together with responsible modules, can be identified for the coagulation network. We show that the task of coagulation triggering is completely regulated by a two-step pathway containing a single positive feedback of factor V activation by thrombin. These theoretical predictions are experimentally confirmed by studies of fibrin generation in normal, factor V-, and factor VIII-deficient plasmas. The function of the factor V-dependent feedback is to minimize temporal and parametrical intervals of fibrin clot instability. We speculate that this pathway serves to lessen possibility of fibrin clot disruption by flow and subsequent thromboembolism. C1 [Panteleev, Mikhail A.; Balandina, Anna N.; Lipets, Elena N.; Ataullakhanov, Fazoil I.] Russian Acad Sci, Ctr Theoret Problems Physicochem Pharmacol, Moscow, Russia. [Panteleev, Mikhail A.; Ataullakhanov, Fazoil I.] Russian Acad Med Sci, Natl Res Ctr Hematol, Moscow, Russia. [Ovanesov, Mikhail V.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Ataullakhanov, Fazoil I.] Moscow MV Lomonosov State Univ, Dept Phys, Moscow, Russia. RP Panteleev, MA (reprint author), Russian Acad Sci, Ctr Theoret Problems Physicochem Pharmacol, Moscow, Russia. EM mapanteleev@yandex.ru RI Ataullakhanov, Fazoil/J-8076-2012; Panteleev, Mikhail/H-5491-2012; OI Panteleev, Mikhail/0000-0002-8128-7757; Balandina, Anna/0000-0002-7032-695X FU Russian Academy of Sciences; Russian Foundation for Basic Research [09-04-0232, 09-04-00357, 09-04-92427, 09-02-00018]; Russian Federation [MK-155.2010.4] FX The study was supported by Russian Academy of Sciences Presidium Basic Research Programs' Molecular and Cellular Biology and Basic Sciences for Medicine, by Russian Foundation for Basic Research grant Nos. 09-04-0232, 09-04-00357, 09-04-92427, and 09-02-00018, and by the Russian Federation President Grant for Young Scientists MK-155.2010.4. NR 41 TC 18 Z9 21 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAY 5 PY 2010 VL 98 IS 9 BP 1751 EP 1761 DI 10.1016/j.bpj.2010.01.027 PG 11 WC Biophysics SC Biophysics GA 592KH UT WOS:000277377300008 PM 20441738 ER PT J AU Urschitz, J Kawasumi, M Owens, J Morozumi, K Yamashiro, H Stoytchev, I Marh, J Dee, JA Kawamoto, K Coates, CJ Kaminski, JM Pelczar, P Yanagimachi, R Moisyadi, S AF Urschitz, Johann Kawasumi, Miyuri Owens, Jesse Morozumi, Kazuto Yamashiro, Hideaki Stoytchev, Ilko Marh, Joel Dee, James A. Kawamoto, Kris Coates, Craig J. Kaminski, Joseph M. Pelczar, Pawel Yanagimachi, Ryuzo Moisyadi, Stefan TI Helper-independent piggyBac plasmids for gene delivery approaches: Strategies for avoiding potential genotoxic effects SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gene therapy; transfection; transgenesis; transposase; transposon ID SLEEPING-BEAUTY; MAMMALIAN-CELLS; STEM-CELLS; IN-VIVO; TRANSPOSON; GENOME; VERTEBRATES; EFFICIENT; THERAPY AB Efficient integration of functional genes is an essential prerequisite for successful gene delivery such as cell transfection, animal transgenesis, and gene therapy. Gene delivery strategies based on viral vectors are currently the most efficient. However, limited cargo capacity, host immune response, and the risk of insertional mutagenesis are limiting factors and of concern. Recently, several groups have used transposon-based approaches to deliver genes to a variety of cells. The piggyBac(pB) transposase in particular has been shown to be well suited for cell transfection and gene therapy approaches because of its flexibility for molecular modification, large cargo capacity, and high transposition activity. However, safety considerations regarding transposase gene insertions into host genomes have rarely been addressed. Here we report our results on engineering helper-independent pB plasmids. The single-plasmid gene delivery system carries both the piggyBac transposase (pBt) expression cassette as well as the transposon cargo flankedby terminal repeat element sequences. Improvements to the helper-independent structure were achieved by developing new plasmids in which the pBt gene is rendered inactive after excision of the transposon from the plasmid. As a consequence, potentially negative effects that may develop by the persistence of an active pBt gene posttransposition are eliminated. The results presented herein demonstrate that our helper-independent plasmids represent an important step in the development of safe and efficient gene delivery methods that should prove valuable in gene therapy and transgenic approaches. C1 [Urschitz, Johann; Kawasumi, Miyuri; Owens, Jesse; Morozumi, Kazuto; Yamashiro, Hideaki; Stoytchev, Ilko; Marh, Joel; Dee, James A.; Kawamoto, Kris; Yanagimachi, Ryuzo; Moisyadi, Stefan] Univ Hawaii, John A Burns Sch Med, Dept Anat Biochem & Physiol, Honolulu, HI 96822 USA. [Kawasumi, Miyuri] Keio Univ, Ctr Integrated Med Res, Tokyo 1608582, Japan. [Morozumi, Kazuto] Int Univ Hlth & Welf, Sanno Hosp, Tokyo 1070052, Japan. [Coates, Craig J.] Texas A&M Univ, Dept Entomol, College Stn, TX 77843 USA. [Coates, Craig J.; Pelczar, Pawel; Moisyadi, Stefan] Manoa BioSci, Honolulu, HI 96819 USA. [Kaminski, Joseph M.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Pelczar, Pawel] Univ Zurich, Inst Lab Anim Sci, CH-8091 Zurich, Switzerland. RP Moisyadi, S (reprint author), Univ Hawaii, John A Burns Sch Med, Dept Anat Biochem & Physiol, Honolulu, HI 96822 USA. EM yana@hawaii.edu; moisyadi@hawaii.edu FU National Center for Research Resources; National Institutes of Health [5P20RR016467-07, PAR-07-229, R01 GM083158-01A1, U54RR014607-09] FX We thank Dr. Malcolm J. Fraser for providing us with the insect piggyBac construct and piggyBac antibody, Dr. Junichi Miyazaki for the CAG promoter, Dr. Allen Bradley for the mouse codon-optimized piggyBac plasmid and Dr. Ming-Li Wang for help with the GATEWAY recombineering system. This work was initially supported by the National Center for Research Resources and the National Institutes of Health Grant 5P20RR016467-07 and is currently supported by National Institutes of Health Grants PAR-07-229 and R01 GM083158-01A1. Additional support came from National Institutes of Health Grant U54RR014607-09 (J. U.). NR 19 TC 33 Z9 41 U1 0 U2 4 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 MAY 4 PY 2010 VL 107 IS 18 BP 8117 EP 8122 DI 10.1073/pnas.1003674107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 591OK UT WOS:000277310400016 PM 20404201 ER PT J AU Kuselman, I Pennecchi, F Burns, C Fajgelj, A de Zorzi, P AF Kuselman, Ilya Pennecchi, Francesca Burns, Cathy Fajgelj, Ales de Zorzi, Paolo TI Investigating out-of-specification test results of chemical composition based on metrological concepts SO ACCREDITATION AND QUALITY ASSURANCE LA English DT Article DE Out-of-specification test results; Validation; Measurement uncertainty; Metrological traceability; Probability AB A metrological background for investigating out-of-specification (OOS) test results of chemical composition is discussed. When an OOS test result is identified, it is important to determine its root causes and to avoid reoccurrence of such results. An investigation of the root causes based on metrological concepts would be beneficial. It includes (1) assessment of validation data of the measurement process, (2) evaluation of the measurement uncertainty contributions, and (3) assessment of metrological traceability chains critical for measurement parameters and environmental conditions influencing the test results. The questions, how can the validation data be applied for this investigation, and how can measurement uncertainty contributions and/or metrological traceability chains change a probability of OOS test results, are analyzed. C1 [Kuselman, Ilya] INPL, IL-91904 Jerusalem, Israel. [Pennecchi, Francesca] Ist Nazl Ric Metrol INRIM, I-10135 Turin, Italy. [Burns, Cathy] US FDA, Denver, CO 80225 USA. [Fajgelj, Ales] IAEA, A-1400 Vienna, Austria. [de Zorzi, Paolo] ISPRA, I-00128 Rome, Italy. RP Kuselman, I (reprint author), INPL, IL-91904 Jerusalem, Israel. EM ilya.kuselman@moital.gov.il RI Pennecchi, Francesca/G-9812-2015 OI Pennecchi, Francesca/0000-0003-1328-3858 NR 37 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0949-1775 J9 ACCREDIT QUAL ASSUR JI Accredit. Qual. Assur. PD MAY PY 2010 VL 15 IS 5 BP 283 EP 288 DI 10.1007/s00769-009-0618-4 PG 6 WC Chemistry, Analytical; Instruments & Instrumentation SC Chemistry; Instruments & Instrumentation GA 590LI UT WOS:000277227200003 ER PT J AU Bezabeh, S Flowers, CM Kortepeter, C Avigan, M AF Bezabeh, S. Flowers, C. M. Kortepeter, C. Avigan, M. TI Clinically significant liver injury in patients treated with natalizumab SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID HEPATITIS-B; DISEASE; INFLIXIMAB; REACTIVATION; TRANSPLANT; THERAPY AB P>Background Natalizumab is a recombinant monoclonal antibody approved for the treatment of patients with multiple sclerosis and patients with Crohn's disease. Because of its immunosuppressive effects, natalizumab has been associated with a number of atypical and opportunistic infections. Aim To describe and summarize six spontaneously reported post-marketing cases of clinically significant drug induced-liver injury associated with natalizumab use. Methods The FDA maintains a database of adverse event reports (AERS). We searched the AERS database for reports of serious liver injury associated with natalizumab use from November 2004, when the drug was approved, through 30 June 2008. Results The search resulted in six spontaneously reported post-marketing cases of severe drug-induced liver injury. Four of six patients developed liver injury with elevations of serum transaminases and hyperbilirubinemia after only a single infusion of natalizumab. One of these patients experienced repeated increases of aminotransferases and bilirubin when natalizumab was re-administered. Conclusions Serious hepatic injury may occur in association with natalizumab use. Health professionals should be alerted to possible serious liver injury in patients receiving natalizumab. C1 [Bezabeh, S.; Flowers, C. M.; Kortepeter, C.; Avigan, M.] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Bezabeh, S (reprint author), US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Room 2470, Silver Spring, MD 20993 USA. EM Shewit.Bezabeh@FDA.HHS.gov NR 14 TC 30 Z9 31 U1 0 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD MAY 1 PY 2010 VL 31 IS 9 BP 1028 EP 1035 DI 10.1111/j.1365-2036.2010.04262.x PG 8 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 579GL UT WOS:000276356900011 PM 20163378 ER PT J AU Min, SS Turner, JR Nada, A DiMino, TL Hynie, I Kleiman, R Kowey, P Krucoff, MW Mason, JW Phipps, A Newton-Cheh, C Pordy, R Strnadova, C Targum, S Uhl, K Finkle, J AF Min, Sherene S. Turner, J. Rick Nada, Adel DiMino, Tara L. Hynie, Ivo Kleiman, Robert Kowey, Peter Krucoff, Mitchell W. Mason, Jay W. Phipps, Alex Newton-Cheh, Christopher Pordy, Robert Strnadova, Colette Targum, Shari Uhl, Kathleen Finkle, John TI Evaluation of ventricular arrhythmias in early clinical pharmacology trials and potential consequences for later development SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY HEART-DISEASE; MITRAL-VALVE-PROLAPSE; QT INTERVAL PROLONGATION; SPONTANEOUS VARIABILITY; AMBULATORY ELECTROCARDIOGRAPHY; PROGNOSTIC-SIGNIFICANCE; PREMATURE COMPLEXES; ELDERLY POPULATION; PSYCHOLOGIC STRESS; HEALTHY-SUBJECTS AB This white paper, prepared by members of the Cardiac Safety Research Consortium, discusses several important issues regarding the evaluation of ventricular arrhythmias in early clinical pharmacology trials and their potential consequences for later clinical drug development. Ventricular arrhythmias are infrequent but potentially important medical events whose occurrence in early clinical pharmacology trials can dramatically increase safety concerns. Given the increasing concern with all potential safety signals and the resultant more extensive electrocardiographic monitoring of subjects participating in early phase trials, an important question must be addressed: Are relatively more frequent observations of ventricular arrhythmias related simply to more extensive monitoring, or are they genuinely related to the drug under development? The discussions in this paper provide current thinking and suggestions for addressing this question. (Am Heart J 2010; 159: 716-29.) C1 [Min, Sherene S.] GlaxoSmithKline, Med Dev Ctr, Res Triangle Pk, NC 27709 USA. [Min, Sherene S.; DiMino, Tara L.; Finkle, John] GlaxoSmithKline, Philadelphia, PA USA. [Turner, J. Rick] Quintiles, Res Triangle Pk, NC USA. [Nada, Adel] Abbott Labs, Waukegan, IL USA. [Hynie, Ivo; Strnadova, Colette] Hlth Canada, Ottawa, ON K1A 0L2, Canada. [Kleiman, Robert] ERT, Philadelphia, PA USA. [Kowey, Peter] Lankenau Inst Med Res, Wynnewood, PA USA. [Krucoff, Mitchell W.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Mason, Jay W.] Univ Utah, Div Cardiol, Salt Lake City, UT 84112 USA. [Phipps, Alex] Pfizer Ltd, Sandwich CT13 9NJ, Kent, England. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Pordy, Robert] Hoffmann La Roche Inc, Nutley, NJ 07110 USA. [Targum, Shari; Uhl, Kathleen] US FDA, Rockville, MD 20857 USA. RP Min, SS (reprint author), GlaxoSmithKline, Med Dev Ctr, 5 Moore Dr, Res Triangle Pk, NC 27709 USA. EM sherene.s.min@gsk.com NR 70 TC 10 Z9 11 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD MAY PY 2010 VL 159 IS 5 BP 716 EP 729 DI 10.1016/j.ahj.2010.02.004 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 590QY UT WOS:000277243300004 PM 20435178 ER PT J AU Lu, M Cohen, MH Rieves, D Pazdur, R AF Lu, Min Cohen, Martin H. Rieves, Dwaine Pazdur, Richard TI FDA report: Ferumoxytol for intravenous iron therapy in adult patients with chronic kidney disease SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; CHRONIC-RENAL-FAILURE; ORAL IRON; PREDIALYSIS PATIENTS; DIALYSIS PATIENTS; ANEMIA; SAFETY; SUPPLEMENTATION; EFFICACY; SUCROSE AB On June 30, 2009, the United States Food and Drug Administration (FDA) approved ferumoxytol (Feraheme (R) injection, AMAG Pharmaceuticals), an iron-containing product for intravenous (IV) administration, for the treatment of iron deficiency anemia in adult patients with chronic kidney disease (CKD). The safety and efficacy of ferumoxytol were assessed in three randomized, open-label, controlled clinical trials. Two trials evaluated patients with nondialysis dependent CKD and a third trial assessed patients undergoing hemodialysis. Randomization was either to ferumoxytol or oral iron. Ferumoxytol was administered as two 510 mg IV injections, separated by 3-8 days. Oral iron, Ferro-Sequels (R), was administered at a dose of 100 mg twice daily for 21 days. In all three clinical trials, ferumoxytol administration increased the mean blood hemoglobin (Hgb) concentrations by similar to 1.0 g/dL over the 35 day period, a mean increase that was greater than what was observed in patients receiving oral iron. Patients receiving ferumoxytol also had increases in blood transferrin saturation (TSAT) and ferritin values. For the proposed ferumoxytol dosing regimen, 4.9% of patients had serum ferritin >= 800 ng/mL and TSAT >= 50% post-treatment. The most important ferumoxytol safety concerns were hypersensitivity reactions and/or hypotension. Anaphylaxis or anaphylactoid reactions were reported in 0.2% of subjects, and other adverse reactions potentially associated with hypersensitivity (e.g., pruritus, rash, urticaria, or wheezing) were reported in 3.7%. Hypotension was observed in 1.9%, including three patients with serious hypotensive reactions. Ferumoxytol administration may transiently affect the diagnostic ability of magnetic resonance imaging and the drug label provides further information regarding this effect. Am. J. Hematol. 85:315-319, 2010. Published 2010 Wiley-Liss, Inc.(dagger) C1 [Lu, Min; Cohen, Martin H.; Rieves, Dwaine; Pazdur, Richard] US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. RP Lu, M (reprint author), US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20903 USA. EM min.lu@fda.hhs.gov NR 34 TC 133 Z9 135 U1 1 U2 25 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2010 VL 85 IS 5 BP 315 EP 319 DI 10.1002/ajh.21656 PG 5 WC Hematology SC Hematology GA 591SY UT WOS:000277325800003 PM 20201089 ER PT J AU Ye, HP Hill, J Kauffman, J Han, XL AF Ye, Hongping Hill, John Kauffman, John Han, Xianlin TI Qualitative and quantitative comparison of brand name and generic protein pharmaceuticals using isotope tags for relative and absolute quantification and matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE iTRAQ/MALDI-MS; Somavert; Miacalcin; Somatropin; GIST; Generic protein drugs ID HUMAN GROWTH-HORMONE; HUMAN PITUITARY EXTRACTS; ESCHERICHIA-COLI; GH-DEFICIENCY; PROTEOMICS; VARIANTS; PEPTIDE; TECHNOLOGY; ANTIBODIES; SOMATROPIN AB The capability of iTRAQ (isotope tags for relative and absolute quantification) reagents coupled with matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS) as a qualitative and quantitative technique for the analysis of complicated protein pharmaceutical mixtures was evaluated. Mixtures of Somavert and Miacalcin with a small amount of bovine serum albumin (BSA) as an impurity were analyzed. Both Somavert and Miacalcin were qualitatively identified, and BSA was detected at levels as low as 0.8 mol%. Genotropin and Somavert were compared in a single experiment, and all of the distinct amino acid residues from the two proteins were readily identified. Four somatropin drug products (Genotropin, Norditropin, Jintropin, and Omnitrope) were compared using the iTRAQ/MALDI-MS method to determine the similarity between their primary structures and quantify the amount of protein in each product. All four product samples were well labeled and successfully compared when a filtration cleanup step preceded iTRAQ labeling. The quantitative accuracy of the iTRAQ method was evaluated. In all cases, the accuracy of experimentally determined protein ratios was higher than 90%, and the relative standard deviation (RSD) was less than 10%. The iTRAQ and global internal standard technology (GIST) methods were compared, and the iTRAQ method provided both higher sequence coverage and enhanced signal intensity. Published by Elsevier Inc. C1 [Ye, Hongping; Kauffman, John] US FDA, Ctr Drug Evaluat & Res, DPA, St Louis, MO 63101 USA. [Hill, John] US FDA, Ctr Drug Evaluat & Res, Off New Drug Qual Assessment, DPMA 1, Silver Spring, MD 20993 USA. [Han, Xianlin] Washington Univ, Sch Med, Dept Internal Med, Div Bioorgan Chem & Mol Pharmacol, St Louis, MO 63110 USA. RP Ye, HP (reprint author), US FDA, Ctr Drug Evaluat & Res, DPA, St Louis, MO 63101 USA. EM hongping.ye@fda.hhs.gov FU Center for Drug Evaluation and Research (CDER) Regulatory Science and Review (RSR) [06-03] FX This work was supported by the Center for Drug Evaluation and Research (CDER) Regulatory Science and Review (RSR) Enhancement Program (06-03). The authors thank Lucinda Buhse for helpful discussions and review. NR 38 TC 9 Z9 9 U1 2 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD MAY 1 PY 2010 VL 400 IS 1 BP 46 EP 55 DI 10.1016/j.ab.2010.01.012 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 572NT UT WOS:000275840400006 PM 20074539 ER PT J AU Yang, MH Bruck, HA Kostov, Y Rasooly, A AF Yang, Minghui Bruck, Hugh Alan Kostov, Yordan Rasooly, Avraham TI Biological Semiconductor Based on Electrical Percolation SO ANALYTICAL CHEMISTRY LA English DT Article ID STAPHYLOCOCCAL-ENTEROTOXIN-B; CARBON NANOTUBES; ATOPIC-DERMATITIS; REAL-TIME; RHEUMATOID-ARTHRITIS; FOOD; BIOSENSOR; FUNCTIONALIZATION; SUPERANTIGENS; IMMUNOASSAY AB We have developed a novel biological semiconductor (BSC) based on electrical percolation through a multilayer three-dimensional carbon nanotube-antibody bionano-composite network, which can measure biological interactions directly and electronically. In electrical percolation, the passage of current through the conductive network is dependent upon the continuity of the network. Molecular interactions, such as binding of antigens to the antibodies, disrupt the network continuity causing increased resistance of the network. A BSC is fabricated by immobilizing a prefunctionalized single-walled carbon nanotubes (SWNTs)-antibody bionanocomposite directly on a poly(methyl methacrylate) (PMMA) surface (also known as plexiglass or acrylic). We used the BSC for direct (label-free) electronic measurements of antibody-antigen binding, showing that, at slightly above the electrical percolation threshold of the network, binding of a specific antigen dramatically increases the electrical resistance. Using anti-staphylococcal enterotoxin B (SEB) IgG as a "gate" and SEB as an "actuator", we demonstrated that the BSC was able to detect SEB at concentrations of 1 ng/mL. The new BSCs may permit assembly of multiple sensors on the same chip to create "biological central processing units (CPUs)" with multiple BSC elements, capable of processing and sorting out information on multiple analytes simultaneously. C1 [Rasooly, Avraham] US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. [Yang, Minghui; Kostov, Yordan] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Bruck, Hugh Alan] Univ Maryland, College Pk, MD 20742 USA. [Yang, Minghui] Univ Jinan, Sch Chem & Chem Engn, Jinan 250022, Peoples R China. [Rasooly, Avraham] NCI, Bethesda, MD 20892 USA. RP Rasooly, A (reprint author), US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. EM rasoolya@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 50 TC 8 Z9 8 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD MAY 1 PY 2010 VL 82 IS 9 BP 3567 EP 3572 DI 10.1021/ac902644z PG 6 WC Chemistry, Analytical SC Chemistry GA 590GO UT WOS:000277213400028 PM 20361741 ER PT J AU David, SAW Volokhov, DV Ye, ZP Chizhikov, V AF David, Selwyn A. Wilson Volokhov, Dmitriy V. Ye, Zhiping Chizhikov, Vladimir TI Evaluation of Mycoplasma Inactivation during Production of Biologics: Egg-Based Viral Vaccines as a Model SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID PATHOGEN-FREE CHICKENS; INFLUENZA-VIRUS; SELECTIVE INACTIVATION; BETA-PROPIOLACTONE; CELL-CULTURES; EMBRYOS; HEMAGGLUTININ; PATIENT; HOMINIS; IMMUNOGENICITY AB Although mycoplasmas are generally considered to be harmless commensals, some mycoplasma species are able to cause infections in pediatric, geriatric, or immunocompromised patients. Thus, accidental contamination of biologics with mycoplasmas represents a potential risk for the health of individuals who receive cell-derived biological and pharmaceutical products. To assess the efficiency of inactivation of mycoplasmas by the agents used in the manufacture of egg-derived influenza vaccines, we carried out a series of experiments aimed at monitoring the viability of mycoplasmas spiked into both chicken allantoic fluid and protein-rich microbiological media and then treated with beta-propiolactone, formalin, cetyltrimethylammonium bromide, Triton X-100, and sodium deoxycholate, which are agents that are commonly used for virus inactivation and disruption of viral particles during influenza vaccine production. Twenty-two mycoplasma species (with one to four strains of each species) were exposed to these inactivating agents at different concentrations. The most efficient inactivation of the mycoplasmas evaluated was observed with either 0.5% Triton X-100 or 0.5% sodium deoxycholate. Cetyltrimethylammonium bromide at concentrations of >= 0.08% was also able to rapidly inactivate (in less than 30 min) all mycoplasmas tested. In contrast, negligible reductions in mycoplasma titers were observed with 0.0125 to 0.025% formaldehyde. However, increasing the concentration of formaldehyde to 0.1 to 0.2% improved the mycoplasmacidal effect. Incubation of mycoplasmas with 0.1% beta-propiolactone for 1 to 24 h had a marked mycoplasmacidal effect. A comparison of the mycoplasma inactivation profiles showed that strains of selected species (Mycoplasma synoviae, Mycoplasma gallisepticum, Mycoplasma orale, Mycoplasma pneumoniae, and Acholeplasma laidlawii) represent a set of strains that can be utilized to validate the effectiveness of mycoplasma clearance obtained by inactivation and viral purification processes used for the manufacture of an inactivated egg-based vaccine. C1 [Volokhov, Dmitriy V.] US FDA, Ctr Biol Evaluat & Res, Off Vaccine Res & Review, Div Viral Prod,Lab Methods Dev, Rockville, MD 20852 USA. RP Volokhov, DV (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Vaccine Res & Review, Div Viral Prod,Lab Methods Dev, HFM 470,1401 Rockville Pike, Rockville, MD 20852 USA. EM dmitriy.volokhov@fda.hhs.gov NR 59 TC 8 Z9 9 U1 0 U2 5 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 MAY PY 2010 VL 76 IS 9 BP 2718 EP 2728 DI 10.1128/AEM.02776-09 PG 11 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 586KP UT WOS:000276907400005 PM 20228111 ER PT J AU DePaola, A Jones, JL Woods, J Burkhardt, W Calci, KR Krantz, JA Bowers, JC Kasturi, K Byars, RH Jacobs, E Williams-Hill, D Nabe, K AF DePaola, Angelo Jones, Jessica L. Woods, Jacquelina Burkhardt, William, III Calci, Kevin R. Krantz, Jeffrey A. Bowers, John C. Kasturi, Kuppuswamy Byars, Robin H. Jacobs, Emily Williams-Hill, Donna Nabe, Khamphet TI Bacterial and Viral Pathogens in Live Oysters: 2007 United States Market Survey SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID NORWALK-LIKE VIRUS; REAL-TIME PCR; VIBRIO-PARAHAEMOLYTICUS INFECTIONS; BIVALVE MOLLUSCAN SHELLFISH; REVERSE TRANSCRIPTION-PCR; HEPATITIS-A VIRUS; ESCHERICHIA-COLI; ENTERIC VIRUSES; COASTAL WATERS; CHESAPEAKE BAY AB Two samples of market oysters, primarily from retail establishments, were collected twice each month in each of nine states during 2007. Samples were shipped refrigerated overnight to five U. S. Food and Drug Administration laboratories on a rotating basis and analyzed by most probable number (MPN) for total and pathogenic Vibrio parahaemolyticus and V. vulnificus numbers and for the presence of toxigenic V. cholerae, Salmonella spp., norovirus (NoV), and hepatitis A virus (HAV). Levels of indicator organisms, including fecal coliforms (MPN), Escherichia coli (MPN), male-specific bacteriophage, and aerobic plate counts, were also determined. V. parahaemolyticus and V. vulnificus levels were distributed seasonally and geographically by harvest region and were similar to levels observed in a previous study conducted in 1998-1999. Levels of pathogenic V. parahaemolyticus were typically several logs lower than total V. parahaemolyticus levels regardless of season or region. Pathogenic V. parahaemolyticus levels in the Gulf and Mid-Atlantic regions were about two logs greater than the levels observed in the Pacific and North Atlantic regions. Pathogens generally associated with fecal pollution were detected sporadically or not at all (toxigenic V. cholerae, 0%; Salmonella, 1.5%; NoV, 3.9%; HAV, 4.4%). While seasonal prevalences of NoV and HAV were generally greater in oysters harvested from December to March, the low detection frequency obscured any apparent seasonal effects. Overall, there was no relationship between the levels of indicator microorganisms and the presence of enteric viruses. These data provide a baseline that can be used to further validate risk assessment predictions, determine the effectiveness of new control measures, and compare the level of protection provided by the U. S. shellfish sanitation system to those in other countries. C1 [DePaola, Angelo; Jones, Jessica L.; Woods, Jacquelina; Burkhardt, William, III; Calci, Kevin R.; Krantz, Jeffrey A.] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. [Bowers, John C.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Kasturi, Kuppuswamy] US FDA, NE Reg Lab, New York, NY 11433 USA. [Byars, Robin H.; Jacobs, Emily] US FDA, SE Reg Lab, Atlanta, GA 30309 USA. [Williams-Hill, Donna] US FDA, Pacific Reg Lab SW, Atlanta, GA 30309 USA. [Nabe, Khamphet] US FDA, Pacific Reg Lab NW, Bothell, WA 98021 USA. RP DePaola, A (reprint author), US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. EM angelo.depaola@fda.hhs.gov FU ISSC; Alabama Department of Public Health, Seafood Branch; Colorado Department of Public Health and Environment, Consumer Protection Division; U.S. Food and Drug Administration, Miami Resident Post, Domestic Operations; Illinois Department of Public Health, Division of Food, Drugs and Dairies; Louisiana Department of Health and Hospitals, of William Long; South Carolina Department of Health and Environmental Control; Virginia Department of Health and Washington Department of Health FX We thank the ISSC for financial support for the purchase of supplies used in this study.; This study would not have been possible without the support from personnel in the states where market samples were collected. We greatly appreciate the support and efforts of Alabama Department of Public Health, Seafood Branch, of the Colorado Department of Public Health and Environment, Consumer Protection Division, of the U.S. Food and Drug Administration, Miami Resident Post, Domestic Operations, of the Illinois Department of Public Health, Division of Food, Drugs and Dairies, of the Louisiana Department of Health and Hospitals, of William Long (for conducting the sampling in Rhode Island), of the South Carolina Department of Health and Environmental Control, State Shellfish Program, and of the Virginia Department of Health and Washington Department of Health. We thank the following for analytical support: the FDA Northeast Regional Laboratory (William Baroletti, Virginia Chung, Eufemia Gonzalez, Thomas Herbst, Kent Hermann, Lawrence James, Patty Kaewussdangkul, Angela Lara, Allan Littell, Jose Obando, Gloria Parra, Morris Paul, Haydee Romero, Juanita Versace, and Joyce Williams), the FDA Southeast Regional Laboratory (Lacresha Chatman, Stacy Eliasberg, Jeffrey Hunsucker, Kathy Noe, LaKenya Patton, Angela Swinford, and Jacquelyn Welch), the FDA Pacific Regional Laboratory-Northwest (Carlos Abeyta, Michael Brown, Moises O'Neill, Cheryl Eklund, Janelle Johnson, Doan Nguyan, and June Wetherington), and the FDA Pacific Regional Laboratory-Southwest (Carlota Agpaoa, Michael Kawalek, Lieuchi Phan, and Nelly Tran). We also acknowledge George Blackstone for his assistance with development of the Salmonella real-time PCR assay. NR 77 TC 65 Z9 66 U1 0 U2 15 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 MAY PY 2010 VL 76 IS 9 BP 2754 EP 2768 DI 10.1128/AEM.02590-09 PG 15 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 586KP UT WOS:000276907400009 PM 20190085 ER PT J AU Buehler, PW Zhou, YP Cabrales, P Jia, YP Sun, GY Harris, DR Tsai, AG Intaglietta, M Palmer, AF AF Buehler, Paul W. Zhou, Yipin Cabrales, Pedro Jia, Yiping Sun, Guoyong Harris, David R. Tsai, Amy G. Intaglietta, Marcos Palmer, Andre F. TI Synthesis, biophysical properties and pharmacokinetics of ultrahigh molecular weight tense and relaxed state polymerized bovine hemoglobins SO BIOMATERIALS LA English DT Article DE Hemoglobin; Red blood cell; Blood substitute; Oxygen carrier; Polymerized hemoglobin; Transfusion ID INTRAOPERATIVE AUTOLOGOUS DONATION; REDUCE TRANSFUSION REQUIREMENTS; TANGENTIAL FLOW FILTRATION; CARRIERS CURRENT STATUS; BYPASS GRAFT-SURGERY; BLOOD SUBSTITUTES; OXYGEN CARRIERS; NITRIC-OXIDE; PHYSICAL-PROPERTIES; LIGHT TRANSMISSION AB Hemoglobin-based oxygen carriers (HBOC) are currently being developed as red blood cell (RBC) substitutes for use in transfusion medicine. Despite significant commercial development, late stage clinical results of polymerized hemoglobin (PolyHb) solutions hamper development. We synthesized two types of PolyHbs with ultrahigh molecular weights: tense (T) state PolyHb (M-W = 16.59 MDa and P-50 = 41 mm Hg) and relaxed (R) state PolyHb (M-W = 26.33 MDa and P-50 = 0.66 mm Hg). By maintaining Hb in either the T- or R-state during the polymerization reaction, we were able to synthesize ultrahigh molecular weight PolyHbs in distinct quaternary states with no tetrameric Hb, high viscosity, low colloid osmotic pressure and the ability to maintain O-2 dissociation, CO association and NO dioxygenation reactions. The PolyHbs elicited some in vitro RBC aggregation that was less than 6% dextran (500 kDa) but more than 5% human serum albumin. In vitro, T-state PolybHb autoxidized faster than R-state PolybHb as expected from previously reported studies, conversely, when administered to guinea pigs as a 20% exchange transfusion, R-state PolybHb oxidized faster and to a greater extent than T-state PolybHb. suggesting a more complex oxidative processes in vivo. Our findings also demonstrate that T-state PolybHb exhibited a longer circulating half-life, slower clearance and longer systemic exposure time compared to R-state PolybHb. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Zhou, Yipin; Sun, Guoyong; Harris, David R.; Palmer, Andre F.] Ohio State Univ, William G Lowrie Dept Chem & Bimol Engn, Columbus, OH 43210 USA. [Buehler, Paul W.; Jia, Yiping] US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Cabrales, Pedro] La Jolla Bioengn Inst, La Jolla, CA 92037 USA. [Tsai, Amy G.; Intaglietta, Marcos] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. RP Palmer, AF (reprint author), Ohio State Univ, William G Lowrie Dept Chem & Bimol Engn, Columbus, OH 43210 USA. EM palmer.351@osu.edu RI Cabrales, Pedro/A-1930-2014 OI Cabrales, Pedro/0000-0002-8794-2839 FU National Institutes of Health [R01HL078840, R01DK070862] FX This work was supported by National Institutes of Health grants R01HL078840 and R01DK070862 to AFP. We would like to thank Dr. Domindor Manalo (FDA/CBER/LBVB) for photography of plasma samples. NR 73 TC 13 Z9 13 U1 0 U2 16 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 EI 1878-5905 J9 BIOMATERIALS JI Biomaterials PD MAY PY 2010 VL 31 IS 13 BP 3723 EP 3735 DI 10.1016/j.biomaterials.2010.01.072 PG 13 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 577WG UT WOS:000276254100034 PM 20149433 ER PT J AU Elmer, J Buehler, PW Jia, YP Wood, F Harris, DR Alayash, AI Palmer, AF AF Elmer, Jacob Buehler, Paul W. Jia, Yiping Wood, Francine Harris, David R. Alayash, Abdu I. Palmer, Andre F. TI Functional Comparison of Hemoglobin Purified by Different Methods and Their Biophysical Implications SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE hemoglobin; purification; tangential flow filtration; anion exchange chromatography; hemoglobin-based oxygen carriers; blood substitute; transfusion; red blood cell ID TANGENTIAL FLOW FILTRATION; CROSS-LINKING; BOVINE HEMOGLOBIN; OXYGEN-TRANSPORT; POLYMERIZATION; AFFINITY; DEXTRAN; BINDING AB Hemoglobin (Hb) that is purified from red blood cells (RBCs) is commonly subjected to harsh processing conditions, such as high temperatures and extensive column separation, which may damage the Hb by altering the heme prosthetic group and/or the Hb protein structure. In this study, bovine and human Hb purified by tangential flow filtration (TFF) was compared to commercial preparations of human Hb (Hemosol, Inc., Toronto, Canada) and bovine Hb (Biopure, Inc., Cambridge, MA). Purified Hbs were characterized by measuring their overall purity (SDS-PAGE, SEC, and ESI-MS), susceptibility to oxidation (k(ox)), responses to physiological conditions (pH, [Cl(-)], [IHP], and T), and ligand binding kinetics (O(2), NO, and CO). All Hbs evaluated possessed comparable biophysical properties, however, a small amount of catalase was detected in the TFF-purified Hbs that reduced the rate of autoxidation. Mass changes observed by mass spectrometry suggest that structural alterations may be introduced into Hbs that are purified by extensive chromatographic separations. These results demonstrate that TFF is a suitable process for the purification of Hb from RBCs with a quality equivalent to that of commercial Hb preparations that employ more extensive purification strategies. This work also shows that TFF can yield highly pure Hb which can be used for Hb-based O(2) carrier synthesis. Biotechnol. Bioeng. 2010;106: 76-85. (C) 2010 Wiley Periodicals, Inc. C1 [Elmer, Jacob; Harris, David R.; Palmer, Andre F.] Ohio State Univ, William C Lowrie Dept Chem & Biomol Engn, Columbus, OH 43210 USA. [Buehler, Paul W.; Jia, Yiping; Wood, Francine; Alayash, Abdu I.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Palmer, AF (reprint author), Ohio State Univ, William C Lowrie Dept Chem & Biomol Engn, Columbus, OH 43210 USA. EM palmer.351@osu.edu FU National Institutes of Health [R01HL078840, R01DK070862] FX Contract grant sponsor: National Institutes of Health; Contract grant number: R01HL078840; R01DK070862 NR 20 TC 14 Z9 14 U1 3 U2 13 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 MAY 1 PY 2010 VL 106 IS 1 BP 76 EP 85 DI 10.1002/bit.22659 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 585QZ UT WOS:000276844500008 PM 20073089 ER PT J AU Slikker, W Liu, F Zhang, X Xou, X Patterson, T Paule, M Wang, C AF Slikker, W. Liu, F. Zhang, X. Xou, X. Patterson, T. Paule, M. Wang, C. TI Genomic Response to Perinatal Anesthetic-Induced Neuronal Cell Death SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Slikker, W.; Liu, F.; Zhang, X.; Xou, X.; Patterson, T.; Paule, M.; Wang, C.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2010 VL 88 IS 5 BP 379 EP 379 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 605AV UT WOS:000278320600101 ER PT J AU Li, DK Andrade, S Scott, P Cheetham, C Cooper, W Davis, R Dublin, S Pawloski, P Raebel, M Smith, D Toh, D AF Li, D. K. Andrade, S. Scott, P. Cheetham, C. Cooper, W. Davis, R. Dublin, S. Pawloski, P. Raebel, M. Smith, D. Toh, D. TI Medication Exposure in Pregnancy Risk Evaluation Program SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Li, D. K.] Kaiser Permanente No Calif, Oakland, CA USA. [Andrade, S.] Meyers Primary Care Inst, Worcester, MA USA. [Scott, P.] US FDA, Silver Spring, MD USA. [Cheetham, C.] Kaiser Permanente So Calif, Los Angeles, CA USA. [Cooper, W.] Vanderbilt Univ, Sch Med, Nashville, TN 37203 USA. [Davis, R.] Kaiser Permanente Georgia, Atlanta, GA USA. [Dublin, S.] Grp Hlth Ctr Hlth Studies, Seattle, WA USA. [Pawloski, P.] HealthPartners Res Fdn, Bloomington, MN USA. [Raebel, M.] Kaiser Permanente Colorado, Denver, CO USA. [Smith, D.] Kaiser Permanente NW, Portland, OR USA. [Toh, D.] Harvard Univ, Sch Med, Boston, MA USA. [Toh, D.] 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 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2010 VL 88 IS 5 BP 409 EP 409 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 605AV UT WOS:000278320600155 ER PT J AU Tabacova, S Szarfman, A Lyndly, JM AF Tabacova, S. Szarfman, A. Lyndly, J. M. TI Adverse Developmental Events Reported to FDA in Association with Maternal Use of Drugs for Treatment of Hyperthyroidism in Pregnancy SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Tabacova, S.; Szarfman, A.; Lyndly, J. M.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2010 VL 88 IS 5 BP 411 EP 411 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 605AV UT WOS:000278320600159 ER PT J AU Parsons, BL Marchant-Miros, KE Delongchamp, RR Verkler, TL Patterson, TA McKinzie, PB Kim, LT AF Parsons, Barbara L. Marchant-Miros, Kathryn E. Delongchamp, Robert R. Verkler, Tracie L. Patterson, Tucker A. McKinzie, Page B. Kim, Lawrence T. TI ACB-PCR Quantification of K-RAS Codon 12 GAT and GTT Mutant Fraction in Colon Tumor and Non-Tumor Tissue SO CANCER INVESTIGATION LA English DT Article DE Cancer biomarkers; Cancer genetics; Carcinogenesis; Colorectal and anal cancer; Oncogenes ID COLORECTAL-CANCER PATIENTS; FECAL OCCULT BLOOD; MUTATIONS; DNA; STOOL; KRAS; PROGNOSIS; CETUXIMAB; ADENOMAS; MUCOSA AB K-RAS mutation is being developed as a cancer biomarker and tumor K-RAS is being used to predict therapeutic response. Yet, levels of K-RAS mutation in normal and pathological tissue samples have not been determined rigorously, nor inter-individual variation in these levels characterized. Therefore, K-RAS codon 12 GAT and GTT mutant fractions were measured in colonic mucosa of individuals without colon cancer, tumor-distal mucosa, tumor-proximal mucosa, normal tumor-adjacent tissues, colonic adenomas, and carcinomas. The results indicate K-RAS codon 12 GAT mutation is present at measurable levels in normal appearing mucosa. All tumors carried K-RAS mutation, in most cases as a mutant subpopulation. C1 [Parsons, Barbara L.; Verkler, Tracie L.; McKinzie, Page B.] US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Marchant-Miros, Kathryn E.] Cent Arkansas Vet Healthcare Syst, Med Res Serv, Little Rock, AR USA. [Delongchamp, Robert R.] Univ Arkansas Med Sci, Coll Publ Hlth, Dept Epidemiol, Little Rock, AR 72205 USA. [Patterson, Tucker A.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Kim, Lawrence T.] Univ Arkansas Med Sci, Dept Surg, Dent Arkansas Vet Healthcare Syst, Surg Serv 112, Little Rock, AR 72205 USA. RP Parsons, BL (reprint author), US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM barbara.parsons@fda.hhs.gov FU National Cancer Institute FX The authors thank Dr. Margie Scott, the CAVHS pathology staff, and Roberta Mittelstaedt for their assistance. The authors thank Drs. Robert Heflich and Fred Beland for their critical review of the manuscript. The contents of this manuscript do not necessarily reflect the views or policies of the US Food & Drug Administration, nor does the mention of trade names or commercial products constitute endorsement or recommendation for use. This material is the result of work supported with resources and the use of facilities at the Central Arkansas Veterans Health-Care System. Tissue samples were provided by the Cooperative Human Tissue Network, which is funded by the National Cancer Institute. Other investigators may have received specimens from the same subjects. NR 36 TC 20 Z9 20 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PD MAY PY 2010 VL 28 IS 4 BP 364 EP 375 DI 10.3109/07357901003630975 PG 12 WC Oncology SC Oncology GA 579IM UT WOS:000276362900005 PM 20307197 ER PT J AU Zdanov, S Klamt, F Shacter, E AF Zdanov, Stephanie Klamt, Fabio Shacter, Emily TI Importance of cofilin oxidation for oxidant-induced apoptosis SO CELL CYCLE LA English DT Editorial Material DE cofilin; apoptosis; mitochondria; oxidative stress; taurine chloramine ID HYPOCHLOROUS ACID; CHLORAMINES; ACTIVATION; INDUCTION; DISEASE C1 [Zdanov, Stephanie; Shacter, Emily] US FDA, Biochem Lab, Bethesda, MD 20014 USA. [Klamt, Fabio] Univ Fed Rio Grande do Sul, Dept Biochem, Porto Alegre, RS, Brazil. RP Shacter, E (reprint author), US FDA, Biochem Lab, Bethesda, MD 20014 USA. EM emily.shacter@fda.hhs.gov RI Zdanov, Stephanie/G-2524-2012 NR 12 TC 3 Z9 3 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAY 1 PY 2010 VL 9 IS 9 BP 1675 EP 1677 PG 3 WC Cell Biology SC Cell Biology GA 592TC UT WOS:000277402200008 PM 20404500 ER PT J AU Antunes, AMM Godinho, ALA Martins, IL Justino, GC Beland, FA Marques, MM AF Antunes, Alexandra M. M. Godinho, Ana L. A. Martins, Ines L. Justino, Goncalo C. Beland, Frederick A. Marques, M. Matilde TI Amino Acid Adduct Formation by the Nevirapine Metabolite, 12-Hydroxynevirapine-A Possible Factor in Nevirapine Toxicity SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID REVERSE-TRANSCRIPTASE INHIBITOR; INDUCED SKIN RASH; TANDEM MASS-SPECTROMETRY; PREVENT HIV TRANSMISSION; TO-CHILD TRANSMISSION; DOSE NEVIRAPINE; SINGLE; BIOTRANSFORMATION; ZIDOVUDINE; UGANDA AB Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor used against the human immunodeficiency virus type-1 (HIV-1), mostly to prevent mother-to-child transmission of the virus in developing countries. However, reports of severe NVP-induced hepatotoxicity and serious adverse cutaneous effects have raised concerns about its use. NVP metabolism involves oxidation of the 4-methyl substituent to 4-hydroxymethyl-NVP (12-hydroxy-NVP) and the formation of phenolic derivatives. Further metabolism, through either oxidation to quinoid derivatives or phase 11 esterification, may produce electrophilic derivatives capable of reacting with bionucleophiles to yield covalent adducts. These adducts could potentially be involved in the initiation of toxic responses. To gain insight into potentially reactive sites in proteins and prepare reliable and fully characterized NVP amino acid adduct standards for subsequent assessment as biomarkers of NVP toxicity, we have used the model electrophile, 12-mesyloxy-NVP, as a synthetic surrogate for the NVP metabolite, 12-sulfoxy-NVP. Reactions of this model ester were conducted with glutathione and the nucleophilic amino acids arginine, cysteine, histidine, and tryptophan. Moreover, because adducts through the N-terminal valine of hemoglobin are convenient biomarkers of exposure to electrophilic toxicants, we also investigated the reaction with valine. We obtained very efficient (>80%) binding through the sulfur of both glutathione and N-acetylcysteine and moderate yields (10-14%) for binding through C2 of the indole ring of tryptophan and NI of the imidazole ring of histidine. Reaction with arginine occurred through the alpha-amino group, possibly due to the high basicity of the guanidino group in the side chain. Reaction at the alpha-amino group of valine occurred to a significant extent (33%); the resulting adduct was converted to a thiohydantoin derivative, to obtain a standard useful for prospective biomonitoring studies. All adducts were characterized by a combination of H-1 and C-13 NMR spectroscopy and mass spectrometry techniques. The NVP conjugates with glutathione and N-acetyleysteine identified in this work were previously reported to he formed in vivo, although the corresponding structures were not fully characterized. Our results support the validity of 12-mesyloxy-NVP as a surrogate for 12-sulfoxy-NVP and suggest that NVP metabolism to 12-hydroxy-NVP, and subsequent esterification, could potentially he a factor in NVP toxicity. They further imply that multiple sites in proteins may he targets for modification by 12-hydroxy-NVP-derived electrophiles in vivo. Additionally, we obtained reliable, fully characterized standards for the assessment of protein modification by NVP in vivo, which should help clarify the potential role of metabolism in NVP-induced toxicity. C1 [Antunes, Alexandra M. M.; Godinho, Ana L. A.; Martins, Ines L.; Justino, Goncalo C.; Marques, M. Matilde] Univ Tecn Lisboa, Inst Super Tecn, Ctr Quim Estrutural, P-1049001 Lisbon, Portugal. [Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Antunes, AMM (reprint author), Univ Tecn Lisboa, Inst Super Tecn, Ctr Quim Estrutural, P-1049001 Lisbon, Portugal. EM alexandra.antunes@ist.utl.pt; matilde.marques@ist.utl.pt RI Justino, Goncalo/B-3190-2011; Marques, M. Matilde/E-2535-2012; PTMS, RNEM/C-1589-2014; Antunes, Alexandra/B-7871-2009; OI Justino, Goncalo/0000-0003-4828-4738; Marques, M. Matilde/0000-0002-7526-4962; Antunes, Alexandra/0000-0003-1827-7369; Lanca Martins, Ines/0000-0003-0797-7642 FU Fundacao para a Ciencia c a Tecnologia (FCT), Portugal; FEDER [POCI/QUI/56582/2004, PPCDT/QUI/56582/2004]; FCT [BPD/SFRH/27563/2006]; National Center for Toxicological Research/Food and Drug Administration and the National Institute for Environmental Health Sciences FX We thank Thomas Heinze and Conceicao Oliveira for the MS analyses. Thanks are also clue to the Portuguese NMR Network (iST-UTL Center) and the Portuguese MS Network (IST-UTL Center) for providing access to the facilities. This work was supported in part by a research grant from Fundacao para a Ciencia c a Tecnologia (FCT), Portugal, and FEDER (POCI/QUI/56582/2004; PPCDT/QUI/56582/2004), by a postdoctoral fellowship (BPD/SFRH/27563/2006) from FCT to G.C.J., and by Interagency Agreement No. 224-93-0001 between the National Center for Toxicological Research/Food and Drug Administration and the National Institute for Environmental Health Sciences/National Toxicology Program. The opinions expressed in this paper do not necessarily represent those of the U.S. Food and Drug Administration. NR 43 TC 26 Z9 26 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAY PY 2010 VL 23 IS 5 BP 888 EP 899 DI 10.1021/tx900443z PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 595FZ UT WOS:000277597400010 PM 20392079 ER PT J AU Kolibab, K Yang, A Derrick, SC Waldmann, TA Perera, LP Morris, SL AF Kolibab, Kristopher Yang, Amy Derrick, Steven C. Waldmann, Thomas A. Perera, Liyanage P. Morris, Sheldon L. TI Highly Persistent and Effective Prime/Boost Regimens against Tuberculosis That Use a Multivalent Modified Vaccine Virus Ankara-Based Tuberculosis Vaccine with Interleukin-15 as a Molecular Adjuvant SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID MYCOBACTERIUM-TUBERCULOSIS; IMMUNE-RESPONSES; T-CELLS; IMMUNODEFICIENCY VIRUS; PROTECTIVE IMMUNITY; CALMETTE-GUERIN; RHESUS MACAQUES; BCG; PRIME; EFFICACY AB Novel immunization strategies are needed to enhance the global control of tuberculosis (TB). In this study, we assessed the immunizing activity of a recombinant modified vaccinia Ankara (MVA) construct (MVA/IL-15/5Mtb) which overexpresses five Mycobacterium tuberculosis antigens (antigen 85A, antigen 85B, ESAT6, HSP60, and Mtb39), as well as the molecular adjuvant interleukin-15 (IL-15). Homologous prime/boost studies showed that the MVA/IL-15/5Mtb vaccine induced moderate but highly persistent protective immune responses for at least 16 months after the initial vaccination and that the interval between the prime and boost did not significantly alter vaccine-induced antituberculosis protective immunity. At 16 months, when the Mycobacterium bovis BCG and MVA/IL-15/5Mtb vaccine-induced protection was essentially equivalent, the protective responses after a tuberculous challenge were associated with elevated levels of gamma interferon (IFN-gamma), IL-17F, Cxcl9, and Cxcl10. To amplify the immunizing potential of the MVA/IL-15/5Mtb vaccine, a heterologous prime/boost regimen was tested using an ESAT6-antigen 85B (E6-85) fusion protein formulated in dimethyldiotacylammonium bromide/monophosphoryl lipid A (DDA/MPL) adjuvant as the priming vaccine and the MVA/IL-15/5Mtb recombinant virus as the boosting agent. When MVA/IL-15/5Mtb vaccine boosting was done at 2 or 6 months following the final fusion protein injections, the prime/boost regimen evoked protective responses against an aerogenic M. tuberculosis challenge which was equivalent to that induced by BCG immunization. Long-term memory after immunization with the E6-85-MVA/IL-15/5Mtb combination regimen was associated with the induction of monofunctional CD4 and CD8 IFN-gamma-producing T cells and multifunctional CD4 and CD8 T cells expressing IFN-gamma/tumor necrosis factor alpha (TNF-alpha), TNF-alpha/IL-2, and IFN-gamma/TNF-alpha/IL-2. In contrast, BCG-induced protection was characterized by fewer CD4 and CD8 monofunctional T cells expressing IFN-gamma and only IFN-gamma/TNF-alpha and IFN-gamma/TNF-alpha/IL-2 expressing multifunctional T (MFT) cells. Taken together, these results suggest that a heterologous prime/boost protocol using an MVA-based tuberculosis vaccines to boost after priming with TB protein/adjuvant preparations should be considered when designing long-lived TB immunization strategies. C1 [Kolibab, Kristopher; Yang, Amy; Derrick, Steven C.; Morris, Sheldon L.] US FDA, Lab Mycobacterial Dis & Cellular Immunol, CBER, Bethesda, MD 20892 USA. [Waldmann, Thomas A.; Perera, Liyanage P.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Morris, SL (reprint author), US FDA, Lab Mycobacterial Dis & Cellular Immunol, CBER, Bldg 29,Room 502,29 Lincoln Dr, Bethesda, MD 20892 USA. EM pereral@mail.nih.gov; sheldon.morris@fda.hhs.gov NR 29 TC 27 Z9 28 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 MAY PY 2010 VL 17 IS 5 BP 793 EP 801 DI 10.1128/CVI.00006-10 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 590QX UT WOS:000277243200014 PM 20357059 ER PT J AU Memoli, MJ Hrabal, RJ Hassantoufighi, A Eichelberger, MC Taubenberger, JK AF Memoli, Matthew J. Hrabal, Rachel J. Hassantoufighi, Arash Eichelberger, Maryna C. Taubenberger, Jeffery K. TI Rapid Selection of Oseltamivir- and Peramivir-Resistant Pandemic H1N1 Virus during Therapy in 2 Immunocompromised Hosts SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID INFLUENZA A/H3N2 VIRUS; SUSCEPTIBILITY; PROPHYLAXIS; INFECTION; ZANAMIVIR AB Pandemic 2009 H1N1 virus isolates containing the neuraminidase inhibitor resistance mutation H275Y have been reported. We describe rapid selection for the H275Y resistance mutation during therapy in 2 immunocompromised individuals at 9 and 14 days of therapy, as well as the first described case of clinically significant resistance to peramivir. C1 [Memoli, Matthew J.; Hrabal, Rachel J.; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Hassantoufighi, Arash; Eichelberger, Maryna C.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Memoli, MJ (reprint author), NIAID, Resp Virus Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, MSC 3203,33 N Dr, Bethesda, MD 20892 USA. EM memolim@niaid.nih.gov OI Hagey, Rachel/0000-0002-4368-3169 FU Intramural NIH HHS [Z99 AI999999] NR 15 TC 87 Z9 89 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 1 PY 2010 VL 50 IS 9 BP 1252 EP 1255 DI 10.1086/651605 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 577UA UT WOS:000276248300008 PM 20345239 ER PT J AU Woodcock, J AF Woodcock, J. TI Precompetitive Research: A New Prescription for Drug Development? SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Woodcock, J (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM janet.woodcock@fda.hhs.gov NR 0 TC 26 Z9 28 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAY PY 2010 VL 87 IS 5 BP 521 EP 523 DI 10.1038/clpt.2010.28 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 586ZT UT WOS:000276956300002 PM 20407454 ER PT J AU Woosley, RL Myers, RT Goodsaid, F AF Woosley, R. L. Myers, R. T. Goodsaid, F. TI The Critical Path Institute's Approach to Precompetitive Sharing and Advancing Regulatory Science SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID DRUG DEVELOPMENT; CONSORTIUM; SEMATECH AB Many successful large industries, such as computer-chip manufacturers, the cable television industry, and high-definition television developers, 1 have established successful precompetitive collaborations focusing on standards, applied science, and technology that advance the field for all stakeholders and benefit the public. 2 The pharmaceutical industry, however, has a well-earned reputation for fierce competition and did not demonstrate willingness to share data or knowledge until the US Food and Drug Administration (FDA) launched the Critical Path Initiative in 2004 (ref. 3). C1 [Woosley, R. L.; Myers, R. T.] Crit Path Inst, Tucson, AZ USA. [Goodsaid, F.] US FDA, Genom Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Woosley, RL (reprint author), Crit Path Inst, Tucson, AZ USA. EM RWoosley@C-Path.org OI Woosley, Raymond L./0000-0002-2588-328X NR 16 TC 19 Z9 20 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 MAY PY 2010 VL 87 IS 5 BP 530 EP 533 DI 10.1038/clpt.2010.27 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 586ZT UT WOS:000276956300005 PM 20407457 ER PT J AU Wagner, JA Prince, M Wright, EC Ennis, MM Kochan, J Nunez, DJR Schneider, B Wang, MD Chen, Y Ghosh, S Musser, BJ Vassileva, MT AF Wagner, J. A. Prince, M. Wright, E. C. Ennis, M. M. Kochan, J. Nunez, D. J. R. Schneider, B. Wang, M-D Chen, Y. Ghosh, S. Musser, B. J. Vassileva, M. T. TI The Biomarkers Consortium: Practice and Pitfalls of Open-Source Precompetitive Collaboration SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID DRUG DEVELOPMENT; INNOVATION AB Precompetitive collaboration is a growing driver for innovation and increased productivity in biomedical science and drug development. The Biomarkers Consortium, a public-private platform for precompetitive collaboration specific to biomarkers, demonstrated that adiponectin has potential utility as a predictor of metabolic responses to peroxisome proliferator-activated receptor (PPAR) agonists in individuals with type 2 diabetes. Despite the challenges overcome by this project, the most important lesson learned is that cross-company precompetitive collaboration is a feasible robust approach to biomarker qualification. C1 [Vassileva, M. T.] Fdn Natl Inst Hlth, Bethesda, MD USA. [Wagner, J. A.; Chen, Y.; Musser, B. J.] Merck, Rahway, NJ USA. [Prince, M.; Wang, M-D] Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. [Wright, E. C.] NIDDKD, NIH, Bethesda, MD 20892 USA. [Ennis, M. M.] Quintiles Inc, Austin, TX USA. [Kochan, J.] Hoffmann La Roche, Nutley, NJ USA. [Nunez, D. J. R.] GlaxoSmithKline Inc, Metab Pathways Ctr Excellence Drug Discovery, Res Triangle Pk, NC USA. [Schneider, B.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Ghosh, S.] N Carolina Cent Univ, Biomed Biotechnol Res Inst, Durham, NC USA. RP Vassileva, MT (reprint author), Fdn Natl Inst Hlth, Bethesda, MD USA. EM mvassileva@fnih.org OI GHOSH, SUJOY/0000-0002-7601-165X NR 10 TC 25 Z9 25 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 MAY PY 2010 VL 87 IS 5 BP 539 EP 542 DI 10.1038/clpt.2009.227 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 586ZT UT WOS:000276956300008 PM 20407460 ER PT J AU Feigenbaum, K Longstaff, L AF Feigenbaum, Kathryn Longstaff, Laura TI Management of the Metabolic Syndrome in Patients With Human Immunodeficiency Virus SO DIABETES EDUCATOR LA English DT Article ID HIV-INFECTED PATIENTS; ANTIRETROVIRAL THERAPY; CARDIOVASCULAR-DISEASE; LIPODYSTROPHY; ADULTS; RISK; POPULATION; DISORDERS; EDUCATION; PROGRAM AB Patients with human immunodeficiency virus (HIV) are an increasing subpopulation of patients seen in endocrine/diabetes clinics. This article explores evidence-based treatment recommendations for patients with metabolic syndrome who are also positive for HIV. Patients infected with HIV may manifest metabolic abnormalities. They often present with low high-density lipoprotein (HDL-C), hypertension, visceral adiposity, and insulin resistance, among other symptoms consistent with features of the metabolic syndrome. The etiologies of the metabolic abnormalities are not completely understood. The role of highly active antiretroviral therapy (HAART) and the separate effect of HIV on patients who are surviving longer may contribute to the increased incidence of the development of the metabolic syndrome. The role of the health care team is to provide patient education to patients with HIV concerning lifestyle modification in order to prevent complications related to the metabolic syndrome. C1 [Feigenbaum, Kathryn] NIH, Ctr Clin, Nursing & Patient Care Serv, Bethesda, MD 20892 USA. [Longstaff, Laura] US PHS, Off Gener Drugs, Ctr Drug Evaluat & Res, Food & Drug Adm, Rockville, MD USA. RP Feigenbaum, K (reprint author), NIH, Ctr Clin, Nursing & Patient Care Serv, 10 Ctr Dr,MSC 1530, Bethesda, MD 20892 USA. EM kfeigenbaum@nih.gov NR 44 TC 5 Z9 5 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD MAY-JUN PY 2010 VL 36 IS 3 BP 457 EP 464 DI 10.1177/0145721710363619 PG 8 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 601ME UT WOS:000278062900005 PM 20348287 ER PT J AU Wang, SJ Bretz, F AF Wang, Sue-Jane Bretz, Frank TI From Adaptive Design to Modern Protocol Design for Drug Development: Part I. Editorial and Summary of Adaptive Designs Session at the Third FDA/DIA Statistics Forum SO DRUG INFORMATION JOURNAL LA English DT Article DE Adaptive design paradigm; Clinical scenario planning; Phase 3 development program ID DOSE-RANGING DESIGNS; PHRMA WORKING GROUP; WHITE PAPER; TRIALS AB The Adaptive Designs session at the Third FDA/DIA Statistics Forum presented an important step in the scientific merits and evaluation of two recently emerging drug development adaptive paradigms: exploratory versus confirmatory. After highlighting the different paradigms, several questions addressing critical issues in confirmatory clinical trials were posed and discussed by an expert panel. So fat; adaptive design and analysis methods have focused mostly on individual trials. The merits of a single adaptive trial may be better suited to the context of a drug development program. We articulate the roles of modeling and simulation for modern protocol design via clinical scenario planning in a phase 3 development program. The clinical scenarios consist of a combination of effect sizes, variability, placebo response, and type I and type II errors. The models are mainly used to improve the precision of effect estimate. These topics are further discussed in Part II. C1 [Wang, Sue-Jane] US FDA, Ctr Drug Evaluat & Res, Off Biostat, Off Translat Sci, Silver Spring, MD 20993 USA. [Wang, Sue-Jane] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Bretz, Frank] Novartis Pharma AG, Stat Methodol, Basel, Switzerland. [Bretz, Frank] Hannover Med Sch, D-3000 Hannover, Germany. RP Wang, SJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Biostat, Off Translat Sci, WO 21,Mailstop 3562,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Suejane.Wang@fda.hhs.gov RI Bretz, Frank/F-6927-2014 FU Drug Information Association; third Annual FDA-DIA Statistics Forum FX The authors thank the distinguished panel members, the Drug Information Association, and the organizing committee members of the third Annual FDA-DIA Statistics Forum for their support and contributions to the adaptive design session. NR 12 TC 7 Z9 7 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 MAY PY 2010 VL 44 IS 3 BP 325 EP 331 PG 7 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 595BI UT WOS:000277585300014 ER PT J AU Siddiqui, O Hershkowitz, N AF Siddiqui, Ohidul Hershkowitz, Norman TI Primary Efficacy Endpoint in Clinical Trials of Antiepileptic Drugs: Change or Percentage Change SO DRUG INFORMATION JOURNAL LA English DT Article DE AED trials; Parametric tests; Nonparametric tests; Change from baseline ID TRANSFORMATIONS AB In randomized clinical trials of antiepileptic drugs (AEDs), the seizure frequency per x days during baseline and treatment phase periods are recorded to evaluate efficacy of a drug. The seizure frequency data are often nonnormal, and hence an appropriate mathematical transformation is necessary for a statistical analysis. The most commonly used transformations in AED development research are (a) log-transformation of the seizure frequency data, and (b) calculation of percentage change (PC) from baseline in seizure frequency. The log-transformed postbaseline seizure frequency data are analyzed using a parametric ANCOVA model including the log-transformed baseline data as a covariate and treatment group as a factor in the model. The PC data are analyzed using either a Wilcoxon rank-sum test on the PCs, or ANOVA/ANCOVA analysis on the ranks of PCs including treatment groups as a factor and any covariate of interest in the model. A limited number of research works is available in the literature regarding a choice of log-transformed or PC of seizure frequency data in the statistical analyses. In this research, an attempt is made to evaluate the impacts of choosing either of the two transformations on seizure frequency data of AED trials. C1 [Siddiqui, Ohidul] US FDA, Ctr Drug Evaluat & Res, Off Biostat, Div Biometr 1, Silver Spring, MD 20993 USA. [Hershkowitz, Norman] US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Div Neurol, Silver Spring, MD 20993 USA. RP Siddiqui, O (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Biostat, Div Biometr 1, 10903 New Hampshire Ave,Rm 4606,Bldg 21, Silver Spring, MD 20993 USA. EM ohidul.siddiqui@fda.hhs.gov NR 11 TC 5 Z9 5 U1 1 U2 3 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 MAY PY 2010 VL 44 IS 3 BP 343 EP 350 PG 8 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 595BI UT WOS:000277585300016 ER PT J AU Wang, SY Chen, CT Yin, JJ AF Wang, Shiow Y. Chen, Chi-Tsun Yin, Jun-Jie TI Effect of allyl isothiocyanate on antioxidants and fruit decay of blueberries SO FOOD CHEMISTRY LA English DT Article DE Allyl isothiocyanate; Antioxidant activity; Anthocyanin; ESR; Total phenol; Rubus idaeus subsp. ID RADICAL SCAVENGING CAPACITY; HYDROGEN-PEROXIDE; BACTERICIDAL ACTIVITY; PENICILLIUM-EXPANSUM; WASABIA-JAPONICA; STRAWBERRY FRUIT; EXTRACTS; RESISTANCE; OXYGEN; MECHANISMS AB The effect of allyl isothiocyanate (AITC) on radical scavenging capacity, and fruit decay of blueberries var. Duke (Vaccinium corymbosum L.) was evaluated. Results from this study showed that AITC was effective in retarding blueberry decay during storage at 10 degrees C. However, AITC-treated fruit decreased the contents of total phenolics and anthocyanins. Compared to control, AITC-treated berries had lower scavenging capacities against radicals of oxygen radical absorbance capacity (pyroxyl radical; ORAC), hydroxyl radical scavenging capacity ((center dot)OH) and 2,2-di(4-tert-octylphenyl)-1-picrylhydrazyl (DPPH(center dot)), but promoted the accumulation of hydrogen peroxide (H(2)O(2)) radicals. The free radical scavenging properties of blueberry fruit with or without AITC treatment were also evaluated by electron spin resonance (ESR). Results of the ESR measurements confirmed that free radical scavenging capacities against (center dot)OH, DPPH(center dot) and O(2)(center dot-) were lower in treated fruit than in control un-treated fruit. The results from this study indicate that AITC does not promote antioxidant property or scavenging of constitutive reactive oxygen species (ROS), but paradoxically generates additional amounts of ROS to inhibit the growth and proliferation of microbial cells, thereby reducing decay in fruit tissue. Published by Elsevier Ltd. C1 [Wang, Shiow Y.; Chen, Chi-Tsun] ARS, Genet Improvement Fruit & Vegetable Lab, Beltsville Agr Res Ctr, USDA, Beltsville, MD 20705 USA. [Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Wang, SY (reprint author), ARS, Genet Improvement Fruit & Vegetable Lab, Beltsville Agr Res Ctr, USDA, Beltsville, MD 20705 USA. EM shiow.wang@ars.usda.gov RI Yin, Jun Jie /E-5619-2014 NR 33 TC 29 Z9 35 U1 1 U2 17 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 MAY 1 PY 2010 VL 120 IS 1 BP 199 EP 204 DI 10.1016/j.foodchem.2009.10.007 PG 6 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA 548AL UT WOS:000273931100028 ER PT J AU Nawaz, M Khan, SA Khan, AA Sung, K Tran, Q Kerdahi, K Steele, R AF Nawaz, Mohamed Khan, Saeed A. Khan, Ashraf A. Sung, Kidon Tran, Quynhtien Kerdahi, Khalil Steele, Roger TI Detection and characterization of virulence genes and integrons in Aeromonas veronii isolated from catfish SO FOOD MICROBIOLOGY LA English DT Article DE Virulence genes; Aeromonas; Catfish; PCR ID FRESH-WATER; HYDROPHILA; SPP.; ENTEROTOXIN; DIARRHEA; GASTROENTERITIS; IDENTIFICATION; MOTILITY AB The presence of virulence genes and integrons was determined in 81 strains of Aeromonas veronii isolated from farm-raised catfish. Polymerase chain reaction (PCR) protocols were used to determine the presence of genes for cytotoxic enterotoxin (act), aerolysin (aerA), two cytotonic enterotoxins (ast, alt), lipase (lip), glycerophospholipid:cholesterol acyltransferase (gcaT), serine protease (ser), DNases (exu), elastase (ahyB) and the structural gene flagellin (fib) in the template DNA. Oligonucleotide primers amplified a 231-bp region of the act gene from the template DNA of 97.0% of the isolates. Primers specific for the amplification of the aerA gene amplified a 431-bp region of the aerA gene from the template DNA of 96.0% of the isolates. None of the isolates contained ast or alt genes. Oligonucleotide primers specific for the amplification of lip, gcaT, ser and fla genes, amplified their respective amplicons from 85.0, 78.0, 82.0 and 80.0% of the isolates. None of the isolates contained exu or the elastase genes. Several of the isolates (48.0%) contained class I integrons that confer resistance to multiple antibiotics; various sizes between 0.6 and 3.1 kb were found. None of the isolates contained Class II integrons. Our results indicate that farm-raised catfish may be a source of pathogenic A. veronii and that the potential health risks posed by virulent strains of A. veronii should not be underestimated. Published by Elsevier Ltd. C1 [Nawaz, Mohamed; Khan, Saeed A.; Khan, Ashraf A.; Sung, Kidon; Tran, Quynhtien; Steele, Roger] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Kerdahi, Khalil] US FDA, Arkansas Reg Lab, Jefferson, AR 72079 USA. RP Nawaz, M (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM Mohamed.nawaz@fda.hhs.gov RI Khan, Ashraf/E-8133-2013 FU National Center for Toxicological Research; US Food and Drug Administration FX We thank Dr Carl E. Cerniglia, Dr. J.B. Sutherland and Dr. Huizhong Chen for critical review of the manuscript. This work was supported by the National Center for Toxicological Research, US Food and Drug Administration. Views presented here do not necessarily reflect those of the FDA. NR 31 TC 44 Z9 55 U1 2 U2 9 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD MAY PY 2010 VL 27 IS 3 BP 327 EP 331 DI 10.1016/j.fm.2009.11.007 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 581YK UT WOS:000276561600002 PM 20227596 ER PT J AU Samaras, GM AF Samaras, George M. TI The Use, Misuse, and Abuse of Design Controls Human-Centered Systems Engineering SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Article DE Design methodology; Performance evaluation; Engineering management C1 [Samaras, George M.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Samaras, George M.] George Washington Univ, Grad Sch Engn, Washington, DC 20052 USA. [Samaras, George M.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Samaras, GM (reprint author), Samaras & Associates Inc, 7755 Soda Creek Rd, Pueblo, CO 81005 USA. EM george@samaras.eng.pro NR 15 TC 1 Z9 1 U1 0 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0739-5175 EI 1937-4186 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD MAY-JUN PY 2010 VL 29 IS 3 BP 12 EP 18 DI 10.1109/MEMB.2010.936551 PG 7 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA 596DL UT WOS:000277664300004 PM 20659853 ER PT J AU Ilev, IK Wang, LHV Boppart, SA Andersson-Engels, S Kim, BM AF Ilev, Ilko K. Wang, Lihong V. Boppart, Stephen A. Andersson-Engels, Stefan Kim, Beop-Min TI Introduction to the Special Issue on Biophotonics-Part 1 SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Editorial Material C1 [Ilev, Ilko K.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Wang, Lihong V.] Washington Univ, Dept Biomed Engn, St Louis, MO 63130 USA. [Boppart, Stephen A.] Univ Illinois, Beckman Inst Adv Sci & Technol, Dept Bioengn, Urbana, IL 61801 USA. [Boppart, Stephen A.] Univ Illinois, Beckman Inst Adv Sci & Technol, Dept Elect & Comp Engn, Urbana, IL 61801 USA. [Andersson-Engels, Stefan] Lund Univ, Div Atom Phys, SE-22100 Lund, Sweden. [Kim, Beop-Min] Korea Univ, Dept Biomed Engn, Seoul 136703, South Korea. RP Ilev, IK (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM ilko.ilev@fda.hhs.gov RI Wang, Lihong/A-7147-2009; Andersson-Engels, Stefan/C-5515-2012 OI Wang, Lihong/0000-0001-9783-4383; Andersson-Engels, Stefan/0000-0001-5640-3122 NR 0 TC 0 Z9 0 U1 0 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD MAY-JUN PY 2010 VL 16 IS 3 BP 475 EP 477 DI 10.1109/JSTQE.2010.2048255 PG 3 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 607WN UT WOS:000278538100001 ER PT J AU Wang, QZ Agrawal, A Wang, NS Pfefer, TJ AF Wang, Quanzeng Agrawal, Anant Wang, Nam Sun Pfefer, T. Joshua TI Condensed Monte Carlo Modeling of Reflectance From Biological Tissue With a Single Illumination-Detection Fiber SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Article DE Cancer; fiber-optics; Monte Carlo (MC); optical properties; reflectance spectroscopy ID LOCAL OPTICAL-PROPERTIES; DIFFUSE-REFLECTANCE; IN-VIVO; TURBID MEDIA; LIGHT TRANSPORT; FLUORESCENCE SPECTROSCOPY; NONINVASIVE MEASUREMENT; BARRETTS-ESOPHAGUS; INVERSE MODEL; WHITE-LIGHT AB In order to facilitate rapid simulation of reflectance spectroscopy for biological tissue, we have derived convolution equations needed to apply the condensed Monte Carlo (MC) modeling approach to single illumination-detection fiber probes. This approach was validated against a standard MC model, and then implemented to perform three computationally demanding tasks. First, by performing simulations at a wide range of optical property combinations, we characterized the effect of fiber diameter on the relationship between reflectance and tissue optical properties. Second, we simulated reflectance from 400 to 500 nm based on the optical properties of malignant and adipose breast tissues to elucidate the effect of fiber diameter on detected reflectance spectra. The third task involved evaluating the effect of adding an illumination-detection fiber to a linear array fiber probe for optical property determination. The implications of this approach for optimization of probe geometries are discussed. In addition to providing an important tool for high-volume MC simulation, this study has generated unique insights into the role of device design for reflectance spectroscopy. C1 [Wang, Quanzeng; Agrawal, Anant; Pfefer, T. Joshua] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Agrawal, Anant] Catholic Univ Amer, Washington, DC 20064 USA. [Wang, Nam Sun] Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA. RP Wang, QZ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM quanzeng.wang@fda.hhs.gov; anant.agrawal@fda.hhs.gov; nsw@umd.edu; joshua.pfefer@fda.hhs.gov RI Pfefer, Josh/I-9055-2012; Wang, Nam Sun/E-4253-2016 FU Oak Ridge Associated Universities FX This work was supported by a fellowship from Oak Ridge Associated Universities. Send correspondence to Q. Wang or N. S. Wang. NR 35 TC 11 Z9 12 U1 0 U2 7 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD MAY-JUN PY 2010 VL 16 IS 3 BP 627 EP 634 DI 10.1109/JSTQE.2009.2029546 PG 8 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 607WN UT WOS:000278538100017 ER PT J AU Bao, L Trucksess, MW White, KD AF Bao, Lei Trucksess, Mary W. White, Kevin D. TI Determination of Aflatoxins B-1, B-2, G(1), and G(2) in Olive Oil, Peanut Oil, and Sesame Oil SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; NATURAL OCCURRENCE; OCHRATOXIN-A; PLANTS; PASTE AB Edible oils are consumed directly, and used as ingredients in food, soaps, and skin products. However, oils such as olive oil, peanut oil, and sesame oil could be contaminated with aflatoxins, which are detrimental to human and animal health. A method using immunoaffinity column cleanup with RPLC separation and fluorescence detection (FLD) for determination of aflatoxins (AF) B-1, B-2, G(1), and G(2) in olive oil, peanut oil, and sesame oil was developed and validated. Test samples were extracted with methanol-water (55 + 45, v/v). After shaking and centrifuging, the lower layer was filtered, diluted with water, and filtered through glass microfiber filter paper. The filtrate was then passed through an immunoaffinity column, and the toxins were eluted with methanol. The toxins were then subjected to RPLC/FLD analysis after postcolumn UV photochemical derivatization. The accuracy and repeatability characteristics of the method were determined. Recoveries of AFB(1) spiked at levels from 1.0 to 10.0 mu g/kg in olive oil, peanut oil, and sesame oil ranged from 82.9 to 98.6%. RSDs ranged from 0.6 to 8.9%. HorRat values were <0.2 for all of the matrixes tested. Recoveries of AF spiked at levels from 2.0 to 20.0 mu g/kg ranged from 87.7 to 102.2%. RSDs ranged from 1.3 to 12.6%. HorRat values were <0.4 for all of the matrixes tested. LC/MS/MS with multiple-reaction monitoring was used to confirm the identities of aflatoxins in a naturally contaminated peanut oil. C1 [Bao, Lei; Trucksess, Mary W.] US FDA, Off Regulatory Sci, Div Bioanalyt Chem, College Pk, MD 20740 USA. [White, Kevin D.] US FDA, Off Regulatory Sci, Div Analyt Chem, College Pk, MD 20740 USA. RP Bao, L (reprint author), Shan Dong Exit Entry Inspect & Quarantine Bur Chi, 70 Qutang Xia Rd, Qing Dao City 266001, Peoples R China. EM baoleiqd@yahoo.com.cn NR 24 TC 10 Z9 13 U1 3 U2 14 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 2010 VL 93 IS 3 BP 936 EP 942 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 615MS UT WOS:000279140000029 PM 20629398 ER PT J AU Emiliano, AB Governale, L Parks, M Cooper, DS AF Emiliano, Ana B. Governale, Laura Parks, Mary Cooper, David S. TI Shifts in Propylthiouracil and Methimazole Prescribing Practices: Antithyroid Drug Use in the United States from 1991 to 2008 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GRAVES-DISEASE; CLINICAL CHARACTERISTICS; HYPERTHYROIDISM; THERAPY AB Context: The thionamide antithyroid drugs methimazole and propylthiouracil are the mainstay of pharmacologic therapy for Graves' disease. However, little is known about the rate of use of these drugs and the prescribing practices of physicians treating hyperthyroidism. Objective: The objective of the study was to examine the frequency of methimazole and propylthiouracil use from years 1991 to 2008. Methods: The data were acquired by the U.S. Food and Drug Administration's Division of Epidemiology through two databases: IMS National Sales Perspectives and the Surveillance Data, Inc. Vector One: National database. Results: There was a 9-fold increase in the annual number of methimazole prescriptions during the study period, from 158,000 to 1.36 million per year. There was a 19% increase in the annual number of propylthiouracil prescriptions, from 348,000 to 415,000 per year. Propylthiouracil, which held two thirds of the market from 1991 to 1995, was surpassed by methimazole in 1996. Patient demographic data indicated that although 72% of methimazole prescriptions were for females, males were more likely to be on methimazole (82%) than females (74%) (P < 0.001, two tailed chi(2) test). The only demographic group in which methimazole use decreased was women of childbearing age (5% decrease, P < 0.001, two tailed chi(2)). The incidence of hyperthyroidism in 2008 was estimated based on the number of new prescriptions of thionamides by age group and data from the 2008 U.S. census: 0.44 per 1000 for ages 0-11 yr, 0.26 per 1000 for ages 12-17 yr, 0.59 per 1000 for ages 18-44 yr, 0.78 per 1000 for ages 45-64 yr, and 1.01 per 1000 for ages 65 + yr. Conclusions: Methimazole has become the most frequently prescribed antithyroid drug. The remarkable increase in the total number of dispensed thionamide prescriptions over the last 18 yr may indicate a trend toward pharmacological treatment as primary treatment of Graves' disease in the United States. (J Clin Endocrinol Metab 95: 2227-2233, 2010) C1 [Emiliano, Ana B.; Cooper, David S.] Johns Hopkins Sch Med, Div Endocrinol & Metab, Baltimore, MD 21287 USA. [Governale, Laura; Parks, Mary] Publ Hlth Serv, US Dept HHS, US FDA, Ctr Drug Evaluat & Res,Office Surveillance & Epid, Silver Spring, MD 20993 USA. RP Cooper, DS (reprint author), Johns Hopkins Univ, Sch Med, Div Endocrinol, 1830 E Monument St,Suite 333, Baltimore, MD 21287 USA. EM dscooper@jhmi.edu FU National Institutes of Health [5 T32 DK007751-09] FX A.B.E. was supported by National Institutes of Health Grant 5 T32 DK007751-09. NR 29 TC 38 Z9 38 U1 0 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2010 VL 95 IS 5 BP 2227 EP 2233 DI 10.1210/jc.2009-2752 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592DW UT WOS:000277356700029 PM 20335447 ER PT J AU Russell, MD Correa, MT Stauber, CE Kase, JA AF Russell, Mindi D. Correa, Maria T. Stauber, Christine E. Kase, Julie A. TI North Carolina Hispanic Farmworkers and Intestinal Parasitism: A Pilot Study of Prevalence and Health-Related Practices, and Potential Means of Foodborne Transmission SO JOURNAL OF FOOD PROTECTION LA English DT Article ID CYCLOSPORIASIS; OUTBREAKS AB Migrant and seasonal farmworkers provide much of the necessary labor to harvest and process agricultural commodities desired by consumers. Little is known about the health status (especially the parasitic burden) of farm laborers, who handpick agricultural items such as fruits and vegetables, despite being implicated as a means of foodborne pathogen transmission. The goal of this research was to develop a framework to investigate enteric parasitic infections among Hispanic farmworkers in Eastern North Carolina. Seventy-one interviews were conducted, 16 stool samples were collected, and two parasite-positive workers were found. In addition, some potentially harmful health practices (e.g., self-medication) were identified. Further research is necessary to fully understand the scope of farmworker health issues and the potential risk of disseminating foodborne pathogens to humans. The study model presented provides a geographically expandable format to allow for various types of health investigations including the prevalence of other pathogens. C1 [Russell, Mindi D.; Kase, Julie A.] N Carolina State Lab Publ Hlth, Raleigh, NC 27601 USA. [Correa, Maria T.] N Carolina State Univ, Coll Vet Med, Raleigh, NC 27695 USA. [Stauber, Christine E.] Georgia State Univ, Inst Publ Hlth, Atlanta, GA 30302 USA. RP Kase, JA (reprint author), US FDA, Div Microbiol, Microbial Methods Dev Branch, Off Regulatory Sci,Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,Room 3E-023,HFS 711, College Pk, MD 20740 USA. EM julie.kase@fda.hhs.gov FU Emerging Infectious Diseases (EID); Centers for Disease Control and Prevention (CDC) FX This research was supported in pan by an appointment (M. D. Russell) to the Emerging Infectious Diseases (EID) Fellowship Program administered by the Association of Public Health Laboratories (APHL) and funded by the Centers for Disease Control and Prevention (CDC). This project would not have been possible without the interviewers, especially Margaret Jackson, the outreach staff at the three collaborating community health centers, and the study participants. We express our deepest gratitude to them and also to Dr. Lee Ann Jaykus for her critical review of the manuscript. Human participant protection: This study was approved by the Institutional Review Board at North Carolina State University. The study was also approved by the board members of each collaborating community health center. NR 12 TC 1 Z9 1 U1 0 U2 3 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD MAY PY 2010 VL 73 IS 5 BP 985 EP 988 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 595DR UT WOS:000277591400025 PM 20501054 ER PT J AU Tournas, VH Feliciano, L Katsoudas, EJ AF Tournas, Valerie H. Feliciano, Lizanel Katsoudas, Eugenia J. TI EVALUATION OF THE PETRIFILM DRY REHYDRATABLE FILM FOR THE ENUMERATION OF YEASTS AND MOULDS IN NATURALLY CONTAMINATED FOODS SO JOURNAL OF FOOD SAFETY LA English DT Article ID MEDIA AB Two hundred thirty-seven samples from six food groups (tree nuts, grains and grain products, dried fruits, fresh produce, fruit juice and dairy products) were tested for levels of fungal contamination using the Petrifilm dry rehydratable film for yeast and mould (PYM ) enumeration (3M Microbiology, St. Paul, MN) and the Food and Drug Administration (FDA) official method. Results indicated that PYM performed very well for all tested commodities giving YM counts similar to those of the FDA method. Statistical analysis of the data (t-test) revealed no significant differences between the two methods for all foods tested. Linear regression analysis showed that the correlation coefficients between the two methods were over 0.90 for 91% of the commodities tested. Some difficulties were encountered during counting of the colonies on PYM as yeast colonies on this medium tend to be very small with rather faded colorations. PRACTICAL APPLICATIONS Assessment of the efficacy of Petrifilm and determining its equivalence to traditional, validated methods will give the testing laboratories and the industry an alternate option for the enumeration of fungi in foods. The use of Petrifilm would be especially useful when analyst time is limited as it requires no media preparation and minimal time for sample inoculation. C1 [Tournas, Valerie H.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Feliciano, Lizanel] Ohio State Univ, Columbus, OH 43210 USA. [Katsoudas, Eugenia J.] US FDA, NE Reg Lab, Jamaica, NY USA. RP Tournas, VH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM valerie.tournas@fda.hhs.gov NR 13 TC 0 Z9 0 U1 0 U2 9 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0149-6085 J9 J FOOD SAFETY JI J. Food Saf. PD MAY PY 2010 VL 30 IS 2 BP 506 EP 514 DI 10.1111/j.1745-4565.2010.00223.x PG 9 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 584ZG UT WOS:000276792900021 ER PT J AU Jackson, LS Zhang, Z Tolleson, WH AF Jackson, Lauren S. Zhang, Zhe Tolleson, William H. TI Thermal Stability of Ricin in Orange and Apple Juices SO JOURNAL OF FOOD SCIENCE LA English DT Article DE bioterrorism; fruit juice; ricin; thermal stability; toxicity ID N-GLYCOSIDASE ACTIVITY; A-CHAIN; SODIUM RICINOLEATE; RIBOSOMAL-RNA; TOXIN RICIN; B-CHAIN; PROTEINS; COMMUNIS; DEOXYNIVALENOL; STABILIZATION AB Ricin is a potent protein toxin that could be exploited for bioterrorism. Although ricin may be detoxified using heat, inactivation conditions in foods are not well characterized. Two brands of pulp-free orange juice and 2 brands of single-strength apple juice (one clarified and the other unclarified) containing 100 mu g/mL added ricin were heated at 60 to 90 degrees C for up to 2 h. With increasing heating times and temperatures the heat-treated juices exhibited decreasing detectability of ricin by enzyme-linked immunosorbent assay (ELISA) and cytotoxicity to cultured cells. Z-values for ricin inactivation in orange juices were 14.4 +/- 0.8 degrees C and 17 +/- 4 degrees C using cytotoxicity assays, compared to 13.4 +/- 1.5 degrees C and 14 +/- 2 degrees C determined by ELISA. Although insignificant differences were apparent for z-values measured for the 2 orange juice brands, significant differences were found in the z-values for the 2 brands of apple juice. The z-values for ricin inactivation in the clarified and unclarified apple juices were 21 +/- 4 degrees C and 9.5 +/- 1.1 degrees C, determined by cytotoxicity assays, and 20 +/- 2 degrees C and 11.6 +/- 0.7 degrees C, respectively, using ELISA. Overall, there were no significant differences between results measured with ELISA and cytotoxicity assays. Ricin stability in orange juice and buffer was evaluated at 25 degrees C. Half-lives of 10 +/- 3 d and 4.9 +/- 0.4 d, respectively, indicated that active ricin in juice could reach consumers. These results indicate that ricin in apple and orange juices can remain toxic under some processing and product storage conditions. Practical Application: Ricin is a potent toxin that is abundant in castor beans and is present in the castor bean mash by-product after cold-press extraction of castor oil. U. S. Health and Human Services recognizes that ricin could be used for bioterrorism. This study reports the stability of ricin in apple and orange fruit juices at temperatures ranging from 60 to 90 degrees C (140 to 194 degrees F). C1 [Tolleson, William H.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Zhang, Zhe] IIT, NCFST, Summit Argo, IL 60501 USA. RP Tolleson, WH (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM william.tolleson@fda.hhs.gov FU Natl. Center for Food Protection and Defense FX The contents of this manuscript do not necessarily reflect the views and policies of the U.S. Food and Drug Administration, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. This project was funded in part by a grant from the Natl. Center for Food Protection and Defense. NR 38 TC 12 Z9 12 U1 0 U2 14 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 MAY PY 2010 VL 75 IS 4 BP T65 EP T71 DI 10.1111/j.1750-3841.2010.01570.x PG 7 WC Food Science & Technology SC Food Science & Technology GA 591KX UT WOS:000277300600042 PM 20546429 ER PT J AU Ohmann, EL Burckart, GJ Brooks, MM Chen, Y Pravica, V Girnita, DM Zeevi, A Webber, SA AF Ohmann, Erin L. Burckart, Gilbert J. Brooks, Maria M. Chen, Yan Pravica, Vera Girnita, Diana M. Zeevi, Adriana Webber, Steven A. TI Genetic polymorphisms influence mycophenolate mofetil-related adverse events in pediatric heart transplant patients SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article DE mycophenolate mofetil; adverse events; multidrug resistance protein 2; ABCC2; inosine monophosphate dehydrogenase 1; inosine monophosphate dehydrogenase 2; genetic polymorphism ID RENAL-ALLOGRAFT RECIPIENTS; SINGLE-NUCLEOTIDE POLYMORPHISMS; ACUTE REJECTION; CONTROLLED-TRIAL; ACID PHARMACOKINETICS; ACYL GLUCURONIDE; PROMOTER REGION; DOUBLE-BLIND; CYCLOSPORINE; UGT1A8 AB BACKGROUND: Mycophenolate mofetil (MMF) is an effective and commonly used immunosuppressant but has frequent adverse events. Genetic polymorphisms may contribute to variability in MMF efficacy and related complications. In this study we explore the distribution frequencies of common single nucleotide polymorphisms (SNPs) of IMPDH1, IMPDH2 and ABCC2 and investigate whether these SNPs influence MMF adverse events in 59 pediatric heart recipients. METHODS: Genotypes were assessed by TaqMan analysis of: ABCC2 rs717620; IMPDH2 rs11706052; and IMPDH1 rs2288553, rs2288549, rs2278293, rs2278294 and rs2228075. Gastrointestinal (GI) intolerance was defined as diarrhea, vomiting, nausea or abdominal pain requiring dose-holding for >48 hours or MMF discontinuation. Bone marrow toxicity was evaluated using Common Terminology Criteria for Adverse Events Version 3 (CTCAE). RESULTS: GI intolerance occurred in 21 patients, and 21 had bone marrow toxicity. The ABCC2 rs717620 A variant was significantly associated with GI intolerance leading to drug discontinuation (p < 0.001); the IMPDH1 rs2278294 A variant and rs2228075 A variant were also associated with greater GI intolerance (p = 0.029 and p = 0.002, respectively). The IMPDH2 rs11706052 G variant was associated with more frequent neutropenia requiring dose-holding (p = 0.046). CONCLUSIONS: In this small sample of pediatric heart transplant patients receiving MMF, ABCC2, IMPDH1 and IMPDH2 SNPs were associated with MMF GI intolerance and bone marrow toxicity. Thus, genetic polymorphisms may directly influence MMF adverse events. J Heart Lung Transplant 2010;29:509-516 (C) 2010 International Society for Heart and Lung Transplantation. All rights reserved. C1 [Webber, Steven A.] Childrens Hosp Pittsburgh, Div Cardiol, Dept Pediat, Pittsburgh, PA 15201 USA. [Burckart, Gilbert J.] US FDA, Off Clin Pharmacol, Silver Spring, MD USA. [Brooks, Maria M.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Chen, Yan; Pravica, Vera] Univ So Calif, Dept Pharm, Los Angeles, CA USA. [Girnita, Diana M.; Zeevi, Adriana] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. RP Webber, SA (reprint author), Childrens Hosp Pittsburgh, Div Cardiol, Dept Pediat, 45th St & Penn Ave, Pittsburgh, PA 15201 USA. EM steve.webber@chp.edu OI Brooks, Maria/0000-0002-2030-7873 FU National Institutes of Health [5P50HL074732-05] FX Supported by Grant 5P50HL074732-05 from the National Institutes of Health. NR 44 TC 25 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD MAY PY 2010 VL 29 IS 5 BP 509 EP 516 DI 10.1016/j.healun.2009.11.602 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 589RG UT WOS:000277169900004 PM 20061166 ER PT J AU Bukh, J Meuleman, P Tellier, R Engle, RE Feinstone, SM Eder, G Satterfield, WC Govindarajan, S Krawczynski, K Miller, RH Leroux-Roels, G Purcell, RH AF Bukh, Jens Meuleman, Philip Tellier, Raymond Engle, Ronald E. Feinstone, Stephen M. Eder, Gerald Satterfield, William C. Govindarajan, Sugantha Krawczynski, Krzysztof Miller, Roger H. Leroux-Roels, Geert Purcell, Robert H. TI Challenge Pools of Hepatitis C Virus Genotypes 1-6 Prototype Strains: Replication Fitness and Pathogenicity in Chimpanzees and Human Liver-Chimeric Mouse Models SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CELL-CULTURE-SYSTEMS; INFECTIOUS IN-VIVO; 6 MAJOR GENOTYPES; UPA-SCID MOUSE; INOCULATED CHIMPANZEES; FULMINANT-HEPATITIS; NUCLEOTIDE-SEQUENCE; MOLECULAR CLONE; CDNA-CLONE; TRANSCRIPTS AB Chimpanzees represent the only animal model for studies of the natural history of hepatitis C virus (HCV). To generate virus stocks of important HCV variants, we infected chimpanzees with HCV strains of genotypes 1-6 and determined the infectivity titer of acute-phase plasma pools in additional animals. The courses of first- and second-passage infections were similar, with early appearance of viremia, HCV RNA titers of >10(4.7) IU/mL, and development of acute hepatitis; the chronicity rate was 56%. The challenge pools had titers of 10(3)-10(5) chimpanzee infectious doses/mL. Human liver-chimeric mice developed high-titer infections after inoculation with the challenge viruses of genotypes 1-6. Inoculation studies with different doses of the genotype 1b pool suggested that a relatively high virus dose is required to consistently infect chimeric mice. The challenge pools represent a unique resource for studies of HCV molecular virology and for studies of pathogenesis, protective immunity, and vaccine efficacy in vivo. C1 [Bukh, Jens; Tellier, Raymond; Engle, Ronald E.; Miller, Roger H.; Purcell, Robert H.] NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Feinstone, Stephen M.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Satterfield, William C.] Univ Texas MD Anderson Canc Ctr, Dept Vet Sci, Michale E Keeling Ctr Comparat Med & Res, Bastrop, TX USA. [Govindarajan, Sugantha] Univ So Calif, Rancho Los Amigos Med Ctr, Liver Res Lab, Downey, CA 90242 USA. [Krawczynski, Krzysztof] Ctr Dis Control & Prevent, Div Viral Hepatitis, Atlanta, GA USA. [Bukh, Jens] Copenhagen Univ Hosp, Copenhagen Hepatitis Program CO HEP C, Dept Infect Dis, Hvidovre, Denmark. [Bukh, Jens] Copenhagen Univ Hosp, Clin Res Ctr, Hvidovre, Denmark. [Bukh, Jens] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, Fac Hlth Sci, Copenhagen, Denmark. [Eder, Gerald] Karl Landsteiner Inst Epidemiol Infect Disorders, St Polten, Austria. [Meuleman, Philip; Leroux-Roels, Geert] Ghent Univ & Hosp, Ctr Vaccinol, Ghent, Belgium. RP Bukh, J (reprint author), NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bldg 50,50 S Dr MSC 8009, Bethesda, MD 20892 USA. EM jbukh@niaid.nih.gov RI Meuleman, Philip/H-2899-2013 OI Meuleman, Philip/0000-0001-6821-234X FU National Institute of Allergy and Infectious Diseases, National Institutes of Health [N01-A0-2713]; University of Copenhagen; Lundbeck Foundation; Ghent University [01G00507]; Belgian State via the Interuniversity Attraction Poles Program [P6/36 HEPRO]; European Union; Research Foundation Flanders (FWO-Vlaanderen) FX Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health (contract N01-A0-2713); University of Copenhagen (professorship to J.B.); Lundbeck Foundation (external funding to J.B.); Ghent University (Concerted Action Grant 01G00507); the Belgian State via the Interuniversity Attraction Poles Program (grant P6/36 HEPRO); European Union (6th Framework-HEPACIVAC); The Research Foundation Flanders (FWO-Vlaanderen; postdoctoral fellowship to P.M.). NR 50 TC 43 Z9 43 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY 1 PY 2010 VL 201 IS 9 BP 1381 EP 1389 DI 10.1086/651579 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 577UB UT WOS:000276248400015 PM 20353362 ER PT J AU Memoli, MJ Hrabal, RJ Hassantoufighi, A Jagger, BW Sheng, ZM Eichelberger, MC Taubenberger, JK AF Memoli, Matthew J. Hrabal, Rachel J. Hassantoufighi, Arash Jagger, Brett W. Sheng, Zong-Mei Eichelberger, Maryna C. Taubenberger, Jeffery K. TI Rapid Selection of a Transmissible Multidrug-Resistant Influenza A/H3N2 Virus in an Immunocompromised Host SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID A H3N2 VIRUSES; OSELTAMIVIR-RESISTANT; SEASONAL INFLUENZA; ISOLATED WORLDWIDE; H1N1; INFECTION; SURVEILLANCE; MORTALITY; ZANAMIVIR; OUTBREAK AB Background. The overall impact of influenza virus infection in immunocompromised patients is largely unknown. Antigenic drift and genetic variations during prolonged influenza infection have been demonstrated. In this report we describe a multidrug-resistant H3N2 influenza virus isolated from an immunocompromised patient after 5 days of therapy. Methods. Multiple nasal wash samples were collected from an infected patient, and viral isolates were characterized. Sensitivity to antiviral agents was evaluated. Fitness and transmissibility were assessed in ferrets and tissue culture. Results. An in-frame 4-amino acid deletion emerged in the neuraminidase (NA) gene of an H3N2 virus after 5 days of oseltamivir therapy. No other changes in the NA or hemagglutinin genes were noted. Drug sensitivity assays revealed resistance to oseltamivir (>10-fold increase in 50% inhibitory concentration [IC(50)]) and reduction in sensitivity to zanamivir (3-7-fold increase in IC(50) or 50% effective concentration). No change in fitness or transmissibility was observed. Conclusions. An in-frame NA gene deletion was rapidly selected for in an immunocompromised patient, resulting in decreased sensitivity of the isolate to available NA inhibitors without a change in fitness or transmissibility. This finding has implications for our understanding of the emergence of antiviral resistance and treatment of patients with influenza A infection, especially those who are immunocompromised. C1 [Memoli, Matthew J.; Hrabal, Rachel J.; Jagger, Brett W.; Sheng, Zong-Mei; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Hassantoufighi, Arash; Eichelberger, Maryna C.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Memoli, MJ (reprint author), NIAID, Resp Virus Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, MSC 3203 33 N Dr, Bethesda, MD 20892 USA. EM memolim@niaid.nih.gov OI Hagey, Rachel/0000-0002-4368-3169 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health; Food and Drug Administration FX Intramural program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and the Food and Drug Administration. NR 38 TC 23 Z9 25 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY 1 PY 2010 VL 201 IS 9 BP 1397 EP 1403 DI 10.1086/651610 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 577UB UT WOS:000276248400017 PM 20350163 ER PT J AU Devadas, K Hewlett, IK Dhawan, S AF Devadas, Krishnakumar Hewlett, Indira K. Dhawan, Subhash TI Lipopolysaccharide suppresses HIV-1 replication in human monocytes by protein kinase C-dependent heme oxygenase-1 induction SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE AIDS; host factors; signal transduction pathway ID NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; IMMUNODEFICIENCY-VIRUS EXPRESSION; CHEMOKINE RECEPTOR 5; ACUTE LUNG INJURY; INDUCED TNF-ALPHA; IN-VITRO; HUMAN MACROPHAGES; GENE-EXPRESSION; BACTERIAL LIPOPOLYSACCHARIDE AB LPS is an important component of the Gram-negative bacteria cell wall. It activates monocytes and induces multiple host immune and inflammatory responses. Interestingly, in spite of inducing host-inflammatory responses, LPS also protects monocyte-derived macrophages from infection by HIV-1. In this report, we have shown that LPS treatment of human monocyte-derived macrophages markedly suppressed HIV-1 replication, even on addition to infected cells 24 h after infection. Inhibition of HIV-1 replication was associated with PKC-dependent induction of HO-1, a cytoprotective enzyme known to catabolize heme. Pretreatment with the PKC inhibitor Go 6976 not only substantially inhibited LPS-mediated induction of HO-1 but also attenuated LPS-induced suppression of HIV replication. Significant reduction of HIV replication by inhibitors of JNK, NF-kappa B, and PI3K was independent of a LPS-mediated anti-HIV effect. Specificity of HO-1 was confirmed by substantial reversal of LPS-induced viral replication by pretreatment of cells with SnPP IX, an inhibitor of HO-1 enzyme activity. These results demonstrate a previously undefined function of HO-1 as a host defense mechanism in LPS-mediated inhibition of HIV-1 replication. J. Leukoc. Biol. 87: 915-924; 2010. C1 [Devadas, Krishnakumar; Hewlett, Indira K.; Dhawan, Subhash] US FDA, Viral Immunol Sect, Mol Virol Lab,Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Rockville, MD 20852 USA. RP Dhawan, S (reprint author), US FDA, Viral Immunol Sect, Mol Virol Lab,Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, 1401 Rockville Pike,HFM 315, Rockville, MD 20852 USA. EM subhash.dhawan@fda.hhs.gov NR 71 TC 18 Z9 18 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAY PY 2010 VL 87 IS 5 BP 915 EP 924 DI 10.1189/jlb.0307172 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 618LI UT WOS:000279355000018 PM 20061555 ER PT J AU Kadegowda, AKG Connor, EE Teter, BB Sampugna, J Delmonte, P Piperova, LS Erdman, RA AF Kadegowda, Anil K. G. Connor, Erin E. Teter, Beverly B. Sampugna, Joseph Delmonte, Pierluigi Piperova, Liliana S. Erdman, Richard A. TI Dietary trans Fatty Acid Isomers Differ in Their Effects on Mammary Lipid Metabolism As Well As Lipogenic Gene Expression in Lactating Mice SO JOURNAL OF NUTRITION LA English DT Article ID CONJUGATED LINOLEIC-ACID; MILK-FAT; DAIRY-COWS; CHREBP; LIVER; IDENTIFICATION; DEPRESSION; STEATOSIS; GLAND; OIL AB The biological activities and mechanisms of action of individual transoctadecenoic acids (trans-18:1 FA) have not been completely elucidated. We examined the effects of several individual trans-18:1 FA isomers and trans-10, cis-12 conjugated linoleic acid (CLA) on fat synthesis, and expression of lipogenic genes in mammary and liver tissue in lactating mice. From d 6 to 10 postpartum, 30 lactating C57BL/6J mice were randomly assigned to either a control (CTR) diet containing 20 g/kg oleic acid or diets in which the oleic acid was either completely replaced by partially hydrogenated vegetable oil (PHVO), trans-7 18:1 (T7), trans-9 18:1 (T9), or trans-11 18:1 (T11) or partially replaced with 6.66 g/kg trans-10, cis-12 CLA. Milk fat percentage was decreased by CLA (44%), T7 (27%), and PHVO (23%), compared with CTR. In the mammary gland, CLA decreased the expression of genes related to de novo FA synthesis, desaturation, triacylglycerol formation, and transcriptional regulation. PHVO and T7 diets decreased the expression of 1-acylglycerol-3-phosphate O-acyltransferase and thyroid hormone responsive SPOT14 homolog (THRSP) mRNA. In contrast, dietary trans FA (tFA) did not affect hepatic lipogenic gene expression. However, mice fed CLA, 17, and PHVO diets had increased liver weights due to hepatic steatosis. Trans-7 18:1 was extensively desaturated to trans-7, cis-9 CLA in mammary and liver tissues. Dietary trans-7 18:1 could lead to milk fat depression in lactating mice, possibly through its desaturation product trans-7, cis-9 CLA. Also, the differences between the effects of trans-10, cis-12 CLA and other tFA could be attributed to its effects on carbohydrate response element binding protein and PPAR gamma, in addition to sterol regulatory element binding transcription factor 1c and THRSP. J. Nutr. 140: 919-924, 2010. C1 [Kadegowda, Anil K. G.; Piperova, Liliana S.; Erdman, Richard A.] Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. [Teter, Beverly B.; Sampugna, Joseph] Univ Maryland, Dept Biochem, College Pk, MD 20742 USA. [Connor, Erin E.] ARS, Bovine Funct Genom Lab, USDA, Beltsville, MD 20705 USA. [Delmonte, Pierluigi] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Erdman, RA (reprint author), Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. EM erdman@umd.edu NR 29 TC 22 Z9 26 U1 2 U2 11 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 2010 VL 140 IS 5 BP 919 EP 924 DI 10.3945/jn.109.110890 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 589CI UT WOS:000277121800007 PM 20220207 ER PT J AU Prodduturi, S Sadrieh, N Wokovich, AM Doub, WH Westenberger, BJ Buhse, L AF Prodduturi, Suneela Sadrieh, Nakissa Wokovich, Anna M. Doub, William H. Westenberger, Benjamin J. Buhse, Lucinda TI Transdermal Delivery of Fentanyl from Matrix and Reservoir Systems: Effect of Heat and Compromised Skin SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE fentanyl; transdermal drug delivery systems; matrix; reservoir; compromised skin; skin permeation AB The United States Food and Drug Administration (FDA) has received numerous reports of serious adverse events, including death, in patients using fentanyl transdermal systems (FTS). To gain a better understanding of these problems, the current research focuses on the in vitro characterization of fentanyl reservoir (Duragesic (R)) and matrix (Mylan) systems with respect to drug release and skin permeation under conditions of elevated temperature and compromised skin. In addition, different synthetic membrane barriers were evaluated to identify the one that best simulates fentanyl skin transport, and thus may be useful as a model for these systems in future studies. The results indicate that reservoir and matrix FTS are comparable when applied to intact skin at normal skin temperature but the kinetics of drug delivery are different in the two systems. At 40 degrees C, the permeation rate of fentanyl was twice that seen at 32 degrees C over the first 24h in both systems; however, the total drug permeation in 72 h is significantly higher in the reservoir FTS. When applied to partially compromised skin, matrix FTS has a greater permeation enhancement effect than reservoir FTS. The intrinsic rate limiting membrane of the reservoir system served to limit drug permeation when the skin (barrier) permeability was compromised. Different ethylene vinyl acetate membranes were shown to have fentanyl permeability values encompassing the variability in human skin. Results using the in vitro model developed using synthetic membranes suggest that they mimic the effect of compromised skin on fentanyl permeability. Especially for highly potent drugs such as fentanyl, it is important that patients follow instructions regarding application of heat and use of the product on compromised skin. (C) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:2357-2366, 2010 C1 [Sadrieh, Nakissa; Wokovich, Anna M.; Doub, William H.; Westenberger, Benjamin J.; Buhse, Lucinda] US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. [Prodduturi, Suneela] Aizant Drug Res Solut Private Ltd, Hyderabad 50014, Andhra Pradesh, India. RP Doub, WH (reprint author), US FDA, Div Pharmaceut Anal, 1114 Market St Room 1002, St Louis, MO 63101 USA. EM william.doub@fda.hhs.gov NR 21 TC 23 Z9 24 U1 0 U2 16 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 MAY PY 2010 VL 99 IS 5 BP 2357 EP 2366 DI 10.1002/jps.22004 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 589FO UT WOS:000277132500013 PM 19967778 ER PT J AU Crane, NT Nalubola, R Schneeman, BO AF Crane, Nancy T. Nalubola, Ritu Schneeman, Barbara O. TI The Role and Relevance of Codex Nutrition Standards SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Editorial Material C1 [Crane, Nancy T.] US FDA, CCNFSDU US Delegate, Off Nutr Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Nalubola, Ritu] US FDA, CCFL US Delegate, Off Commissioner, College Pk, MD USA. [Schneeman, Barbara O.] US FDA, Off Nutr Labeling & Dietary Supplements, College Pk, MD USA. [Schneeman, Barbara O.] US FDA, US Delegate CCNFSDU, College Pk, MD USA. [Schneeman, Barbara O.] US FDA, CCFL, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Crane, NT (reprint author), US FDA, CCNFSDU US Delegate, Off Nutr Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, College Pk, MD USA. NR 24 TC 0 Z9 0 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 MAY PY 2010 VL 110 IS 5 BP 672 EP + DI 10.1016/j.jada.2010.03.030 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 592JF UT WOS:000277374300003 PM 20430126 ER PT J AU Fu, AZ Tang, AS Wang, N Du, D Jiang, JZ AF Fu, Alex Z. Tang, Anne S. Wang, Nan Du, Dongyi (Tony) Jiang, Jenny Z. TI Effect of Medicare Part D on Potentially Inappropriate Medication Use by Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE inappropriate medication; elderly; Medicare Part D; Beers criteria ID NURSING-HOME RESIDENTS; EXPLICIT CRITERIA; CONSENSUS PANEL; DRUG-USE; POPULATION; CARE; HOSPITALIZATION; EXPENDITURES; COVERAGE; IMPACT AB OBJECTIVES To empirically estimate changes of potentially inappropriate medication (PIM) use attributable to the Medicare Part D prescription drug benefit. DESIGN Difference-in-difference strategy in the quasi-experimental design with a control group. SETTING U.S. nationally representative community-dwelling sample of older adults. PARTICIPANTS One thousand seven hundred seventy-four adults aged 65 and older in the 2005 and 2006 Medical Expenditure Panel Surveys were followed up for 2 years with five rounds of interviews. MEASUREMENTS PIM use was identified based on the 2002 Beers criteria. Analyses were conducted for likelihood of PIM use and number of PIM prescriptions using logit models and negative binomial models, respectively. RESULTS There was a trend of less likelihood of PIM use for all older adults from 2005 to 2006 (odds ratio=0.67, 95% confidence interval (CI)=0.52-0.86). After accounting for this secular trend and potential confounders, no significant difference of the likelihood of PIM use was found between Part D enrollees and nonenrollees, although enrollees were found to use significantly more PIM prescriptions in round 5 (in 2006) than nonenrollees (incidence rate ratio=1.56, 95% CI=1.08-2.25). CONCLUSION This initial evidence suggests that Medicare Part D could result in more PIM use in older enrollees than in nonenrollees, although the overall likelihood of PIM use has decreased in all older community-dwelling adults. Future research is needed to examine the effect over the longer term and focusing on particular categories of PIMs. C1 [Fu, Alex Z.; Tang, Anne S.] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA. [Wang, Nan] Cleveland Clin, Qual & Patient Safety Inst, Cleveland, OH 44195 USA. [Du, Dongyi (Tony)] US FDA, Off Planning & Anal, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Jiang, Jenny Z.] Walgreens Hlth Serv, Deerfield, IL USA. RP Fu, AZ (reprint author), Cleveland Clin, Dept Quantitat Hlth Sci, 9500 Euclid Ave JJN3-01, Cleveland, OH 44195 USA. EM fuz@ccf.org FU Merck Co FX The views expressed in this paper are those of the authors, and no official endorsement by the FDA or the Department of Health and Human Services is intended or should be inferred.; Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper.; AZF and AST are supported in part by a research grant from Merck & Co. JZJ is an employee of Walgreen's Health Services.; Author Contributions: AZF: study concept and design, acquisition of subjects and data, analysis and interpretation of data, and preparation of manuscript. AST: acquisition of subjects and data, analysis and interpretation of data, and preparation of manuscript. NW: study concept and design, interpretation of data, and preparation of manuscript. DD: study design, interpretation of data, and preparation of manuscript. JZJ: study concept, analysis of data, and preparation of manuscript.; Sponsor's Role: None. NR 30 TC 11 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2010 VL 58 IS 5 BP 944 EP 949 DI 10.1111/j.1532-5415.2010.02809.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 592XE UT WOS:000277414400022 PM 20406314 ER PT J AU Wang, W Xie, H Ye, ZP Vassell, R Weiss, CD AF Wang, Wei Xie, Hang Ye, Zhiping Vassell, Russell Weiss, Carol D. TI Characterization of lentiviral pseudotypes with influenza H5N1 hemagglutinin and their performance in neutralization assays SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE Hemagglutinin; Influenza; Neutralization; Pseudotype ID VIRUS; ANTIBODIES; PARTICLES; VACCINE; SERA AB Pseudotype reporter viruses are being used as safe, quantitative, and high-throughput tools for assessing antibody neutralization for many viruses, including influenza. However, characterization of pseudotypes containing influenza hemagglutinin (HA-pseudotypes) is needed before this system is widely adopted for evaluating neutralizing antibodies in sera following vaccination or infection. In this report HA-pseudotype stocks were analyzed for HA content, stability, and performance in neutralization assays under various conditions. HA-pseudotypes produced with HA genes of H5 strains representing clades 1, 2.2, and 2.3.4 consistently contain similar HA contents, and infectivity was not greatly affected by the purity of the HA-pseudotype preparations or variations in storage conditions. HA-pseudotype neutralization titers using a reference serum panel were also consistent across a wide range of dilutions of HA-pseudotype stocks and correlated well with results from microneutralization assays involving replicating influenza. Concentrated HA-pseudotypes were further shown to work well in hemagglutination inhibition assays. Finally, antisera elicited by genetically modified HA, with changes in the polybasic cleavage site that have been used in some H5 vaccines and reduce pathogenicity, gave identical neutralization titers against HA-pseudotypes with wild type or modified HA. These findings support continued development of HA-pseudotypes as a robust tool for analyzing sera in vaccine and serologic studies. Published by Elsevier B.V. C1 [Wang, Wei; Xie, Hang; Ye, Zhiping; Vassell, Russell; Weiss, Carol D.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Weiss, CD (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM-466,Bldg 29,Room 532,29 Lincoln Dr, Bethesda, MD 20892 USA. EM carol.weiss@fda.hhs.gov RI Weiss, Carol/F-6438-2011 OI Weiss, Carol/0000-0002-9965-1289 FU FDA FX We thank the following persons for generously supplying key reagents for these studies: Dr. Gary Nabel (NIH, Bethesda, MD) for HIV-luciferase pseudotype system and expression vector CMV/R 8 kappa B; Galina Vodieko and Christine Anderson (FDA, Bethesda, MD) for H5 reference sheep antisera: Dr. Olga Zoueva (FDA, Bethesda, MD) for providing the plasmid for A/duck/Laos/3295/2006 HA gene; and Dr. lain Stephenson (University of Leicester, UK) for the H5N1 reference serum panel. We also thank Dr. Xiyan Xu (CDC, Atlanta, GA) for providing HI titer of ferret anti-Laos H5N1 sera and Drs. Vladimir Lugovtsev and Matthew Sandbulte (FDA, Bethesda, MD) for critical reading of this manuscript. This work was support by institutional research funds from the FDA. NR 21 TC 17 Z9 18 U1 0 U2 3 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 MAY PY 2010 VL 165 IS 2 BP 305 EP 310 DI 10.1016/j.jviromet.2010.02.009 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 597NC UT WOS:000277763700026 PM 20153374 ER PT J AU Plant, EP Rakauskaite, R Taylor, DR Dinman, JD AF Plant, Ewan P. Rakauskaite, Rasa Taylor, Deborah R. Dinman, Jonathan D. TI Achieving a Golden Mean: Mechanisms by Which Coronaviruses Ensure Synthesis of the Correct Stoichiometric Ratios of Viral Proteins SO JOURNAL OF VIROLOGY LA English DT Article ID DOUBLE-STRANDED-RNA; RIBOSOMAL FRAMESHIFTING EFFICIENCY; RESPIRATORY SYNDROME CORONAVIRUS; VIRUS-LIKE PARTICLES; POL FUSION PROTEIN; SACCHAROMYCES-CEREVISIAE; TY1 RETROTRANSPOSITION; SARS CORONAVIRUS; MUTATIONAL ANALYSIS; INFECTIOUS CDNA AB In retroviruses and the double-stranded RNA totiviruses, the efficiency of programmed -1 ribosomal frameshifting is critical for ensuring the proper ratios of upstream-encoded capsid proteins to downstreamencoded replicase enzymes. The genomic organizations of many other frameshifting viruses, including the coronaviruses, are very different, in that their upstream open reading frames encode nonstructural proteins, the frameshift-dependent downstream open reading frames encode enzymes involved in transcription and replication, and their structural proteins are encoded by subgenomic mRNAs. The biological significance of frameshifting efficiency and how the relative ratios of proteins encoded by the upstream and downstream open reading frames affect virus propagation has not been explored before. Here, three different strategies were employed to test the hypothesis that the -1 PRF signals of coronaviruses have evolved to produce the correct ratios of upstream-to downstream-encoded proteins. Specifically, infectious clones of the severe acute respiratory syndrome (SARS)-associated coronavirus harboring mutations that lower frameshift efficiency decreased infectivity by >4 orders of magnitude. Second, a series of frameshift-promoting mRNA pseudoknot mutants was employed to demonstrate that the frameshift signals of the SARS-associated coronavirus and mouse hepatitis virus have evolved to promote optimal frameshift efficiencies. Finally, we show that a previously described frameshift attenuator element does not actually affect frameshifting per se but rather serves to limit the fraction of ribosomes available for frameshifting. The findings of these analyses all support a "golden mean" model in which viruses use both programmed ribosomal frameshifting and translational attenuation to control the relative ratios of their encoded proteins. C1 [Rakauskaite, Rasa; Dinman, Jonathan D.] Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA. [Plant, Ewan P.; Taylor, Deborah R.] US FDA, Lab Hepatitis & Related Emerging Agents, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review,CBER, Bethesda, MD 20892 USA. RP Dinman, JD (reprint author), Univ Maryland, Dept Mol Genet & Cell Biol, Microbiol Bldg,Rm 2135, College Pk, MD 20742 USA. EM dinman@umd.edu OI Plant, Ewan/0000-0003-0166-5939; Dinman, Jonathan/0000-0002-2402-9698 FU National Institutes of Health [AI064307] FX This work was supported by a grant from the National Institutes of Health to J.D.D. (AI064307). NR 60 TC 38 Z9 38 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2010 VL 84 IS 9 BP 4330 EP 4340 DI 10.1128/JVI.02480-09 PG 11 WC Virology SC Virology GA 579GW UT WOS:000276358000021 PM 20164235 ER PT J AU Lewis, SM Lee, FW Ali, AA Allaben, WT Weis, CC Leakey, JEA AF Lewis, Sherry M. Lee, Fei W. Ali, A. Afshan Allaben, William T. Weis, Constance C. Leakey, Julian E. A. TI Modifying a displacement pump for oral gavage dosing of solution and suspension preparations to adult and neonatal mice SO LAB ANIMAL LA English DT Article ID BISPHENOL-A AB To assess a drug's toxic or carcinogenic effects on neonatal and adult mice and rats, researchers often carry out oral gavage studies. Whether dosed singly or in various combinations, provided as soluble solutions or as colloidal suspensions, the drug must be delivered in accurate and precise doses. For studies that require newborn mice to receive multiple daily doses, delicately handling neonates to increase their chances of surviving is just as critical as the ability to accurately dose small volumes. To help ensure accurate and precise delivery of drug doses ranging from 5 for neonatal mice to 400 mu l for adults, the authors adapted an automated pipetting system. By slightly modifying standard gavage needles, the authors delivered, on average, 98-99% of targeted dose volumes to neonatal mice. C1 [Lewis, Sherry M.; Lee, Fei W.; Ali, A. Afshan; Weis, Constance C.; Leakey, Julian E. A.] Natl Ctr Toxicol Res, Off Sci Coordinat, Jefferson, AR 72079 USA. [Allaben, William T.] Ctr Toxicol & Environm Hlth LLC, N Little Rock, AR USA. RP Lewis, SM (reprint author), Natl Ctr Toxicol Res, Off Sci Coordinat, Jefferson, AR 72079 USA. EM sherrym.lewis@fda.hhs.gov FU National Institute of Environmental Health Sciences and the NCTR/Food and Drug Administration [224-93-0001] FX We thank Mr. Clyde Ulmer (Z-TECH Corporation) for computer technical support; Mr. Richard Rasmussen (The Bionetics Corporation) for technical support; Oak Ridge Institute of Science and Education for financially supporting Drs. Lee, Ali and Lewis; and the analytical group of Division of Chemistry at NCTR. These studies were funded by Interagency Agreement 224-93-0001 between the National Institute of Environmental Health Sciences and the NCTR/Food and Drug Administration. This document has been reviewed in accordance with United States Food and Drug Administration (FDA) policy and approved for publication. Approval does not signify that the contents necessarily reflect the position or opinions of the FDA nor does mention of trade names or commercial products constitute endorsement or recommendation for use. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the FDA. NR 6 TC 5 Z9 5 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD MAY PY 2010 VL 39 IS 5 BP 149 EP 154 PG 6 WC Veterinary Sciences SC Veterinary Sciences GA 589NT UT WOS:000277157800014 PM 20410899 ER PT J AU Kweon, O Kim, SJ Freeman, JP Song, J Baek, S Cerniglia, CE AF Kweon, Ohgew Kim, Seong-Jae Freeman, James P. Song, Jaekyeong Baek, Songjoon Cerniglia, Carl E. TI Substrate Specificity and Structural Characteristics of the Novel Rieske Nonheme Iron Aromatic Ring-Hydroxylating Oxygenases NidAB and NidA3B3 from Mycobacterium vanbaalenii PYR-1 SO MBIO LA English DT Article ID SP STRAIN PYR-1; NAPHTHALENE DIOXYGENASE; HYDROCARBON DEGRADATION; DEGRADING MYCOBACTERIUM; BIPHENYL DIOXYGENASE; PYRENE DEGRADATION; PSEUDOMONAS-PUTIDA; MOLECULAR-CLONING; CRYSTAL-STRUCTURE; ACTIVE-SITE AB The Rieske nonheme iron aromatic ring-hydroxylating oxygenases (RHOs) NidAB and NidA3B3 from Mycobacterium vanbaalenii PYR-1 have been implicated in the initial oxidation of high-molecular-weight (HMW) polycyclic aromatic hydrocarbons (PAHs), forming cis-dihydrodiols. To clarify how these two RHOs are functionally different with respect to the degradation of HMW PAHs, we investigated their substrate specificities to 13 representative aromatic substrates (toluene, m-xylene, phthalate, biphenyl, naphthalene, phenanthrene, anthracene, fluoranthene, pyrene, benz[a] anthracene, benzo[a] pyrene, carbazole, and dibenzothiophene) by enzyme reconstitution studies of Escherichia coli. Both Nid systems were identified to be compatible with type V electron transport chain (ETC) components, consisting of a [3Fe-4S]-type ferredoxin and a glutathione reductase (GR)-type reductase. Metabolite profiles indicated that the Nid systems oxidize a wide range of aromatic hydrocarbon compounds, producing various isomeric dihydrodiol and phenolic compounds. NidAB and NidA3B3 showed the highest conversion rates for pyrene and fluoranthene, respectively, with high product regiospecificity, whereas other aromatic substrates were converted at relatively low regiospecificity. Structural characteristics of the active sites of the Nid systems were investigated and compared to those of other RHOs. The NidAB and NidA3B3 systems showed the largest substrate-binding pockets in the active sites, which satisfies spatial requirements for accepting HMW PAHs. Spatially conserved aromatic amino acids, Phe-Phe-Phe, in the substrate-binding pockets of the Nid systems appeared to play an important role in keeping aromatic substrates within the reactive distance from the iron atom, which allows each oxygen to attack the neighboring carbons. IMPORTANCE Since the discovery of microbial ring-hydroxylating oxygenases (RHOs) in 1970, the sequences, structures, and enzyme biochemistry, including enantiospecific products, of RHOs have been studied and discussed extensively from the perspective of biodegradation, biotransformation, and biocatalysis processes. However, with all that effort to elucidate the enzymatic mechanisms of RHOs, little is known about the biochemistry and enzymology underlying high-molecular-weight (HMW) polycyclic aromatic hydrocarbon (PAH) degradation. We used Mycobacterium vanbaalenii PYR-1 Nid enzymes, the first type V RHO members to display an apparent substrate preference for HMW PAHs. Here, we examine the mechanism of the RHO reaction by integrating structural information of the NidAB and NidA3B3 enzymes with substrate and product data. This study gives us an understanding of how the model RHO systems of M. vanbaalenii PYR-1 metabolize HMW PAHs. The information obtained would also be helpful for successful application of RHO enzymes to the production of industrially and medically important chiral chemicals and the development of PAH bioremediation technologies. C1 [Kweon, Ohgew; Kim, Seong-Jae; Song, Jaekyeong; Cerniglia, Carl E.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Freeman, James P.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Song, Jaekyeong] Natl Inst Agr Biotechnol, Div Biosafety, Suwon, South Korea. [Baek, Songjoon] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Cerniglia, CE (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM carl.cerniglia@fda.hhs.gov FU National Center for Toxicological Research FX This work was supported in part by an appointment to the Postgraduate Research Program at the National Center for Toxicological Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 53 TC 12 Z9 13 U1 4 U2 28 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD MAY-JUN PY 2010 VL 1 IS 2 AR e00135-10 DI 10.1128/mBio.00135-10 PG 11 WC Microbiology SC Microbiology GA 686SX UT WOS:000284717100005 ER PT J AU Conti, R Veenstra, DL Armstrong, K Lesko, LJ Grosse, SD AF Conti, Rena Veenstra, David L. Armstrong, Katrina Lesko, Lawrence J. Grosse, Scott D. TI Personalized Medicine and Genomics: Challenges and Opportunities in Assessing Effectiveness, Cost-Effectiveness, and Future Research Priorities SO MEDICAL DECISION MAKING LA English DT Article DE cost-effectiveness analysis; pharmacoeconomics; resource allocation ID EGAPP-WORKING-GROUP; POLICY IMPLICATIONS; DRUG DEVELOPMENT; GENETIC TESTS; WARFARIN; HEALTH; CANCER; INFORMATION; PHARMACOGENETICS; RECOMMENDATIONS AB Personalized medicine is health care that tailors interventions to individual variation in risk and treatment response. Although medicine has long strived to achieve this goal, advances in genomics promise to facilitate this process. Relevant to present-day practice is the use of genomic information to classify individuals according to disease susceptibility or expected responsiveness to a pharmacologic treatment and to provide targeted interventions. A symposium at the annual meeting of the Society for Medical Decision Making on 23 October 2007 highlighted the challenges and opportunities posed in translating advances in molecular medicine into clinical practice. A panel of US experts in medical practice, regulatory policy, technology assessment, and the financing and organization of medical innovation was asked to discuss the current state of practice and research on personalized medicine as it relates to their own field. This article reports on the issues raised, discusses potential approaches to meet these challenges, and proposes directions for future work. The case of genetic testing to inform dosing with warfarin, an anticoagulant, is used to illustrate differing perspectives on evidence and decision making for personalized medicine. C1 [Grosse, Scott D.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA. [Conti, Rena] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. [Conti, Rena] Univ Chicago, Ctr Hlth & Social Sci, Chicago, IL 60637 USA. [Veenstra, David L.] Univ Washington, Dept Pharm, Seattle, WA 98195 USA. [Armstrong, Katrina] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Lesko, Lawrence J.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Grosse, SD (reprint author), Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, 1600 Clifton Rd,Mail Stop E-64, Atlanta, GA 30333 USA. EM SGrosse@cdc.gov FU Agency for Healthcare Research and Quality [R13 HS017305] FX Received 15 November 2008 from the Department of Pediatrics and Center for Health and the Social Sciences, University of Chicago, Chicago, Illinois (RC); Department of Pharmacy, University of Washington, Seattle (DLV); Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia (KA); Office of Clinical Pharmacology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland (LJL); and National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia (SDG). Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention or the Food and Drug Administration. This material was presented in a symposium at the annual meeting of the Society for Medical Decision Making in Pittsburgh, Pennsylvania, on 12 October 2007. The symposium was supported by conference grant R13 HS017305 from the Agency for Healthcare Research and Quality. We acknowledge helpful comments on this manuscript from Cindy Bryce, William D. Dotson, and 4 anonymous reviewers. Revision accepted for publication 12 June 2009. NR 66 TC 45 Z9 46 U1 7 U2 31 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD MAY-JUN PY 2010 VL 30 IS 3 BP 328 EP 340 DI 10.1177/0272989X09347014 PG 13 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 599EH UT WOS:000277892800008 PM 20086232 ER PT J AU Thomadsen, BR Heaton, HT Jani, SK Masten, JP Napolitano, ME Ouhib, Z Reft, CS Rivard, MJ Robin, TT Subramanian, M Suleiman, OH AF Thomadsen, Bruce R. Heaton, H. Thompson, II Jani, Shirish K. Masten, Jeffery P. Napolitano, Mary E. Ouhib, Zoubir Reft, Chester S. Rivard, Mark J. Robin, T. Tydings Subramanian, Manny Suleiman, Orhan H. TI Off-label use of medical products in radiation therapy: Summary of the Report of AAPM Task Group No. 121 SO MEDICAL PHYSICS LA English DT Article DE biomedical equipment; drugs; labelling (packaging); radiation therapy; regulation ID INTRAVASCULAR BRACHYTHERAPY SOURCE; BETA-PARTICLE SOURCES; MONTE-CARLO; P-32 SOURCE; DOSIMETRY CHARACTERIZATION; DOSE DISTRIBUTIONS; SOURCE TRAIN; LINE SOURCES; ENDOVASCULAR IRRADIATION; RESIDUAL PLAQUE AB Medical products (devices, drugs, or biologics) contain information in their labeling regarding the manner in which the manufacturer has determined that the products can be used in a safe and effective manner. The Food and Drug Administration (FDA) approves medical products for use for these specific indications which are part of the medical product's labeling. When medical products are used in a manner not specified in the labeling, it is commonly referred to as off-label use. The practice of medicine allows for this off-label use to treat individual patients, but the ethical and legal implications for such unapproved use can be confusing. Although the responsibility and, ultimately, the liability for off-label use often rests with the prescribing physician, medical physicists and others are also responsible for the safe and proper use of the medical products. When these products are used for purposes other than which they were approved, it is important for medical physicists to understand their responsibilities. In the United States, medical products can only be marketed if officially cleared, approved, or licensed by the FDA; they can be used if they are not subject to or specifically exempt from FDA regulations, or if they are being used in research with the appropriate regulatory safeguards. Medical devices are either cleared or approved by FDA's Center for Devices and Radiological Health. Drugs are approved by FDA's Center for Drug Evaluation and Research, and biological products such as vaccines or blood are licensed under a biologics license agreement by FDA's Center for Biologics Evaluation and Research. For the purpose of this report, the process by which the FDA eventually clears, approves, or licenses such products for marketing in the United States will be referred to as approval. This report summarizes the various ways medical products, primarily medical devices, can legally be brought to market in the United States, and includes a discussion of the approval process, along with manufacturers' responsibilities, labeling, marketing and promotion, and off-label use. This is an educational and descriptive report and does not contain prescriptive recommendations. This report addresses the role of the medical physicist in clinical situations involving off-label use. Case studies in radiation therapy are presented. Any mention of commercial products is for identification only; it does not imply recom-mendations or endorsements of any of the authors or the AAPM. The full report, containing extensive background on off-label use with several appendices, is available on the AAPM website (http://www.aapm.org/pubs/reports/). C1 [Thomadsen, Bruce R.] Univ Wisconsin, Dept Med Phys, Madison, WI 53705 USA. [Jani, Shirish K.] Sharp Mem Hosp & Rehabil Ctr, Dept Radiat Oncol, San Diego, CA 92123 USA. [Napolitano, Mary E.] Elekta Inc, Atlanta Res & Dev, Norcross, GA 30092 USA. [Ouhib, Zoubir] Lynn Reg Canc Ctr, Dept Radiat Oncol, Delray Beach, FL 33484 USA. [Reft, Chester S.] Univ Chicago, Dept Radiat Oncol, Chicago, IL 60637 USA. [Rivard, Mark J.] Tufts Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02111 USA. [Robin, T. Tydings] Theragenics Corp, Buford, GA 30518 USA. [Subramanian, Manny] Best Med Int Inc, Dept Res & Dev, Springfield, VA 22153 USA. [Suleiman, Orhan H.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Masten, Jeffery P.] Rapid City Reg Hosp, Rapid City, SD 57709 USA. RP Thomadsen, BR (reprint author), Univ Wisconsin, Dept Med Phys, Madison, WI 53705 USA. EM thomadsen@humonc.wisc.edu NR 76 TC 7 Z9 7 U1 0 U2 4 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAY PY 2010 VL 37 IS 5 BP 2300 EP 2311 DI 10.1118/1.3392286 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 590QT UT WOS:000277242800038 PM 20527564 ER PT J AU Kanungo, J AF Kanungo, Jyotshnabala TI Exogenously expressed human Ku70 stabilizes Ku80 in Xenopus oocytes and induces heterologous DNA-PK catalytic activity SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE Ku; DNA-PK; Oocyte; Xenopus; Protein-protein interaction ID DEPENDENT PROTEIN-KINASE; MOLECULAR-CLONING; STRANDED DNA; HELA-CELLS; AUTOANTIGEN; PHOSPHORYLATION; BINDING; TRANSLOCATION; LOCALIZATION; ARBACIA AB The Ku protein is a heterodimer composed of 70 kD (Ku70) and 80 kD (Ku80) subunits. Ku is the regulatory component of the DNA-dependent protein kinase (DNA-PK) that has a catalytic subunit of similar to 460 kD (DNA-PKcs). In this study, the two polypeptides (Ku80/Ku70) of the human Ku were expressed in Xenopus oocytes in order to investigate their over-expression, sub-cellular localization, and functional interaction with the Xenopus DNA-PKcs. In vitro-transcribed mRNAs for Ku70 and Ku80 were obtained from the respective plasmid constructs. The exogenously expressed proteins from the injected mRNAs were immunoprecipitated using a specific anti-T7 Tag antibody. The T7 Tag epitope is present in the vector at the amino-terminus and is in-frame with the Ku cDNA sequences. While injected Ku70 mRNA translated to a full-length Ku70 polypeptide that translocated to the nucleus, injected Ku80 mRNA resulted in the expression of a truncated product that was retained in the cytoplasm. Although Ku80 mRNA was stable for a period of 18 h in the oocytes post-microinjection, the protein was only stabilized when co-expressed with Ku70, suggesting that Ku80 is susceptible to proteolytic degradation when not dimerized with Ku70. Furthermore, the immunocomplex was capable of phosphorylating the DNA-PK-specific substrate thereby indicating that the holoenzyme could functionally reconstitute in vivo in the oocytes by heterologous subunits thus demonstrating evolutionary conservation of the enzyme subunit structure and function among diverse species. C1 [Kanungo, Jyotshnabala] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Kanungo, Jyotshnabala] Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA. RP Kanungo, J (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd,Bldg 53D,Rm 302O, Jefferson, AR 72079 USA. EM jyotshnabala.kanungo@fda.hhs.gov FU Institute of Molecular Medicine and Genetics; Mason Trust (Medical College of Georgia) FX This study was supported by funds from the Institute of Molecular Medicine and Genetics and The Mason Trust (Medical College of Georgia). NR 29 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 EI 1573-4919 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD MAY PY 2010 VL 338 IS 1-2 BP 291 EP 298 DI 10.1007/s11010-009-0363-3 PG 8 WC Cell Biology SC Cell Biology GA 584IP UT WOS:000276745400031 PM 20047046 ER PT J AU Mattes, WB Walker, EG Abadie, E Sistare, FD Vonderscher, J Woodcock, J Woosley, RL AF Mattes, William B. Walker, Elizabeth Gribble Abadie, Eric Sistare, Frank D. Vonderscher, Jacky Woodcock, Janet Woosley, Raymond L. TI Research at the interface of industry, academia and regulatory science FOREWORD SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID DRUG DEVELOPMENT; FOOD; PURPOSE; TOXICITY; PERSPECTIVE; BIOMARKERS; MEDICINE; REALITY; SAFETY C1 [Mattes, William B.; Walker, Elizabeth Gribble; Woosley, Raymond L.] Crit Path Inst, Tucson, AZ USA. [Abadie, Eric] European Med Agcy, London, England. [Sistare, Frank D.] Merck Res Labs, Dept Lab Sci & Invest Toxicol, West Point, PA USA. [Vonderscher, Jacky] Novartis, San Diego, CA USA. [Woodcock, Janet] US FDA, Silver Spring, MD USA. RP Mattes, WB (reprint author), Crit Path Inst, Tucson, AZ USA. EM wbmattes@gmail.com NR 28 TC 20 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 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAY PY 2010 VL 28 IS 5 BP 432 EP 433 DI 10.1038/nbt0510-432 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 593KG UT WOS:000277452700020 PM 20458309 ER PT J AU Goodsaid, F Papaluca, M AF Goodsaid, Federico Papaluca, Marisa TI Evolution of biomarker qualification at the health authorities SO NATURE BIOTECHNOLOGY LA English DT Article C1 [Goodsaid, Federico] US FDA, Silver Spring, MD USA. [Papaluca, Marisa] European Med Agcy, London, England. RP Goodsaid, F (reprint author), US FDA, Silver Spring, MD USA. EM federico.goodsaid@fda.hhs.gov; Marisa.Papaluca@ema.europa.eu NR 18 TC 18 Z9 18 U1 0 U2 3 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 MAY PY 2010 VL 28 IS 5 BP 441 EP 443 DI 10.1038/nbt0510-441 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 593KG UT WOS:000277452700022 PM 20458312 ER PT J AU Sistare, FD Dieterle, F Troth, S Holder, DJ Gerhold, D Andrews-Cleavenger, D Baer, W Betton, G Bounous, D Carl, K Collins, N Goering, P Goodsaid, F Gu, YZ Guilpin, V Harpur, E Hassan, A Jacobson-Kram, D Kasper, P Laurie, D Lima, BS Maciulaitis, R Mattes, W Maurer, G Obert, LA Ozer, J Papaluca-Amati, M Phillips, JA Pinches, M Schipper, MJ Thompson, KL Vamvakas, S Vidal, JM Vonderscher, J Walker, E Webb, C Yu, Y AF Sistare, Frank D. Dieterle, Frank Troth, Sean Holder, Daniel J. Gerhold, David Andrews-Cleavenger, Dina Baer, William Betton, Graham Bounous, Denise Carl, Kevin Collins, Nathaniel Goering, Peter Goodsaid, Federico Gu, Yi-Zhong Guilpin, Valerie Harpur, Ernie Hassan, Alita Jacobson-Kram, David Kasper, Peter Laurie, David Lima, Beatriz Silva Maciulaitis, Romaldas Mattes, William Maurer, Gerard Obert, Leslie Ann Ozer, Josef Papaluca-Amati, Marisa Phillips, Jonathan A. Pinches, Mark Schipper, Matthew J. Thompson, Karol L. Vamvakas, Spiros Vidal, Jean-Marc Vonderscher, Jacky Walker, Elizabeth Webb, Craig Yu, Yan TI Towards consensus practices to qualify safety biomarkers for use in early drug development SO NATURE BIOTECHNOLOGY LA English DT Article ID SURROGATE END-POINTS; MYOCARDIAL-INFARCTION AB Application of any new biomarker to support safety-related decisions during regulated phases of drug development requires provision of a substantial data set that critically assesses analytical and biological performance of that biomarker. Such an approach enables stakeholders from industry and regulatory bodies to objectively evaluate whether superior standards of performance have been met and whether specific claims of fit-for-purpose use are supported. It is therefore important during the biomarker evaluation process that stakeholders seek agreement on which critical experiments are needed to test that a biomarker meets specific performance claims, how new biomarker and traditional comparators will be measured and how the resulting data will be merged, analyzed and interpreted. C1 [Sistare, Frank D.; Troth, Sean; Holder, Daniel J.; Gerhold, David; Yu, Yan] Merck Res Labs, West Point, PA USA. [Andrews-Cleavenger, Dina] Amgen Inc, Thousand Oaks, CA 91320 USA. [Dieterle, Frank; Carl, Kevin; Laurie, David; Maurer, Gerard] Nova Pharma AG, Basel, Switzerland. [Baer, William; Hassan, Alita; Schipper, Matthew J.; Webb, Craig] ClinXus, Grand Rapids, MI USA. [Baer, William; Hassan, Alita; Schipper, Matthew J.; Webb, Craig] Van Andel Res Inst, Grand Rapids, MI USA. [Bounous, Denise] Bristol Myers Squibb Co, Princeton, NJ USA. [Collins, Nathaniel; Gu, Yi-Zhong] Schering Plough Res Inst, Summit, NJ USA. [Goering, Peter; Goodsaid, Federico; Jacobson-Kram, David; Thompson, Karol L.] US FDA, Silver Spring, MD USA. [Guilpin, Valerie; Harpur, Ernie] Sanofi Aventis, Malvern, PA USA. [Kasper, Peter; Maciulaitis, Romaldas; Papaluca-Amati, Marisa; Vamvakas, Spiros; Vidal, Jean-Marc] European Med Agcy, London, England. [Lima, Beatriz Silva] Univ Lisbon, IMED UL, P-1699 Lisbon, Portugal. [Mattes, William; Walker, Elizabeth] Crit Path Inst, Tucson, AZ USA. [Obert, Leslie Ann; Ozer, Josef] Pfizer Inc, Groton, CT 06340 USA. [Phillips, Jonathan A.] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. [Vonderscher, Jacky] Hoffmann La Roche AG, Basel, Switzerland. RP Sistare, FD (reprint author), Merck Res Labs, West Point, PA USA. EM frank_sistare@merck.com RI Webb, Craig/I-8123-2012; Silva Lima, Beatriz/A-4284-2014; iMed.ULisboa, iMed.ULisboa/C-6292-2014; iMed.ULisboa, PharmRegSci /B-5723-2014 OI Silva Lima, Beatriz/0000-0003-0910-7245; iMed.ULisboa, PharmRegSci /0000-0003-0910-7245 NR 24 TC 56 Z9 57 U1 0 U2 4 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 MAY PY 2010 VL 28 IS 5 BP 446 EP 454 DI 10.1038/nbt.1634 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 593KG UT WOS:000277452700024 PM 20458314 ER PT J AU Dieterle, F Sistare, F Goodsaid, F Papaluca, M Ozer, JS Webb, CP Baer, W Senagore, A Schipper, MJ Vonderscher, J Sultana, S Gerhold, DL Phillips, JA Maurer, G Carl, K Laurie, D Harpur, E Sonee, M Ennulat, D Holder, D Andrews-Cleavenger, D Gu, YZ Thompson, KL Goering, PL Vidal, JM Abadie, E Maciulaitis, R Jacobson-Kram, D Defelice, AF Hausner, EA Blank, M Thompson, A Harlow, P Throckmorton, D Xiao, S Xu, N Taylor, W Vamvakas, S Flamion, B Lima, BS Kasper, P Pasanen, M Prasad, K Troth, S Bounous, D Robinson-Gravatt, D Betton, G Davis, MA Akunda, J McDuffie, JE Suter, L Obert, L Guffroy, M Pinches, M Jayadev, S Blomme, EA Beushausen, SA Barlow, VG Collins, N Waring, J Honor, D Snook, S Lee, JH Rossi, P Walker, E Mattes, W AF Dieterle, Frank Sistare, Frank Goodsaid, Federico Papaluca, Marisa Ozer, Josef S. Webb, Craig P. Baer, William Senagore, Anthony Schipper, Matthew J. Vonderscher, Jacky Sultana, Stefan Gerhold, David L. Phillips, Jonathan A. Maurer, Gerard Carl, Kevin Laurie, David Harpur, Ernie Sonee, Manisha Ennulat, Daniela Holder, Dan Andrews-Cleavenger, Dina Gu, Yi-Zhong Thompson, Karol L. Goering, Peter L. Vidal, Jean-Marc Abadie, Eric Maciulaitis, Romaldas Jacobson-Kram, David Defelice, Albert F. Hausner, Elizabeth A. Blank, Melanie Thompson, Aliza Harlow, Patricia Throckmorton, Douglas Xiao, Shen Xu, Nancy Taylor, William Vamvakas, Spiros Flamion, Bruno Lima, Beatriz Silva Kasper, Peter Pasanen, Markku Prasad, Krishna Troth, Sean Bounous, Denise Robinson-Gravatt, Denise Betton, Graham Davis, Myrtle A. Akunda, Jackie McDuffie, James Eric Suter, Laura Obert, Leslie Guffroy, Magalie Pinches, Mark Jayadev, Supriya Blomme, Eric A. Beushausen, Sven A. Barlow, Valerie G. Collins, Nathaniel Waring, Jeff Honor, David Snook, Sandra Lee, Jinhe Rossi, Phil Walker, Elizabeth Mattes, William TI Renal biomarker qualification submission: a dialog between the FDA-EMEA and Predictive Safety Testing Consortium SO NATURE BIOTECHNOLOGY LA English DT Article ID DISEASE AB The first formal qualification of safety biomarkers for regulatory decision making marks a milestone in the application of biomarkers to drug development. Following submission of drug toxicity studies and analyses of biomarker performance to the Food and Drug Administration (FDA) and European Medicines Agency (EMEA) by the Predictive Safety Testing Consortium's (PSTC) Nephrotoxicity Working Group, seven renal safety biomarkers have been qualified for limited use in nonclinical and clinical drug development to help guide safety assessments. This was a pilot process, and the experience gained will both facilitate better understanding of how the qualification process will probably evolve and clarify the minimal requirements necessary to evaluate the performance of biomarkers of organ injury within specific contexts. C1 [Dieterle, Frank; Maurer, Gerard; Carl, Kevin; Laurie, David] Novartis Pharma AG, Basel, Switzerland. [Sistare, Frank; Ozer, Josef S.; Gerhold, David L.] Merck Res Labs, Dept Invest Lab Sci, West Point, PA USA. [Goodsaid, Federico; Thompson, Karol L.; Goering, Peter L.; Jacobson-Kram, David; Defelice, Albert F.; Hausner, Elizabeth A.; Blank, Melanie; Thompson, Aliza; Harlow, Patricia; Throckmorton, Douglas; Xiao, Shen; Xu, Nancy; Taylor, William] US FDA, Silver Spring, MD USA. [Papaluca, Marisa; Vidal, Jean-Marc; Abadie, Eric; Maciulaitis, Romaldas; Vamvakas, Spiros; Flamion, Bruno; Lima, Beatriz Silva; Kasper, Peter; Pasanen, Markku; Prasad, Krishna] European Med Agcy, London, England. [Webb, Craig P.; Baer, William; Senagore, Anthony; Schipper, Matthew J.; Sultana, Stefan] ClinXus, Grand Rapids, MI USA. [Webb, Craig P.] Van Andel Res Inst, Grand Rapids, MI USA. [Baer, William] Grand Valley Med Specialists, Grand Rapids, MI USA. [Senagore, Anthony] Spectrum Hlth, Grand Rapids, MI USA. [Schipper, Matthew J.] Innovat Analyt Inc, Kalamazoo, MI USA. [Vonderscher, Jacky; Suter, Laura] Hoffmann La Roche AG, Basel, Switzerland. [Phillips, Jonathan A.; Jayadev, Supriya] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. [Harpur, Ernie; Guffroy, Magalie; Barlow, Valerie G.] Sanofi Aventis, Malvern, PA USA. [Sonee, Manisha; McDuffie, James Eric; Snook, Sandra] Johnson & Johnson, San Diego, CA USA. [Ennulat, Daniela] GlaxoSmith, King Of Prussia, PA USA. [Holder, Dan] Merck Res Labs, Dept Biometr, West Point, PA USA. [Andrews-Cleavenger, Dina] Amgen Inc, Thousand Oaks, CA 91320 USA. [Gu, Yi-Zhong; Collins, Nathaniel] Schering Plough Res Inst, Summit, NJ USA. [Maciulaitis, Romaldas] Kaunas Med Univ, Dept Basic & Clin Pharmacol, Nephrol Clin Kaunas Med Univ Clin, Kaunas, Lithuania. [Maciulaitis, Romaldas] State Med Control Agcy, Kaunas, Lithuania. [Pasanen, Markku] Univ Kuopio, Dept Pharmacol & Toxicol, FIN-70211 Kuopio, Finland. [Troth, Sean] Merck Res Labs, Dept Pathol, West Point, PA USA. [Bounous, Denise] Bristol Myers Squibb Co, Princeton, NJ USA. [Robinson-Gravatt, Denise; Obert, Leslie; Beushausen, Sven A.] Pfizer Inc, Groton, CT 06340 USA. [Betton, Graham; Pinches, Mark] AstraZeneca, Macclesfield, Cheshire, England. [Davis, Myrtle A.] NCI, Natl Inst Hlth, Bethesda, MD 20892 USA. [Akunda, Jackie] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Blomme, Eric A.; Waring, Jeff; Honor, David; Lee, Jinhe] Abbott Labs, Abbott Pk, IL 60064 USA. [Rossi, Phil; Walker, Elizabeth; Mattes, William] Crit Path Inst, Tucson, AZ USA. RP Dieterle, F (reprint author), Novartis Pharma AG, Basel, Switzerland. EM frank.dieterle@novartis.com RI Webb, Craig/I-8123-2012; Silva Lima, Beatriz/A-4284-2014; iMed.ULisboa, iMed.ULisboa/C-6292-2014; iMed.ULisboa, PharmRegSci /B-5723-2014 OI Silva Lima, Beatriz/0000-0003-0910-7245; iMed.ULisboa, PharmRegSci /0000-0003-0910-7245 NR 12 TC 171 Z9 178 U1 0 U2 23 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 MAY PY 2010 VL 28 IS 5 BP 455 EP 462 DI 10.1038/nbt.1625 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 593KG UT WOS:000277452700025 PM 20458315 ER PT J AU Vaidya, VS Ozer, JS Dieterle, F Collings, FB Ramirez, V Troth, S Muniappa, N Thudium, D Gerhold, D Holder, DJ Bobadilla, NA Marrer, E Perentes, E Cordier, A Vonderscher, J Maurer, G Goering, PL Sistare, FD Bonventre, JV AF Vaidya, Vishal S. Ozer, Josef S. Dieterle, Frank Collings, Fitz B. Ramirez, Victoria Troth, Sean Muniappa, Nagaraja Thudium, Douglas Gerhold, David Holder, Daniel J. Bobadilla, Norma A. Marrer, Estelle Perentes, Elias Cordier, Andre Vonderscher, Jacky Maurer, Gerard Goering, Peter L. Sistare, Frank D. Bonventre, Joseph V. TI Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies SO NATURE BIOTECHNOLOGY LA English DT Article ID NEPHROTOXICITY; RECEPTOR; CONFERS; URINE; KIM-1; CELLS AB Kidney toxicity accounts both for the failure of many drug candidates as well as considerable patient morbidity. Whereas histopathology remains the gold standard for nephrotoxicity in animal systems, serum creatinine (SCr) and blood urea nitrogen (BUN) are the primary options for monitoring kidney dysfunction in humans. The transmembrane tubular protein kidney injury molecule-1 (Kim-1) was previously reported to be markedly induced in response to renal injury. Owing to the poor sensitivity and specificity of SCr and BUN, we used rat toxicology studies to compare the diagnostic performance of urinary Kim-1 to BUN, SCr and urinary N-acetyl-beta-d-glucosaminidase (NAG) as predictors of kidney tubular damage scored by histopathology. Kim-1 outperforms SCr, BUN and urinary NAG in multiple rat models of kidney injury. Urinary Kim-1 measurements may facilitate sensitive, specific and accurate prediction of human nephrotoxicity in preclinical drug screens. This should enable early identification and elimination of compounds that are potentially nephrotoxic. C1 [Vaidya, Vishal S.; Collings, Fitz B.; Ramirez, Victoria; Bonventre, Joseph V.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Renal Div,Dept Med, Boston, MA 02115 USA. [Ozer, Josef S.; Thudium, Douglas; Gerhold, David; Sistare, Frank D.] Merck Res Labs, Dept Investigat Lab Sci, West Point, PA USA. [Dieterle, Frank; Marrer, Estelle; Perentes, Elias; Cordier, Andre; Vonderscher, Jacky; Maurer, Gerard] Novartis Inst BioMed Res, Basel, Switzerland. [Troth, Sean; Muniappa, Nagaraja] Merck Res Labs, Dept Pathol, West Point, PA USA. [Holder, Daniel J.] Merck Res Labs, Dept Biometr, West Point, PA USA. [Bobadilla, Norma A.] Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mol Physiol Unit, Mexico City 04510, DF, Mexico. [Bobadilla, Norma A.] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City, DF, Mexico. [Goering, Peter L.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Vaidya, VS (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Renal Div,Dept Med, Boston, MA 02115 USA. EM vvaidya@partners.org; josef_ozer@merck.com OI Ramirez, Victoria/0000-0002-2782-1381 FU National Institutes of Health [ES016723, DK39773, DK72831, DK74099]; Mexican Council of Science and Technology (CONACYT) [G34511M, CO1-40182A-1]; National University of Mexico [DGAPA IN208602-3] FX Part of this work was presented at the American Society of Nephrology meeting in Philadelphia, November 7-11, 2005 and the Society of Toxicology meeting in Charlotte, North Carolina, March 4-9, 2007. This work was supported by National Institutes of Health grants ES016723 to V. S. V.; DK39773, DK72831 and DK74099 to J.V.B., and by research grants G34511M and CO1-40182A-1 from the Mexican Council of Science and Technology (CONACYT) and DGAPA IN208602-3 of National University of Mexico to N.A.B. We thank T. W. Forest, B. Sacre-Salem and T. E. Adams for providing histomorphologic readings for the Merck studies. The Novartis Biomarker CRADA team is acknowledged for contributing to the project, in particular D. R. Roth, A. Mahl, F. Staedtler, P. Verdes, D. Wahl, F. Legay, P. End and S.-D. Chibout. We thank P. Bernd for performing the protein homogenization. S. Leuillet and B. Palate from CIT are acknowledged for performing the Novartis in-life studies and the histopathology assessment. J. Mapes from Rules Based Medicine is acknowledged for the Kim-1 measurements of the Novartis studies. We thank D. Moor and P. Brodmann from Biolytix for the validation and measurements of the RT-PCR assays. We thank M. Topper, W. Bailey, G. Miller and P. Srinivasa for helpful comments on the manuscript. We thank K. Thompson from Center for Drug Evaluation and Research, US FDA for critically reviewing the manuscript. NR 30 TC 219 Z9 241 U1 1 U2 23 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 MAY PY 2010 VL 28 IS 5 BP 478 EP U135 DI 10.1038/nbt.1623 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 593KG UT WOS:000277452700028 PM 20458318 ER PT J AU Perez-De La Cruz, V Elinos-Calderon, D Carrillo-Mora, P Silva-Adaya, D Konigsberg, M Moran, J Ali, SF Chanez-Cardenas, ME Perez-De La Cruz, G Santamaria, A AF Perez-De La Cruz, Veronica Elinos-Calderon, Diana Carrillo-Mora, Paul Silva-Adaya, Daniela Konigsberg, Mina Moran, Julio Ali, Syed F. Elena Chanez-Cardenas, Maria Perez-De La Cruz, Gonzalo Santamaria, Abel TI Time-course correlation of early toxic events in three models of striatal damage: Modulation by proteases inhibition SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article DE Quinolinate; 3-nitropropionic acid; Neurotoxicity; Calpains; Caspases; Protease inhibitors; Neuroprotection; Oxidative stress; Energy depletion; Cell damage ID RAT CORPUS STRIATUM; METHYL-D-ASPARTATE; INDUCED LIPID-PEROXIDATION; ACID-INDUCED NEUROTOXICITY; QUINOLINIC ACID; 3-NITROPROPIONIC ACID; CELL-DEATH; HUNTINGTONS-DISEASE; ENERGY-METABOLISM; OXIDATIVE STRESS AB Metabolic alterations in the nervous system can be produced at early stages of toxicity and are linked with oxidative stress, energy depletion and death signaling. Proteases activation is responsible for triggering deadly cascades during cell damage in toxic models. In this study we evaluated the early time-course of toxic events (oxidative damage to lipids, mitochondrial dysfunction and LDH leakage, all at 1,3 and 6 h) in rat striatal slices exposed to quinolinic acid (QUIN, 100 mu M) as an excitotoxic/pro-oxidant model, 3-nitropropionic acid (3-NP, 1 mM) as an inhibitor of mitochondria] succinate dehydrogenase, and a combined model produced by the co-administration of these two toxins at subtoxic concentrations (21 and 166 mu M for QUIN and 3-NP, respectively). In order to further characterize a possible causality of caspases or calpains on the toxic mechanisms produced in these models, the broad calpain inhibitor IC1 (50 mu M), and the pan-caspase inhibitor Z-VAD (100 mu M) were tested. Lipid peroxidation (LP) was increased at all times and in all models evaluated. Both IC1 and Z-VAD exerted significant protection against LP in all models and at all times evaluated. Mitochondrial dysfunction (MD) was consistently affected by all toxic models at 3 and 6 h, but was mostly affected by 3-NP and QUIN at 1 h. IC1 differentially protected the slices against 3-NP and QUIN at 1 h and against QUIN at 3 h, while Z-VAD exhibited positive actions against QUIN and 3-NP at all times tested, and against their combination at 3 and 6 h. LDH leakage was enhanced at 1 and 3 h in all toxic models, but this effect was evident only for 3-NP + QUIN and 3-NP at 6 h. IC1 protected against LDH leakage at 1 h in 3-NP + QUIN and 3-NP models, at 3 h in all toxic models, and at 6 h in 3-NP + QUIN and 3-NP models. In turn, Z-VAD protected at 1 and 6 h in all models tested, and at 3 h in the combined and QUIN models. Our results suggest differential chronologic and mechanistic patterns, depending on the toxic insult. Although LP, MD and membrane cell rupture are shared by the three models, the occurrence of each event seems to obey to a selective recruitment of damaging signals, including a differential activation of proteases in time. Proteases activation is likely to be an up-stream event influencing oxidative stress and mitochondrial dysfunction in these toxic models. (c) 2010 Elsevier Ltd. All rights reserved. C1 [Perez-De La Cruz, Veronica; Elinos-Calderon, Diana; Carrillo-Mora, Paul; Silva-Adaya, Daniela; Perez-De La Cruz, Gonzalo; Santamaria, Abel] Inst Nacl Neurol & Neurocirugia Manuel Velasco Su, Lab Aminoacidos Excitadores, Mexico City 14269, DF, Mexico. [Perez-De La Cruz, Veronica; Konigsberg, Mina] Univ Autonoma Metropolitana Iztapalapa, Dept Ciencias Salud, Div Ciencias Biol & Salud, Mexico City 09340, DF, Mexico. [Moran, Julio] Univ Nacl Autonoma Mexico, Dept Neurociencias, Inst Fisiol Celular, Mexico City 04510, DF, Mexico. [Ali, Syed F.; Santamaria, Abel] US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Elena Chanez-Cardenas, Maria] Inst Nacl Neurol & Neurocirugia Manuel Velasco Su, Lab Patol Vasc Cerebral, Mexico City 14269, DF, Mexico. RP Santamaria, A (reprint author), Inst Nacl Neurol & Neurocirugia Manuel Velasco Su, Lab Aminoacidos Excitadores, Mexico City 14269, DF, Mexico. EM absada@yahoo.com FU CONACyT [48370-Q] FX This work was supported by CONACyT Grant 48370-Q (A.S.). NR 60 TC 16 Z9 16 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD MAY-JUN PY 2010 VL 56 IS 6-7 BP 834 EP 842 DI 10.1016/j.neuint.2010.03.008 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 605BC UT WOS:000278321300015 PM 20332007 ER PT J AU Ferguson, SA Garey, J Smith, ME Twaddle, NC Doerge, DR Paule, MG AF Ferguson, Sherry A. Garey, Joan Smith, Melody E. Twaddle, Nathan C. Doerge, Daniel R. Paule, Merle G. TI Preweaning behaviors, developmental landmarks, and acrylamide and glycidamide levels after pre- and postnatal acrylamide treatment in rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Acrylamide; Righting; Negative geotaxis; Activity; Rat ID FISCHER-344 RATS; DIETARY-INTAKE; PERIPHERAL NEUROPATHY; EXPOSURE; FOOD; NEUROTOXICITY; WORKERS; TOXICOKINETICS; ADOLESCENTS; METABOLISM AB At high levels of exposure, acrylamide monomer (AA) is a known neurotoxicant (LoPachin, 2004 [23]). The effects of lower levels of exposure, such as those experienced via a typical human diet, have not been widely investigated. Data at these levels are particularly relevant given the widespread human exposure through carbohydrate-containing foods cooked at high temperatures. Additionally, daily AA intake is estimated to be higher for infants and children. Earlier, we described behavioral alterations in preweaning rats resulting from developmental AA treatment (0.5-10.0 mg/kg/day) (Carey et al., 2005 [14]). In the present study, the effects of lower doses were measured as well as serum AA and glycidimide (GA) levels in dams, fetuses, and young pups. Pregnant Fischer 344 dams (n = 48-58/treatment group) were gavaged with 0.0, 0.1, 0.3, 1.0, or 5.0 mg AA/kg/day beginning on gestational day 6 and ending on the day of parturition. Beginning on postnatal day 1 (PND 1) and continuing through PND 21, all pups/litter were gavaged with the same dose as their dam. There were no M treatment effects on offspring fur development, pinnae detachment, or eye opening. Offspring body weight was somewhat decreased by 5.0 mg/kg/day, particularly in males. However, righting reflex (PNDs 4-7), slant board (i.e., negative geotaxis) (PNDs 8-10), forelimb hang (PNDs 12-16), and rotarod behavior (PNDs 21-22) were not significantly altered by AA treatment. Male and female offspring of the 5.0 mg/kg/day group were 30-49% less active in the open field at PNDs 19-20 (p<0.05). Serum AA levels of GD20 dams and their fetuses were comparable, indicating the ability of AA to cross the placental barrier. AA levels of pups were not affected by age (PND 1 and 22) or sex. In all rats, serum AA and GA levels exhibited a dose-response relationship. These data extend those of our previous study (Carey et al., 2005 [14]) and demonstrate that overt preweaning neurobehavioral effects are apparent in rats exposed to acrylamide pre- and postnatally, but only at the highest doses tested. Published by Elsevier Inc. C1 [Ferguson, Sherry A.; Garey, Joan; Smith, Melody E.; Paule, Merle G.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Twaddle, Nathan C.; Doerge, Daniel R.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Ferguson, SA (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM Sherry.Ferguson@fda.hhs.gov FU NCTR/FDA [224-07-007]; National Institute for Environmental Health Sciences/National Toxicology Program [224-07-007]; Oak Ridge Institute for Science and Education FX The authors gratefully appreciate the technical expertise provided by Mr. Delbert Law of the Bionetics Corporation and his incredibly talented staff of animal care technicians. This study was supported by Interagency Agreement #224-07-007 between the NCTR/FDA and the National Institute for Environmental Health Sciences/National Toxicology Program. J. Garey and M. Smith were supported by a postdoctoral fellowship and a Science Internship, respectively, from 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 40 TC 7 Z9 7 U1 3 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2010 VL 32 IS 3 BP 373 EP 382 DI 10.1016/j.ntt.2010.01.010 PG 10 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 602XY UT WOS:000278173600007 PM 20117204 ER PT J AU Dworkin, RH Turk, DC Peirce-Sandner, S Baron, R Bellamy, N Burke, LB Chappell, A Chartier, K Cleeland, CS Costello, A Cowan, P Dimitrova, R Ellenberg, S Farrar, JT French, JA Gilron, I Hertz, S Jadad, AR Jay, GW Kalliomaki, J Katz, NP Kerns, RD Manning, DC McDermott, MP McGrath, PJ Narayana, A Porter, L Quessy, S Rappaport, BA Rauschkolb, C Reeve, BB Rhodes, T Sampaio, C Simpson, DM Stauffer, JW Stucki, G Tobias, J White, RE Witter, J AF Dworkin, Robert H. Turk, Dennis C. Peirce-Sandner, Sarah Baron, Ralf Bellamy, Nicholas Burke, Laurie B. Chappell, Amy Chartier, Kevin Cleeland, Charles S. Costello, Ann Cowan, Penney Dimitrova, Rozalina Ellenberg, Susan Farrar, John T. French, Jacqueline A. Gilron, Ian Hertz, Sharon Jadad, Alejandro R. Jay, Gary W. Kalliomaki, Jarkko Katz, Nathaniel P. Kerns, Robert D. Manning, Donald C. McDermott, Michael P. McGrath, Patrick J. Narayana, Arvind Porter, Linda Quessy, Steve Rappaport, Bob A. Rauschkolb, Christine Reeve, Bryce B. Rhodes, Thomas Sampaio, Cristina Simpson, David M. Stauffer, Joseph W. Stucki, Gerold Tobias, Jeffrey White, Richard E. Witter, James TI Research design considerations for confirmatory chronic pain clinical trials: IMMPACT recommendations SO PAIN LA English DT Review DE Chronic pain; Randomized clinical trials; Research design; Phase 3 trials; Subject selection ID RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; LOW-BACK-PAIN; MAJOR DEPRESSIVE DISORDER; OSTEOARTHRITIS-RESEARCH-SOCIETY; DIABETIC PERIPHERAL NEUROPATHY; OXYMORPHONE EXTENDED-RELEASE; ACTIVE-CONTROL TRIALS; CORE OUTCOME DOMAINS; LEAD-IN PERIOD AB There has been an increase in the number of chronic pain clinical trials in which the treatments being evaluated did not differ significantly from placebo in the primary efficacy analyses despite previous research suggesting that efficacy could be expected. These findings could reflect a true lack of efficacy or methodological and other aspects of these trials that compromise the demonstration of efficacy. There is substantial variability among chronic pain clinical trials with respect to important research design considerations, and identifying and addressing any methodological weaknesses would enhance the likelihood of demonstrating the analgesic effects of new interventions. An IMMPACT consensus meeting was therefore convened to identify the critical research design considerations for confirmatory chronic pain trials and to make recommendations for their conduct. We present recommendations for the major components of confirmatory chronic pain clinical trials, including participant selection, trial phases and duration, treatment groups and dosing regimens, and types of trials. Increased attention to and research on the methodological aspects of confirmatory chronic pain clinical trials has the potential to enhance their assay sensitivity and ultimately provide more meaningful evaluations of treatments for chronic pain. (C) 2010 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved. C1 [Dworkin, Robert H.; Peirce-Sandner, Sarah] Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY 14642 USA. [Turk, Dennis C.] Univ Washington, Seattle, WA 98195 USA. [Baron, Ralf] Univ Kiel, Kiel, Germany. [Bellamy, Nicholas] Univ Queensland, Brisbane, Qld, Australia. [Burke, Laurie B.; Costello, Ann; Hertz, Sharon; Rappaport, Bob A.] US FDA, Silver Spring, MD USA. [Chappell, Amy] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Chartier, Kevin] United BioSource Corp, Newtown, PA USA. [Cleeland, Charles S.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Cowan, Penney] Amer Chron Pain Assoc, Rocklin, CA USA. [Dimitrova, Rozalina] Allergan Pharmaceut Inc, Irvine, CA USA. [Ellenberg, Susan; Farrar, John T.; French, Jacqueline A.] NYU, New York, NY USA. [Gilron, Ian] Queens Univ, Kingston, ON, Canada. [Jadad, Alejandro R.] Univ Toronto, Toronto, ON, Canada. [Jay, Gary W.] Schwarz Biosci, Res Triangle Pk, NC USA. [Kalliomaki, Jarkko] AstraZeneca, Sodertalje, Sweden. [Katz, Nathaniel P.] Analges Res, Needham, MA USA. [Kerns, Robert D.] Dept Vet Affairs, West Haven, CT USA. [Manning, Donald C.] Celgene Corp, Warren, NJ USA. [McDermott, Michael P.] Univ Rochester, Rochester, NY USA. [McGrath, Patrick J.] Dalhousie Univ, Halifax, NS, Canada. [McGrath, Patrick J.] IWK Hlth Ctr, Halifax, NS, Canada. [Narayana, Arvind] Cephalon Inc, Frazer, PA USA. [Quessy, Steve] Qd Consulting LLC, Res Triangle Pk, NC USA. [Rauschkolb, Christine] Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ USA. [Reeve, Bryce B.] NCI, NIH, Bethesda, MD 20892 USA. [Rhodes, Thomas] Merck & Co Inc, Blue Bell, PA USA. [Sampaio, Cristina] Fac Med Lisbon, Lisbon, Portugal. [Simpson, David M.] Mt Sinai Sch Med, New York, NY USA. [Stauffer, Joseph W.] Alpharma, Piscataway, NJ USA. [Stucki, Gerold] Univ Lucerne & Swiss Parapleg Res, Luzern, Switzerland. [Tobias, Jeffrey] NeurogesX Inc, San Carlos, CA USA. [White, Richard E.] Endo Pharmaceut Inc, Chadds Ford, PA 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; Baron, Ralf/E-4298-2010; French, Jacqueline/G-6795-2013; Bellamy, Nicholas/G-3631-2010; OI Farrar, John/0000-0001-8656-5157; French, Jacqueline/0000-0003-2242-8027; McGrath, Patrick/0000-0002-9568-2571 FU US Department of Veterans Affairs; US Food and Drug Administration; US National Institutes of Health; University of Rochester Office of Continuing Professional Education FX The views expressed in this article are those of the authors, none of whom have financial conflicts of interest related to the issues discussed in this manuscript. No official endorsement by the US Department of Veterans Affairs, US Food and Drug Administration, US National Institutes of Health, or the pharmaceutical companies that provided unrestricted grants to the University of Rochester Office of Continuing Professional Education should be inferred.; The authors thank Paul J. Lambiase and Mary Gleichauf for their invaluable assistance in the organization of the IMMPACT meeting and acknowledge NPK's suggestion of the term "Good Research Practice" Unrestricted grants were provided to the University of Rochester Office of Continuing Professional Education to support the activities of IMMPACT, including the consensus meeting on which this article is based, by Allergan, Alpharma, AstraZeneca, Celgene, Cephalon, Eli Lilly, Endo, GlaxoSmithKline, Johnson & Johnson, Merck, NeurogesX, Pfizer, and Schwarz Biosciences. NR 158 TC 131 Z9 132 U1 4 U2 28 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD MAY PY 2010 VL 149 IS 2 BP 177 EP 193 DI 10.1016/j.pain.2010.02.018 PG 17 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 587HK UT WOS:000276980900007 PM 20207481 ER PT J AU Cruz, ML Deyton, LR AF Cruz, Marisa L. Deyton, Lawrence R. TI A New Regulatory Challenge: Youth and Tobacco SO PEDIATRICS LA English DT Editorial Material ID SMOKERS C1 [Cruz, Marisa L.; Deyton, Lawrence R.] US FDA, Ctr Tobacco Prod, Rockville, MD 20850 USA. RP Cruz, ML (reprint author), US FDA, Ctr Tobacco Prod, 9200 Corp Blvd,Room 100B, Rockville, MD 20850 USA. EM marisa.cruz@fda.hhs.gov NR 9 TC 1 Z9 1 U1 1 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 MAY PY 2010 VL 125 IS 5 BP 1066 EP 1067 DI 10.1542/peds.2010-0538 PG 2 WC Pediatrics SC Pediatrics GA 590NI UT WOS:000277232800026 PM 20403927 ER PT J AU Hamburg, M AF Hamburg, Margaret TI Bringing home the genome: the US FDA's role in realizing personalized medicine SO PERSONALIZED MEDICINE LA English DT News Item C1 US FDA, Rockville, MD 20857 USA. RP Hamburg, M (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 1 U2 3 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 MAY PY 2010 VL 7 IS 3 BP 239 EP 242 DI 10.2217/PME.10.27 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 596YX UT WOS:000277722900009 ER PT J AU Silberstein, E Mihalik, K Ulitzky, L Plant, EP Puig, M Gagneten, S Yu, MYW Kaushik-Basu, N Feinstone, SM Taylor, DR AF Silberstein, Erica Mihalik, Kathleen Ulitzky, Laura Plant, Ewan P. Puig, Montserrat Gagneten, Sara Yu, Mei-ying W. Kaushik-Basu, Neerja Feinstone, Stephen M. Taylor, Deborah R. TI Persistent Growth of a Human Plasma-Derived Hepatitis C Virus Genotype 1b Isolate in Cell Culture SO PLOS PATHOGENS LA English DT Article ID DOUBLE-STRANDED-RNA; PROTEIN-KINASE PKR; SMALL INTERFERING RNAS; IN-VITRO; GENOMIC RNA; NEUTRALIZING ANTIBODIES; PRIMARY HEPATOCYTES; ANTIVIRAL PATHWAY; INNATE IMMUNITY; MESSENGER-RNA AB HCV (hepatitis C virus) research, including therapeutics and vaccine development, has been hampered by the lack of suitable tissue culture models. Development of cell culture systems for the growth of the most drug-resistant HCV genotype (1b) as well as natural isolates has remained a challenge. Transfection of cultured cells with adenovirus-associated RNAI (VA RNAI), a known interferon (IFN) antagonist and inhibitor of dsRNA-mediated antiviral pathways, enhanced the growth of plasma-derived HCV genotype 1b. Furthermore, persistent viral growth was achieved after passaging through IFN-alpha/beta-deficient VeroE6 cells for 2 years. Persistently infected cells were maintained in culture for an additional 4 years, and the virus rescued from these cells induced strong cytopathic effect (CPE). Using a CPE-based assay, we measured inhibition of viral production by anti-HCV specific inhibitors, including 2'-C-Methyl-D-Adenosine, demonstrating its utility for the evaluation of HCV antivirals. This virus constitutes a novel tool for the study of one of the most relevant strains of HCV, genotype 1b, which will now be available for HCV life cycle research and useful for the development of new therapeutics. C1 [Silberstein, Erica; Ulitzky, Laura; Plant, Ewan P.; Taylor, Deborah R.] US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Mihalik, Kathleen; Gagneten, Sara; Feinstone, Stephen M.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Puig, Montserrat] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. [Yu, Mei-ying W.] US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Kaushik-Basu, Neerja] Univ Med & Dent New Jersey, Dept Biochem & Mol Biol, Newark, NJ 07103 USA. RP Silberstein, E (reprint author), US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM deborah.taylor@FDA.HHS.gov OI Plant, Ewan/0000-0003-0166-5939 FU Food and Drug Administration, Department of Health and Human Services; National Institutes of Health [DK066837] FX This work was supported by the Food and Drug Administration, Department of Health and Human Services, and by a grant (DK066837) to NK-B from the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation 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 64 TC 13 Z9 13 U1 1 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD MAY PY 2010 VL 6 IS 5 AR e1000910 DI 10.1371/journal.ppat.1000910 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 610TL UT WOS:000278759900029 PM 20502631 ER PT J AU Feng, JH Heinze, TM Xu, HY Cerniglia, CE Chen, HZ AF Feng, Jinhui Heinze, Thomas M. Xu, Haiyan Cerniglia, Carl E. Chen, Huizhong TI Evidence for Significantly Enhancing Reduction of Azo Dyes in Escherichia coli by Expressed Cytoplasmic Azoreductase (AzoA) of Enterococcus faecalis SO PROTEIN AND PEPTIDE LETTERS LA English DT Article DE Enterococcus faecalis; azoreductase; Azo dye; NADH; decolorization ID FMN-DEPENDENT AZOREDUCTASE; SP. STRAIN BN6; MOLECULAR-CLONING; BACILLUS-SUBTILIS; CRYSTAL-STRUCTURE; REDOX MEDIATORS; GENE; BACTERIA; ENZYME; COLORANTS AB Although cytoplasmic azoreductases have been purified and characterized from various bacteria, little evidence demonstrating that these azoreductases are directly involved in azo dye reduction in vivo is known. In order to evaluate the contribution of the enzyme to azo dye reduction in vivo, experiments were conducted to determine the effect of a recombinant cytoplasmic azoreductase (AzoA) from Enterococcus faecalis expressed in Escherichia coli on the rate of metabolism of Methyl Red, Ponceau BS and Orange II. The intact cells that contained IPTG induced AzoA had a higher rate of dye reduction with increases of 2 (Methyl Red), 4 (Ponceau BS) and 2.6 (Orange II)-fold compared to noninduced cells, respectively. Metabolites of Methyl Red isolated from induced cultures were identified as N,N-dimethyl-p-phenylenediamine and 2-aminobenzoic acid through liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) analyses. In conclusion, our data demonstrate that AzoA from Ent. faecalis is capable of increasing the reduction of azo dyes in intact E. coli cells and that cytoplasmic azoreductase is involved in bacterial dye degradation in vivo. C1 [Feng, Jinhui; Xu, Haiyan; Cerniglia, Carl E.; Chen, Huizhong] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Heinze, Thomas M.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Chen, HZ (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM huizhong.chen@fda.hhs.gov FU Office of Women's Health; National Center for Toxicological Research, United States Food and Drug Administration; Oak Ridge Institute for Science and Education FX We thank Drs. Ashraf A. Khan and Kidon Sung for their critical review of the manuscript. This study was funded by the Office of Women's Health and the National Center for Toxicological Research, United States Food and Drug Administration, and supported in part by appointments (J.F. and H.X.) to the Postgraduate Research Fellowship Program by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. The views presented in this article do not necessarily reflect those of the Food and Drug Administration. NR 26 TC 7 Z9 8 U1 2 U2 14 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8665 J9 PROTEIN PEPTIDE LETT JI Protein Pept. Lett. PD MAY PY 2010 VL 17 IS 5 BP 578 EP 584 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 589JM UT WOS:000277143200006 PM 19663804 ER PT J AU Gilbert, ES Huang, L Bouville, A Berg, CD Ron, E AF Gilbert, Ethel S. Huang, Lan Bouville, Andre Berg, Christine D. Ron, Elaine TI Thyroid Cancer Rates and I-131 Doses from Nevada Atmospheric Nuclear Bomb Tests: An Update SO RADIATION RESEARCH LA English DT Article ID INCREASING INCIDENCE; CHERNOBYL ACCIDENT; FALLOUT; RADIATION; PAPILLARY; EXPOSURE; DISEASE; TRENDS; SITE AB Exposure to radioactive iodine (I-131) from atmospheric nuclear tests conducted in Nevada in the 1950s may have increased thyroid cancer risks. To investigate the long-term effects of this exposure, we analyzed data on thyroid cancer incidence (18,545 cases) from eight Surveillance, Epidemiology, and End Results (SEER) tumor registries for the period 1973-2004. Excess relative risks (ERR) per gray (Gy) for exposure received before age 15 were estimated by relating age-, birth year-, sex- and county-specific thyroid cancer rates to estimates of cumulative dose to the thyroid that take age into account. The estimated ERR per Gy for dose received before 1 year of age was 1.8 [95% confidence interval (Cl), 0.5-3.2]. There was no evidence that this estimate declined with follow-up time or that risk increased with dose received at ages 1-15. These results confirm earlier findings based on less extensive data for the period 1973-1994. The lack of a dose response for those exposed at ages 1-15 is inconsistent with studies of children exposed to external radiation or I-131 from the Chernobyl accident, and results need to be interpreted in light of limitations and biases inherent in ecological studies, including the error in doses and case ascertainment resulting from migration. Nevertheless, the study adds support for an increased risk of thyroid cancer due to fallout, although the data are inadequate to quantify it. (C) 2010 by Radiation Research Society C1 [Gilbert, Ethel S.; Bouville, Andre; Ron, Elaine] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Huang, Lan] Fed Drug Adm, Div Biometr 5, Off Biostat, Ctr Drug Evaluat & Res, Bethesda, MD USA. [Berg, Christine D.] NCI, Early Detect Res Grp, Canc Prevent Div, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Huang, Lan] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Gilbert, ES (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, MS 7238,6120 Execut Blvd, Bethesda, MD 20892 USA. EM gilberte@mail.nih.gov FU Intramural NIH HHS [ZIA CP010131-17] NR 23 TC 6 Z9 6 U1 0 U2 2 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD MAY PY 2010 VL 173 IS 5 BP 659 EP 664 DI 10.1667/RR2057.1 PG 6 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 595QS UT WOS:000277628000010 PM 20426666 ER PT J AU Villarruel, AM Zhou, Y Gallegos, EC Ronis, DL AF Villarruel, Antonia M. Zhou, Yan Gallegos, Esther C. Ronis, David L. TI Examining long-term effects of Cuidate-a sexual risk reduction program in Mexican youth SO REVISTA PANAMERICANA DE SALUD PUBLICA-PAN AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article DE Adolescent behavior; sexual behavior; adolescent health; risk reduction behavior; follow-up studies; intervention studies; randomized controlled trial; Mexico ID RANDOMIZED CONTROLLED-TRIAL; SOCIAL-DESIRABILITY-SCALE; HIV PREVENTION PROGRAM; LATINO YOUTH; INTERVENTION; ADOLESCENTS; BEHAVIORS AB Objectives. To examine the effectiveness of a safer sex program (Cuidate) on sexual behavior, use of condoms, and use of other contraceptives among Mexican youth 48 months after the intervention. Methods. A total of 708 or 85% of those who participated in the original randomized control study (n = 829) were assessed in the 48-month follow-up. Each participant completed a questionnaire on sexual behavior. Results. Findings indicated that adolescents who participated in the Cuidate program were more likely to be older at first sex (odds ratio [OR], 1.27; 95% confidence interval [CI], 0.41-2.12; P < 0.05) and to use condoms at first sex (OR, 1.75; 95% CI, 1.14-2.69; P < 0.05) or some other type of contraception at first sex (OR, 1.53; 95% CI, 1.00-2.33; P < 0.05) than those in the control group. Effects of the intervention on consistent condom use, condom use at last sex, and number of sexual partners were not significant. Gender did not moderate any intervention effects. Social desirability moderated the effect of the intervention on age at first sex. Conclusions. Results demonstrate the efficacy of Cuidate among Mexican adolescents. Future research, policy, and practice efforts should be directed at sustaining safe sex practices across adolescents' developmental and relationship trajectory. C1 [Villarruel, Antonia M.; Ronis, David L.] Univ Michigan, Sch Nursing, Ann Arbor, MI 48103 USA. [Zhou, Yan] US FDA, Div Biometr 2, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Gallegos, Esther C.] Univ Autonoma Nuevo Leon, Escuela Enfermeria, Monterrey, NL, Mexico. [Ronis, David L.] US Dept Vet Affairs, Ann Arbor, MI USA. RP Villarruel, AM (reprint author), Univ Michigan, Sch Nursing, 400 North Ingalls, Ann Arbor, MI 48103 USA. EM avillarr@umich.edu FU NINR NIH HHS [R01 NR008059, NR04855] NR 23 TC 13 Z9 13 U1 0 U2 8 PU PAN AMER HEALTH ORGANIZATION PI WASHINGTON PA 525 23RD ST NW, WASHINGTON, DC 20037 USA SN 1020-4989 J9 REV PANAM SALUD PUBL JI Rev. Panam. Salud Publica PD MAY PY 2010 VL 27 IS 5 BP 345 EP 351 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 620UT UT WOS:000279526700004 PM 20602068 ER PT J AU Ruzante, JM Davidson, VJ Caswell, J Fazil, A Cranfield, JAL Henson, SJ Anders, SM Schmidt, C Farber, JM AF Ruzante, Juliana Martins Davidson, Valerie J. Caswell, Julie Fazil, Aamir Cranfield, John A. L. Henson, Spencer J. Anders, Sven M. Schmidt, Claudia Farber, Jeffrey M. TI A Multifactorial Risk Prioritization Framework for Foodborne Pathogens SO RISK ANALYSIS LA English DT Article DE Consumer; DALY; food safety; pathogens; public policy; risk prioritization ID HEMOLYTIC-UREMIC SYNDROME; MULTICRITERIA DECISION-ANALYSIS; ESCHERICHIA-COLI O157-H7; UNITED-STATES; EXPERT ELICITATION; PROMETHEE METHOD; FOOD; INFECTIONS; ILLNESS; BURDEN AB We develop a prioritization framework for foodborne risks that considers public health impact as well as three other factors (market impact, consumer risk acceptance and perception, and social sensitivity). Canadian case studies are presented for six pathogen-food combinations: Campylobacter spp. in chicken; Salmonella spp. in chicken and spinach; Escherichia coli O157 in spinach and beef; and Listeria monocytogenes in ready-to-eat meats. Public health impact is measured by disability-adjusted life years and the cost of illness. Market impact is quantified by the economic importance of the domestic market. Likert-type scales are used to capture consumer perception and acceptance of risk and social sensitivity to impacts on vulnerable consumer groups and industries. Risk ranking is facilitated through the development of a knowledge database presented in the format of info cards and the use of multicriteria decision analysis (MCDA) to aggregate the four factors. Three scenarios representing different stakeholders illustrate the use of MCDA to arrive at rankings of pathogen-food combinations that reflect different criteria weights. The framework provides a flexible instrument to support policymakers in complex risk prioritization decision making when different stakeholder groups are involved and when multiple pathogen-food combinations are compared. C1 [Davidson, Valerie J.] Univ Guelph, Sch Engn, Guelph, ON N1G 2W1, Canada. [Ruzante, Juliana Martins] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. [Caswell, Julie] Univ Massachusetts, Dept Resource Econ, Amherst, MA 01003 USA. [Cranfield, John A. L.; Henson, Spencer J.; Schmidt, Claudia] Univ Guelph, Dept Food Agr & Resource Econ, Guelph, ON N1G 2W1, Canada. [Anders, Sven M.] Univ Alberta, Dept Rural Econ, Edmonton, AB T6G 2M7, Canada. RP Davidson, VJ (reprint author), Univ Guelph, Sch Engn, Guelph, ON N1G 2W1, Canada. EM vdavidso@uoguelph.ca FU Health Canada and the Natural Sciences and Engineering Research Council (NSERC); USDA Cooperative State Research, Education, and Extension Service FX The authors would like to thank Health Canada and the Natural Sciences and Engineering Research Council (NSERC) for financial support to undertake this research. This research was also supported by a USDA Cooperative State Research, Education, and Extension Service (CSREES) Special Grant to the Food Marketing Policy Center, University of Connecticut and by subcontract at the University of Massachusetts Amherst. At the time this research was conducted, Dr. J. M. Ruzante was a postdoctoral fellow at the School of Engineering, University of Guelph. NR 69 TC 26 Z9 26 U1 3 U2 34 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 MAY PY 2010 VL 30 IS 5 BP 724 EP 742 DI 10.1111/j.1539-6924.2009.01278.x PG 19 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 600HM UT WOS:000277976100003 PM 19671103 ER PT J AU Wang, YC Li, N AF Wang, Yong-Cheng Li, Ning TI Statistical Analysis for Treatment Crossover or Nonsynchronized Interval-Censoring Data in a Mortality Trial SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH LA English DT Article DE B-spline; Bootstrap confidence interval; Complementary log-log link; Proportional hazard model ID FAILURE TIME DATA; SURVIVAL ANALYSIS; CLINICAL-TRIALS; RANDOMIZED TRIALS; SWITCH TREATMENTS; RANK-TESTS; MODEL; AIDS; NONCOMPLIANCE; REGRESSION AB In a randomized clinical mortality trial, if some patients switch treatment groups (called treatment crossover in some publications but not to be confused with a classical crossover experimental design), it can cause problems in statistical design, data analysis, and interpretation, because the original randomization scheme has been changed in a nonrandomized manner. These changes can cause treatment effects to be more similar. The data are usually censored at the switching point based on considerations of treatment interaction, that is, the information after switching is not included in the data analysis. Another type of data is nonsynchronized interval-censoring. If the clinical mortality trial has multiple clinical examinations for each patient and a time-to-event variable (survival time), the survival time is interval-censored. In practice, the times of clinical examinations are different so that the data are nonsynchronized interval-censored resulting in difficulties with data analysis. Normally, the interval-censoring is ignored so that the information is not appropriately included in the data analysis where the patient is surviving until the next-to-last visit if an event is observed. In this article, we propose a statistical model with the estimation of the baseline hazard function for data analysis of treatment crossover or non-synchronized interval-censoring. C1 [Wang, Yong-Cheng] Biogen Idec Inc, Dept Biometr, Cambridge, MA 02142 USA. [Li, Ning] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Wang, YC (reprint author), Biogen Idec Inc, Dept Biometr, 14 Cambridge Ctr, Cambridge, MA 02142 USA. EM ycwang_us@yahoo.com; ning.li@fda.hhs.gov NR 25 TC 0 Z9 0 U1 1 U2 1 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 1946-6315 J9 STAT BIOPHARM RES JI Stat. Biopharm. Res. PD MAY PY 2010 VL 2 IS 2 BP 175 EP 181 DI 10.1198/sbr.2009.0068 PG 7 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 791QS UT WOS:000292680300005 ER PT J AU Powell, CL Bradford, BU Craig, CP Tsuchiya, M Uehara, T O'Connell, TM Pogribny, IP Melnyk, S Koop, DR Bleyle, L Threadgill, DW Rusyn, I AF Powell, Christine L. Bradford, Blair U. Craig, Christopher Patrick Tsuchiya, Masato Uehara, Takeki O'Connell, Thomas M. Pogribny, Igor P. Melnyk, Stepan Koop, Dennis R. Bleyle, Lisa Threadgill, David W. Rusyn, Ivan TI Mechanism for Prevention of Alcohol-Induced Liver Injury by Dietary Methyl Donors SO TOXICOLOGICAL SCIENCES LA English DT Article DE acetaldehyde; catalase; cytochrome P4502E1; S-adenosylmethionine; peroxisome proliferator-activated receptor alpha ID ADENOSYL-L-METHIONINE; S-ADENOSYLMETHIONINE; ADENOSYLTRANSFERASE 1A; CYTOCHROME-P450 2E1; OXIDATIVE STRESS; DNA METHYLATION; RAT HEPATOCYTES; ETHANOL; DISEASE; FOLATE AB Alcohol-induced liver injury (ALI) has been associated with, among other molecular changes, abnormal hepatic methionine metabolism, resulting in decreased levels of S-adenosylmethionine (SAM). Dietary methyl donor supplements such as SAM and betaine mitigate ALI in animal models; however, the mechanisms of protection remain elusive. It has been suggested that methyl donors may act via attenuation of alcohol-induced oxidative stress. We hypothesized that the protective action of methyl donors is mediated by an effect on the oxidative metabolism of alcohol in the liver. Male C57BL/6J mice were administered a control high-fat diet or diet enriched in methyl donors with or without alcohol for 4 weeks using the enteral alcohol feeding model. As expected, attenuation of ALI and an increase in reduced glutathione:oxidized glutathione ratio were achieved with methyl donor supplementation. Interestingly, methyl donors led to a 35% increase in blood alcohol elimination rate, and while there was no effect on alcohol metabolism in the stomach, a profound effect on liver alcohol metabolism was observed. The catalase-dependent pathway of alcohol metabolism was induced, yet the increase in CYP2E1 activity by alcohol was blunted, which may be mitigating production of oxidants. Additional factors contributing to the protective effects of methyl donors in ALI were increased activity of low- and high-K(m) aldehyde dehydrogenases leading to lower hepatic acetaldehyde, maintenance of the efficient mitochondrial energy metabolism, and promotion of peroxisomal beta-oxidation. Profound changes in alcohol metabolism represent additional important mechanism of the protective effect of methyl donors in ALI. C1 [Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Michael Hooker Res Ctr 0031, Chapel Hill, NC 27599 USA. [Powell, Christine L.; Threadgill, David W.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [O'Connell, Thomas M.] Univ N Carolina, Dept Mol Pharmaceut, Chapel Hill, NC 27599 USA. [Pogribny, Igor P.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Melnyk, Stepan] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72202 USA. [Koop, Dennis R.; Bleyle, Lisa] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. RP Rusyn, I (reprint author), Univ N Carolina, Dept Environm Sci & Engn, Michael Hooker Res Ctr 0031, Chapel Hill, NC 27599 USA. EM iir@unc.edu RI Rusyn, Ivan/S-2426-2016; Threadgill, David/N-4425-2013 OI Threadgill, David/0000-0003-3538-1635 FU National Institutes of Health [F32 AA016860, R01 AA016258, P30 ES010126]; Ruth L. Kirschstein National Service Award; Leon and Bertha Goldberg Postdoctoral Fellowship in Toxicology (University of North Carolina FX National Institutes of Health (F32 AA016860, R01 AA016258, and P30 ES010126).; C. L. P. was recipient of Ruth L. Kirschstein National Service Award and the Leon and Bertha Goldberg Postdoctoral Fellowship in Toxicology (University of North Carolina). NR 47 TC 17 Z9 18 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 2010 VL 115 IS 1 BP 131 EP 139 DI 10.1093/toxsci/kfq031 PG 9 WC Toxicology SC Toxicology GA 584HN UT WOS:000276742200013 PM 20118189 ER PT J AU Sadrieh, N Wokovich, AM Gopee, NV Zheng, JW Haines, D Parmiter, D Siitonen, PH Cozart, CR Patri, AK McNeil, SE Howard, PC Doub, WH Buhse, LF AF Sadrieh, Nakissa Wokovich, Anna M. Gopee, Neera V. Zheng, Jiwen Haines, Diana Parmiter, David Siitonen, Paul H. Cozart, Christy R. Patri, Anil K. McNeil, Scott E. Howard, Paul C. Doub, William H. Buhse, Lucinda F. TI Lack of Significant Dermal Penetration of Titanium Dioxide from Sunscreen Formulations Containing Nano- and Submicron-Size TiO2 Particles SO TOXICOLOGICAL SCIENCES LA English DT Article DE Sunscreen; TiO2; Nano; skin ID QUANTUM DOTS; IN-VITRO; ZINC-OXIDE; SKIN; NANOPARTICLES; ABSORPTION AB Titanium dioxide (TiO2) is included in some sunscreen formulations to physically block ultraviolet radiation. A dermal penetration study was conducted in minipigs with three TiO2 particles (uncoated submicron sized, uncoated nano-sized, and dimethicone/methicone copolymer-coated nanosized) applied 5% by weight in a sunscreen. These and control formulations were topically applied to minipigs at 2 mg cream/cm(2) skin (4 applications/day, 5 days/week, 4 weeks). Skin (multiple sites), lymph nodes, liver, spleen, and kidneys were removed, and the TiO2 content was determined (as titanium) using inductively coupled plasma mass spectroscopy. Titanium levels in lymph nodes and liver from treated animals were not increased over the values in control animals. The epidermis from minipigs treated with sunscreens containing TiO2 showed elevated titanium. Increased titanium was detected in abdominal and neck dermis of minipigs treated with uncoated and coated nanoscale TiO2. Using electron microscopy-energy dispersive x-ray analysis, all three types of TiO2 particles were found in the stratum corneum and upper follicular lumens in all treated skin samples (more particles visible with coated nanoscale TiO2). Isolated titanium particles were also present at various locations in the dermis of animals treated with all three types of TiO2-containing sunscreens; however, there was no pattern of distribution or pathology suggesting the particles could be the result of contamination. At most, the few isolated particles represent a tiny fraction of the total amount of applied TiO2. These findings indicate that there is no significant penetration of TiO2 nanoparticles through the intact normal epidermis. C1 [Sadrieh, Nakissa] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Wokovich, Anna M.; Doub, William H.; Buhse, Lucinda F.] US FDA, Div Pharmaceut Anal, Off Testing & Res, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, St Louis, MO 63101 USA. [Gopee, Neera V.; Siitonen, Paul H.; Cozart, Christy R.; Howard, Paul C.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Zheng, Jiwen; Haines, Diana; Parmiter, David; Patri, Anil K.; McNeil, Scott E.] NCI, Nanotechnol Characterizat Lab, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. [Haines, Diana] NCI, Pathol Histotechnol Lab, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. RP Sadrieh, N (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM nakissa.sadrieh@fda.hhs.gov RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU National Cancer Institute; National Institutes of Health [N01-CO-12400, HHSN261200800001E] FX National Cancer Institute and the National Institutes of Health under contracts N01-CO-12400 and HHSN261200800001E. NR 34 TC 112 Z9 114 U1 4 U2 54 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 2010 VL 115 IS 1 BP 156 EP 166 DI 10.1093/toxsci/kfq041 PG 11 WC Toxicology SC Toxicology GA 584HN UT WOS:000276742200015 PM 20156837 ER PT J AU Basch, E Reeve, B Cleeland, C Sloan, J Mendoza, T Abernethy, A Bruner, D Hay, J Atkinson, T Sit, L Minasian, L O'Mara, A Burke, L Schrag, D AF Basch, E. Reeve, B. Cleeland, C. Sloan, J. Mendoza, T. Abernethy, A. Bruner, D. Hay, J. Atkinson, T. Sit, L. Minasian, L. O'Mara, A. Burke, L. Schrag, 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.; Hay, J.; Atkinson, T.; Sit, L.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Reeve, B.; Minasian, L.; O'Mara, A.] Natl Canc Inst, Bethesda, MD USA. [Cleeland, C.; Mendoza, T.] UTMD Anderson Canc Ctr, Houston, TX USA. [Sloan, J.] Mayo Clin, Rochester, MN USA. [Abernethy, A.] Duke Univ, Durham, NC USA. [Bruner, D.] Univ Penn, Philadelphia, PA 19104 USA. [Burke, L.] Food & Drug Adm, Silver Spring, MD USA. [Schrag, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 MAY PY 2010 VL 13 IS 3 BP A44 EP A44 DI 10.1016/S1098-3015(10)72198-7 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 589CJ UT WOS:000277121900215 ER PT J AU De Alwis, H Heller, DN AF De Alwis, Hemakanthi Heller, David N. TI Multiclass, multiresidue method for the detection of antibiotic residues in distillers grains by liquid chromatography and ion trap tandem mass spectrometry SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Residue analysis; Antimicrobials; Distillers grain; Feed; Tandem mass spectrometry ID SOLID-PHASE EXTRACTION; VETERINARY DRUG RESIDUES; MACROLIDE ANTIBIOTICS; WASTE-WATER; SURFACE-WATER; FOOD; TETRACYCLINE; MATRICES; AMINOGLYCOSIDES; QUANTIFICATION AB The increased production of ethanol in the US has resulted in large amounts of distillers grains (DG) which is an excellent feed supplement for livestock. However, the use of antimicrobials during ethanol fermentation has led to a growing concern over the possibility of their residues remaining in DG.To enable the detection of antimicrobial residues, a robust LC-MS/MS method was developed that included 13 antibiotics of diverse chemistries, ampicillin, penicillin G, tetracycline, oxytetracycline, chlortetracycline, bacitracin A, virginiamycin M1, chloramphenicol, erythromycin A, clarithromycin, tylosin A, monensin A and streptomycin. The residues were extracted with an aqueous solution of EDTA and trichloroacetic acid followed by methanol. The combined extract was subjected to a two-track cleanup and concentration on either hydrophilic polymeric or weak cation exchange solid phase extraction cartridges. The extracts are analyzed by LC/ion trap tandem mass spectrometry. The method was validated in dry DG matrix. Absolute recoveries of the analytes ranged from 50 to 100%. Accuracy ranged from 89 to 111% based on calibration by processed standards. The limits of detection and relative standard deviation are satisfactory to support future surveillance studies. The method was subsequently tested in three different end-products of DG: distillers dry grains, distillers wet grains and distillers grains solubles. Published by Elsevier B.V. C1 [De Alwis, Hemakanthi; Heller, David N.] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP De Alwis, H (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM hemakanthi.dealwis@fda.hhs.gov NR 41 TC 15 Z9 15 U1 2 U2 39 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 APR 30 PY 2010 VL 1217 IS 18 BP 3076 EP 3084 DI 10.1016/j.chroma.2010.02.081 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 592JC UT WOS:000277373800010 PM 20304405 ER PT J AU Fu, TJ Maks, N Banaszewski, K AF Fu, Tong-Jen Maks, Nicole Banaszewski, Katie TI Effect of Heat Treatment on the Quantitative Detection of Egg Protein Residues by Commercial Enzyme-Linked Immunosorbent Assay Test Kits SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Food allergen; egg; ELISA test kits; thermal treatment ID INTERLABORATORY EVALUATION; THERMAL-DENATURATION; PROCESSED FOODS; WHITE PROTEINS; ALLERGEN; PEANUT; ELISA; ANTIGENICITY; CHOCOLATE; MILK AB This study examined the changes in the solubility of egg proteins as affected by different heat treatments and compared the performances of three commercial test kits for the quantitation of protein residues in heat-treated samples. National Institute of Standards and Technology (NIST) whole egg standard reference material #8415 and Henningsen spray-dried whole egg powder were subjected to heating in the presence of water at 60 and 100 degrees C, autoclaving for 5 or 10 min, or dry heating at 60-400 C for 10 min. The amount of protein in the heated samples was assayed using the bicinchoninic acid total protein assay as well as egg-specific commercial enzyme-linked immunosorbent assay (ELISA) kits. Elevated heat resulted in a lower level of proteins extracted. Neogen's Veratox kit, which is reactive to multiple proteins in egg, greatly underestimated the amount of residual proteins in the boiled or autoclaved samples. Tepnel BioSystems' Biokits assay, which employs antibodies specific to a heat-stable marker protein (ovomucoid), registered a higher level of protein in these samples. Both test kits substantially underestimated the amount of residual proteins in samples dry-heated at temperatures >176 degrees C. The Morinaga test, using an improved extraction buffer, registered the highest level of protein in the heat-treated NIST samples but not the Henningsen samples. The underestimation by the commercial test kits was attributed to changes in the immunoreactivity of residual proteins after heat treatments and not the differences in the amount of protein extracted. These results suggest that thermal processing may affect the quantitative analysis of allergens and needs to be taken into account in the validation of commercial ELISA test kits. C1 [Fu, Tong-Jen] US FDA, Summit Argo, IL 60501 USA. [Maks, Nicole; Banaszewski, Katie] Natl Ctr Food Safety & Technol, IIT, Summit Argo, IL 60501 USA. RP Fu, TJ (reprint author), US FDA, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM tongjen.fu@fda.hhs.gov FU U.S. Food and Drug Administration [FD-000431]; National Center for Food Safety and Technology [FD-000431] FX Received for review October 8, 2009. Revised manuscript received March 1, 2010. Accepted March 2, 2010. This work was supported by Cooperative Agreement FD-000431 between the U.S. Food and Drug Administration and the National Center for Food Safety and Technology. NR 39 TC 23 Z9 23 U1 2 U2 28 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD APR 28 PY 2010 VL 58 IS 8 BP 4831 EP 4838 DI 10.1021/jf903536z PG 8 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 584VR UT WOS:000276782100043 PM 20349964 ER PT J AU Cuevas, E Lantz, S Newport, G Divine, B Wu, QG Paule, MG Tobon-Velasco, JC Ali, SF Santamaria, A AF Cuevas, Elvis Lantz, Susan Newport, Glenn Divine, Becky Wu, Qiangen Paule, Merle G. Cesar Tobon-Velasco, J. Ali, Syed F. Santamaria, Abel TI On the early toxic effect of quinolinic acid: Involvement of RAGE SO NEUROSCIENCE LETTERS LA English DT Article DE Receptor-for-advanced-glycation-end-products; Neurotoxicity; Quinolinic acid; NF-kappa B; Oxidative stress; Neurodegeneration; Huntington's disease ID GLYCATION END-PRODUCTS; RAT CORPUS STRIATUM; HUNTINGTONS-DISEASE; ALZHEIMERS-DISEASE; KAPPA-B; INDUCED NEUROTOXICITY; EXCITOTOXIC DAMAGE; PROTECTIVE ROLE; IN-VIVO; RECEPTOR AB Quinolinic acid (QUIN)-induced toxicity is characterized by N-methyl-u-aspartate receptors over-activation, excitotoxicity and oxidative damage. The characterization of toxic cascades produced by QUIN during the first hours after its striatal infusion is relevant for understanding toxic mechanisms. The role of the receptor-for-advanced-glycation-end-products (RAGE) in the early toxic pattern induced by QUIN was evaluated. RAGE expression - assessed by Western blot analysis and immunofluorescence - was enhanced in the striata of QUIN-lesioned rats at 2 h post-lesion. QUIN-induced RAGE up-regulation was accompanied by expression of a RAGE target molecule, nuclear factor kappa B (NF-kappa B), and genes encoding for different enzymes. Other toxic markers linked to RAGE activation were increased by QUIN, including NO formation, premature glial response, lactate dehydrogenase leakage, mitochondrial dysfunction and nuclear condensation. Our results suggest that RAGE up-regulation may play a role in the early stages of QUIN toxicity. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Cuevas, Elvis; Cesar Tobon-Velasco, J.; Santamaria, Abel] Inst Nacl Neurol & Neurocirug, Lab Aminoacidos Excitadores, Mexico City 14269, DF, Mexico. [Cuevas, Elvis; Lantz, Susan; Newport, Glenn; Divine, Becky; Paule, Merle G.; Ali, Syed F.; Santamaria, Abel] Natl Ctr Toxicol Res FDA, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. [Wu, Qiangen] Natl Ctr Toxicol Res FDA, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Santamaria, A (reprint author), Inst Nacl Neurol & Neurocirug, Lab Aminoacidos Excitadores, SSA Insurgentes 3877, Mexico City 14269, DF, Mexico. EM absada@yahoo.com RI Wu, Qiangen/F-7581-2014; OI Wu, Qiangen/0000-0002-7595-2837; Tobon-Velasco, Julio Cesar/0000-0002-1821-5873 NR 38 TC 3 Z9 3 U1 1 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD APR 26 PY 2010 VL 474 IS 2 BP 74 EP 78 DI 10.1016/j.neulet.2010.03.007 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 594JX UT WOS:000277534800003 PM 20223279 ER PT J AU Wong, HL Breen, EC Pfeiffer, RM Aissani, B Martinson, JJ Margolick, JB Kaslow, RA Jacobson, LP Ambinder, RF Chanock, S Martinez-Maza, O Rabkin, CS AF Wong, Hui-Lee Breen, Elizabeth C. Pfeiffer, Ruth M. Aissani, Brahim Martinson, Jeremy J. Margolick, Joseph B. Kaslow, Richard A. Jacobson, Lisa P. Ambinder, Richard F. Chanock, Stephen Martinez-Maza, Otoniel Rabkin, Charles S. TI Cytokine signaling pathway polymorphisms and AIDS-related non-Hodgkin lymphoma risk in the multicenter AIDS cohort study SO AIDS LA English DT Article DE AIDS-related lymphoma; cytokine; single-nucleotide polymorphisms ID EPSTEIN-BARR-VIRUS; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; NERVOUS-SYSTEM LYMPHOMA; INTERLEUKIN-10; INFECTION; PROMOTER; IL10; EXPRESSION; IL-10; CELLS AB Background: Cytokine stimulation of B-cell proliferation may be an important causative mechanism for acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin lymphoma (NHL). The Epstein-Barr virus (EBV) may be a co-factor, particularly for primary central nervous system (CNS) tumors, which are uniformly EBV-positive in the setting of AIDS. Thus, we examined associations of genetic variation in IL10 and related cytokine-signaling molecules (IL10RA, CXCL12, IL13, IL4, IL4R, CCL5 and BCL6) with AIDS-related NHL risk and evaluated differences between primary CNS and systemic tumors. Patients and materials: We compared 160 Multicenter AIDS Cohort Study (MACS) participants with incident lymphomas, of which 90 followed another AIDS diagnosis, to HIV-1-seropositive controls matched on duration of lymphoma-free survival post-HIV-1 infection (N = 160) or post-AIDS diagnosis (N = 90). We fit conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Carriage of at least one copy of the T allele for the IL10 rs1800871 (as compared to no copies) was associated with decreased AIDS-NHL risk specific to lymphomas arising from the CNS (CC vs. CT/TT: OR = 0.3; 95% CI 0.1, 0.7) but not systemically (CC vs. CT/TT: OR = 1.0; 95% CI 0.5, 1.9) (P(heterogeneity) = 0.03). Carriage of two copies of the 'low IL10' haplotype rs1800896_A/rs1800871_T/rs1800872_A was associated with decreased lymphoma risk that varied by number of copies (P(trend) = 0.02). None of the ORs for the other studied polymorphisms was significantly different from 1.0. Conclusion: Excessive IL10 response to HIV-1 infection may be associated with increased risk of NHL, particularly in the CNS. IL10 dysregulation may be an important causative pathway for EBV-related lymphomagenesis. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Wong, Hui-Lee; Pfeiffer, Ruth M.; Chanock, Stephen; Rabkin, Charles S.] NCI, Rockville, MD USA. [Breen, Elizabeth C.; Martinez-Maza, Otoniel] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Aissani, Brahim; Kaslow, Richard A.] Univ Alabama, Birmingham, AL USA. [Martinson, Jeremy J.] Univ Pittsburgh, Pittsburgh, PA USA. [Margolick, Joseph B.; Jacobson, Lisa P.; Ambinder, Richard F.] Johns Hopkins Univ, Baltimore, MD USA. RP Wong, HL (reprint author), Ctr Devices & Radiol Hlth, Div Epidemiol, Off Surveillance & Biometr, FDA WO66-4561,10903 New Hampshire Av, Silver Spring, MD 20993 USA. EM huilee.wong@fda.hhs.gov RI Pfeiffer, Ruth /F-4748-2011; Ambinder, Richard/G-1607-2011; Martinez-Maza, Otoniel/B-2667-2009; OI Martinez-Maza, Otoniel/0000-0003-1364-0675; Martinson, Jeremy/0000-0003-4673-7238 FU National Cancer Institute, National Institutes of Health; NIH [R01-CA73475, R01-CA57152, P50-CA-096888]; National Institute of Allergy and Infectious Diseases; National Heart, Lung and Blood Institute FX The study was funded in part by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. This work was supported, in part, by grants from the NIH (R01-CA73475, R01-CA57152, P50-CA-096888). Data in this manuscript were collected by the Multicenter AIDS Cohort Study (MACS) with centers (Principal Investigators) at The Johns Hopkins University Bloomberg School of Public Health (Joseph B. Margolick, Lisa Jacobson), Howard Brown Health Center and Northwestern University Medical School (John Phair), University of California, Los Angeles (Roger Detels), and University of Pittsburgh (Charles Rinaldo). The MACS is funded by the National Institute of Allergy and Infectious Diseases, with additional supplemental funding from the National Cancer Institute and the National Heart, Lung and Blood Institute. UO1-AI-35042, 5-MO1-RR-00722 (GCRC), UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041. Website located at http://www.statepi.jhsph.edu/macs/macs.html. NR 34 TC 22 Z9 22 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR 24 PY 2010 VL 24 IS 7 BP 1025 EP 1033 DI 10.1097/QAD.0b013e328332d5b1 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 582AN UT WOS:000276567500012 PM 20299965 ER PT J AU Rao, SS Mohan, KVK Nguyen, N Abraham, B Abdouleva, G Zhang, P Atreya, CD AF Rao, Shilpakala Sainath Mohan, Ketha V. K. Nguyen, Nga Abraham, Bindu Abdouleva, Galina Zhang, Pei Atreya, Chintamani D. TI Peptides panned from a phage-displayed random peptide library are useful for the detection of Bacillus anthracis surrogates B. cereus 4342 and B. anthracis Sterne SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Bacillus anthracis; Counter-terrorism; Peptide ligands; Phage-display; Plasma; Quantum dots ID SPORES; DISCOVERY; THURINGIENSIS; ANTIBODIES; LIGANDS; PROBES; CELLS AB Recent use of Bacillus anthracis as a bioweapon has highlighted the need for a sensitive monitoring system. Current bacterial detection tests use antibodies as bio-molecular recognition elements which have limitations with regard to time, specificity and sensitivity, creating the need for new and improved cost-effective high-affinity detection probes. In this study, we screened a commercially available bacteriophage-displayed random peptide library using Bacillus cereus 4342 cells as bait to identify peptides that could be used for detection of Bacillus. The method enabled us to identify two 12-amino acid consensus peptide sequences that specifically bind to B. cereus 4342 and B. anthracis Sterne, the nonpathogenic surrogates of B. anthracis strain. The two Bacillus-binding peptides (named BBP-1 and BBP-2) were synthesized with biotin tag to confirm their binding by four independent detection assays. Dot-blot analysis revealed that the peptides bind specifically to B. cereus 4342 and B. anthracis Sterne. Quantitative analysis of this interaction by ELISA and fluorometry demonstrated a detection sensitivity of 102 colony forming U/ml (CFU/ml) by both assays. When the peptides were used in combination with Qdots, the sensitivity was enhanced further by enabling detection of even a single bacterium by fluorescence microscopy. Immunoblot analysis and protein sequencing showed that BBP-1 and BBP-2 bound to the S-layer protein of B. anthracis Sterne. Overall, our findings validate the usefulness of synthetic versions of phage-derived peptides in combination with Qdot-liquid nanocrystals as high sensitivity bioprobes for various microbial detection platforms. Published by Elsevier Inc. 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. [Nguyen, Nga; Abdouleva, Galina] US FDA, Facil Biotechnol Resources, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Abraham, Bindu] US FDA, Lab Biochem & Vasc Biol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Zhang, Pei] US FDA, Lab Plasma Derivat, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Mohan, KVK (reprint author), US FDA, Sect Cell Biol, Lab Cellular Hematol, Ctr Biol Evaluat & Res, Bldg 29A,Room 2C-15,HFM 335,NIH Campus,8800 Rockv, Bethesda, MD 20892 USA. EM krishna.ketha@fda.hhs.gov 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 C.A. S.S. 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 thank Drs. Xuan Chi and Mikhail Ovanesov, OBRR, CBER for their review of the manuscript. NR 31 TC 4 Z9 4 U1 1 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 23 PY 2010 VL 395 IS 1 BP 93 EP 98 DI 10.1016/j.bbrc.2010.03.145 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 591JZ UT WOS:000277298000018 ER PT J AU Weiss, KD Osborne, SF Callahan-Lyon, P AF Weiss, Karen D. Osborne, Steven F. Callahan-Lyon, Priscilla TI Prevention of Surgical-Site Infections SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Weiss, Karen D.; Osborne, Steven F.; Callahan-Lyon, Priscilla] US FDA, Silver Spring, MD USA. RP Weiss, KD (reprint author), US FDA, Silver Spring, MD USA. EM karen.weiss@fda.hhs.gov NR 2 TC 2 Z9 2 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 APR 22 PY 2010 VL 362 IS 16 BP 1541 EP 1542 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 586GP UT WOS:000276894700021 PM 20414980 ER PT J AU Abu-Ali, GS Ouellette, LM Henderson, ST Lacher, DW Riordan, JT Whittam, TS Manning, SD AF Abu-Ali, Galeb S. Ouellette, Lindsey M. Henderson, Scott T. Lacher, David W. Riordan, James T. Whittam, Thomas S. Manning, Shannon D. TI Increased Adherence and Expression of Virulence Genes in a Lineage of Escherichia coli O157:H7 Commonly Associated with Human Infections SO PLOS ONE LA English DT Article ID ENTEROCYTE EFFACEMENT GENES; SHIGA-TOXIN; INTESTINAL COLONIZATION; GENOME SEQUENCE; UNITED-STATES; O157-H7; STRAINS; LOCUS; DISEASE; SECRETION AB Background: Enterohemorrhagic Escherichia coli (EHEC) O157:H7, a food and waterborne pathogen, can be classified into nine phylogenetically distinct lineages, as determined by single nucleotide polymorphism genotyping. One lineage (clade 8) was found to be associated with hemolytic uremic syndrome (HUS), which can lead to kidney failure and death in some cases, particularly young children. Another lineage (clade 2) differs considerably in gene content and is phylogenetically distinct from clade 8, but caused significantly fewer cases of HUS in a prior study. Little is known, however, about how these two lineages vary with regard to phenotypic traits important for disease pathogenesis and in the expression of shared virulence genes. Methodology/Principal Findings: Here, we quantified the level of adherence to and invasion of MAC-T bovine epithelial cells, and examined the transcriptomes of 24 EHEC O157:H7 strains with varying Shiga toxin profiles from two common lineages. Adherence to epithelial cells was >2-fold higher for EHEC O157:H7 strains belonging to clade 8 versus clade 2, while no difference in invasiveness was observed between the two lineages. Whole-genome 70-mer oligo microarrays, which probe for 6088 genes from O157:H7 Sakai, O157:H7 EDL 933, pO157, and K12 MG1655, detected significant differential expression between clades in 604 genes following co-incubation with epithelial cells for 30 min; 186 of the 604 genes had a >1.5 fold change difference. Relative to clade 2, clade 8 strains showed upregulation of major virulence genes, including 29 of the 41 locus of enterocyte effacement (LEE) pathogenicity island genes, which are critical for adherence, as well as Shiga toxin genes and pO157 plasmid-encoded virulence genes. Differences in expression of 16 genes that encode colonization factors, toxins, and regulators were confirmed by qRT-PCR, which revealed a greater magnitude of change than microarrays. Conclusions/Significance: These findings demonstrate that the EHEC O157:H7 lineage associated with HUS expresses higher levels of virulence genes and has an enhanced ability to attach to epithelial cells relative to another common lineage. C1 [Abu-Ali, Galeb S.; Ouellette, Lindsey M.; Henderson, Scott T.; Riordan, James T.; Whittam, Thomas S.; Manning, Shannon D.] Michigan State Univ, Natl Food Safety & Toxicol Ctr, Microbial Evolut Lab, E Lansing, MI 48824 USA. [Lacher, David W.] US FDA, Div Mol Biol, Ctr Food Safety & Appl Nutr, Laurel, MD USA. [Manning, Shannon D.] Michigan State Univ, Dept Pediat & Human Dev, E Lansing, MI 48824 USA. RP Abu-Ali, GS (reprint author), Michigan State Univ, Natl Food Safety & Toxicol Ctr, Microbial Evolut Lab, E Lansing, MI 48824 USA. EM Shannon.Manning@ht.msu.edu OI Manning, Shannon/0000-0001-9581-0660 FU NIAID; NIH [N01-AI-30058]; DHHS FX This project was funded by the NIAID, NIH, DHHS, under NIH research contract N01-AI-30058 (TSW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 62 TC 35 Z9 35 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 APR 21 PY 2010 VL 5 IS 4 AR e10167 DI 10.1371/journal.pone.0010167 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 586YS UT WOS:000276952500002 PM 20422047 ER PT J AU Liang, XJ Meng, H Wang, YZ He, HY Meng, J Lu, J Wang, PC Zhao, YL Gao, XY Sun, BY Chen, CY Xing, GM Shen, DW Gottesman, MM Wu, Y Yin, JJ Jia, L AF Liang, Xing-Jie Meng, Huan Wang, Yingze He, Haiyong Meng, Jie Lu, Juan Wang, Paul C. Zhao, Yuliang Gao, Xueyun Sun, Baoyun Chen, Chunying Xing, Genmei Shen, Dingwu Gottesman, Michael M. Wu, Yan Yin, Jun-jie Jia, Lee TI Metallofullerene nanoparticles circumvent tumor resistance to cisplatin by reactivating endocytosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE drug resistance; nanomedicine; nanoimaging; chemotherapy; nanopharmaceutical ID OVARIAN-CARCINOMA CELLS; CHROMATOGRAPHY-MASS SPECTROMETRY; MRI CONTRAST AGENTS; CELLULAR ACCUMULATION; MULTIDRUG-RESISTANCE; REDUCED EXPRESSION; CANCER-CELLS; LINES; PLATINUM; IDENTIFICATION AB Cisplatin is a chemotherapeutic drug commonly used in clinics. However, acquired resistance confines its application in chemotherapeutics. To overcome the acquired resistance to cisplatin, it is reasoned, based on our previous findings of mediation of cellular responses by [Gd@C(82)(OH)(22)](n) nanoparticles, that [Gd@C(82)(OH)(22)](n) may reverse tumor resistance to cisplatin by reactivating the impaired endocytosis of cisplatin-resistant human prostate cancer (CP-r) cells. Here we report that exposure of the CP-r PC-3-luc cells to cisplatin in the presence of nontoxic [Gd@C(82)(OH)(22)](n) not only decreased the number of surviving CP-r cells but also inhibited growth of the CP-r tumors in athymic nude mice as measured by both optical and MRI. Labeling the CP-r PC-3 cells with transferrin, an endocytotic marker, demonstrated that pretreatment of the CP-r PC-3-luc cells with [Gd@C(82)(OH)(22)](n) enhanced intracellular accumulation of cisplatin and formation of cisplatin-DNA adducts by restoring the defective endocytosis of the CP-r cancer cells. The results suggest that [Gd@C(82)(OH)(22)](n) nanoparticles overcome tumor resistance to cisplatin by increasing its intracellular accumulation through the mechanism of restoring defective endocytosis. The technology can be extended to other challenges related to multidrug resistance often found in cancer treatments. C1 [Liang, Xing-Jie; Wang, Yingze; He, Haiyong; Meng, Jie; Lu, Juan; Chen, Chunying; Wu, Yan] Chinese Acad Sci, Key Lab Biomed Effects Nanomat & Nanosafety, Natl Ctr Nanosci & Technol China, Beijing 100190, Peoples R China. [Meng, Huan; Meng, Jie; Zhao, Yuliang; Gao, Xueyun; Sun, Baoyun; Xing, Genmei] Chinese Acad Sci, Key Lab Biomed Effects Nanomat & Nanosafety, Inst High Energy Phys, Beijing 100049, Peoples R China. [Wang, Paul C.] Howard Univ, Dept Radiol, Lab Mol Imaging, Washington, DC 20060 USA. [Shen, Dingwu; Gottesman, Michael M.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Yin, Jun-jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Jia, Lee] NCI, Dev Therapeut Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Liang, XJ (reprint author), Chinese Acad Sci, Key Lab Biomed Effects Nanomat & Nanosafety, Natl Ctr Nanosci & Technol China, Beijing 100190, Peoples R China. EM liangxj@nanoctr.cn; zhaoyuliang@mail.ihep.ac.cn RI Yin, Jun Jie /E-5619-2014 FU China-Finland Nanotechnology [2008DFA01510]; Chinese Academy of Sciences (CAS) [07165111ZX]; 973 program [2006CB705600]; National Basic Research Program of China [2009CB930200]; National Center for Research Resources, National Institutes of Health [2 G12 RR003048] FX We appreciate George Leiman for editing the manuscript. We are also grateful to Dr. Wayne Wamer (Center for Food Safety & Applied Nutrition/US Food and Drug Administration) for his significant input in this study. This work is financially supported by the Project of China-Finland Nanotechnology (2008DFA01510) the Chinese Academy of Sciences (CAS) "Hundred Talents Program" (07165111ZX), the 973 program (2006CB705600), and the National Basic Research Program of China (2009CB930200). This work was partially supported by Grant 2 G12 RR003048 from the Research Centers in Minority Institutions Program, National Center for Research Resources, National Institutes of Health. NR 51 TC 132 Z9 137 U1 9 U2 89 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 20 PY 2010 VL 107 IS 16 BP 7449 EP 7454 DI 10.1073/pnas.0909707107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 586FU UT WOS:000276892300062 PM 20368438 ER PT J AU Poole, CF Poole, SK AF Poole, Colin F. Poole, Salwa K. TI Extraction of organic compounds with room temperature ionic liquids SO JOURNAL OF CHROMATOGRAPHY A LA English DT Review DE Ionic liquids; Extraction; Partition coefficients; Solvation parameter model; Solvatochromism; Liquid-liquid extraction; Liquid-phase microextraction; Supported liquid membrane extraction ID SOLID-PHASE MICROEXTRACTION; AQUEOUS BIPHASIC SYSTEMS; HEADSPACE GAS-CHROMATOGRAPHY; POLYCYCLIC AROMATIC-HYDROCARBONS; ENVIRONMENTAL WATER SAMPLES; SINGLE-DROP MICROEXTRACTION; FREE-ENERGY RELATIONSHIP; OPEN-TUBULAR COLUMNS; LOW VAPOR-PRESSURE; SOLVENT-EXTRACTION AB Room temperature ionic liquids are novel solvents with a rather specific blend of physical and solution properties that makes them of interest for applications in separation science. They are good solvents for a wide range of compounds in which they behave as polar solvents. Their physical properties of note that distinguish them from conventional organic solvents are a negligible vapor pressure, high thermal stability, and relatively high viscosity. They can form biphasic systems with water or low polarity organic solvents and gases suitable for use in liquid-liquid and gas-liquid partition systems. An analysis of partition coefficients for varied compounds in these systems allows characterization of solvent selectivity using the solvation parameter model, which together with spectroscopic studies of solvent effects on probe substances, results in a detailed picture of solvent behavior. These studies indicate that the solution properties of ionic liquids are similar to those of polar organic solvents. Practical applications of ionic liquids in sample preparation include extractive distillation, aqueous biphasic systems, liquid-liquid extraction, liquid-phase microextraction, supported liquid membrane extraction, matrix solvents for headspace analysis, and micellar extraction. The specific advantages and limitations of ionic liquids in these studies is discussed with a view to defining future uses and the need not to neglect the identification of new room temperature ionic liquids with physical and solution properties tailored to the needs of specific sample preparation techniques. The defining feature of the special nature of ionic liquids is not their solution or physical properties viewed separately but their unique combinations when taken together compared with traditional organic solvents. (C) 2009 Elsevier B.V. All rights reserved. C1 [Poole, Colin F.] Wayne State Univ, Dept Chem, Detroit, MI 48202 USA. [Poole, Salwa K.] US FDA, Detroit Dist Lab, Detroit, MI 48207 USA. RP Poole, CF (reprint author), Wayne State Univ, Dept Chem, Rm 183 Chem, Detroit, MI 48202 USA. EM cfp@chem.wayne.edu NR 227 TC 256 Z9 266 U1 19 U2 245 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 APR 16 PY 2010 VL 1217 IS 16 BP 2268 EP 2286 DI 10.1016/j.chroma.2009.09.011 PG 19 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 582AJ UT WOS:000276567100002 PM 19766228 ER PT J AU Vallejos, JR Brorson, KA Moreira, AR Rao, G AF Vallejos, Jose R. Brorson, Kurt A. Moreira, Antonio R. Rao, Govind TI Dissolved Oxygen and pH Profile Evolution After Cryovial Thaw and Repeated Cell Passaging in a T-75 Flask SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE monitoring; cell culture; T-flask; passaging; oxygen; pH ID MONOCLONAL-ANTIBODY PRODUCTION; CONTINUOUS SUSPENSION-CULTURE; STIRRED-TANK BIOREACTOR; HYBRIDOMA GROWTH; MASS-TRANSFER; NUTRIENT CONCENTRATION; PRODUCTION KINETICS; MICROTITER PLATES; BATCH CULTURE; SHAKE FLASKS AB Routine cell culture is done in small-scale disposable vessels (typically 0.1-100mL volumes) in academia and industry. Despite their wide use in bioprocess development (i.e., process optimization and process validation), miniature process scouting devices (PSDs) are considered "black boxes" because they are generally not equipped with sensors. In this study, we show that on-line monitoring of dissolved oxygen (DO) and pH in a T-75 flask-based PSD can be achieved during cell passaging and that this information can be linked to different cellular metabolic states. In this case, on-line monitoring of DO and pH show three distinctive metabolic regions in passages 1-18, 19-28, 29-54 and in particular, the shift in the pH curve, the specific oxygen uptake rate (q(O2)), and the lactate production rate to the oxygen consumption rate yield (Y(Lac/ox)) confirm the existence of these distinctive metabolic regions. These findings are particularly useful because they show that sensor equipped PSDs can help to monitor cell culture behavior after thaw, in pre-and seed culture prior to scale-up and in development/optimization studies. Such routine monitoring will help to develop more consistent cell culture techniques. Biotechnol. Bioeng. 2009; 105: 1040-1047. (C) 2009 Wiley Periodicals, Inc. C1 [Vallejos, Jose R.; Moreira, Antonio R.; Rao, Govind] Univ Maryland, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Vallejos, Jose R.; Moreira, Antonio R.; Rao, Govind] Univ Maryland, Dept Chem & Biochem Engn, Baltimore, MD 21250 USA. [Brorson, Kurt A.] US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Rao, G (reprint author), Univ Maryland, Ctr Adv Sensor Technol, 1000 Hilltop Circle, Baltimore, MD 21250 USA. EM grao@umbc.edu NR 43 TC 8 Z9 9 U1 1 U2 10 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 APR 15 PY 2010 VL 105 IS 6 BP 1040 EP 1047 DI 10.1002/bit.22649 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 577ZQ UT WOS:000276263300004 PM 20047191 ER PT J AU Rahman, Z Zidan, AS Habib, MJ Khan, MA AF Rahman, Ziyaur Zidan, Ahmed S. Habib, Muhammad J. Khan, Mansoor A. TI Understanding the quality of protein loaded PLGA nanoparticles variability by Plackett-Burman design SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE CyA; PLGA; QbD; Plackett-Burman; Nanoparticles and dissolution efficiency ID BIODEGRADABLE POLYMERIC MICROSPHERES; CYCLOSPORINE-A; HYDROXYPROPYL METHYLCELLULOSE; RELEASE PROFILES; DELIVERY-SYSTEMS; FORMULATION; MICROPARTICLES; PHARMACOKINETICS; BIOAVAILABILITY; NEPHROTOXICITY AB The aim of this investigation was to screen and understand the product variability due to important factors affecting the characteristics CyA-PLGA nanoparticles prepared by O/W emulsification-solvent evaporation method. Independent variables studied were cyclosporine A (CyA) (X(1)), PLGA (X(2)), and emulsifier concentration namely SLS (X(3)), stirring rate (X(4)), type of organic solvent employed (chloroform or dichloromethane. X(5)) and organic to aqueous phase ratio (X(6)). The nanoparticles properties considered were encapsulation efficiency (Y(1)), mean particle size (Y(2)), zeta potential (Y(3)), burst effect (Y(4)) and dissolution efficiency (Y(5)). The statistical analysis of the results allowed determining the most influent factors. The nanoparticles were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC). X-ray powder diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. The factors combination showed variability of entrapment efficiency (Y(1)), mean particle size (Y(2)) and zeta potential (Y(3)) from 10.17% to 93.01%, 41.60 to 372.80 nm and 29.60 to 34.90 mV, respectively. Initially, nanoparticles showed burst effect followed by sustained release during the 7-day in vitro release study period. The dissolution efficiency (Y(5)) varied from 52.67% to 84.11%. The nanoparticles revealed Higuchi release pattern and release occurred by coupling of diffusion and erosion. In conclusion, this study revealed the potential of QbD in understanding the effect of formulation and process variables on the characteristics on CyA-PLGA nanoparticles. (C) 2010 Published by Elsevier B.V. C1 [Rahman, Ziyaur; Zidan, Ahmed S.; 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. [Habib, Muhammad J.] Howard Univ, Sch Pharm, Washington, DC 20059 USA. 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 thank the Oak Ridge Institute for Science and Education (ORISE) for its support with a research post-doctoral fellowship. The views presented in this article do not necessarily reflect those of the US Food and Drug Administration. The authors also extend this acknowledgment to Dr. Katherine Tyner and Dr. Alen Carlin for helping with the SEM images and FTIR spectrum, respectively. NR 39 TC 52 Z9 55 U1 2 U2 14 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 APR 15 PY 2010 VL 389 IS 1-2 BP 186 EP 194 DI 10.1016/j.ijpharm.2009.12.040 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 577JO UT WOS:000276219200022 PM 20038446 ER PT J AU Shrivas, K Patel, DK AF Shrivas, Kamlesh Patel, Devesh Kumar TI Separation and preconcentration of trace level of lead in one drop of blood sample by using graphite furnace atomic absorption spectrometry SO JOURNAL OF HAZARDOUS MATERIALS LA English DT Article DE Lead; Blood; Drop-to-drop solvent microextraction; Atomic absorption spectrometry ID DESORPTION/IONIZATION MASS-SPECTROMETRY; GAS CHROMATOGRAPHY/MASS SPECTROMETRY; LIQUID-LIQUID MICROEXTRACTION; SOLVENT MICROEXTRACTION; WATER SAMPLES; PHASE MICROEXTRACTION; EXTRACTION AB Drop-to-drop solvent microextraction (DDSME) assisted with ultrasonication is applied for the determination of lead in one drop (30 mu L) of blood sample by using graphite furnace atomic absorption spectrometry (GF-AAS). The optimum extraction efficiency of lead was observed for 10 min extraction time at pH 5.0 with 2 mu L of organic solvent that containing 0.5 M of Cyanex-302. The optimized methodology exhibited good linearity in the range of 0.3-30.0 ng mL(-1) lead with relative standard deviations (RSD) from 2.5 to 4.4%. The method is found to be simple and rapid for the analysis of lead in micro amount of blood sample with the limit of detection (LOD) of 0.08 ng mL(-1). The application of the proposed method has been successfully tested for the determination of lead in blood samples. The results showed that under the optimized experimental conditions, the method showed good sensitivity and recovery %, as well as advantages such as linearity, simplicity, low cost and high feasibility. (C) 2009 Elsevier B.V. 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 29A,2B20, Bethesda, MD 20892 USA. EM shrikam@rediffmail.com NR 22 TC 19 Z9 20 U1 2 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3894 J9 J HAZARD MATER JI J. Hazard. Mater. PD APR 15 PY 2010 VL 176 IS 1-3 BP 414 EP 417 DI 10.1016/j.jhazmat.2009.11.045 PG 4 WC Engineering, Environmental; Engineering, Civil; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA 559PZ UT WOS:000274839700056 PM 20004520 ER PT J AU Tang, SX Hewlett, I AF Tang, Shixing Hewlett, Indira TI Nanoparticle-Based Immunoassays for Sensitive and Early Detection of HIV-1 Capsid (p24) Antigen SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TIME-RESOLVED FLUORESCENCE; PROSTATE-SPECIFIC ANTIGEN; ULTRASENSITIVE DETECTION; ASSAY; PROTEINS; PLASMA; INFECTION; DIAGNOSIS; PCR AB We evaluated the feasibility of using nanoparticle (NP)-based assays for improving detection sensitivity of human immunodeficiency virus type 1 (HIV-1) p24 antigen. One assay that was evaluated is a gold NP-based biobarcode amplification (BCA) assay, which can detect HIV-1 p24 antigen at levels as low as 0.1 pg/mL. The lower limit of detection for an enzyme-linked immunosorbent assay (ELISA) is 10-15 pg/mL. These results demonstrate that the HIV-1 p24 BCA assay offers 100-150-fold enhancement in the detection limit over the traditional colorimetric ELISA. Furthermore, the BCA assay detected HIV-1 infection 3 days earlier than did ELISA in samples from patients who had experienced seroconversion. The other assay that we tested is the europium NP-based immunoassay, which uses europium NPs to replace gold NPs in the BCA assay to further simplify the detection method and decrease the incubation time. For detection of HIV-1 p24, the lower limit of detection for the europium NP-based immunoassay was 0.5 pg/mL. These results indicate that the universal labeling technology based on NPs and its application may provide a rapid and sensitive testing platform for clinical diagnosis and laboratory research. C1 [Tang, Shixing; Hewlett, Indira] US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Hewlett, I (reprint author), US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bldg 29B,Rm 4NN16,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Indira.hewlett@fda.hhs.gov FU Office of Science and Health Coordination; Food and Drug Administration; National Heart, Lung and Blood Institute; National Institute of Allergy and Infectious Diseases; National Institutes of Health FX Office of Science and Health Coordination, Food and Drug Administration; National Heart, Lung and Blood Institute and National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 21 TC 58 Z9 61 U1 3 U2 36 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 15 PY 2010 VL 201 SU 1 BP S59 EP S64 DI 10.1086/650386 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 568AK UT WOS:000275493500009 PM 20225948 ER PT J AU Chiang, HM Yin, JJ Xia, QS Zhao, YW Fu, PP Wen, KC Yu, HT AF Chiang, Hsiu-Mei Yin, Jun-Jie Xia, Qingsu Zhao, Yuewei Fu, Peter P. Wen, Kuo-Ching Yu, Hongtao TI Photoirradiation of azulene and guaiazulene-Formation of reactive oxygen species and induction of lipid peroxidation SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY LA English DT Article DE Azulene; Guaiazulene; Photoirradiation; UVA light; Reactive oxygen species; Lipid peroxidation ID SINGLET OXYGEN; RETINYL PALMITATE; DNA-DAMAGE; RADICALS; PHOTOCHEMISTRY; PHOTOSTABILITY; PHOTOTOXICITY; SUPEROXIDE; RADIATION; OXIDATION AB Azulene and guaiazulene are popular ingredients in beauty, cosmetic, skin, and body care products. We previously determined that these chemicals are photomutagenic in Salmonella and phototoxic. causing DNA damage in human Jurkat T-cells. In this study we report that photoirradiation of azulene and guaiazulene, respectively. by UVA light at 0-70 J/cm(2) in the presence of a lipid, methyl linoleate, resulted in lipid peroxidation in a light dose-responsive manner. When irradiated in the presence of sodium azide or superoxide dismutase, the level of lipid peroxidation decreased, indicating that lipid peroxidation is mediated by free radical and superoxide in particular. In contrast, lipid peroxidation was not enhanced when deuterated methanol was incorporated to the system, which suggests that singlet oxygen is not a predominant photo-induced product. Electron spin resonance (ESR) spin trapping study confirmed that photoirradiation of azulene predominantly generated superoxide and none or very low quantity of singlet oxygen was produced. These results indicate that photoirradiation of azulene and guaiazulene by UVA light generates reactive oxygen species (ROS), and induces lipid peroxidation when irradiation in the presence of a lipid. These results implicate that azulene and guaiazulene are phototoxic when exposed to sunlight. (C) 2010 Elsevier B.V. All rights reserved. C1 [Chiang, Hsiu-Mei; Wen, Kuo-Ching] China Med Univ, Dept Cosmecut, Taichung, Taiwan. [Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Xia, Qingsu; Zhao, Yuewei; Fu, Peter P.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Yu, Hongtao] Jackson State Univ, Dept Chem & Biochem, Jackson, MS 39217 USA. RP Chiang, HM (reprint author), China Med Univ, Dept Cosmecut, 91 Hsueh Shih Rd, Taichung, Taiwan. EM hmchiang@mail.cmu.edu.tw RI Chiang, Hsiu-Mei/L-8150-2013; Yin, Jun Jie /E-5619-2014 FU China Medical University, Taichung [CMU98-S-37]; National Science Council, Taipei, Taiwan [NSC97-2320-B-039-040-MY3] FX We want to express our thanks to the reviewers providing highly valuable suggestions for discussion of the experimental results. This research was in partly supported by the China Medical University (CMU98-S-37), Taichung, and National Science Council (NSC97-2320-B-039-040-MY3), Taipei, Taiwan. NR 37 TC 15 Z9 15 U1 0 U2 10 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1010-6030 J9 J PHOTOCH PHOTOBIO A JI J. Photochem. Photobiol. A-Chem. PD APR 15 PY 2010 VL 211 IS 2-3 BP 123 EP 128 DI 10.1016/j.jphotochem.2010.02.007 PG 6 WC Chemistry, Physical SC Chemistry GA 597ZN UT WOS:000277801300005 ER PT J AU Liao, GH Wen, ZN Irizarry, K Huang, Y Mitsouras, K Darmani, M Leon, T Shi, LM Bi, XN AF Liao, Guanghong Wen, Zhining Irizarry, Kristopher Huang, Ying Mitsouras, Katherine Darmani, Mariam Leon, Terry Shi, Leming Bi, Xiaoning TI Abnormal gene expression in cerebellum of Npc1-/- mice during postnatal development SO BRAIN RESEARCH LA English DT Article DE Cell adhesion; Cholesterol; Gene expression; Microarray; Niemann-Pick type C disease ID DENSITY-LIPOPROTEIN-CHOLESTEROL; FARNESYL PYROPHOSPHATE SYNTHASE; PICK C1-DEFICIENT NEURONS; CENTRAL-NERVOUS-SYSTEM; STEROL-SENSING DOMAIN; LIVER X RECEPTORS; C DISEASE; APOLIPOPROTEIN-D; MOUSE-BRAIN; ALLOPREGNANOLONE TREATMENT AB Niemann-Pick Type C (NPC) disease is an autosomal recessive neurodegenerative disorder with abnormal lipid storage as the major cellular pathologic hallmark. Genetic analyses have identified mutations in NPC1 gene in the great majority of cases, while mutations in NPC2 account for the remainders. Yet little is known regarding the cellular mechanisms responsible for NPC pathogenesis, especially for neurodegeneration, which is the usual cause of death. To identify critical steps that could account for the pathological manifestations of the disease in one of the most affected brain structures, we performed global gene expression analysis in the cerebellum from 3-week old Npc1+/+ and Npc1-/- mice with two different microarray platforms (Agilent and Illumina). Differentially expressed genes identified by both microarray platforms were then subjected to KEGG pathway analysis. Expression of genes in six pathways was significantly altered in Npc1-/- mice; functionally, these signaling pathways belong to the following three categories: (1) steroid and terpenoid biosynthesis, (2) immune response, and (3) cell adhesion/motility. In addition, the expression of several proteins involved in lipid transport was significantly altered in Npc1-/- mice. Our results provide novel molecular insight regarding the mechanisms of pathogenesis in NPC disease and reveal potential new therapeutic targets. (C) 2010 Elsevier B.V. All rights reserved. C1 [Liao, Guanghong; Mitsouras, Katherine; Darmani, Mariam; Leon, Terry; Bi, Xiaoning] Western Univ Hlth Sci, Dept Basic Med Sci, COMP, Pomona, CA 91766 USA. [Irizarry, Kristopher] Western Univ Hlth Sci, Coll Vet Med, Pomona, CA 91766 USA. [Huang, Ying] Western Univ Hlth Sci, Coll Pharm, Pomona, CA 91766 USA. [Wen, Zhining; Shi, Leming] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Bi, XN (reprint author), Western Univ Hlth Sci, Dept Basic Med Sci, COMP, 309 E 2nd St, Pomona, CA 91766 USA. EM xbi@westemu.edu FU NINDS [NS048423]; Western University; Daljit and Elaine Sarkaria Chair FX Sources of support: This work was supported by a grant from NINDS (NS048423 to XB) and by funds from Western University to X.B. Xiaoning Bi was also supported by funds from the Daljit and Elaine Sarkaria Chair. NR 71 TC 14 Z9 14 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 APR 14 PY 2010 VL 1325 BP 128 EP 140 DI 10.1016/j.brainres.2010.02.019 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 592ZZ UT WOS:000277422100013 PM 20153740 ER PT J AU Andrade, JE Twaddle, NC Helferich, WG Doerge, DR AF Andrade, Juan E. Twaddle, Nathan C. Helferich, William G. Doerge, Daniel R. TI Absolute Bioavailability of Isoflavones from Soy Protein Isolate-Containing Food in Female Balb/c Mice SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Isoflavone; mice; bioavailability; soy protein isolate; pharmacokinetics; genistein ID LIQUID-CHROMATOGRAPHY; SOYBEAN ISOFLAVONES; INTESTINAL BACTERIA; MASS-SPECTROMETRY; GENISTEIN; RATS; PHARMACOKINETICS; DAIDZEIN; BETA; QUANTIFICATION AB Soy isoflavones, genistein and daidzein, are widely consumed in soy-based foods and dietary supplements for their putative health benefits; however, evidence for potential adverse effects has been obtained from experimental animal studies. An important prerequisite for understanding the pharmacodynamics of isoflavones is better information about pharmacokinetics and bioavailability. This study determined the bioavailability of genistein and daidzein in a mouse model by comparing plasma pharmacokinetics of their aglycone and conjugated forms following administration of identical doses (1.2 mg/kg genistein and 0.55 mg/kg daidzein) by either an intravenous injection (IV) or gavage of the aglycones in 90% aqueous solution vs a bolus administration of equimolar doses delivered in a food pellet prepared using commercial soy protein isolate (SPI) as the isoflavone source. The bioavailability of genistein and daidzein was equivalent for the gavage and dietary routes of administration despite the use of isoflavone aglycones in the former and SPI-derived glucosides in the latter. While absorption of total isoflavones was nearly quantitative from both oral routes [>84% of areas under the curve (AUCs) for IV], presystemic and systemic phase II conjugation greatly attenuated internal exposures to the receptor-active aglycone isoflavones (9-14% for genistein and 29-34% for daidzein based on AUCs for IV). These results show that SPI is an efficient isoflavone delivery vehicle capable of providing significant proportions of the total dose into the circulation in the active aglycone form for distribution to receptor-bearing tissues and subsequent pharmacological effects that determine possible health benefits and/or risks. C1 [Andrade, Juan E.; Helferich, William G.] Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. [Twaddle, Nathan C.; Doerge, Daniel R.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Helferich, WG (reprint author), Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. EM helferic@uiuc.edu; daniel.doerge@fda.hhs.gov OI Andrade, Juan/0000-0003-2349-9169 FU National Institute on Aging; National Institute for Complementary and Alternative Medicine; Office of Dietary Supplements; Women's Health Initiative [P01 AG024387] FX This research was funded by the National Institute on Aging with additional support from National Institute for Complementary and Alternative Medicine, Office of Dietary Supplements, and Women's Health Initiative (P01 AG024387 to W.G.H. and D.R.D.). The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration. NR 52 TC 12 Z9 14 U1 0 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD APR 14 PY 2010 VL 58 IS 7 BP 4529 EP 4536 DI 10.1021/jf9039843 PG 8 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 577OG UT WOS:000276232700090 PM 20225898 ER PT J AU Kelly, EP Puri, B Sun, W Falgout, B AF Kelly, Eileen P. Puri, Beena Sun, Wellington Falgout, Barry TI Identification of mutations in a candidate dengue 4 vaccine strain 341750 PDK20 and construction of a full-length cDNA clone of the PDK20 vaccine candidate SO VACCINE LA English DT Article DE Dengue virus; Vaccine virus mutation analysis; Infectious clone ID BORNE ENCEPHALITIS-VIRUS; HEPATITIS-C VIRUS; AMINO-ACID SUBSTITUTION; DOUBLE-STRANDED-RNA; ENVELOPE PROTEIN; VIRAL-RNA; HEMORRHAGIC-FEVER; CRYSTAL-STRUCTURE; NS1 PROTEIN; NONSTRUCTURAL GLYCOPROTEIN-NS1 AB Dengue 4 virus strain 341750 serially passaged 20 times in primary dog kidney (PDK) cells was shown to have reduced infectivity for rhesus monkeys but was immunogenic and protected the monkeys from challenge with low passage parent dengue 4 virus. The dengue 4 PDK20 virus was also shown to be attenuated for human volunteers. We compared the genomic nucleotide sequences of low passage parent and PDK20 attenuated vaccine strains and identified 11 nucleotide (nt) substitutions in the PDK20 genome. Five mutations caused amino acid changes in viral proteins E (N366N/S), NS1 (E146Q), NS4B (S/L112L and A240V), and NS5 (F/L790L). Silent mutations occurred in genes encoding NS1 (nt 2609), NS3 (nt 6113, 6230 and 6239) and NS5 (nt 8081 and 8588). A full-length cDNA clone of the dengue 4 strain 341750 PDK20 was constructed and RNA transcripts of the clone were infectious in monkey kidney (LLC-MK(2)) and Aedes albopictus (C6/36) cells. The sequence analysis and availability of an infectious clone provide molecular tools to investigate the basis for the attenuation of dengue 4 virus. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Kelly, Eileen P.; Sun, Wellington] Walter Reed Army Inst Res, Div Virus Dis, Dept Virus Dis, Silver Spring, MD 20910 USA. [Puri, Beena] USN, Dept Infect Dis, Viral Dis Program, Med Res Ctr, Silver Spring, MD USA. [Falgout, Barry] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20952 USA. RP Kelly, EP (reprint author), Walter Reed Army Inst Res, Div Virus Dis, Dept Virus Dis, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. EM eileen.kelly@amedd.army.mil; beena.puri@fda.hhs.gov; wellington.sun@fda.hhs.gov; barry.falgout@fda.hhs.gov FU United States Army Medical Research and Materiel Command FX We thank Dr. Ken Eckels, Walter Reed Army Institute of Research, for providing the lyophilized parent and vaccine candidate viruses. The studies were supported by the United States Army Medical Research and Materiel Command. NR 53 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 9 PY 2010 VL 28 IS 17 BP 3030 EP 3037 DI 10.1016/j.vaccine.2009.10.084 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 586CE UT WOS:000276877900016 PM 19874927 ER PT J AU Sun, S Francis, J Sapsford, KE Kostov, Y Rasooly, A AF Sun, Steven Francis, Jesse Sapsford, Kim E. Kostov, Yordan Rasooly, Avraham TI Multi-wavelength spatial LED illumination based detector for in vitro detection of botulinum neurotoxin A activity SO SENSORS AND ACTUATORS B-CHEMICAL LA English DT Article DE LED; Electroluminescent excitation; CCD; Fluorescence; Forster Resonance Energy Transfer (FRET); Botulinum neurotoxin A; Biodetection ID LINKED-IMMUNOSORBENT-ASSAY; ARRAY BIOSENSOR; RAPID DETECTION; SEROTYPE-A; NEUROTRANSMITTER RELEASE; PROTEOLYTIC CLEAVAGE; SENSITIVE DETECTION; MEMBRANE-PROTEIN; MOUSE BIOASSAY; B NEUROTOXIN AB A portable and rapid detection system for the activity analysis of botulinum neurotoxins (BoNT) is needed for food safety and bio-security applications. To improve BoNT activity detection, a previously designed portable charge-coupled device (CCD) based detector was modified and equipped with a higher intensity more versatile multi-wavelength spatial light-emitting diode (LED) illumination, a faster CCD detector and the capability to simultaneously detect 30 samples. A FITC/DABCYL Forster Resonance Energy Transfer (FRET)-labeled peptide substrate (SNAP-25), with BoNT-A target cleavage site sequence was used to measure BoNT-A light chain (LcA) activity through the FITC fluorescence increase that occurs upon peptide substrate cleavage. For fluorescence excitation, a multi-wavelength spatial LED illuminator was used and compared to our previous electroluminescent (EL) strips. The LED illuminator was equipped with blue, green, red and white LEDs, covering a spectrum of 450-680 nm (red 610-650 nm, green 492-550 nm, blue 450-495 nm, and white LED 440-680 nm). In terms of light intensity, the blue LED was found to be similar to 80-fold higher than the previously used blue EL strips. When measuring the activity of LcA the CCD detector limit of detection (LOD) was found to be 0.08 nM LcA for both the blue LED (2 s exposure) and the blue EL (which require >= 60s exposure) while the limits of quantitation (LOQ) is about 1 nM. The LOD for white LED was higher at 1.4 nM while the white EL was not used for the assay due to a high variable background. Unlike the weaker intensity EL illumination the high intensity LED illumination enabled shorter exposure times and allowed multi-wavelength illumination without the need to physically change the excitation strip, thus making spectrum excitation of multiple fluorophores possible increasing the versatility of the detector platform for a variety of optical detection assays. Published by Elsevier B.V. C1 [Rasooly, Avraham] NCI, Rockville, MD 20892 USA. [Sun, Steven; Sapsford, Kim E.; Rasooly, Avraham] US FDA, Div Biol, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. [Sun, Steven; Francis, Jesse; Kostov, Yordan] Univ Maryland Baltimore Cty, Baltimore, MD 21227 USA. RP Rasooly, A (reprint author), NCI, Rockville, MD 20892 USA. EM rasoolya@mail.nih.gov FU Office of Public Health Emergency Preparedness (OPHEP) [IAG 224-05-655]; FDA [HHSF223200610765P] FX This work was supported in part by the Office of Public Health Emergency Preparedness (OPHEP) IAG 224-05-655 (to A. Rasooly) and by FDA contract HHSF223200610765P (to Dr. Yordan Rostov). NR 50 TC 18 Z9 18 U1 1 U2 10 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0925-4005 J9 SENSOR ACTUAT B-CHEM JI Sens. Actuator B-Chem. PD APR 8 PY 2010 VL 146 IS 1 BP 297 EP 306 DI 10.1016/j.snb.2010.02.009 PG 10 WC Chemistry, Analytical; Electrochemistry; Instruments & Instrumentation SC Chemistry; Electrochemistry; Instruments & Instrumentation GA 586UA UT WOS:000276937800046 PM 20498728 ER PT J AU Samy, R Faustino, PJ Adams, W Yu, L Khan, MA Yang, YS AF Samy, Raghu Faustino, Patrick J. Adams, Wallace Yu, Lawrence Khan, Mansoor A. Yang, Yongsheng TI Development and validation of an ion chromatography method for the determination of phosphate-binding of lanthanum carbonate SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Lanthanum carbonate; Ion chromatography; Method validation; Phosphate binding ID CHRONIC-RENAL-FAILURE; HEMODIALYSIS-PATIENTS; DIALYSIS PATIENTS; SEVELAMER; BINDER; HYPERPHOSPHATEMIA; CALCIFICATION; CORONARY; DISEASE; ASSAY AB Lanthanum carbonate is indicated to reduce serum phosphate in patients with end stage renal disease (ESRD). When given orally, lanthanum carbonate dissociates in the acid environment of the upper gastrointestinal tract to release lanthanum ions. The free lanthanum ions bind with dietary phosphate released from food during digestion to form highly insoluble lanthanum-phosphate complexes which prevent the absorption of phosphate, consequently reduce the serum phosphate. In order to evaluate the in vitro binding capacity of lanthanum carbonate, a simple and efficient ion chromatography (IC) method was developed and validated for determination of phosphate across the pH range encountered in the gastrointestinal tract. Chromatographic separation was achieved on a Dionex ICS-2000 IC system using a Dionex AS16, lonPac (4 mm x 250 mm) analytical column and Dionex AG16, lonPac (4 mm x 50 mm) guard column. Column temperature was maintained at 30 degrees C. Injection volume was 10 mu L The compounds were eluted isocratically at a flow rate of 1 mL/min and detected by suppressed conductivity. The analytical method was validated according to USP Category I requirements. The validation characteristics included accuracy, precision, quantification limit, linearity, and stability. The intra-day accuracy ranged from 89% to 103% for the solutions of pH 1.2-6.8. The intra-day precision (RSD) ranged from 0.6% to 3.7% for the solutions of pH 1.2-6.8. The analytical range was linear from 2 to 200 ppm (mg/L). The R(2) ranged from 0.9998 to 1.0. This method was found to be simple, robust, sensitive, specific, and accurate. It has been successfully applied for determination of phosphate binding to lanthanum carbonate over the human gastrointestinal pH range at different time-points (from 0.5 to 24 h). Published by Elsevier B.V. C1 [Samy, Raghu; Faustino, Patrick J.; Khan, Mansoor A.; Yang, Yongsheng] US FDA, Div Prod Qual Res, Off Pharmaceut Sci, Silver Spring, MD 20993 USA. [Adams, Wallace; Yu, Lawrence] US FDA, Off Gener Drugs, Rockville, MD 20855 USA. RP Yang, YS (reprint author), US FDA, Div Prod Qual Res, Off Pharmaceut Sci, Life Sci Bldg 64,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM yongsheng.yang@fda.hhs.gov RI Yu, Lawrence/L-6280-2016 NR 25 TC 12 Z9 12 U1 1 U2 11 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 APR 6 PY 2010 VL 51 IS 5 BP 1108 EP 1112 DI 10.1016/j.jpba.2009.11.017 PG 5 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 546TP UT WOS:000273835100016 PM 20031362 ER PT J AU Trentacosti, AM He, RY Burke, LB Griebel, D Kennedy, DL AF Trentacosti, Ann Marie He, Ruyi Burke, Laurie B. Griebel, Donna Kennedy, Dianne L. TI Evolution of Clinical Trials for Irritable Bowel Syndrome: Issues in End Points and Study Design SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material ID 5-HT3 RECEPTOR ANTAGONIST; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; IMMPACT RECOMMENDATIONS; DRUG DEVELOPMENT; SYMPTOM RELIEF; STOOL FORM; TEGASEROD; ALOSETRON; EFFICACY AB Irritable bowel syndrome (IBS) involves a broad range of physiological and psychological alterations that may affect brain-gut dysregulation, gut function, visceral perception, and mucosal integrity and function. Despite advances in our understanding of basic neuroenteric mechanisms and the role of effectors and transmitters in the brain-gut axis, a reliable biologic marker of IBS has yet to be identified (1-8). IBS diagnosis and status depend entirely on an assessment of IBS signs and symptoms. This has made development of optimal end points and study design for evaluation of efficacy of IBS drugs a challenge. This article addresses three main topics: the evolution of primary end points for IBS clinical trials; a potential path forward for IBS end points in new clinical trials; and recommendations for the future development of patient-reported outcome (PRO) instruments for use in IBS clinical trials. C1 [Trentacosti, Ann Marie; Burke, Laurie B.; Kennedy, Dianne L.] US FDA, Ctr Drug Evaluat & Res, Study Endpoints & Labeling Dev, Off New Drugs, Silver Spring, MD 20993 USA. [He, Ruyi; Griebel, Donna] US FDA, Ctr Drug Evaluat & Res, Div Gastroenterol Prod, Off New Drugs, Silver Spring, MD 20993 USA. RP Trentacosti, AM (reprint author), US FDA, Ctr Drug Evaluat & Res, Study Endpoints & Labeling Dev, Off New Drugs, 10903 New Hampshire Ave,Bldg 22,Room 6462, Silver Spring, MD 20993 USA. EM annmarie.trentacost@fda.hhs.gov NR 33 TC 24 Z9 24 U1 1 U2 3 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 APR PY 2010 VL 105 IS 4 BP 731 EP 735 DI 10.1038/ajg.2010.12 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 582FQ UT WOS:000276582300004 PM 20372121 ER PT J AU Fine, AJ Walker, J Basques, KD Leventhal, JR AF Fine, Andrew J. Walker, Jennifer Basques, Kyle D. Leventhal, Joseph R. TI Alemtuzumab Induction and Prednisone-Free Maintenance Immunosuppression in an Older Renal Transplant Population SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Fine, Andrew J.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Walker, Jennifer] New York Presbyterian Cornell Hosp, Dept Pharm, New York, NY USA. [Leventhal, Joseph R.] Northwestern Univ, Feinberg Sch Med, Comprehens Transplant Ctr, Chicago, IL 60611 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 321 EP 321 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921702392 ER PT J AU Karnaukhova, E AF Karnaukhova, Elena TI Interactions of alpha(1)-proteinase inhibitor with small ligands of therapeutic potential: binding with retinoic acid SO AMINO ACIDS LA English DT Article DE Alpha-1 proteinase inhibitor; Antitrypsin; Retinoic acid ID PROTEIN-C INHIBITOR; HUMAN SERUM-ALBUMIN; PREVENT CONFORMATIONAL DISEASE; SERPIN POLYMERIZATION; ALPHA(1)-ANTITRYPSIN DEFICIENCY; ALVEOLAR DEVELOPMENT; MECHANISM; EMPHYSEMA; TRIAL; Z-ALPHA(1)-ANTITRYPSIN AB Human alpha(1)-proteinase inhibitor (alpha(1)-PI), also known as alpha(1)-antitrypsin, is the most abundant plasma serine protease inhibitor (serpin). It is best recognized for inhibition of neutrophil elastase. The alpha(1)-PI interactions with non-protease ligands were investigated mainly in regards to those molecules that may block the aggregation of alpha(1)-PI Z mutant. The objective of this study was to evaluate the potential of alpha(1)-PI to bind small non-peptide ligands of pharmaceutical interest that may attain additional properties to currently available alpha(1)-PI therapeutic preparations. Among putative ligands of bio-medical interest examined in this study, all-trans retinoic acid (RA) was selected due to its recently proposed roles in the lungs, and as an efficient optical probe. The results of this study, including absorption spectroscopy data, fluorescence quenching and the protein-induced chirality of the visible circular dichroism strongly suggest that alpha(1)-PI does bind RA in vitro to non-covalent complexes of up to two moles of RA per one mole of the protein. To our knowledge, this is the first report that provides experimental evidence of the alpha(1)-PI potential towards bi-functional drugs via a combination with RA, or potentially other molecules of pharmaceutical interest, that ultimately, may enhance currently available alpha(1)-PI therapies. C1 US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Karnaukhova, E (reprint author), US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, 8800 Rockville Pike,Natl Inst Hlth Bldg 29, Bethesda, MD 20892 USA. EM elena.karnaukhova@fda.hhs.gov NR 64 TC 2 Z9 2 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD APR PY 2010 VL 38 IS 4 BP 1011 EP 1020 DI 10.1007/s00726-009-0309-9 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 580CA UT WOS:000276423300005 PM 19495939 ER PT J AU Xu, HY Heinze, TM Paine, DD Cerniglia, CE Chen, HZ AF Xu, Haiyan Heinze, Thomas M. Paine, Donald D. Cerniglia, Carl E. Chen, Huizhong TI Sudan azo dyes and Para Red degradation by prevalent bacteria of the human gastrointestinal tract SO ANAEROBE LA English DT Article DE Sudan dyes; Azo dyes; Intestinal bacteria; Aromatic amines; Biodegradation ID HUMAN INTESTINAL MICROFLORA; OXIDATIVE DNA-DAMAGE; PERFORMANCE LIQUID-CHROMATOGRAPHY; TANDEM MASS-SPECTROMETRY; CYTOCHROME-P450 1A1; AROMATIC-AMINES; ARRAY DETECTION; HEPG2 CELLS; PRODUCTS; IV AB Sudan azo dyes have genotoxic effects and ingestion of food products contaminated with Sudan I. II, III, IV, and Para Red could lead to exposure in the human gastrointestinal tract. In this study, we examined thirty-five prevalent species of human intestinal bacteria to evaluate their capacity to degrade Sudan dyes and Para Red. Among these tested bacterial strains, 23, 13, 33, 30, and 29 out of 35 species tested were able to reduce Sudan I, II, III, IV, and Para Red, respectively, to some extent. Bifidobacterium infantis, Clostridium indolis, Enterococcus faecalis, Lactobacillus rhamnosus, and Ruminococcus obeum were able to reduce completely all four tested Sudan dyes and Para Red. Escherichia coli and Peptostreptococcus magnus were the only two strains that were not able to reduce any of the tested Sudan dyes and Para Red to any significant extent. Metabolites of the reduction of the tested Sudan dyes and Para Red by E. faecalis were isolated and identified by HPLC and LC/ESI-MS analyses and compared with authentic standards. Thus it appears that the ability to reduce Sudan dyes and Para Red except Sudan II is common among bacteria in the human colon. Published by Elsevier Ltd. C1 [Xu, Haiyan; Paine, Donald D.; Cerniglia, Carl E.; Chen, Huizhong] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Heinze, Thomas M.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Chen, HZ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM huizhong.chen@fda.hhs.gov FU Office of Women's Health; National Center for Toxicological Research, United States Food and Drug Administration FX We thank Drs. John B. Sutherland and Jinhui Feng for their critical review of the manuscript. We also thank Dr. Christopher A. Elkins for Lactobacillus species. This study was funded by the Office of Women's Health and the National Center for Toxicological Research, United States Food and Drug Administration, and supported in part by an appointment (H.X.) to the Postgraduate Research Fellowship Program by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. The views presented in this article do not necessarily reflect those of the Food and Drug Administration. NR 43 TC 38 Z9 41 U1 1 U2 18 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1075-9964 EI 1095-8274 J9 ANAEROBE JI Anaerobe PD APR PY 2010 VL 16 IS 2 BP 114 EP 119 DI 10.1016/j.anaerobe.2009.06.007 PG 6 WC Microbiology SC Microbiology GA 597CW UT WOS:000277734600008 PM 19580882 ER PT J AU Hong, H Goodsaid, F Shi, L Tong, W AF Hong, H. Goodsaid, F. Shi, L. Tong, W. TI Molecular biomarkers: a US FDA effort SO BIOMARKERS IN MEDICINE LA English DT Review DE drug; labeling; molecular biomarker; pharmacogenomics; qualification; validation ID GENE-EXPRESSION PATTERNS; CONTROL MAQC PROJECT; BREAST-CANCER; DECISION FOREST; DATA SUBMISSIONS; MICROARRAY; SIGNATURE; WARFARIN; POLYMORPHISMS; TRASTUZUMAB AB Molecular biomarkers are used for various purposes, including disease diagnosis and prognosis, prediction and assessment of treatment response, and safety assessment. There has been a significant increase in the number of US FDA-approved drug labels containing information on molecular biomarkers over the last decade. Almost every pharmaceutical company has been developing molecular biomarker programs, either alone, through partnerships or other ventures. More molecular biomarkers are expected to be identified and validated in drug development, and used to support approval of drug products. This article summarizes the current status of molecular biomarkers used for FDA-approved drug products, and discusses the challenges and future perspectives for the identification and qualification of molecular biomarkers. Specific FDA programs and research projects related to molecular biomarkers are also discussed for supporting regulatory review in the future. C1 [Hong, H.] US FDA, Ctr Toxicoinfor, Div Syst toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Hong, H (reprint author), US FDA, Ctr Toxicoinfor, Div Syst toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 50 TC 12 Z9 12 U1 0 U2 4 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 J9 BIOMARK MED JI Biomark. Med. PD APR PY 2010 VL 4 IS 2 BP 215 EP 225 DI 10.2217/BMM.09.81 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 588PY UT WOS:000277086700011 PM 20406066 ER PT J AU Slager, SL Goldin, LR Strom, SS Lanasa, MC Spector, LG Rassenti, L Leis, JF Camp, NJ Kay, NE Vachon, CM Glenn, M Weinberg, JB Rabe, KG Cunningham, JM Achenbach, SJ Hanson, CA Marti, GE Call, TG Caporaso, NE Cerhan, JR AF Slager, Susan L. Goldin, Lynn R. Strom, Sara S. Lanasa, Mark C. Spector, Logan G. Rassenti, Laura Leis, Jose F. Camp, Nicola J. Kay, Neil E. Vachon, Celine M. Glenn, Martha Weinberg, J. Brice Rabe, Kari G. Cunningham, Julie M. Achenbach, Sara J. Hanson, Curtis A. Marti, Gerald E. Call, Timothy G. Caporaso, Neil E. Cerhan, James R. TI Genetic Susceptibility Variants for Chronic Lymphocytic Leukemia SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NON-HODGKIN-LYMPHOMA; TRANSCRIPTION FACTORS; FAMILIES; RISK; LOCI; MUM1/IRF4; SCAN C1 [Slager, Susan L.; Leis, Jose F.; Kay, Neil E.; Vachon, Celine M.; Rabe, Kari G.; Cunningham, Julie M.; Achenbach, Sara J.; Hanson, Curtis A.; Call, Timothy G.; Cerhan, James R.] Mayo Clin, Coll Med, Rochester, MN 55905 USA. [Goldin, Lynn R.; Caporaso, Neil E.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Strom, Sara S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Lanasa, Mark C.; Weinberg, J. Brice] Duke Univ, Med Ctr, Durham, NC USA. [Spector, Logan G.] Univ Minnesota, Minneapolis, MN USA. [Rassenti, Laura] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Camp, Nicola J.; Glenn, Martha] Univ Utah, Sch Med, Salt Lake City, UT USA. [Marti, Gerald E.] US FDA, Bethesda, MD 20014 USA. RP Slager, SL (reprint author), Mayo Clin, Coll Med, 200 1st St SW, Rochester, MN 55905 USA. EM slager@mayo.edu OI Cerhan, James/0000-0002-7482-178X; Spector, Logan/0000-0003-2516-0222 FU NIH [CA118444, CA92153]; Intramural Research Program of the NIH, National Cancer Institute; CLL Research Consortium; NCI [N01-PC-35141]; Utah State Department of Health; University of Utah FX NIH grants CA118444 and CA92153; Intramural Research Program of the NIH, National Cancer Institute; and CLL Research Consortium. Data collection in Utah was made possible by the Utah Population Database and the Utah Cancer Registry. Partial support for all data in the Utah Population Database was provided by the University of Utah Huntsman Cancer Institute. The Utah Cancer Registry is funded by contract N01-PC-35141 from the NCI's SEER program with additional support from the Utah State Department of Health and the University of Utah. NR 15 TC 21 Z9 22 U1 0 U2 1 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 APR PY 2010 VL 19 IS 4 BP 1098 EP 1102 DI 10.1158/1055-9965.EPI-09-1217 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607FL UT WOS:000278484400030 PM 20332261 ER PT J AU Palinkas, LA Reedy, KR Shepanek, M Reeves, D Case, HS Van Do, N Reed, HL AF Palinkas, Lawrence A. Reedy, Kathleen R. Shepanek, Marc Reeves, Dennis Case, H. Samuel Van Do, Nhan Reed, H. Lester TI A randomized placebo-controlled clinical trial of the effectiveness of thyroxine and triiodothyronine and short-term exposure to bright light in prevention of decrements in cognitive performance and mood during prolonged Antarctic residence SO CLINICAL ENDOCRINOLOGY LA English DT Article ID SEASONAL AFFECTIVE-DISORDER; THYROTROPIN LEVELS; SERUM THYROTROPIN; THYROID-HORMONES; PITUITARY; RHYTHM; TSH; HYPOTHYROIDISM; MELATONIN; RESPONSES AB P>Objective We examined the effects of a combined levothyroxine/liothyronine supplement and exposure to bright (10,000 lux) light in euthyroid men and women who spent the austral summer (n = 43) and/or winter (n = 42) in Antarctica. Methods Subjects were randomized to receive 64 nmol of levothyroxine and 16 nmol of liothyronine supplement or a placebo capsule for 93 center dot 2 +/- 3 center dot 0 days in summer and/or 149 center dot 5 +/- 2 center dot 2 days in winter. Subjects were further randomized to receive 10,000 lux bright white light or 50 lux dim red light for 14 days at the end of summer and/or winter. Cognitive performance and mood were assessed using the Automatic Neuropsychological Assessment Metric - Isolated and Confined Environments. Results In winter, bright light exposure was associated with a significantly greater reduction in TSH and anger (P < 0 center dot 05), a significantly greater increase in fT(3) (P < 0 center dot 05), and a significantly smaller increase in depressive symptoms (P < 0 center dot 001), when compared with dim light. The T4/T3 supplement also led to a significantly greater reduction in TSH (P < 0 center dot 05), but a greater reduction in cognitive task efficiency (P < 0 center dot 05) as well, when compared with placebo. Conclusion Administration of bright light leads to a significant reduction in serum TSH and prevents increases in anger and depressive symptoms in winter. However, these associations were not observed in summer, suggesting a seasonal influence of photoperiod over temperature upon this intervention in the polar environment. C1 [Palinkas, Lawrence A.] Univ So Calif, Sch Social Work, Los Angeles, CA 90089 USA. [Palinkas, Lawrence A.] Univ So Calif, Dept Anthropol, Los Angeles, CA 90089 USA. [Palinkas, Lawrence A.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Reedy, Kathleen R.] US FDA, Silver Spring, MD USA. [Shepanek, Marc] NASA, Washington, DC 20546 USA. [Reeves, Dennis] Clinvest Inc, Springfield, MO USA. [Case, H. Samuel] McDaniel Coll, Dept Exercise Sci & Phys Educ, Westminster, MD USA. [Van Do, Nhan] Tricare Management Act, Falls Church, VA USA. [Reed, H. Lester] MultiCare Hlth Syst, Tacoma, WA USA. RP Palinkas, LA (reprint author), Univ So Calif, Sch Social Work, 669 W 34th St, Los Angeles, CA 90089 USA. EM palinkas@usc.edu FU National Science Foundation [OPP-0090343] FX The opinions expressed herein are those of the authors and are not to be construed as reflecting the views of the Department of the Army, the Department of Defense, National Science Foundation, National Aeronautics and Space Administration, or US Food and Drug Administration. This study is supported by the National Science Foundation grant number OPP-0090343. The authors extend a special thanks to Barbara Brittell and Troy Wiles for their role in data collection in the field. NR 38 TC 3 Z9 3 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-0664 EI 1365-2265 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD APR PY 2010 VL 72 IS 4 BP 543 EP 550 DI 10.1111/j.1365-2265.2009.03669.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 563ZS UT WOS:000275180700018 PM 19650782 ER PT J AU Huang, SM Zhao, H Lee, JI Reynolds, K Zhang, L Temple, R Lesko, LJ AF Huang, S-M Zhao, H. Lee, J-I Reynolds, K. Zhang, L. Temple, R. Lesko, L. J. TI Therapeutic Protein-Drug Interactions and Implications for Drug Development SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID MONOCLONAL-ANTIBODIES; METABOLIZING-ENZYMES; TRANSPORTERS; PHARMACOKINETICS; COMBINATION; INFLAMMATION; PERSPECTIVE; CETUXIMAB; DISEASE; IMPACT AB Many intrinsic and extrinsic factors can affect an individual patient's drug exposure and response.(1) The US Food and Drug Administration (FDA) has published a number of guidances that recommend how and when to evaluate these factors during drug development.(2) The most recent FDA draft guidance on drug interactions(3) provides advice for in vitro and in vivo drug interaction studies, including suggestions for study design, dosing strategies and analysis, and interpretation of data for medical product labels. The draft guidance(3) updated the FDA's recommendations on the evaluation of important cytochrome P450 (CYP) enzyme- and transporter-based drug interactions during drug development. C1 [Huang, S-M; Zhao, H.; Lee, J-I; Reynolds, K.; Zhang, L.; Lesko, L. J.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Huang, SM (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM shiewmei.huang@fda.hhs.gov NR 34 TC 61 Z9 63 U1 1 U2 11 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 APR PY 2010 VL 87 IS 4 BP 497 EP 503 DI 10.1038/clpt.2009.308 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 581FL UT WOS:000276506900027 PM 20200513 ER PT J AU Valerio, LG Yang, CH Arvidson, KB Kruhlak, NL AF Valerio, Luis G., Jr. Yang, Chihae Arvidson, Kirk B. Kruhlak, Naomi L. TI A structural feature-based computational approach for toxicology predictions SO EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY LA English DT Review DE computational toxicology; preclinical toxicity; QSAR; safety assessment; SAR ID URINARY-TRACT TOXICITIES; DRUG-INDUCED HEPATOBILIARY; BUILDING-BLOCKS; MDL-QSAR; PHARMACEUTICALS; IDENTIFICATION; SOFTWARE; DATABASE; MODELS; PART AB Importance of the field: Evaluation of pharmaceutical-related toxicities using quantitative structure activity relationship (QSAR) software as decision support tools is becoming practical and is of keen interest to scientists in both product safety and discovery. QSARs can be used to predict preclinical and clinical endpoints, drug metabolism, pharmacokinetics and mechanisms responsible for toxicity. These in silico tools are of interest in supporting regulatory review processes, and priority setting in research and product development. Areas covered in this review: A critical assessment of the current capabilities of a new technology, the Leadscope Model Applier, is presented. Possible strengths and limitations of this technology with emphasis on the chemoinformatics method are described, and supporting literature citations date back to 1983. What the reader will gain: Insight will be gained into the Leadscope Model Applier technology for structural feature-based QSAR models and its potential capability for chemical inference if the training sets are transparently open. Currently, however, there is a lack of transparency due to the protection of the proprietary training set. Take home message: Further research and development is needed in the creation of more stringently validated models with greater transparency and better balance between sensitivity and specificity. C1 [Valerio, Luis G., Jr.; Kruhlak, Naomi L.] US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Sci & Res Staff,Informat & Computat Safety Anal S, Silver Spring, MD 20993 USA. [Yang, Chihae; Arvidson, Kirk B.] US FDA, Ctr Food Safety & Appl Nutr, Div Food Contact Notificat, Off Food Addit Safety, College Pk, MD 20740 USA. RP Valerio, LG (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Sci & Res Staff,Informat & Computat Safety Anal S, White Oak 51 Room 4128,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Luis.Valerio@fda.hhs.gov NR 27 TC 17 Z9 18 U1 0 U2 9 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1742-5255 J9 EXPERT OPIN DRUG MET JI Expert Opin. Drug Metab. Toxicol. PD APR PY 2010 VL 6 IS 4 BP 505 EP 518 DI 10.1517/17425250903499286 PG 14 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 587AV UT WOS:000276959800008 PM 20074001 ER PT J AU Shi, Q Hong, HX Senior, J Tong, WD AF Shi, Qiang Hong, Huixiao Senior, John Tong, Weida TI Biomarkers for drug-induced liver injury SO EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Review DE biomarker; drug-induced liver injury; genomics; hepatotoxicity; idiosyncratic ID ACETAMINOPHEN-PROTEIN ADDUCTS; GENE-EXPRESSION; RAT-LIVER; GLUTAMATE-DEHYDROGENASE; INDUCED HEPATOTOXICITY; INDUCED PHOSPHOLIPIDOSIS; HEPATIC-INJURY; MITOCHONDRIAL DYSFUNCTION; MICROARRAY ANALYSIS; MAJOR DETERMINANT AB Of the estimated 10,000 documented human drugs, more than 1000 have been associated with drug-induced liver injury (DILI), although causality has not always been established clearly. Numerous biomarkers for DILI have been explored, but less than ten are adopted or qualified as valid by the US FDA. The biomarkers for DILI are individual or a panel of proteins, nucleic acids or metabolites from various sources, such as the liver, blood and urine. While most DILI biomarkers are drug independent, some possibly 'drug-specific' DILIs have been explored, but specificity and sensitivity of both types need to be improved for the diagnosis of DILI during drug development and in clinical practice. Novel approaches for DILI biomarkers have been actively investigated recently, but produced mainly animal-based biomarkers, which are possibly useful for drug development, but are not suitable or have not been validated for clinical applications. This review summarizes the current practice and future perspectives for DILI biomarkers. C1 [Shi, Qiang; Hong, Huixiao; Tong, Weida] US FDA, Ctr Toxicoinformat, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Senior, John] US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. RP Tong, WD (reprint author), US FDA, Ctr Toxicoinformat, Div Syst Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM weida.tong@fda.hhs.gov RI Qiang, Shi/E-6266-2012 FU US FDA; Office of Women's Health; Chief Scientist Challenge Grant; NCTR FX This project is supported by the US FDA's Critical Path program, Office of Women's Health and Chief Scientist Challenge Grant. Dr Qiang Shi is supported by the Research Participation Program at the NCTR administrated by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the US FDA. The views presented in this article do not necessarily reflect those of the US FDA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 97 TC 40 Z9 46 U1 3 U2 20 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1747-4124 J9 EXPERT REV GASTROENT JI Expert Rev. Gastroenterol. Hepatol. PD APR PY 2010 VL 4 IS 2 BP 225 EP 234 DI 10.1586/EGH.10.8 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 860XS UT WOS:000297982300015 PM 20350268 ER PT J AU Babu, US Garthoff, LH Calvo, MS AF Babu, Uma Suresh Garthoff, Larry H. Calvo, Mona S. TI Vitamin D2 enriched mushrooms stimulate innate immunity in LPS challenged rats SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Babu, Uma Suresh; Garthoff, Larry H.; Calvo, Mona S.] US FDA, Off Appl Res & Safety Assessment, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675504392 ER PT J AU Holthoff, JH Burns, ST Woodling, KA Doerge, DR Hinson, JA Mayeux, PR AF Holthoff, Joseph H. Burns, Samuel T. Woodling, Kellie A. Doerge, Daniel R. Hinson, Jack A. Mayeux, Philip R. TI The dietary antioxidant resveratrol is a functional scavenger of peroxynitrite in vitro SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Holthoff, Joseph H.; Burns, Samuel T.; Hinson, Jack A.; Mayeux, Philip R.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Woodling, Kellie A.; Doerge, Daniel R.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675501283 ER PT J AU Irwin, D Foreman, B Connor, I Lisk, C Buehler, P AF Irwin, David Foreman, Ben Connor, Ian Lisk, Christina Buehler, Paul TI Low dose chronically infused hemoglobin induces pulmonary hypertension or excerbates hypoxia-induced pulmonary hypertension SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Irwin, David] Unvers Colorado Hlth Sci Centert, Med, Aurora, CO USA. [Foreman, Ben; Connor, Ian; Lisk, Christina] Univ Colorado, Hlth Sci Ctr, Aurora, CO USA. [Buehler, Paul] US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Lab Biochem & Vasc Biol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675506886 ER PT J AU Juan, WY Crane, N AF Juan, WenYen Crane, Nancy TI Levels and variability of sodium content in soups, baked products, and breakfast cereals in the United States SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Juan, WenYen; Crane, Nancy] US FDA, Off Nutrt Labeling & Dietary Supplements, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500838 ER PT J AU Leonard, SA Labiner-Wolfe, J Rasmussen, KM AF Leonard, Stephanie A. Labiner-Wolfe, Judy Rasmussen, Kathleen M. TI Associations among high prepregnancy body mass index, use of a breast pump and breastfeeding outcomes: Data from the Infant Feeding Practices Study II SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Leonard, Stephanie A.; Rasmussen, Kathleen M.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. [Labiner-Wolfe, Judy] US FDA, Ctr Safety & Appl Nutr, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675505180 ER PT J AU Slikker, W Shi, Q Guo, L Patterson, TA Dial, S Li, Q Sadovova, N Zhang, X Hanig, JP Paule, MG Wang, C AF Slikker, William Shi, Qiang Guo, Lei Patterson, Tucker A. Dial, Stacey Li, Quan Sadovova, Natalya Zhang, Xuan Hanig, Joseph P. Paule, Merle G. Wang, Cheng TI Confirmation of the mode of action of anesthetic-induced developmental neurotoxicity with gene expression studies SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Slikker, William; Shi, Qiang; Guo, Lei; Patterson, Tucker A.; Dial, Stacey; Zhang, Xuan; Paule, Merle G.; Wang, Cheng] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Li, Quan] UTSW Med Ctr, Microarray Core Facil, Dallas, TX USA. [Sadovova, Natalya] Toxicol Pathol Associates, Jefferson, AR USA. [Hanig, Joseph P.] US FDA, CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675502854 ER PT J AU Adkins, S Webster, CG McCollum, TG Albano, JP Kousik, CS Roberts, PD Webb, SE Baker, CA Turechek, WW AF Adkins, Scott Webster, Craig G. McCollum, T. Greg Albano, Joseph P. Kousik, Chandrasekar S. Roberts, Pamela D. Webb, Susan E. Baker, Carlye A. Turechek, William W. TI Update on the Watermelon Vine Decline Virus and Other Whitefly-transmitted Cucurbit Viruses in Florida, and Their Effects on Watermelon SO HORTSCIENCE LA English DT Meeting Abstract CT Northeast Region Annual Meeting of the American-Society-for-Horticultural-Science CY JAN 04-07, 2010 CL Cambridge, MA C1 [Adkins, Scott; Webster, Craig G.; McCollum, T. Greg; Albano, Joseph P.; Turechek, William W.] USDA ARS, Ft Pierce, FL USA. [Kousik, Chandrasekar S.] USDA ARS, Charleston, SC USA. [Roberts, Pamela D.] Univ Florida, SWFREC, Immokalee, FL USA. [Webb, Susan E.] Univ Florida, Gainesville, FL USA. [Baker, Carlye A.] FDACS DPI, Gainesville, FL USA. 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 APR PY 2010 VL 45 IS 4 BP 510 EP 510 PG 1 WC Horticulture SC Agriculture GA 588DR UT WOS:000277048100133 ER PT J AU Angelone, LM Ahveninen, J Belliveau, JW Bonmassar, G AF Angelone, Leonardo M. Ahveninen, Jyrki Belliveau, John W. Bonmassar, Giorgio TI Analysis of the Role of Lead Resistivity in Specific Absorption Rate for Deep Brain Stimulator Leads at 3T MRI SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Head model; intracranial electrodes; safety; simulations ID TO-NOISE RATIO; PARKINSONS-DISEASE; BIRDCAGE COIL; HUMAN HEAD; NEUROSTIMULATION SYSTEMS; TEMPERATURE ELEVATION; METALLIC IMPLANTS; FIELD; SAFETY; SAR AB Magnetic resonance imaging (MRI) on patients with implanted deep brain stimulators (DBSs) can be hazardous because of the antenna-effect of leads exposed to the incident radio-frequency field. This study evaluated electromagnetic field and specific absorption rate (SAR) changes as a function of lead resistivity on an anatomically precise head model in a 3T system. The anatomical accuracy of our head model allowed for detailed modeling of the path of DBS leads between epidermis and the outer table. Our electromagnetic finite difference time domain (FDTD) analysis showed significant changes of 1 g and 10 g averaged SAR for the range of lead resistivity modeled, including highly conductive leads up to highly resistive leads. Antenna performance and whole-head SAR were sensitive to the presence of the DBS leads only within 10%, while changes of over one order of magnitude were observed for the peak 10 g averaged SAR, suggesting that local SAR values should be considered in DBS guidelines. With rho(lead) = rho(copper), and the MRI coil driven to produce a wholehead SAR without leads of 3.2 W/kg, the 1 g averaged SAR was 1080 W/kg and the 10 g averaged SAR 120 W/kg at the tip of the DBS lead. Conversely, in the control case without leads, the 1 g and 10 g averaged SAR were 0.5 W/kg and 0.6 W/kg, respectively, in the same location. The SAR at the tip of lead was similar with electrically homogeneous and electrically heterogeneous models. Our results showthat computational models can support the development of novel lead technology, properly balancing the requirements of SAR deposition at the tip of the lead and power dissipation of the system battery. C1 [Angelone, Leonardo M.] US FDA, Div Phys, Off Sci, Silver Spring, MD 20993 USA. [Angelone, Leonardo M.] US FDA, Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Ahveninen, Jyrki; Belliveau, John W.; Bonmassar, Giorgio] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. RP Angelone, LM (reprint author), US FDA, Div Phys, Off Sci, Silver Spring, MD 20993 USA. EM leonardo.an-gelone@fda.hhs.gov OI Angelone, Leonardo/0000-0002-1105-021X FU National Institute of Neurological Disorders And Stroke [R01 NS037462]; National Institute of Biomedical Imaging and Bioengineering [R01EB006385]; National Center for Research Resources (NCRR) [P41-RR14075]; MIND institute FX This work was supported in part by the National Institute of Neurological Disorders And Stroke (R01 NS037462), in part by the National Institute of Biomedical Imaging and Bioengineering (R01EB006385), in part by the National Center for Research Resources (NCRR) (P41-RR14075), and in part by the MIND institute. NR 54 TC 14 Z9 14 U1 0 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD APR PY 2010 VL 29 IS 4 BP 1029 EP 1038 DI 10.1109/TMI.2010.2040624 PG 10 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 575TJ UT WOS:000276091000006 PM 20335090 ER PT J AU Witten, JM Park, S Myers, KJ AF Witten, Joel M. Park, Subok Myers, Kyle J. TI Partial Least Squares: A Method to Estimate Efficient Channels for the Ideal Observers SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Bayesian ideal observer; channelized Hotelling observer; channelized ideal observer; efficient channels; image quality; partial least squares ID DISTRIBUTED LUMPY BACKGROUNDS; DETECTION PERFORMANCE; GAUSSIAN SIGNAL; REGRESSION; TOOL AB We advocate a task-based approach to the assessment of image quality using the Bayesian ideal observer. The Bayesian ideal observer provides an absolute upper bound for performance estimates. However, using the full images as inputs to the observer is often infeasible due to their high dimensionality. A practical alternative is to reduce the dimensionality of the images by applying channels, while approximating the ideal observer by an observer constrained to the channels. Laguerre-Gauss (LG) channels and those derived from the singular value decomposition (SVD) of the system operator have previously been used with the Bayesian ideal observer. However, the channelized observer with LG and SVD channels was only applicable in situations with a rotationally symmetric signal or known system operator, respectively. We investigate a method using partial least squares (PLS) to compute efficient channels directly from the images, without prior knowledge of the background, signal, or system operator. Results show that the channelized ideal observer with PLS channels approximates the nonchannelized observer, and does so with fewer channels than the observer with either LG or SVD channels. The images are reduced from 4096 pixel values to 20 channel outputs, yet preserve the salient information. Furthermore, PLS reveals that the background image statistics provide important information necessary in signal-detection tasks. Overall, PLS is shown to be a viable channel generation method and may be applicable to real-life situations. C1 [Park, Subok] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Witten, Joel M.; Myers, Kyle J.] US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math, White Oak, MD 20993 USA. [Witten, Joel M.] Columbia Univ, Dept Stat, New York, NY 10027 USA. RP Park, S (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM subok.park@fda.hhs.gov NR 21 TC 17 Z9 18 U1 0 U2 4 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 APR PY 2010 VL 29 IS 4 BP 1050 EP 1058 DI 10.1109/TMI.2010.2041514 PG 9 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 575TJ UT WOS:000276091000008 PM 20335088 ER PT J AU Chen, T Mei, N Fu, PP AF Chen, Tao Mei, Nan Fu, Peter P. TI Genotoxicity of pyrrolizidine alkaloids SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Review DE pyrrolizidine alkaloid; genotoxicity; mutation; DNA damage; carcinogenesis; mutational signature ID VENO-OCCLUSIVE DISEASE; DNA ADDUCT FORMATION; BIG BLUE RATS; HEPATOCYTE MICRONUCLEUS ASSAY; HEPATIC VENOOCCLUSIVE DISEASE; COMFREY SYMPHYTUM-OFFICINALE; TRADITIONAL MEDICINAL HERBS; BONE-MARROW CELLS; S-PHASE SYNTHESIS; FORMATION IN-VIVO AB Pyrrolizidine alkaloids (PAs) are common constituents of many plant species around the world. PA-containing plants are probably the most common poisonous plants affecting livestock and wildlife. They can inflict harm to humans through contaminated food sources, herbal medicines and dietary supplements. Half of the identified PAs are genotoxic and many of them are tumorigenic. The mutagenicity of PAs has been extensively studied in different biological systems. Upon metabolic activation, PAs produce DNA adducts, DNA cross-linking, DNA breaks, sister chromatid exchange, micronuclei, chromosomal aberrations, gene mutations and chromosome mutations in vivo and in vitro. PAs induced mutations in the cll gene of rat liver and in the p53 and K-ras genes of mouse liver tumors. It has been suggested that all PAs produce a set of (+/-)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine-derived DNA adducts and similar types of gene mutations. The signature types of mutations are G:C -> T:A transversion and tandem base substitutions. Overall, PAs are mutagenic in vivo and in vitro and their mutagenicity appears to be responsible for the carcinogenesis of PAs. Published in 2010 by John Wiley & Sons, Ltd. C1 [Chen, Tao; Mei, Nan; Fu, Peter P.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Chen, T (reprint author), HFT 130,3900 NCTR Rd, Jefferson, AR 72079 USA. EM tao.chen@fda.hhs.gov RI mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 NR 151 TC 52 Z9 53 U1 3 U2 43 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD APR PY 2010 VL 30 IS 3 BP 183 EP 196 DI 10.1002/jat.1504 PG 14 WC Toxicology SC Toxicology GA 594GK UT WOS:000277524000001 PM 20112250 ER PT J AU Moore, KM Duddy, A Lee, GM Velentgas, P Burwen, DR Platt, R Brown, JS AF Moore, Kristen M. Duddy, April Lee, Grace M. Velentgas, Priscilla Burwen, Dale R. Platt, Richard Brown, Jeffrey S. TI Outpatient urticaria diagnosis codes have limited predictive value for same-day influenza vaccine adverse event detection SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE Diagnosis code; Urticaria; Vaccine safety surveillance; Influenza vaccine; Predictive value; Claims databases ID MEDICARE POPULATION; SAFETY; CARE; SURVEILLANCE; SYSTEM; THERAPEUTICS; OUTCOMES; CHILDREN AB Objectives: To assess the predictive value of claims-based outpatient urticaria diagnosis codes to identify potential vaccine-related adverse events (AEs) when recorded on the same day as influenza vaccination. Study Design and Setting: Health plan members with outpatient claims for influenza vaccination and urticaria on the same day between October 1, 2002, and December 31, 2007, were eligible for inclusion. Electronic medical records (EMRs) for 50 eligible patients with the most recent visits of interest occurring at a large group practice were sampled for review. Results: EMRs were available and reviewed for 42 of 50 patients. An influenza vaccination was confirmed in all reviewed medical charts. Urticaria occurring on the day of influenza vaccination was confirmed for 40% of participants (17/42); 3 confirmed urticaria diagnoses were potential AEs and 14 urticaria events occurred before vaccination. Among those with unconfirmed diagnoses, 17 had no evidence of urticaria on physical examination on the day of interest (4 had evidence of a nonurticarial rash and 13 had no evidence of rash on examination) and 8 had insufficient information to make a clinical determination. Conclusion: Outpatient diagnosis codes for urticaria found in health insurance claims data are limited in their predictive value to identify same-day vaccine AEs. (C) 2010 Elsevier Inc. All rights reserved. C1 [Moore, Kristen M.; Duddy, April; Lee, Grace M.; Velentgas, Priscilla; Platt, Richard; Brown, Jeffrey S.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA 02115 USA. [Moore, Kristen M.; Duddy, April; Lee, Grace M.; Velentgas, Priscilla; Platt, Richard; Brown, Jeffrey S.] Harvard Pilgrim Hlth Care, Boston, MA USA. [Burwen, Dale R.] US FDA, Div Epidemiol, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Brown, JS (reprint author), Harvard Univ, Sch Med, Dept Populat Med, Boston, MA 02115 USA. EM jeff_brown@harvardpilgrim.org FU Department of Health and Human Services, Office of the Assistant Secretary for Planning and Evaluation; Centers for Disease Control and Prevention; FDA [HHSF 223200710017C] FX This study was sponsored by the US Food and Drug Administration (FDA), Center for Biologics Evaluation and Research, with funding from the Department of Health and Human Services, Office of the Assistant Secretary for Planning and Evaluation, and administrative collaboration from the Centers for Disease Control and Prevention; FDA Contract No. HHSF 223200710017C. Study collaborators at the FDA reviewed the protocol and contributed to the interpretation of the data and review and approval of the manuscript. Investigators at the Department of Ambulatory Care and Prevention (DACP) contributed to the design and conduct of the study, data collection, management, analysis, and interpretation of the data, and preparation, review and approval of the manuscript.; The authors thank Ping Shi, MA, of DACP for data extraction and analysis and Robert Ball MD, MPH, ScM, Hector Izurieta, MD, MPH, and Sukhminder Sandhu, PhD, MPH, of FDA for their participation in study design and review of the manuscript. NR 21 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD APR PY 2010 VL 63 IS 4 BP 407 EP 411 DI 10.1016/j.jclinepi.2009.08.002 PG 5 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 569ID UT WOS:000275588900009 PM 19889513 ER PT J AU Peters, MG Perrillo, RP Jacobson, IM Ross, DB Doo, EC Murray, JS Wong, JB AF Peters, Marion G. Perrillo, Robert P. Jacobson, Ira M. Ross, David B. Doo, Edward C. Murray, Jeffrey S. Wong, John B. TI Entering the new era of therapy for HBV and HCV infections SO JOURNAL OF FAMILY PRACTICE LA English DT Article ID CHRONIC HEPATITIS-C; HUMAN-IMMUNODEFICIENCY-VIRUS; UNITED-STATES; PLUS RIBAVIRIN; PEGYLATED INTERFERON; ANTIVIRAL TREATMENT; GENOTYPE 1; PEGINTERFERON; MANAGEMENT; MORTALITY C1 [Peters, Marion G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Perrillo, Robert P.] Baylor Reg Transplant Inst, Dallas, TX USA. [Jacobson, Ira M.] Weill Cornell Med Coll, New York, NY USA. [Ross, David B.] Dept Vet Affairs, Washington, DC USA. [Doo, Edward C.] NIH, Bethesda, MD 20892 USA. [Murray, Jeffrey S.] US FDA, Silver Spring, MD USA. [Wong, John B.] Tufts Med Ctr, Boston, MA USA. RP Peters, MG (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. FU Genentech; Anadys; Boehringer Ingelheim; Gilead Sciences Inc.; GlobeImmune, Inc; Human Genome Sciences; Idenix; Intarcia; Merck; Novartis; Pharmasset; Roche Pharmaceuticals; Romark; Schering-Plough; Tibotec; Valeant; Vertex Pharmaceuticals FX Dr Peters reports the following: Consultant: Clinical Care Options, Genentech, Pharmasset. Salary: Dr Peters' spouse receives a salary from Genentech; Dr Jacobson reports the following: Consultant: Abbott, Anadys, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences Inc., GlobeImmune, Inc, Human Genome Sciences, Idenix, Intermune, Merck, Novartis, Pfizer, Pharmasset, Progenics, Roche Pharmaceuticals, Sanofi-Aventis, Schering-Plough, Tibotec, Vertex Pharmaceuticals, Virochem, Zymogenetics. Grant/Research Support: Anadys, Boehringer Ingelheim, Gilead Sciences Inc., GlobeImmune, Inc, Human Genome Sciences, Idenix, Intarcia, Merck, Novartis, Pharmasset, Roche Pharmaceuticals, Romark, Schering-Plough, Tibotec, Valeant, Vertex Pharmaceuticals. Speakers Bureau: Bristol-Myers Squibb, Gilead Sciences Inc., Novartis, Schering-Plough NR 57 TC 1 Z9 1 U1 0 U2 1 PU DOWDEN HEALTH MEDIA PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD APR PY 2010 VL 59 IS 4 SU S BP S51 EP S57 PG 7 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 796XH UT WOS:000293086300008 PM 20398591 ER PT J AU Endrikat, S Gallagher, D Pouillot, R Quesenberry, HH Labarre, D Schroeder, CM Kause, J AF Endrikat, Sarah Gallagher, Daniel Pouillot, Regis Quesenberry, Heather Hicks Labarre, David Schroeder, Carl M. Kause, Janell TI A Comparative Risk Assessment for Listeria monocytogenes in Prepackaged versus Retail-Sliced Deli Meat SO JOURNAL OF FOOD PROTECTION LA English DT Article ID SODIUM DIACETATE; POTASSIUM LACTATE; GROWTH-RATE; CONTAMINATION; PRODUCTS; MOISTURE; DEATHS; STATES; PHASE; HACCP AB Deli meat was ranked as the highest-risk ready-to-eat food vehicle of Listeria monocytogenes within the 2003 U.S. Food and Drug Administration and U.S. Department of Agriculture, Food Safety and Inspection Service risk assessment. The comparative risk of L. monocytogenes in retail-sliced versus prepackaged deli meats was evaluated with a modified version of this model. Other research has found that retail-sliced deli meats have both higher prevalence and levels of L. monocytogenes than have product sliced and packaged at the manufacturer level. The updated risk assessment model considered slicing location as well as the use of growth inhibitors. The per annum comparative risk ratio for the number of deaths from retail-sliced versus prepackaged deli meats was found to be 4.89, and the per-serving comparative risk ratio was 4.27. There was a significant interaction between the use of growth inhibitors and slicing location. Almost 70% of the estimated deaths occurred from retail-sliced product that did not possess a growth inhibitor. A sensitivity analysis, assessing the effect of the model's consumer storage time and shelf life assumptions, found that even if retail-sliced deli meats were stored for a quarter of the time prepackaged deli meats were stored, retail-sliced product is 1.7 times more likely to result in death from listeriosis. Sensitivity analysis also showed that the shelf life assumption had little effect on the comparative risk ratio. C1 [Endrikat, Sarah; Gallagher, Daniel] Virginia Polytech Inst & State Univ, Dept Civil & Environm Engn, Blacksburg, VA 24061 USA. [Pouillot, Regis] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Quesenberry, Heather Hicks; Labarre, David; Schroeder, Carl M.; Kause, Janell] US Food Safety & Inspect Serv, Risk Assessment Div, Off Publ Hlth Sci, USDA, Washington, DC 20228 USA. RP Gallagher, D (reprint author), Virginia Polytech Inst & State Univ, Dept Civil & Environm Engn, 409 Durham Hall, Blacksburg, VA 24061 USA. EM dang@vt.edu RI Pouillot, Regis/E-8103-2010 OI Pouillot, Regis/0000-0002-6107-5212 NR 32 TC 36 Z9 37 U1 0 U2 17 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 APR PY 2010 VL 73 IS 4 BP 612 EP 619 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 579ZW UT WOS:000276417100001 PM 20377948 ER PT J AU Garber, EAE Brewer, VA AF Garber, Eric A. E. Brewer, Vickery A. TI Enzyme-Linked Immunosorbent Assay Detection of Melamine in Infant Formula and Wheat Food Products SO JOURNAL OF FOOD PROTECTION LA English DT Article ID MASS-SPECTROMETRY; PET FOOD; TOXICITY; DOGS AB The adulteration of food products with melamine to inflate the nitrogen content necessitates the establishment of analytical methods that can distinguish between proteinaceous ingredients and such adulterants. The specificity and ability to detect melamine by two commercial enzyme-linked immunosorbent assay (ELISA) kits were evaluated along with three protocols for sample preparation. Both ELISAs displayed cross-reactivity with ammeline, but neither was able to detect ammelide or cyanuric acid, indicating either a requirement for the 4,6-diamino-1,3,5-triazine structure or inability to bind 1,3,5-triazine-4,6-diones. The limits of detection for melamine in powder infant formula ranged from 0.2 to 3 mu g/g depending on the ELISA kit and the method used to prepare the sample. The limits of detection for melamine in liquid infant formula and wheat products were <1 mu g/ml and <2.5 mu g/g, respectively. The ELISA kits provide an effective alternative for the analysis of samples suspected of containing melamine without relying on extensive sample preparation or expensive instrumentation. C1 [Garber, Eric A. E.; Brewer, Vickery A.] US FDA, Div Bioanalyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Garber, EAE (reprint author), US FDA, Div Bioanalyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM Eric.Garber@fda.hhs.gov NR 24 TC 16 Z9 16 U1 0 U2 13 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD APR PY 2010 VL 73 IS 4 BP 701 EP 707 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 579ZW UT WOS:000276417100012 PM 20377959 ER PT J AU Nyman, PJ Wamer, WG Begley, TH Diachenko, GW Perfetti, GA AF Nyman, Patricia J. Wamer, Wayne G. Begley, Timothy H. Diachenko, Gregory W. Perfetti, Gracia A. TI Evaluation of Accelerated UV and Thermal Testing for Benzene Formation in Beverages Containing Benzoate and Ascorbic Acid SO JOURNAL OF FOOD SCIENCE LA English DT Article DE accelerated testing; ascorbic acid; benzene; benzoate; beverages ID GAS CHROMATOGRAPHY/MASS SPECTROMETRY; SOFT DRINKS; FOODS; ANTIOXIDANTS; SYSTEMS AB Under certain conditions, benzene can form in beverages containing benzoic and ascorbic acids. The American Beverage Assn. (ABA) has published guidelines to help manufacturers mitigate benzene formation in beverages. These guidelines recommend accelerated testing conditions to test product formulations, because exposure to ultraviolet (UV) light and elevated temperature over the shelf life of the beverage may result in benzene formation in products containing benzoic and ascorbic acids. In this study, the effects of UVA exposure on benzene formation were determined. Benzene formation was examined for samples contained in UV stabilized and non-UV stabilized packaging. Additionally, the usefulness of accelerated thermal testing to simulate end of shelf-life benzene formation was evaluated for samples containing either benzoic or ascorbic acid, or both. The 24 h studies showed that under intense UVA light benzene levels increased by as much as 53% in model solutions stored in non-UV stabilized bottles, whereas the use of UV stabilized polyethylene terephthalate bottles reduced benzene formation by about 13% relative to the non-UV stabilized bottles. Similar trends were observed for the 7 d study. Retail beverages and positive and negative controls were used to study the accelerated thermal testing conditions. The amount of benzene found in the positive controls and cranberry juice suggests that testing at 40 degrees C for 14 d may more reliably simulate end of shelf-life benzene formation in beverages. Except for cranberry juice, retail beverages were not found to contain detectable amounts of benzene (<0.05 ng/g) at the end of their shelf lives. C1 [Nyman, Patricia J.; Wamer, Wayne G.; Begley, Timothy H.; Diachenko, Gregory W.; Perfetti, Gracia A.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. RP Nyman, PJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, HFS-706,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Patricia.Nyman@fda.hhs.gov NR 16 TC 6 Z9 6 U1 1 U2 17 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD APR PY 2010 VL 75 IS 3 BP C263 EP C267 DI 10.1111/j.1750-3841.2010.01536.x PG 5 WC Food Science & Technology SC Food Science & Technology GA 579FH UT WOS:000276353000038 PM 20492277 ER PT J AU Hong, HX Su, ZQ Ge, WG Shi, LM Perkins, R Fang, H Mendrick, D Tong, WD AF Hong, Huixiao Su, Zhenqiang Ge, Weigong Shi, Leming Perkins, Roger Fang, Hong Mendrick, Donna Tong, Weida TI Evaluating variations of genotype calling: a potential source of spurious associations in genome-wide association studies SO JOURNAL OF GENETICS LA English DT Article DE genotype calling; genome-wide association studies; missing call rate; calling algorithm; spurious association ID BREAST-CANCER; SUSCEPTIBILITY VARIANT; COLORECTAL-CANCER; CROHN-DISEASE; HAPLOTYPE MAP; RISK LOCUS; SCAN; SNPS; GENES; POLYMORPHISM AB Genome-wide association studies (GWAS) examine the entire human genome with the goal of identifying genetic variants (usually single nucleotide polymorphisms (SNPs)) that are associated with phenotypic traits such as disease status and drug response. The discordance of significantly associated SNPs for the same disease identified from different GWAS indicates that false associations exist in such results. In addition to the possible sources of spurious associations that have been investigated and discussed intensively, such as sample size and population stratification, an accurate and reproducible genotype calling algorithm is required for concordant GWAS results from different studies. However, variations of genotype calling of an algorithm and their effects on significantly associated SNPs identified in downstream association analyses have not been systematically investigated. In this paper, the variations of genotype calling using the Bayesian Robust Linear Model with Mahalanobis distance classifier (BRLMM) algorithm and the resulting influence on the lists of significantly associated SNPs were evaluated using the raw data of 270 HapMap samples analysed with the Affymetrix Human Mapping 500K Array Set (Affy500K) by changing algorithmic parameters. Modified were the Dynamic Model (DM) call confidence threshold (threshold) and the number of randomly selected SNPs (size). Comparative analysis of the calling results and the corresponding lists of significantly associated SNPs identified through association analysis revealed that algorithmic parameters used in BRLMM affected the genotype calls and the significantly associated SNPs. Both the threshold and the size affected the called genotypes and the lists of significantly associated SNPs in association analysis. The effect of the threshold was much larger than the effect of the size. Moreover, the heterozygous calls had lower consistency compared to the homozygous calls. C1 [Hong, Huixiao; Su, Zhenqiang; Ge, Weigong; Shi, Leming; Perkins, Roger; Mendrick, Donna; Tong, Weida] US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Fang, Hong] US FDA, Z Tech Corp, ICF Int Co, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Hong, HX (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 Su, Zhenqiang/H-3914-2012 NR 42 TC 8 Z9 8 U1 0 U2 1 PU INDIAN ACAD SCIENCES PI BANGALORE PA C V RAMAN AVENUE, SADASHIVANAGAR, P B #8005, BANGALORE 560 080, INDIA SN 0022-1333 J9 J GENET JI J. Genet. PD APR PY 2010 VL 89 IS 1 BP 55 EP 64 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 597PD UT WOS:000277769500007 PM 20505247 ER PT J AU Akkoyunlu, M Katsenelson, N Blake, M Kanswal, S AF Akkoyunlu, Mustafa Katsenelson, Nora Blake, Milan Kanswal, Sunita TI Downregulation of TACI by Neisseria meningitidis type C polysaccharide vaccine is responsible for its weak immunogenicity SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Akkoyunlu, Mustafa; Katsenelson, Nora; Blake, Milan; Kanswal, Sunita] US FDA, DBPAP, CBER, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 137.4 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304057 ER PT J AU Alam, M Wilson, J Ernst, P AF Alam, Mohammad Wilson, Jeff Ernst, Peter TI Role of Adenosine A2B Receptors in Regulating Inflammatory Responses of TNBS-induced Experimental Colitis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Alam, Mohammad] US FDA, Immunobiol DVA, Ctr Food Safety & Nutr, Laurel, MD USA. [Wilson, Jeff; Ernst, Peter] Univ Virginia, Charlottesville, VA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 87.2 PG 2 WC Immunology SC Immunology GA V44OM UT WOS:000209758302001 ER PT J AU Berkower, I Virnik, K Ni, YS Prutzman, K Spadaccini, A AF Berkower, Ira Virnik, Konstantin Ni, Yisheng Prutzman, Kirk Spadaccini, Angelo TI Stable expression of a foreign protein by a live rubella viral vector SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Berkower, Ira; Virnik, Konstantin; Ni, Yisheng; Prutzman, Kirk; Spadaccini, Angelo] US FDA, Ctr Biol, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 45.25 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301022 ER PT J AU Butts, C Wang, V Puig, M Verthelyi, D AF Butts, Cherie Wang, Vivian Puig, Montserrat Verthelyi, Daniela TI Progesterone minimizes immunoprotective effect of CpG ODN against infection by skewing immune responses toward Th17 SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Butts, Cherie; Wang, Vivian; Puig, Montserrat; Verthelyi, Daniela] US FDA, Lab Immunol, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 136.2 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304001 ER PT J AU Choi, SC Narayanan, S Krzewski, K Borrego, F Coligan, J AF Choi, Seung-Chul Narayanan, Sriram Krzewski, Konrad Borrego, Francisco Coligan, John TI Expression and regulation of Toso, a new Fc receptor for IgM, during B cell development SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Choi, Seung-Chul; Narayanan, Sriram; Krzewski, Konrad; Coligan, John] NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Rockville, MD USA. [Borrego, Francisco] US FDA, Lab Mol & Dev Biol, DMA, CDER, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 132.15 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303194 ER PT J AU Gold, D Hillyer, P Raviv, N Heuer, M Chi, B Rabin, R AF Gold, Doria Hillyer, Philippa Raviv, Nataly Heuer, Melissa Chi, Bo Rabin, Ronald TI Differential effects of Human Interferon-alpha subtypes on CD4 T cell function SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Gold, Doria; Hillyer, Philippa; Raviv, Nataly; Heuer, Melissa; Chi, Bo; Rabin, Ronald] USFDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 134.10 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303238 ER PT J AU Hillyer, P Chen, A Schramm, L Mane, V Navarro, M Luongo, C Raviv, N Collins, P Rabin, R AF Hillyer, Philippa Chen, Aaron Schramm, Lynnsie Mane, Viraj Navarro, Maria Luongo, Cindy Raviv, Nataly Collins, Peter Rabin, Ronald TI An attenuated innate immune response to a clinical strain of respiratory syncytial virus (RSV) in human monocyte derived dendritic cells (MDDC) SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Hillyer, Philippa; Chen, Aaron; Schramm, Lynnsie; Mane, Viraj; Navarro, Maria; Raviv, Nataly; Rabin, Ronald] USFDA, Ctr Biol Evaluat & Res, Lab Immunobiochem, Bethesda, MD USA. [Luongo, Cindy; Collins, Peter] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 37.43 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300103 ER PT J AU Kapnick, S Zaitseva, M Scott, J Meseda, C Nielsen, H Merchlinsky, M Weir, J Golding, H AF Kapnick, Senta Zaitseva, Marina Scott, John Meseda, Clement Nielsen, Henriette Merchlinsky, Michael Weir, Jerry Golding, Hana TI Quantitative bioimaging of WRvFire and of IHDJ-Luc vaccinia virus dissemination in mice and the effects of prophylactic and therapeutic treatments with IgG and antiviral. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Kapnick, Senta; Zaitseva, Marina; Meseda, Clement; Merchlinsky, Michael; Weir, Jerry; Golding, Hana] US FDA, Div Viral Prod, CBER, Bethesda, MD 20014 USA. [Scott, John] US FDA, Off Biostat, CBER, Bethesda, MD 20014 USA. [Nielsen, Henriette] Symphogen, Lyngby, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 45.18 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301016 ER PT J AU Lillehoj, H Lee, K Li, GX Lee, SH Jang, SI Babu, U Lillehoj, E Siragusa, G AF Lillehoj, H. Lee, Kyungwoo Li Guangxing Lee, Sung Hyen Jang, Seung Ik Babu, Uma Lillehoj, Erik Siragusa, Gregory TI Effect of Bacillus-based direct-fed microbials on macrophage functions and Eimeria maxima infection in broiler chickens SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Lillehoj, H.; Lee, Kyungwoo; Li Guangxing; Lee, Sung Hyen; Jang, Seung Ik] Anim & Nat Resources Inst, Beltsville, MD USA. [Babu, Uma] FDA, Laurel, MD USA. [Lillehoj, Erik] Univ Maryland, Baltimore, MD 21201 USA. [Siragusa, Gregory] Danisco, Waukesha, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 46.18 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758301047 ER PT J AU Puig, M Tosh, K Grajkowska, L Verthelyi, D AF Puig, Montse Tosh, Kevin Grajkowska, Lucia Verthelyi, Daniela TI Differential IFN signature for TLR7 and 9 agonists SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Puig, Montse; Tosh, Kevin; Grajkowska, Lucia; Verthelyi, Daniela] US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 136.16 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758303295 ER PT J AU Savan, R Reynolds, D McFarland, A Feigenbaum, L Ramakrishnan, K Shirota, H Klinman, D Donnelly, R Young, H AF Savan, Ram Reynolds, Della McFarland, AdeIle Feigenbaum, Lionel Ramakrishnan, Karthika Shirota, Hidekazu Klinman, Dennis Donnelly, Raymond Young, Howard TI Ectopic expression of Interleukin-22 receptors (IL-22R1) on lymphocytes induces multi-organ inflammation and premature death SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Savan, Ram; Reynolds, Della; McFarland, AdeIle; Feigenbaum, Lionel; Ramakrishnan, Karthika; Shirota, Hidekazu; Klinman, Dennis; Young, Howard] Natl Canc Inst, Frederick, MD USA. [Donnelly, Raymond] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 35.12 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300034 ER PT J AU Schramm, L Mane, V Bykadi, S Navarro, M Jubin, R Rabin, R AF Schramm, Lynnsie Mane, Viraj Bykadi, Srikant Navarro, Maria Jubin, Ronald Rabin, Ronald TI Expression patterns of Human Interferon-alpha and Interferon -lambda subtypes by monocytes, dendritic cells and B cells. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Schramm, Lynnsie; Mane, Viraj; Bykadi, Srikant; Navarro, Maria; Rabin, Ronald] US FDA, CBER, Bethesda, MD 20014 USA. [Jubin, Ronald] PBL InterferonSource, Piscataway, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 136.14 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304029 ER PT J AU Tami, C Pedras-Vasconcelos, J Puig, M Wang, VV Butts, C Verthelyi, D AF Tami, Cecilia Pedras-Vasconcelos, Joao Puig, Montserrat Wang, Vivian Butts, Cherie Verthelyi, Daniela TI MyD88 expressing T cells are required for neuropathogenesis of Tacaribe virus SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Tami, Cecilia; Pedras-Vasconcelos, Joao; Puig, Montserrat; Wang, Vivian; Butts, Cherie; Verthelyi, Daniela] FDA, CDER, OBP, DTP, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 39.6 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300169 ER PT J AU Yu, MJ Moreno, J Keegan, A AF Yu, Minjun Moreno, Jose Keegan, Achsah TI Regulation of the Receptor Activator of NF-kappa B Ligand (RANKL)-induced activation of the alternative NF-kappa B pathways by interleukin-4 (IL-4) SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Yu, Minjun; Keegan, Achsah] Univ Maryland, Baltimore, MD 21201 USA. [Moreno, Jose] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 142.8 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758304130 ER PT J AU Zhao, Z Rabin, R AF Zhao, Zeng Rabin, Ronald TI Three functional regions in human tonsil distinguished by in situ gene expression SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Zhao, Zeng; Rabin, Ronald] US FDA, DBPAP, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2010 VL 184 SU 1 MA 37.1 PG 1 WC Immunology SC Immunology GA V44OM UT WOS:000209758300120 ER PT J AU Olivier, KJ Price, KD Hutto, DL Lerche, NW Mansfield, KG Simmons, JH Taylor, K Myers, LP Ouyang, YL Evans, EW AF Olivier, Kenneth J. Price, Karen D. Hutto, David L. Lerche, Nicholas W. Mansfield, Keith G. Simmons, Joe H. Taylor, Katrina Myers, L. Peyton Ouyang, Yanli Evans, Ellen W. TI Naturally occurring infections in non-human primates (NHP) and immunotoxicity implications: Discussion sessions SO JOURNAL OF IMMUNOTOXICOLOGY LA English DT Review ID T-CELL DEPLETION; VIRAL LOAD; TRANSPLANT RECIPIENTS; RHESUS-MONKEYS; PATHOGEN-FREE; MACAQUES; VIRUS; DIARRHEA; PLASMA; DISEASE AB Non-human primates (NHP) are used to best understand and address pharmacology and toxicology obligations for human patients with highest and/or unmet need. In order to ensure the most appropriate care and use of NHP, it is important to understand the normal micro flora and fauna of NHP and ensure their utmost health to generate the most valuable and applicable data. There are many infections, including viral, bacterial, parasitic, and fungal that may perturb physiologic endpoints relevant to human health, and are essential to monitor and/or eradicate for NHP health. This publication captures a discussion involving the experience, knowledge and opinion from academic, industry and government experts regarding emerging and normal infections in NHP as they relate to immunotoxicity, and treatment and consequences of known infections.= 20 years who reported their past-year alcoholic beverage consumption and 24-hour dietary intake. Alcoholic beverage consumption was defined by drinking status (never, former, current drinker) and, among current drinkers, by drinking level (number of drinks per day, on average: men <1 to >= 5; women <1 to >= 3). Results Among men, there was no association between drinking status and intakes of energy, most nutrients, or total HEI-2005 score. Among women, former and current (compared to never) drinkers had significantly higher intakes of energy and several nutrients, and current drinkers had significantly lower total HEI-2005 scores (current drinkers 58.9; never drinkers 63.2). Among current drinkers of both sexes, as drinking level increased, intakes of energy and several nutrients significantly increased, whereas total HEI-2005 scores significantly decreased (from 55.9 to 41.5 in men, and from 59.5 to 51.8 in women). Conclusions Among men and women, increasing alcoholic beverage consumption was associated with a decline in total diet quality as measured by the HEI-2005, apparently due to higher energy intake from alcohol as well as other differences in food choices. Educational messages should focus on nutrition and chronic disease risk associated with high consumption of alcoholic beverages and poor food choices, including excessive energy intake. J Am Diet Assoc. 2010;110:551-562. C1 [Breslow, Rosalind A.] NIAAA, Div Epidemiol & Prevent Res, NIH, Bethesda, MD USA. [Guenther, Patricia M.] USDA, Ctr Nutr Policy & Promot, Alexandria, VA USA. [Juan, Wenyen] Food & Drug Adm, Ctr Food Safety & Appl Nutr, Off Nutr Labeling & Dietary Supplements, College Pk, MD USA. [Graubard, Barry I.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Breslow, RA (reprint author), NIAAA, Div Epidemiol & Prevent Res, 5635 Fishers Ln,Rm 2071, Rockville, MD 20892 USA. EM rbreslow@mail.nih.gov FU Intramural NIH HHS [Z99 AA999999] NR 38 TC 50 Z9 50 U1 0 U2 7 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 APR PY 2010 VL 110 IS 4 BP 551 EP 562 DI 10.1016/j.jada.2009.12.026 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 581LS UT WOS:000276525200013 PM 20338281 ER PT J AU Lin, CTJ Yen, ST AF Lin, Chung-Tung J. Yen, Steven T. TI Knowledge of Dietary Fats among US Consumers SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID NUTRITION KNOWLEDGE; PROBIT MODEL AB Dietary advice emphasizes that some dietary fats increase the risk of heart disease, whereas other dietary fats decrease risk if they are substituted for more risk-increasing fats. Thus, it is important that consumers understand the differences between dietary fats. Existing evidence in the United States suggests troublesome consumer misunderstanding. As part of its continuing effort to promote public health, the US Food and Drug Administration measured consumer awareness and understanding of dietary fats in its Health and Diet Survey-2004 Supplement. After cognitive interviews and pretests of the questionnaire, telephone interviews of randomly selected noninstitutionalized adults aged 18 years and older in the United States were conducted between October 12, 2004, and January 21, 2005. Using cross-sectional data collected from 1,798 respondents who completed the survey, this study estimated the prevalence of awareness and understanding of six dietary fats among US adults and identified the characteristics of adults with different levels of awareness and understanding. Descriptive analyses were used, along with logistic regression models, developed to accommodate the survey design and responses. There was a wide disparity among US consumers in their awareness and understanding. Saturated fat was most recognized and understood, whereas awareness of other fats was much lower. Most importantly, having heard of a fat did not necessarily mean understanding its relationship to heart disease. Only half of those who had heard of trans fat and n-3 fatty acids understood that the fats raise and lower the risk of heart disease, respectively. Only a minority of those who had heard of partially hydrogenated oil and polyunsaturated fat knew the fats raise and lower the risk of heart disease, respectively. Many admitted being uncertain about how a fat relates to the risk of heart disease. College or more-educated adults had better awareness and understanding. Nonwhite adults were less knowledgeable. Findings on the awareness and understanding and how they are related to individual characteristics can inform deliberations about educational messages, nutrition programs, and food labeling about dietary fats to promote public health. J Am diet Assoc. 2010;110:613-618. C1 [Yen, Steven T.] Univ Tennessee, Dept Agr Econ, Knoxville, TN 37996 USA. [Lin, Chung-Tung J.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Yen, ST (reprint author), Univ Tennessee, Dept Agr Econ, 302 Morgan Hall,2621 Morgan Cir, Knoxville, TN 37996 USA. EM syen@utk.edu FU US Food and Drug Administration [HHSF223200730654] FX This research was supported by funding issued by the US Food and Drug Administration to The University of Tennessee, requisition no. HHSF223200730654. NR 37 TC 16 Z9 16 U1 1 U2 6 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 APR PY 2010 VL 110 IS 4 BP 613 EP 618 DI 10.1016/j.jada.2009.12.020 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 581LS UT WOS:000276525200020 PM 20338288 ER PT J AU Junod, S AF Junod, Suzanne TI The Estrogen Elixir: A History of Hormone Replacement Therapy in America SO JOURNAL OF THE HISTORY OF MEDICINE AND ALLIED SCIENCES LA English DT Book Review C1 [Junod, Suzanne] US FDA, Rockville, MD 20857 USA. RP Junod, S (reprint author), US FDA, 5600 Fishers Lane,HFC-24,Room 12-69, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-5045 J9 J HIST MED ALL SCI JI J. Hist. Med. Allied Sci. PD APR PY 2010 VL 65 IS 2 BP 272 EP 275 DI 10.1093/jhmas/jrp062 PG 4 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 585VI UT WOS:000276857800013 ER PT J AU Reimschuessel, R Evans, E Andersen, WC Turnipseed, SB Karbiwnyk, CM Mayer, TD Nochetto, C Rummel, NG Gieseker, CM AF Reimschuessel, R. Evans, E. Andersen, W. C. Turnipseed, S. B. Karbiwnyk, C. M. Mayer, T. D. Nochetto, C. Rummel, N. G. Gieseker, C. M. TI Residue depletion of melamine and cyanuric acid in catfish and rainbow trout following oral administration SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID RENAL-FAILURE; CATS; EXCRETION; DOGS; RATS; CARCINOGENICITY; UROLITHIASIS; ABSORPTION; TOXICITY; STONES AB The intentional addition of triazines such as melamine to animal feeds and the lack of information about residue accumulation in food animals caused global concerns for food safety during 2007 and 2008. We report the results of a good laboratory practices (GLP) study to determine melamine and cyanuric acid residues in catfish and trout filets harvested at 1, 3, 7, 14, 28, and 42 days after a single oral dose of 20 mg/kg body weight of melamine, cyanuric acid, or melamine and cyanuric acid together. Peak melamine concentrations were 12.73 mg/kg (ppm) in catfish (mean = 9.98), 12.26 mg/kg in trout (mean = 7.89) on day 1. Within 7 days (catfish) or 14 days (trout) residues were < 2.5 mg/kg, a level in foods accepted by many risk assessors worldwide to be unlikely to pose health risks to consumers. Peak cyanuric acid residues also occurred on day 1, 0.68 mg/kg in catfish (mean = 0.46), 2.59 mg/kg in trout (mean = 0.86). Cyanuric acid muscle residues were < 2.5 mg/kg by day 3. The half-lives for melamine and cyanuric acid ranged between 1 and 4 days. Renal crystals formed in fish given both melamine and cyanuric acid, persisting for weeks after the single dose. C1 [Reimschuessel, R.] US FDA, Coll Vet Med, Ctr Vet Med, Laurel, MD 20708 USA. [Andersen, W. C.; Turnipseed, S. B.; Karbiwnyk, C. M.] US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Denver, CO USA. RP Reimschuessel, R (reprint author), US FDA, Coll Vet Med, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM renate.reimschuessel@fda.hhs.gov NR 52 TC 15 Z9 15 U1 2 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 APR PY 2010 VL 33 IS 2 BP 172 EP 182 DI 10.1111/j.1365-2885.2009.01111.x PG 11 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 565YF UT WOS:000275334000008 PM 20444042 ER PT J AU Watanabe, H Wells, F Major, ME AF Watanabe, H. Wells, F. Major, M. E. TI Clearance of hepatitis C in chimpanzees is associated with intrahepatic T-cell perforin expression during the late acute phase SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE hepatitis C virus; immune responses; intrahepatic; perforin; T cells; viral clearance ID VIRUS-INFECTION; LIVER-INJURY; CASPASE ACTIVATION; HCV INFECTION; APOPTOSIS; PROLIFERATION; CYTOTOXICITY; REPLICATION; LYMPHOCYTES; PERSISTENCE AB The liver is the primary site of hepatitis C virus (HCV) replication. Therefore, we undertook detailed intrahepatic studies of T-cell dynamics, apoptosis, and gene expression during the acute phase of infection using liver biopsies from chimpanzees that developed persistent infection or spontaneously cleared the virus. We examined more than 40 liver biopsies histologically and quantitatively for T-cell infiltration, hepatocyte apoptosis and perforin expression. These data were correlated with outcome and viral kinetics. We observed intrahepatic T-cell infiltration in both groups of animals with CD8+ T cells representing the major population. The appearance of T cells was always associated with apoptosis and mild alanine aminotransferase (ALT) elevations. Apoptosis (5-20% of hepatocytes) always occurred prior to serum ALT peak. Quantification of intrahepatic ALT mRNA revealed no upregulation of gene expression confirming that serum ALT increases were due to release of this enzyme from cells. During the late acute phase, cleared animals showed an increased frequency of hepatocyte apoptosis relative to persistently infected animals (P < 0.05). This correlated with a higher intrahepatic CD8+ T-cell frequency in the cleared group (P < 0.01) with a greater proportion of lymphocytes expressing perforin compared with the persistent group (P < 0.001). All infected animals mounted intrahepatic immune responses during the acute phase, but these were not maintained in frequency or efficacy in persistent infections. There is a reduction in the numbers of intrahepatic T cells during the late acute phase in infections that become persistent with significantly fewer of these cells functional in clearing the virus by killing infected hepatocytes. C1 [Watanabe, H.; Wells, F.; Major, M. E.] US FDA, Lab Hepatitis Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Major, ME (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 20014 USA. EM marian.major@fda.hhs.gov FU National Vaccine Program Office; FDA FX This work was supported by a grant from the National Vaccine Program Office and by FDA intramural research funding. We would like to thank Dr Phil Snoy and members of the CBER veterinary staff for their expert care and handling of chimpanzees and samples. We also thank Steven Rubin and Stephen Feinstone for critical reading of the manuscript. NR 34 TC 10 Z9 10 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD APR PY 2010 VL 17 IS 4 BP 245 EP 253 DI 10.1111/j.1365-2893.2009.01172.x PG 9 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 568OJ UT WOS:000275531700003 PM 19709361 ER PT J AU Cancellotti, E Bradford, BM Tuzi, NL Hickey, RD Brown, D Brown, KL Barron, RM Kisielewski, D Piccardo, P Manson, JC AF Cancellotti, Enrico Bradford, Barry M. Tuzi, Nadia L. Hickey, Raymond D. Brown, Debbie Brown, Karen L. Barron, Rona M. Kisielewski, Dorothy Piccardo, Pedro Manson, Jean C. TI Glycosylation of PrPC Determines Timing of Neuroinvasion and Targeting in the Brain following Transmissible Spongiform Encephalopathy Infection by a Peripheral Route SO JOURNAL OF VIROLOGY LA English DT Article ID FOLLICULAR DENDRITIC CELLS; CREUTZFELDT-JAKOB-DISEASE; PRION PROTEIN EXPRESSION; NERVOUS-SYSTEM; BLOOD-TRANSFUSION; LYMPHOID-TISSUE; VARIANT CJD; SCRAPIE; MICE; ACCUMULATION AB Transmissible spongiform encephalopathy (TSE) infectivity naturally spreads from site of entry in the periphery to the central nervous system where pathological lesions are formed. Several routes and cells within the host have been identified as important for facilitating the infectious process. Expression of the glycoprotein cellular PrP (PrPC) is considered a key factor for replication of infectivity in the central nervous system (CNS) and its transport to the brain, and it has been suggested that the infectious agent propagates from cell to cell via a domino-like effect. However, precisely how this is achieved and what involvement the different glycoforms of PrP have in these processes remain to be determined. To address this issue, we have used our unique models of gene-targeted transgenic mice expressing different glycosylated forms of PrP. Two TSE strains were inoculated intraperitoneally into these mice to assess the contribution of diglycosylated, monoglycosylated, and unglycosylated PrP in spreading of infectivity to the brain. This study demonstrates that glycosylation of host PrP has a profound effect in determining the outcome of disease. Lack of diglycosylated PrP slowed or prevented disease onset after peripheral challenge, suggesting an important role for fully glycosylated PrP in either the replication of the infectious agent in the periphery or its transport to the CNS. Moreover, mice expressing unglycosylated PrP did not develop clinical disease, and mice expressing monoglycosylated PrP showed strikingly different neuropathologic features compared to those expressing diglycosylated PrP. This demonstrates that targeting in the brain following peripheral inoculation is profoundly influenced by the glycosylation status of host PrP. C1 [Cancellotti, Enrico; Bradford, Barry M.; Tuzi, Nadia L.; Hickey, Raymond D.; Brown, Debbie; Brown, Karen L.; Barron, Rona M.; Kisielewski, Dorothy; Manson, Jean C.] Univ Edinburgh, Roslin Inst, Neuropathogenesis Div, Roslin EH25 9PS, Midlothian, Scotland. [Cancellotti, Enrico; Bradford, Barry M.; Tuzi, Nadia L.; Hickey, Raymond D.; Brown, Debbie; Brown, Karen L.; Barron, Rona M.; Kisielewski, Dorothy; Manson, Jean C.] Univ Edinburgh, Royal Dick Sch Vet Studies, Roslin EH25 9PS, Midlothian, Scotland. [Piccardo, Pedro] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Cancellotti, E (reprint author), Univ Edinburgh, Roslin Inst, Neuropathogenesis Div, Roslin EH25 9PS, Midlothian, Scotland. EM enrico.cancellotti@roslin.ed.ac.uk RI Bradford, Barry/B-3783-2013; Barron, Rona/C-7703-2013; OI Bradford, Barry/0000-0002-4007-1685; Barron, Rona/0000-0003-4512-9177 FU Biotechnology and Biological Science Research Council; Medical Research Council; University of Edinburgh FX This work was supported by Biotechnology and Biological Science Research Council and Medical Research Council. R. D. H. was funded by Research in Life Sciences Program, University of Edinburgh. NR 48 TC 25 Z9 25 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 APR PY 2010 VL 84 IS 7 BP 3464 EP 3475 DI 10.1128/JVI.02374-09 PG 12 WC Virology SC Virology GA 565PV UT WOS:000275307400032 PM 20106922 ER PT J AU Deer, DM Lampel, KA Gonzalez-Escalona, N AF Deer, D. M. Lampel, K. A. Gonzalez-Escalona, N. TI A versatile internal control for use as DNA in real-time PCR and as RNA in real-time reverse transcription PCR assays SO LETTERS IN APPLIED MICROBIOLOGY LA English DT Article DE internal control; PCR; real-time PCR; reverse transcription PCR ID POLYMERASE-CHAIN-REACTION; AMPLIFICATION CONTROL; SHIGELLA-FLEXNERI; RT-PCR; SALMONELLA; FOOD AB Aims: To develop and evaluate a TaqMan-based internal amplification control (IAC) that can be used as DNA in real-time PCR (qPCR) or as RNA in reverse transcription real-time PCR (qRT-PCR) to identify the presence of assay inhibition and to evaluate its incorporation into existing qPCR and qRT-PCR methods for bacterial detection. Methods and Results: A DNA IAC was constructed by generating a 198-bp random sequence that was synthesized and inserted into a pZErO-2 vector and transformed into Escherichia coli. The RNA IAC was generated through in vitro transcription of the DNA IAC. Both IAC formats were tested individually in singleplex TaqMan reactions and also included in existing multiplex assays. The DNA IAC was incorporated in a Shigella spp. detection qPCR assay (targeting ipaH). The RNA IAC was successfully evaluated in a Salmonella spp. detection qRT-PCR (using invA mRNA as target). Conclusions: A highly versatile IAC that can be supplemented to qPCR and qRT-PCR pathogen detection methods was developed, greatly reducing the confounding effects of false negatives because of PCR inhibitors without affecting pathogen detection. Significance and Impact of the Study: The frequency of false negatives associated with qPCR analyses is prevalent in certain matrices, particularly those involving complex foods. Hence, the IAC presented here provides a solution to unforeseen false-negative reactions in PCR. C1 [Deer, D. M.; Lampel, K. A.; Gonzalez-Escalona, N.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Gonzalez-Escalona, N (reprint author), 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM narjol.gonzalez-escalona@fda.hhs.gov RI Gonzalez-Escalona, Narjol/A-7598-2009; OI Gonzalez-Escalona, Narjol/0000-0003-4568-0022 NR 18 TC 36 Z9 38 U1 0 U2 18 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0266-8254 J9 LETT APPL MICROBIOL JI Lett. Appl. Microbiol. PD APR PY 2010 VL 50 IS 4 BP 366 EP 372 DI 10.1111/j.1472-765X.2010.02804.x PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 566TO UT WOS:000275396300007 PM 20149084 ER PT J AU Wang, X Viswanath, R Zhao, JQ Tang, SX Hewlett, I AF Wang, Xue Viswanath, Ragupathy Zhao, Jiangqin Tang, Shixing Hewlett, Indira TI Changes in the level of apoptosis-related proteins in Jurkat cells infected with HIV-1 versus HIV-2 SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE Apoptosis; Bax; Bcl-X(L); DISC; FLIP; HIV1/2 ID MAP KINASE; SIGNALING COMPLEX; T-CELLS; ACTIVATION; DEATH; FLIP; MECHANISMS; PATHWAYS; STRESS; TYPE-2 AB Human immunodeficiency virus (HIV) infection-induced apoptosis of infected CD4 T cells as well as uninfected (bystander) CD4 T cells and other types of cells is a major factor in the pathogenesis of AIDS. Clinically, HIV-2 patients have a higher CD4 cell count at the time of an AIDS diagnosis, and generally have longer survival after development of symptoms. The mortality after an AIDS diagnosis has been reported to be more influenced by CD4 cell count than HIV type. Previous studies have shown significant variations in cytopathic effects following in vitro infection with primary isolates of HIV-1 or HIV-2 subtypes; however, the relative contributions of HIV-1 and HIV-2 infection leading to cell death remain unclear. Using a human cell line, Jurkat, we examined differences in key molecules involved in apoptotic signaling pathways during infection with either HIV-1 or HIV-2. HIV-1 infection generated more reactive oxygen species (ROS), increased the expression of a larger number of molecules involved in cell signaling such as p47, p38 alpha, JNK, c-Yes, total PKC, and decreased the expression of molecules such as p38 beta, ERK1/2, and XIAP relative to HIV-2 infection. HIV-1 induced a higher degree of cell death through stronger activation of both apoptotic pathways. HIV-1 infection downregulated both Bcl-X(L) and FLIP expressions at later time points postinfection, while HIV-2 infection dramatically upregulated both Bcl-X(L) and FLIP expression. We also found that the expression of Bcl-X(L) or FLIP resulted in significant inhibition of HIV replication in Jurkat cells. These findings suggest that HIV-1 infection with high levels of cytotoxicity results in a higher level of cell death through apoptosis during a short time postinfection. The longer period of infection observed with HIV-2 with a lower degree of cytotoxicity was accompanied by increased Bcl-X(L) and FLIP expression. High protein levels of Bcl-X(L) or FLIP inhibit HIV replication and may be one explanation for the clinical observation that HIV-2 infected patients generally tend to be long-term nonprogressors with high CD4 lymphocyte counts compared with HIV-1 infected persons. C1 [Wang, Xue; Viswanath, Ragupathy; Zhao, Jiangqin; Tang, Shixing; Hewlett, Indira] US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20892 USA. RP Wang, X (reprint author), US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20892 USA. EM xue.wang@fda.hhs.gov; indira.hewlett@fda.hhs.gov NR 27 TC 8 Z9 8 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD APR PY 2010 VL 337 IS 1-2 BP 175 EP 183 DI 10.1007/s11010-009-0297-9 PG 9 WC Cell Biology SC Cell Biology GA 567UI UT WOS:000275471700018 PM 19841866 ER PT J AU Ross, JA Blackman, CF Thai, SF Li, ZG Kohan, M Jones, CP Chen, T AF Ross, Jeffrey A. Blackman, Carl F. Thai, Sheau-Fung Li, Zhiguang Kohan, Michael Jones, Carlton P. Chen, Tao TI A Potential microRNA Signature for Tumorigenic Conazoles in Mouse Liver SO MOLECULAR CARCINOGENESIS LA English DT Article DE microRNA; conazole; fungicides; tumorigenicity; expression ID PROFILES; CANCER; FUNGICIDES; EXPRESSION; PROPICONAZOLE; MYCLOBUTANIL; TRIADIMEFON AB Triadimefon, propiconazole, and myclobutanil are conazoles, an important class of agricultural fungicides. Triadimefon and propiconazole are mouse liver tumorigens, while myclobutanil is not. As part of a coordinated study to understand the molecular determinants of conazole tumorigenicity, we analyzed the microRNA expression levels in control and conazole-treated mice after 90 d of administration in feed. MicroRNAs (miRNAs) are small noncoding RNAs composed of approximately 19-24 nucleotides in length, and have been shown to interact with mRNA (usually 3' UTR) to suppress its expression. MicroRNAs play a key role in diverse biological processes, including development, cell proliferation, differentiation, and apoptosis. Groups of mice were fed either control diet or diet containing 1800 ppm triadimefon, 2500 ppm propiconazole, or 2000 ppm myclobutanil. MicroRNA was isolated from livers and analyzed using Superarray whole mouse genome miRNA PCR arrays from SABioscience. Data were analyzed using the significance analysis of microarrays (SAM) procedure. We identified those miRNAs whose expression was either increased or decreased relative to untreated controls with q <= 0.01. The tumorigenic conazoles induced many more changes in miRNA expression than the nontumorigenic conazole. A group of 19 miRNAs was identified whose expression was significantly altered in both triadimefon- and propiconazole-treated animals but not in myclobutanil-treated animals. All but one of the altered miRNAs were downregulated compared to controls. This pattern of altered miRNA expression may represent a signature for tumorigenic conazole exposure in mouse liver after 90 d of treatment. Published 2010 Wiley-Liss, Inc.(dagger) C1 [Ross, Jeffrey A.; Blackman, Carl F.; Thai, Sheau-Fung; Kohan, Michael; Jones, Carlton P.] US EPA, NHEERL, Integrated Syst Toxicol Div, Res Triangle Pk, NC USA. [Li, Zhiguang; Chen, Tao] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Ross, JA (reprint author), 109 TW Alexander Dr,MD B143-06, Res Triangle Pk, NC 27711 USA. RI Ross, Jeffrey/E-4782-2010; OI Ross, Jeffrey/0000-0002-7002-4548; Blackman, Carl/0000-0003-3267-5224 NR 14 TC 21 Z9 21 U1 0 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD APR PY 2010 VL 49 IS 4 BP 320 EP 323 DI 10.1002/mc.20620 PG 4 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 584CY UT WOS:000276728900002 PM 20175128 ER PT J AU Chowdhury, BA Dal Pan, G AF Chowdhury, Badrul A. Dal Pan, Gerald TI The FDA and Safe Use of Long-Acting Beta-Agonists in the Treatment of Asthma. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID RISKS C1 [Chowdhury, Badrul A.] US FDA, Div Pulm & Allergy Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Dal Pan, Gerald] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Chowdhury, BA (reprint author), US FDA, Div Pulm & Allergy Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 5 TC 137 Z9 140 U1 0 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 1 PY 2010 VL 362 IS 13 BP 1169 EP 1171 DI 10.1056/NEJMp1002074 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 577QQ UT WOS:000276239500004 PM 20181964 ER PT J AU Mishra, PJ Ha, L Rieker, J Sviderskaya, EV Bennett, DC Oberst, MD Kelly, K Merlino, G AF Mishra, P. J. Ha, L. Rieker, J. Sviderskaya, E. V. Bennett, D. C. Oberst, M. D. Kelly, K. Merlino, G. TI Dissection of RAS downstream pathways in melanomagenesis: a role for Ral in transformation SO ONCOGENE LA English DT Article DE anchorage-independent growth; BRaf; melanoma; NRas; PI3K; RalGEF ID CELLULAR-TRANSFORMATION; MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; SIGNALING PATHWAYS; BRAF MUTATIONS; CANCER; GTPASES; CELLS; ACTIVATION; MIGRATION AB Cutaneous malignant melanoma is considered one of the most deadly human cancers, based on both its penchant for metastatic spread and its typical resistance to currently available therapy. Long known to harbor oncogenic NRAS mutations, melanomas were more recently reported to be frequent bearers of activating mutations in BRAF, one of the effectors situated downstream of wild-type NRAS. NRAS and BRAF mutations are rarely found in the same melanoma, suggesting that they may possess important overlapping oncogenic activities. Here, we compare and contrast the oncogenic roles of the three major NRas downstream effectors, Raf, phosphatidylinositol 3-kinase (PI3K) and Ral guanine exchange factor (RalGEF), using genetically engineered Arf-deficient immortalized mouse melanocytes as a model system. Although no single downstream pathway could recapitulate all of the consequences of oncogenic NRas expression, our data indicate a prominent role for BRaf and PI3K in melanocyte senescence and invasiveness, respectively. More surprisingly, we discovered that constitutive RalGEF activation had a major impact on several malignant phenotypes, particularly anchorage-independent growth, indicating that this often overlooked pathway should be more carefully evaluated as a possible therapeutic target. Oncogene (2010) 29, 2449-2456; doi:10.1038/onc.2009.521; published online 1 February 2010 C1 [Mishra, P. J.; Ha, L.; Rieker, J.; Merlino, G.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Ha, L.] US FDA, Div Monoclonal Antibody, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. [Sviderskaya, E. V.; Bennett, D. C.] Univ London, Div Basic Med Sci, London, England. [Oberst, M. D.; Kelly, K.] NCI, Cell & Canc Biol Branch, Bethesda, MD 20892 USA. RP Merlino, G (reprint author), NCI, Lab Canc Biol & Genet, NIH, Bldg 37,Room 5002,37 Convent Dr, Bethesda, MD 20892 USA. EM gmerlino@helix.nih.gov RI Sviderskaya, Elena/D-2419-2009; Bennett, Dorothy/C-2418-2008 OI Bennett, Dorothy/0000-0002-3639-7527 FU NCI [N01-CO-12400]; National Institutes of Health; Wellcome Trust [078327] FX We thank Dr Christopher Counter (Duke University) for useful discussions, and for communicating data before publication. We acknowledge Dr Paul Khavari (Stanford University) for gifting the NRas, PI3K and BRaf retroviral vectors, and Drs Frederique Zindy and Charles Sherr (St Jude Children's Research Hospital) for the Arf-deficient mouse skins from which the immortalized melanocytes were generated. The PEP7 and PEP8H antibodies were a gift from Dr Vince Hearing (NCI). The pEF-CAAX-Raf-1 vector was a gift from Dr Silvio J Gutkind (NIH/NIDCR). This work was supported in part by the Intramural Research Program of the NCI, National Institutes of Health, in part by NCI Contract N01-CO-12400, and in part by Wellcome Trust Program Grant 078327 (to EVS). NR 41 TC 37 Z9 37 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR PY 2010 VL 29 IS 16 BP 2449 EP 2456 DI 10.1038/onc.2009.521 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 586YK UT WOS:000276951500013 PM 20118982 ER PT J AU Seyfert-Margolis, V Feng, S AF Seyfert-Margolis, Vicki Feng, Sandy TI Tolerance: Is It Achievable in Pediatric Solid Organ Transplantation? SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Pediatric solid organ transplantation; Allo-immune response; Tolerance; Immunosuppression withdrawal ID REGULATORY T-CELLS; DONOR LIVER-TRANSPLANTATION; OPERATIONAL TOLERANCE; IMMUNOSUPPRESSION WITHDRAWAL; ALLOGRAFT TOLERANCE; B-CELLS; RECIPIENTS; CHIMERISM; KIDNEY; ALLOTRANSPLANTATION AB In the clinical arena of transplantation, tolerance remains, for the most part, a concept rather than a reality. Although modern immunosuppression regimens have effectively handled acute rejection, nearly all organs except the liver commonly suffer chronic immunologic damage that impairs organ function, threatening patient and allograft survival. In addition to the imperfect control of the donor-directed immune response, there are additional costs. First, there is the burden of mortality from infection and malignancy that can be directly attributed to a crippled immune system. Second, there are insidious effects on renal function, cardiovascular profile (hypertension, hyperglycemia, and dyslipidemia), bone health, growth, psychological and neurocognitive development, and overall quality of life. It is likely that the full consequences of lifelong immunosuppression on our pediatric transplant recipients will not be fully appreciated until survival routinely extends beyond 1 or 2 decades after transplantation. Therefore, it can be argued that the holy grail of transplantation tolerance is of the utmost importance to children who undergo solid organ transplantation. C1 [Feng, Sandy] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Seyfert-Margolis, Vicki] US FDA, Silver Spring, MD 20903 USA. RP Feng, S (reprint author), Univ Calif San Francisco, 505 Parnassus Ave,Box 0780, San Francisco, CA 94143 USA. EM Sandy.feng@ucsfmedctr.org NR 59 TC 14 Z9 14 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD APR PY 2010 VL 57 IS 2 BP 523 EP + DI 10.1016/j.pcl.2010.01.015 PG 18 WC Pediatrics SC Pediatrics GA 590CN UT WOS:000277201500011 PM 20371050 ER PT J AU Zaslavsky, BG AF Zaslavsky, Boris G. TI Empirical Bayes models of Poisson clinical trials and sample size determination SO PHARMACEUTICAL STATISTICS LA English DT Article DE gamma distribution; negative binomial distribution; maximum likelihood; Poisson distribution; WinBUGS AB Bayesian methods are often used to reduce the sample sizes and/or increase the power of clinical trials. The right choice of the prior distribution is a critical step in Bayesian modeling. If the prior not completely specified, historical data may be used to estimate it. In the empirical Bayesian analysis, the resulting prior can be used to produce the posterior distribution. In this paper, we describe a Bayesian Poisson model with a conjugate Gamma prior. The parameters of Gamma distribution are estimated in the empirical Bayesian framework under two estimation schemes. The straightforward numerical search for the maximum likelihood (ML) solution using the marginal negative binomial distribution is unfeasible occasionally. We propose a simplification to the maximization procedure. The Markov Chain Monte Carlo method is used to create a set of Poisson parameters from the historical count data. These Poisson parameters are used to uniquely define the Gamma likelihood function. Easily computable approximation formulae may be used to find the ML estimations for the parameters of gamma distribution. For the sample size calculations, the ML solution is replaced by its upper confidence limit to reflect an incomplete exchangeability of historical trials as opposed to current studies. The exchangeability is measured by the confidence interval for the historical rate of the events. With this prior, the formula for the sample size calculation is completely defined. Published in (C) 2009 by John Wiley & Sons, Ltd. C1 US FDA, CBER HFM 219, Rockville, MD 20852 USA. RP Zaslavsky, BG (reprint author), US FDA, CBER HFM 219, Rockville, MD 20852 USA. EM Boris.Zaslavsky@FDA.HHS.gov FU Critical Path Initiative FX This research was partially supported by the Critical Path Initiative CBER grant. NR 20 TC 4 Z9 4 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 APR-JUN PY 2010 VL 9 IS 2 BP 133 EP 141 DI 10.1002/pst.383 PG 9 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 620RW UT WOS:000279518000005 PM 19513984 ER PT J AU Lesko, LJ Zineh, I AF Lesko, Lawrence J. Zineh, Issam TI DNA, drugs and chariots: on a decade of pharmacogenomics at the US FDA SO PHARMACOGENOMICS LA English DT Article DE FDA; genomics; personalized medicine; pharmacogenomics; regulatory ID MEDICINE AB Over the past 10 years, the US FDA has become a strong pharmacogenomics advocate as part of its mission to both protect and advance public health by enabling innovations that make medicines safer to use and more effective. The agency has evolved its advocacy cautiously on a foundation of science-based information from novel programs, such as the Voluntary Genomics Data Submission initiative, and on careful regulatory assessment of the extraordinary advances in clinical pharmacogenomics that have supported the update of drug labels with genetic information. This commentary goes into detail on the evolution of these achievements. However, many challenges remain for pharmacogenomics, and they will continue to evolve, and all stakeholders must work together. As the decade draws to a close, we have presented four major areas that need to be addressed collectively to assure that pharmacogenomics continues to mature over the next 10 years into a science that is essential to the practice of medicine. C1 [Lesko, Lawrence J.; Zineh, Issam] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Lesko, LJ (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, HFD 850,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM lawrence.lesko@fda.hhs.gov NR 8 TC 33 Z9 33 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 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD APR PY 2010 VL 11 IS 4 SI SI BP 507 EP 512 DI 10.2217/PGS.10.16 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 584RD UT WOS:000276769300009 PM 20350131 ER PT J AU Matthews, EJ Frid, AA AF Matthews, Edwin J. Frid, Anna A. TI Prediction of drug-related cardiac adverse effects in humans-A: Creation of a database of effects and identification of factors affecting their occurrence SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE AERS; BioEpisteme (TM); Clinical indication; Drug-induced cardiac toxicity; Drug-related adverse effect; In silico; Mechanism of action; MedDRA; QSAR; Quantitative structure-activity relationships; SRS; Therapeutic target ID URINARY-TRACT TOXICITIES; INDUCED HEPATOBILIARY; PHARMACEUTICALS; PART; QSAR AB This is the first of two reports that describes the compilation of a database of drug-related cardiac adverse effects (AEs) that was used to construct quantitative structure-activity relationship (QSAR) models to predict these AEs. to identify properties of pharmaceuticals correlated with the AEs, and to identify plausible mechanisms of action (MOAs) causing the AEs This database of 396,985 cardiac AE reports was linked to 1632 approved drugs and their chemical structures, 1851 clinical indications (CIs), 997 therapeutic targets (TTs), 432 pharmacological MOAs, and 21,180 affinity coefficients (ACs) for the MOA receptors AEs were obtained from the Food and Drug Administration's (FDA's) Spontaneous Reporting System (SRS) and Adverse Event Reporting System (AERS) and publicly available medical literature Drug TTs were obtained from Integrity (TM), drug MOAs and ACs were predicted by BioEpisteme (TM) Significant cardiac AEs and patient exposures were estimated based on the proportional reporting ratios (PRRs) for each drug and each AE endpoint as a percentage of the total AEs Cardiac AE endpoints were bundled based oil toxicological mechanism and concordance of drug-related findings. Results revealed that significant cardiac AEs formed 9 clusters affecting Purkinje nerve fibers (arrhythmia, bradycardia, conduction disorder, electrocardiogram, palpitations, QT prolongation, rate rhythm composite, tachycardia, and Torsades de pointes), and 5 Clusters affecting the heart muscle (coronary artery disorders. heart failure, myocardial disorders, myocardial infarction, and valve disorders). Based on the observation that each drug had one TT and up to 9 off-target MOAs, cardiac AEs were highly correlated with drugs affecting cardiovascular and cardioneurological functions and certain MOAs (e g, alpha- and beta-adeno. dopamine, and hydroxytryptomine receptors) (C) 2010 Published by Elsevier Inc C1 [Matthews, Edwin J.] US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, College Pk, MD 20740 USA. [Frid, Anna A.] GlobalNet Serv, Rockville, MD 20852 USA. RP Matthews, EJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety Senior Sci & Policy Staff, 5100 Paint Branch Pkway, College Pk, MD 20740 USA. NR 17 TC 12 Z9 12 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD APR PY 2010 VL 56 IS 3 BP 247 EP 275 DI 10.1016/j.yrtph.2009.11.006 PG 29 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 570ON UT WOS:000275687700002 PM 19932726 ER PT J AU Frid, AA Matthews, EJ AF Frid, Anna A. Matthews, Edwin J. TI Prediction of drug-related cardiac adverse effects in humans-B: Use of QSAR programs for early detection of drug-induced cardiac toxicities SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE AERS; BioEpisteme (TM); Clinical indication; Drug-induced cardiac toxicity; Drug-related adverse effect; In silico; Leadscope FDA Model Applier; MC4PC; Mechanism of action; QSAR; Quantitative structure-activity relationship; SRS; Therapeutic target ID URINARY-TRACT TOXICITIES; DISCRIMINATING STRUCTURAL FEATURES; DEVELOPMENTAL TOXICITY; IN-SILICO; HAZARD IDENTIFICATION; INDUCED HEPATOBILIARY; CARCINOGENICITY DATA; COMPREHENSIVE MODEL; GENETIC TOXICITY; BUILDING-BLOCKS AB This report describes the use of three quantitative structure-activity relationship (QSAR) programs to predict drug-related cardiac adverse effects (AEs), BioEpisteme (TM), MC4PC, and Leadscope Predictive Data Miner. QSAR models were constructed for 9 cardiac AE clusters affecting Purkinje nerve fibers (arrhythmia, bradycardia. conduction disorder, electrocardiogram, palpitations, QT prolongation, rate rhythm composite, tachycardia, and Torsades de pointes) and 5 clusters affecting the heart muscle (coronary artery disorders, heart failure, myocardial disorders, myocardial infarction, and valve disorders) The models were based on a database of post-marketing AEs linked to 1632 chemical structures, and identical training data sets were configured for three QSAR programs Model performance was optimized and shown to be affected by the ratio of the number of active to inactive drugs Results revealed that the three programs were complementary and predictive performances using any single positive, consensus two positives, or consensus three positives were as follows. respectively 70 7%, 91 7%, and 98 0% specificity, 74 7%, 47.2%, and 21.0% sensitivity: and 138 2, 206 3, and 144 2 chi(2) In addition, a prospective study using AE data from the U S Food and Drug Administration's (FDA's) MedWatch Program showed 82.4% specificity and 94.3% sensitivity. Furthermore, an external validation study of 18 drugs with serious cardiotoxicity not considered in the models had 88.9% sensitivity (C) Published by Elsevier Inc C1 [Matthews, Edwin J.] US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, College Pk, MD 20740 USA. [Frid, Anna A.] GlobalNet Serv, Rockville, MD 20852 USA. RP Matthews, EJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety Senior Sci & Policy Staff, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 43 TC 20 Z9 20 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD APR PY 2010 VL 56 IS 3 BP 276 EP 289 DI 10.1016/j.yrtph.2009.11.005 PG 14 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 570ON UT WOS:000275687700003 PM 19941924 ER PT J AU Hill, W AF Hill, Walt TI Red Tape: Strangling Science? SO SCIENTIST LA English DT Letter C1 [Hill, Walt] FDA, Seattle, WA USA. [Hill, Walt] FSIS, Seattle, WA USA. RP Hill, W (reprint author), FDA, Seattle, WA USA. EM foodsafetyconsultants@earthlink.net NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 400 MARKET ST, STE 1250, PHILADELPHIA, PA 19106 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD APR PY 2010 VL 24 IS 4 BP 16 EP 16 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 574TX UT WOS:000276017700007 ER PT J AU Lorentzen, RJ AF Lorentzen, Ronald J. TI Carcinogenesis, Bioassays, and the Regulatory Modus Operandi SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Lorentzen, RJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM longgg@sbcglobal.net NR 0 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD APR PY 2010 VL 38 IS 3 BP 506 EP 507 DI 10.1177/0192623309358908 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 592EA UT WOS:000277357200017 PM 20124497 ER PT J AU Shi, Q Guo, L Patterson, TA Dial, S Li, Q Sadovova, N Zhang, X Hanig, JP Paule, MG Slikker, W Wang, C AF Shi, Q. Guo, L. Patterson, T. A. Dial, S. Li, Q. Sadovova, N. Zhang, X. Hanig, J. P. Paule, M. G. Slikker, W., Jr. Wang, C. TI GENE EXPRESSION PROFILING IN THE DEVELOPING RAT BRAIN EXPOSED TO KETAMINE SO NEUROSCIENCE LA English DT Article DE ketamine; gene expression; microarray; Taq Man; N-methyl-D-aspartate (NMDA) receptor ID CYANIDE-INDUCED APOPTOSIS; CORTICAL-NEURONS; NMDA RECEPTORS; UP-REGULATION; ASPARTATE RECEPTORS; CELL-DEATH; CULTURE; NEURODEGENERATION; NEUROTOXICITY; TRANSLOCATION AB Ketamine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, is associated with accelerated neuronal apoptosis in the developing rodent brain. In this study, postnatal day (PND) 7 rats were treated with 20 mg/kg ketamine or saline in six successive doses (s.c.) at 2-h intervals. Brain frontal cortical areas were collected 6 h after the last dose and RNA isolated and hybridized to Illumina Rat Ref-12 Expression Bead Chips containing 22,226 probes. Many of the differentially expressed genes were associated with cell death or differentiation and receptor activity. Ingenuity Pathway Analysis software identified perturbations in NMDA-type glutamate, GABA and dopamine receptor signaling. Quantitative polymerase chain reaction (Q-PCR) confirmed that NMDA receptor subunits were significantly upregulated. Up-regulation of NMDA receptor mRNA signaling was further confirmed by in situ hybridization. These observations support our working hypothesis that prolonged ketamine exposure produces up-regulation of NMDA receptors and subsequent over-stimulation of the glutamatergic system by endogenous glutamate, triggering enhanced apoptosis in developing neurons. Published by Elsevier Ltd on behalf of IBRO. C1 [Shi, Q.; Guo, L.; Dial, S.; Zhang, X.; Paule, M. G.; Slikker, W., Jr.; Wang, C.] US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Patterson, T. A.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Li, Q.] Univ Texas SW Med Ctr Dallas, Microarray Core Facil, Dallas, TX 75390 USA. [Sadovova, N.] Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Hanig, J. P.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20933 USA. RP Wang, C (reprint author), US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM cheng.wang@fda.hhs.gov RI Guo, Lei/E-9232-2011; Qiang, Shi/E-6266-2012 FU NCTR/FDA [IAG 224-07-007]; National Institute for Environmental Health Sciences (NIEHS) [IAG 224-07-007]; Center for Drug Evaluation and Research (CDER)IFDA; National Institute of Child Health and Human Development (NICHD) FX This work was supported in part by an Interagency Agreement (IAG 224-07-007) between NCTR/FDA and the National Institute for Environmental Health Sciences (NIEHS)/National Toxicology Program (NTP), the Center for Drug Evaluation and Research (CDER)IFDA, and the National Institute of Child Health and Human Development (NICHD). NR 37 TC 32 Z9 33 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD MAR 31 PY 2010 VL 166 IS 3 BP 852 EP 863 DI 10.1016/j.neuroscience.2010.01.007 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 582LD UT WOS:000276597900011 PM 20080153 ER PT J AU Liu, XF Doub, WH Guo, CN AF Liu, Xiaofei Doub, William H. Guo, Changning TI Evaluation of droplet velocity and size from nasal spray devices using phase Doppler anemometry (PDA) SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE Nasal spray; In vitro test; Aerosol; Velocity; Size; Phase Doppler anemometry ID METERED-DOSE INHALERS AB To determine aerosol deposition during the inhalation drug delivery, it is important to understand the combination of velocity and droplet size together. In this study, phase Doppler anemometry (PDA) was used to simultaneously characterize the aerosol velocity and droplet size distribution (DSD) of three nasal spray pumps filled with water. Thirteen sampling positions were located in the horizontal cross-sectional area of the nasal spray plumes at a distance of 3 cm from the pump orifice. The results showed droplet velocities near the center of the spray plume were higher and more consistent than those near the edge. The pumps examined showed significant differences in their aerosol velocity at the center of the spray plume, which suggest that this metric might be used as a discriminating parameter for in vitro testing of nasal sprays. Droplet size measurements performed using PDA were compared with results from laser light scattering measurements. The ability of PDA to provide simultaneous measurements of aerosol velocity and size makes it a powerful tool for the detailed investigation of nasal spray plume characteristics. Published by Elsevier B.V. C1 [Liu, Xiaofei; Doub, William H.; Guo, Changning] 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. EM changning.guo@fda.hhs.gov FU U.S. Food and Drugs Administration [1165] FX This work was Supported by U.S. Food and Drugs Administration through its Critical Path Initiative fund (Project #1165). NR 12 TC 11 Z9 13 U1 0 U2 11 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 MAR 30 PY 2010 VL 388 IS 1-2 BP 82 EP 87 DI 10.1016/j.ijpharm.2009.12.041 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 568MI UT WOS:000275526100010 PM 20043981 ER PT J AU Stroncek, DF Puri, RK AF Stroncek, David F. Puri, Raj K. TI Cell and gene therapies: moving from research to clinic SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Editorial Material C1 [Stroncek, David F.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Puri, Raj K.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Stroncek, DF (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. EM dstroncek@cc.nih.gov NR 5 TC 2 Z9 2 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD MAR 29 PY 2010 VL 8 AR 31 DI 10.1186/1479-5876-8-31 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 589HA UT WOS:000277136500001 PM 20350323 ER PT J AU Xu, Y Karmakar, A Wang, DY Mahmood, MW Watanabe, F Zhang, YB Fejleh, A Fejleh, P Li, ZR Kannarpady, G Ali, S Biris, AR Biris, AS AF Xu, Yang Karmakar, Alokita Wang, Daoyuan Mahmood, Meena W. Watanabe, Fumiya Zhang, Yongbin Fejleh, Ashley Fejleh, Phillip Li, Zhongrui Kannarpady, Ganesh Ali, Syed Biris, Alexandru R. Biris, Alexandru S. TI Multifunctional Fe3O4 Cored Magnetic-Quantum Dot Fluorescent Nanocomposites for RF Nanohyperthermia of Cancer Cells SO JOURNAL OF PHYSICAL CHEMISTRY C LA English DT Article ID IRON-OXIDE NANOPARTICLES; BIOMEDICAL APPLICATIONS; NANOCRYSTALS; CYTOTOXICITY; THERAPY; PROTEIN; GROWTH; BRIGHT AB Highly biocompatible luminescent superparamagnetic nanocomposites have been synthesized front Fe3O4/SiO2-Ds (IQ). Fe3O4 nanoparticles coated with a silica shell, Fe3O4/SiO2 (IOS), and water-soluble CdSe-ZnS quantum dots (QDs) were assembled together by the conjugation of an SH group. X-ray diffraction (XRD), transmission electron microscopy (TEM), energy-dispersive X-ray analysis (EDX), UV-vis absorption and emission spectroscopy, and magnetometry were applied to characterize the nanocomposites. The nanocomposites exhibited multifunctional superparamagnetic and photoluminescent properties. Bright orange IQ nanoparticles were found to be successfully uptaken into pancreatic human cancer cells (Panc-1) after 24 h incubation. The IQ nanocomposites Showed virtually no cytotoxicity toward the Panc-1 cells when the exposure concentration was below 50 mu g/mL or 200 mu g/mL as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) or lactate dehydrogenase (LDH) release measurements. After the inclusion Of a very low dose (1.66 mu g/ml) Of fluorescent magnetic nanocomposites and exposure to a radio frequency (RF) treatment for only 2 min, most of the Panc-1 cells (99.2%) were found to die. The apoptosis process call be traceable because of the Unique optical properties of the water-soluble IQs. It was also confirmed that the structure-controlled IQ nanocomposites have reasonable magnetic properties, self-heating temperature-rising characteristics, and high biocompatibility. This suggests that these IQ nanocomposites may be considered as biopotential materials for applications involving in vivo nanohyperthermia and cancer treatment. C1 [Xu, Yang; Karmakar, Alokita; Mahmood, Meena W.; Watanabe, Fumiya; Fejleh, Ashley; Fejleh, Phillip; Li, Zhongrui; Kannarpady, Ganesh; Biris, Alexandru S.] Univ Arkansas, Nanotechnol Ctr, Little Rock, AR 72204 USA. [Wang, Daoyuan] Univ Arkansas, Dept Chem, Little Rock, AR 72204 USA. [Zhang, Yongbin; Ali, Syed] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Biris, Alexandru R.] Natl Inst Res & Dev Isotop & Mol Technol, RO-3400 Cluj Napoca, Romania. RP Xu, Y (reprint author), Univ Arkansas, Nanotechnol Ctr, Little Rock, AR 72204 USA. EM yxxu@ualr.edu; asbiris@ualr.edu RI Biris, Alexandru/A-8507-2010; Biris, Alexandru /C-4517-2011 FU Arkansas Science and Technology Authority (ASTA) [08-CAT-03] FX Financial support from Arkansas Science and Technology Authority (ASTA) grant #08-CAT-03 is highly appreciated. We also thank Prof. Dr. Aoki for help with part of the TEM measurements and Dr. Ran Gupta for the SQUID Measurement. NR 29 TC 63 Z9 66 U1 3 U2 76 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1932-7447 J9 J PHYS CHEM C JI J. Phys. Chem. C PD MAR 25 PY 2010 VL 114 IS 11 BP 5020 EP 5026 DI 10.1021/jp9103036 PG 7 WC Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 570WH UT WOS:000275708600036 ER PT J AU Davila, G Irsik, M Greiner, EC AF Davila, Gabriel Irsik, Max Greiner, Ellis C. TI Toxocara vitulorum in beef calves in North Central Florida SO VETERINARY PARASITOLOGY LA English DT Article DE Florida beef calves; Toxocara vitulorum; Fenbendazole ID BUBALUS-BUBALIS; LARVAE; MICE; COWS AB In this study, we evaluated the prevalence of Toxocara vitulorum in beef calves in North Central Florida. Fecal samples from 433 calves under 9 months of age were analyzed for the presence of eggs in their feces. The prevalence in calves less than 3 months of age was 17.6%, 3-4 months of age was 0.4% and those 5-6 months old had a 0.9% prevalence. As expected, no eggs were detected in any calves older than 6 months. Calves were treated with fenbendazole (10% FBZ) at 5 mg/kg after fecal samples were collected. Twenty calves that had T. vitulorum eggs in the feces were resampled 2 weeks after treatment to evaluate effectiveness of FBZ. No T. vitulorum eggs were seen in the feces of 17/20(85%) of the calves that were sampled after FBZ treatment. FBZ was effective in 85% of calves treated for T. vitulorum infection in calves. We would like to make beef ranchers and veterinarians in the southern states aware that the prevalence of this parasite has greatly increased recently in northern Florida beef units. (C) 2010 Published by Elsevier B.V. C1 [Greiner, Ellis C.] Univ Florida, Coll Vet Med, Dept Infect Dis & Pathol, Gainesville, FL 32611 USA. [Davila, Gabriel] US FDA, Ctr Vet Med, Rockville, MD 20857 USA. RP Greiner, EC (reprint author), Univ Florida, Coll Vet Med, Dept Infect Dis & Pathol, Box 110880, Gainesville, FL 32611 USA. EM greinere@vetmed.ufl.edu NR 18 TC 13 Z9 15 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4017 J9 VET PARASITOL JI Vet. Parasitol. PD MAR 25 PY 2010 VL 168 IS 3-4 BP 261 EP 263 DI 10.1016/j.vetpar.2009.11.026 PG 3 WC Parasitology; Veterinary Sciences SC Parasitology; Veterinary Sciences GA 581KD UT WOS:000276520400012 PM 20138706 ER PT J AU Kukreja, RV Sharma, SK Singh, BR AF Kukreja, Roshan V. Sharma, Shashi K. Singh, Bal Ram TI Molecular Basis of Activation of Endopeptidase Activity of Botulinum Neurotoxin Type E SO BIOCHEMISTRY LA English DT Article ID BLOCK NEUROTRANSMITTER RELEASE; TOXIN TYPE-A; CLOSTRIDIUM-BOTULINUM; LIGHT-CHAIN; PHARMACOLOGICAL ACTIONS; SUBSTRATE RECOGNITION; IN-VITRO; PROTEINS; TETANUS; TRANSLOCATION AB Botulinum neurotoxins (BoNTs) are a groups of large proteins that are responsible for the clinical syndrome of botulism. The seven immunologically distinct serotypes of BoNTs (A-G), each produced by various strains of Clostridium botulinum, act on the neuromuscular junction by blocking the release of the neurotransmitter acetylcholine, thereby resulting flaccide muscle paralysis. BoNTs are synthesized as single inactive polypeptide chains that are cleaved by endogenous Or exogenous proteases to generate the active dichain form of the toxin. Nicking of the single chain BoNT/E to the dichain form is associated with 100-fold increase in toxicity. Here we investigated the activation mechanism of botulinum neurotoxin type F, upon nicking and subsequent reduction of disulfide bond. It was observed that. nicking of BoNT/E significantly. enhances its endopeptidase activity and that at the physiological temperature of 37 degrees C the reduced form of nicked BoNT/E adopts a dynamically flexible conformation resulting from the exposure of hydrophobic segments and facilitating optimal cleavage of its substrate SNAP-25. Such reduction-induced increase lit the flexibility of the polypeptide folding provides a rationale for the mechanism of BoNT/E endopeptidase against its intracellular substrate, SNAP-25, and complements current Understanding of the mechanistics of interaction between the substrate and BoNT endopeptidase. C1 [Kukreja, Roshan V.; Singh, Bal Ram] Univ Massachusetts Dartmouth, Botulinum Res Ctr, N Dartmouth, MA 02747 USA. [Kukreja, Roshan V.; Singh, Bal Ram] Univ Massachusetts Dartmouth, Dept Chem & Biochem, N Dartmouth, MA 02747 USA. [Sharma, Shashi K.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Singh, BR (reprint author), Univ Massachusetts Dartmouth, Botulinum Res Ctr, 285 Old Westport Rd, N Dartmouth, MA 02747 USA. EM bsingh@umassd.edu FU NIAID NIH HHS [U54 AI057159, AI057159-01] NR 45 TC 9 Z9 9 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 23 PY 2010 VL 49 IS 11 BP 2510 EP 2519 DI 10.1021/bi902096r PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 570XI UT WOS:000275711400023 PM 20178376 ER PT J AU Davis, EM Elabd, YA Winey, KI Regnault, WF Benetatos, NM AF Davis, Eric M. Elabd, Yossef A. Winey, Karen I. Regnault, William F. Benetatos, Nicholas M. TI New characterization techniques for assessing the structure and water transport properties of parylene coatings SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Drexel Univ, Dept Chem & Biol Engn, Philadelphia, PA 19104 USA. Univ Penn, Dept Mat Sci & Engn, Philadelphia, PA 19104 USA. US FDA, Div Chem Mat Sci, Silver Spring, MD USA. RI Elabd, Yossef/G-9866-2014 OI Elabd, Yossef/0000-0002-7790-9445 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 MAR 21 PY 2010 VL 239 MA 39-PMSE PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V21DW UT WOS:000208189304600 ER PT J AU Palmer, PT Gregory, H Baker, PE Jacobs, R AF Palmer, Peter T. Gregory, H. Baker, P. E. Jacobs, R. TI FDA applications of field portable XRF for consumer product analysis: Cl to U down to low ppm levels in 60 seconds or less SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 San Francisco State Univ, Dept Chem & Biochem, San Francisco, CA 94132 USA. US FDA, San Francisco Dist Lab, Alameda, CA 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 MAR 21 PY 2010 VL 239 MA 43-AGRO PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V21DW UT WOS:000208189300227 ER PT J AU Park, JT Read, EK AF Park, Jun T. Read, Erik K. TI Updated regulatory database of aggregates and particles for monoclonal antibodies SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Park, Jun T.; Read, Erik K.] OBP CDER Food & Drug Adm, Div Monoclonal Antibodies, 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 MAR 21 PY 2010 VL 239 MA 51-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V21DW UT WOS:000208189300644 ER PT J AU Read, EK Park, J Brorson, K AF Read, Erik K. Park, Jun Brorson, Kurt TI Analysis of glycoform characterization within monoclonal antibody regulatory submissions SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Read, Erik K.; Park, Jun; Brorson, Kurt] OBP CDER FDA, Div Monoclonal Antibodies, Silver Spring, MD USA. 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 MAR 21 PY 2010 VL 239 MA 50-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V21DW UT WOS:000208189300637 ER PT J AU Vivekanandan, S Rademacher, C Lowary, TL Freedberg, DI AF Vivekanandan, Subramanian Rademacher, Christoph Lowary, Todd L. Freedberg, Daron I. TI Secret life of sugars: Using heteronuclear NMR to unveil molecular motion in carbohydrate TB-antigens SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Div Bacterial Prod & Allergen Prod, Bethesda, MD 20014 USA. Univ Alberta, Dept Chem, Edmonton, AB, Canada. RI Subramanian, Vivekanandan/F-5865-2012; S, Vivekanandan/E-5197-2011; Rademacher, Christoph/H-3101-2012 OI Rademacher, Christoph/0000-0001-7082-7239 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 MAR 21 PY 2010 VL 239 MA 100-CARB PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V21DW UT WOS:000208189300707 ER PT J AU Yu, DL Rummel, NG Shaikh, B AF Yu, Donglei Rummel, Nathan G. Shaikh, Badaruddin TI Determination of albendazole and its metabolites in the muscle tissue of yellow perch using liquid chromatography with fluorescence detection SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Yu, Donglei; Rummel, Nathan G.; Shaikh, Badaruddin] US FDA, Ctr Vet Med, Laural, MD 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 MAR 21 PY 2010 VL 239 MA 97-AGRO PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V21DW UT WOS:000208189300252 ER PT J AU Chen, HZ Feng, JH Kweon, O Xu, HY Cerniglia, CE AF Chen, Huizhong Feng, Jinhui Kweon, Ohgew Xu, Haiyan Cerniglia, Carl E. TI Identification and molecular characterization of a novel flavin-free NADPH preferred azoreductase encoded by azoB in Pigmentiphaga kullae K24 SO BMC BIOCHEMISTRY LA English DT Article ID RHODOBACTER-SPHAEROIDES AS1.1737; FMN-DEPENDENT AZOREDUCTASE; ENTEROCOCCUS-FAECALIS; BACILLUS SP; AEROBIC AZOREDUCTASE; CLONING; DYES; DEGRADATION; ENZYME; FLAVOPROTEIN AB Background: Microbial degradation of azo dyes is commonly initiated by the reduction of the azo bond(s) by a group of NADH or NADPH dependant azoreductases with many requiring flavin as a cofactor. In this study, we report the identification of a novel flavin-free NADPH preferred azoreductase encoded by azoB in Pigmentiphaga kullae K24. Results: The deduced amino acid sequence of azoB from P. kullae K24 showed 61% identity to a previously studied azoreductase (AzoA) from the same strain. azoB encoded a protein of 203 amino acids and heterologously expressed in Escherichia coli. The purified recombinant enzyme was a monomer with a molecular mass of 22 kDa. Both NADH and NADPH can be used as an electron donor for its activity with 4-(4-hydroxy-1-naphthylazo) benzenesulfonic acid (Orange I) as substrate. The apparent K-m values for both NADH and Orange I were 170 and 8.6 mu M, respectively. The K-m of NADPH for the enzyme is 1.0 mu M. When NADPH served as the electron donor, the activity of the enzyme is 63% higher than that when NADH was used. The pH and temperature optima for activity of the enzyme with Orange I as the substrate were at pH 6.0 and between 37 and 45 degrees C. Phylogenetic analysis shows that AzoB belongs to the flavin-free azoreductase group which has a key fingerprint motif GXXGXXG for NAD(P) H binding at the N-terminus of the amino acid sequences. The 3D structure of AzoB was generated by comparative modeling approach. The structural combination of three conserved glycine residues (G(7)xxG(10)xxG(13)) in the pyrophosphate-binding loop with the Arg-32 explains the preference for NADPH of AzoB. Conclusion: The biochemical and structural properties of AzoB from P. kullae K24 revealed its preference for NADPH over NADH and it is a member of the monomeric flavin-free azoreductase group. Our studies show the substrate specificity of AzoB based on structure and cofactor requirement and the phylogenetic relationship among azoreductase groups. C1 [Chen, Huizhong; Feng, Jinhui; Kweon, Ohgew; Xu, Haiyan; Cerniglia, Carl E.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Chen, HZ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM huizhong.chen@fda.hhs.gov FU Office of Women's Health; National Center for Toxicological Research; United States Food and Drug Administration; U. S. Department of Energy; U. S. Food and Drug Administration FX We thank Drs. Steven L. Foley and Huanli Liu for their critical review of the manuscript and Mr. Siwei Chen (NCTR summer intern) for technical assistance in cloning and expression. This study was funded by the Office of Women's Health and the National Center for Toxicological Research, United States Food and Drug Administration, and supported in part by an appointment (JF and HX) to the Postgraduate Research Fellowship Program by the Oak Ridge Institute for Science and Education through an interagency agreement between the U. S. Department of Energy and the U. S. Food and Drug Administration. The views presented in this article do not necessarily reflect those of the Food and Drug Administration. NR 33 TC 15 Z9 16 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2091 J9 BMC BIOCHEM JI BMC Boichem. PD MAR 16 PY 2010 VL 11 AR 13 DI 10.1186/1471-2091-11-13 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 587NZ UT WOS:000277000800001 PM 20233432 ER PT J AU Jin, YX Tan, ZW He, MZ Tian, BH Tang, SX Hewlett, I Yang, M AF Jin, Yinxue Tan, Zhiwu He, Meizi Tian, Baohe Tang, Shixing Hewlett, Indira Yang, Ming TI SAR and molecular mechanism study of novel acylhydrazone compounds targeting HIV-1 CA SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE HIV-1; Capsid assembly; Antiviral; Acylhydrazone derivatives ID CAPSID PROTEIN AB We synthesized a series of acylhydrazone compounds bearing naturally occurring amino acids' side chains as HIV assembly inhibitors. Biological evaluation indicated that the compounds had anti-SIV and capsid assembly inhibitory activities. The structure-activity relationship (SAR) study showed that compounds bearing proper aromatic side chains had potential antiviral activities. The molecular modeling experiments revealed the molecular mechanism that they could bind to CA in the same manner as CAP-1 and occupy two more grooves. (C) 2010 Published by Elsevier Ltd. C1 [Jin, Yinxue; Tan, Zhiwu; He, Meizi; Tian, Baohe; 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, POB 261, Beijing 100191, Peoples R China. EM yangm@bjmu.edu.cn FU National Natural Science Foundation of China [30670415] FX The project was supported by the National Natural Science Foundation of China (No. 30670415). NR 10 TC 23 Z9 25 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD MAR 15 PY 2010 VL 18 IS 6 BP 2135 EP 2140 DI 10.1016/j.bmc.2010.02.003 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 568HR UT WOS:000275513700009 PM 20188575 ER PT J AU Mott, TM Everley, RA Wyatt, SA Toney, DM Croley, TR AF Mott, Tiffany M. Everley, Robert A. Wyatt, Shane A. Toney, Denise M. Croley, Timothy R. TI Comparison of MALDI-TOF/MS and LC-QTOF/MS methods for the identification of enteric bacteria SO INTERNATIONAL JOURNAL OF MASS SPECTROMETRY LA English DT Article DE Intact protein; MALDI-TOF/MS; LC/QTOF/MS; Identification and characterization ID LIQUID CHROMATOGRAPHY/MASS SPECTROMETRY; FLIGHT MASS-SPECTROMETRY; ASSISTED-LASER-DESORPTION/IONIZATION; DESORPTION IONIZATION-TIME; ESCHERICHIA-COLI; TEMPLATE PREPARATION; INTACT PROTEINS; UNITED-STATES; MICROORGANISMS; DATABASE AB Two complementary mass spectrometric techniques were evaluated for their applicability as methods for foodborne pathogen characterization, biomarker candidate discovery and identification. Ten clinical isolates of closely related organisms, Escherichia coli. Shigella sonnei and Shigella flexneri, were chosen for this study. Whole cell lysates were analyzed using both matrix assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF/MS) and liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). Evaluation of isolate mass spectra revealed unique protein profile patterns and potential biomarkers capable of species and sub-species identification. Strengths of each MS method, in addition to their advantages over traditional methods, are highlighted and a brief discussion of their potential as standard tools in the laboratory is presented. Published by Elsevier B.V. C1 [Mott, Tiffany M.; Everley, Robert A.; Wyatt, Shane A.; Toney, Denise M.; Croley, Timothy R.] Commonwealth Virginia, Div Consolidated Lab Serv, Richmond, VA 23219 USA. [Everley, Robert A.; Wyatt, Shane A.; Croley, Timothy R.] Virginia Commonwealth Univ, Dept Chem, Richmond, VA 23284 USA. RP Croley, TR (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM timothy.croley@fda.hhs.gov FU Centers for Disease Control and Prevention (CDC) [U90/CCU317014] FX A portion of this research was funded by the Centers for Disease Control and Prevention (CDC) grant #: U90/CCU317014. T.M.M. was supported by an appointment to the Emerging Infectious Disease (EID) Fellowship Program administered by the Association of Public Health Laboratories (APHL) and funded by the CDC. NR 23 TC 9 Z9 9 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1387-3806 EI 1873-2798 J9 INT J MASS SPECTROM JI Int. J. Mass Spectrom. PD MAR 15 PY 2010 VL 291 IS 1-2 BP 24 EP 32 DI 10.1016/j.ijms.2009.12.015 PG 9 WC Physics, Atomic, Molecular & Chemical; Spectroscopy SC Physics; Spectroscopy GA 577LC UT WOS:000276223600004 ER PT J AU Keire, DA Trehy, ML Reepmeyer, JC Kolinski, RE Ye, W Dunn, J Westenberger, BJ Buhse, LF AF Keire, David A. Trehy, Michael L. Reepmeyer, John C. Kolinski, Richard E. Ye, Wei Dunn, Jamie Westenberger, Benjamin J. Buhse, Lucinda F. TI Analysis of crude heparin by H-1 NMR, capillary electrophoresis, and strong-anion-exchange-HPLC for contamination by over sulfated chondroitin sulfate SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Heparin; Over-sulfated or fully-sulfated chondroitin sulfate; Dermatan sulfate; Glycosaminoglycan; SAX-HPLC; NMR; CE ID ADVERSE CLINICAL EVENTS AB We previously published a strong-anion-exchange-high performance liquid chromatography (SAX-HPLC) method for the detection of the contaminant over sulfated chondroitin sulfate (OSCS) in heparin sodium active pharmaceutical ingredient (API). While APIs have been processed to remove impurities, crude heparins contain insoluble material, chondroitin sulfates, heparan sulfate, and proteins that may interfere with the recovery and measurement of OSCS. We examined 500 MHz H-1 NMR, capillary electrophoresis (CE), and SAX-HPLC to quantify OSCS in crude heparin. Using our standard API protocol on OSCS spiked crude heparin samples; we observed a weight percent LOD and LOQ for the NMR approach of 0.1% and 0.3%, respectively, while the SAX-HPLC method gave values of 0.03% and 0.09%, respectively. CE data was not amenable to quantitative measurement of OSCS in crude heparin. We developed a modified HPLC sample preparation protocol using crude dissolved at the 100 mg/mL level with a 2.5 M NaCl solution. This SAX-HPLC approach gave a weight percent LOD of 0.02% and a LOQ of 0.07% and had better performance characteristics than that of the protocol used for APIs. Published by Elsevier B.V. C1 [Keire, David A.; Trehy, Michael L.; Reepmeyer, John C.; Kolinski, Richard E.; Ye, Wei; Dunn, Jamie; Westenberger, Benjamin J.; 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. EM david.keire@fda.hhs.gov NR 18 TC 35 Z9 38 U1 3 U2 28 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 MAR 11 PY 2010 VL 51 IS 4 BP 921 EP 926 DI 10.1016/j.jpba.2009.10.017 PG 6 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 542QT UT WOS:000273510600017 PM 19959313 ER PT J AU Schmeisser, F Vodeiko, GM Lugovtsev, VY Stout, RR Weir, JP AF Schmeisser, Falko Vodeiko, Galina M. Lugovtsev, Vladimir Y. Stout, Richard R. Weir, Jerry P. TI An alternative method for preparation of pandemic influenza strain-specific antibody for vaccine potency determination SO VACCINE LA English DT Article DE Pandemic influenza; Vaccine potency; Single-radial immunodiffusion assay ID SINGLE-RADIAL-IMMUNODIFFUSION; PERFORMANCE LIQUID-CHROMATOGRAPHY; VIRUS-LIKE PARTICLES; MATRIX PROTEIN; HEMAGGLUTININ; QUANTIFICATION; CHALLENGE; IMMUNITY; ANTIGEN; ASSAY AB The traditional assay used to measure potency of inactivated influenza vaccines is a single-radial immunodiffusion (SRID) assay that utilizes an influenza strain-specific antibody to measure the content of virus hemagglutinin (HA) in the vaccine in comparison to a homologous HA reference antigen. Since timely preparation of potency reagents by regulatory authorities is challenging and always a potential bottleneck in influenza vaccine production, it is extremely important that additional approaches for reagent development be available, particularly in the event of an emerging pandemic influenza virus. An alternative method for preparation of strain-specific antibody that can be used for SRID potency assay is described. The approach does not require the presence or purification of influenza virus, and furthermore, is not limited by the success of the traditional technique of bromelain digestion and purification of virus HA. Multiple mammalian expression vectors, including plasmid and modified vaccinia virus Ankara (MVA) vectors expressing the HAs of two H5N1 influenza viruses and the HA of the recently emerging pandemic H1N1 (2009) virus, were developed. An immunization scheme was designed for the sequential immunization of animals by direct vector injection followed by protein booster immunization using influenza HA produced in vitro from MVA vector infection of cells in culture. Each HA antibody was highly specific as shown by hemagglutination inhibition assay and the ability to serve as a capture antibody in ELISA. Importantly, each H5N1 antibody and the pandemic H1N1 (2009) antibody preparation were suitable for use in SRID assays for determining the potency of pandemic influenza virus vaccines. The results demonstrate a feasible approach for addressing one of the potential bottlenecks in inactivated pandemic influenza vaccine production and are particularly important in light of the difficulties in preparation of potency reagent antibody for pandemic H1N1 (2009) virus vaccines. Published by Elsevier Ltd. C1 [Schmeisser, Falko; Vodeiko, Galina M.; Lugovtsev, Vladimir Y.; Weir, Jerry P.] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. [Stout, Richard R.] Bioject Inc, Tualatin, OR USA. RP Weir, JP (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM jerry.weir@fda.hhs.gov FU National Vaccine Program Office, Department of Health and Human Services FX We thank Gary Nabel (Vaccine Research Center, NIH) for the plasmid expression vector pVRC-8400, Bernard Moss (National Institute of Allergy and Infections Diseases, NIH) for the MVA insertion vector pLW44, Zhiping Ye and Maryna Eichelberger (CBER/FDA) for critical reading of the manuscript, and Arunima Kumar, Benjamin Blumberg, and Jackeline Soto for technical assistance. This work was supported in part by the National Vaccine Program Office, Department of Health and Human Services. NR 23 TC 17 Z9 18 U1 0 U2 7 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 MAR 11 PY 2010 VL 28 IS 12 BP 2442 EP 2449 DI 10.1016/j.vaccine.2009.12.079 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 576HN UT WOS:000276135200012 PM 20074687 ER PT J AU Yang, L Chen, J Shi, LM Hudock, MP Wang, KJ He, L AF Yang, Lun Chen, Jian Shi, Leming Hudock, Michael P. Wang, Kejian He, Lin TI Identifying Unexpected Therapeutic Targets via Chemical-Protein Interactome SO PLOS ONE LA English DT Article ID HISTONE DEACETYLASE INHIBITORS; ADVERSE DRUG-REACTIONS; HUMAN ACETYLCHOLINESTERASE; SMALL-MOLECULE; IDENTIFICATION; DOCKING; DATABASE; LIGAND; DISEASE; SYSTEM AB Drug medications inevitably affect not only their intended protein targets but also other proteins as well. In this study we examined the hypothesis that drugs that share the same therapeutic effect also share a common therapeutic mechanism by targeting not only known drug targets, but also by interacting unexpectedly on the same cryptic targets. By constructing and mining an Alzheimer's disease (AD) drug-oriented chemical-protein interactome (CPI) using a matrix of 10 drug molecules known to treat AD towards 401 human protein pockets, we found that such cryptic targets exist. We recovered from CPI the only validated therapeutic target of AD, acetylcholinesterase (ACHE), and highlighted several other putative targets. For example, we discovered that estrogen receptor (ER) and histone deacetylase (HDAC), which have recently been identified as two new therapeutic targets of AD, might already have been targeted by the marketed AD drugs. We further established that the CPI profile of a drug can reflect its interacting character towards multi-protein sets, and that drugs with the same therapeutic attribute will share a similar interacting profile. These findings indicate that the CPI could represent the landscape of chemical-protein interactions and uncover "behind-the-scenes" aspects of the therapeutic mechanisms of existing drugs, providing testable hypotheses of the key nodes for network pharmacology or brand new drug targets for one-target pharmacology paradigm. C1 [Yang, Lun; Chen, Jian; Hudock, Michael P.; Wang, Kejian; He, Lin] Shanghai Jiao Tong Univ, Minist Educ, Key Lab Genet Dev & Neuropsychiat Disorders, Bio Ctr X, Shanghai 200030, Peoples R China. [Yang, Lun; Chen, Jian; He, Lin] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China. [Shi, Leming] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [He, Lin] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai, Peoples R China. RP Yang, L (reprint author), Shanghai Jiao Tong Univ, Minist Educ, Key Lab Genet Dev & Neuropsychiat Disorders, Bio Ctr X, Shanghai 200030, Peoples R China. EM lunyang@gmail.com; helinhelin@gmail.com RI Yang, Lun/B-4859-2012 FU National Natural Science Foundation of China [30900841]; Postdoctoral Science Foundation of China [200902243]; China Postdoctoral Science Foundation [20070420660]; Shanghai Postdoctoral Science Foundation [61444] FX This work was supported by National Natural Science Foundation of China [ 30900841], Special Reward Funding from Postdoctoral Science Foundation of China (200902243), China Postdoctoral Science Foundation (20070420660) and Shanghai Postdoctoral Science Foundation (No. 61444). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 34 Z9 38 U1 1 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 8 PY 2010 VL 5 IS 3 BP A71 EP A81 AR e9568 DI 10.1371/journal.pone.0009568 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 565WZ UT WOS:000275328200007 PM 20221449 ER PT J AU Parks, M Rosebraugh, C AF Parks, Mary Rosebraugh, Curtis TI Weighing Risks and Benefits of Liraglutide -- The FDA's Review of a New Antidiabetic Therapy. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID COHORT C1 [Parks, Mary] US FDA, Div Metab & Endocrinol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Rosebraugh, Curtis] US FDA, Off Drug Evaluat 2, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Parks, M (reprint author), US FDA, Div Metab & Endocrinol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 4 TC 139 Z9 149 U1 1 U2 7 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 MAR 4 PY 2010 VL 362 IS 9 BP 774 EP 777 DI 10.1056/NEJMp1001578 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 563DQ UT WOS:000275108300003 PM 20164475 ER PT J AU Marsh, L Biglan, KM Williams, JR AF Marsh, Laura Biglan, Kevin M. Williams, James R. TI Randomized Placebo-controlled Trial of Memantine for Dementia in Parkinson's Disease SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Geriatric-Psychiatry CY MAR 05-08, 2010 CL Savannah, GA SP Amer Assoc Geriat Psychiat C1 [Marsh, Laura] Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. [Biglan, Kevin M.] Univ Rochester, Sch Med, Dept Neurol, Rochester, NY USA. [Williams, James R.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2010 VL 18 IS 3 SU 1 BP S78 EP S79 PG 2 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 753PB UT WOS:000289790800088 ER PT J AU Saylor, DM Richardson, DC Dair, BJ Pollack, SK AF Saylor, David M. Richardson, D. Coleman Dair, Benita J. Pollack, Steven K. TI Osmotic cavitation of elastomeric intraocular lenses SO ACTA BIOMATERIALIA LA English DT Article DE Intraocular lens (IOL); Elastomer; Diffusion; Osmotic pressure; Cavitation ID POLY(METHYL METHACRYLATE); WATER-ABSORPTION; CATARACT-SURGERY; SMALL-INCISION; GLISTENINGS; IMPLANTATION; POLYMERS; OPACIFICATION; MECHANISM; SILICONE AB In recent years, traditional rigid materials have been replaced with softer elastomers in intraocular lenses to minimize the size of the required surgical incision, thereby reducing patient recuperation time However, water-filled cavities that may impact visual acuity are found in many of these new implants We demonstrate that the cavitation observed in vivo can occur due to an osmotic pressure difference between the aqueous solution within the cavity and the external media in which the lens is immersed By reducing the osmolarity of the external solution from 300 to 0 mM. we observe an increase in cavity volume of almost a factor of 30 Further. we have developed a model for cavity growth assuming the controlling factor is diffusion of hydrophilic molecules from the polymer matrix into the cavity. We find that the experimental observations are consistent with the model and suggest that oligomeric species generated during polymerization are responsible for the observed cavitation Published by Elsevier Ltd. C1 [Saylor, David M.] US FDA, CDRH, OSEL, DCMS, Silver Spring, MD 20993 USA. RP Saylor, DM (reprint author), US FDA, CDRH, OSEL, DCMS, 10903 New Hamsphire Ave, Silver Spring, MD 20993 USA. NR 40 TC 10 Z9 10 U1 2 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1742-7061 J9 ACTA BIOMATER JI Acta Biomater. PD MAR PY 2010 VL 6 IS 3 BP 1090 EP 1098 DI 10.1016/j.actbio.2009.08.030 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 560ZD UT WOS:000274943500043 PM 19712761 ER PT J AU Kohlstadt, I Vitiello, B AF Kohlstadt, Ingrid Vitiello, Benedetto TI Use of Atypical Antipsychotics in Children: Balancing Safety and Effectiveness SO AMERICAN FAMILY PHYSICIAN LA English DT Editorial Material C1 [Kohlstadt, Ingrid] US FDA, Off Pediat Therapeut, Rockville, MD 20857 USA. [Vitiello, Benedetto] NIMH, Bethesda, MD 20892 USA. RP Kohlstadt, I (reprint author), US FDA, Off Pediat Therapeut, Rockville, MD 20857 USA. EM kohlstadt@fda.hhs.gov NR 9 TC 5 Z9 5 U1 2 U2 2 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD MAR 1 PY 2010 VL 81 IS 5 BP 585 EP + PG 2 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 565MK UT WOS:000275297200002 PM 20187594 ER PT J AU LaPointe, NMA Sun, JL Kaplan, S AF LaPointe, Nancy M. Allen Sun, Jie-Lena Kaplan, Sigal TI In-hospital management of patients with atrial flutter SO AMERICAN HEART JOURNAL LA English DT Article ID CONTEMPORARY MANAGEMENT; CATHETER ABLATION; FIBRILLATION; GUIDELINES; RHYTHM; RISK AB Background Little is known about the use of drugs or procedures for management of atrial flutter (AFl) in routine clinical practice. We describe the extent of use of conversion therapies during AFl hospitalizations. Methods We examined hospitalizations for primary diagnoses of AFl using hospital claims from January 2000 to December 2004. Patients who received antiarrhythmic drugs, ablation, and/or electrical cardioversion for AFl were categorized as receiving a conversion therapy. Characteristics associated with use of conversion therapy versus no conversion therapy were determined. Results The study cohort included 19,825 hospitalizations. Of these, 13,059 (65.9%) included in-hospital use of >= 1 conversion therapies. Care by a noncardiologist (adjusted odds ratio [OR] 0.37, 95% CI 0.33-0.41), female sex (adjusted OR 0.84, 95% CI 0.79-0.90), nonwhite race (adjusted OR 0.83, 95% CI 0.74-0.92), and increasing age >70 years (adjusted OR 0.88, 95% CI 0.85-0.91) were associated with lower odds of conversion versus no-conversion therapy. Cardiomyopathy (adjusted OR 1.33, 95% CI 1.17-1.51), heart failure (adjusted OR 1.17, 95% CI 1.06-1.28), coronary artery disease (adjusted OR 1.14, 95% CI 1.05-1.22), secondary diagnosis of atrial fibrillation (adjusted OR 1.28, 95% CI 1.18-1.38), and hospitalization in 2000 or 2001 versus later years (adjusted OR 1.22, 95% CI 1.12-1.33) were associated with greater odds of conversion therapy versus no conversion therapy. Conclusion One or more methods of conversion to sinus rhythm were used in two thirds of the hospitalizations with a primary diagnosis of AFl. Greater use of conversion therapies in patients with other heart disease were expected; however, lower use among elderly persons, females, and racial minorities may indicate some disparities in use and warrant further study. (Am Heart J 2010; 159: 370-6.) C1 [LaPointe, Nancy M. Allen; Sun, Jie-Lena] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27715 USA. [Kaplan, Sigal] US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Silver Spring, MD USA. RP LaPointe, NMA (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM allen003@mc.duke.edu NR 17 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAR PY 2010 VL 159 IS 3 BP 370 EP 376 DI 10.1016/j.ahj.2009.12.013 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 571XH UT WOS:000275788900006 PM 20211297 ER PT J AU Husten, CG AF Husten, Corinne G. TI A Call for ACTTION Increasing Access to Tobacco-Use Treatment in Our Nation SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID UNITED-STATES; SMOKING AB The Consumer Demand Roundtable defined consumer demand for tobacco-use treatments as the degree to which tobacco users who are motivated or activated to quit know about, expect, seek, advocate for, demand, purchase, access, and use tobacco-cessation products and services that have been proven to increase abstinence. Two critical requirements for consumer demand are that tobacco users know about effective treatments and that they have access to these treatments. Despite tobacco use being the leading preventable cause of death in this country, neither of these critical conditions is met in the U.S., particularly for low-income and blue-collar populations, where smoking rates remain highest. (Am J Prev Med 2010;38(3S):S414-S417) (C) 2010 American journal of Preventive Medicine C1 [Husten, Corinne G.] Partnership Prevent, Washington, DC USA. RP Husten, CG (reprint author), US FDA, Ctr Tobacco Prod, 9200 Corp Blvd, Rockville, MD 20850 USA. EM Corinne.Husten@fda.hhs.gov NR 21 TC 3 Z9 3 U1 0 U2 0 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 MAR PY 2010 VL 38 IS 3 SU 3 BP S414 EP S417 DI 10.1016/j.amepre.2009.12.006 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 566OX UT WOS:000275383200017 PM 20176316 ER PT J AU Myers, MJ Farrell, DE Howard, KD Kawalek, JC AF Myers, Michael J. Farrell, Dorothy E. Howard, Karyn D. Kawalek, Joseph C. TI Effects of intravenous administration of lipopolysaccharide on cytochrome P450 isoforms and hepatic drug metabolizing enzymes in swine SO AMERICAN JOURNAL OF VETERINARY RESEARCH LA English DT Article ID INFECTION ACTINOBACILLUS-PLEUROPNEUMONIAE; ACID-POLYCYTIDYLIC ACID; ACUTE-PHASE RESPONSE; MESSENGER-RNA LEVELS; INFLAMMATORY MEDIATORS; NUCLEAR RECEPTORS; INDUCTION; SUPPRESSION; CYTOKINES; GENES AB Objective-To investigate effects of bacteria-mediated inflammation on hepatic drug metabolizing enzymes (DMEs) in swine via a lipopolysaccharide (LPS) challenge technique. Animals-22 Poland China-Landrace crossbred barrows. Procedures-in experiment 1, 10 market-weight swine were treated with LPS (20 mu g/kg, IV [n = 5 swine]) or sham-injected (5) 24 hours before slaughter. In experiment 2, 12 growing and finishing swine were treated with LPS at 2 or 20 mu g/kg, IV (n = 3 swine/age group/treatment) 24 hours before slaughter. Hepatic DMEs, cytochrome P450 (CYP) isoforms, and CYP-mediated reactions were measured. Results-In experiment 1, LIPS administered at 20 mu g/kg decreased most hepatic DME components and inhibited enzymatic activities. In experiment 2, both doses reduced protein content in subcellular fractions and inhibited some DME- and CYP-mediated activities. In growing and finishing swine, CYP2A and CYP2B isoforms were not detected after treatment with LIPS; the CYP1A2 isoform was eliminated in growing but not in finishing swine. Lipopolysaccharide also reduced CYP2D6 content in growing and finishing swine but increased CYP2E content. Lipopolysaccharide had no effect on swine CYP2C11, CYP2C13, or CYP3A content. The CYP2B-mediated 7-pentoxyresorufin O-dealkylase activity in growing and finishing swine was totally eliminated, and 7-ethoxyresorufin (indicating CYP1A activity) and aniline (mediated by CYP2E) metabolism was decreased. Conclusions and Clinical Relevance-Effect of LIPS treatment on swine CYPs appeared to be isoform specific; age-related metabolic status of the swine and the LPS dose modified this effect. Lipopolysaccharide-induced inflammation may affect metabolism of drugs and xenobiotics in swine. (Am J Vet Res 2010;71:342-348) C1 [Myers, Michael J.; Farrell, Dorothy E.; Howard, Karyn D.; Kawalek, Joseph C.] US FDA, Div Anim Res, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. RP Myers, MJ (reprint author), US FDA, Div Anim Res, Res Off, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM michael.myers@fda.hhs.gov NR 30 TC 5 Z9 6 U1 0 U2 3 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0002-9645 J9 AM J VET RES JI Am. J. Vet. Res. PD MAR PY 2010 VL 71 IS 3 BP 342 EP 348 PG 7 WC Veterinary Sciences SC Veterinary Sciences GA 564KI UT WOS:000275212600012 PM 20187837 ER PT J AU Garber, EAE Perry, J AF Garber, Eric A. E. Perry, Jesse TI Detection of hazelnuts and almonds using commercial ELISA test kits SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE Almond. Hazelnut; ELISA; Food allergen; Foods/beverages; Immunoassays/ELISA; Bioanalytical methods ID TREE NUT ALLERGY; DIAL TELEPHONE SURVEY; CROSS-REACTIVITY; NATURAL-HISTORY; FOOD ALLERGENS; SANDWICH-ELISA; PCR METHOD; PEANUT; PROTEINS; TRACES AB Three commercial sandwich enzyme-linked immunosorbent assay (ELISA) test kits for the detection of hazelnuts and almonds were evaluated. Limits of detection and dynamic ranges were determined for hazelnuts and almonds spiked into cooked oatmeal, dipping chocolate, and muffins (baked). The limit of detection values varied from 1 to 38 mu g/g, depending on the food matrix and ELISA test kit. Percent recoveries based on the standards supplied with the test kits varied from 10% to 170%. It is impossible to ascertain whether the percent recoveries reflect the performance of the ELISAs or differences between the protein content of the nuts used to spike the samples and the test kit standards. Unfortunately, reference materials do not exist that can be used to compare the results from different test kits and standardize the test kit standards. Also, insufficient knowledge regarding the epitope specificity of the antibodies used in the ELISAs further hinders interpretation of the results generated by the different test kits. C1 [Garber, Eric A. E.; Perry, Jesse] US FDA, Div Bioanalyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Garber, EAE (reprint author), US FDA, Div Bioanalyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Eric.Garber@fda.hhs.gov NR 31 TC 16 Z9 16 U1 2 U2 22 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD MAR PY 2010 VL 396 IS 5 BP 1939 EP 1945 DI 10.1007/s00216-009-3424-2 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 558LD UT WOS:000274742900035 PM 20091297 ER PT J AU Rappaport, BA Cerny, I Sanhai, WR AF Rappaport, Bob A. Cerny, Igor Sanhai, Wendy R. TI ACTION on the Prevention of Chronic Pain after Surgery Public-Private Partnerships, the Future of Analgesic Drug Development SO ANESTHESIOLOGY LA English DT Editorial Material C1 [Rappaport, Bob A.; Cerny, Igor] US FDA, Div Anesthesia Analgesia & Rheumatol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Sanhai, Wendy R.] US FDA, Rockville, MD 20857 USA. RP Rappaport, BA (reprint author), US FDA, Div Anesthesia Analgesia & Rheumatol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM bob.rappaport@fda.hhs.gov NR 1 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAR PY 2010 VL 112 IS 3 BP 509 EP 510 DI 10.1097/ALN.0b013e3181cf4279 PG 2 WC Anesthesiology SC Anesthesiology GA 565CN UT WOS:000275266800001 PM 20124974 ER PT J AU Elkins, CA Mullis, LB Lacher, DW Jung, CM AF Elkins, Christopher A. Mullis, Lisa B. Lacher, David W. Jung, Carina M. TI Single Nucleotide Polymorphism Analysis of the Major Tripartite Multidrug Efflux Pump of Escherichia coli: Functional Conservation in Disparate Animal Reservoirs despite Exposure to Antimicrobial Chemotherapy SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ENTERICA SEROVAR TYPHIMURIUM; LARGE PERIPLASMIC LOOPS; SUBSTRATE-SPECIFICITY; PHYLOGENETIC NETWORKS; MEMBRANE PROTEINS; RESISTANCE; SALMONELLA; MUTATIONS; RECOMBINATION; TETRACYCLINE AB AcrAB-TolC imparts a strong intrinsic resistance phenotype to many clinically significant molecules in Escherichia coli. This complex is composed of a pump, AcrB, and a periplasmic protein, AcrA, that exports substrates through a common outer membrane porin, TolC. A sequence survey of the pump-specific components, acrA and acrB, was conducted on three discrete animal reservoirs: rodents, bovines, and catfish. Although two of the reservoirs (bovine and catfish) were agrarian, and antibiotic use (ceftiofur and oxytetracycline/Romet 30, respectively) was reported for them, the vast majority of structural polymorphisms were silent except for T104A (AcrA) and Q733R (AcrB), found in certain bovine-derived strains. Overall, the genes were well conserved, with high ratios of synonymous to nonsynonymous substitutions (d(S)/d(N) ratios), consistent with or, in the case of acrB, better than those of standard multilocus sequence typing (MLST) loci. Furthermore, predicted recombination points from single nucleotide polymorphism (SNP) patterns in acrB support a modular evolution of transporter proteins, consistent with an ancient origin. However, functional studies with clones representing the major silent SNPs and the nonsilent mutation in acrB failed to generate significant differences in resistance to a range of common efflux pump substrates. Interestingly, a comparison between log-phase acrA and acrB expression profiles yielded inconsistent trends, with acrB expression increasing modestly (<1.8-fold) in many strains from the antibiotic-enriched pools. Our results suggest that structural polymorphisms in this major efflux pump system may not contribute significantly to adaptive resistance by altering function or substrate specificity but may have a potential use in improving phylogenetic relationships and/or source tracking. C1 [Elkins, Christopher A.; Lacher, David W.] US FDA, Div Mol Biol, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Elkins, Christopher A.; Mullis, Lisa B.; Jung, Carina M.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Jung, Carina M.] USA, Engineer Res & Dev Ctr, Vicksburg, MS 39180 USA. RP Elkins, CA (reprint author), US FDA, Div Mol Biol, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM chris.elkins@fda.hhs.gov NR 35 TC 6 Z9 6 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAR PY 2010 VL 54 IS 3 BP 1007 EP 1015 DI 10.1128/AAC.01126-09 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 558HY UT WOS:000274733300006 PM 20038628 ER PT J AU Binet, R Bowlin, AK Maurelli, AT Rank, RG AF Binet, Rachel Bowlin, Anne K. Maurelli, Anthony T. Rank, Roger G. TI Impact of Azithromycin Resistance Mutations on the Virulence and Fitness of Chlamydia caviae in Guinea Pigs SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID 23S RIBOSOMAL-RNA; ANTIBIOTIC-RESISTANCE; MACROLIDE RESISTANCE; PSITTACI 6BC; TRACHOMATIS; COST; INFECTION; DIVERSITY; FREQUENCY; EFFICACY AB Azithromycin (AZM) is a major drug used in the treatment and prophylaxis of infections caused by Chlamydia, yet no significant clinical resistance has been reported for these obligate intracellular bacteria. Nevertheless, spontaneous AZM resistance (Azm(r)) arose in vitro at frequencies ranging from 3 x 10(-8) to 8 x 10(-10) for clonal isolates of Chlamydia caviae, which is a natural pathogen of guinea pigs. Sequencing of the unique 23S rRNA gene copy in 44 independent Azm(r) isolates identified single mutations at position A(2058) or A(2059) (Escherichia coli numbering system). While SP(6)AZ(1) (A(2058)C) and SP(6)AZ(2) (A(2059)C) Azm(r) mutants showed growth defects in cell culture and were less pathogenic in the guinea pig ocular infection model than in the parent SP(6), the three isogenic C. caviae isolates grew equally well in the animal. On the other hand, coinoculation of the C. caviae parent strain with one of the Azm(r) strains was detrimental for the mutant strain. This apparent lack of association between pathology and bacterial load in vivo showed that virulence of the two Azm(r) mutants of C. caviae was attenuated. While chlamydial growth in vitro reflects the ability of the bacteria to multiply in permissive cells, survival in the host is a balance between cellular multiplication and clearance by the host immune system. The obligate intracellular nature of Chlamydia may therefore limit emergence of resistance in vivo due to the strength of the immune response induced by the wild-type antibiotic-sensitive bacteria at the time of antibiotic treatment. C1 [Binet, Rachel; Maurelli, Anthony T.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. [Bowlin, Anne K.; Rank, Roger G.] Arkansas Childrens Hosp, Res Inst, Dept Microbiol & Immunol, Little Rock, AR 72205 USA. [Bowlin, Anne K.; Rank, Roger G.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. RP Binet, R (reprint author), US FDA, Off Regulatory Sci, HFS-711,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM rachel.binet@fda.hhs.gov FU National Institute of Allergy and Infectious Diseases, NIH [AI44033, AI59650] FX This work was supported by grants AI44033 (A. T. M.) and AI59650 (R. G. R.) from the National Institute of Allergy and Infectious Diseases, NIH. NR 36 TC 21 Z9 21 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAR PY 2010 VL 54 IS 3 BP 1094 EP 1101 DI 10.1128/AAC.01321-09 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 558HY UT WOS:000274733300017 PM 20065052 ER PT J AU Xia, XD Meng, JH McDermott, PF Ayers, S Blickenstaff, K Tran, TT Abbott, J Zheng, J Zhao, SH AF Xia, Xiaodong Meng, Jianghong McDermott, Patrick F. Ayers, Sherry Blickenstaff, Karen Tran, Thu-Thuy Abbott, Jason Zheng, Jie Zhao, Shaohua TI Presence and Characterization of Shiga Toxin-Producing Escherichia coli and Other Potentially Diarrheagenic E. coli Strains in Retail Meats SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID INTESTINAL MUCUS; VIRULENCE GENES; GROUND-BEEF; LISTERIA-MONOCYTOGENES; INTIMIN TYPES; SAO-PAULO; FOOD; PREVALENCE; HUMANS; SEROTYPES AB To determine the presence of Shiga toxin-producing Escherichia coli (STEC) and other potentially diarrheagenic E. coli strains in retail meats, 7,258 E. coli isolates collected by the U. S. National Antimicrobial Resistance Monitoring System (NARMS) retail meat program from 2002 to 2007 were screened for Shiga toxin genes. In addition, 1,275 of the E. coli isolates recovered in 2006 were examined for virulence genes specific for other diarrheagenic E. coli strains. Seventeen isolates (16 from ground beef and 1 from a pork chop) were positive for stx genes, including 5 positive for both stx(1) and stx(2), 2 positive for stx(1), and 10 positive for stx(2). The 17 STEC strains belonged to 10 serotypes: O83:H8, O8:H16, O15:H16, O15:H17, O88:H38, ONT:H51, ONT:H2, ONT:H10, ONT:H7, and ONT:H46. None of the STEC isolates contained eae, whereas seven carried enterohemorrhagic E. coli (EHEC) hlyA. All except one STEC isolate exhibited toxic effects on Vero cells. DNA sequence analysis showed that the stx(2) genes from five STEC isolates encoded mucus-activatable Stx2d. Subtyping of the 17 STEC isolates by pulsed-field gel electrophoresis (PFGE) yielded 14 distinct restriction patterns. Among the 1,275 isolates from 2006, 11 atypical enteropathogenic E. coli (EPEC) isolates were identified in addition to 3 STEC isolates. This study demonstrated that retail meats, mainly ground beef, were contaminated with diverse STEC strains. The presence of atypical EPEC strains in retail meat is also of concern due to their potential to cause human infections. C1 [Xia, Xiaodong; Meng, Jianghong; Zheng, Jie] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Meng, Jianghong] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. [McDermott, Patrick F.; Ayers, Sherry; Blickenstaff, Karen; Tran, Thu-Thuy; Abbott, Jason; Zhao, Shaohua] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [Zheng, Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Meng, JH (reprint author), Univ Maryland, Dept Nutr & Food Sci, 0112 Skinner Bldg, College Pk, MD 20742 USA. EM jmeng@umd.edu FU Joint Institute for Food Safety and Applied Nutrition (JIFSAN) of the University of Maryland; U.S. Food & Drug Administration FX This study was made possible by grants from the Joint Institute for Food Safety and Applied Nutrition (JIFSAN) of the University of Maryland and the U.S. Food & Drug Administration. NR 55 TC 29 Z9 34 U1 1 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD MAR PY 2010 VL 76 IS 6 BP 1709 EP 1717 DI 10.1128/AEM.01968-09 PG 9 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 564DQ UT WOS:000275193900001 PM 20080990 ER PT J AU Zhang, CX Sauder, C Malik, T Rubin, SA AF Zhang, Cheryl X. Sauder, Christian Malik, Tahir Rubin, Steven A. TI A mouse-based assay for the pre-clinical neurovirulence assessment of vaccinia virus-based smallpox vaccines SO BIOLOGICALS LA English DT Article DE Vaccine; Vaccinia; Smallpox; Neurovirulence; Mouse; Safety testing ID DRYVAX(R) CHALLENGE; VACCINATION; BIOTERRORISM; MONKEYPOX; EFFICACY; STRAINS; MICE; LINE; MVA AB Post-vaccinal encephalitis, although relatively uncommon, is a known adverse event associated with many live, attenuated smallpox vaccines. Although smallpox vaccination ceased globally in 1980, vaccine manufacture has resumed in response to concerns over the possible use of smallpox virus as an agent of bioterrorism. To better support the production of safer smallpox vaccines, we previously reported the development of a mouse model in which a relatively attenuated vaccine strain (Dryvax (R)) could be discerned from a more virulent laboratory strain (WR). Here we have further tested the performance of this assay by evaluating the neurovirulence of several vaccinia virus-based smallpox vaccines spanning a known range in neurovirulence for humans. Our data indicate that testing of 10-100 pfu of virus in mice following intracranial inoculation reliably assesses the virus's neurovirulence potential for humans. Published by Elsevier Ltd on behalf of The International Association for Biologicals. C1 [Zhang, Cheryl X.; Sauder, Christian; Malik, Tahir; Rubin, Steven A.] US FDA, Div Viral Prod, Bethesda, MD 20892 USA. RP Rubin, SA (reprint author), US FDA, Div Viral Prod, Bldg 29A,Room 2C-20,Lincoln Dr, Bethesda, MD 20892 USA. EM steven.rubin@fda.hhs.gov FU CBER/FDA - NIAID/NIH [Y1-AI-6153-01] FX This work was supported by CBER/FDA - NIAID/NIH Interagency Agreement Y1-AI-6153-01 and in part by an appointment to the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. The 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 33 TC 3 Z9 3 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD MAR PY 2010 VL 38 IS 2 BP 278 EP 283 DI 10.1016/j.biologicals.2009.09.007 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 597ZE UT WOS:000277800400016 PM 19896867 ER PT J AU Starlard-Davenport, A Tryndyak, VP James, SR Karpf, AR Latendresse, JR Beland, FA Pogribny, IP AF Starlard-Davenport, Athena Tryndyak, Volodymyr P. James, Smitha R. Karpf, Adam R. Latendresse, John R. Beland, Frederick A. Pogribny, Igor P. TI Mechanisms of epigenetic silencing of the Rassf1a gene during estrogen-induced breast carcinogenesis in ACI rats SO CARCINOGENESIS LA English DT Article ID DNA METHYLATION; CPG ISLAND; CANCER STATISTICS; TUMOR-SUPPRESSOR; CELL-LINES; HYPERMETHYLATION; HEPATOCARCINOGENESIS; METHYLTRANSFERASES; ASSOCIATION; REPRESSION AB Breast cancer, the most common malignancy in women, emerges through a multistep process, encompassing the progressive sequential evolution of morphologically distinct stages from a normal cell to hyperplasia (with and without atypia), carcinoma in situ, invasive carcinoma and metastasis. The success of treatment of breast cancer could be greatly improved by the detection at early stages of cancer. In the present study, we investigated the underlying molecular mechanisms involved in breast carcinogenesis in Augustus and Copenhagen-Irish female rats, a cross between the ACI strains, induced by continuous exposure to 17 beta-estradiol. The results of our study demonstrate that early stages of estrogen-induced breast carcinogenesis are characterized by altered global DNA methylation, aberrant expression of proteins responsible for the proper maintenance of DNA methylation pattern and epigenetic silencing of the critical Rassf1a (Ras-association domain family 1, isoform A) tumor suppressor gene. Interestingly, transcriptional repression of the Rassf1a gene in mammary glands during early stages of breast carcinogenesis was associated with an increase in trimethylation of histones H3 lysine 9 and H3 lysine 27 and de novo CpG island methylation and at the Rassf1a promoter and first exon. In conclusion, we demonstrate that epigenetic alterations precede formation of preneoplastic lesions indicating the significance of epigenetic events in induction of oncogenic pathways in early stages of carcinogenesis. C1 [Starlard-Davenport, Athena; Tryndyak, Volodymyr P.; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [James, Smitha R.; Karpf, Adam R.] Roswell Pk Canc Inst, Dept Pharmacol & Therapeut, Buffalo, NY 14263 USA. [Latendresse, John R.] Toxicol Pathol Associates, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov FU DA-National Center for Toxicological Research FX Intramural Research Program, FDA-National Center for Toxicological Research. NR 44 TC 15 Z9 15 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 2010 VL 31 IS 3 BP 376 EP 381 DI 10.1093/carcin/bgp304 PG 6 WC Oncology SC Oncology GA 564VE UT WOS:000275245200007 PM 20008439 ER PT J AU Fu, PP Chou, MW Churchwell, M Wang, YP Zhao, YW Xia, QS da Costa, GG Marques, MM Beland, FA Doerge, DR AF Fu, Peter P. Chou, Ming W. Churchwell, Mona Wang, Yuping Zhao, Yuewei Xia, Qingsu da Costa, Goncalo Gamboa Marques, M. Matilde Beland, Frederick A. Doerge, Daniel R. TI High-Performance Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry for the Detection and Quantitation of Pyrrolizidine Alkaloid-Derived DNA Adducts in Vitro and in Vivo SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID METABOLIC-ACTIVATION; DIETARY-SUPPLEMENTS; MEDICINAL-PLANTS; CROSS-LINKING; RIDDELLIINE; TOXICITY; DEHYDRORETRONECINE; TUMORIGENICITY; MONOCROTALINE; MECHANISMS AB Pyrrolizidine alkaloid-containing plants are widespread in the world and are probably the most common poisonous plants affecting livestock, wildlife, and humans. Pyrrolizidine alkaloids require metabolism to exert their genotoxicity and tumorigenicity. We have determined that the metabolism of a series of tumorigenic pyrrolizidine alkaloids in vitro or in vitro generates a common set of (+/-)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts that are responsible for tumor induction. The identification and quantitation of the DHP-derived DNA adducts formed in vivo and in vitro were accomplished previously by P-32-postlabeling/HPLC methodology. In this article, we report the development of a sensitive and specific liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ES-MS/MS) method to detect DFIP-derived DNA adducts formed in vitro and in vivo. The method is used to quantify the levels of DHP-2'-deoxyguanosine (dG) and DHP-2'-deoxyadenosine (dA) adducts by multiple reaction monitoring (MRM) analysis in the presence of known quantities of isotopically labeled DHP-dG and DHP-dA internal standards. This HPLC-ES-MS/MS method is accurate and precise. When applied to liver samples from rats treated with the pyrrolizidine alkaloids riddelliine and monocrotaline, the method provided significant new information regarding the mechanism of DNA adduct formation. C1 [Fu, Peter P.; Chou, Ming W.; Churchwell, Mona; Wang, Yuping; Zhao, Yuewei; Xia, Qingsu; da Costa, Goncalo Gamboa; Beland, Frederick A.; Doerge, Daniel R.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Marques, M. Matilde] Univ Tecn Lisboa, Inst Super Tecn, Ctr Quim Estrutural, P-1049001 Lisbon, Portugal. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM peter.fu@fda.hhs.gov RI Marques, M. Matilde/E-2535-2012; PTMS, RNEM/C-1589-2014 OI Marques, M. Matilde/0000-0002-7526-4962; FU U.S. Department of Energy; FDA FX We thank Dr. Po-Chuen Chan of NTP for supplying riddelhine and the NTP rat livers. This research was supported in part by appointments (Y.W. and Y.Z.) to the Postgraduate Research Program at the NCTR administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the FDA. This article is not an official U.S. Food anti Drug Administration (FDA) guidance or policy statement. No official support or endorsement by the U.S. FDA is intended or should be inferred. NR 51 TC 28 Z9 28 U1 1 U2 26 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAR PY 2010 VL 23 IS 3 BP 637 EP 652 DI 10.1021/tx900402x PG 16 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 566ZJ UT WOS:000275411700025 PM 20078085 ER PT J AU Abernethy, DR Burckart, GJ AF Abernethy, D. R. Burckart, G. J. TI Pediatric Dose Selection SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID PHARMACOKINETICS; CHILDREN; AGE AB Selection of a drug dose in pediatrics is generally based on no or incomplete pharmacokinetic data. Traditionally, allometric, or scaling, techniques have been used; however, they have inherent limitations and may not make optimal use of the drug-specific clinical pharmacokinetic information that is available. Modeling is a tool that holds promise. The future challenge is to create a structured approach to determining pediatric doses for new therapeutic agents. C1 [Abernethy, D. R.; Burckart, G. J.] US FDA, Off Clin Pharmacol, Silver Spring, MD USA. RP Abernethy, DR (reprint author), US FDA, Off Clin Pharmacol, Silver Spring, MD USA. EM darrell.abernethy@fda.hhs.gov NR 11 TC 18 Z9 18 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 MAR PY 2010 VL 87 IS 3 BP 270 EP 271 DI 10.1038/clpt.2009.292 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 564JP UT WOS:000275210500011 PM 20160747 ER PT J AU Burkhart, KK Szarfman, A Lyndly, J AF Burkhart, K. K. Szarfman, A. Lyndly, J. TI Drugs Associated with Hemorrhagic Pancreatitis in the Food and Drug Administration Adverse Event Database and Mitochondrial Toxicity SO CLINICAL TOXICOLOGY LA English DT Meeting Abstract C1 [Burkhart, K. K.; Szarfman, A.; Lyndly, J.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1556-3650 J9 CLIN TOXICOL JI Clin. Toxicol. PD MAR PY 2010 VL 48 IS 3 MA 238 BP 295 EP 296 PG 2 WC Toxicology SC Toxicology GA 584OO UT WOS:000276762200253 ER PT J AU Burkhart, KK Sundberg, L Nalluswami, K Marcus, S AF Burkhart, K. K. Sundberg, L. Nalluswami, K. Marcus, S. TI Acute Hemolysis Following the Extravasation of an Intravenous Phosphatidylcholine Product SO CLINICAL TOXICOLOGY LA English DT Meeting Abstract C1 [Burkhart, K. K.] US FDA, CDER, Silver Spring, MD USA. [Sundberg, L.; Nalluswami, K.] PaDOH, Bur Epidemiol, Harrisburg, PA USA. [Marcus, S.] UMDNJ, Dept Pediat, Newark, NJ USA. [Marcus, S.] UMDNJ, Dept Prevent Med & Community Hlth, Newark, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1556-3650 J9 CLIN TOXICOL JI Clin. Toxicol. PD MAR PY 2010 VL 48 IS 3 MA 325 BP 314 EP 314 PG 1 WC Toxicology SC Toxicology GA 584OO UT WOS:000276762200340 ER PT J AU Colatsky, TJ AF Colatsky, Thomas J. TI 'Impedance matching' of data sets in biomarker research SO CURRENT OPINION IN INVESTIGATIONAL DRUGS LA English DT Editorial Material ID SURROGATE END-POINTS AB The goal of biomarker research in drug development is to identify better ways of monitoring the effects of drugs on biological systems. Biomarker data are used to support decision making at various stages in the drug development process, and are also used to provide information on how drug use might be optimized in different patient populations. The evaluation and qualification of new safety biomarkers includes a rigorous analysis of the ability of a given biomarker to report specific pathological events at the cellular, tissue or systemic level. This evaluation often relies on the mapping of a continuous data set (eg, biomarker levels) onto discrete phenotypic descriptors (eg, pathology scores). The approach has been applied successfully to discover new and improved biomarkers of tissue injury, but may involve uncertainty when used to evaluate the ability of a biomarker to detect early events or events occurring near the threshold of drug action. Alternative approaches based on study endpoints that provide continuous descriptions of a disease state or drug action, coupled with measurements of changes in biological function, may provide a better 'impedance match' between input and output data in biomarker research, and improve the early assessment and prediction of drug safety issues. C1 US FDA, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Colatsky, TJ (reprint author), US FDA, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM Thomas.Colatsky@fda.hhs.gov NR 11 TC 0 Z9 0 U1 0 U2 1 PU THOMSON REUTERS (SCIENTIFIC) LTD PI LONDON PA 77 HATTON GARDEN, LONDON, EC1N 8JS, ENGLAND SN 1472-4472 J9 CURR OPIN INVEST DR JI Curr. Opin. Investig. Drugs PD MAR PY 2010 VL 11 IS 3 BP 262 EP 264 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 557FI UT WOS:000274654600001 PM 20178038 ER PT J AU Kennedy, D AF Kennedy, Donald TI The future of science news SO DAEDALUS LA English DT Article C1 [Kennedy, Donald] Medieval Acad Amer, Cambridge, MA 02138 USA. [Kennedy, Donald] Stanford Univ, Woods Inst Environm, Stanford, CA 94305 USA. [Kennedy, Donald] US FDA, Rockville, MD 20857 USA. RP Kennedy, D (reprint author), Medieval Acad Amer, 1430 Massachusetts Ave, Cambridge, MA 02138 USA. NR 5 TC 2 Z9 2 U1 0 U2 1 PU M I T PRESS PI CAMBRIDGE PA 238 MAIN STREET, STE 500, CAMBRIDGE, MA 02142-1046 USA SN 0011-5266 J9 DAEDALUS-US JI Daedalus PD SPR PY 2010 VL 139 IS 2 BP 57 EP 65 DI 10.1162/daed.2010.139.2.57 PG 9 WC Humanities, Multidisciplinary; Social Sciences, Interdisciplinary SC Arts & Humanities - Other Topics; Social Sciences - Other Topics GA 588WI UT WOS:000277104900007 ER PT J AU Sorbello, A Komo, S Valappil, T AF Sorbello, Alfred Komo, Scott Valappil, Thamban TI Noninferiority Margin for Clinical Trials of Antibacterial Drugs for Nosocomial Pneumonia SO DRUG INFORMATION JOURNAL LA English DT Article DE Noninferiority margin; All-cause mortality; Nosocomial pneumonia ID VENTILATOR-ASSOCIATED PNEUMONIA; INTENSIVE-CARE-UNIT; DOUBLE-BLIND; HOSPITALIZED-PATIENTS; ANTIBIOTIC-TREATMENT; IMIPENEM-CILASTATIN; OPEN-LABEL; MULTICENTER; PIPERACILLIN/TAZOBACTAM; THERAPY AB Noninferiority (NI) clinical trials have been used to assess antibacterial drug efficacy in treating nosocomial and ventilator-associated pneumonia. Previously published trials have employed prespecified NI margins of 15% or 20% based on clinical response or microbiological endpoints. However, as those studies do not describe the statistical and clinical considerations underpinning the margins selected, their scientific plausibility cannot be substantiated. In this report, a fixed NI margin of 7% with re-spect to all-cause mortality is determined based on the 29% cross-study difference between the two-sided 95% confidence intervals (CI) for the placebo estimate of 62% (95% Cl: 52%, 71%) and the active control estimate of 20% (95% CI: 18%, 23%) obtained from meta-analyses of various published clinical studies. After applying discounting, we estimated the active control treatment benefit to be 14%. Due to clinical concerns, 50% of the active control treatment benefit was preserved, yielding a 7% NI margin. C1 [Sorbello, Alfred] US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Off Antimicrobial Prod, Silver Spring, MD 20993 USA. [Komo, Scott; Valappil, Thamban] US FDA, Ctr Drug Evaluat & Res, Div Biometr 4, Silver Spring, MD 20993 USA. RP Sorbello, A (reprint author), US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Off Antimicrobial Prod, 10903 New Hampshire Averme, Silver Spring, MD 20993 USA. EM alfred.sorbello@fda.hhs.gov NR 36 TC 4 Z9 4 U1 0 U2 0 PU DRUG INFORMATION ASSOC PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD MAR PY 2010 VL 44 IS 2 BP 165 EP 176 PG 12 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 560GP UT WOS:000274890500008 ER PT J AU Dobrovolsky, VN Boctor, SY Twaddle, NC Doerge, DR Bishop, ME Manjanatha, MG Kimoto, T Miura, D Heflich, RH Ferguson, SA AF Dobrovolsky, Vasily N. Boctor, Sherin Y. Twaddle, Nathan C. Doerge, Daniel R. Bishop, Michelle E. Manjanatha, Mugimane G. Kimoto, Takafumi Miura, Daishiro Heflich, Robert H. Ferguson, Sherry A. TI Flow Cytometric Detection of Pig-A Mutant Red Blood Cells Using an Erythroid-Specific Antibody: Application of the Method for Evaluating the In Vivo Genotoxicity of Methylphenidate in Adolescent Rats SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE HIS49; Sprague-Dawley rats; N-ethyl-N-nitrosourea; micronucleus; glycosyl phosphotidylinositol anchor; ritalinic acid ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; CHILDREN; HYDROCHLORIDE; SINGLE; ASSAY; PHARMACOKINETICS; PERSISTENCE; DAMAGE AB A modified flow cytometry assay for Pig-A mutant rat red blood cells (RBCs) was developed using an antibody that positively identifies rat RBCs (monoclonal antibody HIS49). The assay was used in conjunction with a flow cytometric micronucleus (MN) assay to evaluate gene mutation and clastogenicity/aneugenicity in adolescent male and female rats treated with methylphenidate hydrochloride (MPH). Sprague-Dawley rats were treated orally with 3 mg/kg MPH (70/sex) or water (40/sex) 3 X /day on postnatal days (PNDs) 29-50. Eight additional rats (4/sex) were injected i.p. with N-ethyl-N-nitrosourea (ENU) on PND 28. Blood was collected on PNDs 29, 50, and 90, and used for determining serum MPH levels and/or conducting genotoxicity assays. On the first and lost days of MPH treatment (PNDs 29 and 50), serum MPH levels averaged 2 1 pg/mu l, well within the clinical treatment range. Relative to our previously published method (Miura et al. [2008]; Environ Mal Mutagen 49: 614-629), the HIS49 Pig-A mutation assay significantly reduced the background RBC mutant frequency; in the experiments with ENU-treated rats, the modification increased the overall sensitivity of the assay 2-3 fold. Even with the increased assay sensitivity, the 21 consecutive days of MPH treatment produced no evidence of Pig-A mutation induction (measured at PND 90); in addition, MPH treatment did not increase MN frequency (measured at PND 50). These results support the consensus view that the genotoxicity of MPH in pediatric patients reported earlier (El-Zein et al. [2005]: Cancer Lett 230: 284-291) cannot be reproduced in animal models, suggesting that MPH at clinically relevant levels may be nongenotoxic in humans. Environ. Mol. Mutagen. 51:138-145, 2010. Published 2009 by Wiley-Liss, Inc.(dagger) C1 [Dobrovolsky, Vasily N.; Bishop, Michelle E.; Manjanatha, Mugimane G.; Heflich, Robert H.] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Boctor, Sherin Y.; Ferguson, Sherry A.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Boctor, Sherin Y.; Ferguson, Sherry A.] Univ Arkansas Med Sci, Dept Interdisciplinary Biomed Sci, Little Rock, AR 72205 USA. [Twaddle, Nathan C.; Doerge, Daniel R.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Kimoto, Takafumi; Miura, Daishiro] Teijin Pharma Ltd, Tokyo 1918512, Japan. RP Dobrovolsky, VN (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM Vasily.Dobrovolsky@fda.hhs.gov FU Dr. Suzanne Morris, Division of Genetic and Reproductive Toxicology, NCTR; Oak Ridge Institute for Science and Education FX The authors gratefully acknowledge the assistance and support of Dr. Suzanne Morris, Division of Genetic and Reproductive Toxicology, NCTR. The skillful expertise of the animal care technicians of the Bionetics Corporation, especially Lee McVay, are very much appreciated. Sherin Y. Boctor was Supported by a predoctoral fellowship from the Oak Ridge Institute for Science and Education. NR 22 TC 25 Z9 27 U1 0 U2 2 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 MAR PY 2010 VL 51 IS 2 BP 138 EP 145 DI 10.1002/em.20519 PG 8 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 555HA UT WOS:000274498400005 PM 19658152 ER PT J AU Meng, FX Knapp, GW Green, T Ross, JA Parsons, BL AF Meng, Fanxue Knapp, Geremy W. Green, Terry Ross, Jeffrey A. Parsons, Barbara L. TI K-Ras Mutant Fraction in A/J Mouse Lung Increases as a Function of Benzo[a]pyrene Dose SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE allele-specific competitive blacker PCR; risk assessment; mutation; lung cancer; B[a]P DNA adduct; K-Ras, mutant fraction; lung; carcinogenesis; A/J mouse ID POLYCYCLIC AROMATIC-HYDROCARBONS; EPOXIDE-DNA ADDUCTS; DIOL-EPOXIDE; ONCOGENE MUTATIONS; TP53 MUTATIONS; MICE; ACTIVATION; TUMORS; P53; ADENOCARCINOMA AB K-Ras mutant fraction (MF) was measured to examine the default assumption of low-dose linearity in the benzo[a]pyrene (B[a]P) mutational response. Groups of 10 male AA mice (7- to 9-weeks old) received a single i.p. injection of 0, 0.05, 0.5, 5, or 50 mg/kg B[a]P and were sacrificed 28 days after treatment. K-Ras codon 12 TGT and GAT MFs in lung DNAs were measured using Allele-specific Competitive Blocker-PCR (ACB-PCR). The K-Ras codon 12 TGT geometric mean MF was 3.88 x 10(-4) in controls, indicating an average of 1 mutation in every similar to 1,288 lung cells. The K-Ras codon 12 TGT geometric mean MFs were as follows: 3.56 x 10(-4); 6.19 x 10(-4); 2.02 x 10(-3), and 3.50 x 10(-3) for the 0.05, 0.5, 5, and 50 mg/kg B[a]P treatment groups, respectively. The 5 and 50 mg/kg dose groups had TGT MFs significantly higher than did controls. Although 10(-5) is considered as the limit of accurate ACB-PCR quantitation, K-Ras codon 12 GAT geometric mean MFs were as follows: 8.38 x 10(-7), 1.47 x 10(-6), 2.19 x 10(-6), 571 x 10(-6), and 8.99 x 10(-6) for the 0, 0.05, 0.5, 5, and 50 mg/kg B[a]P treatment groups, respectively. The K-Ras TGT and GAT MFs increased in a B[a]P-dose-dependent manner, with response approximately linear over the 0.05 to 5 mg/kg dose range. K-Ras MF increased with B[a]P adduct burden measured for identical doses in a separate study. Thus, ACB-PCR may be useful in characterizing the shape of a dose-response curve at low doses and establishing relationships between DNA adducts and tumor-associated mutations. Environ. Mal. Mutagen. 51:146-155, 2010. Published 2009 Wiley-Liss, Inc.(dagger) C1 [Meng, Fanxue; Parsons, Barbara L.] Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Knapp, Geremy W.; Green, Terry; Ross, Jeffrey A.] US EPA, Natl Hlth & Environm Effects Res Lab, Div Environm Carcinogenesis, Res Triangle Pk, NC 27711 USA. RP Meng, FX (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM fanxue.meng@fda.hhs.gov RI Ross, Jeffrey/E-4782-2010 OI Ross, Jeffrey/0000-0002-7002-4548 NR 40 TC 11 Z9 11 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 MAR PY 2010 VL 51 IS 2 BP 146 EP 155 DI 10.1002/em.20513 PG 10 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 555HA UT WOS:000274498400006 PM 19658153 ER PT J AU Chen, T Heflich, RH Moore, MM Mei, N AF Chen, Tao Heflich, Robert H. Moore, Martha M. Mei, Nan TI Differential Mutagenicity of Aflatoxin B-1 in the Liver of Neonatal and Adult Mice SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE aflatoxin B-1; neonate; mutagenicity; mutation; glutathione 5-transferase ID N-NITROSOUREA ENU; RAT-LIVER; TRANSGENIC MICE; DNA-ADDUCTS; P53 GENE; HEPATOCELLULAR-CARCINOMA; MUTATIONS; INVIVO; MOUSE; 4-AMINOBIPHENYL AB Children are generally more sensitive to toxicants than adults, including an increased sensitivity to genotoxic carcinogens. We previously demonstrated that neonatal mice are also more sensitive to the mutagenic effects of the direct alkylating agents N-ethyl-N-nitrosoamine and the arylamine 4-aminobiphenyl than adult mice. In this study, we have evaluated the effect of age on the mutagenicity of the fungal toxin and liver carcinogen aflatoxin B-1 (AFB(1)). Neonatal Big Blue transgenic mice were treated with 6 mg/kg AFB(1), a treatment that produces liver tumors, while adult mice were treated with 6 and 60 mg/kg AFB(1), treatments that do not result in tumors. The c// liver mutant frequency IMF) in mice treated with AFB(1) as neonates was 22-fold higher than in control neonatal mice, whereas the treatment of adult mice with either dose of AFB(1) did not significantly increase the liver MF over the controls. In AFB(1)-treated neonatal mice, the frequency of G:C -> T:A transversion, a major type of mutation induced by AFB(1), was about 82-fold higher than for the control and 31-fold higher than for adult mice treated with 60 mg/kg AFB(1). Our mutagenicity findings parallel the relative carcinogenicity of AFB(1) in neonatal and adult mice, and are consistent with previous observations of the lower level of hepatic glutathione S-transferase and higher level of hepatic AFB(1)-DNA adduction in neonatal mice compared to adult mice. Environ. Mal. Mutagen. 51:156-163, 2010. Published 2009 by Wiley-Liss, Inc.(dagger) C1 [Chen, Tao; Heflich, Robert H.; Moore, Martha M.; Mei, Nan] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Chen, T (reprint author), HFT-130,3900 NCTR Rd, Jefferson, AR 72079 USA. EM tao.chen@fda.hhs.gov RI mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 NR 37 TC 7 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD MAR PY 2010 VL 51 IS 2 BP 156 EP 163 DI 10.1002/em.20518 PG 8 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 555HA UT WOS:000274498400007 PM 19642212 ER PT J AU Kisby, GE Kohama, SG Olivas, A Churchwell, M Doerge, D Spangler, E de Cabo, R Ingram, DK Imhof, B Bao, GB Kow, YW AF Kisby, Glen E. Kohama, Steven G. Olivas, Antoinette Churchwell, Mona Doerge, Daniel Spangler, Edward de Cabo, Rafael Ingram, Donald K. Imhof, Barry Bao, Gaobin Kow, Yoke W. TI Effect of caloric restriction on base-excision repair (BER) in the aging rat brain SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE Exonuclease; Apyrimidinic/apurinic endonuclease (APE); DNA polymerase beta; DNA ligase III; Frontal/parietal cortex; 8-Oxodeoxyguanosine ID OXIDATIVE DNA-DAMAGE; SENESCENCE-ACCELERATED MICE; ALZHEIMERS-DISEASE; DIETARY RESTRICTION; MITOCHONDRIAL-DNA; GENOMIC STABILITY; AGE; STRESS; MOUSE; ENDONUCLEASE AB Apyrimidinic/apurinic endonuclease (APE) is a key protein involved in the base-excision DNA repair (BER) pathway of oxidative DNA lesions. Using a novel oligonucleotide substrate, we demonstrate that APE activity in the frontal/parietal cortex (F/PCTX), cerebellum, brainstem, midbrain and hypothalamus declined with age in rats on an ad libitum (AL) diet. In contrast, APE activity for these brain regions was similar to 1.5-3 times higher in young, caloric restricted (CR) rats. Despite continuous CR treatment in all animals since six weeks of age, APE activity in the CR group started to decline by middle-age and continued into old age. However, CR maintained APE activity at a level that was significantly higher than that in AL rats across age and in the brain regions examined. Because Western analysis of APE, DNA polymerase 0 and DNA ligase III levels in the F/PCTX of both CR and AL rats remained unchanged with age, this suggests that the increased APE activity in CR rats is the result of differential post-translational modification of APE. (C) 2009 Elsevier Inc. All rights reserved. C1 [Kisby, Glen E.; Olivas, Antoinette] Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97239 USA. [Kohama, Steven G.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Portland, OR 97239 USA. [Churchwell, Mona; Doerge, Daniel] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Spangler, Edward; de Cabo, Rafael; Ingram, Donald K.] NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. [Imhof, Barry; Bao, Gaobin; Kow, Yoke W.] Emory Univ, Sch Med, Dept Radiat Oncol, Atlanta, GA 30322 USA. RP Kisby, GE (reprint author), Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM kisby@ohsu.edu RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 FU NIH [CA90860]; NIEHS [PO1 ES011163, RR00163, DAMD 17-98-1-8625] FX We thank Dr. Vilhelm Bohr for his valuable comments on the manuscript. This work is supported by NIH CA90860 (YWK), NIEHS PO1 ES011163 (YWK), RR00163 (SGK) and DAMD 17-98-1-8625 (GK). NR 48 TC 10 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD MAR PY 2010 VL 45 IS 3 BP 208 EP 216 DI 10.1016/j.exger.2009.12.003 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 574KD UT WOS:000275987100007 PM 20005284 ER PT J AU Hildebrandt, S Garber, EAE AF Hildebrandt, Sabine Garber, Eric A. E. TI Effects of processing on detection and quantification of the parvalbumin gene in Atlantic salmon (Salmo salar) SO FOOD CHEMISTRY LA English DT Article DE Parvalbumin; Salmon; PCR; Baking; Processing; Pressure cooking ID CROSS-REACTIVITY; EXTRACTION METHODS; DNA-DEGRADATION; FISH ALLERGY; FOOD; CODFISH; PROTEINS; BINDING; INVIVO; ADULTS AB Consumption of Atlantic salmon is a common cause of fish allergies with parvalbumin (Sal s1) being the major allergen. The presence of DNA encoding Sal s1 indicates the presence of Atlantic salmon in food. Using real-time polymerase chain reaction (PCR), the effects of food processing on the ability to detect and quantify the Sal s1 gene were determined. The method was specific for salmon and did not cross-react with 53 other species. Baking and pressure cooking caused a 5-100-fold decrease in detectable copies of the Sal s1 gene. Despite a 98% reduction in detectable copies following pressure cooking for 60 min, the relative standard deviation (RSD) between replicates was 20% and the response was 100-fold grater than the lowest copy number of Sal s1 reliably detected by the assay. Despite efforts to develop a quantitative assay, the PCR assay was qualitative. It is impossible to predict the effects of food matrices not included in this study, some of which may affect the reliability of the assay. Analyses of raw and pressure cooked salmon using a commercial PCR kit indicated comparable results to the PCR assay. Published by Elsevier Ltd. C1 [Hildebrandt, Sabine; Garber, Eric A. E.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, Div Bioanalyt Chem, College Pk, MD 20740 USA. RP Garber, EAE (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, Div Bioanalyt Chem, HFS 716,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Eric.Garber@fda.hhs.gov NR 26 TC 10 Z9 10 U1 4 U2 17 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 MAR 1 PY 2010 VL 119 IS 1 BP 75 EP 80 DI 10.1016/j.foodchem.2009.05.074 PG 6 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA 520CS UT WOS:000271818200012 ER PT J AU Miller, HI AF Miller, Henry I. TI Tempering Regulation with Common Sense SO GENETIC ENGINEERING & BIOTECHNOLOGY NEWS LA English DT Editorial Material C1 Stanford Univ, Hoover Inst, Stanford, CA 94305 USA. [Miller, Henry I.] NIH, Bethesda, MD USA. [Miller, Henry I.] US FDA, Rockville, MD 20857 USA. RP Miller, HI (reprint author), Stanford Univ, Hoover Inst, Stanford, CA 94305 USA. EM henry.miller@stanford.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1935-472X J9 GENET ENG BIOTECHN N JI Genet. Eng. Biotechnol. News PD MAR 1 PY 2010 VL 30 IS 5 BP 6 EP 7 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 668LF UT WOS:000283270000003 ER PT J AU Spelic, DC Kaczmarek, RV Hilohi, MC Moyal, AE AF Spelic, David C. Kaczmarek, Richard V. Hilohi, Mike C. Moyal, Albert E. TI NATIONWIDE SURVEYS OF CHEST, ABDOMEN, LUMBOSACRAL SPINE RADIOGRAPHY, AND UPPER GASTROINTESTINAL FLUOROSCOPY: A SUMMARY OF FINDINGS SO HEALTH PHYSICS LA English DT Article DE dose, population; medical radiation; surveys; x rays ID DIAGNOSTIC-RADIOLOGY; ATTENUATION PHANTOM; EXPOSURE; QUALITY; VALUES AB This paper reports findings from Nationwide Evaluation of X-ray Trends surveys conducted in 2001, 2002, and 2003 of clinical facilities that perform routine radiographic examinations of the adult chest, abdomen, lumbosacral spine, and upper gastrointestinal fluoroscopic examinations. Randomly identified clinical facilities were surveyed in approximately 40 participating states. For the surveyed radiographic exams, additional facilities that use computed radiography or digital radiography were surveyed to ensure adequate sample sizes for determining comparative statistics. State radiation control personnel performed site visits and collected data on patient exposure, radiographic/fluoroscopic technique factors, image quality, and quality-control and quality-assurance practices. Results of the NEXT surveys are compared with those of previous surveys conducted in 1964 and 1970 by the U.S. Public Health Service and the Food and Drug Administration. An estimated 155 million routine adult chest exams were performed in 2001. Average patient entrance skin air kerma from chest radiography at facilities using digital-based imaging modalities was found to be significantly higher (p < 0.001), but not so for routine abdomen or lumbosacral spine radiography. Digital-based imaging showed a substantial reduction in patient exposure for the radiographic portion of the routine upper gastrointestinal fluoroscopy exam. Long-term trends in surveyed diagnostic examinations show that average patient exposures are at their lowest levels. Of concern is the observation that a substantial fraction of surveyed non-hospital sites indicated they do not regularly have a medical physics survey conducted on their radiographic equipment. These facilities are likely unaware of the radiation doses they administer to their patients. Health Phys. 98(3):498-514; 2010 C1 [Spelic, David C.; Kaczmarek, Richard V.; Hilohi, Mike C.; Moyal, Albert E.] US FDA, Div Mammog Qual & Radiat Programs, Silver Spring, MD 20993 USA. [Hilohi, Mike C.] Global N Amer, Crofton, MD 21114 USA. RP Spelic, DC (reprint author), US FDA, Div Mammog Qual & Radiat Programs, 10903 New Hampshire Ave W066-4524, Silver Spring, MD 20993 USA. EM david.spelic@fda.hhs.gov NR 34 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD MAR PY 2010 VL 98 IS 3 BP 498 EP 514 DI 10.1097/HP.0b013e3181c182cd PG 17 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 555IJ UT WOS:000274502500005 PM 20147791 ER PT J AU Weininger, S Kapur, KC Pecht, M AF Weininger, Sandy Kapur, Kailash C. Pecht, Michael TI Exploring Medical Device Reliability and Its Relationship to Safety and Effectiveness SO IEEE TRANSACTIONS ON COMPONENTS AND PACKAGING TECHNOLOGIES LA English DT Article DE medical device; reliability; safety; effectiveness; design for reliability AB It may seem intuitive that reliability is essential for modern products that need to be safe and effective, particularly healthcare and medical devices. One would expect to find reliability cited in regulations, engineering articles, and consensus standards. Yet typical industrial processes in which high reliability is needed often do not explicitly provide evidence to support a safety and effectiveness (S&E) argument. The lack of a consistent and standardized framework for achieving reliability that is tied explicitly to safety and effectiveness undermines S&E evaluation. Regulators and manufacturers who are unable to take full advantage of the information generated by the reliability engineering processes fail to maximize product S&E. This paper explores a reliability engineering framework to provide the arguments, claims, and evidence important to product S&E, and the artifacts suitable for integrating reliability into S&E assessments. C1 [Weininger, Sandy] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Kapur, Kailash C.] Univ Washington, Dept Ind & Syst Engn, Seattle, WA 98195 USA. [Pecht, Michael] City Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. [Pecht, Michael] Univ Maryland, CALCE, College Pk, MD 20742 USA. RP Weininger, S (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. OI Pecht, Michael/0000-0003-1126-8662 NR 5 TC 4 Z9 4 U1 1 U2 9 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1521-3331 J9 IEEE T COMPON PACK T JI IEEE Trans. Compon. Packaging Technol. PD MAR PY 2010 VL 33 IS 1 BP 240 EP 245 DI 10.1109/TCAPT.2010.2044093 PG 6 WC Engineering, Manufacturing; Engineering, Electrical & Electronic; Materials Science, Multidisciplinary SC Engineering; Materials Science GA 568XR UT WOS:000275560000027 ER PT J AU Gubernot, D Lee, KC Conley, GB Holness, LG O'Callaghan, S Cannon, S Cowan, E Nakhasi, H Wise, RP AF Gubernot, D. Lee, K. C. Conley, G. B. Holness, L. G. O'Callaghan, S. Cannon, S. Cowan, E. Nakhasi, H. Wise, R. P. TI Transfusion-associated Babesia infections: Reports received by the FDA 1997 to 2008 SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 [Gubernot, D.; Lee, K. C.; Conley, G. B.; Holness, L. G.; O'Callaghan, S.; Cannon, S.; Cowan, E.; Nakhasi, H.; Wise, R. P.] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD MAR PY 2010 VL 14 SU 1 BP E113 EP E114 DI 10.1016/j.ijid.2010.02.1737 PG 2 WC Infectious Diseases SC Infectious Diseases GA 578MQ UT WOS:000276298200258 ER PT J AU Uhlenhaut, C McClenahan, SD Sosnovtsev, S Bok, K Kapikian, AZ Green, KY Krause, PR AF Uhlenhaut, C. McClenahan, S. D. Sosnovtsev, S. Bok, K. Kapikian, A. Z. Green, K. Y. Krause, P. R. TI Enteric virus detection and identification with a universal virus discovery assay SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 [Uhlenhaut, C.; McClenahan, S. D.; Krause, P. R.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Sosnovtsev, S.; Bok, K.; Kapikian, A. Z.] NIH, Bethesda, MD 20892 USA. [Green, K. Y.] NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD MAR PY 2010 VL 14 SU 1 BP E188 EP E189 DI 10.1016/j.ijid.2010.02.1907 PG 2 WC Infectious Diseases SC Infectious Diseases GA 578MQ UT WOS:000276298200425 ER PT J AU Iarikov, DE Irizarry-Acosta, M Martorell, C Rauch, CA Hoffman, RP Skiest, DJ AF Iarikov, Dmitri E. Irizarry-Acosta, Melina Martorell, Claudia Rauch, Carol A. Hoffman, Robert P. Skiest, Daniel J. TI Use of HIV Resistance Testing After Prolonged Treatment Interruption SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV-1 genotypic resistance testing; resistance testing in treatment-experienced patients; persistence of resistance mutations ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL COMBINATION THERAPY; REVERSE-TRANSCRIPTASE INHIBITORS; DRUG-RESISTANCE; IMMUNOLOGICAL CONSEQUENCES; PROTEASE INHIBITORS; PERSISTENCE; MUTATIONS; INFECTION; ADULTS AB Background: HIV-1 genotypic resistance testing is not routinely recommended for patients who have been off antiretroviral therapy (ART) for longer than 4 weeks. We assessed the results and use of resistance testing in patients off ART. Methods: All HIV resistance genotypes from November 2003 through April 2008 were reviewed from one large teaching hospital and two private HIV practices. Inclusion criterion was having a genotypic resistance test after an ART interruption of at least 2 months. Medical records were reviewed using a standardized data collection sheet. Results: Sixty-two of 304 treatment-experienced patients with HIV genotypes met the inclusion criteria. Prior cumulative ART class exposure included nucleoside reverse transcriptase inhibitors in 54 patients, nonnucleoside reverse transcriptase inhibitors in 32 patients, and protease inhibitors in 30 patients. Resistance testing was performed at a mean of 12 months (range, 2.5-48 months) after ART interruption. The mean time between ART interruption and resistance testing did not differ for patients with mutations and those without mutations detected. Seventeen of 62 (27.4%) patients were found to have resistance mutations. Eleven patients were found to have mutations to nonnucleoside reverse transcriptase inhibitors, four patients had mutations to nucleoside reverse transcriptase inhibitors, and two patients had protease inhibitor-associated mutations. No patient had multiclass resistance. Among the 17 patients with mutations after treatment interruption, 15 had mutations that were either not present on a prior genotype (n = 2) or did not have a prior genotype (n = 13). Conclusions: HIV genotypic resistance assays may identify mutations even when performed after a prolonged treatment interruption and may offer clinically significant information. Current guidelines that discourage resistance testing after treatment interruptions of longer than 4 weeks should be re-evaluated. C1 [Iarikov, Dmitri E.; Skiest, Daniel J.] Tufts Univ, Sch Med, Div Infect Dis, Springfield, MA 01199 USA. [Irizarry-Acosta, Melina] Tufts Univ, Sch Med, Dept Med, Springfield, MA 01199 USA. [Rauch, Carol A.] Tufts Univ, Sch Med, Dept Pathol, Baystate Med Ctr, Springfield, MA 01199 USA. [Martorell, Claudia] Res Inst, Springfield, MA USA. [Hoffman, Robert P.] Mercy Med Ctr, Springfield, MA USA. RP Iarikov, DE (reprint author), US FDA, 10903 New Hampshire Ave,Bldg 22,Room 6211, Silver Spring, MD 20993 USA. EM Dmitri.Iarikov@fda.hhs.gov NR 23 TC 4 Z9 4 U1 0 U2 1 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 MAR 1 PY 2010 VL 53 IS 3 BP 333 EP 337 DI 10.1097/QAI.0b013e3181c79ab0 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 565VX UT WOS:000275324500007 PM 20009764 ER PT J AU Boyle, T Njoroge, JM Jones, RL Principato, M AF Boyle, Thomas Njoroge, Joyce M. Jones, Robert L., Jr. Principato, Maryann TI Detection of Staphylococcal Enterotoxin B in Milk and Milk Products Using Immunodiagnostic Lateral Flow Devices SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID CLASS-II MOLECULES; BIOLOGICAL-PROPERTIES; TOXIN SUPERANTIGENS; YOGURT PRODUCTION; FOOD; AUREUS; OUTBREAK; IMMUNOASSAY; STIMULATION; INTERACT AB Staphylococcal enterotoxin B (SEB) is an extracellular pyrotoxin produced by Staphylococcus aureus, a known etiologic agent of food poisoning in humans. Lateral flow immunochromatographic devices (LFDs) designed for the environmental detection of SEB were adapted for use in this study to detect SEB in milk containing 2% fat, chocolate-flavored milk, and milk-derived products such as yogurt, infant formula, and ice cream. The advantage of using LFDs in these particular food products was its ease and speed of use with no additional extraction methods needed. No false positives were observed with any of the products used in this study. Dilution of the samples overcame the Hook effect and permitted capillary flow into the membrane. Thus, semisolid products such as ice cream and some yogurts, and products containing thickeners needed to be diluted using a phosphate-buffered saline-based buffer, pH 7.2. SEB was easily detected at concentrations of 5 mu g/mL and 500 ng/mL when the LFDs were used. SEB was also reliably detected at concentrations below 5 and 0.25 ng/mL, which may induce serious disease. C1 [Boyle, Thomas; Njoroge, Joyce M.; Jones, Robert L., Jr.; Principato, Maryann] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Principato, M (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM MaryAnn.Principato@fda.hhs.gov NR 40 TC 9 Z9 9 U1 0 U2 2 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2010 VL 93 IS 2 BP 569 EP 575 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 589FR UT WOS:000277132800027 PM 20480905 ER PT J AU Anderson, DL AF Anderson, David L. TI Analysis of Beverages for Hg, As, Pb, and Cd with a Field Portable X-Ray Fluorescence Analyzer SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MULTIELEMENT ANALYSIS; SPECTROMETER; PRODUCTS; ELEMENTS; XRF AB Analytical capabilities of a handheld X-ray tube analyzer for analysis of beverages were evaluated. Sets of standard solutions for the elements Hg, As, Pb, and Cd were prepared with mass fractions up to 5000 mg/kg. A thirst quencher beverage was spiked with these elements up to mass fractions of 2500 mg/kg. Portions of these solutions were placed in standard X-ray fluorescence (XRF) cells, as well as the original container, and analyzed by using a field portable Innov-X alpha-6000s XRF tube-type analyzer. Uncorrected analyzer output usually yielded qualitative or semiquantitative results for the spiked beverages in X-ray cells. Average correction factors applied to analyzer output yielded accurate (in terms of z-scores) quantitative results for As above 20 mg/kg and qualitative or semiquantitative results for the other elements. Weighted quadratic fit calibrations provided accurate quantitative or semiquantitative results for all elements at levels above 20 mg/kg. The instrument's preset X-ray overlap correction algorithm worked well for the beverage spiked with all four elements. Spiked beverages analyzed through the wall of the original polyethylene terephthalate container produced accurate results within measurement uncertainties after application of "container wall" correction factors. C1 US FDA, Ctr Food Safety & Appl Nutr, Chem Contaminants Branch, College Pk, MD 20740 USA. RP Anderson, DL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Chem Contaminants Branch, HFS 716,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM david.anderson@fda.hhs.gov NR 17 TC 7 Z9 8 U1 3 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 MAR-APR PY 2010 VL 93 IS 2 BP 683 EP 693 PG 11 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 589FR UT WOS:000277132800038 PM 20480916 ER PT J AU Wang, JY Chen, T AF Wang, Jianyong Chen, Tao TI Sequencing analysis of mutations induced by N-ethyl-N-nitrosourea at different sampling times in mouse bone marrow SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE Big Blue transgenic mice; N-ethyl-N-nitrosourea; transgenic mutation assay; bone marrow; mutation frequency; mutation spectrum ID LACI TRANSGENIC MICE; EXPOSED IN-VIVO; MUTANT FREQUENCIES; HPRT GENE; MOLECULAR CHARACTERISTICS; GERM-CELLS; SPECTRA; DNA; ETHYLNITROSOUREA; REPAIR AB In our previous study (Wang et al., 2004, Toxicol. Sci. 82: 124-128), we observed that the cll gene mutant frequency (MF) in the bone marrow of Big Blue mice showed significant increase as early as day 1, reached the maximum at day 3 and then decreased to a plateau by day 15 after a single dose of carcinogen N-ethyl-N-nitrosourea (ENU) treatment, which is different from the longer mutation manifestation time and the constancy of MFs after reaching their maximum in some other tissues. To determine the mechanism underlying the quick increase in MF and the peak formation in the mutant manifestation, we examined the mutation frequencies and spectra of the ENU-induced mutants collected from different sampling times in this study. The cll mutants from days 1, 3 and 120 after ENU treatment were randomly selected from different animals. The mutation frequencies were 33, 217, 305 and 144 x 10(-6) for control, days 1, 3, and 120, respectively. The mutation spectra at days 1 and 3 were significantly different from that at day 120. Considering that stem cells are responsible for the ultimate MF plateau (day 120) and transit cells are accountable for the earlier MF induction (days 1 or 3) in mouse bone marrow, we conclude that transit cells are much more sensitive to mutation induction than stem cells in mouse bone marrow, which resulted in the specific mutation manifestation induced by ENU. Published in 2009 by John Wiley & Sons, Ltd. C1 [Wang, Jianyong; Chen, Tao] US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Chen, T (reprint author), US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, HFT-130,3900 NCTR Rd, Jefferson, AR 72079 USA. EM tao.chen@fda.hhs.gov NR 44 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD MAR PY 2010 VL 30 IS 2 BP 133 EP 141 DI 10.1002/jat.1479 PG 9 WC Toxicology SC Toxicology GA 568JW UT WOS:000275519600005 PM 19764070 ER PT J AU Espandiari, P Rosenzweig, B Zhang, J Zhou, Y Schnackenberg, L Vaidya, VS Goering, PL Brown, RP Bonventre, JV Mahjoob, K Holland, RD Beger, RD Thompson, K Hanig, J Sadrieh, N AF Espandiari, P. Rosenzweig, B. Zhang, J. Zhou, Y. Schnackenberg, L. Vaidya, V. S. Goering, P. L. Brown, R. P. Bonventre, J. V. Mahjoob, K. Holland, R. D. Beger, R. D. Thompson, K. Hanig, J. Sadrieh, N. TI Age-related differences in susceptibility to cisplatin-induced renal toxicity SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE cisplatin; age-related nephrotoxicity; biomarkers; Kim-1; metabonomics ID ADVERSE DRUG-REACTIONS; KIDNEY INJURY MOLECULE-1; CHILDRENS SUSCEPTIBILITY; INDUCED NEPHROTOXICITY; VALPROIC ACID; PHARMACOKINETICS; GENTAMICIN; ADULTS; RATS; METAANALYSIS AB Limited experimental models exist to assess drug toxicity in pediatric populations. We recently reported how a multi-age rat model could be used for pre-clinical studies of comparative drug toxicity in pediatric populations. The objective of this study was to expand the utility of this animal model, which previously demonstrated an age-dependent sensitivity to the classic nephrotoxic compound, gentamicin, to another nephrotoxicant, namely cisplatin (Cis). Sprague-Dawley rats (10, 25, 40 and 80 days old) were injected with a single dose of Cis (0, 1, 3 or 6 mg kg(-1) i.p.). Urine samples were collected prior and up to 72 h after treatment in animals that were >= 25 days old. Several serum, urinary and 'omic' injury biomarkers as well as renal histopathology lesions were evaluated. Statistically significant changes were noted with different injury biomarkers in different age groups. The order of age-related Cis-induced nephrotoxicity was different than our previous study with gentamicin: 80 > 40 > 10 > 25 day-old vs 10 >= 80 > 40 > 25-day-old rats, respectively. The increased levels of kidney injury molecule-1 (Kim-1: urinary protein/tissue mRNA) provided evidence of early Cis-induced nephrotoxicity in the most sensitive age group (80 days old). Levels of Kim-1 tissue mRNA and urinary protein were significantly correlated to each other and to the severity of renal histopathology lesions. These data indicate that the multi-age rat model can be used to demonstrate different age-related sensitivities to renal injury using mechanistically distinct nephrotoxicants, which is reflected in measurements of a variety of metabolite, gene transcript and protein biomarkers. Published in 2009 by John Wiley & Sons, Ltd. C1 [Espandiari, P.] US FDA, Div Appl Pharmacol Res HFD 910, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Zhou, Y.; Goering, P. L.; Brown, R. P.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Schnackenberg, L.; Holland, R. D.; Beger, R. D.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR USA. [Vaidya, V. S.; Bonventre, J. V.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Espandiari, P (reprint author), US FDA, Div Appl Pharmacol Res HFD 910, Ctr Drug Evaluat & Res, Life Sci Lab Bldg 64,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM parvaneh.espandiari@fda.hhs.gov FU NIEHS [R00 ES016723] FX The authors thank Dr E Herman, A Knapton, and L Noory for assistance during this project. In addition, thanks to Dr D Portilla for supplying urine samples that led us to identify hydroxyproline as a biomarker of Cis nephrotoxicity. Work in Vaidya laboratory was supported by R00 ES016723 grant by NIEHS to VSV. NR 49 TC 14 Z9 15 U1 0 U2 8 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD MAR PY 2010 VL 30 IS 2 BP 172 EP 182 DI 10.1002/jat.1484 PG 11 WC Toxicology SC Toxicology GA 568JW UT WOS:000275519600009 PM 19839026 ER PT J AU Wood, SC Tang, X Tesfamariam, B AF Wood, Steven C. Tang, Xing Tesfamariam, Belay TI Paclitaxel Potentiates Inflammatory Cytokine-induced Prothrombotic Molecules in Endothelial Cells SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE paclitaxel; tumor necrosis factor; endothelial cells; tissue factor; Plasminogen activator inhibitor; microparticles; adhesion molecules ID NECROSIS-FACTOR-ALPHA; TISSUE FACTOR EXPRESSION; PLASMINOGEN-ACTIVATOR INHIBITOR-1; FACTOR PATHWAY INHIBITOR; DRUG-ELUTING STENTS; PROTEIN-C RECEPTOR; TNF-ALPHA; CARDIOVASCULAR-DISEASES; ADHESION MOLECULES; NITRIC-OXIDE AB To overcome the limitations of balloon expandible metal stent-induced neointimal smooth muscle cell proliferation, drug-coated stent devices have been developed. Drug eluting steins release high concentrations of antiproliferative agents, such as paclitaxel, to reduce neointimal hyperplasia. The proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), is known to cause severe endothelial dysfunction and accelerate atherosclerotic lesion progression. The interaction of TNF-alpha and paclitaxel on the release of prothrombotic molecules was examined in endothelial cells. Treatment of endothelial cells with paclitaxel had no direct effect on tissue factor (TF) expression, but TNF-alpha increased TF. Cotreatment of paclitaxel with TNF-alpha markedly augmented the release of TF. TNF-alpha induced release of plasminogen activator inhibitor but no synergism occurred with paclitaxel. Treatment of endothelial cells with paclitaxel and TNF-alpha reduced expression of thrombomodulin and protein C receptor. Tissue factor pathway inhibitor expression was reduced by prolonged treatment with either paclitaxel or TNF-alpha. The adhesion molecule, CD62 E, was induced by TNF-alpha; however, CD31, CD62 P, and CD 106 were not affected by paclitaxel and TNF-alpha. Apoptosis was not observed with cotreatment of endothelial cells with paclitaxel and TNF-alpha. CD59-positive microparticles were released in response to TNF-alpha, but the release was not augmented by paclitaxel. Paclitaxel and TNF-alpha increased the nitrotyrosination of proteins. These findings indicate that paclitaxel enhances TNF-alpha induced release of TF, and downregulated thrombomodulin, increased protein nitration, which may subsequently favor prothrombotic intimal surface. C1 [Wood, Steven C.; Tang, Xing] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Tesfamariam, Belay] US FDA, Div Cardiovasc & Renal Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Wood, SC (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Bldg 64,Rm 3026,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM steven.wood@fda.hhs.gov FU Office of Engineering and Science Laboratories; CDRH; FDA FX These studies were supported by funds provided by the Office of Engineering and Science Laboratories, CDRH, FDA. Disclaimer: The views and conclusions of the authors do not claim to represent the regulatory posture of the US FDA. NR 45 TC 9 Z9 11 U1 0 U2 3 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 MAR PY 2010 VL 55 IS 3 BP 276 EP 285 PG 10 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 576HU UT WOS:000276135900009 PM 20075745 ER PT J AU Havery, DC Wright, SF AF Havery, Donald C. Wright, Shontell Fleming TI COSMETIC COLOR ADDITIVES: AN OVERVIEW AND COMMON MISUNDERSTANDINGS SO JOURNAL OF COSMETIC SCIENCE LA English DT Article; Proceedings Paper CT Annual Scientific Meeting and Technology Showcase of Cosmetic Science CY DEC 10-11, 2009 CL New York, NY C1 [Havery, Donald C.; Wright, Shontell Fleming] US FDA, College Pk, MD USA. RP Havery, DC (reprint author), US FDA, College Pk, MD USA. NR 3 TC 0 Z9 0 U1 0 U2 3 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 MAR-APR PY 2010 VL 61 IS 2 BP 199 EP 200 PG 2 WC Chemistry, Applied; Dermatology SC Chemistry; Dermatology GA 655LA UT WOS:000282250300018 ER PT J AU Ross, LF Loup, A Nelson, RM Botkin, JR Kost, R Smith, GR Gehlert, S AF Ross, Lainie Friedman Loup, Allan Nelson, Robert M. Botkin, Jeffrey R. Kost, Rhonda Smith, George R., Jr. Gehlert, Sarah TI HUMAN SUBJECTS PROTECTIONS IN COMMUNITY-ENGAGED RESEARCH: A RESEARCH ETHICS FRAMEWORK SO JOURNAL OF EMPIRICAL RESEARCH ON HUMAN RESEARCH ETHICS LA English DT Article DE human subjects protections; research ethics; risks; moral agency; autonomy; community; community-engaged research; community-based participatory research; academic-community partnerships ID PARTICIPATORY RESEARCH; HEALTH AB IN THE 30 YEARS SINCE THE BELMONT Report, the role of the community in research has evolved and has taken on greater moral significance. Today, more and more translational research is being performed with the active engagement of individuals and communities rather than merely upon them. This engagement requires a critical examination of the range of risks that may arise when communities become partners in research. In attempting to provide such an examination, one must distinguish between established communities (groups that have their own organizational structure and leadership and exist regardless of the research) and unstructured groups (groups that may exist because of a shared trait but do not have defined leadership or internal cohesiveness). In order to participate in research as a community, unstructured groups must develop structure either by external means (by partnering with a Community-Based Organization) or by internal means (by empowering the group to organize and establish structure and leadership). When groups participate in research, one must consider risks to well-being due to process and outcomes. These risks may occur to the individual qua individual, but there are also risks that occur to the individual qua member of a group and also risks that occur to the group qua group. There are also risks to agency, both to the individual and the group. A 3-by-3 grid including 3 categories of risks (risks to well-being secondary to process, risks to well-being secondary to outcome and risks to agency) must be evaluated against the 3 distinct agents: individuals as individual participants, individuals as members of a group (both as participants and as non-participants) and to communities as a whole. This new framework for exploring the risks in community-engaged research can help academic researchers and community partners ensure the mutual respect that community-engaged research requires. C1 [Ross, Lainie Friedman] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. [Loup, Allan] Washington Univ, Sch Law, St Louis, MO 63130 USA. [Nelson, Robert M.] US FDA, Off Pediat Therapeut, Off Commissioner, Rockville, MD 20857 USA. [Botkin, Jeffrey R.] Univ Utah, Salt Lake City, UT 84112 USA. [Kost, Rhonda] Rockefeller Univ, Clin Res Support Off, New York, NY 10021 USA. [Smith, George R., Jr.] Healthcare Consortium Illinois Dolton, Off Community Hlth, Dolton, IL USA. [Gehlert, Sarah] Washington Univ, Brown Sch, St Louis, MO 63130 USA. RP Ross, LF (reprint author), Univ Chicago, Dept Pediat, 5841 S Maryland Ave,MC 6082, Chicago, IL 60637 USA. EM lross@uchicago.edu FU National Center for Research Resources (NCRR); National Institutes of Health (NIH); Clinical and Translational Science Awards Program (CTSA); Roadmap Initiative, Re-Engineering the Clinical Research Enterprise [UL1RR024999] FX This project has been funded in whole with Federal funds from the National Center for Research Resources (NCRR), National Institutes of Health (NIH), through the Clinical and Translational Science Awards Program (CTSA), part of the Roadmap Initiative, Re-Engineering the Clinical Research Enterprise, UL1RR024999. The manuscript was approved by the CTSA Consortium Publications Committee. NR 33 TC 56 Z9 57 U1 7 U2 13 PU UNIV CALIFORNIA PRESS PI BERKELEY PA C/O JOURNALS DIVISION, 2000 CENTER ST, STE 303, BERKELEY, CA 94704-1223 USA SN 1556-2646 J9 J EMPIR RES HUM RES JI J. Empir. Res. Hum. Res. Ethics PD MAR PY 2010 VL 5 IS 1 BP 5 EP 17 DI 10.1525/jer.2010.5.1.5 PG 13 WC Ethics; Medical Ethics SC Social Sciences - Other Topics; Medical Ethics GA 579CE UT WOS:000276343600003 PM 20235860 ER PT J AU Ross, LF Loup, A Nelson, RM Botkin, JR Kost, R Smith, GR Gehlert, S AF Ross, Lainie Friedman Loup, Allan Nelson, Robert M. Botkin, Jeffrey R. Kost, Rhonda Smith, George R., Jr. Gehlert, Sarah TI THE CHALLENGES OF COLLABORATION FOR ACADEMIC AND COMMUNITY PARTNERS IN A RESEARCH PARTNERSHIP: POINTS TO CONSIDER SO JOURNAL OF EMPIRICAL RESEARCH ON HUMAN RESEARCH ETHICS LA English DT Article DE community-engaged research; community-based participatory research; community-academic partnerships; community; community-based organizations; memorandum of understanding; data dissemination AB THE PHILOSOPHICAL UNDERPINNING OF Community-Engaged Research (CEnR) entails a collaborative partnership between academic researchers and the community. The Community-Based Participatory Research (CBPR) model is the partnership model most widely discussed in the CEnR literature and is the primary model we draw upon in this discussion of the collaboration between academic researchers and the community. In CPBR, the goal is for community partners to have equal authority and responsibility with the academic research team, and that the partners engage in respectful negotiation both before the research begins and throughout the research process to ensure that the concerns, interests, and needs of each party are addressed. The negotiation of a fair, successful, and enduring partnership requires transparency and understanding of the different assets, skills and expertise that each party brings to the project. Delineating the expectations of both parties and documenting the terms of agreement in a memorandum of understanding or similar document may be very useful. This document is structured to provide a "points-to-consider" roadmap for academic and community research partners to establish and maintain a research partnership at each stage of the research process. C1 [Ross, Lainie Friedman] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. [Loup, Allan] Washington Univ, Sch Law, St Louis, MO 63130 USA. [Nelson, Robert M.] US FDA, Off Pediat Therapeut, Off Commissioner, Rockville, MD 20857 USA. [Botkin, Jeffrey R.] Univ Utah, Salt Lake City, UT 84112 USA. [Kost, Rhonda] Rockefeller Univ, Clin Res Support Off, New York, NY 10021 USA. [Smith, George R., Jr.] Healthcare Consortium Illinois Dolton, Off Community Hlth, Dolton, IL USA. [Gehlert, Sarah] Washington Univ, Brown Sch, St Louis, MO 63130 USA. RP Ross, LF (reprint author), Univ Chicago, Dept Pediat, 5841 S Maryland Ave,MC 6082, Chicago, IL 60637 USA. EM lross@uchicago.edu FU National Center for Research Resources (NCRR); National Institutes of Health (NIH); Clinical and Translational Science Awards Program (CTSA); Clinical Research Enterprise [UL1RR024999] FX This project has been funded in whole with Federal funds from the National Center for Research Resources (NCRR), National Institutes of Health (NIH), through the Clinical and Translational Science Awards Program (CTSA), part of the Roadmap Initiative, Re-Engineering the Clinical Research Enterprise, UL1RR024999. The manuscript was approved by the CTSA Consortium Publica-tions Committee. NR 16 TC 27 Z9 27 U1 2 U2 11 PU UNIV CALIFORNIA PRESS PI BERKELEY PA C/O JOURNALS DIVISION, 2000 CENTER ST, STE 303, BERKELEY, CA 94704-1223 USA SN 1556-2646 J9 J EMPIR RES HUM RES JI J. Empir. Res. Hum. Res. Ethics PD MAR PY 2010 VL 5 IS 1 BP 19 EP 31 DI 10.1525/jer.2010.5.1.19 PG 13 WC Ethics; Medical Ethics SC Social Sciences - Other Topics; Medical Ethics GA 579CE UT WOS:000276343600004 PM 20235861 ER PT J AU Whichard, JM Medalla, F Hoekstra, RM McDermott, PF Joyce, K Chiller, T Barrett, TJ White, DG AF Whichard, Jean M. Medalla, Felicita Hoekstra, Robert M. McDermott, Patrick F. Joyce, Kevin Chiller, Tom Barrett, Timothy J. White, David G. TI Evaluation of Antimicrobial Resistance Phenotypes for Predicting Multidrug-Resistant Salmonella Recovered from Retail Meats and Humans in the United States SO JOURNAL OF FOOD PROTECTION LA English DT Article ID SEROTYPE TYPHIMURIUM; NONTYPHOIDAL SALMONELLA; ANIMAL ORIGIN; INFECTIONS; ILLNESS; BURDEN; DEATH AB Although multidrug-resistant (MDR) non-Typhi Salmonella (NTS) strains are a concern in food production, determining resistance to multiple antimicrobial agents at slaughter or processing may be impractical. Single antimicrobial resistance results for predicting multidrug resistance are desirable. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value were used to determine each antimicrobial agent's ability to predict MDR phenotypes of human health significance: ACSSuT (resistance to at least ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, tetracycline) in NTS isolates, and MDR-AmpC-SN (resistance to ACSSuT, additional resistance to amoxicillin-clavulanate and to ceftiofur, and decreased Susceptibility [MIC >= 2 mu g/ml] to ceftriaxone) in NTS serotype Newport. The U.S. National Antimicrobial Resistance Monitoring System determined MICs to 15 or more antimicrobial agents for 9,955 NTS isolates from humans from 1999 to 2004 and 689 NTS isolates from retail meat from 2002 to 2004. A total of 847 (8.5%) human and 26 (3.8%) retail NTS isolates were ACSSuT; 995 (10.0%) human and 16 (2.3%) retail isolates were serotype Newport. Among Salmonella Newport. 204 (20.5%) human and 9 (56.3%) retail isolates were MDR-AmpC-SN. Chloramphenicol resistance provided the highest PPVs for ACSSuT among human (90.5%; 95% confidence interval, 88.4 to 92.3) and retail NTS isolates (96.3%; 95% confidence interval, 81.0 to 99.9). Resistance to ceftiofur and to amoxicillin-clavulanate and decreased susceptibility to ceftriaxone provided the highest PPVs (97.1, 98.1, and 98.6%, respectively) for MDR-AmpC-SN from humans. High PPVs for these agents applied to retail meat MDR-AmpC-SN, but isolate numbers were lower. Variations in MIC results may complicate ceftriaxone's predictive utility. Selecting specific antimicrobial resistance offers practical alternatives for predicting MDR phenotypes. Chloramphenicol resistance works best for ACSSuT-NTS, and resistance to ceftiofur, amoxicillin-clavulanate, or chloramphenicol works best for MDR-AmpC-SN. C1 [Whichard, Jean M.; Medalla, Felicita; Hoekstra, Robert M.; Joyce, Kevin; Chiller, Tom; Barrett, Timothy J.] Ctr Dis Control & Prevent, Div Foodborne Bacterial & Mycot Dis, Atlanta, GA 30333 USA. [McDermott, Patrick F.; White, David G.] US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. RP Whichard, JM (reprint author), Ctr Dis Control & Prevent, Div Foodborne Bacterial & Mycot Dis, Atlanta, GA 30333 USA. EM zyr3@cdc.gov FU Food and Drug Administration; CDC FX We thank the state and local laboratories for participating in the NARMS surveillance program and the USDA-FSIS and Agricultural Research Set-vice for technical review of this manuscript, This work was funded by an Interagency Agreement between the Food and Drug Administration and the CDC. NR 31 TC 6 Z9 6 U1 0 U2 5 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD MAR PY 2010 VL 73 IS 3 BP 445 EP 451 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 570LB UT WOS:000275677900005 PM 20202328 ER PT J AU Apana, SM Anderson, LW Berridge, MS AF Apana, Scott M. Anderson, Lawrence W. Berridge, Marc S. TI Synthesis and biodistribution of [C-11]SN-38 SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE carbon-11; chemotherapy; cancer; PET; radiation dosimetry ID METASTATIC COLORECTAL-CANCER; CELL LUNG-CANCER; PHASE-II TRIAL; POLYMERIC MICELLE; GRIGNARD-REAGENTS; ALKYL-HALIDES; IRINOTECAN; TUMORS; NK012; INFUSION AB SN-38 (7-ethyl-10-hydroxy camptothecin) is a topoisomerase I inhibitor that is the active chemotherapeutic agent of irinotecan, indicated for colon cancer. Because the rate of response to irinotecan treatment is low, it is of interest to have a prognostic indicator to identify and more selectively treat those who are likely to respond to treatment. We have therefore prepared SN-38 labeled with carbon-11. SN-38 was prepared by radical oxidation of 3-[C-11]propionaldehyde and subsequent radical addition of the ethyl fragment to 10-hydroxycamptothecin. Labeled propionaldehyde was prepared by reaction of methyl iodide with 2-lithiomethyl-1,3-dioxolane. Overall chemical yield was 34% from carbon dioxide. The murine biodistribution and radiation dosimetry of [C-11]SN-38 was measured by PET scanning in preparation for initial human studies. Biodistribution was fairly uniform except for hepatobiliary and urinary excretion. C1 [Apana, Scott M.; Berridge, Marc S.] 3D Imaging LLC, Little Rock, AR 72205 USA. [Anderson, Lawrence W.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Berridge, Marc S.] Univ Arkansas Med Sci, Dept Radiol, Little Rock, AR 72205 USA. [Berridge, Marc S.] Univ Arkansas Med Sci, Dept Pharmaceut Sci, Little Rock, AR 72205 USA. RP Berridge, MS (reprint author), 3D Imaging LLC, Cyclotron Suite Rm PS010,UAMS Radiol 556,4301 W M, Little Rock, AR 72205 USA. EM MBerridge@3DImagingLLC.com FU U.S. National Cancer Institute, National Institutes of Health [NO1-CO-12400, 27XS129] FX This project has been funded in whole or in part with Federal Funds from the U.S. National Cancer Institute, National Institutes of Health, under Contract No. NO1-CO-12400, SAIC-Frederick subcontract 27XS129. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 21 TC 2 Z9 2 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD MAR-APR PY 2010 VL 53 IS 3-4 BP 178 EP 182 DI 10.1002/jlcr.1746 PG 5 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 597KW UT WOS:000277757000034 ER PT J AU Fohlmeister, JF Cohen, ED Newman, EA AF Fohlmeister, Juergen F. Cohen, Ethan D. Newman, Eric A. TI Mechanisms and Distribution of Ion Channels in Retinal Ganglion Cells: Using Temperature as an Independent Variable SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID GATED POTASSIUM CHANNELS; TIGER SALAMANDER RETINA; RAT RETINA; ALPHA-GANGLION; XENOPUS-LAEVIS; SODIUM; CURRENTS; NEURONS; CAT; CONDUCTANCE AB Fohlmeister JF, Cohen ED, Newman EA. Mechanisms and distribution of ion channels in retinal ganglion cells: using temperature as an independent variable. J Neurophysiol 103: 1357-1374, 2010. First published January 6, 2010; doi: 10.1152/jn.00123.2009. Trains of action potentials of rat and cat retinal ganglion cells (RGCs) were recorded intracellularly across a temperature range of 7-37 degrees C. Phase plots of the experimental impulse trains were precision fit using multicompartment simulations of anatomically reconstructed rat and cat RGCs. Action potential excitation was simulated with a "Five-channel model" [Na, K(delayed rectifier), Ca, K(A), and K(Ca-activated) channels] and the nonspace- clamped condition of the whole cell recording was exploited to determine the channels' distribution on the dendrites, soma, and proximal axon. At each temperature, optimal phase-plot fits for RGCs occurred with the same unique channel distribution. The "waveform" of the electrotonic current was found to be temperature dependent, which reflected the shape changes in the experimental action potentials and confirmed the channel distributions. The distributions are cell-type specific and adequate for soma and dendritic excitation with a safety margin. The highest Na-channel density was found on an axonal segment some 50-130 mu m distal to the soma, as determined from the temperature-dependent "initial segment-somadendritic (IS-SD) break." The voltage dependence of the gating rate constants remains invariant between 7 and 23 degrees C and between 30 and 37 degrees C, but undergoes a transition between 23 and 30 degrees C. Both gating-kinetic and ion-permeability Q10s remain virtually constant between 23 and 37 degrees C (kinetic Q10s = 1.9-1.95; permeability Q10s = 1.49-1.64). The Q10s systematically increase for T <23 degrees C (kinetic Q10 = 8 at T = 8 degrees C). The Na channels were consistently "sleepy" (non-Arrhenius) for T <8 degrees C, with a loss of spiking for T <7 degrees C. C1 [Fohlmeister, Juergen F.] Univ Minnesota, Dept Integrat Biol & Physiol, Minneapolis, MN 55455 USA. [Newman, Eric A.] Univ Minnesota, Dept Neurosci, Minneapolis, MN 55455 USA. [Cohen, Ethan D.] US FDA, Off Sci, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Cohen, Ethan D.] US FDA, Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Fohlmeister, JF (reprint author), Univ Minnesota, Dept Integrat Biol Physiol, 6-125 Jackson Hall,321 Church St SE, Minneapolis, MN 55455 USA. EM jurgen@umn.edu FU National Eye Institute [R01EY-012833] FX This research was supported in part by National Eye Institute Grant R01EY-012833 to R. F. Miller. NR 66 TC 30 Z9 31 U1 1 U2 14 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAR PY 2010 VL 103 IS 3 BP 1357 EP 1374 DI 10.1152/jn.00123.2009 PG 18 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 570EY UT WOS:000275656200020 PM 20053849 ER PT J AU Zidan, AS Rahman, Z Habib, MJ Khan, MA AF Zidan, Ahmed S. Rahman, Ziyaur Habib, Muhammad J. Khan, Mansoor A. TI Spectral and Spatial Characterization of Protein Loaded PLGA Nanoparticles SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE nanoparticles; encapsulation; biodegradable polymers; near infrared spectroscopy; partial least squares; and cyclosporine A ID NEAR-INFRARED SPECTROSCOPY; MOLECULAR-WEIGHT; RELEASE; MICROSPHERES; CYCLOSPORINE; FORMULATION; VARIABLES; DELIVERY; MICROPARTICLES; NANOSPHERES AB The objective of this study was to evaluate near infrared (NIR) spectroscopy and imaging as approaches to assess drug contents in poly(dl-lactide-co-glycolide) (PLGA) based nanoparticles of a model protein, cyclosporine A (CyA). A 6-factors 12-runs designed set of experiments with Plackett-Burman (PB) screening was applied in order to examine the effects of drug loading (X(1)), polymer loading (X(2)), emulsifier concentration (X(3)), stirring rate (X(4)), type of organic solvent (X(5)), and ratio of organic to aqueous phases' volumes (X(6)), on drug entrapment efficiency (EFF). After omitting the factors with nonsignificant influences on EFF, a reduced mathematical relationship, EFF = 48.34 + 7.3X(1) - 29.95X(3), was obtained to explain the effect of the significant factors on EFF. Using two different sets for calibration and validation, the developed NIR calibration model was able to assess CyA contents within the 12 PB formulations. NIR spectral imaging was capable of clearly distinguishing the 12 formulations, both qualitatively and quantitatively. A good correlation with a coefficient of 0.9727 was obtained for constructing a quantile-quantile plot for the actual drug loading percentage and the % standard deviation obtained for the drug loading prediction using the hyperspectral images. (C) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:1180-1192, 2010 C1 [Zidan, Ahmed S.; Rahman, Ziyaur; 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. [Habib, Muhammad J.] Howard Univ, Sch Pharm, Washington, DC 20059 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 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. The authors also extend this acknowledgment to Dr. Katherine Tyner and Dr. Christopher Ellison for helping to capture the SEM images and NIR images, respectively. NR 25 TC 5 Z9 5 U1 0 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 MAR PY 2010 VL 99 IS 3 BP 1180 EP 1192 DI 10.1002/jps.21928 PG 13 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 564LF UT WOS:000275215100007 PM 19774658 ER PT J AU Abraham, MH Smith, RE Luchtefeld, R Boorem, AJ Luo, RS Acree, WE AF Abraham, Michael H. Smith, Robert E. Luchtefeld, Ron Boorem, Aaron J. Luo, Rensheng Acree, William E., Jr. TI Prediction of Solubility of Drugs and Other Compounds in Organic Solvents SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE physicochemical properties; solubility; structure-property relationship (SPR); distribution; QSPR ID SOLVATION PARAMETER MODEL; CRYSTALLINE NONELECTROLYTE SOLUTES; CARBOXYLIC-ACID SOLUTES; AROMATIC-HYDROCARBONS PAHS; MATHEMATICAL CORRELATION; PARTITION-COEFFICIENTS; GAS-PHASE; THERMOCHEMICAL BEHAVIOR; PART 2; WATER AB We have set out a procedure for the prediction of solubilities of drugs and other compounds in a wide range of solvents, based on the Abraham solvation equations. The method requires a knowledge of solubilities of a given compound in a few solvents, as shown by our own experimental data on apocynin, diapocynin, dehydrodivanillin, and dehydrodi(methyl vanillate). The procedure is especially useful for very hydrophobic compounds such as cholesteryl acetate and cholesterol that we give as examples. Other examples include vanillin and 3,4-dichlorobenzoic acid. If the solubility in water is available, then this alone is sufficient to predict solubilities in organic solvents, provided that the Abraham descriptors are available for the compound. Predictions can be made for solubilities in some 85 solvents. (C) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:1500-1515, 2010 C1 [Abraham, Michael H.] UCL, Dept Chem, London WC1H 0AJ, England. [Smith, Robert E.; Luchtefeld, Ron] US FDA, Total Diet & Pesticide Res Ctr, Lenexa, KS 66214 USA. [Smith, Robert E.; Boorem, Aaron J.] Park Univ, Dept Chem, Parkville, MO 64152 USA. [Luo, Rensheng] Univ Missouri, Dept Chem & Biochem, St Louis, MO 63121 USA. [Acree, William E., Jr.] Univ N Texas, Dept Chem, Denton, TX 76203 USA. RP Abraham, MH (reprint author), UCL, Dept Chem, 20 Gordon St, London WC1H 0AJ, England. EM m.h.abraham@ucl.ac.uk NR 77 TC 109 Z9 110 U1 5 U2 44 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 MAR PY 2010 VL 99 IS 3 BP 1500 EP 1515 DI 10.1002/jps.21922 PG 16 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 564LF UT WOS:000275215100033 PM 19774653 ER PT J AU Wu, HQ Khan, MA AF Wu, Huiquan Khan, Mansoor A. TI Quality-by-Design (QbD): An Integrated Process Analytical Technology (PAT) Approach for Real-Time Monitoring and Mapping the State of a Pharmaceutical Coprecipitation Process SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE Quality-by-Design (QbD); process analytical technology (PAT); coprecipitation; real-time process monitoring; incubation; nucleation; crystal growth; crystal size distribution (CSD); principal component analysis; process trajectory ID NEAR-INFRARED SPECTROSCOPY; POWDER BLEND HOMOGENEITY; FORMULATION VARIABLES; RAMAN-SPECTROSCOPY; AUTOMATED-SYSTEM; CRYSTALLIZATION; NUCLEATION; INHIBITOR; RITONAVIR; IBUPROFEN AB In this work, an integrated PAT approach was developed for monitoring a pharmaceutical (naproxen) and a polymer (eudragit) coprecipitation process: real-time in-line near-infrared (NIR) absorbance monitoring, real-time on-line turbidity monitoring, and in situ crystal size monitoring. The data and information obtained through these three monitoring techniques confirmed the observation of the onsets of three distinct stages: incubation, nucleation, and crystal growth. The process trajectory constructed based on results of applying principal component analysis (PCA) to either process NIR spectra data or process turbidity profile, clearly demonstrated that various distinguishable process events, including incubation, nucleation, and crystal growth, could be accurately tracked and differentiated. These findings were further supported by process knowledge and information, such as process design, process sequence, thermodynamic and mass-transfer analysis. Therefore, this work provides a case study that illustrated a rational approach to develop a science-based and knowledge-based process monitoring strategy, which is essential for establishing both a suitable process control strategy and an operational process space for a pharmaceutical unit operation. (C) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:1516-1534, 2010 C1 [Wu, Huiquan; Khan, Mansoor A.] US FDA, Div Prod Qual Res HFD 940, Off Testing & Res, Off Pharmaceut Sci,CDER, Silver Spring, MD 20993 USA. RP Wu, HQ (reprint author), US FDA, Div Prod Qual Res HFD 940, Off Testing & Res, Off Pharmaceut Sci,CDER, Silver Spring, MD 20993 USA. EM huiquan.wu@fda.hhs.gov NR 55 TC 25 Z9 27 U1 1 U2 36 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 MAR PY 2010 VL 99 IS 3 BP 1516 EP 1534 DI 10.1002/jps.21923 PG 19 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 564LF UT WOS:000275215100034 PM 19774654 ER PT J AU Goteti, K Garner, CE Mahmood, I AF Goteti, Kosalaram Garner, C. Edwin Mahmood, Iftekhar TI Prediction of Human Drug Clearance from Two Species: A Comparison of Several Allometric Methods SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE two-species scaling; clearance; multiexponential allometry; rule of exponents; fixed exponents ID CARBOLINE DERIVATIVE ABECARNIL; TRANSFER PROTEIN INHIBITOR; TYROSINE KINASE INHIBITOR; IN-VITRO DATA; RHESUS-MONKEYS; COMPARATIVE PHARMACOKINETICS; CLINICAL PHARMACOKINETICS; ANIMAL PHARMACOKINETICS; DISPOSITION KINETICS; LABORATORY-ANIMALS AB The objective of the study was to assess the degree of accuracy in human drug clearance prediction from two species using four different allometric approaches: simple allometry (SA), multiexponential allometry (ME), rule of exponents (ROE), and fixed exponents (FE) as suggested by Tang et al. There were 45 compounds in this analysis and the two species used were either rat-dog or rat-monkey. In addition, >= 3 species scaling was also performed to evaluate the comparative accuracy in the prediction of human drug clearance between two or more than two-species scaling. The results of the study indicated that the two-species scaling with different methods provided different degrees of accuracy in the prediction of clearance. Prediction by a particular method was also species dependent. For example, a given drug with rat-dog scaling provided a reasonably accurate prediction of clearance whereas with rat-monkey scaling the prediction of clearance was highly erratic or vice versa. The results of the study indicated that the two-species scaling can be useful for prediction purposes but the prediction of clearance from >= 3 species was far more accurate than two-species scaling. (C) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:1601-1613, 2010 C1 [Goteti, Kosalaram; Garner, C. Edwin] AstraZeneca R&D Boston, Dept Drug Metab & Pharmacokinet, Waltham, MA 02451 USA. [Mahmood, Iftekhar] US FDA, OBRR, Ctr Biol Evaluat & Res, Rockville, MD USA. RP Goteti, K (reprint author), AstraZeneca R&D Boston, Dept Drug Metab & Pharmacokinet, 35 Gatehouse Dr, Waltham, MA 02451 USA. EM kosalaram.goteti@astrazeneca.com NR 85 TC 9 Z9 9 U1 2 U2 7 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 MAR PY 2010 VL 99 IS 3 BP 1601 EP 1613 DI 10.1002/jps.21926 PG 13 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 564LF UT WOS:000275215100040 PM 19827101 ER PT J AU Gallauresi, B DiPaola, L Parekh, A Uhl, K AF Gallauresi, Beverly DiPaola, Lauren Parekh, Ameeta Uhl, Kathleen TI The FDA Pregnancy Exposure Registry Website: Information for Pregnant Women Taking Prescription Drugs SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Gallauresi, Beverly; DiPaola, Lauren; Parekh, Ameeta; Uhl, Kathleen] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAR PY 2010 VL 19 IS 3 MA 29 BP 613 EP 613 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 574IS UT WOS:000275983200057 ER PT J AU Khanijow, K Parekh, A AF Khanijow, Keshav Parekh, Ameeta TI Participation of Women in Clinical Trials: A Fifteen Year Assessment by the FDA Office of Women's Health (OWH) SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Khanijow, Keshav; Parekh, Ameeta] US FDA, Off Womens Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAR PY 2010 VL 19 IS 3 MA 49 BP 620 EP 621 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 574IS UT WOS:000275983200077 ER PT J AU Nguyen, T Fadiran, EO Parekh, A AF Nguyen, Tien Fadiran, Emmanuel O. Parekh, Ameeta TI FDA Office of Women's Health Funded Oncology Studies-1994-2009 SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Nguyen, Tien] Univ So Calif, Sch Pharm, Los Angeles, CA 90089 USA. [Fadiran, Emmanuel O.; Parekh, Ameeta] US FDA, Off Womens Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAR PY 2010 VL 19 IS 3 MA 63 BP 625 EP 625 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 574IS UT WOS:000275983200091 ER PT J AU Perry, S Pedley, K Scholz, L Glenn, Z AF Perry, Susana Pedley, Krista Scholz, L. Glenn, Z. TI The Patient Safety and Clinical Pharmacy Services Collaborative SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Perry, Susana] US FDA, Off Womens Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAR PY 2010 VL 19 IS 3 MA 67 BP 626 EP 627 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 574IS UT WOS:000275983200095 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 Optimizing Clinical Research: Identification of Barriers and Opportunities in Recruiting Women from the Clinical Research Personnel Perspective SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Pinnow, Ellen; Ritchey, Mary E.; Marinac-Dabic, Danica] US FDA, Silver Spring, MD USA. [Tilley, Andrea] Assoc Clin Res Profess, Alexandria, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAR PY 2010 VL 19 IS 3 MA 69 BP 627 EP 627 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 574IS UT WOS:000275983200097 ER PT J AU Yakes, BJ Etheridge, SM Mulvaney, SP Tamanaha, CR AF Yakes, Betsy Jean Etheridge, Stacey M. Mulvaney, Shawn P. Tamanaha, Cy R. TI Fluidic Force Discrimination Assays: A New Technology for Tetrodotoxin Detection SO MARINE DRUGS LA English DT Article DE tetrodotoxin; antibody inhibition assay; bioassay; Fluidic Force Discrimination; microbead labels ID SELF-ASSEMBLED MONOLAYERS; RECEPTOR-BINDING ASSAY; TOXINS; CHROMATOGRAPHY; ACCUMULATION; SAXITOXIN; MATRICES; ANALOGS; MARINE; TTX AB Tetrodotoxin (TTX) is a low molecular weight (similar to 319 Da) neurotoxin found in a number of animal species, including pufferfish. Protection from toxin tainted food stuffs requires rapid, sensitive, and specific diagnostic tests. An emerging technique for the detection of both proteins and nucleic acids is Fluidic Force Discrimination ( FFD) assays. This simple and rapid method typically uses a sandwich immunoassay format labeled with micrometer-diameter beads and has the novel capability of removing nonspecifically attached beads under controlled, fluidic conditions. This technique allows for near realtime, multiplexed analysis at levels of detection that exceed many of the conventional transduction methods (e.g., ELISAs). In addition, the large linear dynamic range afforded by FFD should decrease the need to perform multiple sample dilutions, a common challenge for food testing. By applying FFD assays to an inhibition immunoassay platform specific for TTX and transduction via low magnification microscopy, levels of detection of similar to 15 ng/mL and linear dynamic ranges of 4 to 5 orders of magnitude were achieved. The results from these studies on the first small molecule FFD assay, along with the impact to detection of seafood toxins, will be discussed in this manuscript. C1 [Yakes, Betsy Jean; Etheridge, Stacey M.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Mulvaney, Shawn P.; Tamanaha, Cy R.] USN, Res Lab, Washington, DC 20375 USA. RP Yakes, BJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM betsy.yakes@fda.hhs.gov; stacey.etheridge@fda.hhs.gov; shawn.mulvaney.ctr@nrl.navy.mil; cy.tamanaha@nrl.navy.mil RI Yakes, Betsy/K-2646-2012; OI DeGrasse, Stacey/0000-0001-7808-4193 NR 36 TC 8 Z9 9 U1 0 U2 13 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1660-3397 J9 MAR DRUGS JI Mar. Drugs PD MAR PY 2010 VL 8 IS 3 BP 565 EP 576 DI 10.3390/md8030565 PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 574VH UT WOS:000276021800012 PM 20411115 ER PT J AU Desai, VG Moland, CL Branham, WS Fuscoe, JC AF Desai, Varsha G. Moland, Carrie L. Branham, William S. Fuscoe, James C. TI Title: Use of MitoChip to understand the mechanism of mitochondrial dysfunction in mice exposed to anti-HIV SO MITOCHONDRION LA English DT Meeting Abstract C1 [Desai, Varsha G.; Moland, Carrie L.; Branham, William S.; Fuscoe, James C.] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Ctr Fdn Genom, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 J9 MITOCHONDRION JI Mitochondrion PD MAR PY 2010 VL 10 IS 2 MA 109 BP 230 EP 231 DI 10.1016/j.mito.2009.12.101 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 561PC UT WOS:000274989300116 ER PT J AU Xu, ZL Smith, JS Tian, J Byrnes, AP AF Xu, Zhili Smith, Jeffrey S. Tian, Jie Byrnes, Andrew P. TI Induction of Shock After Intravenous Injection of Adenovirus Vectors: A Critical Role for Platelet-activating Factor SO MOLECULAR THERAPY LA English DT Article ID INNATE IMMUNE-RESPONSES; RECEPTOR ANTAGONIST; VASCULAR-PERMEABILITY; CLINICAL-TRIALS; KUPFFER CELLS; P53 GENE; PAF; RAT; MECHANISM; TOXICITY AB Innate immune responses are a major barrier to safe systemic gene therapy with adenovirus (Ad) vectors. We show that intravenous (IV) injection of rats with Ad5 vectors causes a novel rapid shock reaction that involves hypotension, hemoconcentration, tissue edema, and vasocongestion, with notable pathology in the pancreas and the gastrointestinal system. We show for the first time that this reaction is dependent on platelet-activating factor (PAF), a lipid signaling molecule that is a known shock inducer. Ad upregulated PAF within 5 minutes in vivo, and antagonists of the PAF receptor were able to prevent Ad-induced shock. Ad upregulated PAF via the reticuloendothelial system (RES), because splenectomy or depletion of phagocytes blocked the ability of Ad to induce both PAF and shock. Rats were considerably more sensitive to Ad-induced shock than were mice, but PAF mediated shock in both species. Other Ad-induced innate immune responses such as cytokine induction and thrombocytopenia were not mediated by PAF. In summary, systemic IV injection of Ad stimulates the RES to upregulate PAF within a matter of minutes, which results in shock. The identification of this novel pathway suggests strategies to improve the safety of systemic gene therapy with Ad vectors. C1 [Xu, Zhili; Smith, Jeffrey S.; Tian, Jie; Byrnes, Andrew P.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Byrnes, AP (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, HFM-725,8800 Rockville Pike, Bethesda, MD 20014 USA. EM Andrew.Byrnes@fda.hhs.gov RI Byrnes, Andrew/D-2808-2013 OI Byrnes, Andrew/0000-0003-1135-2629 FU FDA FX This work was supported by the FDA, including FDA's Critical Path program. We thank Boris Perelman and Peter Vadas for their helpful suggestions on PAF purification. We also thank Ying Huang, Cheng-Hong Wei, Philip Ng and Nicola Brunetti-Pierri for helpful comments on the manuscript. NR 50 TC 6 Z9 7 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAR PY 2010 VL 18 IS 3 BP 609 EP 616 DI 10.1038/mt.2009.279 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 567NS UT WOS:000275454500021 PM 19953082 ER PT J AU Lovas, G Nielsen, JA Johnson, KR Hudson, LD AF Lovas, G. Nielsen, J. A. Johnson, K. R. Hudson, L. D. TI Alterations in neuronal gene expression profiles in response to experimental demyelination and axonal transection SO MULTIPLE SCLEROSIS JOURNAL LA English DT Article DE axonal transection; experimental demyelination; injury response; microarray; rat ID LYSOLECITHIN-INDUCED DEMYELINATION; MAGNETIC-RESONANCE-SPECTROSCOPY; THYROTROPIN-RELEASING-HORMONE; MULTIPLE-SCLEROSIS; SPINAL-CORD; AXOTOMIZED NEURONS; GANGLION NEURONS; NERVOUS-SYSTEM; MESSENGER-RNAS; RAT-BRAIN AB The main pathological features of multiple sclerosis, demyelination and axonal transection, are considered to cause reversible and irreversible neurological deficits, respectively. This study aimed to separately analyze the effects of these pathological hallmarks on neuronal gene expression in experimental paradigms. The pontocerebellar pathway was targeted with either lysolecithin-induced chemical demyelination or a complete pathway transection (axonal transection) in rats. Transcriptional changes in the pontocerebellar neurons were investigated with microarrays at days 4, 10 and 37 post-intervention, which was confirmed by immunohistochemistry on protein level. A common as well as unique set of injury-response genes was identified. The increased expression of activating transcription factor 3 (Atf3) and thyrotropin-releasing hormone (Trh) in both injury paradigms was validated by immunohistochemistry. The expression of Atf3 in a patient with Marburg's variant of multiple sclerosis was also detected, also confirming the activation of the Atf3 pathway in a human disease sample. It was concluded that this experimental approach may be useful for the identification of pathways that could be targeted for remyelinative or neuroprotective drug development. C1 [Lovas, G.] Semmelweis Univ, Dept Neurol, H-1083 Budapest, Hungary. [Lovas, G.; Nielsen, J. A.; Hudson, L. D.] NINDS, Sect Dev Genet, NIH, Bethesda, MD 20892 USA. [Johnson, K. R.] NINDS, Bioinformat Neurosci Grp, Div Intramural Res, Informat Technol Program,NIH, Bethesda, MD 20892 USA. [Nielsen, J. A.] US FDA, Div Gen Restorat & Neurol Devices, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Lovas, G (reprint author), Semmelweis Univ, Dept Neurol, Balassa Str 6, H-1083 Budapest, Hungary. EM lovasgab@hotmail.com RI Messier, Claude/A-2322-2008 OI Messier, Claude/0000-0002-4791-1763 FU NINDS FX We thank Andras Boros (Richter Inc.) for assistance with the animal surgeries, tissue isolation, and RNA preparation and Gabor G Kovacs (Department of Neuropathology, National Institute of Psychiatry and Neurology) for providing the Marburg's samples. We thank Abdel Elkahloun, (Genome Technologies Branch, NHGRI) for his help with the microarrays. This work was supported by NINDS intramural funds. NR 48 TC 2 Z9 2 U1 0 U2 4 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 MAR PY 2010 VL 16 IS 3 BP 303 EP 316 DI 10.1177/1352458509357063 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 563ZF UT WOS:000275179200005 PM 20086029 ER PT J AU Huang, SM Woodcock, J AF Huang, Shiew-Mei Woodcock, Janet TI Transporters in drug development: advancing on the Critical Path SO NATURE REVIEWS DRUG DISCOVERY LA English DT Editorial Material C1 [Woodcock, Janet] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Huang, Shiew-Mei] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Woodcock, J (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. EM janet.woodcock@fda.hhs.gov NR 4 TC 23 Z9 23 U1 0 U2 5 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 MAR PY 2010 VL 9 IS 3 BP 175 EP 176 DI 10.1038/nrd3124 PG 2 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 566GG UT WOS:000275357500001 PM 20222180 ER PT J AU Giacomini, KM Huang, SM Tweedie, DJ Benet, LZ Brouwer, KLR Chu, XY Dahlin, A Evers, R Fischer, V Hillgren, KM Hoffmaster, KA Ishikawa, T Keppler, D Kim, RB Lee, CA Niemi, M Polli, JW Sugiyama, Y Swaan, PW Ware, JA Wright, SH Yee, SW Zamek-Gliszczynski, MJ Zhang, L AF Giacomini, Kathleen M. Huang, Shiew-Mei Tweedie, Donald J. Benet, Leslie Z. Brouwer, Kim L. R. Chu, Xiaoyan Dahlin, Amber Evers, Raymond Fischer, Volker Hillgren, Kathleen M. Hoffmaster, Keith A. Ishikawa, Toshihisa Keppler, Dietrich Kim, Richard B. Lee, Caroline A. Niemi, Mikko Polli, Joseph W. Sugiyama, Yuicchi Swaan, Peter W. Ware, Joseph A. Wright, Stephen H. Yee, Sook Wah Zamek-Gliszczynski, Maciej J. Zhang, Lei CA International Transporter TI Membrane transporters in drug development SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID CANCER RESISTANCE PROTEIN; BLOOD-BRAIN-BARRIER; ORGANIC CATION TRANSPORTER-2; VITRO-IN-VIVO; CENTRAL-NERVOUS-SYSTEM; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; SINGLE NUCLEOTIDE POLYMORPHISMS; PHARMACOPHORE-BASED DISCOVERY; POSITRON-EMISSION-TOMOGRAPHY; DUBIN-JOHNSON-SYNDROME AB Membrane transporters can be major determinants of the pharmacokinetic, safety and efficacy profiles of drugs. This presents several key questions for drug development, including which transporters are clinically important in drug absorption and disposition, and which in vitro methods are suitable for studying drug interactions with these transporters. In addition, what criteria should trigger follow-up clinical studies, and which clinical studies should be conducted if needed. In this article, we provide the recommendations of the International Transporter Consortium on these issues, and present decision trees that are intended to help guide clinical studies on the currently recognized most important drug transporter interactions. The recommendations are generally intended to support clinical development and filing of a new drug application. Overall, it is advised that the timing of transporter investigations should be driven by efficacy, safety and clinical trial enrolment questions (for example, exclusion and inclusion criteria), as well as a need for further understanding of the absorption, distribution, metabolism and excretion properties of the drug molecule, and information required for drug labelling. C1 [Giacomini, Kathleen M.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. [Huang, Shiew-Mei] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Durg Evaluat & Res, Silver Spring, MD 20993 USA. [Tweedie, Donald J.] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. RP Giacomini, KM (reprint author), Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, 513 Parnassus Ave, San Francisco, CA 94143 USA. EM kathy.giacomini@ucsf.edu; ShiewMei.Huang@fda.hhs.gov; donald.tweedie@boehringer-ingelheim.com RI Keppler, Dietrich/A-5528-2013; Benet, Leslie/K-8286-2016; Niemi, Mikko/A-1088-2008; OI Swaan, Peter/0000-0003-1767-1487; Niemi, Mikko/0000-0003-4550-2189 FU National Institutes of Health [GM61390]; FDA Critical Path FX This report is dedicated to the memory of John M. Strong (1937-2008), Deputy Director of the Laboratory of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration (FDA). J.M.S's insight and research career focused on understanding the determinants of drug-drug interactions, clinical pharmacology, drug-induced liver injury, and the translation of transporter biology to the drug safety evaluation paradigm. We are grateful for the able assistance of R. Bogenrief and C. Weiss in preparing this manuscript. We would like to acknowledge partial support from an National Institutes of Health grant, GM61390 and funds from the FDA Critical Path for the workshop leading to this report. NR 225 TC 1198 Z9 1230 U1 35 U2 258 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 MAR PY 2010 VL 9 IS 3 BP 215 EP 236 DI 10.1038/nrd3028 PG 22 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 566GG UT WOS:000275357500022 ER PT J AU Rodriguez, JS Morris, SM Hotchkiss, CE Doerge, DR Allen, RR Mattison, DR Paule, MG AF Rodriguez, J. S. Morris, S. M. Hotchkiss, C. E. Doerge, D. R. Allen, R. R. Mattison, D. R. Paule, M. G. TI The effects of chronic methylphenidate administration on operant test battery performance in juvenile rhesus monkeys SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Methylphenidate; Juvenile; Operant; Learning; Memory; Attention ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; NMDA RECEPTOR ANTAGONISTS; BEHAVIORAL-TEST BATTERY; NONHUMAN-PRIMATES; PERIADOLESCENT RATS; DEVELOPMENTAL ASPECTS; BRAIN-FUNCTION; DOUBLE-BLIND; CHILDREN; ADHD AB Methylphenidate (MPH) is an amphetamine derivative widely prescribed for the treatment of attention deficit-hyperactivity disorder. Recent concern over its genotoxic potential in children [11] spurred a study on the effects of chronic MPH treatment in a nonhuman primate population and the studies reported here were conducted in conjunction with that study in the same animals. Here, the focus was on the ability of juvenile rhesus monkeys to learn how to perform a battery of operant behavioral tasks while being treated chronically with MPH. Performance of the National Center for Toxicological Research (NCTR) Operant Test Battery (OTB) was used to quantify the learning of tasks thought to model specific aspects of cognitive function including learning, motivation, color and position discrimination, and short-term memory. The OTB tasks designed to assess these specific behaviors included Incremental Repeated Acquisition (IRA), Progressive Ratio (PR), Conditioned Position Responding (CPR), and Delayed Matching-to-Sample (DMTS), respectively. juvenile males (n =10/group) pressed levers and press-plates for banana-flavored food pellets. Subjects were treated orally, twice a day, five days per week (M-F) for 66 weeks with escalating doses (0.15 mg/kg initially, increased to 2.5 mg/kg for the low dose group and to 12.5 mg/kg for the high dose group) and tested in OTB tasks 30 to 60 min after the morning dose. The findings indicate that MPH at doses up to 2.5 mg/kg twice per day were well tolerated (performance was no different than controls) but at doses of 12.5 mg/kg twice per day there was a significant decrement in OTB performance, characterized by decreases in both percent task completed and response rates for all tasks. These effects of MPH seem primarily due to decreases in motivation to perform for food, which is not surprising given the well known appetite suppressing effects of amphetamine-like stimulants. Thus, the current data do not strongly suggest cognitive impairments following chronic MPH administration. (C) 2009 Elsevier Inc. All rights reserved. C1 [Rodriguez, J. S.; Paule, M. G.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Morris, S. M.] US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Hotchkiss, C. E.] US FDA, Bionet Corp, Natl Ctr Toxicol Res, Jefferson, AR USA. [Doerge, D. R.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Allen, R. R.] Peak Stat Serv, Evergreen, CO USA. [Mattison, D. R.] NICHHD, Obstet & Pediat Pharmacol Branch, NIH, Bethesda, MD 20892 USA. RP Rodriguez, JS (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. EM rodriguezj13@uthscsa.edu RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 FU National Institute on Child Health and Human Development; National Center for Toxicological Research [224-05-0003]; Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the FDA FX Funding: These studies were supported through an interagency agreement between the National Institute on Child Health and Human Development and the National Center for Toxicological Research, 224-05-0003 and a postdoctoral fellowship from the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the FDA (to J. Rodriguez). NR 44 TC 18 Z9 18 U1 3 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAR-APR PY 2010 VL 32 IS 2 BP 142 EP 151 DI 10.1016/j.ntt.2009.08.011 PG 10 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 583TJ UT WOS:000276702500004 PM 19737611 ER PT J AU Neese, SL Wang, VC Doerge, DR Woodling, KA Andrade, JE Helferich, WG Korol, DL Schantz, SL AF Neese, Steven L. Wang, Victor C. Doerge, Daniel R. Woodling, Kellie A. Andrade, Juan E. Helferich, William G. Korol, Donna L. Schantz, Susan L. TI Impact of dietary genistein and aging on executive function in rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Genistein; Aging; Executive function; Dopamine; Prefrontal ID ESTROGEN-RECEPTOR-ALPHA; DELAYED ALTERNATION TASK; MEDIAL PREFRONTAL CORTEX; AGED RHESUS-MONKEYS; CHROMATOGRAPHY-MASS-SPECTROMETRY; HORMONE-REPLACEMENT THERAPY; WORKING-MEMORY PERFORMANCE; AFFECTS SPATIAL REFERENCE; CENTRAL-NERVOUS-SYSTEM; DOPAMINE UPTAKE SITES AB Genistein is an estrogenic soy isoflavone widely promoted for healthy aging, but its effects on cognitive function are not well-understood. We examined the cognitive effects of once daily oral genistein treatment at two doses (approximately 162 mu g/kg/day low dose and a 323 pg/kg/day high dose) in ovariectomized young (7 month), middle-aged (16 month), and old (22 month) Long-Evans rats. Operant tasks including delayed spatial alternation (DSA), differential reinforcement of low rates of responding (DRL), and reversal learning that tap prefrontal cortical function were used to assess working memory, inhibitory control/timing, and strategy shifting, respectively. At the conclusion of cognitive testing, brains were collected and relative densities of D1 and D2 dopamine receptors and dopamine transporter (DAT) were measured in the prefrontal cortex. On the DSA task, the high dose old group performed worse than both the high dose young and middle-aged groups. On the DRL task, the high dose of genistein resulted in a marginally significant impairment in the ratio of reinforced to non-reinforced lever presses. This effect was present across age groups. Age effects were also found as old rats performed more poorly than the young and middle-aged rats on the DSA overall. In contrast, middle-aged and old rats made fewer lever presses on the DRL than did the young rats, a pattern of behavior associated with better performance on this task. Moreover, while DAT levels overall decreased with age, genistein treatment produced an increase in DAT expression in old rats relative to similarly aged control rats. D1 and 02 densities did not differ between genistein dose groups or by age. These results highlight the fact that aspects of executive function are differentially sensitive to both genistein exposure and aging and suggest that altered prefrontal dopamine function could potentially play a role in mediating these effects. (C) 2009 Elsevier Inc. All rights reserved. C1 [Neese, Steven L.; Wang, Victor C.; Schantz, Susan L.] Univ Illinois, Dept Vet Sci, Urbana, IL 61802 USA. [Neese, Steven L.; Wang, Victor C.; Korol, Donna L.; Schantz, Susan L.] Univ Illinois, Neurosci Program, Urbana, IL 61801 USA. [Doerge, Daniel R.; Woodling, Kellie A.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Andrade, Juan E.; Helferich, William G.] Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. [Korol, Donna L.] Univ Illinois, Dept Psychol, Champaign, IL 61820 USA. [Korol, Donna L.] Univ Illinois, Dept Vet Sci, Inst Genom Biol, Urbana, IL 61801 USA. RP Neese, SL (reprint author), Dept Vet Sci, 2001 S Lincoln Ave, Urbana, IL 61902 USA. EM stlneese@illinois.edu; vwang@illinois.edu; daniel.doerge@fda.hhs.org; kellie.woodling@fda.hhs.gov; jandrade@illinois.edu; helferich@illinois.edu; dkorol@illinois.edu; schantz@illinois.edu OI Andrade, Juan/0000-0003-2349-9169 FU National Institute of Aging [PO1 AG024387]; NSF IOB [0520876]; National Institute of Environmental Health Sciences [132 ES007326]; 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 FX This research was supported by the National Institute of Aging Grant PO1 AG024387 (SLS) and NSF IOB 0520876 (DLK). Steven Neese and Victor Wang also received support from National Institute of Environmental Health Sciences Grant 132 ES007326. Kellie A. Woodling 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. The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration. NR 96 TC 19 Z9 21 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAR-APR PY 2010 VL 32 IS 2 BP 200 EP 211 DI 10.1016/j.ntt.2009.11.003 PG 12 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 583TJ UT WOS:000276702500012 PM 19945528 ER PT J AU Garey, J Paule, MG AF Garey, Joan Paule, Merle G. TI Effects of chronic oral acrylamide exposure on incremental repeated acquisition (learning) task performance in Fischer 344 rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Acrylamide; Rats; Behavior; Learning; Incremental repeated acquisition; Motivation ID BEHAVIORAL-TEST BATTERY; YOUNG-ADULT RATS; COMPLEX; METABOLISM; CARCINOGEN; MONKEYS; MILK; FOOD AB Acrylamide (ACR) is a relatively potent neurotoxicant. The ingestion of carbohydrate-containing foods cooked at high temperature exposes humans to low levels of ACR virtually daily. At relatively high levels of exposure (i.e., sub-chronic through chronic levels of exposure of >= 20 mg/kg body weight/day). ACR has been shown in both rats and humans to produce a variety of effects on the nervous system. The possibility that chronic dietary exposure to ACR might produce brain toxicity which could impede the development of learning skills is a question of current concern. This research evaluated the effects of ACR on learning task performance in Fischer 344 rats exposed daily beginning prenatally and continuing throughout the lifespan. Dams were gavaged with ACR since implantation [gestation day (GD) 6] with 0, 0.1, 0.3, 1.0 or 5.0 mg/kg/day through parturition. Gavaging continued at the same doses to pups through weaning on post-natal day (PND) 22 after which dosing continued via their drinking water. One male and one female per litter (8-9 per treatment group) were tested. Using an incremental repeated acquisition (IRA) task to assess learning ability, ACR-exposed Fischer 344 rats exhibited altered performance by 4 months of age. From approximately 1-8 months of age (through similar to PND 240), over 52 testing sessions, a significant treatment effect was found on percent task completed (PTC), with Tukey's post-hoc test (P<0.05) indicating a significantly lower FTC for the 5.0 mg/kg/day group compared to controls. While there was no treatment effect on accuracy (P=0.53), a significant decrease in response rate was seen at 5.0 mg/kg/day, suggesting that the noted decrease in PTC was due to a decrease in rate of responding, not to an effect on accuracy of task solution. Previous findings in these same animals performing a progressive ratio task for the assessment of motivation, as well as a range of tests of motoric function, suggest that this decreased response rate could be due to subtle motoric effects, or possibly due to decreases in psychomotor speed, but is most likely due to motivational effects. (C) 2009 Elsevier Inc. All rights reserved. C1 [Garey, Joan; Paule, Merle G.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72211 USA. RP Garey, J (reprint author), SRC, Ctr Environm Sci, 2451 Crystal Dr,Suite 804, Arlington, VA 22202 USA. EM jgarey@srcinc.com FU NIEHS [NTP 224-93-0001]; Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the FDA FX Many thanks to the staff of Bionetics Corporation, especially Delbert Law, for their outstanding work on this experiment. Additional thanks to Matt Fogle of NCTR and Martin Jackson of Z-Tech Corporation for their dedication in maintaining the NCTR operant testing apparatus. This study was supported through an interagency agreement between the FDA and the National Toxicology Program of NIEHS (NTP 224-93-0001) and a postdoctoral fellowship from the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the FDA (to J. Garey). The findings and interpretations of the data presented here are those of the authors and do not necessarily reflect the opinion of the US Food and Drug Administration. NR 29 TC 3 Z9 4 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAR-APR PY 2010 VL 32 IS 2 BP 220 EP 225 DI 10.1016/j.ntt.2009.10.001 PG 6 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 583TJ UT WOS:000276702500014 PM 19846048 ER PT J AU Lund, PE Hunt, RC Gottesman, MM Kimchi-Sarfaty, C AF Lund, Paul E. Hunt, Ryan C. Gottesman, Michael M. Kimchi-Sarfaty, Chava TI Pseudovirions as Vehicles for the Delivery of siRNA SO PHARMACEUTICAL RESEARCH LA English DT Review DE pseudoviral delivery vehicle; pseudovirion; siRNA delivery ID HVJ ENVELOPE VECTOR; SMALL INTERFERING RNA; SIMPLEX-VIRUS TYPE-1; HSV-1 AMPLICON VECTORS; MEDIATED GENE-TRANSFER; PHAGE-DISPLAY VECTORS; CAPSID PROTEIN VP1; HUMAN GLIOMA-CELLS; ADULT-RAT LIVER; IN-VIVO AB Over the last two decades, small interfering RNA (siRNA)-mediated gene silencing has quickly become one of the most powerful techniques used to study gene function in vitro and a promising area for new therapeutics. Delivery remains a significant impediment to realizing the therapeutic potential of siRNA, a problem that is also tied to immunogenicity and toxicity. Numerous delivery vehicles have been developed, including some that can be categorized as pseudovirions: these are vectors that are directly derived from viruses but whose viral coding sequences have been eliminated, preventing their classification as viral vectors. Characteristics of the pseudovirions discussed in this review, namely phagemids, HSV amplicons, SV40 in vitro-packaged vectors, influenza virosomes, and HVJ-Envelope vectors, make them attractive for the delivery of siRNA-based therapeutics. Pseudovirions were shown to deliver siRNA effector molecules and bring about RNA interference (RNAi) in various cell types in vitro, and in vivo using immune-deficient and immune-competent mouse models. Levels of silencing were not always determined directly, but the duration of siRNA-induced knockdown lasted at least 3 days. We present examples of the use of pseudovirions for the delivery of synthetic siRNA as well as the delivery and expression of DNA-directed siRNA. C1 [Hunt, Ryan C.; Kimchi-Sarfaty, Chava] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Lund, Paul E.; Gottesman, Michael M.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kimchi-Sarfaty, C (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. EM Chava.Kimchi-Sarfaty@fda.hhs.gov FU National Institutes of Health, National Cancer Institute; Center for Biologics Evaluation and Research FX The authors thank George Leiman for his editorial assistance with this manuscript as well as his insightful aide in the preparation of the figures. This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute and by the Research Participation program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 134 TC 8 Z9 8 U1 0 U2 8 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 MAR PY 2010 VL 27 IS 3 BP 400 EP 420 DI 10.1007/s11095-009-0012-2 PG 21 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 563JB UT WOS:000275123600003 PM 19998056 ER PT J AU Huang, WT Chang, S Miller, ER Woo, EJ Hoffmaster, AR Gee, JE Clark, TA Iskander, JK Ball, R Broder, KR AF Huang, Wan-Ting Chang, Soju Miller, Elaine R. Woo, Emily Jane Hoffmaster, Alex R. Gee, Jay E. Clark, Thomas A. Iskander, John K. Ball, Robert Broder, Karen R. TI Safety assessment of recalled Haemophilus influenzae type b (Hib) conjugate vaccines-United States, 2007-2008 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE vaccine safety; Bacillus cereus; Haemophilus vaccines ID EVENT REPORTING SYSTEM; BACILLUS-CEREUS; VACCINATION; VAERS AB Purpose On 13 December 2007, Merck & Co., Inc. voluntarily recalled 1.2 million doses of Haemophilus influenzae type b (Hib) vaccines that had been distributed since April 2007 for concerns regarding potential Bacillus cereus contamination. Enhanced postrecall surveillance was conducted to detect vaccine-associated B. cereus infections. Methods We reviewed reports involving recalled Hib vaccines received by the Vaccine Adverse Event Reporting System (VAERS) during 1 April 2007-29 February 2008. For each reported death, autopsy review sought evidence of B. cereus infections, For each specified outcome, the proportional reporting ratios (PRRs) were calculated to compare the recalled I-lib vaccines with the manufacturer's nonrecalled Hib vaccines in the VAERS databases. On 20 December 2007, we used the Epidemic Information Exchange (Epi-X) to solicit nongastrointestinal vaccine-associated B. cereus infections, and requested B. cereus isolates for genotyping to compare with the manufacturing facility isolate. Results VAERS received 75 reports involving recalled Hib vaccines; none described a confirmed B. cereus infection. Comparative analyses did not reveal disproportionate reporting of specified outcomes for recalled Hib vaccines. The Epi-X posting triggered one report of vaccine-associated B. cereus bacteremia from a child who received a nonrecalled Hib vaccine manufactured by Merck; the genotypes of isolates from the patient and the manufacturing facility differed. Conclusions No evidence of vaccine-associated B. cereus infection had been found in recipients of recalled Hib vaccines. Conducting laboratory surveillance through Epi-X was feasible and may enhance public health response capacities for future vaccine safety emergencies. Published in 2010 by John Wiley & Sons, Ltd. C1 [Huang, Wan-Ting] CDC, Epidemic Intelligence Serv, Career Dev Div, Off Workforce & Career Dev,Ctr Dis Control & Prev, Atlanta, GA 30333 USA. [Huang, Wan-Ting; Miller, Elaine R.; Iskander, John K.; Broder, Karen R.] CDC, Immunizat Safety Off, Div Healthcare Qual Promot Proposed, Natl Ctr Preparedness Detect & Control Infect Dis, Atlanta, GA 30333 USA. [Chang, Soju; Woo, Emily Jane; Ball, Robert] US FDA, Div Epidemiol, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Hoffmaster, Alex R.; Gee, Jay E.] CDC, Bacterial Zoonoses Branch, Div Foodborne Bacterial & Mycot Dis, Natl Ctr Zoonot Vector Borne & Enter Dis, Atlanta, GA 30333 USA. [Clark, Thomas A.] CDC, Meningitis & Vaccine Preventable Dis Branch, Div Bacterial Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. RP Broder, KR (reprint author), Ctr Dis Control & Prevent, Immunizat Safety Off, Div Healthcare Qual Promot Proposed, 1600 Clifton Rd NE,MS D26, Atlanta, GA 30333 USA. EM kbroder@cdc.gov RI Huang, Wan-Ting/E-3497-2010 OI Huang, Wan-Ting/0000-0002-4344-9567 FU US Department of Health and Human Services FX We thank Merck for voluntarily providing an isolate of B. cereus from the manufacturing equipment to CDC for genotyping. We also thank Christopher Paddock, MD, MPHTM (CDC Infectious Disease Pathology Branch), state health department staff and local medical examiners for their contributions to the autopsy reviews. The following CDC staff assisted in the surveillance through the Vaccine Adverse Event Reporting System: Penina Haber, MPH, Beth Hibbs, RN, MPH, Susan Duderstadt, MD, MPH, and Tracy Thomas, MPH. This work was financially supported by US Department of Health and Human Services. NR 15 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD MAR PY 2010 VL 19 IS 3 BP 306 EP 310 DI 10.1002/pds.1909 PG 5 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 570QT UT WOS:000275693700012 PM 20084617 ER PT J AU Aquilante, CL Kosmiski, LA Zineh, I Rome, LC Knutsen, SD AF Aquilante, Christina L. Kosmiski, Lisa A. Zineh, Issam Rome, Lucille Capo Knutsen, Shannon D. TI Pharmacodynamic Effects of Rosiglitazone in Nondiabetic Patients with Metabolic Syndrome SO PHARMACOTHERAPY LA English DT Article DE rosiglitazone; metabolic syndrome; adiponectin; resistin ID DENSITY-LIPOPROTEIN CHOLESTEROL; PLASMA ADIPONECTIN LEVELS; C-REACTIVE PROTEIN; INFLAMMATORY MARKERS; INSULIN-RESISTANCE; ENDOTHELIAL FUNCTION; RISK-FACTORS; MYOCARDIAL-INFARCTION; GENE-EXPRESSION; PIOGLITAZONE AB Study Objectives. To determine the effects of the thiazolidinedione rosiglitazone on the adipocyte-derived cytokines adiponectin (all antiinflammatory and insulin-sensitizing cytokine, low levels have been associated with metabolic syndrome) and resistin (an inflammation mediator, high levels slave been associated with metabolic syndrome) in nondiabetic patients with metabolic syndrome, and to characterize the effects of rosiglitazone on other components of the metabolic syndrome phenotype in this Population. Design. Prospective, randomized, double-blind, placebo-controlled study Setting Outpatient general clinical research center Patients. Thirty-two nondiabetic men and women with a clinical diagnosis of metabolic syndrome (as defined in the American Heart Association-National Heart, Lung, and Blood Institute scientific statement) Intervention. Patients were randomly assigned to receive either oral rosiglitazone 4 mg/day or matching placebo for 12 weeks Measurements and Main Results. The primary end point. was change in serum adiponectin concentrations from baseline to week 12 Secondary end points were Changes in serum resistin concentrations, insulin resistance, fasting glucose level, fasting insulin level, body weight, lipid levels, systolic and diastolic blood pressure, and waist circumference from baseline to week 12 Also, changes from baseline in adiponectin and resistin concentrations and insulin resistance were assessed over time at weeks 2, 4, 8, and 12 Rosiglitazone was associated with a significant increase. in serum adiponectin concentration after 12 weeks compared with placebo (45.8% vs 2 6%, p=0.002). The increase in adiponectin concentration occurred quickly; with a significant difference observed after 2 weeks of therapy Compared with placebo, rosiglitazone was clot associated with significant 12-week changes in serum resistin concentrations, insulin resistance, fasting glucose level, fasting insulin level, body weight, lipid levels, systolic or diastolic blood pressure, or waist circumference Conclusion. Rosiglitazone had beneficial effects on adiponectin concentrations without significantly affecting other components of the metabolic syndrome phenotype. Additional studies that further elucidate the lime Course of thiazolidinedione pharmacodynamic effects, along with their effects on cardiovascular end points, are warranted in nondiabetic patients with metabolic syndrome C1 [Aquilante, Christina L.; Rome, Lucille Capo; Knutsen, Shannon D.] Univ Colorado, Dept Pharmaceut Sci, Sch Pharm, Denver, CO 80202 USA. [Kosmiski, Lisa A.] Univ Colorado, Sch Med, Div Endocrinol Diabet & Metab, Denver, CO USA. [Zineh, Issam] US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Silver Spring, MD USA. RP Aquilante, CL (reprint author), Univ Colorado Denver, Sch Pharm, Dept Pharmaceut Sci, 12700 E 19th Ave,Box C238-P15, Aurora, CO 80045 USA. FU NCRR NIH HHS [M01 RR000051] NR 45 TC 6 Z9 6 U1 0 U2 2 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 MAR PY 2010 VL 30 IS 3 BP 236 EP 247 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 566FT UT WOS:000275356200004 PM 20180607 ER PT J AU Pope, SJ Godar, DE AF Pope, Stanley J. Godar, Dianne E. TI Solar UV Geometric Conversion Factors: Horizontal Plane to Cylinder Model dagger SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID ARBITRARILY ORIENTED SURFACES; INCLINED SURFACES; IRRADIANCE; RADIATION; EXPOSURE AB Most solar UV measurements are relative to the horizontal plane. However, problems arise when one uses those UV measurements to perform risk or benefit assessments because they do not yield the actual doses people get while they are outdoors. To better estimate the UV doses people actually get while outdoors, scientists need geometric conversion factors (GCF) that change horizontal plane irradiances to average irradiances on the human body. Here we describe a simple geometric method that changes unweighted, erythemally weighted and previtamin D(3)-weighted UV irradiances on the horizontal plane to full cylinder and semicylinder irradiances. Scientists can use the full cylinder model to represent the complete human body, while they can use the semicylinder model to represent the face, shoulders, tops of hands and feet. We present daily, monthly and seasonally calculated averages of the GCF for these cylinder models every 5 degrees from 20 to 70 degrees N so that scientists can now get realistic UV doses for people who are outdoors doing a variety of different activities. The GCF show that people actually get less than half their annual erythemally weighted, and consequently half their previtamin D(3)-weighted, UV doses relative to the horizontal plane. Thus, scientists can now perform realistic UV risk and benefit assessments. C1 [Godar, Dianne E.] US FDA, Silver Spring, MD USA. [Pope, Stanley J.] Sun Syst & Svc Inc, Oak Pk, MI USA. RP Godar, DE (reprint author), US FDA, Silver Spring, MD USA. EM Dianne.Godar@fda.hhs.gov OI GODAR, DIANNE/0000-0002-7690-5223 NR 23 TC 15 Z9 15 U1 0 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD MAR-APR PY 2010 VL 86 IS 2 BP 457 EP 466 DI 10.1111/j.1751-1097.2009.00679.x PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 563DM UT WOS:000275107700031 PM 20059727 ER PT J AU Joffe, HV Parks, MH Temple, R AF Joffe, Hylton V. Parks, Mary H. Temple, Robert TI Impact of cardiovascular outcomes on the development and approval of medications for the treatment of diabetes mellitus SO REVIEWS IN ENDOCRINE & METABOLIC DISORDERS LA English DT Article DE Diabetes mellitus; Cardiovascular disease; Drug development; Food and Drug Administration ID CORONARY-HEART-DISEASE; BLOOD-GLUCOSE CONTROL; PRIMARY PREVENTION; RISK FACTOR; TYPE-2; MORTALITY; ROSIGLITAZONE; COMPLICATIONS; WOMEN; TRIAL AB All medications currently approved by the Food and Drug Administration (FDA) for the treatment of type 2 diabetes mellitus are indicated to improve glycemic control. Since 1995, FDA has used HbA1c as the primary basis for approval of these therapies because a reduction in blood glucose lessens the symptoms of hyperglycemia and lowering of HbA1c has been shown to reduce the risk for some of the chronic complications of diabetes. Despite evidence of clinical benefit with therapies that reduce HbA1c, concerns have been raised that some diabetes medications may increase cardiovascular risk in a patient population that is already vulnerable to cardiovascular disease. Therefore, FDA convened a public advisory committee meeting to discuss the role of cardiovascular assessment in the pre-approval and post-approval settings for medications developed for the treatment of type 2 diabetes. After considering the advisory panel's recommendations and other data, FDA published a guidance document requesting evidence showing that new treatments for type 2 diabetes do not result in an unacceptable increase in cardiovascular risk. This review article begins by summarizing the events leading up to publication of this guidance. Subsequent sections discuss the guidance itself as well as general considerations for implementing the new cardiovascular recommendations. The new approach to developing medications for the treatment of type 2 diabetes will lead to evaluation in patients more representative of those who will use these therapies, if approved, and will help healthcare providers make informed decisions when choosing a medication within the growing treatment armamentarium for type 2 diabetes. C1 [Joffe, Hylton V.; Parks, Mary H.] US FDA, Div Metab & Endocrinol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Joffe, HV (reprint author), US FDA, Div Metab & Endocrinol Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Room 3340, Silver Spring, MD 20993 USA. EM hylton.joffe@fda.hhs.gov NR 29 TC 14 Z9 14 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9155 J9 REV ENDOCR METAB DIS JI Rev. Endocr. Metab. Disord. PD MAR PY 2010 VL 11 IS 1 SI SI BP 21 EP 30 DI 10.1007/s11154-010-9130-8 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 576MW UT WOS:000276149600003 PM 20195772 ER PT J AU Rosenfeldt, H Kropp, T Benson, K Ricci, MS McGuinn, WD Verbois, SL AF Rosenfeldt, Hans Kropp, Timothy Benson, Kimberly Ricci, M. Stacey McGuinn, W. David Verbois, S. Leigh TI Regulatory aspects of oncology drug safety evaluation: Past practice, current issues, and the challenge of new drugs SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Review DE Cancer; Preclinical; Drug development; Regulation; Lehman ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; EARLY CLINICAL-TRIALS; RENAL-CELL CARCINOMA; IMATINIB MESYLATE; BREAST-CANCER; CONDITIONAL EXPRESSION; K-RAS; CARDIOTOXICITY; THERAPY AB The drug development of new anti-cancer agents is streamlined in response to the urgency of bringing effective drugs to market for patients with limited life expectancy. FDA's regulation of oncology drugs has evolved from the practices set forth in Arnold Lehman's seminal work published in the 1950s through the Current drafting of a new International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) safety guidance for anti-cancer drug nonclinical evaluations. The ICH combines the efforts of the regulatory authorities of Europe, Japan. and the United States and the pharmaceutical industry from these three regions to streamline the scientific and technical aspects of drug development. The recent development of new oncology drug classes with novel mechanisms of action has improved survival rates for some cancers but also brings new challenges for safety evaluation. Here we present the legacy of Lehman and colleagues in the context of past and present oncology drug development practices and focus on some of the current issues at the center of an evolving harmonization process that will generate a new safety guidance for oncology drugs, ICH S9. The purpose of this new guidance will be to facilitate oncology drug development on a global scale by standardizing regional safety requirements. Published by Elsevier Inc. C1 [Rosenfeldt, Hans] US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Div Drug Oncol Prod, Silver Spring, MD 20993 USA. [Ricci, M. Stacey] US FDA, Div Biol Oncol Prod, Silver Spring, MD 20993 USA. RP Rosenfeldt, H (reprint author), US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Div Drug Oncol Prod, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM hans.rosenfeldt@fda.hhs.gov NR 48 TC 5 Z9 5 U1 0 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAR 1 PY 2010 VL 243 IS 2 SI SI BP 125 EP 133 DI 10.1016/j.taap.2009.12.020 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 565NS UT WOS:000275301400002 PM 20045015 ER PT J AU Zhang, L Reynolds, KS Zhao, P Huang, SM AF Zhang, Lei Reynolds, Kellie S. Zhao, Ping Huang, Shiew-Mei TI Drug interactions evaluation: An integrated part of risk assessment of therapeutics SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Review DE Drug interactions; Risk assessment; Cytochrome P450 enzymes; Transporter proteins; Inhibition; Induction ID IN-VITRO DATA; ORGANIC CATION TRANSPORTER; METABOLIZING-ENZYMES; P-GLYCOPROTEIN; PHARMACEUTICAL RESEARCH; GENETIC-VARIATION; HUMAN LIVER; QUANTITATIVE PREDICTION; PHARMACOKINETIC MODELS; MIDAZOLAM CLEARANCE AB Pharmacokinetic drug interactions can lead to serious adverse events or decreased drug efficacy. The evaluation of a new molecular entity's (NME's) drug-drug interaction potential is an integral part of risk assessment during drug development and regulatory review. Alteration of activities of enzymes or transporters involved in the absorption, distribution, metabolism, or excretion of a new molecular entity by concomitant drugs may alter drug exposure, which can impact response (safety or efficacy). The recent Food and Drug Administration (FDA) draft drug interaction guidance (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072101.pdf) highlights the methodologies and criteria that may be used to guide drug interaction evaluation by industry and regulatory agencies and to construct informative labeling for health practitioner and patients. In addition, the Food and Drug Administration established a "Drug Development and Drug Interactions" website to provide up-to-date information regarding evaluation of drug interactions (http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm080499.htm). This review summarizes key elements in the FDA drug interaction guidance and new scientific developments that can guide the evaluation of drug-drug interactions during the drug development process. Published by Elsevier Inc. C1 [Zhang, Lei; Reynolds, Kellie S.; Zhao, Ping; Huang, Shiew-Mei] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Huang, SM (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Bldg 51,Room 3188,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM shiewmei.huang@fda.hhs.gov NR 92 TC 68 Z9 76 U1 1 U2 20 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 MAR 1 PY 2010 VL 243 IS 2 SI SI BP 134 EP 145 DI 10.1016/j.taap.2009.12.016 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 565NS UT WOS:000275301400003 PM 20045016 ER PT J AU Beger, RD Sun, JC Schnackenberg, LK AF Beger, Richard D. Sun, Jinchun Schnackenberg, Laura K. TI Metabolomics approaches for discovering biomarkers of drug-induced hepatotoxicity and nephrotoxicity SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Review DE Metabolomics; Metabonomics; Heptatotoxicity; Nephrotoxicity ID CHROMATOGRAPHY-MASS SPECTROMETRY; MAGNETIC-RESONANCE-SPECTROSCOPY; PERFORMANCE LIQUID-CHROMATOGRAPHY; STANDARD REPORTING REQUIREMENTS; CORN BRAN HEMICELLULOSE; GENTAMICIN-INDUCED NEPHROTOXICITY; PRINCIPAL COMPONENT ANALYSIS; PATTERN-RECOGNITION ANALYSIS; COMPLEX BIOLOGICAL MIXTURES; NMR-BASED METABOLOMICS AB Hepatotoxicity and nephrotoxicity are two major reasons that drugs are withdrawn post-market, and hence it is of major concern to both the FDA and pharmaceutical companies. The number of cases of serious adverse effects (SAES) in marketed drugs has climbed faster than the number of total drug prescriptions issued. In some cases, preclinical animal studies fail to identify the potential toxicity of a new chemical entity (NCE) under development. The current clinical chemistry biomarkers of liver and kidney injury are inadequate in terms of sensitivity and/or specificity, prompting the need to discover new translational specific biomarkers of organ injury. Metabolomics along with genomics and proteomics technologies have the capability of providing translational diagnostic and prognostic biomarkers specific for early stages of liver and kidney injury. Metabolomics has several advantages over the other omics platforms such as ease of sample preparation, data acquisition and use of biofluids collected through minimally invasive procedures in preclinical and clinical studies. The metabolomics platform is reviewed with particular emphasis on applications involving drug-induced hepatotoxicity and nephrotoxicity. Analytical platforms for metabolomics, chemometrics for mining metabolomics data and the applications of the metabolomics technologies are covered in detail with emphasis on recent work in the field. Published by Elsevier Inc. C1 [Beger, Richard D.; Sun, Jinchun; Schnackenberg, Laura K.] US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Beger, RD (reprint author), US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM richard.beger@fda.hhs.gov NR 153 TC 115 Z9 124 U1 8 U2 84 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAR 1 PY 2010 VL 243 IS 2 SI SI BP 154 EP 166 DI 10.1016/j.taap.2009.11.019 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 565NS UT WOS:000275301400005 PM 19932708 ER PT J AU Carrington, CD Bolger, PM AF Carrington, Clark D. Bolger, P. Michael TI The limits of regulatory toxicology SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Review DE Safety; Risk; Hazard; Food; Uncertainty; Contaminants AB The Acceptable Daily Intake (ADI) has been used by regulatory and public health organizations (e.g., the U.S. Food and Drug and Administration, and the World Health Organization) for chemicals for more than 50 years. The ADI concept was also initially employed at the U.S. Environmental Protection Agency at its inception in 1971, although with the adoption of newer terminology, it later became known as the Reference Dose (RfD). It is clear from the literature that both were first devised as instruments of regulatory policy. In the intervening years, it has become common to use language that implies that these standards are statements of scientific fact. Similarly, some of the discretionary or default values that are used to derive regulatory standards are represented as scientific assumptions when in fact they also represent regulatory policy. This confusion impedes both the best use of the available science and informed public participation in policy making. In addition, the misconception of the ADI or the RfD as statements of scientific fact may impede the consideration of alternative means to reduce exposure to chemicals that may be harmful, including regulatory measures that do not involve prescribing a regulatory concentration limit. Published by Elsevier Inc. C1 [Carrington, Clark D.; Bolger, P. Michael] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Bolger, PM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM mike.bolger@fda.hhs.gov NR 34 TC 5 Z9 6 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAR 1 PY 2010 VL 243 IS 2 SI SI BP 191 EP 197 DI 10.1016/j.taap.2009.12.017 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 565NS UT WOS:000275301400008 PM 20035778 ER PT J AU Mei, N Hu, JX Xia, QS Fu, PP Moore, MM Chen, T AF Mei, Nan Hu, Jiaxiang Xia, Qingsu Fu, Peter P. Moore, Martha M. Chen, Tao TI Cytotoxicity and mutagenicity of retinol with ultraviolet A irradiation in mouse lymphoma cells SO TOXICOLOGY IN VITRO LA English DT Article DE Retinal; UVA; Mouse lymphoma assay; Photomutagenicity; Loss of heterozygosity ID GENE MUTATION ASSAY; VITAMIN-A; LIPID-PEROXIDATION; SERTOLI-CELLS; PHOTODECOMPOSITION PRODUCTS; INTERNATIONAL WORKSHOP; DNA-DAMAGE; PALMITATE; PHOTOMUTAGENICITY; SUPPLEMENTATION AB Vitamin A (all-trans-retinol; retinol) is an essential human nutrient and plays an important role in several biological functions. However, under certain circumstances, retinol treatment can cause free radical generation and induce oxidative stress. In this study, we investigated photocytotoxicity and photomutagenicity of retinol using L5178Y/Tk(+/-) mouse lymphoma cells concomitantly exposed to retinal and ultraviolet A (UVA) light. While the cells treated with retinal alone at the doses of 5 or 10 mu g/ml in the absence of light did not increase the mutant frequency (MF) in the Tk gene, the treatment of the cells with 1-4 mu g/ml retinal under UVA light (1.38 mW/cm(2) for 30 min) increased the MF in the Tk gene in a dose-responsive manner. To elucidate the underlying mechanism of action, we also examined the mutational types of the Tk mutants by determining their loss of heterozygosity (LOH) at four microsatellite loci spanning the entire chromosome 11 on which the Tk gene is located. The mutational spectrum for the retinol + UVA treatment was significantly different from those of the control and UVA alone. More than 93% of the mutants from retinol + UVA treatment lost heterozygosity at the Tk1 locus and the major type (58%) of mutations was LOHs extending to D11Mit42, an alternation involving approximately 6 cM of the chromosome, whereas the main type of mutations in the control was non-LOH mutations. These results suggest that retinol is mutagenic when exposed to UVA in mouse lymphoma cells through a clastogenic mode-of-action. Published by Elsevier Ltd. C1 [Mei, Nan; Hu, Jiaxiang; Moore, Martha M.; Chen, Tao] Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Xia, Qingsu; Fu, Peter P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Mei, N (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. EM nan.mei@fda.hhs.gov RI mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 FU US Department of Energy; US Food and Drug Administration FX This research was partly supported by an appointment (JXH) 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 thank Drs. Frederick A. Beland, Vasily N. Dobrovolsky, and Page B. McKinzie for their helpful discussions and comments. The views presented in this paper do not necessarily reflect those of the US Food and Drug Administration, but express the opinions of the authors. NR 42 TC 8 Z9 8 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-2333 J9 TOXICOL IN VITRO JI Toxicol. Vitro PD MAR PY 2010 VL 24 IS 2 BP 439 EP 444 DI 10.1016/j.tiv.2009.10.004 PG 6 WC Toxicology SC Toxicology GA 574LW UT WOS:000275991700013 PM 19835946 ER PT J AU Vinh, DC Patel, SY Uzel, G Anderson, VL Freeman, AF Olivier, KN Spalding, C Hughes, S Pittaluga, S Raffeld, M Sorbara, LR Elloumi, HZ Kuhns, DB Turner, ML Cowen, EW Fink, D Long-Priel, D Hsu, AP Ding, L Paulson, ML Whitney, AR Sampaio, EP Frucht, DM Deleo, FR Holland, SM AF Vinh, Donald C. Patel, Smita Y. Uzel, Gulbu Anderson, Victoria L. Freeman, Alexandra F. Olivier, Kenneth N. Spalding, Christine Hughes, Stephen Pittaluga, Stefania Raffeld, Mark Sorbara, Lynn R. Elloumi, Houda Z. Kuhns, Douglas B. Turner, Maria L. Cowen, Edward W. Fink, Danielle Long-Priel, Debra Hsu, Amy P. Ding, Li Paulson, Michelle L. Whitney, Adeline R. Sampaio, Elizabeth P. Frucht, David M. Deleo, Frank R. Holland, Steven M. TI Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia SO BLOOD LA English DT Article ID PULMONARY ALVEOLAR PROTEINOSIS; HAIRY-CELL LEUKEMIA; ACUTE MYELOID-LEUKEMIA; BONE-MARROW ORIGIN; INTERFERON-GAMMA; BLOOD MONOCYTES; AVIUM INFECTION; KAPOSI-SARCOMA; KUPFFER CELLS; IFN-GAMMA AB We identified 18 patients with the distinct clinical phenotype of susceptibility to disseminated nontuberculous mycobacterial infections, viral infections, especially with human papillomaviruses, and fungal infections, primarily histoplasmosis, and molds. This syndrome typically had its onset in adulthood (age range, 7-60 years; mean, 31.1 years; median, 32 years) and was characterized by profound circulating monocytopenia (mean, 13.3 cells/mu L; median, 14.5 cells/mu L), B lymphocytopenia (mean, 9.4 cells/mu L; median, 4 cells/mu L), and NK lymphocytopenia (mean, 16 cells/mu L; median, 5.5 cells/mu L). T lymphocytes were variably affected. Despite these peripheral cytopenias, all patients had macrophages and plasma cells at sites of inflammation and normal immunoglobulin levels. Ten of these patients developed 1 or more of the following malignancies: 9 myelodysplasia/leukemia, 1 vulvar carcinoma and metastatic melanoma, 1 cervical carcinoma, 1 Bowen disease of the vulva, and 1 multiple Epstein-Barr virus(+) leiomyosarcoma. Five patients developed pulmonary alveolar proteinosis without mutations in the granulocyte-macrophage colony-stimulating factor receptor or anti-granulocyte-macrophage colony-stimulating factor autoantibodies. Among these 18 patients, 5 families had 2 generations affected, suggesting autosomal dominant transmission as well as sporadic cases. This novel clinical syndrome links susceptibility to mycobacterial, viral, and fungal infections with malignancy and can be transmitted in an autosomal dominant pattern. (Blood. 2010;115:1519-1529) C1 [Vinh, Donald C.; Patel, Smita Y.; Uzel, Gulbu; Anderson, Victoria L.; Freeman, Alexandra F.; Olivier, Kenneth N.; Spalding, Christine; Elloumi, Houda Z.; Hsu, Amy P.; Ding, Li; Paulson, Michelle L.; Sampaio, Elizabeth P.; Holland, Steven M.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Freeman, Alexandra F.] SAIC, Intramural Clin Management & Operat Branch, Frederick, MD USA. [Hughes, Stephen] Newcastle Gen Hosp, Paediat Immunol Unit, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. [Pittaluga, Stefania; Raffeld, Mark] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Sorbara, Lynn R.] NCI, Canc Biomarkers Res Grp, Bethesda, MD 20892 USA. [Turner, Maria L.; Cowen, Edward W.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Whitney, Adeline R.; Deleo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Frucht, David M.] US FDA, Cell Biol Lab, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Holland, SM (reprint author), NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bldg 10 CRC,Rm B3-4141,MSC 1684, Bethesda, MD 20892 USA. EM smh@nih.gov OI VINH, DONALD/0000-0003-1347-7767; DeLeo, Frank/0000-0003-3150-2516 FU Division of Intramural Research; National Institute of Allergy and Infectious Diseases; National Institutes of Health; National Cancer Institute; National Institutes of Health [N01-CO-12400, HHSN261200800001E]; Canadian Institutes of Health Research fellowship FX This work was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, and in part with federal funds from the National Cancer Institute, National Institutes of Health (contracts N01-CO-12400 and HHSN261200800001E). D.C.V. is supported by a Canadian Institutes of Health Research fellowship and by a National Institutes of Health Supplemental Visiting fellowship. NR 59 TC 107 Z9 109 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 25 PY 2010 VL 115 IS 8 BP 1519 EP 1529 DI 10.1182/blood-2009-03-208629 PG 11 WC Hematology SC Hematology GA 561KB UT WOS:000274974200009 PM 20040766 ER PT J AU Martinez, MN Rathbone, MJ Burgess, D Huynh, M AF Martinez, Marilyn N. Rathbone, Michael J. Burgess, Diane Huynh, Mai TI Breakout session summary from AAPS/CRS joint workshop on critical variables in the in vitro and in vivo performance of parenteral sustained release products SO JOURNAL OF CONTROLLED RELEASE LA English DT Review DE Parenteral; Long acting; Sustained release; Modified release; In vitro drug release testing; Microsphere; Liposome; Implant; In situ forming implant; Lipophilic solution; In vivo-in vitro relationship; Quality by design ID FORMING HYDROGELS; MICROSPHERES; DESIGN; PLGA; BIOSIMILARS AB Parenteral drug delivery systems can be designed to provide the flexible delivery characteristics needed in an evolving therapeutic landscape. The goal of some parenteral formulations is to maintain effective drug concentrations over a period of months or years, thereby enhancing patient compliance. When functioning as intended, these formulations can be used to minimize undesirable effects that may occur in response to the fluctuating drug concentrations effected by immediate release products. In other cases, targeted parenteral delivery systems allow for the deposition of drug directly to its site of action, thereby minimizing systemic toxicity. While these novel formulations can be beneficial to both human and veterinary patients, disastrous effects can occur if there is an unanticipated change in product quality or performance. With these thoughts in mind, the Controlled Release Society (CRS) hosted a 2007 workshop entitled "In Vitro and In Vivo Considerations Associated with Parenteral Sustained Release Products". The objective of that workshop was to explore the physicochemical properties of parenteral products and the factors that could alter their in vitro and in vivo performance characteristics. The outcomes of that workshop were summarized in a journal of Controlled Release article [1]. In response to questions raised during that workshop, the CRS and the American Association of Pharmaceutical Scientist (AAPS) co-hosted the follow-up 2008 workshop entitled "Critical Variables in the In Vitro and In Vivo Performance of Parenteral Sustained Release Products". This 2008 workshop provided a platform for exploring the application of design space concepts to these complex pharmaceuticals, and to consider the corresponding in vitro test methods that can be used to set batch release specifications. To foster discussion, the workshop provided two afternoon breakout sessions where critical questions were explored. This manuscript captures the results of those discussions. Published by Elsevier B.V. C1 [Martinez, Marilyn N.; Huynh, Mai] US FDA, Ctr Vet Med, Rockville, MD 20855 USA. [Rathbone, Michael J.] Griffith Univ, Sch Pharm, Griffith, Qld 4222, Australia. [Burgess, Diane] Univ Connecticut, Storrs, CT 06269 USA. RP Martinez, MN (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl, Rockville, MD 20855 USA. EM marilyn.martinez@fda.hhs.gov NR 25 TC 20 Z9 20 U1 4 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD FEB 25 PY 2010 VL 142 IS 1 BP 2 EP 7 DI 10.1016/j.jconrel.2009.09.028 PG 6 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 569HH UT WOS:000275586700002 PM 19808069 ER PT J AU Ackerman, LK Noonan, GO Heiserman, WM Roach, JA Limm, W Begley, TH AF Ackerman, Luke K. Noonan, Gregory O. Heiserman, Wendy M. Roach, John A. Limm, William Begley, Timothy H. TI Determination of Bisphenol A in US Infant Formulas: Updated Methods and Concentrations SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE BPA; MS/MS; infant formula; can ID TANDEM MASS-SPECTROMETRY; CANNED FOODS; LIQUID-CHROMATOGRAPHY; GAS-CHROMATOGRAPHY; DIGLYCIDYL ETHER; COATINGS; MIGRATION; EPOXY; CONTAMINATION; DERIVATIVES AB An updated survey of U.S. infant formula was conducted to determine the concentrations of bisphenol A (BPA). The purpose was to accurately assess BPA concentrations across the infant formula market, accounting for lot variability, and determine if geographic location or can age influences BPA concentrations. A method was developed to measure BPA in formula utilizing isotope dilution, solid-phase extraction, and liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The method was tested and found to be reproducible (10% relative standard deviation), reliable (47 +/- 1% recovery), and sensitive (0.15 ng g(-1) method detection limit). Over 160 analyses were conducted using 104 formula containers representing 36 products. Samples from U.S. east and west coast markets demonstrated no significant difference, and concentrations in older cans were not higher. BPA concentrations in liquid formula (0.48-11 ng g(-1)) were consistent with previous studies, and BPA was detected in only 1 of 14 powder formula products analyzed. C1 [Ackerman, Luke K.; Noonan, Gregory O.; Heiserman, Wendy M.; Roach, John A.; Limm, William; Begley, Timothy H.] US FDA, Div Analyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Ackerman, LK (reprint author), US FDA, Div Analyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Luke.Ackerman@fda.hhs.gov RI Ackerman, Luke/E-4597-2011; OI Ackerman, Luke/0000-0001-6626-3039; zaraat, javad/0000-0001-5341-7481 NR 24 TC 39 Z9 39 U1 3 U2 34 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD FEB 24 PY 2010 VL 58 IS 4 BP 2307 EP 2313 DI 10.1021/jf903959u PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 555QZ UT WOS:000274530100037 PM 20102208 ER PT J AU Sridhara, R Johnson, JR Justice, R Keegan, P Chakravarty, A Pazdur, R AF Sridhara, Rajeshwari Johnson, John R. Justice, Robert Keegan, Patricia Chakravarty, Aloka Pazdur, Richard TI Review of Oncology and Hematology Drug Product Approvals at the US Food and Drug Administration Between July 2005 and December 2007 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RENAL-CELL CARCINOMA; ACUTE LYMPHOBLASTIC-LEUKEMIA; 1ST-LINE TREATMENT; MULTIPLE-MYELOMA; ATTRITION RATES; COMBINATION; CANCER; INTOLERANT; LYMPHOMA; IMATINIB AB The Office of Oncology Drug Products (OODP) in the Center for Drug Evaluation and Research at the US Food and Drug Administration began reviewing marketing applications for oncological and hematologic indications in July 2005. We conducted an overview of products that were reviewed by the OODP for marketing approval and the regulatory actions taken during July 2005 to December 2007. We identified all applications that were reviewed by the OODP from July 1, 2005, through December 31, 2007, and reviewed the actions that OODP took. We also sought the basis for the actions taken, including the clinical trial design, endpoints used, patient accrual in the trial(s) supporting approval, and the type of regulatory approval. During the study period, the OODP reviewed marketing applications for 60 new indications and took regulatory action on 58 indications. Regulatory action was based on a risk-benefit evaluation of the data submitted with each application. Products that demonstrated efficacy and had an acceptable risk-benefit ratio were granted either regular or accelerated marketing approval for use in the specific indication that was studied. Regular approval was based on endpoints that demonstrated that the drug provided clinical benefit as evidenced by a longer or better life or a favorable effect on an established surrogate for a longer or better life. Accelerated approval was based on a less well-established surrogate endpoint that was reasonably likely to predict a longer or better life. Of the 53 new indications that were approved during the study period, 39 received regular approval, nine received accelerated approval, and five were converted from accelerated to regular approval. Five applications were not approved, and two applications were withdrawn before any regulatory action was taken. Eighteen of the 53 indications that were approved were for new molecular entities. During the study period, regulatory action was taken on 58 of the 60 marketing applications. Fifty-three applications were approved. A variety of clinical trial endpoints were used in the approval trials. C1 [Sridhara, Rajeshwari; Chakravarty, Aloka] US FDA, Ctr Drug Evaluat & Res, Div Biometr 5, Off Translat Sci, Silver Spring, MD USA. [Johnson, John R.; Justice, Robert; Keegan, Patricia; Pazdur, Richard] US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, Silver Spring, MD USA. RP Sridhara, R (reprint author), 10903 New Hampshire Ave,White Oak Bldg 21,Rm 3512, Silver Spring, MD 20993 USA. EM rajeshwari.sridhara@fda.hhs.gov NR 50 TC 48 Z9 48 U1 0 U2 1 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 FEB 24 PY 2010 VL 102 IS 4 BP 230 EP 243 DI 10.1093/jnci/djp515 PG 14 WC Oncology SC Oncology GA 561NM UT WOS:000274984500009 PM 20118413 ER PT J AU Liebertz, DJ Lechner, MG Masood, R Sinha, UK Han, J Puri, RK Correa, AJ Epstein, AL AF Liebertz, Daniel J. Lechner, Melissa G. Masood, Rizwan Sinha, Uttam K. Han, Jing Puri, Raj K. Correa, Adrian J. Epstein, Alan L. TI Establishment and Characterization of a Novel Head and Neck Squamous Cell Carcinoma Cell Line USC-HN1 SO HEAD & NECK ONCOLOGY LA English DT Article ID GENE-EXPRESSION PROFILES; STEM-LIKE CELLS; CANCER; EXPANSION; BIOLOGY; PCR; HPV AB Background: Head and neck squamous cell carcinoma (HNSCC) is an aggressive and lethal malignancy. Publically available cell lines are mostly of lingual origin, or have not been carefully characterized. Detailed characterization of novel HNSCC cell lines is needed in order to provide researchers a concrete keystone on which to build their investigations. Methods: The USC-HN1 cell line was established from a primary maxillary HNSCC biopsy explant in tissue culture. The immortalized cells were then further characterized by heterotransplantation in Nude mice; immunohistochemical staining for relevant HNSCC biomarkers; flow cytometry for surface markers; cytogenetic karyotypic analysis; human papillomavirus and Epstein-Barr virus screening; qRT-PCR for oncogene and cytokine analysis; investigation of activated, cleaved Notch1 levels; and detailed 35,000 gene microarray analysis. Results: Characterization experiments confirmed the human HNSCC origin of USC-HN1, including a phenotype similar to the original tumor. Viral screening revealed no HPV or EBV infection, while western blotting displayed significant upregulation of activated, cleaved Notch1. Conclusions: USC-HN1, a novel immortalized cell line has been derived from a maxillary HNSCC. Characterization studies have shown that the cell line is of HNSCC origin and displays many of the same markers previously reported in the literature. USC-HN1 is available for public research and will further the investigation of HNSCC and the development of new therapeutic modalities. C1 [Liebertz, Daniel J.; Lechner, Melissa G.; Correa, Adrian J.; Epstein, Alan L.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. [Masood, Rizwan; Sinha, Uttam K.] Univ So Calif, Keck Sch Med, Dept Otolaryngol, Los Angeles, CA 90033 USA. [Han, Jing; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Epstein, AL (reprint author), Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. EM aepstein@usc.edu OI Lechner, Melissa/0000-0002-4744-6566 FU American Type Tissue Collection; Cancer Therapeutics Laboratories, Los Angeles, CA FX The authors wish to acknowledge the expert technical assistance of the City of Hope Cytogenetic Core Facility (Duarte, CA) in performing the cytogenetic studies on the USC-HN1 cell line, Ms. Lillian Young for her help with the IHC studies, Dr. Clive Taylor for his assistance with microphotography, Dr. Dixon Gray for his help with the flow cytometry studies, and Mr. James Pang for performing the animal investigations. This work was supported in part by a grant from the American Type Tissue Collection and from funds provided by Cancer Therapeutics Laboratories, Los Angeles, CA. NR 26 TC 19 Z9 19 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-3284 J9 HEAD NECK ONCOL JI Head Neck Oncol. PD FEB 22 PY 2010 VL 2 AR 5 DI 10.1186/1758-3284-2-5 PG 14 WC Oncology SC Oncology GA 840HK UT WOS:000296429900001 PM 20175927 ER PT J AU Feigelstock, DA Mihalik, KB Kaplan, G Feinstone, SM AF Feigelstock, Dino A. Mihalik, Kathleen B. Kaplan, Gerardo Feinstone, Stephen M. TI Increased susceptibility of Huh7 cells to HCV replication does not require mutations in RIG-I SO VIROLOGY JOURNAL LA English DT Article ID HEPATITIS-C VIRUS; RNA REPLICATION; HEPATOMA-CELLS; INFECTION; CULTURE; LINES AB Background: The cytosolic retinoic acid-inducible gene I (RIG-I) is a pattern recognition receptor that senses HCV double-stranded RNA and triggers type I interferon pathways. The clone Huh7.5 of human hepatoma Huh7 cells contains a mutation in RIG-I that is believed to be responsible for the improved replication of HCV in these cells relative to the parental strain. We hypothesized that, in addition to RIG-I, other determinant(s) outside the RIG-I coding sequence are involved in limiting HCV replication in cell culture. To test our hypothesis, we analyzed Huh7 cell clones that support the efficient replication of HCV and analyzed the RIG-I gene. Results: One clone, termed Huh7D, was more permissive for HCV replication and more efficient for HCV-neomycin and HCV-hygromycin based replicon colony formation than parental Huh7 cells. Nucleotide sequence analysis of the RIG-I mRNA coding region from Huh7D cells showed no mutations relative to Huh7 parental cells. Conclusions: We derived a new Huh7 cell line, Huh7D, which is more permissive for HCV replication than parental Huh7 cells. The higher permissiveness of Huh7D cells is not due to mutations in the RIG-I protein, indicating that cellular determinants other than the RIG-I amino-acid sequence are responsible for controlling HCV replication. In addition, we have selected Huh7 cells resistant to hygromycin via newly generated HCV-replicons carrying the hygromycin resistant gene. Further studies on Huh7D cells will allow the identification of cellular factors that increased the susceptibility to HCV infection, which could be targeted for anti-HCV therapies. C1 [Feigelstock, Dino A.; Mihalik, Kathleen B.; Feinstone, Stephen M.] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. [Kaplan, Gerardo] US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20892 USA. RP Feigelstock, DA (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, 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. We thank Dr Charles Rice for providing the J6/JFH1 cDNA, Dr Ralf Bartenschlager for providing the pFK i389neoNS3-3'/NK5.1, pFK i389neoNS3-3'/delta5B, and pFK i389neoNS3-3'/wt plasmids, Dr Jake Liang for providing the Huh7 and Huh7.5 cells, and Dr Takaji Wakita for providing the JFH1 virus. NR 20 TC 8 Z9 9 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD FEB 19 PY 2010 VL 7 AR 44 DI 10.1186/1743-422X-7-44 PG 8 WC Virology SC Virology GA 568GG UT WOS:000275509700002 PM 20170495 ER PT J AU DeKruyff, RH Bu, X Ballesteros, A Santiago, C Chim, YLE Lee, HH Karisola, P Pichavant, M Kaplan, GG Umetsu, DT Freeman, GJ Casasnovas, JM AF DeKruyff, Rosemarie H. Bu, Xia Ballesteros, Angela Santiago, Cesar Chim, Yee-Ling E. Lee, Hyun-Hee Karisola, Piia Pichavant, Muriel Kaplan, Gerardo G. Umetsu, Dale T. Freeman, Gordon J. Casasnovas, Jose M. TI T Cell/Transmembrane, Ig, and Mucin-3 Allelic Variants Differentially Recognize Phosphatidylserine and Mediate Phagocytosis of Apoptotic Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TIM GENE FAMILY; IMMUNE-RESPONSES; IN-VIVO; PERIPHERAL TOLERANCE; AIRWAY INFLAMMATION; AUTOIMMUNE-DISEASE; ACTIVATION; RECEPTOR; MECHANISMS; EXPOSURE AB T cell/transmembrane, Ig, and mucin (TIM) proteins, identified using a congenic mouse model of asthma, critically regulate innate and adaptive immunity. TIM-1 and TIM-4 are receptors for phosphatidylserine (PtdSer), exposed on the surfaces of apoptotic cells. Herein, we show with structural and biological studies that TIM-3 is also a receptor for PtdSer that binds in a pocket on the N-terminal IgV domain in coordination with a calcium ion. The TIM-3/PtdSer structure is similar to that of TIM-4/PtdSer, reflecting a conserved PtdSer binding mode by TIM family members. Fibroblastic cells expressing mouse or human TIM-3 bound and phagocytosed apoptotic cells, with the BALB/c allelic variant of mouse TIM-3 showing a higher capacity than the congenic C.D2 Es-Hba-allelic variant. These functional differences were due to structural differences in the BC loop of the IgV domain of the TIM-3 polymorphic variants. In contrast to fibroblastic cells, T or B cells expressing TIM-3 formed conjugates with but failed to engulf apoptotic cells. Together these findings indicate that TIM-3-expressing cells can respond to apoptotic cells, but the consequence of TIM-3 engagement of PtdSer depends on the polymorphic variants of and type of cell expressing TIM-3. These findings establish a new paradigm for TIM proteins as PtdSer receptors and unify the function of the TIM gene family, which has been associated with asthma and autoimmunity and shown to modulate peripheral tolerance. The Journal of Immunology, 2010,184: 1918-1930. C1 [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [DeKruyff, Rosemarie H.; Chim, Yee-Ling E.; Lee, Hyun-Hee; Karisola, Piia; Pichavant, Muriel; Umetsu, Dale T.] Harvard Univ, Sch Med, Div Immunol, Childrens Hosp Boston, Cambridge, MA 02138 USA. [DeKruyff, Rosemarie H.; Chim, Yee-Ling E.; Lee, Hyun-Hee; Karisola, Piia; Pichavant, Muriel; Umetsu, Dale T.] Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. [Bu, Xia; Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Ballesteros, Angela; Santiago, Cesar; Casasnovas, Jose M.] Consejo Super Invest Cient, Ctr Nacl Biotecnol, Madrid, Spain. [Kaplan, Gerardo G.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Freeman, GJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM gordon_freeman@dfci.harvard.edu RI Casasnovas, Jose/L-6299-2014; Santiago, Cesar/K-4240-2014 OI Casasnovas, Jose/0000-0002-2873-6410; Santiago, Cesar/0000-0002-5149-1722 FU National Institutes of Health [P01 AI054456, HL069507]; Ministerio de Ciencia e Innovacion [BFU2005-05972, BFU2008-00971] FX This work was supported by National Institutes of Health Grants P01 AI054456 (to D.T.U., G.J.F., R.H.D., and G.G.K.) and HL069507 (to R.H.D.) and Ministerio de Ciencia e Innovacion Grants BFU2005-05972 and BFU2008-00971 (to J.M.C.). NR 46 TC 79 Z9 85 U1 0 U2 11 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 15 PY 2010 VL 184 IS 4 BP 1918 EP 1930 DI 10.4049/jimmunol.0903059 PG 13 WC Immunology SC Immunology GA 556IU UT WOS:000274585100028 PM 20083673 ER PT J AU Heo, MS Kim, Y Xue, XN Kim, MY AF Heo, Moonseong Kim, Yongman Xue, Xiaonan Kim, Mimi Y. TI Sample size requirement to detect an intervention effect at the end of follow-up in a longitudinal cluster randomized trial SO STATISTICS IN MEDICINE LA English DT Article DE longitudinal cluster RCT; three-level data; power function; sample size; intervention effect size ID CLINICAL-TRIALS; STATISTICAL POWER; PRIMARY-CARE; DESIGNS; ATTRITION; FREQUENCY; DURATION AB It is often anticipated in a longitudinal cluster randomized clinical trial (cluster-RCT) that the course of outcome over time will diverge between intervention arms. In these situations, testing the significance of a local intervention effect at the end of the trial may be more clinically relevant than evaluating overall mean differences between treatment groups. In this paper, we present a closed-form power function for detecting this local intervention effect based on maximum likelihood estimates from a mixed-effects linear regression model for three-level continuous data. Sample size requirements for the number of units at each data level are derived from the power function. The power function and the corresponding sample size requirements are verified by a simulation study. Importantly, it is shown that sample size requirements computed with the proposed power function are smaller than that required when testing group mean difference using data only at the end of trial and ignoring the course of outcome over the entire study period. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Heo, Moonseong; Xue, Xiaonan; Kim, Mimi Y.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Div Biostat, Bronx, NY 10461 USA. [Kim, Yongman] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Heo, MS (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Div Biostat, 1300 Morris Pk Ave,Belfer 1303E, Bronx, NY 10461 USA. EM mheo@aecom.yu.edu FU National Institutes of Health [MH 060447, DA023021, AI051519] FX Contract/grant sponsor: National Institutes of Health; contract/grant numbers: MH 060447, DA023021, AI051519 NR 29 TC 9 Z9 9 U1 0 U2 5 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 FEB 10 PY 2010 VL 29 IS 3 BP 382 EP 390 DI 10.1002/sim.3806 PG 9 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 552VP UT WOS:000274322000007 PM 20014353 ER PT J AU Barr, IG McCauley, J Cox, N Daniels, R Engelhardt, OG Fukuda, K Grohmann, G Hay, A Kelso, A Klimov, A Odagiri, T Smith, D Russell, C Tashiro, M Webby, R Wood, J Ye, ZP Zhang, WQ AF Barr, Ian G. McCauley, John Cox, Nancy Daniels, Rod Engelhardt, Othmar G. Fukuda, Keiji Grohmann, Gary Hay, Alan Kelso, Anne Klimov, Alexander Odagiri, Takato Smith, Derek Russell, Colin Tashiro, Masato Webby, Richard Wood, John Ye, Zhiping Zhang, Wenqing CA World Hlth Org Consultation No Hem TI Epidemiological, antigenic and genetic characteristics of seasonal influenza A(H1N1), A(H3N2) and B influenza viruses: Basis for the WHO recommendation on the composition of influenza vaccines for use in the 2009-2010 Northern Hemisphere season SO VACCINE LA English DT Article DE Influenza; Vaccine; Human; Seasonal ID SOUTH EAST-ASIA; ADAMANTANE RESISTANCE; ISOLATED WORLDWIDE; AUSTRALIA; COUNTRIES; EMERGENCE AB Influenza vaccines form an important component of the global response against infections and subsequent illness caused in man by influenza viruses. Twice a year, in February and September, the World Health Organisation through its Global Influenza Surveillance Network (GISN), recommends appropriate influenza viruses to be included in the seasonal influenza vaccine for the upcoming Northern and Southern Hemisphere winters. This recommendation is based on the latest data generated from many sources and the availability of viruses that are suitable for vaccine manufacture. This article gives a summary of the data and background to the recommendations for the 2009-2010 Northern Hemisphere influenza vaccine formulation. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Barr, Ian G.; Kelso, Anne] VIDRL, WHO Collaborating Ctr Reference & Res Influenza, Melbourne, Vic, Australia. [Cox, Nancy; Klimov, Alexander] CDC, WHO Collaborating Ctr Surveillance Epidemiol & Co, Atlanta, GA 30333 USA. [McCauley, John; Daniels, Rod; Hay, Alan] NIMR, WHO Collaborating Ctr Reference & Res Influenza, London, England. [Odagiri, Takato; Tashiro, Masato] NIID, WHO Collaborating Ctr Reference & Res Influenza, Tokyo, Japan. [Fukuda, Keiji; Zhang, Wenqing] WHO GIP, Geneva, Switzerland. [Engelhardt, Othmar G.; Wood, John] NIBSC, London, England. [Ye, Zhiping] CBER, Bethesda, MD USA. [Grohmann, Gary] TGA, Canberra, ACT, Australia. [Smith, Derek; Russell, Colin] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Smith, Derek; Russell, Colin] Univ Cambridge, Cambridge CB2 1TN, England. [Webby, Richard] St Jude Childrens Hosp, WHO Collaborating Ctr Studies Ecol Influenza Anim, Memphis, TN 38105 USA. RP Barr, IG (reprint author), WHO Collaborating Ctr Reference & Res Influenza, VIDRL, 10 Wreckyn St, Melbourne, Vic 3051, Australia. EM Ian.Barr@influenzacentre.org; GISN@who.int OI Russell, Colin/0000-0002-2113-162X FU Medical Research Council [MC_U117585868, MC_U117512723] NR 18 TC 78 Z9 80 U1 2 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD FEB 3 PY 2010 VL 28 IS 5 BP 1156 EP 1167 DI 10.1016/j.vaccine.2009.11.043 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 563IN UT WOS:000275122200005 PM 20004635 ER PT J AU Spadaccini, A Virnik, K Ni, YS Prutzman, K Berkower, I AF Spadaccini, Angelo Virnik, Konstantin Ni, Yisheng Prutzman, Kirk Berkower, Ira TI Stable expression of a foreign protein by a replication-competent rubella viral vector SO VACCINE LA English DT Article DE Rubella; Live; Replicating; Viral; Vector ID SIMIAN IMMUNODEFICIENCY VIRUS; EQUINE ENCEPHALITIS-VIRUS; NONSTRUCTURAL PROTEIN; SINDBIS VIRUS; VACCINE; DELETION; SITE; PATHOGENESIS; COMPLEXES; INFECTION AB Live, attenuated rubella vaccine has been used successfully for many years. By expressing additional viral antigens in rubella, we could expand its range and utility as a live, replicating viral vector. Previously, limitations on insert size and stability restricted rubella's ability to express exogenous antigens and immunize against other viruses. in this study, we have overcome this problem by creating a deletion in non-structural protein P150 that makes room for the insert. The resulting rubella hybrid stably expressed a model protein for over 10 passages, while replicating and expressing rubella proteins normally. The foreign protein, GFP, was as large as many important viral antigens, and the virus grew to sufficiently high titers for vaccine use. Further progress in expressing exogenous viral antigens in rubella may produce live viral vectors capable of immunizing against viruses for which attenuation is not currently feasible. Published by Elsevier Ltd. C1 [Spadaccini, Angelo; Virnik, Konstantin; Ni, Yisheng; Prutzman, Kirk; Berkower, Ira] US FDA, Immunoregulat Lab, DVP, Off Vaccine Res & Review,Ctr Biol, Rockville, MD 20857 USA. RP Berkower, I (reprint author), Bldg 29,Room 523,NIH Campus, Bethesda, MD 20892 USA. EM ira.berkower@fda.hhs.gov NR 30 TC 7 Z9 8 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 FEB 3 PY 2010 VL 28 IS 5 BP 1181 EP 1187 DI 10.1016/j.vaccine.2009.11.037 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 563IN UT WOS:000275122200008 PM 19945412 ER PT J AU Fiszman, ML Ricart, KC Latini, A Rodriguez, G Sica, REP AF Fiszman, M. L. Ricart, K. C. Latini, A. Rodriguez, G. Sica, R. E. P. TI In vitro neurotoxic properties and excitatory aminoacids concentration in the cerebrospinal fluid of amyotrophic lateral sclerosis patients. Relationship with the degree of certainty of disease diagnoses SO ACTA NEUROLOGICA SCANDINAVICA LA English DT Article DE excitatory aminoacids; neuronal cultures; neurotoxicity; amyotrophic lateral sclerosis; cerebrospinal fluid; pathogenesis ID MOTOR-NEURON DISEASE; GLUTAMATE NEUROTOXICITY; CELL-CULTURE; SPINAL-CORD; RECEPTORS; PLASMA; MICE; ALS; CSF; ASPARTATE AB Objective - To determine glutamate and aspartate levels in the cerebrospinal fluid (CSF) in patients with sporadic amyotrophic lateral sclerosis (SALS) grouped according to El Escorial diagnostic criteria, and to perform an in vitro assessment of the neurotoxicity of the CSF in murine cortical neurons. Methods - SALS patients were sorted according to El Escorial diagnostic criteria. Glutamate and aspartate were measured in the CSF using high performance liquid chromatography. Cultured cortical neuron viability was determined after exposure to CSF for 24 h. Results - Glutamate levels were elevated in 28 out of the 29 patients with definite, probable or possible SALS. There were no differences in glutamate concentrations when the three clinical forms of the disease were compared; neither there were significant variation across disease duration and clinical presentation. In agreement with previous reports, we concluded that CSF-SALS-induced in vitro neurotoxicity is mediated by ionotropic glutamate receptors. We found no relationship between the degree of in vitro neurotoxicity and glutamate concentration in the CSF. Conclusions - Glutamate but not aspartate CSF levels may contribute to ALS pathogenesis. However, glutamate levels may not influence the degree of diagnosis certainty or lesion extension. C1 [Fiszman, M. L.; Ricart, K. C.] Consejo Nacl Invest Cient & Tecn, Inst Invest Farmacol, RA-1033 Buenos Aires, DF, Argentina. [Latini, A.] Univ Nacl Cordoba, CEMECO, RA-5000 Cordoba, Argentina. [Rodriguez, G.; Sica, R. E. P.] Hosp Ramos Mejia, Div Neurol, Buenos Aires, DF, Argentina. RP Fiszman, ML (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Room 4181, Silver Spring, MD 20993 USA. EM Monica.Fiszman@fda.hhs.gov OI Latini, Alexandra/0000-0003-4255-3589 FU Carrillo-Onativia Fellowship; Public Health Ministry, Argentina; FITEN, Argentina FX The authors acknowledge Dr Raquel Kremer for the loan of the equipment to perform the HPLC measurements and Ms Carola Grosso for assisting in those experiments. This study was supported by a Carrillo-Onativia Fellowship, Public Health Ministry, Argentina (Dr Fiszman) and FITEN, Argentina (Dr Sica). NR 33 TC 15 Z9 15 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0001-6314 J9 ACTA NEUROL SCAND JI Acta Neurol. Scand. PD FEB PY 2010 VL 121 IS 2 BP 120 EP 126 DI 10.1111/j.1600-0404.2009.01200.x PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 541EC UT WOS:000273395700008 PM 19804473 ER PT J AU Marks, NS Weiss, K AF Marks, Norman S. Weiss, Karen TI Boxed Warnings and Other FDA Communication Tools SO AMERICAN FAMILY PHYSICIAN LA English DT Editorial Material C1 [Marks, Norman S.; Weiss, Karen] US FDA, Silver Spring, MD USA. RP Marks, NS (reprint author), US FDA, Silver Spring, MD USA. EM norman.marks@fda.hhs.gov NR 7 TC 4 Z9 4 U1 0 U2 1 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD FEB 1 PY 2010 VL 81 IS 3 BP 259 EP 260 PG 2 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 551NS UT WOS:000274216900002 PM 20112882 ER PT J AU Irwin, D Buehler, PW Alayash, AI Jia, YP Bonventura, J Foreman, B White, M Jacobs, R Piteo, B TissotvanPatot, MC Hamilton, KL Gotshall, RW AF Irwin, David Buehler, Paul W. Alayash, Abdu I. Jia, Yiping Bonventura, Joe Foreman, Ben White, Molly Jacobs, Robert Piteo, Brian TissotvanPatot, Martha C. Hamilton, Karyn L. Gotshall, Robert W. TI Mixed S-Nitrosylated Polymerized Bovine Hemoglobin Species Moderate Hemodynamic Effects in Acutely Hypoxic Rats SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE S-nitrosylation; hemoglobin-based oxygen carrier; oxygen delivery; cardiac output; blood pressure ID CELL-FREE HEMOGLOBIN; RED-BLOOD-CELLS; NITRIC-OXIDE; OXYGEN CARRIERS; HEMORRHAGIC-SHOCK; EXCHANGE-TRANSFUSION; TISSUE OXYGENATION; CROSS-LINKING; RESUSCITATION; SUBSTITUTES AB Hemoglobin (Hb)-based oxygen carriers (HBOCs) are being developed as a potential therapy for Increasing tissue oxygenation, yet they have not reached their full potential because of unwanted hemodynamic side effects (vasoconstriction, low cardiac output, and oxygen delivery) due In part to nitric oxide (NO) scavenging by cell-free Hb. It may be possible to overcome the NO scavenging effect by coinfusing S-nitrosylated (SNO) HBOC along with unmodified HBOC. SNO-HBOC, like free Hb, may act as an NO donor In low-oxygen conditions. We hypothesized that an unaltered HBOC, polymerized bovine Hb (PBvHb), coinfused with an SNO-PBvHb, would Improve hemodynamics and oxygen delivery during hypoxia. Vascular oxygen content and hemodynamics were determined after euvolemic rats were Infused (3 ml) with lactated Ringer's solution, PBvHb, SNO-PBvHb, or PBvHb plus SNO-F`BvHb (1:10) during normoxia or acute hypoxia (fraction of Inspired oxygen 10%, 120 min). Hemodynamic side effects resulting from PBvHb Infusion (vasoconstriction, elevated pulmonary blood pressure, and reduced cardiac output) were offset by SNO-PBvHb In acute hypoxic, but not normoxic, conditions. These data support the potential use of HBOC mixed with SNO-HBOC for the treatment of conditions In which acute hypoxia Is present, such as tumor oxygenation, wound healing, hemorrhagic trauma, and sickle cell and hemolytic anemia. C1 [Irwin, David] Univ Colorado, Hlth Sci Ctr, Cardiovasc Pulm Res Lab, Sch Med,Cardiovasc Pulm Res Grp, Denver, CO 80262 USA. [Buehler, Paul W.; Alayash, Abdu I.; Jia, Yiping] US FDA, Lab Biochem & Vasc Biol, Off Blood Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Bonventura, Joe] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. Duke Univ, Marine Lab, Nicholas Sch Environm, Beaufort, NC 28516 USA. [Jacobs, Robert; Piteo, Brian; Hamilton, Karyn L.; Gotshall, Robert W.] Colorado State Univ, Dept Hlth & Exercise Sci, Ft Collins, CO 80523 USA. [TissotvanPatot, Martha C.] Univ Colorado, Hlth Sci Ctr, Dept Anesthesiol, Aurora, CO USA. RP Irwin, D (reprint author), Univ Colorado, Hlth Sci Ctr, Cardiovasc Pulm Res Lab, Sch Med,Cardiovasc Pulm Res Grp, 4200 E 9th Ave, Denver, CO 80262 USA. EM david.irwin@uchsc.edu RI Jacobs, Robert/G-8439-2015 OI Jacobs, Robert/0000-0003-0180-8266 FU Defense Advanced Research Projects Agency; U.S. Army Research Office [W911NF-06-1-0318]; National Institutes of Health National Research Service [5-T32-HL07171] FX This work was supported by the Defense Advanced Research Projects Agency and the U.S. Army Research Office contract number W911NF-06-1-0318, and in part by National Institutes of Health National Research Service Award training grant 5-T32-HL07171 (D.I.) NR 37 TC 6 Z9 7 U1 1 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD FEB PY 2010 VL 42 IS 2 BP 200 EP 209 DI 10.1165/rcmb.2008-0364OC PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 549EL UT WOS:000274028500009 PM 19395680 ER PT J AU Lee, A Mcvey, J Faustino, P Lute, S Sweeney, N Pawar, V Khan, M Brorson, K Hussong, D AF Lee, A. McVey, J. Faustino, P. Lute, S. Sweeney, N. Pawar, V. Khan, M. Brorson, K. Hussong, D. TI Use of Hydrogenophaga pseudoflava Penetration To Quantitatively Assess the Impact of Filtration Parameters for 0.2-Micrometer-Pore-Size Filters SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID MICRON RATED FILTERS; FORMERLY PSEUDOMONAS PSEUDOFLAVA; BACTERIAL CHALLENGE TESTS; WATER-BORNE BACTERIA; REMOVAL PERFORMANCE; ESCHERICHIA-COLI; CELL-SIZE; PART II; STERILE FILTRATION; MEMBRANE FILTERS AB Filters rated as having a 0.2-mu m pore size (0.2-mu m-rated filters) are used in laboratory and manufacturing settings for diverse applications of bacterial and particle removal from process fluids, analytical test articles, and gasses. Using Hydrogenophaga pseudoflava, a diminutive bacterium with an unusual geometry (i.e., it is very thin), we evaluated passage through 0.2-mu m-rated filters and the impact of filtration process parameters and bacterial challenge density. We show that consistent H. pseudoflava passage occurs through 0.2-mu m-rated filters. This is in contrast to an absence of significant passage of nutritionally challenged bacteria that are of similar size (i.e., hydrodynamic diameter) but dissimilar geometry. C1 [Lee, A.; Lute, S.; Brorson, K.] US FDA, Off Biotechnol Prod, Silver Spring, MD 20903 USA. [McVey, J.; Pawar, V.; Hussong, D.] US FDA, Off Pharmaceut Sci New Drug Microbiol Staff, Silver Spring, MD 20903 USA. [Sweeney, N.] US FDA, Off Gener Drugs, Silver Spring, MD 20903 USA. [Faustino, P.; Khan, M.] US FDA, Off Testing & Res, Silver Spring, MD 20903 USA. RP Brorson, K (reprint author), US FDA, Off Biotechnol Prod, 10903 New Hampshire Ave,Bldg 64,Rm 1036, Silver Spring, MD 20903 USA. EM kurt.brorson@fda.hhs.gov FU CDER/FDA; Center for Drug Evaluation and Research; Oak Ridge Institute for Science and Education; U.S. Department of Energy and the U.S. Food and Drug Administration FX This project was supported in part by a Regulatory Science and Review Enhancement Program grant from CDER/FDA and by the Research Participation Program at the Center for Drug Evaluation and Research, administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 40 TC 3 Z9 4 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD FEB PY 2010 VL 76 IS 3 BP 695 EP 700 DI 10.1128/AEM.01825-09 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 549BV UT WOS:000274017400009 PM 19966023 ER PT J AU Rump, LV Feng, PCH Fischer, M Monday, SR AF Rump, Lydia V. Feng, Peter C. H. Fischer, Markus Monday, Steven R. TI Genetic Analysis for the Lack of Expression of the O157 Antigen in an O Rough:H7 Escherichia coli Strain SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID IDENTIFICATION; BIOSYNTHESIS; ELEMENTS; CLUSTER; O111 AB The O-antigen (rfb) operon and related genes of MA6, an O rough:H7 Shiga-toxigenic Escherichia coli strain, were examined to determine the cause of the lack of O157 expression. A 1,310-bp insertion, homologous to IS629, was observed within its gne gene. trans complementation with a functional gne gene from O157: H7 restored O157 antigen expression in MA6. C1 [Rump, Lydia V.; Feng, Peter C. H.; Monday, Steven R.] US FDA, Div Microbiol, College Pk, MD 20740 USA. [Rump, Lydia V.; Fischer, Markus] Univ Hamburg, Inst Food Chem, Hamburg, Germany. RP Feng, PCH (reprint author), US FDA, Div Microbiol, HFS-711,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM peter.feng@fda.hhs.gov FU Center for Food Safety and Applied Nutrition 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 17 TC 8 Z9 10 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 FEB PY 2010 VL 76 IS 3 BP 945 EP 947 DI 10.1128/AEM.02046-09 PG 3 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 549BV UT WOS:000274017400039 PM 19948859 ER PT J AU Guerraty, MA Grant, GR Karanian, JW Chiesa, OA Pritchard, WF Davies, PF AF Guerraty, Marie A. Grant, Gregory R. Karanian, John W. Chiesa, Oscar A. Pritchard, William F. Davies, Peter F. TI Hypercholesterolemia Induces Side-Specific Phenotypic Changes and Peroxisome Proliferator-Activated Receptor-gamma Pathway Activation in Swine Aortic Valve Endothelium SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE Valves; Endothelium; Cholesterol; Genes; Molecular Biology ID ACID-BINDING PROTEIN; SHEAR-STRESS; HEART-VALVES; CELLS; ATHEROSCLEROSIS; CALCIFICATION; COREPRESSORS; PERSPECTIVE; EXPRESSION; APOPTOSIS AB Background-The endothelium of healthy aortic valves expresses different phenotypes on the aortic and ventricular sides. On the aortic side, which is susceptible to aortic valve sclerosis, there is a balanced coexpression of both propathological and protective pathways. Side-specific global gene expression can address endothelial phenotype balance in early aortic valve sclerosis. Methods and Results-Adult male swine were fed a hypercholesterolemic or an isocaloric normal diet for 2-week and 6-month periods. Hypercholesterolemia induced localized lipid insudation confined to the aortic side of the leaflet. Transcript profiling of valve endothelial populations showed that the susceptible aortic side was more sensitive to 2-week hypercholesterolemia than the ventricular side (1,325 vs 87 genes were differentially expressed). However, greater sensitivity was not evidence of a dysfunctional phenotype. Instead, pathway analyses identified differential expression of caspase 3-, peroxisome proliferator-activated receptor gamma-, TNF-alpha-, and nuclear factor-kappa B-related pathways that were consistent with a protective endothelial phenotype. This was confirmed at the protein level at 2 weeks and persisted at 6 months. Conclusions-In a large animal model at high spatial resolution, endothelium on the pathosusceptible side of the aortic valve leaflet is responsive to hypercholesterolemia. Transcript profiles indicative of a protective phenotype were induced and persisted on the side prone to aortic valve sclerosis. (Arterioscler Thromb Vasc Biol. 2010;30:225-231.) C1 [Davies, Peter F.] Univ Penn, Inst Med & Engn, Vagelos Labs 1010, Philadelphia, PA 19104 USA. [Grant, Gregory R.] Univ Penn, Ctr Bioinformat, Philadelphia, PA 19104 USA. [Davies, Peter F.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Karanian, John W.; Chiesa, Oscar A.; Pritchard, William F.] US FDA, Lab Cardiovasc & Intervent Therapeut, Laurel, MD USA. RP Davies, PF (reprint author), Univ Penn, Inst Med & Engn, Vagelos Labs 1010, 3340 Smith Walk, Philadelphia, PA 19104 USA. EM pfd@pobox.upenn.edu FU NRSA [HL079877]; National Institutes of Health; University of Pennsylvania Medical Scientist Training Program; [HL62250] FX This study was supported by grants NRSA HL079877 (Dr Guerraty) and HL62250 from the National Institutes of Health (Dr Davies); and the University of Pennsylvania Medical Scientist Training Program. NR 36 TC 20 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD FEB PY 2010 VL 30 IS 2 BP 225 EP 231 DI 10.1161/ATVBAHA.109.198549 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 546GT UT WOS:000273799900018 PM 19926833 ER PT J AU Sun, JC Schnackenberg, LK Hansen, DK Beger, RD AF Sun, Jinchun Schnackenberg, Laura K. Hansen, Deborah K. Beger, Richard D. TI Study of valproic acid-induced endogenous and exogenous metabolite alterations using LC-MS-based metabolomics SO BIOANALYSIS LA English DT Article ID DRUG; RATS; METABONOMICS; TOXICITY; LIVER; HYPERCREATINURIA; HEPATOTOXICITY; GLUTATHIONE; INJURY AB Background: Valproic acid (VPA; an anticonvulsant drug) therapy is associated with hepatotoxicity as well as renal toxicity. An LC-MS-based metabolomics approach was undertaken in order to detect urinary VPA metabolites and to discover early biomarkers of the adverse effects induced by VPA. Results: CD-I mice were either subcutaneously injected with 600-mg VPA/kg body weight or vehicle only, and urine samples were collected at 6, 12,24 and 48 h postinjection. A metabolomics approach combined with principal component analysis was utilized to identify VPA-related metabolites and altered endogenous metabolites in urine. Some VPA metabolites indicated potential liver toxicity caused by VPA administration. Additionally, some altered endogenous metabolites suggested that renal function might be perturbed by VPA dosing. Conclusion: LC-MS-based metabolomics is capable of rapidly profiling VPA drug metabolites and is a powerful tool for the discovery of potential early biomarkers related to perturbations in liver and kidney function. C1 [Sun, Jinchun; Schnackenberg, Laura K.; Beger, Richard D.] US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Hansen, Deborah K.] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Beger, RD (reprint author), US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM Richard.Beger@fda.hhs.gov NR 40 TC 11 Z9 11 U1 0 U2 7 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 J9 BIOANALYSIS JI Bioanalysis PD FEB PY 2010 VL 2 IS 2 BP 207 EP 216 DI 10.4155/BIO.09.173 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 644VQ UT WOS:000281410200015 PM 21083304 ER PT J AU Sapsford, KE Blanco-Canosa, JB Dawson, PE Medintz, IL AF Sapsford, Kim E. Blanco-Canosa, Juan B. Dawson, Philip E. Medintz, Igor L. TI Detection of HIV-1 Specific Monoclonal Antibodies Using Enhancement of Dye-Labeled Antigenic Peptides SO BIOCONJUGATE CHEMISTRY LA English DT Article ID RESONANCE ENERGY-TRANSFER; ENZYME-IMMUNOASSAY; MATRIX PROTEIN; P17; BINDING; EXCITATION; BIOSENSOR; BEACONS; SENSORS; SERUM AB A simple bifunctional colorimetric/fluorescent sensing assay is demonstrated for the detection of HIV-1 specific antibodies. This assay makes use of a short peptide sequence coupled to an environmentally sensitive dye that absorbs and emits in the visible portion of the spectrum. The core peptide sequence is derived from the highly antigenic six-residue epitope of the HIV-1 p17 protein and is situated adjacent to a terminal cysteine residue which enables site-specific fluorescent labeling with Cy3 cyanine dye. Interaction of the Cy3-labeled p17 peptide with monoclonal anti-p17 antibody resulted in an up to 4-fold increase in dye absorption and greater than 5-fold increase in fluorescent emission, yielding a limit of detection as low as 73 pM for the target antibody. This initial study demonstrates both proof-of-concept for this approach and suggests that the resulting sensor could potentially be used as a rapid screening method for HIV-1 infection while requiring minimal equipment and reagents. The potential for utilizing this assay in simple field-portable point-of-care and diagnostic devices is discussed. C1 [Medintz, Igor L.] USN, Res Lab, Ctr BioMol Sci & Engn, Washington, DC 20375 USA. [Sapsford, Kim E.] US FDA, Off Sci & Engn Labs, Div Biol, Silver Spring, MD 20993 USA. [Blanco-Canosa, Juan B.; Dawson, Philip E.] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA. [Blanco-Canosa, Juan B.; Dawson, Philip E.] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. [Blanco-Canosa, Juan B.; Dawson, Philip E.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. RP Medintz, IL (reprint author), USN, Res Lab, Ctr BioMol Sci & Engn, Code 6900, Washington, DC 20375 USA. EM Igor.Medintz@nrl.navy.mil FU B Directorate/Physical S&T Division DTRA/ARO; ONR; NRL; NRL-NSI; Marie Curie Foundation FX The authors thank Dr. J. Golden (NRL/CBMSE) for the digital photograph shown in Figure 3. This work was supported in part by CDRWOSEL/Division of Biology funds. 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. IM acknowledges the CB Directorate/Physical S&T Division DTRA/ARO, ONR, NRL, and the NRL-NSI for financial support. J.B.B-C. gratefully acknowledges the Marie Curie Foundation for a postdoctoral fellowship. NR 28 TC 13 Z9 13 U1 1 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD FEB PY 2010 VL 21 IS 2 BP 393 EP 398 DI 10.1021/bc9003712 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 555MG UT WOS:000274514300025 PM 20058910 ER PT J AU Ravenscroft-Chang, MS Stohlman, JM Molnar, P Natarajan, A Canavan, HE Teliska, M Stancescu, M Krauthamer, V Hickman, JJ AF Ravenscroft-Chang, Melissa S. Stohlman, Jayna M. Molnar, Peter Natarajan, Anupama Canavan, Heather E. Teliska, Maggie Stancescu, Maria Krauthamer, Victor Hickman, James J. TI Altered calcium dynamics in cardiac cells grown on silane-modified surfaces SO BIOMATERIALS LA English DT Article DE Biocompatibility; Calcium; Cardiomyocyte; Cell culture; Image analysis; Surface modification ID SELF-ASSEMBLED MONOLAYERS; CHEMICAL-MODIFICATION; HIPPOCAMPAL-NEURONS; ELECTRIC SHOCKS; DEFINED SYSTEM; IN-VITRO; ADHESION; BIOCOMPATIBILITY; BIOMATERIALS; POLYETHYLENE AB Chemically defined surfaces were created using self-assembled monolayers (SAMs) of hydrophobic and hydrophilic silanes as models for implant coatings, and the morphology and physiology of cardiac myocytes plated on these surfaces were studied in vitro. We focused on changes in intracellular Ca(2+) because of its essential role in regulating heart cell function. The SAM-modified coverslips were analyzed using X-ray Photoelectron Spectroscopy to verify composition. The morphology and physiology of the cardiac cells were examined using fluorescence microscopy and intracellular Ca(2+) imaging. The imaging experiments used the fluorescent ratiometric dye fura-2, AM to establish both the resting Ca(2+) concentration and the dynamic responses to electrical stimulation. A significant difference in excitation-induced Ca(2+) changes on the different silanated surfaces was observed. However, no significant change was noted based on the morphological analysis. This result implies a difference in internal Ca(2+) dynamics, and thus cardiac function, occurs when the composition of the surface is different, and this effect is independent of cellular morphology. This finding has implications for histological examination of tissues surrounding implants, the choice of materials that could be beneficial as implant coatings and understanding of cell-surface interactions in cardiac systems. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Molnar, Peter; Natarajan, Anupama; Stancescu, Maria; Hickman, James J.] Univ Cent Florida, NanoSci Technol Ctr, Orlando, FL 32826 USA. [Ravenscroft-Chang, Melissa S.; Canavan, Heather E.; Teliska, Maggie; Hickman, James J.] George Washington Univ, Dept Chem, Washington, DC 20052 USA. [Ravenscroft-Chang, Melissa S.; Stohlman, Jayna M.; Krauthamer, Victor] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Hickman, JJ (reprint author), Univ Cent Florida, NanoSci Technol Ctr, 12424 Res Pkwy,Suite 400, Orlando, FL 32826 USA. EM jhickman@mail.ucf.edu FU Department of Energy [DE-FG02-96ER14588]; NIH [5R01EB005459] FX We gratefully acknowledge the support of the Department of Energy grant DE-FG02-96ER14588 and NIH grant 5R01EB005459 for funding this work. NR 48 TC 5 Z9 5 U1 3 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD FEB PY 2010 VL 31 IS 4 BP 602 EP 607 DI 10.1016/j.biomaterials.2009.09.084 PG 6 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 538EP UT WOS:000273167400003 PM 19828193 ER PT J AU Read, EK Park, JT Shah, RB Riley, BS Brorson, KA Rathore, AS AF Read, E. K. Park, J. T. Shah, R. B. Riley, B. S. Brorson, K. A. Rathore, A. S. TI Process Analytical Technology (PAT) for Biopharmaceutical Products: Part I. Concepts and Applications SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE process analytical technology (PAT); cell culture; harvest; chromatography; UF/DF; virus filtration ID AUTOMATED FLOW-CYTOMETRY; MULTIVARIATE DATA-ANALYSIS; PROTEIN-PRODUCTION; UNIT OPERATIONS; ELECTRONIC NOSE; CELL-CULTURES; DESIGN; ANTIBODIES; RESOLUTION; FILTERS AB Process analytical technology (PAT) has been gaining momentum in the biotech community due to the potential for continuous real-time quality assurance resulting in improved operational control and compliance. In this two part series, we address PAT as it applies to processes that produce biotech therapeutic products. In the first part, we address evolution of the underlying concepts and applications in biopharmaceutical manufacturing. We also present a literature review of applications in the areas of upstream and downstream processing to illustrate how implementation of PAT can help realize advanced approaches to ensuring product quality in real time. In the second part, we will explore similar applications in the areas of drug product manufacturing, rapid microbiology, and chemometrics as well as evolution of PAT in biotech processing. Biotechnol. Bioeng. 2010;105: 276-284. Published 2009 Wiley Periodicals, Inc.dagger C1 [Rathore, A. S.] Indian Inst Technol, Dept Chem Engn, Amgen Inc, New Delhi 110016, India. [Read, E. K.; Park, J. T.; Shah, R. B.; Riley, B. S.; Brorson, K. A.] US FDA, Off Pharmaceut Sci, CDER, Silver Spring, MD USA. RP Rathore, AS (reprint author), Indian Inst Technol, Dept Chem Engn, Amgen Inc, New Delhi 110016, India. EM asrathore@biotechcmz.com FU CDER/FDA [1500] FX The authors thank Chris Watts, Carla Lankford, Keith Webber, and Ali Afnan for careful review of this manuscript. This work was supported in part by a CDER/FDA Critical Path Grant, project number 1500. Views expressed in the article are those of the authors and not necessarily policy of the Food and Drug Administration or the US Government. NR 46 TC 74 Z9 75 U1 5 U2 55 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 FEB 1 PY 2010 VL 105 IS 2 BP 276 EP 284 DI 10.1002/bit.22528 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 545EO UT WOS:000273715500006 PM 19731252 ER PT J AU Read, EK Shah, RB Riley, BS Park, JT Brorson, KA Rathore, AS AF Read, E. K. Shah, R. B. Riley, B. S. Park, J. T. Brorson, K. A. Rathore, A. S. TI Process Analytical Technology (PAT) for Biopharmaceutical Products: Part II. Concepts and Applications SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE process analytical technology (PAT); rapid microbiological techniques; lyophilization; NIR; chemometrics ID NEAR-INFRARED SPECTROSCOPY; MULTIVARIATE DATA-ANALYSIS; MANOMETRIC TEMPERATURE-MEASUREMENT; FREEZE-DRYING PROCESSES; REAL-TIME PCR; CELL-CULTURE; DESIGN SPACE; LARGE-SCALE; BIOTECH PRODUCTS; NIR SPECTROSCOPY AB Implementing real-time product quality control meets one or both of the key goals outlined in FDA's PAT guidance: "variability is managed by the process" and 11 product quality attributes can be accurately and reliably predicted over the design space established for materials used, process parameters, manufacturing ring, environmental, and other conditions." The first part of the paper presented an overview of PAT concepts and applications in the areas of upstream and downstream processing. In this second part, we present principles and case studies to illustrate implementation of PAT for drug product manufacturing, rapid microbiology, and chemometrics. We further present Our thoughts on how PAT will be applied to biotech processes going forward. The role of PAT as an enabling component of the Quality by Design framework is highlighted. Integration of PAT with the principles stated in the ICH Q8, Q9, and Q10 guidance documents is also discussed. Biotechnol. Bioeng. 2010;105: 285-295. Published 2009 Wiley Periodicals, Inc.dagger C1 [Rathore, A. S.] Indian Inst Technol, Dept Chem Engn, Amgen Inc, New Delhi 110016, India. [Read, E. K.; Shah, R. B.; Riley, B. S.; Park, J. T.; Brorson, K. A.] US FDA, Off Pharmaceut Sci, CDER, Silver Spring, MD USA. RP Rathore, AS (reprint author), Indian Inst Technol, Dept Chem Engn, Amgen Inc, New Delhi 110016, India. EM asrathore@biotechcmz.com NR 90 TC 53 Z9 53 U1 7 U2 58 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 FEB 1 PY 2010 VL 105 IS 2 BP 285 EP 295 DI 10.1002/bit.22529 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 545EO UT WOS:000273715500007 PM 19731253 ER PT J AU Shord, SS Chan, LN Camp, JR Vasquez, EM Jeong, HY Molokie, RE Baum, CL Xie, H AF Shord, Stacy S. Chan, Lingtak-Neander Camp, Joseph R. Vasquez, Eva M. Jeong, Hyun-Young Molokie, Robert E. Baum, Charles L. Xie, Hui TI Effects of oral clotrimazole troches on the pharmacokinetics of oral and intravenous midazolam SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE clotrimazole; CYP3A4; extraction; drug-drug interaction; pharmacokinetics; ratiomidazolam ID CYTOCHROME-P450 3A ACTIVITY; HUMAN LIVER-MICROSOMES; PREGNANE-X-RECEPTOR; P-GLYCOPROTEIN; TRANSPLANT PATIENTS; ANTIFUNGAL AGENTS; OROPHARYNGEAL CANDIDIASIS; CLINICAL-RELEVANCE; COMPARATIVE TRIAL; HUMAN HEPATOCYTES AB AIMS The aim of the study was to determine the effects of oral clotrimazole troches on the pharmacokinetics of oral and intravenous midazolam in the plasma. METHODS We conducted a randomized, open-label, four-way crossover study in 10 healthy volunteers. Each volunteer received oral midazolam 2 mg or intravenous midazolam 0.025 mg kg(-1) with and without oral clotrimazole troches 10 mg taken three times daily for 5 days. Each study period was separated by 14 days. Serial blood samples were collected up to 24 h after oral midazolam and 6 h after intravenous midazolam. Plasma concentrations for midazolam and its metabolite 1-hydroxymidazolam were measured and fitted to a noncompartmental model to estimate the pharmacokinetic parameters. RESULTS Ten healthy volunteers aged 21-26 years provided written informed consent and were enrolled into the study. Clotrimazole decreased the apparent oral clearance of midazolam from 57 +/- 13 l h(-1) [95% confidence interval 48, 66] to 36 +/- 9.8 l h(-1) (95% confidence interval 29, 43) (P = 0.003). These changes were accompanied by a decrease in the area under the concentration-time curve (mean difference 22 mu g h(-1) l(-1), P = 0.001) and bioavailability (mean difference 0.21, P = NS). There were no significant differences in the systemic clearance of midazolam with or without clotrimazole troches. CONCLUSIONS Oral clotrimazole troches decreased the apparent oral clearance of midazolam; no significant differences in the systemic clearance of midazolam were found. C1 [Shord, Stacy S.; Chan, Lingtak-Neander; Camp, Joseph R.; Vasquez, Eva M.; Jeong, Hyun-Young] Univ Illinois, Coll Pharm, Dept Pharm Practice, Chicago, IL USA. [Molokie, Robert E.] Univ Illinois, Coll Med, Dept Med, Sect Hematol & Oncol, Chicago, IL USA. [Baum, Charles L.] Univ Illinois, Coll Nursing, Dept Publ Hlth Mental Hlth & Adm Nursing, Chicago, IL USA. [Xie, Hui] Univ Illinois, Ctr Clin & Translat Sci, Div Epidemiol & Biostat, Chicago, IL USA. RP Shord, SS (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM shordfamily@gmail.com FU American Association for Colleges of Pharmacy; General Clinical Research Center at the University of Illinois at Chicago [M01-RR-13987] FX This study was supported in part by a New Investigator Programgrant awarded by the American Association for Colleges of Pharmacy to S. S. S. and the General Clinical Research Center at the University of Illinois at Chicago (NIH grant M01-RR-13987). NR 42 TC 7 Z9 7 U1 0 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0306-5251 J9 BRIT J CLIN PHARMACO JI Br. J. Clin. Pharmacol. PD FEB PY 2010 VL 69 IS 2 BP 160 EP 166 DI 10.1111/j.1365-2125.2009.03559.x PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 547KV UT WOS:000273887200008 PM 20233179 ER PT J AU Tavris, D Shoaibi, A Chen, AY Uchida, T Roe, MT Chen, JP AF Tavris, Dale Shoaibi, Azadeh Chen, Anita Y. Uchida, Takahiro Roe, Matthew T. Chen, Jiping TI Gender Differences in the Treatment of Non-ST-Segment Elevation Myocardial Infarction SO CLINICAL CARDIOLOGY LA English DT Article AB Background: Women are at greater risk for worse outcomes associated with acute coronary syndrome (ACS) than are men. One explanation may be that they tend to be treated less aggressively than men even when more aggressive treatment is warranted. The purpose of this analysis was to assess this issue. Methods: We used the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation (CRUSADE) Quality Improvement Initiative registry, an observational data collection that began in November 2001, with retrospective data collection from January 2001 to December 2006. A total Of 32 888 subjects met the inclusion/exclusion criteria for our study, based on strong biochemical evidence of myocardial infarction and acute onset of typical cardiac chest pain. We stratified subjects into 16 cells for coronary intervention, based on 4 age groups and 4 cardiac catheterization findings (insignificant, 1-vessel disease, 2-vessel disease, 3-vessel disease). We also stratified subjects into 20 cells for medical treatment, based on 4 age groups and 5 medical treatments. In each cell we compared the rate of coronary intervention (coronary artery bypass grafting or percutaneous coronary intervention) or medical treatment (glycoprotein IIb/IIIa inhibitors, aspirin, clopidogrel, beta-blocker, and statins) for men vs women. Results: Men demonstrated significantly higher rates (P < 0.05) of coronary intervention in 7 of the 16 cells and 9 of the 20 medical treatment cells, compared to no cells in which women had statistically higher rates than men. Conclusion: These findings suggest that men are more likely than women to receive coronary intervention and to be medically treated when presenting with evidence of non-ST-segment myocardial infarction, controlled for age, cardiac catheterization findings, and biochemical evidence of myocardial infarction. C1 [Tavris, Dale; Shoaibi, Azadeh; Chen, Jiping] US FDA, Ctr Devices & Radiol Hlth, Div Epidemiol, Rockville, MD 20857 USA. [Uchida, Takahiro] Boston Sci Corp, Boston, MA USA. [Chen, Anita Y.; Roe, Matthew T.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA. RP Tavris, D (reprint author), 10903 New Hampshire Ave,White Oak Campus,Bldg 66, Silver Spring, MD 20993 USA. EM dale.tavris@fda.hhs.gov FU FDA Office of Women's Health (OWH) FX This study was supported by a grant from the FDA Office of Women's Health (OWH). The findings in this study reflect the views of the authors and not necessarily the views of the Food and Drug Administrafion. NR 20 TC 24 Z9 25 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD FEB PY 2010 VL 33 IS 2 BP 99 EP 103 DI 10.1002/clc.20691 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 561PQ UT WOS:000274990700009 PM 20186991 ER PT J AU Regnier, FE Skates, SJ Mesri, M Rodriguez, H Tezak, Z Kondratovich, MV Alterman, MA Levin, JD Roscoe, D Reilly, E Callaghan, J Kelm, K Brown, D Philip, R Carr, SA Liebler, DC Fisher, SJ Tempst, P Hiltke, T Kessler, LG Kinsinger, CR Ransohoff, DF Mansfield, E Anderson, NL AF Regnier, Fred E. Skates, Steven J. Mesri, Mehdi Rodriguez, Henry Tezak, Zivana Kondratovich, Marina V. Alterman, Michail A. Levin, Joshua D. Roscoe, Donna Reilly, Eugene Callaghan, James Kelm, Kellie Brown, David Philip, Reena Carr, Steven A. Liebler, Daniel C. Fisher, Susan J. Tempst, Paul Hiltke, Tara Kessler, Larry G. Kinsinger, Christopher R. Ransohoff, David F. Mansfield, Elizabeth Anderson, N. Leigh TI Protein-Based Multiplex Assays: Mock Presubmissions to the US Food and Drug Administration SO CLINICAL CHEMISTRY LA English DT Article AB As a part of ongoing efforts of the NCI-FDA Interagency Oncology Task Force subcommittee on molecular diagnostics, members of the Clinical Proteomic Technology Assessment for Cancer program of the National Cancer Institute have submitted 2 protein-based multiplex assay descriptions to the Office of In Vitro Diagnostic Device Evaluation and Safety, US Food and Drug Administration. The objective was to evaluate the analytical measurement criteria and studies needed to validate protein-based multiplex assays. Each submission described a different protein-based platform: a multiplex immunoaffinity mass spectrometry platform for protein quantification, and an immunological array platform quantifying glycoprotein isoforms. Submissions provided a mutually beneficial way for members of the proteomics and regulatory communities to identify the analytical issues that the field should address when developing protein-based multiplex clinical assays. (C) 2009 American Association for Clinical Chemistry C1 [Anderson, N. Leigh] Plasma Proteome Inst, Washington, DC 20009 USA. [Regnier, Fred E.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Skates, Steven J.] Massachusetts Gen Hosp, Dana Farber Harvard Canc Ctr, Boston, MA 02114 USA. [Mesri, Mehdi; Rodriguez, Henry; Hiltke, Tara; Kinsinger, Christopher R.] NCI, Ctr Strateg Sci Initiat, NIH, Bethesda, MD 20892 USA. [Tezak, Zivana; Kondratovich, Marina V.; Levin, Joshua D.; Roscoe, Donna; Reilly, Eugene; Callaghan, James; Kelm, Kellie; Philip, Reena; Mansfield, Elizabeth] US FDA, Off Vitro Diagnost Device Evaluat & Safety, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Alterman, Michail A.] TVBB, Ctr Biol Evaluat & Res, OCTGT, DCGT, Bethesda, MD USA. [Brown, David] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Carr, Steven A.] MIT & Harvard, Broad Inst, Cambridge, MA USA. [Liebler, Daniel C.] Vanderbilt Univ, Med Ctr, Jim Ayers Inst Precancer Detect & Diag, Nashville, TN USA. [Fisher, Susan J.] Univ Calif San Francisco, Biomol Ctr, San Francisco, CA 94143 USA. [Fisher, Susan J.] Univ Calif San Francisco, Mass Spectrometry Ctr, San Francisco, CA 94143 USA. [Tempst, Paul] Mem Sloan Kettering Canc Ctr, Prot Ctr, New York, NY 10021 USA. [Kessler, Larry G.] Univ Washington, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. [Ransohoff, David F.] Univ N Carolina, Chapel Hill, NC USA. RP Anderson, NL (reprint author), Plasma Proteome Inst, POB 53450, Washington, DC 20009 USA. EM leighanderson@plasmaproteome.org OI Liebler, Daniel/0000-0002-7873-3031 FU National Cancer Institute, Clinical Proteomic Technology Assessment for Cancer; National Cancer Institute-NIH; Agilent Technologies FX Research Funding: F.E. Regnier, National Cancer Institute, Clinical Proteomic Technology Assessment for Cancer; P. Tempst, National Cancer Institute-NIH; L.G. Kessler, National Cancer Institute; N.L. Anderson, Agilent Technologies. NR 3 TC 37 Z9 37 U1 0 U2 5 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD FEB PY 2010 VL 56 IS 2 BP 165 EP 171 DI 10.1373/clinchem.2009.140087 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 551QD UT WOS:000274223200005 PM 20007858 ER PT J AU Rodriguez, H Tezak, Z Mesri, M Carr, SA Liebler, DC Fisher, SJ Tempst, P Hiltke, T Kessler, LG Kinsinger, CR Philip, R Ransohoff, DF Skates, SJ Regnier, FE Anderson, NL Mansfield, E AF Rodriguez, Henry Tezak, Zivana Mesri, Mehdi Carr, Steven A. Liebler, Daniel C. Fisher, Susan J. Tempst, Paul Hiltke, Tara Kessler, Larry G. Kinsinger, Christopher R. Philip, Reena Ransohoff, David F. Skates, Steven J. Regnier, Fred E. Anderson, N. Leigh Mansfield, Elizabeth CA Workshop Participants TI Analytical Validation of Protein-Based Multiplex Assays: A Workshop Report by the NCI-FDA Interagency Oncology Task Force on Molecular Diagnostics SO CLINICAL CHEMISTRY LA English DT Review AB Clinical proteomics has the potential to enable the early detection of cancer through the development of multiplex assays that can inform clinical decisions. However, there has been some uncertainty among translational researchers and developers as to the specific analytical measurement criteria needed to validate protein-based multiplex assays. To begin to address the causes of this uncertainty, a day-long workshop titled "Interagency Oncology Task Force Molecular Diagnostics Workshop" was held in which members of the proteomics and regulatory communities discussed many of the analytical evaluation issues that the field should address in development of protein-based multiplex assays for clinical use. This meeting report explores the issues raised at the workshop and details the recommendations that came out of the day's discussions, such as a workshop summary discussing the analytical evaluation issues that specific proteomic technologies should address when seeking US Food and Drug Administration approval. (C) 2009 American Association for Clinical Chemistry C1 [Rodriguez, Henry] NCI, Ctr Strateg Sci Initiat, NIH, US FDA, Bethesda, MD 20892 USA. RP Rodriguez, H (reprint author), NCI, Ctr Strateg Sci Initiat, NIH, US FDA, Bethesda, MD 20892 USA. EM rodriguezh@mail.nih.gov OI Liebler, Daniel/0000-0002-7873-3031 FU NCI; NCI/NIH FX Research Funding: D.C. Liebler, NCI; P. Tempst, NCI/NIH; F.E. Regnier, NCI. NR 3 TC 38 Z9 39 U1 0 U2 7 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD FEB PY 2010 VL 56 IS 2 BP 237 EP 243 DI 10.1373/clinchem.2009.136416 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 551QD UT WOS:000274223200013 PM 20007859 ER PT J AU Frankos, VH Street, DA O'Neill, RK AF Frankos, V. H. Street, D. A. O'Neill, R. K. TI FDA Regulation of Dietary Supplements and Requirements Regarding Adverse Event Reporting SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article AB In 1994, the Dietary Supplement Health and Education Act (DSHEA) amended the Federal Food, Drug, and Cosmetic Act (FDC Act) to set up a distinct regulatory framework for what we now call dietary supplements. The DSHEA was passed with the intent of striking a balance between providing consumers access to safe dietary supplements to help maintain or improve their health and giving the US Food and Drug Administration (FDA) authority to regulate and take action against manufacturers of supplements or supplement ingredients that present safety problems, are presented with false or misleading claims, or are adulterated or misbranded. This article will present FDA's recent experience in collecting and evaluating dietary supplement adverse event data for the purpose of assuring the public that the dietary supplements they purchase are safe. C1 [Frankos, V. H.] US FDA, Div Dietary Supplement Programs, College Pk, MD USA. [Street, D. A.] US FDA, Emergency Response & Surveillance Branch, College Pk, MD USA. [O'Neill, R. K.] US FDA, Div Publ Hlth & Biostat, College Pk, MD USA. RP Frankos, VH (reprint author), US FDA, Div Dietary Supplement Programs, College Pk, MD USA. EM vasilios.frankos@fda.hhs.gov NR 2 TC 14 Z9 16 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2010 VL 87 IS 2 BP 239 EP 244 DI 10.1038/clpt.2009.263 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 550PK UT WOS:000274140200023 PM 20032973 ER PT J AU Duarte, JD Welder, GJ Schofield, RS Johnson, JA Zineh, I AF Duarte, J. D. Welder, G. J. Schofield, R. S. Johnson, J. A. Zineh, I. TI SIRTUIN-1 GENE EXPRESSION CORRELATES WITH SYSTEMIC CYTOKINE CONCENTRATIONS IN ATORVASTATIN-TREATED HEALTHY SUBJECTS. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 111th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 17-20, 2010 CL Atlanta, GA SP Amer Soc Clin Pharmacol & Therapeut C1 [Duarte, J. D.; Welder, G. J.; Schofield, R. S.; Johnson, J. A.] Univ Florida, Gainesville, FL USA. [Schofield, R. S.] Malcom Randall VAMC, Gainesville, FL USA. [Zineh, I.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2010 VL 87 SU 1 BP S46 EP S46 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 550PY UT WOS:000274141600142 ER PT J AU Fadiran, EO Parekh, A Uhl, K AF Fadiran, E. O. Parekh, A. Uhl, K. TI THE SCIENCE OF SEX DIFFERENCES IN THE PHARMACOKINETICS AND PHARMACODYNAMICS OF DRUGS-CASE STUDIES. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 111th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 17-20, 2010 CL Atlanta, GA SP Amer Soc Clin Pharmacol & Therapeut C1 [Fadiran, E. O.; Parekh, A.; Uhl, K.] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2010 VL 87 SU 1 BP S93 EP S93 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 550PY UT WOS:000274141600292 ER PT J AU Stanek, EJ Sanders, CL Hawk, G Frueh, FW Pacanowsi, M Zineh, I Lesko, L Epstein, RS AF Stanek, E. J. Sanders, C. L. Hawk, G. Frueh, F. W. Pacanowsi, M. Zineh, I. Lesko, L. Epstein, R. S. TI NATIONAL BENCHMARKING STUDY OF PHARMACOGENETIC TESTING FOR WARFARIN. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 111th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 17-20, 2010 CL Atlanta, GA SP Amer Soc Clin Pharmacol & Therapeut C1 [Stanek, E. J.; Sanders, C. L.; Hawk, G.; Frueh, F. W.; Epstein, R. S.] Medco Hlth Solut Inc, Bethesda, MD USA. [Pacanowsi, M.; Zineh, I.; Lesko, L.] US FDA, White Oak, MD USA. NR 0 TC 2 Z9 2 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 FEB PY 2010 VL 87 SU 1 BP S44 EP S44 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 550PY UT WOS:000274141600136 ER PT J AU Umarjee, S Lemtouni, S Fadiran, E Parekh, A AF Umarjee, S. Lemtouni, S. Fadiran, E. Parekh, A. TI PATIENT DEMOGRAPHICS IN CARDIOVASCULAR DRUG TRIALS: FDA REVIEWS FROM 2007 TO 2008. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 111th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 17-20, 2010 CL Atlanta, GA SP Amer Soc Clin Pharmacol & Therapeut C1 [Umarjee, S.; Lemtouni, S.; Fadiran, E.; Parekh, A.] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2010 VL 87 SU 1 BP S75 EP S75 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 550PY UT WOS:000274141600235 ER PT J AU Zhao, P Zhang, L Lesko, L Huang, S AF Zhao, P. Zhang, L. Lesko, L. Huang, S. TI UTILITY OF PHYSIOLOGICALLY- BASED PHARMACOKINETIC MODELING AND SIMULATION IN DRUG DEVELOPMENT AND CHALLENGES IN REGULATORY REVIEWS. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 111th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 17-20, 2010 CL Atlanta, GA SP Amer Soc Clin Pharmacol & Therapeut C1 [Zhao, P.; Zhang, L.; Lesko, L.; Huang, S.] US FDA, Silver Spring, MD USA. NR 0 TC 3 Z9 3 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 FEB PY 2010 VL 87 SU 1 BP S72 EP S72 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 550PY UT WOS:000274141600227 ER PT J AU Chang, YL Zou, F Wright, FA AF Chang, Yu-Ling Zou, Fei Wright, Fred A. TI An approximate Bayesian approach for quantitative trait loci estimation SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article ID CHAIN MONTE-CARLO AB Bayesian approaches have been widely used in quantitative trait locus (QTL) linkage analysis in experimental crosses, and have advantages in interpretability and in constructing parameter probability intervals. Most existing Bayesian linkage methods involve Monte Carlo sampling, which is computationally prohibitive for high-throughput applications such as eQTL analysis. In this paper, we present a Bayesian linkage model that offers directly interpretable posterior densities or Bayes factors for linkage. For our model, we employ the Laplace approximation for integration over nuisance parameters in backcross (BC) and F2 intercross designs. Our approach is highly accurate, and very fast compared with alternatives, including grid search integration, importance sampling, and Markov Chain Monte Carlo (MCMC). Our approach is thus suitable for high-throughput applications. Simulated and real datasets are used to demonstrate our proposed approach. Published by Elsevier B.V. C1 [Chang, Yu-Ling; Zou, Fei; Wright, Fred A.] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. RP Chang, YL (reprint author), US FDA, Off Biostat, OTS CDER, Silver Spring, MD 20993 USA. EM yu-ling.chang@fda.hhs.gov; fzou@bios.unc.edu; fwright@bios.unc.edu NR 30 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 EI 1872-7352 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD FEB 1 PY 2010 VL 54 IS 2 BP 565 EP 574 DI 10.1016/j.csda.2009.09.029 PG 10 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 523YL UT WOS:000272110900025 ER PT J AU Silva-Lima, B Carlson, D Jones, DR Laurie, D Stahl, E Maria, V Janssens, W Robinson, WT AF Silva-Lima, Beatriz Carlson, David Jones, David R. Laurie, David Stahl, Elke Maria, Vasco Janssens, Walter Robinson, William T. TI The European and American Use of Exploratory Approaches for First-in-Human Studies* SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Article DE expCTA; expIND; eIND; fi rst-in-human studies; exploratory clinical trial; ICH M3 AB Exploratory approaches for first-in-human clinical studies have evolved over the last few years and have stimulated the issuance of national regulatory guidances in some European countries as well as the United States. With the increasing implementation of these approaches and the recent preparation of a multiregional regulatory guidance (ICH M3 rev2), an exchange of experiences on the opportunities and challenges of exploratory clinical trials was desirable; thus, a workshop focusing on the use of this clinical approach was planned and conducted in Lisbon, Portugal, March 18-19, 2009 sponsored by the Portuguese Health Authority (INFARMED) and DIA. The structure of the workshop focused in three main areas. Regulatory representatives from Portugal, Belgium, Germany, the United Kingdom and the United States formally reviewed their experiences. This was followed by a discussion on issues from an ethics review perspective as well as an insight to the opportunities in the area of biologics. The industry perspective was presented by representatives from Merck, Pfizer, J&J, Novartis, Speedel, AstraZeneca, GSK, and Roche. Finally, through break out sessions, issues were identified to be addressed moving forward. It is the purpose of this paper to report on the outcome of this workshop. Clin Trans Sci 2010; Volume #: 1-4. C1 [Silva-Lima, Beatriz] Univ Lisbon, IMED, INFARMED, P-1699 Lisbon, Portugal. [Carlson, David] FDA CDER, Washington, DC USA. [Jones, David R.] Med & Healthcare Prod Agcy MHRA, London, England. [Laurie, David] Novartis Pharma AG, Basel, Switzerland. [Stahl, Elke] Fed Inst Drugs & Med Devices BfArM, Div Sci Serv, Clin Trial Unit, Bonn, Germany. [Maria, Vasco] Portuguese Med Agcy, INFARMED, Lisbon, Portugal. [Maria, Vasco] Univ Lisbon, Fac Med, P-1699 Lisbon, Portugal. [Janssens, Walter] Fed Agcy Med & Hlth Prod, Brussels, Belgium. [Robinson, William T.] Novartis Pharmaceut, Chester, NJ USA. RP Silva-Lima, B (reprint author), Univ Lisbon, IMED, INFARMED, P-1699 Lisbon, Portugal. EM beatrizlima@netcabo.pt RI Silva Lima, Beatriz/A-4284-2014; iMed.ULisboa, PharmRegSci /B-5723-2014; iMed.ULisboa, iMed.ULisboa/C-6292-2014; OI Silva Lima, Beatriz/0000-0003-0910-7245; iMed.ULisboa, PharmRegSci /0000-0003-0910-7245; Maria, Vasco/0000-0003-4378-0265 NR 8 TC 0 Z9 0 U1 1 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1752-8054 J9 CTS-CLIN TRANSL SCI JI CTS-Clin. Transl. Sci. PD FEB PY 2010 VL 3 IS 1 BP 38 EP 41 DI 10.1111/j.1752-8062.2010.00174.x PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 566UP UT WOS:000275399000015 PM 20443952 ER PT J AU Diarra, B Siddiqui, S Sogoba, D Traore, B Maiga, M Washington, J Tounkara, A Polis, MA AF Diarra, Bassirou Siddiqui, Sophia Sogoba, Dramane Traore, Brehima Maiga, Mamoudou Washington, Janice Tounkara, Anatole Polis, Michael A. TI Mycobacterium tuberculosis Beijing Strain, Bamako, Mali SO EMERGING INFECTIOUS DISEASES LA English DT Letter ID GENOTYPE; RESISTANCE C1 [Siddiqui, Sophia] NIAID, Collaborat Clin Res Branch, NIH, Bethesda, MD 20892 USA. [Washington, Janice] US FDA, Silver Spring, MD USA. [Diarra, Bassirou; Sogoba, Dramane; Traore, Brehima; Maiga, Mamoudou; Tounkara, Anatole] Univ Bamako, Res Colloborat HIV TB, Project SEREFO NIAID, Bamako, Mali. RP Siddiqui, S (reprint author), NIAID, Collaborat Clin Res Branch, NIH, 6700A Rockledge Dr,Rm 1105, Bethesda, MD 20892 USA. EM ssiddiqui@niaid.nih.gov OI Traore, Brehima/0000-0001-9075-9157; Polis, Michael/0000-0002-9151-2268 NR 10 TC 2 Z9 2 U1 0 U2 0 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 FEB PY 2010 VL 16 IS 2 BP 362 EP 363 DI 10.3201/eid1602.090501 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 553XO UT WOS:000274400300045 PM 20113590 ER PT J AU Zolnik, BS Gonzalez-Fernandez, A Sadrieh, N Dobrovolskaia, MA AF Zolnik, Banu S. Gonzalez-Fernandez, Africa Sadrieh, Nakissa Dobrovolskaia, Marina A. TI Minireview: Nanoparticles and the Immune System SO ENDOCRINOLOGY LA English DT Review ID WALLED-CARBON-NANOTUBES; ACCELERATED BLOOD CLEARANCE; ALBUMIN-BOUND PACLITAXEL; PEGYLATED LIPOSOMES; COMPLEMENT ACTIVATION; LIPID NANOPARTICLES; HYPERSENSITIVITY REACTIONS; PATHOTROPIC NANOPARTICLES; IMMUNOLOGICAL-PROPERTIES; CYTOKINE PRODUCTION AB Today nanotechnology is finding growing applications in industry, biology, and medicine. The clear benefits of using nanosized products in various biological and medical applications are often challenged by concerns about the lack of adequate data regarding their toxicity. One area of interest involves the interactions between nanoparticles and the components of the immune system. Nanoparticles can be engineered to either avoid immune system recognition or specifically inhibit or enhance the immune responses. We review herein reported observations on nanoparticle-mediated immunostimulation and immunosuppression, focusing on possible theories regarding how manipulation of particle physicochemical properties can influence their interaction with immune cells to attain desirable immunomodulation and avoid undesirable immunotoxicity. (Endocrinology 151: 458-465, 2010) C1 [Dobrovolskaia, Marina A.] NCI, Nanotechnol Characterizat Lab, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21703 USA. [Zolnik, Banu S.; Sadrieh, Nakissa] US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Silver Spring, MD 20993 USA. [Gonzalez-Fernandez, Africa] Univ Vigo, Area Inmunol, Vigo 36310, Pontevedra, Spain. [Gonzalez-Fernandez, Africa] Univ Vigo, Unidad Compartida Complejo Hosp Univ Vigo, Vigo 36310, Pontevedra, Spain. RP Dobrovolskaia, MA (reprint author), NCI, Nanotechnol Characterizat Lab, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21703 USA. EM marina@mail.nih.gov RI Gonzalez-Fernandez, Africa/E-2641-2012; Nanotechnology Characterization Lab, NCL/K-8454-2012 OI Gonzalez-Fernandez, Africa/0000-0002-9226-4825; FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Ministerio de Ciencia y Tecnologia [CSD2006-12]; Xunta de Galicia [PGIDIT06TMT31402PR] FX The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. This paper reflects the current thinking and experience of the authors (B.S.Z. and N.S.). However, this is not a policy document and should not be used in lieu of regulations, published Food and Drug Administration guidance documents, or direct discussions with the agency. We are grateful to Dr. Scott McNeil for critique and helpful discussion during manuscript preparation.; Address all correspondence and requests for reprints to: Marina A. Dobrovolskaia, Nanotechnology Characterization Laboratory, Science Applications Internation Corp.-Frederick Inc., National Cancer Institute-Frederick, Frederick, Maryland 21703. E-mail: marina@mail.nih.gov.; This work was supported in whole or part by federal funds from the National Cancer Institute, National Institutes of Health, under Contract HHSN261200800001E (to M.A.D.) and the Ministerio de Ciencia y Tecnologia under Contract Consolider Ingenio 2010 (CSD2006-12, to A.G.-F.) and the Xunta de Galicia under Contract PGIDIT06TMT31402PR (to A.G.-F.).; Disclosure Summary: B.S.Z, A.G.-F., N.S., and M.A.D. have nothing to disclose. NR 77 TC 246 Z9 250 U1 11 U2 96 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 2010 VL 151 IS 2 BP 458 EP 465 DI 10.1210/en.2009-1082 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 548GR UT WOS:000273948600004 PM 20016026 ER PT J AU Landers, DH Simonich, SM Jaffe, D Geiser, L Campbell, DH Schwindt, A Schreck, C Kent, M Hafner, W Taylor, HE Hageman, K Usenko, S Ackerman, L Schrlau, J Rose, N Blett, T Erway, MM AF Landers, Dixon H. Simonich, Staci Massey Jaffe, Daniel Geiser, Linda Campbell, Donald H. Schwindt, Adam Schreck, Carl Kent, Michael Hafner, Will Taylor, Howard E. Hageman, Kimberly Usenko, Sascha Ackerman, Luke Schrlau, Jill Rose, Neil Blett, Tamara Erway, Marilyn Morrison TI The Western Airborne Contaminant Assessment Project (WACAP): An Interdisciplinary Evaluation of the Impacts of Airborne Contaminants in Western US National Parks SO ENVIRONMENTAL SCIENCE & TECHNOLOGY LA English DT Article ID PESTICIDES; DEPOSITION; TROUT; PBDES; PAHS; PCBS; FISH C1 [Landers, Dixon H.] US EPA, Western Ecol Div, Freshwater Ecol Branch, Corvallis, OR USA. [Simonich, Staci Massey] Oregon State Univ, Dept Chem, Corvallis, OR 97331 USA. [Jaffe, Daniel] Univ Washington, Bothell, WA USA. [Geiser, Linda] US Forest Serv, Pacific NW Reg Air Program, Corvallis, OR USA. [Campbell, Donald H.] US Geol Survey, Colorado Water Sci Ctr, Denver, CO 80225 USA. [Schwindt, Adam] Ecotox Grp, Denver, CO USA. [Kent, Michael] Oregon State Univ, Dept Microbiol, Coll Agr Sci & Biomed sci, Coll Vet Med, Corvallis, OR 97331 USA. [Hafner, Will] Sci Applicat Int Corp, Seattle, WA USA. [Schreck, Carl] US Geol Survey, Corvallis, OR USA. [Taylor, Howard E.] US Geol Survey, Natl Res Program, Water Resources Discipline, Boulder, CO USA. [Hageman, Kimberly] Univ Otago, Dept Chem, Dunedin, New Zealand. [Usenko, Sascha] Baylor Univ, Waco, TX 76798 USA. [Ackerman, Luke] US FDA, College Pk, MD USA. [Rose, Neil] UCL, Environm Change Res Ctr, London, England. [Blett, Tamara] Natl Pk Serv, Denver, CO USA. [Erway, Marilyn Morrison] Dynamac Corp, Corvallis, OR USA. RP Landers, DH (reprint author), US EPA, Western Ecol Div, Freshwater Ecol Branch, Corvallis, OR USA. EM Landers.Dixon@epamail.epa.gov RI Ackerman, Luke/E-4597-2011; Guenat, Heather/H-6528-2014; Usenko, Sascha/N-8730-2015; OI Ackerman, Luke/0000-0001-6626-3039; Hageman, Kimberly/0000-0001-9187-5256; Usenko, Sascha/0000-0003-3303-2909 FU U.S. Environmental Protection Agency FX The completion of WACAP represents a tremendous coordinated effort by many individuals to whom we are indebted. An expanded list of acknowledgements is in SI-H. The information in this document has been funded wholly or in part by the U.S. Environmental Protection Agency. It has been subjected to review by the National Health and Environmental Effects Research Laboratory's Western Ecology Division and approved for publication. Approval does not signify that the content reflects the views of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. NR 11 TC 27 Z9 28 U1 0 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0013-936X J9 ENVIRON SCI TECHNOL JI Environ. Sci. Technol. PD FEB 1 PY 2010 VL 44 IS 3 BP 855 EP 859 DI 10.1021/es901866e PG 5 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA 548HD UT WOS:000273950100004 PM 20050680 ER PT J AU Guo, L Shi, Q Dial, S Xia, QS Mei, N Li, QZ Chan, PC Fu, P AF Guo, Lei Shi, Qiang Dial, Stacey Xia, Qingsu Mei, Nan Li, Quan-zhen Chan, Po-Chuen Fu, Peter TI Gene expression profiling in male B6C3F1 mouse livers exposed to kava identifies - Changes in drug metabolizing genes and potential mechanisms linked to kava toxicity SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Drug metabolizing enzyme; Drug metabolizing gene; Gene expression; Kava extract; Microarray; TaqMan assay ID HEPATIC CYTOCHROME-P450; DIETARY-SUPPLEMENTS; HUMAN HEPATOCYTES; ORAL TREATMENT; GINKGO-BILOBA; NRF2; EXTRACT; ACTIVATION; RATS; MICE AB The association of kava products with liver-related health risks has prompted regulatory action in many countries We used a genome-wide gene expression approach to generate global gene expression profiles from the livers of male B6C3F1 mice administered kava extract by gavage for 14 weeks, and identified the differentially expressed drug metabolizing genes in response to kava treatments. Analyses of gene functions and pathways reveal that the levels of significant numbers of genes involving drug metabolism were changed and that the pathways involving xenobiotics metabolism, Nrf2-mediated oxidative stress response, mitochondrial functions and others, were altered. Our results indicate that kava extract can significantly modulate drug metabolizing enzymes, potentially leading to herb-drug interactions and hepatotoxicity. Published by Elsevier Ltd. C1 [Guo, Lei; Shi, Qiang; Dial, Stacey] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. [Xia, Qingsu; Fu, Peter] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Mei, Nan] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Li, Quan-zhen] UTSW Med Ctr, Microarray Core Facil, Dallas, TX 75390 USA. [Chan, Po-Chuen] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Guo, L (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. RI Guo, Lei/E-9232-2011; mei, nan/E-8915-2011; Qiang, Shi/E-6266-2012 OI mei, nan/0000-0002-3501-9014; FU NIH; National Institute of Environmental Health Sciences FX We thank Drs. Frederick A. Beland, Donna Mendrick, James C. Fuscoe, Tucker Patterson, Rick Irwin and Scott Auerbach for their critical review of this manuscript. Dr. Qiang Shi IS Supported by the Research Participation Program at the NCTR administrated by the Oak Ridge Institute for Science and Education through an Interagency agreement between the US Department of Energy and the US Food and Drug Administration. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 42 TC 17 Z9 18 U1 1 U2 7 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 FEB PY 2010 VL 48 IS 2 BP 686 EP 696 DI 10.1016/j.fct.2009.11.050 PG 11 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 561VK UT WOS:000275007700034 PM 19948201 ER PT J AU Folster, JP Pecic, G Bolcen, S Theobald, L Hise, K Carattoli, A Zhao, SH McDermott, PF Whichard, JM AF Folster, Jason P. Pecic, Gary Bolcen, Shanna Theobald, Lisa Hise, Kelley Carattoli, Alessandra Zhao, Shaohua McDermott, Patrick F. Whichard, Jean M. TI Characterization of Extended-Spectrum Cephalosporin-Resistant Salmonella enterica Serovar Heidelberg Isolated from Humans in the United States SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID AMPC BETA-LACTAMASE; ESCHERICHIA-COLI; RETAIL MEATS; PLASMID; INFECTIONS; POULTRY; OUTBREAKS; ANIMALS; FRANCE; STRAIN AB During the past decade, extended-spectrum cephalosporin resistance has increased among human isolates of Salmonella enterica serovar Heidelberg, the fourth most common serotype in the United States. We therefore characterized 54 Heidelberg isolates with decreased susceptibility (minimum inhibitory concentrations >= 2 mg/L) to ceftriaxone or ceftiofur; 49 (90.7%) contained the CMY-type beta-lactamase (bla(CMY)) gene. The 49 bla(CMY)-positive human Heidelberg isolates demonstrated a high degree of relatedness; 4 clusters (25 isolates total) had indistinguishable XbaI and BlnI patterns by pulsed-field gel electrophoresis and were indistinguishable from 42 retail meat Heidelberg isolates. Further characterization of 15 of these isolates demonstrated that all of the bla genes were bla(CMY-2) and plasmid-encoded, and most (11/15) of the plasmids were approximately 100 kb in size and belong to the incompatibility group I1 (IncI1). All five IncI1 plasmids tested by plasmid multilocus sequence typing analysis were ST12. This report suggests that extended-spectrum cephalosporin resistance among human Heidelberg isolates is mediated by the spread of a common IncI1 bla(CMY-2) plasmid, which may have a preference for a particular genetic background. C1 [Folster, Jason P.] Ctr Dis Control & Prevent, CCID, NCZVED, DFBMD,EDLB, Atlanta, GA 30329 USA. [Folster, Jason P.; Pecic, Gary] Atlanta Res & Educ Fdn, Decatur, GA USA. [Carattoli, Alessandra] Ist Super Sanita, Dept Infect Parasit & Immune Mediated Dis, I-00161 Rome, Italy. [Zhao, Shaohua; McDermott, Patrick F.] US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD USA. RP Folster, JP (reprint author), Ctr Dis Control & Prevent, CCID, NCZVED, DFBMD,EDLB, 1600 Clifton Rd, Atlanta, GA 30329 USA. EM gux8@cdc.gov OI Carattoli, Alessandra/0000-0002-6120-6526 FU CDC; FDA-CVM FX We thank the NARMS-participating public health laboratories for submitting the isolates, Anne Whitney for DNA sequencing, and Maria Karlsson for her critical review. This work was supported by an interagency agreement between CDC and the FDA-CVM. NR 31 TC 29 Z9 29 U1 1 U2 8 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 FEB PY 2010 VL 7 IS 2 BP 181 EP 187 DI 10.1089/fpd.2009.0376 PG 7 WC Food Science & Technology SC Food Science & Technology GA 547CD UT WOS:000273862200010 PM 19785533 ER PT J AU Chen, WJ Metz, CE Giger, ML Drukker, K AF Chen, Weijie Metz, Charles E. Giger, Maryellen L. Drukker, Karen TI A Novel Hybrid Linear/Nonlinear Classifier for Two-Class Classification: Theory, Algorithm, and Applications SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Computer-aided diagnosis (CAD); hybrid linear/nonlinear classifier; linear classifier; linear discriminant analysis; receiver operating characteristic (ROC) analysis ID MAXIMUM-LIKELIHOOD-ESTIMATION; COMPUTER-AIDED DIAGNOSIS; BINORMAL ROC CURVES; DISCRIMINANT-ANALYSIS; SAMPLE-SIZE; BREAST; PERFORMANCE; POPULATION; DATASETS; DESIGN AB Classifier design for a given classification task needs to take into consideration both the complexity of the classifier and the size of the dataset that is available for training the classifier. With limited training data, as often is the situation in computer-aided diagnosis of medical images, a classifier with simple structure (e.g., a linear classifier) is more robust and therefore preferred. We propose a novel two-class classifier, which we call a hybrid linear/nonlinear classifier (HLNLC), that involves two stages: the input features are linearly combined to form a scalar variable in the first stage and then the likelihood ratio of the scalar variable is used as the decision variable for classification. We first develop the theory of HLNLC by assuming that the feature data follow normal distributions. We show that the commonly used Fisher's linear discriminant function is generally not the optimal linear function in the first stage of the HLNLC. We formulate an optimization problem to solve for the optimal linear function in the first stage of the HLNLC, i.e., the linear function that maximizes the area under the receiver operating characteristic (ROC) curve of the HLNLC. For practical applications, we propose a robust implementation of the HLNLC by making a loose assumption that the two-class feature data arise from a pair of latent (rather than explicit) multivariate normal distributions. The novel hybrid classifier fills a gap between linear discriminant analysis (LDA) and quadratic discriminant analysis (QDA) in the sense that both its theoretical performance and its complexity lie between those of the LDA and those of the QDA. Simulation studies show that the hybrid linear/nonlinear classifier performs better than LDA without increasing the classifier complexity accordingly. With a finite number of training samples, the HLNLC can perform better than that of the ideal observer due to its simplicity. Finally, we demonstrate the application of the HLNLC in computer-aided diagnosis of breast lesions in ultrasound images. C1 [Chen, Weijie] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Metz, Charles E.; Giger, Maryellen L.; Drukker, Karen] Univ Chicago, Dept Radiol, Comm Med Phys, Chicago, IL 60637 USA. RP Chen, WJ (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM weijie.chen@fda.hhs.gov RI Chen, Weijie/A-3712-2012; OI Giger, Maryellen/0000-0001-5482-9728 FU Department of Defense (DOD) [DAMD17-03-1-0245]; National Institutes of Health (NIH) [R01-CA89452, R21-CA113800, P50-CA125183] FX Manuscript received August 03, 2009; revised September 10, 2009; accepted September 20, 2009. First published October 09, 2009; current version published February 03, 2010. This work was supported in part by a Department of Defense (DOD) Breast Cancer Research Program Predoctoral Traineeship Award under Grant DAMD17-03-1-0245, in part by the Lawrence H. Lanzl Graduate Student Fellowship in Medical Physics (Committee on Medical Physics, The University of Chicago), and in part by the National Institutes of Health (NIH) under Grant R01-CA89452, Grant R21-CA113800, and Grant P50-CA125183. C. E. Metz and M. L. Giger were shareholders in R2 Technology/Hologic, Sunnyvale, CA. It is the policy of the University of Chicago that investigators disclose publicly actual or potential significant financial interests that may appear to be affected by the research activities. NR 38 TC 7 Z9 7 U1 2 U2 10 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 FEB PY 2010 VL 29 IS 2 BP 428 EP 441 DI 10.1109/TMI.2009.2033596 PG 14 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 551LS UT WOS:000274211700017 PM 19822471 ER PT J AU Harrel, SM Milot, RL Schleicher, JM Schmuttenmaer, CA AF Harrel, Shayne M. Milot, Rebecca L. Schleicher, James M. Schmuttenmaer, Charles A. TI Influence of free-carrier absorption on terahertz generation from ZnTe(110) SO JOURNAL OF APPLIED PHYSICS LA English DT Article DE II-VI semiconductors; optical harmonic generation; terahertz wave generation; terahertz wave spectra; two-photon processes; wide band gap semiconductors; zinc compounds ID FEMTOSECOND OPTICAL PULSES; NONLINEAR PROCESSES; 2-PHOTON ABSORPTION; THZ GENERATION; RECTIFICATION; RADIATION; SPECTROSCOPY; COMPETITION; ZNTE; DYNAMICS AB ZnTe(110) is widely used as a source of terahertz radiation generated by optical rectification. However, when ZnTe(110) is excited with 800 nm light, optical rectification is not the only process which can occur. Specifically, second harmonic generation and two-photon absorption are also possibilities. In addition, free carriers generated by two-photon absorption can absorb terahertz radiation, further reducing the efficiency of optical rectification. We have used terahertz emission spectroscopy to study these effects by analyzing the dependence of the terahertz waveform on excitation fluence. At high excitation fluences, the overall efficiency is reduced and the trailing edge of the waveform is attenuated. A simple model reproduces the measured behavior. C1 [Harrel, Shayne M.; Milot, Rebecca L.; Schleicher, James M.; Schmuttenmaer, Charles A.] Yale Univ, Dept Chem, New Haven, CT 06520 USA. RP Harrel, SM (reprint author), US FDA, Winchester Analyt & Engn Ctr, 109 Holton St, Winchester, MA 01890 USA. EM charles.schmuttenmaer@yale.edu FU National Science Foundation [CHE-0616875] FX We acknowledge the National Science Foundation (Grant No. CHE-0616875) for partial support of this work. S. M. H. and R. L. M. contributed equally to this work. NR 24 TC 16 Z9 16 U1 2 U2 18 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-8979 J9 J APPL PHYS JI J. Appl. Phys. PD FEB PY 2010 VL 107 IS 3 AR 033526 DI 10.1063/1.3296064 PG 5 WC Physics, Applied SC Physics GA 555MZ UT WOS:000274517300043 ER PT J AU Thompson, J Hill, KK Smith, TJ Pikis, A AF Thompson, John Hill, Karen K. Smith, Theresa J. Pikis, Andreas TI The Gene CBO0515 from Clostridium botulinum Strain Hall A Encodes the Rare Enzyme N-5-(Carboxyethyl) Ornithine Synthase, EC 1.5.1.24 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID LACTOCOCCUS-LACTIS K1; STREPTOCOCCUS-LACTIS; NADP+ OXIDOREDUCTASE; N5-(L-1-CARBOXYETHYL)-L-ORNITHINE; PURIFICATION; SEQUENCE; DEHYDROGENASE; NEUROTOXIN; PROTEIN AB Sequencing of the genome of Clostridium botulinum strain Hall A revealed a gene (CBO0515), whose putative amino acid sequence was suggestive of the rare enzyme N-5-(1-carboxyethyl) ornithine synthase. To test this hypothesis, CBO0515 has been cloned, and the encoded polypeptide was purified and characterized. This unusual gene appears to be confined to proteolytic strains assigned to group 1 of C. botulinum. C1 [Thompson, John; Pikis, Andreas] NIDCR, Microbial Biochem & Genet Unit, Oral Infect & Immun Branch, NIH,DHHS, Bethesda, MD 20892 USA. [Pikis, Andreas] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Hill, Karen K.] Los Alamos Natl Lab, Biosci Div, Los Alamos, NM 87545 USA. [Smith, Theresa J.] USA, Med Res Inst Infect Dis, Integrated Toxicol Div, Ft Detrick, MD 21702 USA. RP Thompson, J (reprint author), NIDCR, Microbial Biochem & Genet Unit, Oral Infect & Immun Branch, NIH,DHHS, Bldg 30,Rm 325,Convent Dr MSC-4350, Bethesda, MD 20892 USA. EM jthompson@dir.nidcr.nih.gov FU Intramural Research Program of the National Institute of Dental and Craniofacial Research; National Institutes of Health, Bethesda, MD FX This investigation was supported by the Intramural Research Program of the National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD. NR 20 TC 0 Z9 1 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD FEB PY 2010 VL 192 IS 4 BP 1151 EP 1155 DI 10.1128/JB.01044-09 PG 5 WC Microbiology SC Microbiology GA 549DF UT WOS:000274021900026 PM 19933367 ER PT J AU Antonucci, JM Regnault, WF Skrtic, D AF Antonucci, J. M. Regnault, W. F. Skrtic, D. TI Polymerization Shrinkage and Stress Development in Amorphous Calcium Phosphate/Urethane Dimethacrylate Polymeric Composites SO JOURNAL OF COMPOSITE MATERIALS LA English DT Article DE amorphous calcium phosphate; composite; urethane dimethacrylate; polymerization shrinkage stress ID PHOSPHATE/METHACRYLATE COMPOSITES; RESIN-COMPOSITES; PHOSPHATES; CONVERSION; HYBRID AB This study explores how substituting a new high molecular mass oligomeric poly(ethylene glycol) extended urethane dimethacrylate (UDMA) (PEG-U) for 2-hydroxyethyl methacrylate (HEMA) in photo-activated UDMA resins affects degree of vinyl conversion (DC), polymerization shrinkage (PS), stress development (PSSD) and biaxial flexure strength (BFS) of their amorphous calcium phosphate (ACP) composites. The composites were prepared from four types of resins (UDMA, PEG-U, UDMA/HEMA, and UDMA/PEG-U) and zirconia-hybridized ACP. Introducing PEG-U improved DC, while not adversely affecting PS, PSSD, and the BFS of composites. This improvement in DC is attributed to the long, more flexible structure between the vinyl groups of PEG-U and its higher molecular mass compared to poly(HEMA). The results imply that PEG-U has the potential to serve as an alternative to HEMA in dental and other biomedical applications. C1 [Skrtic, D.] Amer Dent Assoc Hlth Fdn, Paffenbarger Res Ctr, Gaithersburg, MD 20899 USA. [Antonucci, J. M.] Natl Inst Stand & Technol, Div Polymers, Gaithersburg, MD 20899 USA. [Regnault, W. F.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Skrtic, D (reprint author), Amer Dent Assoc Hlth Fdn, Paffenbarger Res Ctr, Gaithersburg, MD 20899 USA. EM drago.skrtic@nist.gov FU National Institute of Dental and Craniofacial Research [Y1-DE-7006]; American Dental Association Foundation [13169]; FDA; NIST; ADAF FX Reported work was supported by the National Institute of Dental and Craniofacial Research (NIST-NIDCR Interagency Agreement Y1-DE-7006 and grant 13169 to the American Dental Association Foundation). It is a part of the dental material research program supported by FDA, NIST, and ADAF. Generous contribution of UDMA, PEGU, and HEMA monomers from Esstech, Essington, PA, USA, is gratefully acknowledged. NR 16 TC 9 Z9 9 U1 0 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0021-9983 J9 J COMPOS MATER JI J. Compos Mater. PD FEB PY 2010 VL 44 IS 3 BP 355 EP 367 DI 10.1177/0021998309345180 PG 13 WC Materials Science, Composites SC Materials Science GA 548MS UT WOS:000273968100007 PM 20169007 ER PT J AU Boehmer, JL Ward, JL Peters, RR Shefcheck, KJ McFarland, MA Bannerman, DD AF Boehmer, J. L. Ward, J. L. Peters, R. R. Shefcheck, K. J. McFarland, M. A. Bannerman, D. D. TI Proteomic analysis of the temporal expression of bovine milk proteins during coliform mastitis and label-free relative quantification SO JOURNAL OF DAIRY SCIENCE LA English DT Article DE bovine milk proteome; liquid chromatography-tandem mass spectrometry; coliform mastitis; label-free quantification ID GLOBULE-MEMBRANE PROTEOME; SHOTGUN PROTEOMICS; ESCHERICHIA-COLI; QUANTITATIVE PROTEOMICS; INTRAMAMMARY INFECTION; MASS-SPECTROMETRY; LIPOPOLYSACCHARIDE; IDENTIFICATION; ABUNDANCE; MIXTURES AB The discovery of biomarkers in milk indicative of local inflammation or disease in the bovine mammary gland has been hindered by the extreme biological complexity of milk, the dynamic range of proteins in the matrix that renders the identification of low-abundance proteins difficult, and the challenges associated with quantifying changes during disease in the abundance of proteins for which no antibody exists. The objectives of the current study were to characterize the temporal expression of milk proteins following Escherichia coli challenge and to evaluate change in relative abundance of identified proteins using a liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) label-free semiquantitative approach. Liquid chromatography-MS/MS conducted on whey from milk samples collected just before infusion with E. coli and at 12, 187 24, 36, 48, and 60 h following infection resulted in the identification of the high- to medium-abundance proteins alpha(S1)-, alpha(S2)- beta-, and kappa-caseins and the whey proteins serum albumin, beta-lactoglobulin, and a-lactalbumin. Additionally, a select number of lower abundance markers of inflammation were also identified, including lactoferrin, transferrin, apolipoprotein AI, fibrinogen, glycosylation-dependent cell adhesion molecule-1, peptidoglycan recognition receptor protein, and cyclic dodecapeptide-1. Normalized peptide counts for each protein identified were used to evaluate temporal changes in milk proteins following infection. For comparison with relative protein abundance determined using proteomic-based methods, changes in serum albumin, lactoferrin, and transferrin in milk during disease were also measured using ELISA. Label-free, proteomic-based quantification revealed relative changes in milk proteins that corresponded to expression profiles generated by ELISA. The results indicate that label-free LC-MS/MS methods are a viable means of tracking changes in relative protein abundance in milk during disease. Despite the identification of primarily abundant milk proteins, the results indicate that, with further refinement, LC-MS/MS could be used to evaluate temporal changes in proteins related to host response for which no antibody or ELISA currently exists. C1 [Boehmer, J. L.; Ward, J. L.] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [Boehmer, J. L.; Peters, R. R.] Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. [Shefcheck, K. J.; McFarland, M. A.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20742 USA. [Bannerman, D. D.] USDA ARS, Bovine Funct Genom Lab, Beltsville, MD 20705 USA. RP Boehmer, JL (reprint author), US FDA, Ctr Vet Med, Laurel, MD 20708 USA. EM jamie.boehmer@fda.hhs.gov RI McFarland, Melinda/A-1866-2013 NR 34 TC 30 Z9 34 U1 3 U2 16 PU AMER DAIRY SCIENCE ASSOC-ADSA PI CHAMPAIGN PA 2441 VILLAGE GREEN PL, CHAMPAIGN, IL 61822 USA SN 0022-0302 J9 J DAIRY SCI JI J. Dairy Sci. PD FEB PY 2010 VL 93 IS 2 BP 593 EP 603 DI 10.3168/jds.2009-2526 PG 11 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA 550BR UT WOS:000274102500017 PM 20105531 ER PT J AU Lin, WS Cheng, CM Van, KT AF Lin, Wen S. Cheng, Chorng-Ming Van, Khanh T. TI A Quantitative PCR Assay for Rapid Detection of Shigella Species in Fresh Produce SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ENTEROINVASIVE ESCHERICHIA-COLI; REAL-TIME PCR; MULTIPLEX PCR; FOODBORNE PATHOGENS; ANTIGEN GENE; IPAH; BACTERIAL; VIRULENCE; SPP.; FOOD AB A quantitative PCR (qPCR) assay with two primers and a TaqMan probe targeting conserved regions of the specific ipaH gene of Shigella species and enteroinvasive Escherichia coli (EIEC) were developed. This qPCR assay was used to identify 206 Shigella strains (including four Shigella species with all serotypes and two provisional Shigella species), 3 EIEC strains, and 113 non-Shigella strains with 100% accuracy. Pure cultures of six Shigella reference strains were used to derive standard curves to determine the detection limit and efficiency of the qPCR method. The ipaH qPCR assay had an equally low detection limit (0.12 to 0.74 CFU per PCR) for the four Shigella species tested. The average qPCR efficiency was 99.29% (95.36 to 103.92%). The detection limit of the qPCR assay tested on 15 varieties of inoculated fresh produce ranged from 0.4 to 16 CFU/100 ml of buffer rinse. This qPCR assay took the variation of wild-type nucleotides into consideration and Was used successfully to screen fresh produce. This highly sensitive qPCR assay can be completed within 24 h and has potential use as a Screening tool for all four Shigella species and EIEC in food samples. C1 [Lin, Wen S.] US FDA, Div Field Sci, Rockville, MD 20857 USA. [Cheng, Chorng-Ming; Van, Khanh T.] US FDA, Pacific Reg Lab SW, Irvine, CA 92612 USA. RP Lin, WS (reprint author), US FDA, Div Field Sci, 5600 Fishers Lane,Room 12-41, Rockville, MD 20857 USA. EM wen.lin@fda.hhs.gov NR 41 TC 17 Z9 17 U1 2 U2 7 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 FEB PY 2010 VL 73 IS 2 BP 221 EP 233 PG 13 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 558RS UT WOS:000274763600002 PM 20132666 ER PT J AU Pouillot, R Lubran, MB Cates, SC Dennis, S AF Pouillot, Regis Lubran, Meryl B. Cates, Sheryl C. Dennis, Sherri TI Estimating Parametric Distributions of Storage Time and Temperature of Ready-to-Eat Foods for US Households SO JOURNAL OF FOOD PROTECTION LA English DT Article ID WEB-BASED SURVEY; LISTERIA-MONOCYTOGENES; UNITED-STATES; REFRIGERATORS; KNOWLEDGE; SAFETY; HOME AB Home refrigeration temperatures and product storage times are important factors for controlling the growth of Listeria monocytogenes in refrigerated ready-to-eat foods. In 2005, RTI International, in collaboration with Tennessee State University and Kansas State University, conducted a national survey of U.S. adults to characterize consumers' home storage and refrigeration practices for 10 different categories of refrigerated ready-to-eat foods. No distributions of storage time or refrigeration temperature were presented in any of the resulting publications. This Study used classical parametric survival modeling to derive parametric distributions from the RTI International storage practices data set. Depending on the food category, variability in product storage times was best modeled using either exponential or Weibull distributions. The shape and scale of the distributions varied greatly depending oil the food category. Moreover, the results indicated that Consumers tend to keep a product that is packaged by a manufacturer for a longer period of time than a product that is packaged at retail. Refrigeration temperatures were comparable to those previously, reported. with the variability in temperatures best fit using a Laplace distribution, as an alternative to the empirical distribution. In contrast to previous research. limited support was found for a correlation between storage time and temperature. The distributions provided ill this study can be used to better model consumer behavior in future risk assessments. C1 [Pouillot, Regis; Dennis, Sherri] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Lubran, Meryl B.] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Cates, Sheryl C.] RTI Int, Res Triangle Pk, NC 27709 USA. RP Dennis, S (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM Sherri.Dennis@fda.hhs.gov RI Pouillot, Regis/E-8103-2010 OI Pouillot, Regis/0000-0002-6107-5212 FU Center for Food Safety and Applied Nutrition; U.S. Department of Energy; U.S. Food and Drug Administration; Joint Institute for Food Safety and Applied Nutrition, University of Maryland FX This project was supported in part by an appointment to the Research Participation Program at the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration and by the Joint Institute for Food Safety and Applied Nutrition, University of Maryland. NR 29 TC 16 Z9 16 U1 1 U2 6 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD FEB PY 2010 VL 73 IS 2 BP 312 EP 321 PG 10 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 558RS UT WOS:000274763600013 PM 20132677 ER PT J AU O'Callaghan, K Camacho, M Martin, T Lockard, KL Miller, MA Young, JB AF O'Callaghan, K. Camacho, M. Martin, T. Lockard, K. L. Miller, M. A. Young, J. B. TI Sex Differences in Usage of Mechanical Circulatory Support and Pre-Implant Baseline Characteristics Using the INTERMACS Database SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 30th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 21-24, 2010 CL Chicago, IL SP Int Soc Heart & Lung Transplantat C1 [O'Callaghan, K.] US FDA, Silver Spring, MD USA. [Camacho, M.; Martin, T.] Newark Beth Israel Med Ctr, Newark, NJ USA. [Lockard, K. L.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Miller, M. A.] NHLBI, Bethesda, MD 20892 USA. [Young, J. B.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2010 VL 29 IS 2 SU S MA 103 BP S40 EP S40 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 558PF UT WOS:000274756100103 ER PT J AU Nathan, AT Hoehn, KS Ittenbach, RF Gaynor, JW Nicolson, S Wernovsky, G Nelson, RM AF Nathan, Aruna T. Hoehn, K. Sarah Ittenbach, Richard F. Gaynor, J. William Nicolson, Susan Wernovsky, Gil Nelson, Robert M. TI Assessment of parental decision-making in neonatal cardiac research: a pilot study SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID INFORMED-CONSENT; ALZHEIMERS-DISEASE; COMPETENCE; CAPACITY; SCHIZOPHRENIA; TRIAL AB Objective To assess parental permission for a neonate's research participation using the MacArthur competence assessment tool for clinical research (MacCAT-CR), specifically testing the components of understanding, appreciation, reasoning and choice. Study Design Quantitative interviews using study-specific MacCAT-CR tools. Hypothesis Parents of critically ill newborns would produce comparable MacCAT-CR scores to healthy adult controls despite the emotional stress of an infant with critical heart disease or the urgency of surgery. Parents of infants diagnosed prenatally would have higher MacCAT-CR scores than parents of infants diagnosed postnatally. There would be no difference in MacCAT-CR scores between parents with respect to gender or whether they did or did not permit research participation. Participants Parents of neonates undergoing cardiac surgery who had made decisions about research participation before their neonate's surgery. Methods The MacCAT-CR. Results 35 parents (18 mothers; 17 fathers) of 24 neonates completed 55 interviews for one or more of three studies. Total scores: magnetic resonance imaging (mean 36.6, SD 7.71), genetics (mean 38.8, SD 3.44), heart rate variability (mean 37.7, SD 3.30). Parents generally scored higher than published subject populations and were comparable to published control populations with some exceptions. Conclusions The MacCAT-CR can be used to assess parental permission for neonatal research participation. Despite the stress of a critically ill neonate requiring surgery, parents were able to understand study-specific information and make informed decisions to permit their neonate's participation. C1 [Nathan, Aruna T.; Nicolson, Susan] Univ Penn, Dept Anesthesiol & Crit Care Med, Philadelphia, PA 19104 USA. [Hoehn, K. Sarah] St Christophers Hosp Children, Dept Pediat, Philadelphia, PA 19133 USA. [Ittenbach, Richard F.] Cincinnati Childrens Hosp, Med Ctr, Dept Pediat, Cincinnati, OH USA. [Gaynor, J. William; Nicolson, Susan; Wernovsky, Gil] Childrens Hosp Philadelphia, Cardiac Ctr, Philadelphia, PA 19104 USA. [Gaynor, J. William] Childrens Hosp Philadelphia, Dept Surg, Philadelphia, PA 19104 USA. [Gaynor, J. William; Wernovsky, Gil] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Wernovsky, Gil] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [Nelson, Robert M.] US FDA, Off Pediat Therapeut, Off Commissioner, Rockville, MD 20857 USA. RP Nathan, AT (reprint author), Childrens Hosp Philadelphia, Dept Anesthesiol & Crit Care Med, 12 NW 40,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM nathan@email.chop.edu RI Ittenbach, Richard/Q-1806-2015; gaynor, James william/E-5194-2013 OI gaynor, James william/0000-0001-7955-5604 FU Joseph Stokes, Jr Research Institute of The Children's Hospital of Philadelphia FX Supported in part by a grant from the Florence RC Murray Program of the Joseph Stokes, Jr Research Institute of The Children's Hospital of Philadelphia. NR 25 TC 6 Z9 7 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD FEB PY 2010 VL 36 IS 2 BP 106 EP 110 DI 10.1136/jme.2009.030676 PG 5 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 552NK UT WOS:000274298600011 PM 20133406 ER PT J AU Burda, ST Viswanath, R Zhao, JQ Kinge, T Anyangwe, C Tinyami, ET Haldar, B Powell, RLR Jarido, V Hewlett, IK Nyambi, PN AF Burda, Sherri T. Viswanath, Ragupathy Zhao, Jiangqin Kinge, Thompson Anyangwe, Christopher Tinyami, Erick T. Haldar, Bijayesh Powell, Rebecca L. R. Jarido, Veronica Hewlett, Indira K. Nyambi, Phillipe N. TI HIV-1 Reverse Transcriptase Drug-Resistance Mutations in Chronically Infected Individuals Receiving or Naive to HAART in Cameroon SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE drug-resistance mutations; HIV-1; NRTI; NNRTI; HAART; drug naive ID IMMUNODEFICIENCY-VIRUS TYPE-1; NEWLY-DIAGNOSED PATIENTS; FIXED-DOSE COMBINATION; ANTIRETROVIRAL THERAPY; HIGH PREVALENCE; SOUTH-AFRICA; SUBTYPE-B; ZIDOVUDINE; NEVIRAPINE; LAMIVUDINE AB The most common first-line, highly active anti-retroviral therapy (HAART) received by individuals infected with HIV-1 in Cameroon is the combination therapy Triomune, comprised of two nucleoside reverse transcriptase inhibitors (NRTI) and one non-NRTI (NNRTI). To examine the efficacy of these drugs in Cameroon, where diverse non-B HIV-1 subtypes and recombinant viruses predominate, the reverse transcriptase (RT) viral sequences in patient plasma were analyzed for the presence of mutations that confer drug resistance. Forty-nine HIV-1-positive individuals were randomly selected from those receiving care in HIV/AIDS outpatient clinics in the South-West and North-West Regions of Cameroon. Among the 28 patients receiving HAART, 39% (11/28) had resistance to NRTIs, and 46% (13/28) to NNRTIs after a median of 12 months from the start of therapy. Among those with drug-resistance mutations, there was a median of 14 months from the start of HAART, versus 9 months for those without; no difference was observed in the average viral load (10,997copies/ml vs. 8,056copies/ml). In contrast, drug-naive individuals had a significantly higher average viral load (27,929 copies/ml) than those receiving HAART (9,527copies/ml). Strikingly, among the 21 drug-naive individuals, 24% harbored viruses with drug-resistance mutations, suggesting that HIV-1 drug-resistant variants are being transmitted in Cameroon. Given the high frequency of resistance mutations among those on first-line HAART, coupled with the high prevalence of HIV-1 variants with drug-resistance mutations among drug-naive individuals, this study emphasizes the need for extensive monitoring of resistance mutations and the introduction of a second-line HAART strategy in Cameroon. J. Med. Virol. 82:187-196, 2010. (C) 2009 Wiley-Liss, Inc. C1 [Nyambi, Phillipe N.] NYU, Sch Med, Dept Pathol, VA Med Ctr, New York, NY 10010 USA. [Viswanath, Ragupathy; Zhao, Jiangqin; Hewlett, Indira K.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Kinge, Thompson] Limbe Reg Hosp, Limbe, Cameroon. [Anyangwe, Christopher] Alpha Royal Clin, Bamenda, Cameroon. [Powell, Rebecca L. R.] NYU, Sch Med, Dept Microbiol, New York, NY 10010 USA. [Jarido, Veronica] NYU, Sch Med, Summer Undergrad Res Program, New York, NY 10010 USA. [Nyambi, Phillipe N.] Vet Affairs New York Harbor Healthcare Syst, New York, NY USA. RP Nyambi, PN (reprint author), NYU, Sch Med, Dept Pathol, VA Med Ctr, 423 E 23rd St,Room 18124N, New York, NY 10010 USA. EM phillipe.nyambi@med.nyu.edu FU Ministry of Public Health, Cameroon FX The authors are grateful to the individuals who have donated their specimens for these studies. The authors wish to acknowledge the continued support of the Ministry of Public Health, Cameroon. 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 28 TC 10 Z9 10 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD FEB PY 2010 VL 82 IS 2 BP 187 EP 196 DI 10.1002/jmv.21677 PG 10 WC Virology SC Virology GA 540XN UT WOS:000273374500001 PM 20029816 ER PT J AU Lo, JC O'Ryan, FS Gordon, NP Yang, JR Hui, RL Martin, D Hutchinson, M Lathon, PV Sanchez, G Silver, P Chandra, M McCloskey, CA Staffa, JA Willy, M Selby, JV Go, AS AF Lo, Joan C. O'Ryan, Felice S. Gordon, Nancy P. Yang, Jingrong Hui, Rita L. Martin, Daniel Hutchinson, Matthew Lathon, Phenius V. Sanchez, Gabriela Silver, Paula Chandra, Malini McCloskey, Carolyn A. Staffa, Judy A. Willy, Mary Selby, Joe V. Go, Alan S. CA Predicting Risk Osteonecrosis Jaw TI Prevalence of Osteonecrosis of the Jaw in Patients With Oral Bisphosphonate Exposure SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT 90th Annual Meeting of the Endocrine-Society CY JUN 15-18, 2008 CL San Francisco, CA SP Endocrine Soc ID MULTIPLE-MYELOMA PATIENTS; RISK-FACTORS; AVASCULAR NECROSIS; CLINICAL-FEATURES; CANCER-PATIENTS; BONE; FREQUENCY; THERAPY; PREVENTION AB Purpose: Osteonecrosis of the jaw (ONJ) is a serious complication associated with bisphosphonate therapy, but its epidemiology in the setting of oral bisphosphonate therapy is poorly understood. The present study examined the prevalence of ONJ in patients receiving chronic oral bisphosphonate therapy. Materials and Methods: We mailed a survey to 13,946 members who had received chronic oral bisphosphonate therapy as of 2006 within a large integrated health care delivery system in Northern California. Respondents who reported ONJ, exposed bone or gingival sores, moderate periodontal disease, persistent symptoms, or complications after dental procedures were invited for examination or to have their dental records reviewed. ONJ was defined as exposed bone (of >8 weeks' duration) in the maxillofacial region in the absence of previous radiotherapy. Results: Of the 8,572 survey respondents (71 +/- 9 years, 93% women), 2,159(25%) reported pertinent dental symptoms. Of these 2,159 patients, 11,005 were examined and an additional 536 provided dental records. Nine ONJ cases were identified, representing a prevalence of 0.10% (95% confidence interval 0.05% to 0.20%) among the survey respondents. Of the 9 cases, 5 had occurred spontaneously (3 in palatal tori) and 4 occurred in previous extraction sites. An additional 3 patients had mandibular osteomyelitis (2 after extraction and 1 with implant failure) but without exposed bone. Finally, 7 other patients had bone exposure that did not fulfill the criteria for ONJ. Conclusions: ONJ occurred in 1 of 952 survey respondents with oral bisphosphonate exposure (minimum prevalence of 1 in 1,537 of the entire mailed cohort). A similar number had select features concerning for ONJ that did not meet the criteria. The results of the present study provide important data on the spectrum of jaw complications among patients with oral bisphosphonate exposure. (C) 2010 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 68:243-253, 2010 C1 [Lo, Joan C.; Gordon, Nancy P.; Yang, Jingrong; Lathon, Phenius V.; Sanchez, Gabriela; Silver, Paula; Chandra, Malini; Selby, Joe V.; Go, Alan S.] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. [Lo, Joan C.; Go, Alan S.] Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA 94143 USA. [O'Ryan, Felice S.; Martin, Daniel; Hutchinson, Matthew] Kaiser Permanente Oakland Med Ctr, Div Maxillofacial Surg, Oakland, CA USA. [Hui, Rita L.] Kaiser Permanente Calif, Drug Informat Serv, Pharm Outcomes Res Grp, Oakland, CA USA. [Martin, Daniel; Hutchinson, Matthew] Highland Gen Hosp, Dept Oral & Maxillofacial Surg, Oakland, CA USA. [McCloskey, Carolyn A.; Staffa, Judy A.; Willy, Mary] US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Silver Spring, MD USA. [Go, Alan S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, Sch Med, San Francisco, CA 94143 USA. RP Lo, JC (reprint author), Kaiser Permanente No Calif, Div Res, 2000 Broadway, Oakland, CA 94612 USA. EM Joan.C.Lo@kp.org FU NCRR NIH HHS [UL1 RR024131]; NICHD NIH HHS [K12 HD052163]; PHS HHS [HHSF223200510008C] NR 43 TC 141 Z9 145 U1 2 U2 32 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD FEB PY 2010 VL 68 IS 2 BP 243 EP 253 DI 10.1016/j.joms.2009.03.050 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 617KX UT WOS:000279280700003 PM 19772941 ER PT J AU Campbell, L Olson, RJ Sosik, HM Abraham, A Henrichs, DW Hyatt, CJ Buskey, EJ AF Campbell, Lisa Olson, Robert J. Sosik, Heidi M. Abraham, Ann Henrichs, Darren W. Hyatt, Cammie J. Buskey, Edward J. TI FIRST HARMFUL DINOPHYSIS (DINOPHYCEAE, DINOPHYSIALES) BLOOM IN THE US IS REVEALED BY AUTOMATED IMAGING FLOW CYTOMETRY SO JOURNAL OF PHYCOLOGY LA English DT Article DE automated; dinoflagellate; early warning; flow cytometry; Gulf of Mexico; harmful algae; imaging; life history; monitoring ID KARENIA-BREVIS; DIVISION RATES; GROWTH-RATES; SHELLFISH; DINOFLAGELLATE; ACUMINATA; CELLS; ABUNDANCE; HISTORY; CAUDATA AB Imaging FlowCytobot (IFCB) combines video and flow cytometric technology to capture images of nano- and microplankton (similar to 10 to > 100 mu m) and to measure the chlorophyll fluorescence associated with each image. The images are of sufficient resolution to identify many organisms to genus or even species level. IFCB has provided > 200 million images since its installation at the entrance to the Mission-Aransas estuary (Port Aransas, TX, USA) in September 2007. In early February 2008, Dinophysis cells (1-5 . mL(-1)) were detected by manual inspection of images; by late February, abundance estimates exceeded 200 cells . mL(-1). Manual microscopy of water samples from the site confirmed that D. cf. ovum F. Schutt was the dominant species, with cell concentrations similar to those calculated from IFCB data, and toxin analyses showed that okadaic acid was present, which led to closing of shellfish harvesting. Analysis of the time series using automated image classification (extraction of image features and supervised machine learning algorithms) revealed a dynamic phytoplankton community composition. Before the Dinophysis bloom, Myrionecta rubra (a prey item of Dinophysis) was observed, and another potentially toxic dinoflagellate, Prorocentrum, was observed after the bloom. Dinophysis cell-division rates, as estimated from the frequency of dividing cells, were the highest at the beginning of the bloom. Considered on a daily basis, cell concentration increased roughly exponentially up to the bloom peak, but closer inspection revealed that the increases generally occurred when the direction of water flow was into the estuary, suggesting the source of the bloom was offshore. C1 [Campbell, Lisa] Texas A&M Univ, Dept Oceanog, College Stn, TX 77843 USA. [Campbell, Lisa; Henrichs, Darren W.] Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. [Olson, Robert J.; Sosik, Heidi M.] Woods Hole Oceanog Inst, Dept Biol, Woods Hole, MA 02543 USA. [Abraham, Ann] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. [Hyatt, Cammie J.; Buskey, Edward J.] Univ Texas, Inst Marine Sci, Port Aransas, TX 78373 USA. RP Campbell, L (reprint author), Texas A&M Univ, Dept Oceanog, College Stn, TX 77843 USA. EM lcampbell@ocean.tamu.edu RI Campbell, Lisa/E-6587-2011; Hyatt, Cammie/J-1100-2016; OI Campbell, Lisa/0000-0003-2756-2743; Hyatt, Cammie/0000-0002-6397-8407; Sosik, Heidi/0000-0002-4591-2842 FU University of Texas Marine Science Institute [1508]; [CICEET-07-025] FX We thank E. Quiroz, S. Lanoux, Marc Teller, and staff at UTMSI for their assistance and support in setting up field operation, J. Corn for maintenance in keeping IFCB running, J. Hamm for help with manual classification, and H. R. Granade for LC-MS technical assistance. We also thank B. Reguera, K. Steidinger, and A. Zingone for examining images. Funding for this research was provided by CICEET-07-025 to R. J. O., H. M. S., and L. C. University of Texas Marine Science Institute Contribution number 1508. NR 42 TC 68 Z9 71 U1 3 U2 36 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3646 EI 1529-8817 J9 J PHYCOL JI J. Phycol. PD FEB PY 2010 VL 46 IS 1 BP 66 EP 75 DI 10.1111/j.1529-8817.2009.00791.x PG 10 WC Plant Sciences; Marine & Freshwater Biology SC Plant Sciences; Marine & Freshwater Biology GA 546PN UT WOS:000273822800007 ER PT J AU Pawar, RS Grundel, E Mazzola, E White, KD Krynitsky, AJ Rader, JI AF Pawar, Rahul S. Grundel, Erich Mazzola, Eugene White, Kevin D. Krynitsky, Alexander J. Rader, Jeanne I. TI Chiral stationary phases for separation of intermedine and lycopsamine enantiomers from Symphytum uplandicum SO JOURNAL OF SEPARATION SCIENCE LA English DT Article DE Chiral separation; Comfrey; Intermedine; Lycopsamine; Pyrrolizidine ID PYRROLIZIDINE ALKALOIDS; RESOLUTION AB Enantioseparation of the pyrrolizidine alkaloid isomers intermedine and lycopsamine, isolated from Symphytum uplandicum, is discussed. The separatory power of two immobilized carbohydrate-based chiral HPLC columns, Chiralpak IA and IC, in different chromatographic conditions is compared. The study demonstrated the importance of solvent and column selection while developing such chiral HPLC separation methods. The baseline HPLC separation of the two alkaloid isomers in preparatory scale is reported for the first time. The optimized separations were achieved on a Chiralpak IA column with mobile phases of ACN/methanol (80:20) and methanol/methyl-t-butyl ether (90:10), both containing 0.1% diethylamine. C1 [Pawar, Rahul S.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, HFS 717, College Pk, MD 20740 USA. RP Pawar, RS (reprint author), US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, HFS 717, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM rahul.pawar@fda.hhs.gov RI Pawar, Rahul/B-4712-2008 NR 10 TC 3 Z9 3 U1 2 U2 6 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9306 J9 J SEP SCI JI J. Sep. Sci. PD FEB PY 2010 VL 33 IS 2 BP 200 EP 205 DI 10.1002/jssc.200900611 PG 6 WC Chemistry, Analytical SC Chemistry GA 556GK UT WOS:000274578000009 PM 20029846 ER PT J AU Kim, MJ Huang, SM Rahman, A Zineh, I Gobburu, JV Burckart, GJ Lesko, LJ AF Kim, M. J. Huang, S. M. Rahman, A. Zineh, I. Gobburu, J. V. Burckart, G. J. Lesko, L. J. TI Scientific and Clinical Evidence to Inform Genotypye-Specific Dosing When Initiating Warfarin Therapy SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Meeting Abstract C1 [Kim, M. J.; Huang, S. M.; Rahman, A.; Zineh, I.; Gobburu, J. V.; Burckart, G. J.; Lesko, L. J.] US FDA, Off Clin Pharmacol, CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD FEB PY 2010 VL 29 IS 2 BP 259 EP 259 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 550AJ UT WOS:000274097500054 ER PT J AU Myers, MJ Scott, ML Deaver, CM Farrell, DE Yancy, HF AF Myers, M. J. Scott, M. L. Deaver, C. M. Farrell, D. E. Yancy, H. F. TI Biomarkers of inflammation in cattle determining the effectiveness of anti-inflammatory drugs SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID MESSENGER-RNA EXPRESSION; RAT PERITONEAL-MACROPHAGES; THROMBOXANE BIOSYNTHESIS; DIFFERENTIAL INHIBITION; PROSTANOID BIOSYNTHESIS; CYCLOOXYGENASE-2 GENE; WHOLE-BLOOD; CELLS; LIPOPOLYSACCHARIDE; SUPPRESSION AB The impact of nonsteroidal anti-inflammatory drugs (NSAID) on prostaglandin E(2) (PGE(2)) production and cyclooxygenase 2 (COX-2) mRNA expression in bovine whole blood (WB) cultures stimulated by lipopolysaccharide (LPS) was determined, using the blood from six Holstein dairy cattle in various stages of lactation. Peak production of PGE(2) occurred 24 h after LPS stimulation but did not result in detectable concentrations of thromboxane B(2) (TXB(2)). The NSAID indomethacin, aspirin, flunixin meglumine, and 4-[5-phenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzene sulfonamide (PTPBS; celecoxib analogue), along with dexamethasone, were all equally effective in reducing the concentration of PGE(2) in the bovine WB culture supernatants. Bradykinin exhibited peak supernatant concentrations 1 h after LPS stimulation. Dexamethasone and the NSAID used in this study were equally effective at inhibiting bradykinin production. Peak induction of COX-2 mRNA occurred 3 h post-LPS stimulation. However, neither dexamethasone nor any of the NSAID used in this study altered COX-2 mRNA concentrations. In contrast, aspirin, flunixin meglumine, and PTPBS reduced tumor necrosis factor-alpha (TNF alpha) mRNA concentration. These results demonstrate that bovine blood cells respond to NSAID therapy like other mammalian cells with respect to inhibition of PGE(2) production and suppression of TNF mRNA induction, but do not inhibit induction of COX-2 mRNA. C1 [Myers, M. J.; Scott, M. L.; Deaver, C. M.; Farrell, D. E.; Yancy, H. F.] US FDA, Div Anim Res, Ctr Vet Med, Laurel, MD 20708 USA. RP Myers, MJ (reprint author), US FDA, Div Anim Res, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM michael.myers@fda.hhs.gov NR 33 TC 5 Z9 5 U1 1 U2 15 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 FEB PY 2010 VL 33 IS 1 BP 1 EP 8 DI 10.1111/j.1365-2885.2009.01096.x PG 8 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 543RK UT WOS:000273595800001 PM 20444018 ER PT J AU Kawalek, JC Howard, KD AF Kawalek, J. C. Howard, K. D. TI Effect of recombinant porcine somatotropin (rpST) on drug disposition in swine SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID GROWTH-HORMONE; PIGS; PROPRANOLOL; PERFORMANCE; METABOLISM AB Treatment of pigs with recombinant porcine somatotropin (rpST) causes a marked increase in feed utilization with increased weight-gain over untreated controls. Physiological parameters such as creatinine clearance were increased by rpST treatment. Clearance of drugs eliminated by hepatic extraction, like indocyanine green (ICG), were also increased by rpST treatment. However, clearance of intravenous (i.v.)-dosed propranolol (PPL) was not affected by rpST treatment and data from oral (p.o.)-dosing was inconclusive because of the low bioavailability, probably because of a high first-pass effect. The very low oral bioavailability indicates that intestinal metabolism of PPL is probably quite high. Analysis of urinary metabolites indicated production of the two phenolic isomers, but there was no metabolite corresponding to N-dealkylase activity; although the latter metabolite could have been eliminated in the bile with subsequent fecal elimination. PPL was an excellent in vitro substrate for measuring hepatic DME activity in vitro; two phenolic and one N-dealkylated metabolite were formed. The overall conclusions regarding this study must be that the effects of rpST on drug bioavailability and elimination were equivocal. As ICG and creatinine clearances were both increased significantly, one cannot rule out the probability that rpST would increase drug elimination in pigs as a result of increased hepatic uptake and/or renal clearance. One can only speculate that clearance of concurrently administered drugs would be increased. This would reduce residue levels, but it might also reduce efficacy. C1 [Kawalek, J. C.; Howard, K. D.] US FDA, Div Anim Res, Res Off, Ctr Vet Med, Laurel, MD USA. RP Kawalek, JC (reprint author), FDA CVM, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM joseph.kawalek@fda.hhs.gov NR 16 TC 1 Z9 1 U1 0 U2 1 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 FEB PY 2010 VL 33 IS 1 BP 69 EP 75 DI 10.1111/j.1365-2885.2009.01107.x PG 7 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 543RK UT WOS:000273595800011 PM 20444028 ER PT J AU Zhang, WW Li, F Nie, L AF Zhang, Weiwen Li, Feng Nie, Lei TI Integrating multiple 'omics' analysis for microbial biology: application and methodologies SO MICROBIOLOGY-SGM LA English DT Review ID YEAST SACCHAROMYCES-CEREVISIAE; MESSENGER-RNA EXPRESSION; ESCHERICHIA-COLI; MASS-SPECTROMETRY; DESULFOVIBRIO-VULGARIS; FUNCTIONAL GENOMICS; BACILLUS-SUBTILIS; GENE-EXPRESSION; CHROMATIN IMMUNOPRECIPITATION; METABOLOME ANALYSIS AB Recent advances in various 'omics' technologies enable quantitative monitoring of the abundance of various biological molecules in a high-throughput manner, and thus allow determination of their variation between different biological states on a genomic scale. Several popular 'omics' platforms that have been used in microbial systems biology include transcriptomics, which measures mRNA transcript levels; proteomics, which quantifies protein abundance; metabolomics, which determines abundance of small cellular metabolites; interactomics, which resolves the whole set of molecular interactions in cells;, and fluxomics, which establishes dynamic changes of molecules within a cell over time. However, no single 'omics' analysis can fully unravel the complexities of fundamental microbial biology. Therefore, integration of multiple layers of information, the multi, 'omics' approach, is required to acquire a precise picture of living micro-organ isms. In spite of this being a challenging task, some attempts have been made recently to integrate heterogeneous 'omics' datasets in various microbial systems and the results have demonstrated that the multi-'omics' approach is a powerful tool for understanding the functional principles and dynamics of total cellular systems. This article reviews some basic concepts of various experimental 'omics' approaches, recent application of the integrated 'omics' for exploring metabolic and regulatory mechanisms in microbes, and advances in computational and statistical methodologies associated with integrated 'omics' analyses. Online databases and bioinformatic infrastructure available for integrated 'omics' analyses are also briefly discussed. C1 [Zhang, Weiwen] Arizona State Univ, Ctr Ecogenom, Biodesign Inst, Tempe, AZ 85287 USA. [Li, Feng] US FDA, CDER, OTS, Div Biometr 2,Off Biometr, Silver Spring, MD 20993 USA. [Nie, Lei] US FDA, CDER, OTS, Div Biometr 4,Off Biometr, Silver Spring, MD 20993 USA. RP Zhang, WW (reprint author), Arizona State Univ, Ctr Ecogenom, Biodesign Inst, Tempe, AZ 85287 USA. EM Weiwen.Zhang@asu.edu RI Li, Feng/B-8021-2011 NR 148 TC 157 Z9 164 U1 9 U2 105 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD FEB PY 2010 VL 156 BP 287 EP 301 DI 10.1099/mic.0.034793-0 PN 2 PG 15 WC Microbiology SC Microbiology GA 563NR UT WOS:000275139800001 PM 19910409 ER PT J AU Webb, K Allard, M AF Webb, Kristen Allard, Marc TI Assessment of minimum sample sizes required to adequately represent diversity reveals inadequacies in datasets of domestic dog mitochondrial DNA SO MITOCHONDRIAL DNA LA English DT Article DE Domestic dog; mitochondrial control region; haplotype; polymorphism ID CONTROL REGION; GENETIC IDENTIFICATION; SUBSTITUTION RATE; ANCIENT DNA; MULTIPLE; ORIGIN; WOLVES; MTDNA; GENOMES; BREEDS AB Background and aims: Evolutionary and forensic studies commonly choose the mitochondrial control region as the locus for which to evaluate the domestic dog. However, the number of dogs that need to be sampled in order to represent the control region variation present in the worldwide population is yet to be determined. Materials and methods: Following the methods of Pereira et al. (2004), we have demonstrated the importance of surveying the complete control region rather than only the popular left domain. We have also evaluated sample saturation in terms of the haplotype number and the number of polymorphisms within the control region. Results: Of the most commonly cited evolutionary research, only a single study has adequately surveyed the domestic dog population, while all forensic studies have failed to meet the minimum values. Conclusion: We recommend that future studies consider dataset size when designing experiments and ideally sample both domains of the control region in an appropriate number of domestic dogs. C1 [Webb, Kristen] ARS, USDA, APDL, BARC E, Beltsville, MD 20705 USA. [Allard, Marc] US FDA, Mol Methods & Subtyping Branch, Div Microbiol, Off Regulatory Sci,Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Webb, K (reprint author), ARS, USDA, APDL, BARC E, Bldg 1180, Beltsville, MD 20705 USA. EM kristen.webb@ars.usda.gov NR 51 TC 8 Z9 8 U1 0 U2 11 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1940-1736 J9 MITOCHONDR DNA JI Mitochondrial DNA PD FEB PY 2010 VL 21 IS 1 BP 19 EP 31 DI 10.3109/19401730903532044 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 551VX UT WOS:000274241600008 PM 20121654 ER PT J AU Pariser, A AF Pariser, Anne TI Regulation and review of small clinical trials SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 6th Annual World Symposium of the Lysosomal-Disease-Network CY FEB 10-12, 2010 CL Miami, FL SP Lysosomal Dis Network C1 [Pariser, Anne] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2010 VL 99 IS 2 MA 101 BP S29 EP S29 DI 10.1016/j.ymgme.2009.10.118 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 548XV UT WOS:000274004300114 ER PT J AU Valerio, LG Arvidson, KB Busta, E Minnier, BL Kruhlak, NL Benz, RD AF Valerio, Luis G., Jr. Arvidson, Kirk B. Busta, Emily Minnier, Barbara L. Kruhlak, Naomi L. Benz, R. Daniel TI Testing computational toxicology models with phytochemicals SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Article DE Computational toxicology; Phytochemicals; Quantitative structure-activity relationship; Rodent carcinogenicity; Safety assessment ID TOXICITY DATABASES; MDL-QSAR; CARCINOGENICITY; PHARMACEUTICALS; PRODUCTS; PREDICTIONS; PERFORMANCE; SOFTWARE; RODENTS; MC4PC AB Computational toxicology employing quantitative structure-activity relationship (QSAR) modeling is an evidence-based predictive method being evaluated by regulatory agencies for risk assessment and scientific decision support for toxicological endpoints of interest such as rodent carcinogenicity. Computational toxicology is being tested for its usefulness to support the safety assessment of drug-related substances (e.g. active pharmaceutical ingredients, metabolites, impurities), indirect food additives, and other applied uses of value for protecting public health including safety assessment of environmental chemicals. The specific use of QSAR as a chemoinformatic tool for estimating the rodent carcinogenic potential of phytochemicals present in botanicals, herbs, and natural dietary sources is investigated here by an external validation study, which is the most stringent scientific method of measuring predictive performance. The external validation statistics for predicting rodent carcinogenicity of 43 phytochemicals, using two computational software programs evaluated at the FDA, are discussed. One software program showed very good performance for predicting non-carcinogens (high specificity), but both exhibited poor performance in predicting carcinogens (sensitivity), which is consistent with the design of the models. When predictions were considered in combination with each other rather than based on any one software, the performance for sensitivity was enhanced, However, Chi-square values indicated that the overall predictive performance decreases when using the two computational programs with this particular data set. This study suggests that complementary multiple computational toxicology software need to be carefully selected to improve global QSAR predictions for this complex toxicological endpoint. C1 [Valerio, Luis G., Jr.; Minnier, Barbara L.; Kruhlak, Naomi L.; Benz, R. Daniel] US FDA, Informat & Computat Safety Anal Staff, Sci & Res Staff, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Arvidson, Kirk B.; Busta, Emily] US FDA, Div Food Contact Notificat, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, College Pk, MD USA. [Minnier, Barbara L.] GlobalNet Serv Inc, Rockville, MD USA. RP Valerio, LG (reprint author), US FDA, Informat & Computat Safety Anal Staff, Sci & Res Staff, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, White Oak 51 Room 4128,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Luis.Valerio@fda.hhs.gov NR 21 TC 5 Z9 8 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1613-4125 EI 1613-4133 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD FEB PY 2010 VL 54 IS 2 BP 186 EP 194 DI 10.1002/mnfr.200900259 PG 9 WC Food Science & Technology SC Food Science & Technology GA 563OA UT WOS:000275140800003 PM 20024931 ER PT J AU Ellwood, KC Trumbo, PR Kavanaugh, CJ AF Ellwood, Kathleen C. Trumbo, Paula R. Kavanaugh, Claudine J. TI How the US Food and Drug Administration evaluates the scientific evidence for health claims SO NUTRITION REVIEWS LA English DT Review DE evidence-based review; health claim; intervention study; observational study; significant scientific agreement AB Health claims describe the relationship between a substance (food or component of food) and a disease or health-related condition. They were first authorized through the Nutrition Labeling and Education Act of 1990. The standard set by the US Congress for the scientific evidence required to authorize a claim was the significant scientific agreement standard. This strong standard was challenged by several manufacturers of dietary supplements. Several court decisions directed the US Food and Drug Administration (FDA) to provide for dietary supplement claims not meeting the significant scientific agreement standard by adding a disclaimer to the claim that would eliminate the claim's potential to be misleading. In December 2002, the FDA announced a major new initiative, "The Consumer Health Information for Better Nutrition Initiative," which, among other things, provided for the use of qualified health claims for both conventional foods and dietary supplements. The process for reviewing the scientific evidence for a claim reaching significant scientific agreement and for those that require qualifying language is the same. In January 2009, the FDA issued a guidance document entitled "Evidence-Based Review System for the Scientific Evaluation of Health Claims." The process used by the FDA to review the scientific evidence for health claims and qualified health claims are described in this article. No claim to U.S. Government works. Journal compilation (C) 2010 International Life Sciences Institute C1 [Ellwood, Kathleen C.] US FDA, CFSAN, HFS 830, Off Nutr Labeling & Dietary Supplements, College Pk, MD 20742 USA. [Kavanaugh, Claudine J.] Off Commissioner, Off Foods, Silver Spring, MD USA. RP Ellwood, KC (reprint author), US FDA, CFSAN, HFS 830, Off Nutr Labeling & Dietary Supplements, 5100 Paint Branch Pkwy, College Pk, MD 20742 USA. EM kathy.ellwood@fda.hhs.gov NR 13 TC 9 Z9 10 U1 0 U2 15 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD FEB PY 2010 VL 68 IS 2 BP 114 EP 121 DI 10.1111/j.1753-4887.2009.00267.x PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 548VV UT WOS:000273998100004 PM 20137056 ER PT J AU Guo, L Mei, N Liao, W Chan, PC Fu, PP AF Guo, Lei Mei, Nan Liao, Wayne Chan, Po-Chuen Fu, Peter P. TI Ginkgo Biloba Extract Induces Gene Expression Changes in Xenobiotics Metabolism and the Myc-Centered Network SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY LA English DT Article ID HERBAL DIETARY-SUPPLEMENTS; HUMAN CYTOCHROMES P450; ST-JOHNS-WORT; C-MYC; BOTANICAL SUPPLEMENTATION; PYRROLIZIDINE ALKALOIDS; DRUG INTERACTIONS; ORAL TREATMENT; KAVA EXTRACT; PHASE-I AB The use of herbal dietary supplements in the United States is rapidly growing, and it is crucial that the quality and safety of these preparations be ensured. To date, it is still a challenge to determine the mechanisms of toxicity induced by mixtures containing many chemical components, such as herbal dietary supplements. We previously proposed that analyses of the gene expression profiles using microarrays in the livers of rodents treated with herbal dietary supplements is a potentially practical approach for understanding the mechanism of toxicity. In this study, we utilized microarrays to analyze gene expression changes in the livers of male B6C3F1 mice administered Ginkgo biloba leaf extract (GBE) by gavage for 2 years, and to determine pathways and mechanisms associated with GBE treatments. Analysis of 31,802 genes revealed that there were 129, 289, and 2,011 genes significantly changed in the 200, 600, and 2,000 mg/kg treatment groups, respectively, when compared with control animals. Drug metabolizing genes were significantly altered in response to GBE treatments. Pathway and network analyses were applied to investigate the gene relationships, functional clustering, and mechanisms involved in GBE exposure. These analyses indicate alteration in the expression of genes coding for drug metabolizing enzymes, the NRF2-mediated oxidative stress response pathway, and the Myc gene-centered network named "cell cycle, cellular movement, and cancer" were found. These results indicate that Ginkgo biloba-related drug metabolizing enzymes may cause herb-drug interactions and contribute to hepatotoxicity. In addition, the outcomes of pathway and network analysis may be used to elucidate the toxic mechanisms of Ginkgo biloba. C1 [Guo, Lei] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. [Mei, Nan] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Liao, Wayne] PhalanxBio Inc, Palo Alto, CA USA. [Chan, Po-Chuen] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Fu, Peter P.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Guo, L (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. EM lei.guo@fda.hhs.gov; peter.fu@fda.hhs.gov RI Guo, Lei/E-9232-2011; mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 FU NIH, National Institute of Environmental Health Sciences FX We thank Drs. Tucker A. Patterson and James C. Fuscoe for their critical review of this manuscript. This article is not an official guidance or policy statement of the National Toxicology Program (NTP) or U.S. Food and Drug Administration (FDA). No official support or endorsement by the FDA or NTP is intended or should be inferred. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 58 TC 22 Z9 22 U1 1 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1536-2310 J9 OMICS JI OMICS PD FEB PY 2010 VL 14 IS 1 BP 75 EP 90 DI 10.1089/omi.2009.0115 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 554GO UT WOS:000274423700004 PM 20141330 ER PT J AU Audino, AN Blatt, J Carcamo, B Castaneda, V Dinndorf, P Wang, WC Whitlock, JA Hord, JD AF Audino, Anthony N. Blatt, Julie Carcamo, Benjamin Castaneda, Victoria Dinndorf, Patricia Wang, Winfred C. Whitlock, James A. Hord, Jeffrey D. TI High-Dose Cyclophosphamide Treatment for Refractory Severe Aplastic Anemia in Children SO PEDIATRIC BLOOD & CANCER LA English DT Article DE aplastic anemia; children; cyclophosphamide; refractory ID BONE-MARROW-TRANSPLANTATION; IMMUNOSUPPRESSIVE THERAPY; ANTITHYMOCYTE GLOBULIN; CELL TRANSPLANTATION; UNRELATED DONORS; CYCLOSPORINE; DIAGNOSIS; REMISSION; PROGRAM; 1ST AB Objective. To determine if high-close cyclophosphamide is an effective therapy for children with refractory severe aplastic anemia (SAA). Background. SAA is an illness characterized by the depletion of hematopoietic precursors associated with life-threatening complications. Hematopoietic stern cell transplant (HSCT) is the treatment of choice if a human leukocyte antigen (HLA)-related donor is available. Immunosuppression with anti-thymocyte globulin (ATG) and cyclosporine A (CSA) is an option for patients who are not HSCT candidates. Unrelated donor HSCT has been used with limited success. High-dose cyclophosphamide has been used Successfully in the treatment Of adults with SAA, but experience in children is limited. Procedure. Five pediatric patients who had failed previous immunosuppressive therapy for SAA were treated with high-close cyclophosphamide (45 mg/kg/day x 4 clays). Results. After 12 months of treatment, two of five patients experienced a complete response with high-dose cyclophosphamide therapy. The two complete responders achieved red cell recovery with a hematocrit of >36% at clays 2 12 and 112 and platelet recovery with a platelet count of >1 00 x 10(9)/L at days 126 and 324. Of the remaining patients, one patient failed to respond, and two patients expired from infectious complications. Conclusions. High-dose cyclophosphamide can lead to complete responses in children with SAA who have failed to respond to traditional immunosuppressive therapy. Pediatr Blood Cancer 2010;54:269-272. (C) 2009 Wiley-Liss, Inc. C1 [Audino, Anthony N.; Hord, Jeffrey D.] Akron Childrens Hosp, Akron, OH USA. [Blatt, Julie] Univ N Carolina, Chapel Hill, NC USA. [Carcamo, Benjamin] Providence Mem Hosp, El Paso, TX USA. [Castaneda, Victoria] E Tennessee Childrens Hosp, Knoxville, TN USA. [Dinndorf, Patricia] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Dinndorf, Patricia] US FDA, Silver Spring, MD USA. [Wang, Winfred C.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Whitlock, James A.] Vanderbilt Univ, Nashville, TN USA. RP Hord, JD (reprint author), Div Pediat Hematol Oncol, 1 Perkins Sq, Akron, OH 44308 USA. EM jhord@chmca.org RI Audino, Anthony/D-2023-2013 NR 25 TC 6 Z9 6 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD FEB PY 2010 VL 54 IS 2 BP 269 EP 272 DI 10.1002/pbc.22312 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 538TK UT WOS:000273206700018 PM 19827142 ER PT J AU Pamer, CA Hammad, TA Wu, YT Kaplan, S Rochester, G Governale, L Mosholder, AD AF Pamer, Carol A. Hammad, Tarek A. Wu, Yu-te Kaplan, Sigal Rochester, George Governale, Laura Mosholder, Andrew D. TI Changes in US antidepressant and antipsychotic prescription patterns during a period of FDA actions SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE antidepressant drugs; antipsychotic drugs; prescription patterns; interrupted time series analysis; drug promotional spending; regulatory actions ID INTERRUPTED TIME-SERIES; PEDIATRIC SUICIDALITY; UNITED-STATES; DEPRESSION; WARNINGS; SSRIS; RISK; ADOLESCENTS; CHILDREN AB Purpose To determine if paroxetine versus non-paroxetine selective serotonin reuptake inhibitors (SSRls) prescribing changed after the June 2003 FDA Paroxetine Public Health Advisory (PPHA) and if antidepressant and antipsychotic prescribing changed after the February 2004 FDA Advisory Committee Meeting (FDACM). Methods Ecologic analysis using estimates of patients dispensed antidepressants and antipsychotics, census data, and promotional spending data. Data sources were SDI: Vector One(R), US Census, and IMS Health(R). Measures were monthly use levels (number of patients dispensed antidepressants, antipsychotics, paroxetine, and non-paroxetine SSRIs prescriptions by age group per population count). Percent changes pre- to post-PPHA were used to assess changes in paroxetine versus non-paroxetine SSRIs prescribing. Interrupted time series (ITS) analysis was performed to examine use level changes post-FDACM by drug groups (all antidepressants and all anti psychotics). Results Post-PPHA mean paroxetine use levels decreased for all age groups (range: 5.5-34.1%). Mean non-paroxetine SSRIs use levels increased (range: 4.6-17.1%). Post-PPHA changes were greatest for 6-12 and 13-17 year olds. Decreased mean antidepressant drug use levels from pre- to post-FDACM were observed in all groups under 25 years old. A statistically significant decrease in the slopes from pre- to post-FDACM was observed for persons aged 13-17 and 18-24 years. The difference between the forecasted mean use level and the observed mean use level (in 12-month intervals) was statistically significant for all ages combined (-107.26; 95% Cl: -166.32, -48.20) and 1-5 (-3.1; 95% Cl: -4.62, -1.58), 6-12 (-36.02; 95% Cl: -62.92, -9.12) and 25 years, and older groups (-83.17; 95% CI: -153.95, -12.39). For all age groups, decreases in the slopes of antipsychotic drugs use from pre- to post-FDACM were observed, although these slope changes were not statistically significant. The difference between the forecasted mean antipsychotic drugs use level and the observed mean use level (in 12-month intervals) was statistically significantly lower for all age groups. Conclusions Antidepressant use changed post-PPHA and -FDACM, with a differential pattern by age. There was no evidence of increased antipsychotic use post-FDACM. Ecologic data cannot determine if changes were due to depression not treated with medications or the prescribing of fewer antidepressants for other conditions. Published in 2010 by John Wiley & Sons, Ltd. C1 [Pamer, Carol A.] US FDA, Div Epidemiol, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. [Wu, Yu-te; Rochester, George] US FDA, Off Biostat, Silver Spring, MD 20993 USA. RP Pamer, CA (reprint author), US FDA, Div Epidemiol, Off Surveillance & Epidemiol, White Oak Campus Bldg 22 Room 2408,10903 New Hamp, Silver Spring, MD 20993 USA. EM carol.pamer@fda.hhs.gov FU Director of the FDA Division of Epidemiology FX The opinions expressed in this manuscript are those of the authors and not intended to represent the opinions of the United States Food and Drug Administration. The authors would like to acknowledge Dr. Solomon Iyasu, MD, MPH, Director of the FDA Division of Epidemiology for his feedback and support of this study. The study authors have no financial interests in this manuscript and no funding was received to conduct this study. NR 27 TC 20 Z9 20 U1 2 U2 7 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 FEB PY 2010 VL 19 IS 2 BP 158 EP 174 DI 10.1002/pds.1886 PG 17 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 561DX UT WOS:000274957000007 PM 20049836 ER PT J AU Burckart, GJ Amur, S AF Burckart, Gilbert J. Amur, Shashi TI Update on the clinical pharmacogenomics of organ transplantation SO PHARMACOGENOMICS LA English DT Review DE biomarker; CYP3A5; drug development; gene-expression array; organ transplantation; p-glycoprotein; pharmacogenomics ID SINGLE-NUCLEOTIDE POLYMORPHISMS; ISCHEMIA-REPERFUSION INJURY; ALLOMAP GENE-EXPRESSION; KIDNEY-TRANSPLANTATION; ACUTE REJECTION; LIVER-TRANSPLANTATION; ALLOGRAFT-REJECTION; CYP3A5 GENOTYPE; MDR1 GENE; TRANSCRIPTIONAL SIGNALS AB Organ transplantation suffers from a static graft and patient survival rate, and a high incidence of serious adverse drug effects. The pharmacogenomics of organ transplantation has emerged only recently and is complementary to the immunogenetic information that has accumulated over the past decade. Gene polymorphism studies have focused on the genes that interact across the group of immunosuppressants, including ciclosporin, tacrolimus, sirolimus and corticosteroids. The polymorphisms that hold the most potential for use in a drug selection algorithm are in genes CYP3A5, ABCB1, IMPDH1 and IMPDH2, and cytokines and growth factors. Gene-expression arrays have led to gene-expression testing, such as the use of AlloMap (R) with heart transplant patients. The expanded use of gene-expression assays, proteomics and drug selection algorithms in organ transplantation will progress slowly and may be outpaced by drug test co-development programs for new transplant drugs. In the future, clinical pharmacogenomics will be a routine part of patient care for organ transplant patients. C1 [Burckart, Gilbert J.; Amur, Shashi] Ctr Drug Evaluat & Res, Off Clin Pharmacol, Off Translat Sci, Silver Spring, MD 20993 USA. RP Burckart, GJ (reprint author), Ctr Drug Evaluat & Res, Off Clin Pharmacol, Off Translat Sci, 10903 New Hampshire Ave,Bldg 51,Room 3184, Silver Spring, MD 20993 USA. EM gilbert.burckart@fda.hhs.gov NR 73 TC 12 Z9 13 U1 0 U2 4 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD FEB PY 2010 VL 11 IS 2 BP 227 EP 236 DI 10.2217/PGS.09.177 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 555IP UT WOS:000274503300012 PM 20136361 ER PT J AU Bai, JPF Lesko, LJ Burckart, GJ AF Bai, Jane P. F. Lesko, Lawrence J. Burckart, Gilbert J. TI Understanding the Genetic Basis for Adverse Drug Effects: The Calcineurin Inhibitors SO PHARMACOTHERAPY LA English DT Review DE personalized medicine; calcineurin inhibitors; adverse drug effect; adverse drug event; ADE; genetics ID TYPE-2 DIABETES-MELLITUS; ANGIOTENSIN-CONVERTING ENZYME; RENAL-TRANSPLANT RECIPIENTS; CHRONIC ALLOGRAFT NEPHROPATHY; OXIDE SYNTHASE GENE; RISK-FACTORS; KIDNEY-TRANSPLANTATION; BLOOD-PRESSURE; VITAMIN-D; INDUCED HYPERTENSION AB The calcineurin inhibitors-cyclosporine and tacrolimus-are the mainstay of immunosuppressive therapy in solid organ transplantation. These drugs produce severe adverse drug effects (ADEs) such as nephrotoxicity, posttransplantation diabetes mellitus, and hypertension. Accumulated evidence suggests that the development of type 2 diabetes, hypertension, and renal failure may be associated with specific DNA genotypes. In this review, the genes involved with the development of these disease processes are compared with those implicated in calcineurin inhibitor-induced ADEs. The renin-angiotensin system genes, cytokine-encoding genes, and plasminogen activator inhibitor type I genes have been implicated in calcineurin inhibitor-induced nephrotoxicity, as well as in development of renal failure. A number of genes are implicated in contributing to diabetes, and these include the vitamin D receptor gene, VDR; hepatocyte nuclear factor genes, HNF; transcription factor 7-like 2 gene, TCF7L2; angiotensin-converting enzyme gene, ACE; cytokines; peroxisome proliferator-activated receptor gamma gene, PPARG; and others. Studies have suggested that the VDR, PPARG, HNF1A, and adenosine 5'-triphosphate-binding cassette ABCC8 (which encodes the sulfonylurea receptor) genes are associated with calcineurin inhibitor-induced diabetes. The genes encoding for the angiotensin-converting enzyme, endothelial constitutive nitric oxide synthase, and cytochrome P450 3A isoenzyme have been involved in the development of hypertension and in calcineurin inhibitor-induced hypertension. The genetic study of disease states can be the stepping stones for thoroughly understanding the genetic basis of ADEs. Gene polymorphisms are implicated in the development of diseases and corresponding disease-like ADEs. The disease-associated genes provide candidate genes for exploring ADEs and may provide genomic biomarkers for assessing the risk for developing severe calcineurin inhibitor-related ADEs as well as for developing preventive strategies. C1 [Bai, Jane P. F.; Lesko, Lawrence J.; Burckart, Gilbert J.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Burckart, GJ (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51,Room 3184, Silver Spring, MD 20993 USA. EM gilbert.burckart@fda.hhs.gov NR 73 TC 14 Z9 14 U1 1 U2 16 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 FEB PY 2010 VL 30 IS 2 BP 195 EP 209 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 550ZL UT WOS:000274173800009 PM 20099993 ER PT J AU Lee, KW Lee, SH Lillehoj, HS Li, GX Jang, SI Babu, US Park, MS Kim, DK Lillehoj, EP Neumann, AP Rehberger, TG Siragusa, GR AF Lee, K. W. Lee, S. H. Lillehoj, H. S. Li, G. X. Jang, S. I. Babu, U. S. Park, M. S. Kim, D. K. Lillehoj, E. P. Neumann, A. P. Rehberger, T. G. Siragusa, G. R. TI Effects of direct-fed microbials on growth performance, gut morphometry, and immune characteristics in broiler chickens SO POULTRY SCIENCE LA English DT Article DE chicken; direct-fed microbial; immune response; growth performance; intestinal morphometry ID MOUSE LYMPHOCYTE-PROLIFERATION; TURKEY POULT PERFORMANCE; CYTOKINE GENE-EXPRESSION; ACUTE-PHASE PROTEINS; MEAT-TYPE CHICKENS; EIMERIA-ACERVULINA; PROBIOTICS LACTOBACILLUS; SACCHAROMYCES-CEREVISIAE; CAMPYLOBACTER-JEJUNI; NECROTIC ENTERITIS AB This study was conducted to compare growth performance, gut morphometry, and parameters of local and systemic immunity in broiler chickens fed for 22 consecutive days with a diet supplemented with Bacillus spp. as direct-fed microbials (DFM), a commercial product incorporating 3 DFM, or a non-supplemented diet. Direct-fed microbials did not significantly modify BW gain and most failed to affect serum antibody levels in response to immunization with a recombinant Eimeria protein. However, altered intestinal morphometric measurements were readily apparent in DFM-fed chickens as revealed by increased villus height and crypt depth compared with non-DFM-fed controls. In addition, serum levels of alpha-1-acid glycoprotein as an inflammatory marker were reduced in DFM-fed birds, whereas splenic lymphocyte proliferation, intestine intraepithelial lymphocyte subpopulations, and cytokine mRNA levels in intraepithelial lymphocytes were increased, decreased, or unchanged compared with controls depending on the DFM used. These results provide a rational scientific basis for future studies to investigate DFM as immunomodulating agents to enhance host protective immunity against enteric pathogens in broiler chickens. C1 [Lee, K. W.; Lee, S. H.; Lillehoj, H. S.; Li, G. X.; Jang, S. I.; Park, M. S.; Kim, D. K.] ARS, Anim Parasit Dis Lab, Anim & Nat Resources Inst, USDA, Beltsville, MD 20705 USA. [Lee, K. W.] Minist Food Agr Forestry & Fisheries, Natl Vet Res & Quarantine Serv, Anyang 430824, Kyunggido, South Korea. [Babu, U. S.] US FDA, Immunobiol Branch, Div Virulence Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Lillehoj, E. P.] Univ Maryland, Dept Pediat, Sch Med, Baltimore, MD 21201 USA. [Neumann, A. P.; Rehberger, T. G.; Siragusa, G. R.] Danisco, Waukesha, WI 53186 USA. RP Lillehoj, HS (reprint author), ARS, Anim Parasit Dis Lab, Anim & Nat Resources Inst, USDA, Beltsville, MD 20705 USA. EM Hyun.Lillehoj@ars.usda.gov OI Lee, Kyung-Woo/0000-0002-3533-7979 FU Agricultural Research Service-USDA; Danisco; Agricultural Research Service [1265-32000-086-00D]; Ministry of Public Administration and Security, South Korea FX This project was supported by a trust agreement established between Agricultural Research Service-USDA and Danisco and partially by the Agricultural Research Service in-house project 1265-32000-086-00D. We thank Marjorie Nichols and Stacy Torreyson (Animal Parasitic Diseases Laboratory) for their technical assistance. We also acknowledge J. P. Dubey in the Animal Parasitic Diseases Laboratory, Animal and Natural Resources Institute, Agricultural Research Service-USDA, for his help on morphological examination. K. W. Lee is the recipient of a Korean Government Short-Term Overseas Research Fellowship, Ministry of Public Administration and Security, South Korea. NR 67 TC 58 Z9 66 U1 1 U2 13 PU POULTRY SCIENCE ASSOC INC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874-9604 USA SN 0032-5791 J9 POULTRY SCI JI Poult. Sci. PD FEB 1 PY 2010 VL 89 IS 2 BP 203 EP 216 DI 10.3382/ps.2009-00418 PG 14 WC Agriculture, Dairy & Animal Science SC Agriculture GA 544GA UT WOS:000273640500003 PM 20075271 ER PT J AU Gavrielides, MA Myers, KJ Petrick, N AF Gavrielides, Marios A. Myers, Kyle J. Petrick, Nicholas TI Three-dimensional Volumetric Assessment with Thoracic CT: A Reliable Approach for Noncalcified Lung Nodules? Response SO RADIOLOGY LA English DT Letter C1 [Gavrielides, Marios A.; Myers, Kyle J.; Petrick, Nicholas] US FDA, Div Imaging & Appl Math, Offi Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Gavrielides, MA (reprint author), US FDA, Div Imaging & Appl Math, Offi Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62,Room 3139, Silver Spring, MD 20993 USA. EM marios.gavrielides@fda.hhs.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 2010 VL 254 IS 2 BP 635 EP 635 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 546QF UT WOS:000273824600039 ER PT J AU Wu, KM Dou, JH Ghantous, H Chen, S Bigger, A Birnkrant, D AF Wu, Kuei-Meng Dou, Jinhui Ghantous, Hanan Chen, Shaw Bigger, Anita Birnkrant, Debra TI Current regulatory perspectives on genotoxicity testing for botanical drug product development in the USA SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Editorial Material DE Botanical drugs; Herbals; Genotoxicity; Regulatory toxicology ID JUNCTIONAL INTERCELLULAR COMMUNICATION; INSECTICIDE ENDOSULFAN; ORGANOCHLORINE PESTICIDES; SACCHAROMYCES-CEREVISIAE; METABOLIZING-ENZYMES; SALMONELLA TEST; ADULT-RATS; HUMAN-MILK; MUTAGENICITY; EXPOSURE AB Genotoxicity testing is an important part of preclinical safety assessment of new drugs and is required prior to Phase I/II clinical trials. It is designed to detect genetic damage such as gene mutations and chromosomal aberration, which may be reflected in tumorigenic or heritable mutation potential of the drug. Botanical new drugs in the U.S. are entitled to a waiver for preclinical pharmacology/toxicology studies, including genotoxicity testing, in support of an initial clinical trial under IND, contingent on previous human experience. Recently, ethical concerns have been raised over conducting Phase I/II clinical trials of new drugs with positive genotoxicity findings in healthy volunteers. Although the relevance of this issue to patients, as opposed to healthy volunteers, depends on the drug's indication, duration of treatment, and specific findings related to the assays, the regulatory view is to avoid exposing patients to genotoxic compounds unnecessarily in clinical trials. This philosophy may impact on herbal Supplement marketing and botanical drug development, in that genotoxicity data are often lacking while consumers are exposed to the herbal supplement, or healthy volunteers are tested in an initial Phase I/II clinical trial on the botanical drug. This paper presents results of a Survey conducted on genotoxicity data in botanical INDs submitted to the Agency and discusses the significance of this information. The information presented indicates that the sponsors of botanical INDs have increasingly recognized the importance of genotoxicity information and may have prioritized its acquisition in their strategic drug development programs. Published by Elsevier Inc. C1 [Wu, Kuei-Meng; Dou, Jinhui; Ghantous, Hanan; Chen, Shaw; Bigger, Anita; Birnkrant, Debra] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Wu, KM (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM kueimeng.wu@fda.hhs.gov NR 119 TC 9 Z9 9 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD FEB PY 2010 VL 56 IS 1 BP 1 EP 17 DI 10.1016/j.yrtph.2009.09.012 PG 17 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 559WS UT WOS:000274859600001 PM 19782117 ER PT J AU Huque, MF Quasem, M Rahman, A Dubey, SD AF Huque, Mohammad F. Quasem, Mohammed Rahman, Atiar Dubey, Satya D. TI An Improved Ad-Hoc Multiplicity Adjustment Method for Correlated Response Variables SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH LA English DT Article DE Ad-hoc methods; Correlated test statistics; Family-wise error rate; Modifications of the independence formula; Multiplicity adjustments ID CLINICAL-TRIALS; BONFERRONI PROCEDURE; END-POINTS; TESTS AB Clinical trials and many other scientific studies perform statistical tests for multiple response variables for finding whether an experimental treatment of interest is better than a specified control for some of these variables. Multiplicity adjustments for such tests of multiple response variables, having varying degrees of correlations, have been a challenging task for achieving a meaningful control of the Type I error rate. A way out of this difficulty has been simply to ignore correlations among response variables and use methods such as the Bonferroni procedure or the. Sidak (1967) adjustment formula under independence. This, however, can make the multiplicity adjustments conservative when the correlations are in the moderate to high range and reduce the power of the tests for finding beneficial treatment effects. On the other hand,. Sidak's adjustment formula under independence is quite attractive; it's easy to use for multiplicity adjustments and for setting simultaneous confidence intervals. Therefore, there has been interest in ad-hoc modifications of this formula that incorporate correlation information for making it less conservative and for gaining power, but at the same time retaining its simplicity. There have been several attempts in this regard but without much success. We review prior attempts at such modifications and propose a new one which is easy to use and controls the family-wise error rate nicely. An attractive feature of the proposed method is that its tests easily convert to simultaneous confidence intervals-most popular methods, such as step-up and step-down type methods lack this property. C1 [Huque, Mohammad F.] Georgia So Univ, JP Hsu Coll Publ Hlth, Div Biometr 4, Off Biostat OTS CDER FDA, Silver Spring, MD 20993 USA. [Huque, Mohammad F.] Georgia So Univ, JP Hsu Coll Publ Hlth, Adjunct Fac, Silver Spring, MD 20993 USA. [Quasem, Mohammed] Howard Univ, Dept Informat Syst & Decis Sci, Sch Business, Washington, DC 20059 USA. [Dubey, Satya D.] Off Biostat OTS CDER FDA, Bethesda, MD 20817 USA. RP Huque, MF (reprint author), Georgia So Univ, JP Hsu Coll Publ Hlth, Div Biometr 4, Off Biostat OTS CDER FDA, 10903 New Hampshire Ave,WO Bldg 21,Room 3510, Silver Spring, MD 20993 USA. EM mohammad.huque@fda.hhs.gov NR 22 TC 0 Z9 0 U1 1 U2 5 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 1946-6315 J9 STAT BIOPHARM RES JI Stat. Biopharm. Res. PD FEB PY 2010 VL 2 IS 1 BP 1 EP 21 DI 10.1198/sbr.2009.0052 PG 21 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 791HZ UT WOS:000292657100001 ER PT J AU Lee, MH Arcidiacono, JA Bilek, AM Wille, JJ Hamill, CA Wonnacott, KM Wells, MA Oh, SS AF Lee, Mark H. Arcidiacono, Judith A. Bilek, Anastacia M. Wille, Jeremiah J. Hamill, Caitilin A. Wonnacott, Keith M. Wells, Martha A. Oh, Steven S. TI Considerations for Tissue-Engineered and Regenerative Medicine Product Development Prior to Clinical Trials in the United States SO TISSUE ENGINEERING PART B-REVIEWS LA English DT Article AB Tissue-engineered and regenerative medicine products are promising innovative therapies that can address unmet clinical needs. These products are often combinations of cells, scaffolds, and other factors and are complex in both structure and function. Their complexity introduces challenges for product developers to establish novel manufacturing and characterization techniques to ensure that these products are safe and effective prior to clinical trials in humans. Although there are only a few commercial products that are currently in the market, many more tissue-engineered and regenerative medicine products are under development. Therefore, it is the purpose of this article to help product developers in the early stages of product development by providing insight into the Food and Drug Administration (FDA) process and by highlighting some of the key scientific considerations that may be applicable to their products. We provide resources that are publically available from the FDA and others that are of potential interest. As the provided information is general in content, product developers should contact the FDA for feedback regarding their specific products. Also described are ways through which product developers can informally and formally interact with the FDA early in the development process to help in the efficient progression of products toward clinical trials. C1 [Lee, Mark H.] US FDA, Cellular Therapies Branch, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies,Ctr Biol Eva, Rockville, MD 20852 USA. [Bilek, Anastacia M.] US FDA, Ctr Device & Radiol Hlth, Rockville, MD 20852 USA. [Wille, Jeremiah J.; Hamill, Caitilin A.] US FDA, Off Commissioner, Rockville, MD 20852 USA. RP Lee, MH (reprint author), US FDA, Cellular Therapies Branch, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies,Ctr Biol Eva, 1401 Rockville Pike,HFM 715, Rockville, MD 20852 USA. EM mark.lee@fda.hhs.gov NR 44 TC 46 Z9 48 U1 0 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3368 J9 TISSUE ENG PART B-RE JI Tissue Eng. Part B-Rev. PD FEB PY 2010 VL 16 IS 1 BP 41 EP 54 DI 10.1089/ten.teb.2009.0449 PG 14 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 554GJ UT WOS:000274423200006 PM 19728784 ER PT J AU Wear, KA AF Wear, Keith A. TI DECOMPOSITION OF TWO-COMPONENT ULTRASOUND PULSES IN CANCELLOUS BONE USING MODIFIED LEAST SQUARES PRONY METHOD - PHANTOM EXPERIMENT AND SIMULATION SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE Prony's method; Cancellous bone; Attenuation; Phase velocity ID BIOT-ATTENBOROUGH MODEL; WAVE-PROPAGATION; NEGATIVE DISPERSION; TRABECULAR BONE; STRUCTURAL ANISOTROPY; ACOUSTIC PROPAGATION; PHASE-VELOCITY; INTERFERENCE; SIGNALS; DEFORMATION AB Porous media such as cancellous bone often support the simultaneous propagation of two compressional waves. When small bone samples are interrogated in through-transmission with broadband sources, these two waves often overlap in time. The modified least-squares Prony's (MLSP) method was tested for decomposing a 500 kHz-center-frequency signal containing two overlapping components: one passing through a polycarbonate plate (to produce the "fast'' wave) and another passing through a cancellous-bone-mimicking phantom (to produce the "slow'' wave). The MLSP method yielded estimates of attenuation slopes accurate to within 7% (polycarbonate plate) and 2% (cancellous bone phantom). The MLSP method yielded estimates of phase velocities accurate to within 1.5% (both media). The MLSP method was also tested on simulated data generated using attenuation slopes and phase velocities corresponding to bovine cancellous bone. Throughout broad ranges of signal-to-noise ratio (SNR), the MLSP method yielded estimates of attenuation slope that were accurate to within 1.0% and estimates of phase velocity that were accurate to within 4.3% (fast wave) and 1.3% (slow wave). (E-mail: keith.wear@fda.hhs.gov) Published by Elsevier Inc. on behalf of World Federation for Ultrasound in Medicine & Biology. C1 US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Bldg 62,Room 3108,10903 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 regarding Prony's method. The author is grateful for funding from the FDA Office of Women's Health. NR 44 TC 26 Z9 27 U1 0 U2 6 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 FEB PY 2010 VL 36 IS 2 BP 276 EP 287 DI 10.1016/j.ultrasmedbio.2009.06.1092 PG 12 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 600TR UT WOS:000278012300010 PM 20113862 ER PT J AU Shephard, GS Berthiller, F Dorner, J Krska, R Lombaert, GA Malone, B Maragos, C Sabino, M Solfrizzo, M Trucksess, MW van Egmond, HP Whitaker, TB AF Shephard, G. S. Berthiller, F. Dorner, J. Krska, R. Lombaert, G. A. Malone, B. Maragos, C. Sabino, M. Solfrizzo, M. Trucksess, M. W. van Egmond, H. P. Whitaker, T. B. TI Developments in mycotoxin analysis: an update for 2008-2009 SO WORLD MYCOTOXIN JOURNAL LA English DT Article DE aflatoxin; alternaria; cyclopiazonic acid; fumonisin; ochratoxin; patulin; trichothecenes; zearalenone; sampling ID PERFORMANCE LIQUID-CHROMATOGRAPHY; LINKED-IMMUNOSORBENT-ASSAY; TANDEM MASS-SPECTROMETRY; CORN-BASED FOOD; IMMUNOAFFINITY COLUMN CLEANUP; FLUORESCENCE DETECTION METHOD; SINGLE-LABORATORY VALIDATION; NEAR-INFRARED SPECTROSCOPY; RESORCYLIC ACID LACTONES; AFLATOXIN M-1 DETECTION AB This review highlights developments in mycotoxin analysis and sampling over a period between mid-2008 and mid-2009. It covers the major mycotoxins: aflatoxins, alternaria toxins, cyclopiazonic acid, fumonisins, ochratoxin, patulin, trichothecenes and zearalenone. Developments in mycotoxin analysis continue, with emphasis on novel immunological methods and further description of LC-MS and LC-MS/MS, particularly as multimycotoxin applications for different ranges of mycotoxins. Although falling outside the main emphasis of the review, some aspects of natural occurrence have been mentioned, especially if linked to novel method developments. C1 [Shephard, G. S.] MRC, PROMEC Unit, ZA-7505 Tygerberg, South Africa. [Berthiller, F.; Krska, R.] Univ Bodenkultur Wien, Dept Agrobiotechnol IFATulln, Ctr Analyt Chem, Christian Doppler Lab Mycotoxin Res, A-3430 Tulin, Austria. [Dorner, J.] ARS, USDA, Natl Peanut Res Lab, Dawson, GA 31742 USA. [Lombaert, G. A.] Hlth Canada, Winnipeg, MB R2J 3Y1, Canada. [Malone, B.] Tril Analyt Lab, Washington, MO 63090 USA. [Maragos, C.] ARS, USDA, Natl Ctr Agr Utilizat Res, Peoria, IL 61604 USA. [Sabino, M.] Adolfo Lutz Inst, Sao Paulo, Brazil. [Solfrizzo, M.] CNR, Inst Sci Food Prod, I-700126 Bari, Italy. [Trucksess, M. W.] US FDA, College Pk, MD 20740 USA. [van Egmond, H. P.] RIKILT, Cluster Nat Toxins & Pesticides, NL-6700 AE Wageningen, Netherlands. [Whitaker, T. B.] N Carolina State Univ, Biol & Agr Engn Dept, Raleigh, NC 27695 USA. RP Shephard, GS (reprint author), MRC, PROMEC Unit, POB 19070, ZA-7505 Tygerberg, South Africa. EM gordon.shephard@mrc.ac.za OI Shephard, Gordon Seymour/0000-0002-1267-9036 NR 192 TC 21 Z9 23 U1 2 U2 27 PU WAGENINGEN ACADEMIC PUBLISHERS PI WAGENINGEN PA PO BOX 220, WAGENINGEN, 6700 AE, NETHERLANDS SN 1875-0710 J9 WORLD MYCOTOXIN J JI World Mycotoxin J. PD FEB PY 2010 VL 3 IS 1 BP 3 EP 23 DI 10.3920/WMJ2009.1172 PG 21 WC Food Science & Technology; Mycology; Toxicology SC Food Science & Technology; Mycology; Toxicology GA 664WY UT WOS:000282995800002 ER PT J AU Yang, YS Gupta, A Carlin, AS Faustino, PJ Lyon, RC Ellison, CD Rothman, B Khan, MA AF Yang, Yongsheng Gupta, Abhay Carlin, Alan S. Faustino, Patrick J. Lyon, Robbe C. Ellison, Christopher D. Rothman, Barry Khan, Mansoor A. TI Comparative stability of repackaged metoprolol tartrate tablets SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE Analysis; Dissolution; HPLC (high-performance/pressure liquid chromatography) Hydration; Near-infrared spectroscopy; Stability ID UNIT-DOSE CONTAINERS; MOISTURE PERMEATION; RELATIVE HUMIDITY AB The stability of metoprolol tartrate tablets packaged in original high density polyethylene containers and repackaged in USP Class A unit-dose blister packs was investigated Studies were conducted at 25 degrees C/60% relative humidity (RH) for 52 weeks and at 40 degrees C/75% RH for 13 weeks The potency, dissolution, water content, loss on drying and hardness of the drug products were analyzed. Results indicated no differences in the stability between the tablets in both packages stored under 25 degrees C/60% RH. No difference in potency was found in both packages under either condition. However, a significant weight increase due to moisture uptake was observed for the repackaged tablets stored under 40 degrees C/75% RH. The weight increase was accompanied by a decrease in tablet hardness (6.5-0kp) and a increase in dissolution rate (51-92%) in 5 min. Near-infrared (NIR) chemical imaging also monitored moisture uptake of the tablet non-invasively through the package. The observed changes in product stability may adversely affect the products bioavailability profile, even though the potency of the active drug remained within USP specification range of 90-110% Study results suggest product quality can be negatively impacted even when using USP Class A repackaging materials. Published by Elsevier B.V. C1 [Yang, Yongsheng; Gupta, Abhay; Carlin, Alan S.; Faustino, Patrick J.; Lyon, Robbe C.; Ellison, Christopher D.; Khan, Mansoor A.] US FDA, Ctr Drug Evaluat & Res, Div Prod Qual Res, Silver Spring, MD 20993 USA. [Rothman, Barry] US FDA, Ctr Drug Evaluat & Res, Off Compliance, Silver Spring, MD 20993 USA. RP Khan, MA (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Prod Qual Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM masoor.khan@fda.hhs.gov NR 23 TC 4 Z9 4 U1 1 U2 9 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 JAN 29 PY 2010 VL 385 IS 1-2 BP 92 EP 97 DI 10.1016/j.ijpharm.2009.10.040 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 551TV UT WOS:000274234100014 PM 19879937 ER PT J AU Binienda, ZK Ross, IA Gough, B Riccio, T Kim, CS Ali, SF AF Binienda, Z. K. Ross, I. A. Gough, B. Riccio, T. Kim, C. S. Ali, S. F. TI Striatal dopamine in the response of brain and liver unsaturated and saturated free fatty acids following administration of C75 in CD-1 mice SO NEUROSCIENCE LETTERS LA English DT Article DE C75; Dopamine; Serotonin; Free fatty acids; Liver; Brain ID CARNITINE PALMITOYLTRANSFERASE-I; FOOD-INTAKE; BODY-WEIGHT; LEPTIN; HOMEOSTASIS; OXIDATION; GLUCOSE; OBESITY; EXPRESSION; ADDICTION AB In order to clarify the mechanism of action of cerulenin analog, C75, known to suppress feeding behavior, food intake was measured in adult CD-1 male mice n = 5 per group, treated i.p. with 10 and 20 mg/kg of C75. Animals in both treatment groups had significantly lower 24 h food consumption rate relative to the control group injected with vehicle. Striatal monoamine neurotransmitters and striatal as well as liver long chain free fatty acids concentrations were subsequently evaluated in another group treated i.p. with 20 mg/kg C75. Acute exposure to C75 at 20 mg/kg led to approximately 50% increase in the striatal dopamine levels and a decrease in dopamine turnover for up to 24 h following the injection. The concentration of serotonin remained unchanged. Concentration of saturated fatty acids in the liver and striatum did not change, while striatal unsaturated myristoleic acid (cis-9-tetradecenoic acid) levels were significantly higher as early as 2 h post-injection and remained elevated at 24 h post-injection. These preliminary data suggest a central regulatory role of unsaturated fatty acids under dopaminergic control in the C75-induced anorexia. Pharmacological alterations in fatty acid metabolism may prove beneficial in the treatment of obesity. Published by Elsevier Ireland Ltd. C1 [Binienda, Z. K.] US FDA, Natl Ctr Toxicol Res, DNT, Div Neurotoxicol,HFT 132, Jefferson, AR 72079 USA. [Ross, I. A.; Kim, C. S.] US FDA, Div Toxicol, CFSAN, Laurel, MD 20708 USA. RP Binienda, ZK (reprint author), US FDA, Natl Ctr Toxicol Res, DNT, Div Neurotoxicol,HFT 132, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM zbigniew.binienda@fda.hhs.gov FU NCTR/FDA [E-07110.31]; Sigma Tau Research, Inc. [88-05] FX This research was supported by the NCTR/FDA protocol E-07110.31. The authors thank Mr. Brett Thorn (NCTR, Division of Personalized Nutrition and Medicine) for food intake data analysis and Ms. Bonnie L. Robinson (NCTR, TPA) for technical support in the study. The financial support of Sigma Tau Research, Inc. Gaithersburg, MD under CRADA Nr. 88-05 (T.R.) is greatly acknowledged. NR 33 TC 0 Z9 0 U1 0 U2 1 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 JAN 29 PY 2010 VL 469 IS 3 BP 324 EP 327 DI 10.1016/j.neulet.2009.12.019 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 558DX UT WOS:000274722100009 PM 20026180 ER PT J AU Van Doren, JM Condon, LR DeSouza-Goding, A Miller, TM Bopp, JC Viggiano, AA AF Van Doren, Jane M. Condon, Laura R. DeSouza-Goding, Antonet Miller, Thomas M. Bopp, Joseph C. Viggiano, A. A. TI Electron Affinity of trans-2-C4F8 from Electron Attachment-Detachment Kinetics SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID UNSATURATED FLUOROCARBONS; GASEOUS DIELECTRICS; MOLECULES; EXCHANGE; ETCH; HOLE; SF6 AB Electron attachment and detachment kinetics of 2-C4F8 were studied over the temperature range 298-487 K with a flowing-afterglow Langmuir-probe apparatus. Only parent anions were formed in the attachment process throughout this temperature range, At the highest temperatures, thermal electron detachment of the parent anions is important. Analysis of the 2-C4F8 gas showed an 82/18 mixture of trans/cis isomers. The kinetic data at the higher temperatures were used to determine the electron affinity EA(trans-2-C4F8) = 0.79 +/- 0.06 eV after making some reasonable assumptions. The same quantity Wits calculated using the G3(MP2) compound method, yielding 0.74 eV. The kinetic data were not sufficient to establish a reliable Value for EA(cis-2-C4F8), but G3(MP2) calculations give it Value 0.017 eV greater than that for trans-2-C4F8. MP2 and density functional theory were used to study the structural properties of the neutral and anion isomers. C1 [Van Doren, Jane M.; Condon, Laura R.; DeSouza-Goding, Antonet] Coll Holey Cross, Dept Chem, Worcester, MA 01610 USA. [Miller, Thomas M.; Bopp, Joseph C.; Viggiano, A. A.] USAF, Space Vehicles Directorate, Bedford, MA 01731 USA. [Van Doren, Jane M.] US FDA, CFSAN, OFDCER, DEC,SC, College Pk, MD 20740 USA. [Miller, Thomas M.] Boston Coll, Inst Sci Res, Chestnut Hill, MA 02167 USA. [Bopp, Joseph C.] Nalco Co, Naperville, IL 60563 USA. RP Van Doren, JM (reprint author), Coll Holey Cross, Dept Chem, Worcester, MA 01610 USA. EM jane.vandoren@gmail.com FU National Academy of Science of Sciences Air Force Summer Faculty Fellowship Program; Research Corporation; College of the Holey Cross; Institute for Scientific Research of Boston College [FA8718-04-C0006] FX We are grateful for the support of the Air force Office of Scientific Research for this work, and for a grant of computer time from the DOD High Performance Computing Modernization Program at the Maui High Performance Computing Center. J.M.V.D. acknowledges support from the National Academy of Science of Sciences Air Force Summer Faculty Fellowship Program, the Research Corporation, and the College of the Holey Cross. T.M.M. is under contract (FA8718-04-C0006) to the Institute for Scientific Research of Boston College, NR 32 TC 2 Z9 2 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD JAN 28 PY 2010 VL 114 IS 3 BP 1420 EP 1426 DI 10.1021/jp907154m PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 544QB UT WOS:000273672600025 PM 20020708 ER PT J AU Lin, WJ Hsueh, HM Chen, JJ AF Lin, Wei-Jiun Hsueh, Huey-Miin Chen, James J. TI Power and sample size estimation in microarray studies SO BMC BIOINFORMATICS LA English DT Article ID FALSE DISCOVERY RATE; FDR-CONTROL AB Background: Before conducting a microarray experiment, one important issue that needs to be determined is the number of arrays required in order to have adequate power to identify differentially expressed genes. This paper discusses some crucial issues in the problem formulation, parameter specifications, and approaches that are commonly proposed for sample size estimation in microarray experiments. Common methods for sample size estimation are formulated as the minimum sample size necessary to achieve a specified sensitivity (proportion of detected truly differentially expressed genes) on average at a specified false discovery rate (FDR) level and specified expected proportion (pi 1) of the true differentially expression genes in the array. Unfortunately, the probability of detecting the specified sensitivity in such a formulation can be low. We formulate the sample size problem as the number of arrays needed to achieve a specified sensitivity with 95% probability at the specified significance level. A permutation method using a small pilot dataset to estimate sample size is proposed. This method accounts for correlation and effect size heterogeneity among genes. Results: A sample size estimate based on the common formulation, to achieve the desired sensitivity on average, can be calculated using a univariate method without taking the correlation among genes into consideration. This formulation of sample size problem is inadequate because the probability of detecting the specified sensitivity can be lower than 50%. On the other hand, the needed sample size calculated by the proposed permutation method will ensure detecting at least the desired sensitivity with 95% probability. The method is shown to perform well for a real example dataset using a small pilot dataset with 4-6 samples per group. Conclusions: We recommend that the sample size problem should be formulated to detect a specified proportion of differentially expressed genes with 95% probability. This formulation ensures finding the desired proportion of true positives with high probability. The proposed permutation method takes the correlation structure and effect size heterogeneity into consideration and works well using only a small pilot dataset. C1 [Lin, Wei-Jiun; Chen, James J.] US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. [Hsueh, Huey-Miin] Natl Chengchi Univ, Dept Stat, Taipei 11623, Taiwan. [Chen, James J.] China Med Univ, Grad Inst Biostat, Taichung, Taiwan. [Chen, James J.] China Med Univ, Ctr Biostat, Taichung, Taiwan. RP Chen, JJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. EM jamesj.chen@fda.hhs.gov OI HSUEH, HUEY-MIIN/0000-0003-0536-9440 NR 15 TC 23 Z9 23 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JAN 25 PY 2010 VL 11 AR 48 DI 10.1186/1471-2105-11-48 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 568UA UT WOS:000275547300001 PM 20100337 ER PT J AU Zhang, XY Kutner, RH Bialkowska, A Marino, MP Klimstra, WB Reiser, J AF Zhang, Xian-Yang Kutner, Robert H. Bialkowska, Agnieszka Marino, Michael P. Klimstra, William B. Reiser, Jakob TI Cell-specific targeting of lentiviral vectors mediated by fusion proteins derived from Sindbis virus, vesicular stomatitis virus, or avian sarcoma/leukosis virus SO RETROVIROLOGY LA English DT Article ID HEMATOPOIETIC PROGENITOR CELLS; MESENCHYMAL STEM-CELLS; IN-VIVO; RETROVIRAL VECTORS; BRIDGE PROTEIN; INTRAVENOUS-INJECTION; ENVELOPE PROTEINS; HEPARAN-SULFATE; SARCOMA-VIRUSES; GENE DELIVERY AB Background: The ability to efficiently and selectively target gene delivery vectors to specific cell types in vitro and in vivo remains one of the formidable challenges in gene therapy. We pursued two different strategies to target lentiviral vector delivery to specific cell types. In one of the strategies, vector particles bearing a membrane-bound stem cell factor sequence plus a separate fusion protein based either on Sindbis virus strain TR339 glycoproteins or the vesicular stomatitis virus G glycoprotein were used to selectively transduce cells expressing the corresponding stem cell factor receptor (c-kit). An alternative approach involved soluble avian sarcoma/leukosis virus receptors fused to cell-specific ligands including stem cell factor and erythropoietin for targeting lentiviral vectors pseudotyped with avian sarcoma/leukosis virus envelope proteins to cells that express the corresponding receptors. Results: The titers of unconcentrated vector particles bearing Sindbis virus strain TR339 or vesicular stomatitis virus G fusion proteins plus stem cell factor in the context of c-kit expressing cells were up to 3.2 x 10(5) transducing units per ml while vector particles lacking the stem cell factor ligand displayed titers that were approximately 80 fold lower. On cells that lacked the c-kit receptor, the titers of stem cell factor-containing vectors were approximately 40 times lower compared to c-kit-expressing cells. Lentiviral vectors pseudotyped with avian sarcoma/leukosis virus subgroup A or B envelope proteins and bearing bi-functional bridge proteins encoding erythropoietin or stem cell factor fused to the soluble extracellular domains of the avian sarcoma/leukosis virus subgroup A or B receptors resulted in efficient transduction of erythropoietin receptor or c-kit-expressing cells. Transduction of erythropoietin receptor-expressing cells mediated by bi-functional bridge proteins was found to be dependent on the dose, the correct subgroup-specific virus receptor and the correct envelope protein. Furthermore, transduction was completely abolished in the presence of anti-erythropoietin antibody. Conclusions: Our results indicate that the avian sarcoma/leukosis virus bridge strategy provides a reliable approach for cell-specific lentiviral vector targeting. The background levels were lower compared to alternative strategies involving Sindbis virus strain TR339 or vesicular stomatitis virus fusion proteins. C1 [Zhang, Xian-Yang; Kutner, Robert H.; Bialkowska, Agnieszka; Reiser, Jakob] Louisiana State Univ, Gene Therapy Program, Dept Med, Hlth Sci Ctr, New Orleans, LA 70112 USA. [Zhang, Xian-Yang] Univ Miami, Leonard M Miller Sch Med, Miami, FL 33136 USA. [Bialkowska, Agnieszka] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Marino, Michael P.; Reiser, Jakob] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Klimstra, William B.] Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA 15261 USA. RP Reiser, J (reprint author), Louisiana State Univ, Gene Therapy Program, Dept Med, Hlth Sci Ctr, New Orleans, LA 70112 USA. EM Jakob.Reiser@fda.hhs.gov FU NIH [NS044832] FX This work was supported by NIH grant NS044832 to JR. We thank Gitanjali Srivastava and Ted Diehl for technical assistance. We thank Andrew Byrnes and Jeffrey Smith (FDA/CBER) for helpful comments on the manuscript. NR 52 TC 5 Z9 5 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD JAN 25 PY 2010 VL 7 AR 3 DI 10.1186/1742-4690-7-3 PG 15 WC Virology SC Virology GA 562XG UT WOS:000275088500001 PM 20100344 ER PT J AU Swisher, JFA Burton, N Bacot, SM Vogel, SN Feldman, GM AF Swisher, Jennifer F. A. Burton, Nicholas Bacot, Silvia M. Vogel, Stefanie N. Feldman, Gerald M. TI Annexin A2 tetramer activates human and murine macrophages through TLR4 SO BLOOD LA English DT Article ID HUMAN PERIPHERAL MONOCYTES; TOLL-LIKE RECEPTOR; PLASMINOGEN-ACTIVATOR; CELL ACTIVATION; II-RECEPTOR; LIPOPOLYSACCHARIDE; ANTIBODIES; SECRETION; CANCER; GENE AB Annexins are a large family of intracellular phospholipid-binding proteins, yet several extracellular roles have been identified. Specifically, annexin A2, found in a heterotetrameric complex with S100A10, not only serves as a key extracellular binding partner for pathogens and host proteins alike, but also can be shed or secreted. We reported previously that soluble annexin A2 tetramer (A2t) activates human monocyte-derived macrophages (MDM), resulting in secretion of inflammatory mediators and enhanced phagocytosis. Although a receptor for A2t has been cloned from bone marrow stromal cells, data contained in this study demonstrate that it is dispensable for A2t-dependent activation of MDM. Furthermore, A2t activates wild-type murine bone marrow-derived macrophages, whereas macrophages from myeloid differentiation factor 88-deficient mice display a blunted response, suggesting a role for Toll-like receptor (TLR) signaling. Small interfering RNA knockdown of TLR4 in human MDM reduced the response to A2t, blocking antibodies against TLR4 (but not TLR2) blocked activation altogether, and bone marrow-derived macrophages from TLR4(-/-) mice were refractory to A2t. These data demonstrate that the modulation of macrophage function by A2t is mediated through TLR4, suggesting a previously unknown, but important role for this stress-sensitive protein in the detection of danger to the host, whether from injury or invasion. (Blood. 2010; 115: 549-558) C1 [Swisher, Jennifer F. A.; Burton, Nicholas; Bacot, Silvia M.; Feldman, Gerald M.] US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Vogel, Stefanie N.] Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. RP Feldman, GM (reprint author), US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, Off Biotechnol Prod,Ctr Drug Evaluat & Res, 29 Lincoln Dr,Bldg 29A,Rm 3C24,HFD-123, Bethesda, MD 20892 USA. EM gerald.feldman@fda.hhs.gov FU National Institutes of Health [AI-18797] FX This work was supported in part by National Institutes of Health grant AI-18797 (S.N.V.). NR 50 TC 54 Z9 56 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 21 PY 2010 VL 115 IS 3 BP 549 EP 558 DI 10.1182/blood-2009-06-226944 PG 10 WC Hematology SC Hematology GA 546OR UT WOS:000273820600016 PM 19965653 ER PT J AU Zhang, K Katz, E Kim, DH Kang, JU Ilev, IK AF Zhang, K. Katz, E. Kim, D. H. Kang, J. U. Ilev, I. K. TI Common-path optical coherence tomography guided fibre probe for spatially precise optical nerve stimulation SO ELECTRONICS LETTERS LA English DT Article AB A simple and effective common-path optical coherence tomography guided fibre probe for optical nerve stimulation has been developed and tested. The probe is capable of real-time monitoring of the fibre-to-nerve distance up to more than 1 mm at an axial resolution of approximately 3 mu m, thus improving the precision and safety of stimulation laser power delivery. C1 [Zhang, K.; Kang, J. U.] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. [Katz, E.; 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 7 TC 11 Z9 11 U1 1 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 JAN 21 PY 2010 VL 46 IS 2 BP 118 EP 119 DI 10.1049/el.2010.3221 PG 2 WC Engineering, Electrical & Electronic SC Engineering GA 547LJ UT WOS:000273889600011 ER PT J AU Unger, EF Thompson, AM Blank, MJ Temple, R AF Unger, Ellis F. Thompson, Aliza M. Blank, Melanie J. Temple, Robert TI Erythropoiesis-Stimulating Agents - Time for a Reevaluation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CHRONIC KIDNEY-DISEASE; EPOETIN; ALPHA C1 [Unger, Ellis F.; Thompson, Aliza M.; Blank, Melanie J.; Temple, Robert] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Unger, EF (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 5 TC 134 Z9 142 U1 0 U2 5 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 JAN 21 PY 2010 VL 362 IS 3 BP 189 EP 192 DI 10.1056/NEJMp0912328 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 545NE UT WOS:000273738400001 PM 20054037 ER PT J AU Christ, A Kainz, W Hahn, EG Honegger, K Zefferer, M Neufeld, E Rascher, W Janka, R Bautz, W Chen, J Kiefer, B Schmitt, P Hollenbach, HP Shen, JX Oberle, M Szczerba, D Kam, A Guag, JW Kuster, N AF Christ, Andreas Kainz, Wolfgang Hahn, Eckhart G. Honegger, Katharina Zefferer, Marcel Neufeld, Esra Rascher, Wolfgang Janka, Rolf Bautz, Werner Chen, Ji Kiefer, Berthold Schmitt, Peter Hollenbach, Hans-Peter Shen, Jianxiang Oberle, Michael Szczerba, Dominik Kam, Anthony Guag, Joshua W. Kuster, Niels TI The Virtual Family-development of surface-based anatomical models of two adults and two children for dosimetric simulations SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID VISIBLE HUMAN PROJECT; BODY-MASS INDEX; HUMAN HEAD; ELECTROMAGNETIC-FIELDS; FREQUENCY-RANGE; VOXEL MODELS; ABSORPTION; SEGMENTATION; PHANTOMS; TISSUES AB The objective of this study was to develop anatomically correct whole body human models of an adult male (34 years old), an adult female (26 years old) and two children (an 11-year-old girl and a six-year-old boy) for the optimized evaluation of electromagnetic exposure. These four models are referred to as the Virtual Family. They are based on high resolution magnetic resonance (MR) images of healthy volunteers. More than 80 different tissue types were distinguished during the segmentation. To improve the accuracy and the effectiveness of the segmentation, a novel semi-automated tool was used to analyze and segment the data. All tissues and organs were reconstructed as three-dimensional (3D) unstructured triangulated surface objects, yielding high precision images of individual features of the body. This greatly enhances the meshing flexibility and the accuracy with respect to thin tissue layers and small organs in comparison with the traditional voxel-based representation of anatomical models. Conformal computational techniques were also applied. The techniques and tools developed in this study can be used to more effectively develop future models and further improve the accuracy of the models for various applications. For research purposes, the four models are provided for free to the scientific community. C1 [Christ, Andreas; Honegger, Katharina; Zefferer, Marcel; Neufeld, Esra; Oberle, Michael; Szczerba, Dominik; Kuster, Niels] Fdn Res Informat Technol Soc ITIS, CH-8004 Zurich, Switzerland. [Kainz, Wolfgang; Guag, Joshua W.] US FDA, CDRH, Silver Spring, MD 20993 USA. [Hahn, Eckhart G.; Rascher, Wolfgang; Janka, Rolf; Bautz, Werner] Univ Erlangen Nurnberg, Univ Klinikum Erlangen, D-91054 Erlangen, Germany. [Neufeld, Esra; Kuster, Niels] Swiss Fed Inst Technol ETHZ, CH-8092 Zurich, Switzerland. [Chen, Ji; Shen, Jianxiang] Univ Houston, Dept Elect & Comp Engn, Houston, TX 77204 USA. [Kiefer, Berthold; Schmitt, Peter; Hollenbach, Hans-Peter] Siemens Healthcare, MR Applicat Dev, D-91052 Erlangen, Germany. [Kam, Anthony] Johns Hopkins Bayview Med Ctr, Dept Imaging, Baltimore, MD 21224 USA. RP Christ, A (reprint author), Fdn Res Informat Technol Soc ITIS, Zeughausstr 43, CH-8004 Zurich, Switzerland. EM christ@itis.ethz.ch RI Foundation, IT'IS/B-9559-2008; OI Janka, Rolf/0000-0003-1698-9741 FU Schmid & Partner Engineering AG, Switzerland; Mobile Manufacturers Forum (MMF), Belgium; GSM Association, Ireland FX The authors acknowledge the support and expertise of Stephan Kunzelmann for the acquisition of the MR images. This work was greatly supported by Schmid & Partner Engineering AG, Switzerland, the Mobile Manufacturers Forum (MMF), Belgium and the GSM Association, Ireland. NR 62 TC 424 Z9 427 U1 1 U2 23 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JAN 21 PY 2010 VL 55 IS 2 BP N23 EP N38 DI 10.1088/0031-9155/55/2/N01 PG 16 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 535IG UT WOS:000272960400015 PM 20019402 ER PT J AU Zhang, MJ Daniel, S Huang, Y Chancey, C Huang, QS Lei, YF Grinev, A Mostowski, H Rios, M Dayton, A AF Zhang, Mingjie Daniel, Sylvester Huang, Yong Chancey, Caren Huang, Qingsheng Lei, Ying F. Grinev, Andriyan Mostowski, Howard Rios, Maria Dayton, Andrew TI Anti-West Nile virus activity of in vitro expanded human primary natural killer cells SO BMC IMMUNOLOGY LA English DT Article ID FLAVIVIRUS INFECTION; NK CELLS; RECOGNITION; EXPRESSION; CARCINOMA AB Background: Natural Killer (NK) cells are a crucial component of the host innate immune system with anti-viral and anti-cancer properties. However, the role of NK cells in West Nile virus (WNV) infection is controversial, with reported effects ranging from active suppression of virus to no effect at all. It was previously shown that K562-mb15-41BBL (K562D2) cells, which express IL-15 and 4-1BBL on the K562 cell surface, were able to expand and activate human primary NK cells of normal peripheral blood mononuclear cells (PBMC). The expanded NK cells were tested for their ability to inhibit WNV infection in vitro. Results: Co-culture of PBMC with irradiated K562D2 cells expanded the NK cell number by 2-3 logs in 2-3 weeks, with more than 90% purity; upregulated NK cell surface activation receptors; downregulated inhibitory receptors; and boosted interferon gamma (IFN-gamma) production by similar to 33 fold. The expanded NK (D2NK) cell has strong natural killing activity against both K562 and Vero cells, and killed the WNV infected Vero cells through antibody-dependent cellular cytotoxicity (ADCC). The D2NK cell culture supernatants inhibited both WNV replication and WNV induced cytopathic effect (CPE) in Vero cells when added before or after infection. Anti-IFN-gamma neutralizing antibody blocked the NK supernatant-mediated anti-WNV effect, demonstrating a noncytolytic activity mediated through IFN-gamma. Conclusions: Co-culture of PBMC with K562D2 stimulatory cells is an efficient technique to prepare large quantities of pure and active NK cells, and these expanded NK cells inhibited WNV infection of Vero cells through both cytolytic and noncytolytic activities, which may imply a potential role of NK cells in combating WNV infection. C1 [Zhang, Mingjie; Daniel, Sylvester; Huang, Yong; Chancey, Caren; Huang, Qingsheng; Lei, Ying F.; Grinev, Andriyan; Rios, Maria; Dayton, Andrew] US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Rockville, MD 20892 USA. [Mostowski, Howard] US FDA, Cellular & Tissue Therapy Branch, Ctr Biol Evaluat & Res, Rockville, MD 20892 USA. [Huang, Yong; Huang, Qingsheng] NW Polytech Univ, Dept Life Sci, Xian 710072, Shaanxi, Peoples R China. [Lei, Ying F.] 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.gov; andrew.dayton@fda.hhs.gov RI Huang, Yong/G-9365-2011 NR 17 TC 17 Z9 17 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2172 J9 BMC IMMUNOL JI BMC Immunol. PD JAN 20 PY 2010 VL 11 AR 3 DI 10.1186/1471-2172-11-3 PG 9 WC Immunology SC Immunology GA 557IG UT WOS:000274662200001 PM 20089143 ER PT J AU Khurana, S Chearwae, W Castellino, F Manischewitz, J King, LR Honorkiewicz, A Rock, MT Edwards, KM Del Giudice, G Rappuoli, R Golding, H AF Khurana, Surender Chearwae, Wanida Castellino, Flora Manischewitz, Jody King, Lisa R. Honorkiewicz, Agnieszka Rock, Michael T. Edwards, Kathryn M. Del Giudice, Giuseppe Rappuoli, Rino Golding, Hana TI Vaccines with MF59 Adjuvant Expand the Antibody Repertoire to Target Protective Sites of Pandemic Avian H5N1 Influenza Virus SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID A VIRUSES; IMMUNOGENICITY; HEMAGGLUTININ; SAFETY; BINDING; MEMORY; ADULTS AB Vaccines against influenza viruses with pandemic potential, including H5N1, are under development. Because of a lack of preexisting immunity to these viruses, adjuvants (immune potentiators or enhancers) are needed to improve immune responses, to conserve scarce vaccine, and for cross-protection against strains that have drifted evolutionarily from the original. Aluminum-based adjuvants do not improve vaccine immunogenicity for influenza subunit vaccines, whereas oil-in-water adjuvants are effective, especially with H5N1-inactivated vaccines. We used whole-genome-fragment phage display libraries followed by surface plasmon resonance (SPR) technologies to elucidate the effect of different adjuvants on the antibody repertoire against H5N1 vaccine in humans. The oil-in-water adjuvant MF59 induced epitope spreading from HA2 to HA1 in hemagglutinin (HA) and neuraminidase relative to unadjuvanted or aluminum-adjuvanted vaccines. Moreover, we observed an increase by a factor of 20 in the frequency of HA1-to-HA2-specific phage clones in sera after MF59-adjuvanted vaccine administration and a factor of 2 to 3 increase in the avidity of antibodies binding to properly folded HA1 (28-319), as measured by SPR. The adjuvant-dependent increase in binding to conformational HA1 epitopes correlated with broadening of cross-clade neutralization and predicted improved in vivo protection. Thus, MF59 adjuvant improves the immune response to a H5N1 vaccine by inducing qualitative and quantitative expansion of the antibody repertoires with protective potential. C1 [Khurana, Surender; Chearwae, Wanida; Manischewitz, Jody; King, Lisa R.; Honorkiewicz, Agnieszka; Golding, Hana] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. [Castellino, Flora; Del Giudice, Giuseppe; Rappuoli, Rino] Novartis Vaccines & Diagnost Res Ctr, I-53100 Siena, Italy. [Rock, Michael T.; Edwards, Kathryn M.] Vanderbilt Univ, Med Ctr, Div Pediat Infect Dis, Nashville, TN 37232 USA. RP Golding, H (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. EM hana.golding@fda.hhs.gov FU NCRR NIH HHS [RR00095]; NIAID NIH HHS [N01-AI-25462] NR 17 TC 62 Z9 65 U1 1 U2 10 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 JAN 20 PY 2010 VL 2 IS 15 AR 15ra5 DI 10.1126/scitranslmed.3000624 PG 7 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 590YJ UT WOS:000277264100004 PM 20371470 ER PT J AU Melchior, WB Tolleson, WH AF Melchior, William B., Jr. Tolleson, William H. TI A functional quantitative polymerase chain reaction assay for ricin, Shiga toxin, and related ribosome-inactivating proteins SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE Ricin; Ribosome-inactivating proteins; Quantitative PCR; Reverse transcriptase ID LOCKED NUCLEIC-ACID; A-CHAIN; RNA; LOOP; DNA; ELECTROCHEMILUMINESCENCE; INHIBITORS; PRIMERS AB The potent toxins ricin, abrin, and other ribosome-inactivating proteins deadenylate a specific base in 28S ribosomal RNA that destroys ribosomes and leads to cell death. We have taken advantage of the fact that reverse transcriptase preferentially inserts an adenine opposite to an abasic site in RNA to create a quantitative polymerase chain reaction (PCR) assay to detect the damage. This assay detects as little as 30 pg of ricin. We used the assay to study enzymatic properties of ricin such as pH and temperature optima (pH 4.5-5.0 and 60 degrees C). Published by Elsevier Inc. C1 [Melchior, William B., Jr.; Tolleson, William H.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Melchior, WB (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM william.melchior@fda.hhs.gov NR 26 TC 25 Z9 26 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 EI 1096-0309 J9 ANAL BIOCHEM JI Anal. Biochem. PD JAN 15 PY 2010 VL 396 IS 2 BP 204 EP 211 DI 10.1016/j.ab.2009.09.024 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 529GM UT WOS:000272504100006 PM 19766090 ER PT J AU Nakamura, AJ Rao, VA Pommier, Y Bonner, WM AF Nakamura, Asako J. Rao, V. Ashutosh Pommier, Yves Bonner, William M. TI The complexity of phosphorylated H2AX foci formation and DNA repair assembly at DNA double-strand breaks SO CELL CYCLE LA English DT Article DE DNA double strand breaks; phosphorylated H2AX; MDC1; 53BP1; NBS1 ID DAMAGE RESPONSE; HISTONE H2AX; HOMOLOGOUS RECOMBINATION; IONIZING-RADIATION; GAMMA-H2AX; 53BP1; ATM; MDC1; RECRUITMENT; IRRADIATION AB The maintenance of genome stability requires efficient DNA double-stranded break (DSB) repair mediated by the phosphorylation of multiple histone H2AX molecules near the break sites. The phosphorylated H2AX (gamma H2AX) molecules form foci covering many megabases of chromatin. The formation of gamma-H2AX foci is critical for efficient DNA damage response (DDR) and for the maintenance of genome stability, however, the mechanisms of protein organization in foci is largely unknown. To investigate the nature of gamma H2AX foci formation, we analyzed the distribution of gamma H2AX and other DDR proteins at DSB sites using a variety of techniques to visualize, expand and partially disrupt chromatin. We report here that gamma H2AX foci change composition during the cell cycle, with proteins 53BP1, NBS1 and MRE11 dissociating from foci in G 2 and mitosis to return at the beginning of the following G(1). In contrast, MDC1 remained colocalized with gamma-H2AX during mitosis. In addition, while gamma H2AX was found to span large domains flanking DSB sites, 53BP1 and NBS1 were more localized and MDC1 colocalized in doublets in foci. H2AX and MDC1 were found to be involved in chromatin relaxation after DSB formation. Our data demonstrates that the DSB repair focus is a heterogeneous and dynamic structure containing internal complexity. C1 [Nakamura, Asako J.; Pommier, Yves; Bonner, William M.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Rao, V. Ashutosh] US FDA, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Nakamura, AJ (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM nakamuraa@mail.nih.gov FU National Cancer Institute; CCR; NIH FX We thank Jennifer S. Dickey, Christophe E. Redon and Olga A. Sedelnikova, for critical reading of this manuscript, and other members of Laboratory of Molecular Pharmacology for help in this work. We thank Brittany Flood for technical assistance. We are grateful to Peter Franklin with the technical support for DeltaVision OMX (TM) 3D-SIM (TM) Super Resolution Imaging System. This work was supported by the Intramural Research Program of the National Cancer Institute, CCR, NIH. NR 45 TC 57 Z9 60 U1 3 U2 11 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JAN 15 PY 2010 VL 9 IS 2 BP 389 EP 397 PG 9 WC Cell Biology SC Cell Biology GA 550PG UT WOS:000274139800036 PM 20046100 ER PT J AU Shimamura, T Fujisawa, T Husain, SR Joshi, B Puri, RK AF Shimamura, Takeshi Fujisawa, Toshio Husain, Syed R. Joshi, Bharat Puri, Raj K. TI Interleukin 13 Mediates Signal Transduction through Interleukin 13 Receptor alpha 2 in Pancreatic Ductal Adenocarcinoma: Role of IL-13 Pseudomonas Exotoxin in Pancreatic Cancer Therapy SO CLINICAL CANCER RESEARCH LA English DT Article ID CHIMERIC FUSION PROTEINS; CARCINOMA-CELLS; NECK-CANCER; HUMAN HEAD; CHAIN; GROWTH; MODEL; EXPRESSION; TARGET; GLIOMA AB Purpose: Interleukin-13 receptor alpha 2 (IL-13R alpha 2) is a tumor antigen that is overexpressed in certain human tumors. However, its significance and expression in pancreatic cancer is not known. It is also not known whether IL-13 can signal through IL-13R alpha 2 in cancer. Experimental Design: The expression of IL-13R alpha 2 was assessed in pancreatic cancer samples by immunohistochemistry and in cell lines by flow cytometry and reverse transcription-PCR. The role of IL-13R alpha 2 was examined by IL-13-induced signaling in pancreatic cancer cell lines. IL-13R alpha 2-positive tumors were targeted by IL-13PE cytotoxin in vitro and in vivo in an orthotopic murine model of human pancreatic cancer. Results: Of the pancreatic tumor samples 71% overexpressed moderate to high-density IL-13R alpha 2 chain compared with normal pancreatic samples. IL-13 induced transforming growth factor-beta 1 promoter activity in IL-13R alpha 2-positive tumor cells and in cells engineered to express IL-13R alpha 2 but not in IL-13R alpha 2-negative or RNA interference knockdown cells. c-Jun and c-Fos of the AP-1 family of nuclear factors were activated by IL-13 only in IL-13R alpha 2-positive cells. In the orthotopic mouse model, IL13-PE significantly decreased tumor growth when assessed by whole-body imaging and prolonged the mean survival time. Similar results were observed in mice xenografted with a surgically resected human pancreatic tumor sample. Conclusions: These results indicate that IL-13R alpha 2 is a functional receptor as IL-13 mediates signaling in human pancreatic cancer cell lines. IL-13 causes transforming growth factor-beta activation via AP-1 pathway, which may cause tumor induced immunosuppression in the host. In addition, IL13-PE cytotoxin may be an effective therapeutic agent for the treatment of pancreatic cancer. Clin Cancer Res; 16(2); 577-86. (C)2010 AACR. C1 [Shimamura, Takeshi; Fujisawa, Toshio; Husain, Syed R.; Joshi, Bharat; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN20 HFM-735,29 Lincoln Dr, Bethesda, MD 20892 USA. EM raj.puri@fda.hhs.gov NR 31 TC 24 Z9 26 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2010 VL 16 IS 2 BP 577 EP 586 DI 10.1158/1078-0432.CCR-09-2015 PG 10 WC Oncology SC Oncology GA 607ZE UT WOS:000278545000022 PM 20068108 ER PT J AU Fan, XH Shi, LM Fang, H Cheng, YY Perkins, R Tong, WD AF Fan, Xiaohui Shi, Leming Fang, Hong Cheng, Yiyu Perkins, Roger Tong, Weida TI DNA Microarrays Are Predictive of Cancer Prognosis: A Re-evaluation SO CLINICAL CANCER RESEARCH LA English DT Article ID GENE-EXPRESSION PROFILES; BREAST-CANCER; QUALITY-CONTROL; CLASSIFICATION; ADENOCARCINOMA; SIGNATURE; SELECTION; SURVIVAL AB Purpose: The reliability of microarray-based cancer prognosis is questioned by Michiels et al. They reanalyzed seven studies published in the prominent journals as successful stories of microarray-based cancer prognosis and concluded that the originally reported assessments are overoptimistic. We set to investigate the reality of microarrays for predicting cancer prognosis by using the same data sets with commonly accepted data analysis approaches. Experiment Design: Michiels et al.'s analysis protocol used a correlation-based feature selection method, split sample validation, and a nearest-centroid rule classifier. We examined their results through systematically replacing their analysis approaches with other commonly used methods as a parameter study. In addition, we applied a widely accepted permutation test in conjunction with 5-fold cross-validation to verify Michiels et al.'s findings. Results: The stability of signature genes is likely obtained when a fold change-based feature selection method is applied. When cross-validation procedures are used to replace Michiels et al.'s split sample validation, only one of the seven studies yielded uninformative classifiers. The permutation test reveals that the confidence interval based on the split sample used in the Michiels et al.'s review is not a rigorous and robust approach to assess the validity of a classifier. Conclusions: We concluded that the use of DNA microarrays for cancer prognosis can be demonstrated. We also stressed that caution should be exercised when a general conclusion is withdrawn based on a single statistical practice without alternative validation, which can leave a false impression and pessimistic perspective for emerging biomarker methodologies to advance cancer research. Clin Cancer Res; 16(2); 629-36. (C) 2010 AACR. C1 [Fan, Xiaohui; Cheng, Yiyu] Zhejiang Univ, Coll Pharmaceut Sci, Pharmaceut Informat Inst, Hangzhou 310003, Zhejiang, Peoples R China. [Fang, Hong] US FDA, ICF Int, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Tong, WD (reprint author), 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] FX The Chinese Key Technologies R&D Program grant no. 2005CB23402 and the National Science Foundation of China grant no. 30801556 (X. Fan) for participating in the projects at National Center for Toxicological Research of the U.S. Food and Drug Administration through the ORISE research program. NR 29 TC 34 Z9 35 U1 1 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2010 VL 16 IS 2 BP 629 EP 636 DI 10.1158/1078-0432.CCR-09-1815 PG 8 WC Oncology SC Oncology GA 607ZE UT WOS:000278545000027 PM 20068095 ER PT J AU Surendran, K Boyle, S Barak, H Kim, M Stomberski, C McCright, B Kopan, R AF Surendran, Kameswaran Boyle, Scott Barak, Hila Kim, Mijin Stomberski, Colin McCright, Brent Kopan, Raphael TI The contribution of Notch1 to nephron segmentation in the developing kidney is revealed in a sensitized Notch2 background and can be augmented by reducing Mint dosage SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Nephron segmentation; Notch; Mint; RBP-J; Alagille syndrome; Six2 ID DEVELOPING MOUSE KIDNEY; SIGNALING PATHWAY; ALAGILLE-SYNDROME; PROGENITOR POPULATION; CELLS; EXPRESSION; MICE; NEPHROGENESIS; PROTEIN; DIFFERENTIATION AB We previously determined that Notch2, and not Notch1, was required for forming proximal nephron segments. The dominance of Notch2 may be conserved in humans, since Notch2 mutations occur in Alagille syndrome (ALGS) 2 patients, which includes renal complications. To test whether mutations in Notch1 could increase the severity of renal complications in ALGS, we inactivated conditional Notch1 and Notch2 alleles in mice using a Six2-GFP::Cre. This BAC transgene is expressed mosaically in renal epithelial progenitors but uniformly in cells exiting the progenitor pool to undergo mesenchymal-to-epithelial transition. Although delaying Notch2 inactivation had a marginal effect on nephron numbers, it created a sensitized background in which the inactivation of Notch1 severely compromised nephron formation, function, and survival. These and additional observations indicate that Notch1 in concert with Notch2 contributes to the morphogenesis of renal vesicles into S-shaped bodies in a RBP-J-dependent manner. A significant implication is that elevating Notch1 activity could improve renal functions in ALGS2 patients. As proof of principle, we determined that conditional inactivation of Mint, an inhibitor of Notch-RBP-J interaction, resulted in a moderate rescue of Notch2 null kidneys, implying that temporal blockage of Notch signaling inhibitors downstream of receptor activation may have therapeutic benefits for ALGS patients. (C) 2009 Elsevier Inc. All rights reserved. C1 [Surendran, Kameswaran; Boyle, Scott; Barak, Hila; Stomberski, Colin; Kopan, Raphael] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA. [Kim, Mijin] Univ Chicago, Dept Organismal Biol & Anat, Chicago, IL 60615 USA. [McCright, Brent] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Kopan, R (reprint author), Washington Univ, Sch Med, Dept Dev Biol, 660 S Euclid Ave, St Louis, MO 63110 USA. EM kopan@wustl.edu FU Digestive Diseases Research Core Center, NIH [P30DK052574]; NCI Cancer Center [P30 CA91842]; National Institutes of Diabetes and Digestive and Kidney Disease [DK066408]; O'brien Center [5P30DK07933]; institutional training grant [5T32DK007126] FX We thank the histology core of the Department of Developmental Biology for preparation of tissue sections. We thank the Mouse Genetics Core and the Digestive Diseases Research Core Center (supported by NIH P30DK052574) for the generation of genetically altered mice. We thank Mary Blandford and Tao Shen for assistance with animal husbandry and mouse genotyping. We thank Dr. Tasuku Honjo for the Mint and RBP-J floxed mice. We thank Andrew McMahon for the Six2 antibody. We thank William Eades and Jacqueline Hughes in the Siteman Cancer Center High Speed Sorter Core Facility for performing cell-sorting segments of our experiments. The Siteman Cancer Center is supported in part by NCI Cancer Center Support Grant P30 CA91842. This work was supported by National Institutes of Diabetes and Digestive and Kidney Disease (DK066408) and the O'brien Center Grant (5P30DK07933). S.B. was supported by institutional training grant (5T32DK007126). NR 41 TC 28 Z9 28 U1 0 U2 1 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 JAN 15 PY 2010 VL 337 IS 2 BP 386 EP 395 DI 10.1016/j.ydbio.2009.11.017 PG 10 WC Developmental Biology SC Developmental Biology GA 548GO UT WOS:000273948300018 PM 19914235 ER PT J AU Ito, Y Qi, L AF Ito, Yoichiro Qi, Lin TI Centrifugal precipitation chromatography SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Review DE Centerifugal precipitation chromatography; Protein purification by ammonium sulfate; Rotary-seal-free flow-through centrifuge; Separation of proteins ID AMMONIUM-SULFATE; PREPARATIVE SEPARATION; PLASMID DNA; FRACTIONATION; PROTEIN; SOLUBILITY; RNA; TEA AB Centrifugal precipitation chromatography separates analytes according their solubility in ammonium sulfate(AS)solution and other precipitants. The separation column is made from a pair of long spiral channels partitioned with a semipermeable membrane. In a typical separation, concentrated ammonium sulfate is eluted through one channel while water is eluted through the other channel in the opposite direction This countercurrent process forms an exponential AS concentration gradient through the water channel. Consequently, protein samples injected into the water channel is subjected to a steadily increasing AS concentration and at the critical AS concentration they are precipitated and deposited in the channel bed by the centrifugal force Then the chromatographic separation is started by gradually reducing the AS concentration in the AS channel which lowers the AS gradient concentration in the water channel This results in dissolution of deposited proteins which are again precipitated at an advanced critical point as they move through the channel. Consequently, proteins repeat precipitation and dissolution through a long channel and finally eluted out front the column in the order of their solubility in the AS solution The present method has been successfully applied to a number of analytes including human serum proteins. recombinant ketosteroid isomerase, carotenoid cleavage enzymes, plasmid DNA, polysaccharide. polymerized pigments, PEG-protein conjugates. etc. The method is capable to single out the target species of proteins by affinity ligand or immunoaffinity separation. Published by Elsevier B.V. C1 [Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. [Qi, Lin] US FDA, CDER, OPS, Off New Drug Qual Assessment, Silver Spring, MD 20993 USA. RP Ito, Y (reprint author), NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, 10 Ctr Dr,Bldg 10,Room 8N230, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 HL001047-09] NR 20 TC 8 Z9 8 U1 4 U2 29 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 EI 1873-376X J9 J CHROMATOGR B JI J. Chromatogr. B PD JAN 15 PY 2010 VL 878 IS 2 SI SI BP 154 EP 164 DI 10.1016/j.jchromb.2009.05.055 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 551PG UT WOS:000274220900005 PM 19541553 ER PT J AU Klein, NP Gans, HA Sung, P Yasukawa, LL Johnson, J Sarafanov, A Chumakov, K Hansen, J Black, S Dekker, CL AF Klein, Nicola P. Gans, Hayley A. Sung, Phillip Yasukawa, Linda L. Johnson, Joanie Sarafanov, Andrey Chumakov, Konstantin Hansen, John Black, Steven Dekker, Cornelia L. TI Preterm Infants' T Cell Responses to Inactivated Poliovirus Vaccine SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ACELLULAR PERTUSSIS-VACCINE; HEPATITIS-B-VACCINE; FULL-TERM INFANTS; LOW-BIRTH-WEIGHT; PNEUMOCOCCAL CONJUGATE VACCINE; EXTREMELY PREMATURE-INFANTS; BACILLUS-CALMETTE-GUERIN; MEASLES-MUMPS-RUBELLA; IMMUNE-RESPONSE; FOLLOW-UP AB Background. The antigen-specific T cell responses of preterm infants to immunization are not well understood. The aim of the present study was to compare the T cell responses of preterm infants after inactivated poliovirus vaccination with those of term infants. Methods. We prospectively enrolled 2-month-old preterm (gestational age, <= 33 weeks) and term (gestational age, >= 37 weeks) infants to receive 3 doses of diphtheria-tetanus toxoids-acellular pertussis-hepatitis B virus-inactivated poliovirus vaccine. Whole blood and peripheral blood mononuclear cells (PBMCs) were stimulated with poliovirus vaccine, and memory T cell activation was analyzed by flow cytometry and lymphoproliferation, respectively. Levels of poliovirus neutralizing antibodies were measured in serum. Results. We enrolled 33 preterm and 50 term infants. Preterm infants had fewer circulating CD4(+)CD45RO(+) memory (P=.005) and CD4(+)CD69(+)IFN-gamma(+) cells activated by staphylococcus enterotoxin B at 2 (P=.015) and 7 (P=.05) months of age. After immunization, preterm and term infants had comparable frequencies of poliovirus-specific CD4(+)CD45RO(+)CD69(+)IFN-gamma(+) memory T cells (P=.79). PBMCs from preterm infants had diminished poliovirus-specific lymphoproliferation (P<.001). Although all infants developed seroprotective poliovirus antibody titers, serotype 1 titers were lower among preterm infants (P=.03). Conclusions. Preterm infants develop poliovirus-specific T cell responses that are comparable to those of term infants. However, they demonstrate nonspecific and poliovirus-specific functional T cell limitations, suggesting that investigations into whether T cell differences remain as preterm infants mature are warranted. C1 [Klein, Nicola P.; Johnson, Joanie; Hansen, John] Kaiser Permanente, Vaccine Study Ctr, Oakland, CA 94612 USA. [Klein, Nicola P.; Gans, Hayley A.; Sung, Phillip; Yasukawa, Linda L.; Dekker, Cornelia L.] Stanford Univ, Div Pediat Infect Dis, Sch Med, Stanford, CA 94305 USA. [Sarafanov, Andrey; Chumakov, Konstantin] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Black, Steven] Cincinnati Childrens Hosp, Ctr Global Hlth, Cincinnati, OH USA. RP Klein, NP (reprint author), Kaiser Permanente, Vaccine Study Ctr, 1 Kaiser Plaza,16th Floor, Oakland, CA 94612 USA. EM Nicola.Klein@kp.org FU Centers for Disease Control and Prevention (CDC); America's Health Insurance Plans Vaccine Safety Fellowship program FX This study was funded by the Centers for Disease Control and Prevention (CDC). N. P. K. received support for this study from the CDC through an agreement with the America's Health Insurance Plans Vaccine Safety Fellowship program. NR 46 TC 12 Z9 14 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 15 PY 2010 VL 201 IS 2 BP 214 EP 222 DI 10.1086/649590 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 536NN UT WOS:000273051200008 PM 20017631 ER PT J AU Umbach, JL Wang, K Tang, S Krause, PR Mont, EK Cohen, JI Cullen, BR AF Umbach, Jennifer L. Wang, Kening Tang, Shuang Krause, Philip R. Mont, Erik K. Cohen, Jeffrey I. Cullen, Bryan R. TI Identification of Viral MicroRNAs Expressed in Human Sacral Ganglia Latently Infected with Herpes Simplex Virus 2 SO JOURNAL OF VIROLOGY LA English DT Article ID HERPES-SIMPLEX-VIRUS-1; SEQUENCE AB Deep sequencing of small RNAs isolated from human sacral ganglia latently infected with herpes simplex virus 2 (HSV-2) was used to identify HSV-2 microRNAs (miRNAs) expressed during latent infection. This effort resulted in the identification of five distinct HSV-2 miRNA species, two of which, miR-H3/miR-I and miR-H4/miR-II, have been previously reported. Three novel HSV-2 miRNAs were also identified, and two of these, miR-H7 and miR-H9, are derived from the latency-associated transcript (LAT) and are located antisense to the viral transcript encoding transactivator ICP0. A third novel HSV-2 miRNA, miR-H10, is encoded within the unique long (U(L)) region of the genome, 3' to the U(L)15 open reading frame, and is presumably excised from a novel, latent HSV-2 transcript distinct from LAT. C1 [Umbach, Jennifer L.; Cullen, Bryan R.] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. [Umbach, Jennifer L.; Cullen, Bryan R.] Duke Univ, Med Ctr, Ctr Virol, Durham, NC 27710 USA. [Wang, Kening; Cohen, Jeffrey I.] NIAID, Med Virol Sect, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Tang, Shuang; Krause, Philip R.] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Off Vaccines Res & Review, Bethesda, MD 20892 USA. [Mont, Erik K.] Miami Dade Cty Med Examiner Dept, Miami, FL 33136 USA. RP Cullen, BR (reprint author), Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. EM bryan.cullen@duke.edu RI Tang, Shuang/F-9115-2014; OI Tang, Shuang/0000-0002-3084-0903; Krause, Philip/0000-0002-1045-7536 FU National Institute of Allergy and Infectious Diseases [AI067968]; National Institute of Allergy and Infectious Diseases; National Cancer Institute [T32-CA009111] FX This work was supported by Public Health Service grant AI067968 from the National Institute of Allergy and Infectious Diseases to B. R. C. and the intramural research program of the National Institute of Allergy and Infectious Diseases. J. L. U. was supported by NIH training grant T32-CA009111 from the National Cancer Institute. NR 14 TC 35 Z9 43 U1 2 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN 15 PY 2010 VL 84 IS 2 BP 1189 EP 1192 DI 10.1128/JVI.01712-09 PG 4 WC Virology SC Virology GA 535TN UT WOS:000272994300049 PM 19889786 ER PT J AU Rosada, RS Moreira, AP Frantz, FG Puri, RK Rahman, A Standiford, TJ Zarate-Blades, CR Silva, CL Hogaboam, CM AF Rosada, Rogerio S. Moreira, Ana P. Frantz, Fabiani G. Puri, Raj K. Rahman, Aquilur Standiford, Theodore J. Zarate-Blades, Carlos R. Silva, Celio L. Hogaboam, Cory M. TI Therapeutic Efficacy of Cintredekin Besudotox (IL13-PE38QQR) in Murine Lung Fibrosis Is Unaffected by Immunity to Pseudomonas aeruginosa Exotoxin A SO PLOS ONE LA English DT Article ID INDUCED PULMONARY-FIBROSIS; PARACOCCIDIOIDES-BRASILIENSIS CONIDIA; ALLERGIC AIRWAY DISEASE; RECEPTOR ALPHA-2 CHAIN; IL-13 RECEPTOR; INTERLEUKIN-13 RECEPTOR; CHIMERIC PROTEIN; CARCINOMA-CELLS; PERIBRONCHIAL FIBROSIS; SIGNAL-TRANSDUCTION AB Background: We have previously explored a therapeutic strategy for specifically targeting the profibrotic activity of IL-13 during experimental pulmonary fibrosis using a fusion protein comprised of human IL-13 and a mutated form of Pseudomonas aeruginosa exotoxin A (IL13-PE) and observed that the intranasal delivery of IL13-PE reduced bleomycin-induced pulmonary fibrosis through its elimination of IL-13-responsive cells in the lung. The aim of the present study was to determine whether the presence of an immune response to P. aeruginosa and/or its exotoxin A (PE) would diminish the anti-fibrotic properties of IL13-PE. Methodology/Principal Findings: Fourteen days after P. aeruginosa infection, C57BL/6 mice were injected with bleomycin via the intratracheal route. Other groups of mice received 4 doses of saline or IL13-PE by either intranasal or intraperitoneal application, and were challenged i.t. with bleomycin 28 days later. At day 21 after bleomycin, all mice received either saline vehicle or IL13-PE by the intranasal route and histopatological analyses of whole lung samples were performed at day 28 after bleomycin. Intrapulmonary P. aeruginosa infection promoted a neutralizing IgG2A and IgA antibody response in BALF and serum. Surprisingly, histological analysis showed that a prior P. aeruginosa infection attenuated the development of bleomycin-induced pulmonary fibrosis, which was modestly further attenuated by the intranasal administration of IL13-PE. Although prior intranasal administration of IL13-PE failed to elicit an antibody response, the systemic administration of IL13-PE induced a strong neutralizing antibody response. However, the prior systemic sensitization of mice with IL13-PE did not inhibit the anti-fibrotic effect of IL13-PE in fibrotic mice. Conclusions: Thus, IL13-PE therapy in pulmonary fibrosis works regardless of the presence of a humoral immune response to Pseudomonas exotoxin A. Interestingly, a prior infection with P. aeruginosa markedly attenuated the pulmonary fibrotic response suggesting that the immune elicitation by this pathogen exerts anti-fibrotic effects. C1 [Rosada, Rogerio S.; Frantz, Fabiani G.; Zarate-Blades, Carlos R.; Silva, Celio L.] Univ Sao Paulo, Dept Bioquim & Imunol, Nucleo Pesquisa Tuberculose, Sao Paulo, Brazil. [Moreira, Ana P.; Hogaboam, Cory M.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. [Standiford, Theodore J.] Univ Michigan, Sch Med, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA. [Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Bethesda, MD 20014 USA. [Rahman, Aquilur] NeoPharm Inc, Lake Bluff, IL USA. RP Rosada, RS (reprint author), Univ Sao Paulo, Dept Bioquim & Imunol, Nucleo Pesquisa Tuberculose, Sao Paulo, Brazil. EM hogaboam@umich.edu RI Rosada, Rogerio/B-1396-2010; hogaboam, cory /M-3578-2014; Zarate-Blades, Carlos/C-9663-2015; Silva, Celio/C-4639-2012; Frantz, Fabiani/B-9204-2016 OI Zarate-Blades, Carlos/0000-0002-7728-7869; Frantz, Fabiani/0000-0001-6960-2438 FU National Institutes of Health (NIH); Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP); NeoPharm, Inc FX Funding: These studies were supported by funding provided by the National Institutes of Health (NIH), the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), and NeoPharm, Inc. Neither the NIH nor the FAPESP had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Aquil Rahman is an employee of NeoPharm, Inc., and he was involved in the design of the experiments reported in this manuscript. Neither he nor NeoPharm, Inc. had any role in data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 5 Z9 6 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 15 PY 2010 VL 5 IS 1 AR e8721 DI 10.1371/journal.pone.0008721 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 545EI UT WOS:000273714900003 PM 20090941 ER PT J AU Deisseroth, A Farrell, A Justice, R Kane, R Sridhara, R Chen, HY He, K Pazdur, R AF Deisseroth, Albert Farrell, Ann Justice, Robert Kane, Robert Sridhara, Rajeshwari Chen, Huanyu He, Kun Pazdur, Richard TI Toxicity of laromustine plus high-dose cytarabine in patients with relapsed acute myeloid leukemia SO BLOOD LA English DT Letter C1 [Deisseroth, Albert; Farrell, Ann; Justice, Robert; Kane, Robert; Sridhara, Rajeshwari; Chen, Huanyu; He, Kun; Pazdur, Richard] US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Deisseroth, A (reprint author), US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Rm 6378, Silver Spring, MD 20993 USA. EM albert.deisseroth@yahoo.com NR 1 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 14 PY 2010 VL 115 IS 2 BP 430 EP 430 DI 10.1182/blood-2009-09-244236 PG 1 WC Hematology SC Hematology GA 544AE UT WOS:000273622600036 PM 20075171 ER PT J AU Wang, YS Jester, ELE El Said, KR Abraham, A Hooe-Rollman, J Plakas, SM AF Wang, Yuesong Jester, Edward L. E. El Said, Kathleen R. Abraham, Ann Hooe-Rollman, Jennifer Plakas, Steven M. TI Cyano Metabolite as a Biomarker of Nitrofurazone in Channel Catfish SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Nitrofurazone; channel catfish; LC-MS; biomarker; cyano metabolite ID TISSUE-BOUND METABOLITES; SEMICARBAZIDE; FURAZOLIDONE; MICROSOMES; DEPLETION; SWINE; FOOD AB The use of nitrofuran drugs in food-producing animals continues to attract international concern as a food safety issue. Methods for monitoring nitrofuran residues have been directed to the intact side chain of tissue-bound metabolites. Semicarbazide, the side chain of nitrofurazone (NFZ), can enter food products from non-NFZ sources, suggesting the need for an alternative biomarker for confirmatory purposes. We characterized a cyano derivative as a major metabolite of NFZ in channel catfish (Ictalurus punctatus). The depletion of cyano metabolite was examined in the muscle of channel catfish after oral dosing (10 mg of NFZ/kg of body weight). Parent NFZ was rapidly eliminated in muscle, with a half-life of 6.3 h. The cyano, metabolite was detected for up to 2 weeks, with an elimination half-life of 81 h. The cyano, metabolite represents an alternative biomarker for confirming the use of NFZ in channel catfish. C1 [Wang, Yuesong; Jester, Edward L. E.; El Said, Kathleen R.; Abraham, Ann; Hooe-Rollman, Jennifer; Plakas, Steven M.] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Wang, YS (reprint author), US FDA, Gulf Coast Seafood Lab, POB 158,1 Iberville Dr, Dauphin Isl, AL 36528 USA. EM yuesong.wang@fda.hhs.gov NR 18 TC 13 Z9 13 U1 1 U2 11 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 JAN 13 PY 2010 VL 58 IS 1 BP 313 EP 316 DI 10.1021/jf902743a PG 4 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 539PJ UT WOS:000273268100042 PM 19950980 ER PT J AU Pos, Z Selleri, S Spivey, TL Wang, JK Liu, H Worschech, A Sabatino, M Monaco, A Leitman, SF Falus, A Wang, E Alter, HJ Marincola, FM AF Pos, Zoltan Selleri, Silvia Spivey, Tara L. Wang, Jeanne K. Liu, Hui Worschech, Andrea Sabatino, Marianna Monaco, Alessandro Leitman, Susan F. Falus, Andras Wang, Ena Alter, Harvey J. Marincola, Francesco M. TI Genomic scale analysis of racial impact on response to IFN-alpha SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE African-American; European American; microarray; signal transducers and activators of transcription; hepatitis C virus ID CHRONIC HEPATITIS-C; GENETIC-VARIATION; VIRUS-INFECTION; INTERFERON; RIBAVIRIN; THERAPY; IL28B; ASSOCIATION; MECHANISMS; CLEARANCE AB Limited responsiveness to IFN-alpha in hepatitis C virus (HCV)-infected African-Americans compared to European Americans (AAs vs. EAs) hinders the management of HCV. Here, we studied healthy non-HCV-infected AA and EA subjects to test whether immune cell response to IFN-alpha is determined directly by race. We compared baseline and IFN-alpha-induced signal transducer and activator of transcription (STAT)-1, STAT-2, STAT-3, STAT-4, and STAT-5 protein and phosphorylation levels in purified T cells, global transcription, and a genomewide single-nucleotide polymorphism (SNP) profile of healthy AA and EA blood donors. In contrast to HCV-infected individuals, healthy AAs displayed no evidence of reduced STAT activation or IFN-alpha-stimulated gene expression compared to EAs. Although >200 genes reacted to IFN-alpha treatment, race had no impact on any of them. The only gene differentially expressed by the two races (NUDT3, P < 10(-7)) was not affected by IFN-alpha and bears no known relationship to IFN-alpha signaling or HCV pathogenesis. Genomewide analysis confirmed the self-proclaimed racial attribution of most donors, and numerous race-associated SNPs were identified within loci involved in IFN-alpha signaling, although they clearly did not affect responsiveness in the absence of HCV. We conclude that racial differences observed in HCV-infected patients in the responsiveness to IFN-alpha are unrelated to inherent racial differences in IFN-alpha signaling and more likely due to polymorphisms affecting the hosts' response to HCV, which in turn may lead to a distinct disease pathophysiology responsible for altered IFN signaling and treatment response. C1 [Pos, Zoltan; Spivey, Tara L.; Liu, Hui; Monaco, Alessandro; Wang, Ena; Alter, Harvey J.; Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Pos, Zoltan; Spivey, Tara L.; Liu, Hui; Monaco, Alessandro; Wang, Ena; Alter, Harvey J.; Marincola, Francesco M.] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA. [Selleri, Silvia] Sci Inst HS Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy. [Wang, Jeanne K.] US FDA, Div Med Imaging & Hematol Prod, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Worschech, Andrea] Genelux Corp, San Diego Sci Ctr, San Diego, CA 92109 USA. [Worschech, Andrea] Univ Wurzburg, Inst Biochem, Virchow Ctr Expt Biomed, D-97074 Wurzburg, Germany. [Worschech, Andrea] Univ Wurzburg, Inst Mol Infect Biol, D-97074 Wurzburg, Germany. [Sabatino, Marianna] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Leitman, Susan F.] NIH, Blood Serv Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Falus, Andras] Semmelweis Univ, Dept Genet Cell & Immunobiol, H-1089 Budapest, Hungary. [Falus, Andras] Semmelweis Univ, Hungarian Acad Sci, Inflammat Biol & Immungenom Res Grp, H-1089 Budapest, Hungary. RP Pos, Z (reprint author), NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bldg 10,R1C711,9000 Rockville Pike, Bethesda, MD 20892 USA. EM posz@cc.nih.gov; HAlter@cc.nih.gov; Fmarincola@mail.cc.nih.gov RI Worschech, Andrea/I-3919-2012; Pos, Zoltan/C-3623-2014; Monaco, Alessandro/O-5338-2015 OI Worschech, Andrea/0000-0002-4303-8653; Pos, Zoltan/0000-0002-2574-7616; Monaco, Alessandro/0000-0002-9941-7003 NR 20 TC 11 Z9 12 U1 0 U2 0 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 JAN 12 PY 2010 VL 107 IS 2 BP 803 EP 808 DI 10.1073/pnas.0913491107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 543FY UT WOS:000273559300053 PM 20080756 ER PT J AU Sahu, G Wang, DF Chen, CB Zhurkin, VB Harrington, RE Appella, E Hager, GL Nagaich, AK AF Sahu, Geetaram Wang, Difei Chen, Claudia B. Zhurkin, Victor B. Harrington, Rodney E. Appella, Ettore Hager, Gordon L. Nagaich, Akhilesh K. TI p53 Binding to Nucleosomal DNA Depends on the Rotational Positioning of DNA Response Element SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR; GLUCOCORTICOID-RECEPTOR; TUMOR-SUPPRESSOR; CRYSTAL-STRUCTURE; IN-VITRO; STRUCTURAL BASIS; SWI/SNF COMPLEX; DOMAIN PEPTIDES; CORE DOMAIN; PROTEIN AB The sequence-specific binding to DNA is crucial for the p53 tumor suppressor function. To investigate the constraints imposed on p53-DNA recognition by nucleosomal organization, we studied binding of the p53 DNA binding domain (p53DBD) and full-length wild-type p53 protein to a single p53 response element (p53RE) placed near the nucleosomal dyad in six rotational settings. We demonstrate that the strongest p53 binding occurs when the p53RE in the nucleosome is bent in the same direction as observed for the p53-DNA complexes in solution and in co-crystals. The p53RE becomes inaccessible, however, if its orientation in the core particle is changed by similar to 180 degrees. Our observations indicate that the orientation of the binding sites on a nucleosome may play a significant role in the initial p53-DNA recognition and subsequent cofactor recruitment. C1 [Nagaich, Akhilesh K.] US FDA, Chem Lab, Div Therapeut Prot, OBP,OPS,CDER, Bethesda, MD 20892 USA. [Wang, Difei; Zhurkin, Victor B.; Appella, Ettore] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. [Harrington, Rodney E.] Arizona State Univ, Dept Microbiol, Tempe, AZ 85287 USA. RP Nagaich, AK (reprint author), US FDA, Chem Lab, Div Therapeut Prot, OBP,OPS,CDER, 29 Lincoln Dr, Bethesda, MD 20892 USA. EM akhilesh.nagaich@fda.hhs.gov RI Wang, Difei/E-7066-2010 FU Oak Ridge Institute for Science and Education through an intraagency agreement between the United States Department of Energy and the United States Food and Drug Administration; National Institutes of Health [R01 CA 70274]; National Cancer Institute; Center for Cancer Research FX This work was supported, in whole or in part, by an appointment of G. Sahu to the Postgraduate Research Program at the Center for Drug Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an intraagency agreement between the United States Department of Energy and the United States Food and Drug Administration. This work was also supported in part by National Institutes of Health Grant R01 CA 70274 (to R.E.H.) and by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 57 TC 20 Z9 20 U1 1 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 JAN 8 PY 2010 VL 285 IS 2 BP 1321 EP 1332 DI 10.1074/jbc.M109.081182 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 539MH UT WOS:000273258200053 PM 19887449 ER PT J AU He, Y Meseda, CA Vassell, RA Merchlinsky, M Weir, JP Weiss, CD AF He, Yong Meseda, Clement A. Vassell, Russell A. Merchlinsky, Michael Weir, Jerry P. Weiss, Carol D. TI Recombinant A27 protein synergizes with modified vaccinia Ankara in conferring protection against a lethal vaccinia virus challenge SO VACCINE LA English DT Article DE A27 protein; Modified vaccinia Ankara; Smallpox vaccine ID NEUTRALIZING MONOCLONAL-ANTIBODIES; SURFACE HEPARAN-SULFATE; SMALLPOX VACCINE; IN-VITRO; CPG OLIGODEOXYNUCLEOTIDES; POXVIRUS CHALLENGE; NONHUMAN-PRIMATES; ENVELOPE PROTEIN; MICE; MONKEYPOX AB Highly attenuated modified vaccinia virus Ankara (MVA) is being considered as a safer alternative to conventional smallpox vaccines such as Dryvax or ACAM 2000, but it requires higher doses or more-frequent boosting than replication-competent Dryvax. Previously. we found that passive transfer of A27 antibodies can enhance protection afforded by vaccinia immune globulin (VIG), which is derived from Dryvax immunized subjects. Here we investigated whether protective immunity elicited by MVA could be augmented by prime-boost or combination immunizations with a recombinant A27 (rA27) protein We found that a prime/boost immunization regimen with rA27 protein and MVA, in either sequence order, conferred protection to mice challenged with a lethal dose of vaccinia virus strain Western Reserve (VV-WR), compared to no protection after immunizations with a similar dose of either MVA or rA27 alone. Moreover, protection was achieved in mice primed simultaneously with combination of both MVA and rA27 in different vaccination routes, without any boost. even though MVA or rA27 alone at the same dose gave no protection. These findings show that rA27 can synergize with MVA to elicit robust protection that has a dose-sparing effect on MVA and can accelerate protection by eliminating the need for a booster dose Published by Elsevier Ltd C1 [He, Yong; Meseda, Clement A.; Vassell, Russell A.; Merchlinsky, Michael; Weir, Jerry P.; Weiss, Carol D.] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. RP Weiss, CD (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, HFM 466,29 Lincoln Dr, Bethesda, MD 20892 USA. RI Weiss, Carol/F-6438-2011 OI Weiss, Carol/0000-0002-9965-1289 FU FDA FX The authors thank Drs. Marina Zaitseva and Ira Berkower of the Center for Biologics Evaluation and Research (CBER) for critical reading of the manuscript and Dr. Konstantin Chumakov (CBER) for suggestions about the recombinant MVA experiment. The study was supported by institutional research funds from the FDA. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the FDA. NR 50 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JAN 8 PY 2010 VL 28 IS 3 BP 699 EP 706 DI 10.1016/j.vaccine.2009.10.078 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 561YE UT WOS:000275015200015 PM 19887133 ER PT J AU Hassantoufighi, A Zhang, H Sandbulte, M Gao, J Manischewitz, J King, L Golding, H Straight, TM Eichelberger, MC AF Hassantoufighi, Arash Zhang, Henry Sandbulte, Matthew Gao, Jin Manischewitz, Jody King, Lisa Golding, Hana Straight, Timothy M. Eichelberger, Maryna C. TI A practical influenza neutralization assay to simultaneously quantify hemagglutinin and neuraminidase-inhibiting antibody responses SO VACCINE LA English DT Article DE Influenza; Neutralization assay; Neuraminidase ID A H5N1 VIRUS; AVIAN INFLUENZA; POULTRY WORKERS; HONG-KONG; VACCINE; INFECTION; CHILDREN; LIVE; IMMUNOGENICITY; INTRANASAL AB Influenza vaccine immunogenicity is commonly assessed by determining hemagglutination inhibition (HAI) titers in serum samples. HAI titers have been used to predict vaccine efficacy, but this often fails when live attenuated vaccines are evaluated, because it does not encompass all immune mediators of protection. Although antibodies that inhibit viral neuraminidase (NA) also contribute to protection against disease, there is currently no routine assessment of NA inhibition titers. A serological method with the capacity to measure functional inhibition of both HA and NA would be valuable We developed a high-throughput virus neutralization assay that uses viral NA activity to quantify influenza replication (the AVINA assay), and showed its capacity to identify antivirals with a broad range of target specificities In this report we demonstrate that antibodies with specificity for either HA or NA are detected in this assay, whereas a commonly used virus neutralization assay only detects those with HA-specificity. We also compared human responses to seasonal influenza vaccines measured by HAI, micro-neutralization, NA inhibition and AVINA assays. The response rates to both trivalent inactivated and live attenuated vaccines were greater when measured by the AVINA than the other assays, reflecting the dual antigen reactivity and increased sensitivity of the assay The potential of this single assay to predict protection against influenza-induced tachypnea was demonstrated in vaccinated cotton rats. The AVINA assay is therefore a practical, comprehensive method to determine influenza vaccine immunogenicity and potential efficacy. Published by Elsevier Ltd. C1 [Hassantoufighi, Arash; Zhang, Henry; Sandbulte, Matthew; Gao, Jin; Manischewitz, Jody; King, Lisa; Golding, Hana; Eichelberger, Maryna C.] US FDA, Div Viral Prod, CBER, Off Vaccine Res & Review, Bethesda, MD 20892 USA. [Straight, Timothy M.] Brooke Army Med Ctr, Dept Clin Invest, Ft Sam Houston, TX 78234 USA. RP Eichelberger, MC (reprint author), US FDA, Div Viral Prod, CBER, Off Vaccine Res & Review, 8800 Rockville Pike,Bldg 29A,Room 1D24, Bethesda, MD 20892 USA. NR 27 TC 34 Z9 34 U1 1 U2 7 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 JAN 8 PY 2010 VL 28 IS 3 BP 790 EP 797 DI 10.1016/j.vaccine.2009.10.066 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 561YE UT WOS:000275015200026 PM 19887135 ER PT J AU George, NI Lupton, JR Turner, ND Chapkin, RS Davidson, LA Wang, NS AF George, Nysia I. Lupton, Joanne R. Turner, Nancy D. Chapkin, Robert S. Davidson, Laurie A. Wang, Naisyin TI Evaluation of fecal mRNA reproducibility via a marginal transformed mixture modeling approach SO BMC BIOINFORMATICS LA English DT Article AB Background: Developing and evaluating new technology that enables researchers to recover gene-expression levels of colonic cells from fecal samples could be key to a non-invasive screening tool for early detection of colon cancer. The current study, to the best of our knowledge, is the first to investigate and report the reproducibility of fecal microarray data. Using the intraclass correlation coefficient (ICC) as a measure of reproducibility and the preliminary analysis of fecal and mucosal data, we assessed the reliability of mixture density estimation and the reproducibility of fecal microarray data. Using Monte Carlo-based methods, we explored whether ICC values should be modeled as a beta-mixture or transformed first and fitted with a normal-mixture. We used outcomes from bootstrapped goodness-of-fit tests to determine which approach is less sensitive toward potential violation of distributional assumptions. Results: The graphical examination of both the distributions of ICC and probit transformed ICC (PT ICC) clearly shows that there are two components in the distributions. For ICC measurements, which are between 0 and 1, the practice in literature has been to assume that the data points are from a beta-mixture distribution. Nevertheless, in our study we show that the use of a normal-mixture modeling approach on PT-ICC could provide superior performance. Conclusions: When modeling ICC values of gene expression levels, using mixture of normals in the probit-transformed (PT) scale is less sensitive toward model mis-specification than using mixture of betas. We show that a biased conclusion could be made if we follow the traditional approach and model the two sets of ICC values using the mixture of betas directly. The problematic estimation arises from the sensitivity of beta-mixtures toward model mis-specification, particularly when there are observations in the neighborhood of the the boundary points, 0 or 1. Since beta-mixture modeling is commonly used in approximating the distribution of measurements between 0 and 1, our findings have important implications beyond the findings of the current study. By using the normal-mixture approach on PT-ICC, we observed the quality of reproducible genes in fecal array data to be comparable to those in mucosal arrays. C1 [Wang, Naisyin] Univ Michigan, Dept Stat, Ann Arbor, MI 48109 USA. [George, Nysia I.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Lupton, Joanne R.; Turner, Nancy D.; Chapkin, Robert S.; Davidson, Laurie A.] Texas A&M Univ, Program Integrat Nutr & Complex Dis, College Stn, TX 77843 USA. RP Wang, NS (reprint author), Univ Michigan, Dept Stat, Ann Arbor, MI 48109 USA. EM nwangstat@gmail.com OI Chapkin, Robert/0000-0002-6515-3898 FU US NCI [CA74552, CA59034, CA129444]; NSBRI [NASA NCC 9-58] FX This work is supported by grants from US NCI CA74552, CA59034, CA129444 and NSBRI (NASA NCC 9-58). NR 19 TC 0 Z9 0 U1 0 U2 0 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 JAN 7 PY 2010 VL 11 AR 13 DI 10.1186/1471-2105-11-13 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 564FM UT WOS:000275198700002 PM 20055994 ER PT J AU Ou, W King, H Delisle, J Shi, DS Wilson, CA AF Ou, Wu King, Harlan Delisle, Josie Shi, Dashuang Wilson, Carolyn A. TI Phenylalanines at positions 88 and 159 of Ebolavirus envelope glycoprotein differentially impact envelope function SO VIROLOGY LA English DT Article DE Ebolavirus; Envelope glycoprotein; Viral entry; Mutagenesis ID FOLATE RECEPTOR-ALPHA; VIRUS GLYCOPROTEIN; CELLULAR ENTRY; DC-SIGN; INFECTION; BINDING; RESIDUES; ANTIBODY; IDENTIFICATION; PROTEOLYSIS AB The envelope glycoprotein (GP) of Ebolavirus (EBOV) mediates viral entry into host cells. Through mutagenesis, we and other groups reported that two phenylalanines at positions 88 and 159 of GP are critical for viral entry. However, it remains elusive which steps of viral entry are impaired by F88 or F159 mutations and how. In this study, we further characterized these two phenylalanines through mutagenesis and examined the impact on GP expression, function, and structure. Our data Suggest that F159 plays an indirect role in viral entry by maintaining EBOV GP's overall structure. In contrast, we did not detect any evidence for conformational differences in GP with F88 mutations. The data suggest that F88 influences viral entry during a step after cathepsin processing, presumably impacting viral fusion. Published by Elsevier Inc. C1 [Ou, Wu; King, Harlan; Delisle, Josie; Wilson, Carolyn A.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Shi, Dashuang] George Washington Univ, Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA. RP Wilson, CA (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bldg 29B,Room 5NN22,8800 Rockville Pike, Bethesda, MD 20892 USA. EM carolyn.wilson@fda.hhs.gov NR 27 TC 6 Z9 6 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 5 PY 2010 VL 396 IS 1 BP 135 EP 142 DI 10.1016/j.virol.2009.10.028 PG 8 WC Virology SC Virology GA 531EX UT WOS:000272647600015 PM 19906395 ER PT J AU Ausin, C Kauffman, JS Duff, RJ Shivaprasad, S Beaucage, SL AF Ausin, Cristina Kauffman, Jon S. Duff, Robert J. Shivaprasad, Shankaramma Beaucage, Serge L. TI Assessment of heat-sensitive thiophosphate protecting groups in the development of thermolytic DNA oligonucleotide prodrugs SO TETRAHEDRON LA English DT Article ID SOLID-PHASE SYNTHESIS; CONTROLLED-PORE GLASS; PROOLIGONUCLEOTIDE APPROACH; BACTERIAL-DNA; PHOSPHOROTHIOATES; OLIGODEOXYRIBONUCLEOTIDES; PHOSPHODIESTER; REVERSIBILITY; CLEAVAGE; REAGENT AB Heat-sensitive thiophosphate protecting groups derived from the alcohol 4 or 10 have provided insights in the design of DNA oligonucleotide prodrugs. Indeed, functional groups stemming from the alcohol 9, 15, 16 or 22 may be applicable to thiophosphate protection of immunostimulatory CpG DNA motifs, whereas those originating from the alcohol 3, 5,12,13,18, 20 or 22 offer adequate protection of terminal phosphodiester functions against ubiquitous exonucleases that may be found in biological environments. Functional groups derived from the alcohol 9, 15, 16, 19 or 23 are suitable for the protection of phosphodiester functions flanking the CpG motifs of immunomodulatory DNA sequences. Published by Elsevier Ltd. C1 [Ausin, Cristina; Beaucage, Serge L.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Kauffman, Jon S.; Duff, Robert J.; Shivaprasad, Shankaramma] Lancaster Labs, Lancaster, PA 17605 USA. RP Beaucage, SL (reprint author), US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM serge.beaucage@fda.hhs.gov FU 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; Proteomics and Mass Spectrometry Facility; NIDDK; NIH FX This research is supported in part by an appointment to the Postgraduate Research Participation Program at the Center for Drug Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. We acknowledge the assistance of Dr. John Lloyd (Proteomics and Mass Spectrometry Facility, NIDDK, NIH) who kindly performed'the accurate mass determination of 6, 7, 18, 19, and 22. NR 45 TC 16 Z9 16 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD JAN 2 PY 2010 VL 66 IS 1 BP 68 EP 79 DI 10.1016/j.tet.2009.10.096 PG 12 WC Chemistry, Organic SC Chemistry GA 536TH UT WOS:000273066200003 ER PT J AU Ilev, I AF Ilev, Ilko GP IEEE TI Innovative Combined Sensing and Imaging Approaches in Biophotonics SO 2010 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) AND QUANTUM ELECTRONICS AND LASER SCIENCE CONFERENCE (QELS) LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO)/Quantum Electronics and Laser Science Conference (QELS) CY MAY 16-21, 2010 CL San Jose, CA AB Using simple fiber-optic based approaches, we have developed some advanced biophotonics and nanobiophotonics combined imaging and sensing techniques that can be exploited for high-resolution bioimaging and biosensing at cellular, intracellular and bulk tissue level. (C)2010 Optical Society of America C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. RP Ilev, I (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. EM ilko.ilev@eob.cdrh.fda.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-55752-890-2 PY 2010 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BUW45 UT WOS:000290513600017 ER PT J AU Zhang, K Katz, E Kim, DH Kang, JU Ilev, IK AF Zhang, Kang Katz, Elizabeth Kim, Do-Hyun Kang, Jin U. Ilev, Ilko K. GP IEEE TI A Fiber-Optic Nerve Stimulation Probe Integrated with a Precise Common-Path Optical Coherence Tomography Distance Sensor SO 2010 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) AND QUANTUM ELECTRONICS AND LASER SCIENCE CONFERENCE (QELS) LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO)/Quantum Electronics and Laser Science Conference (QELS) CY MAY 16-21, 2010 CL San Jose, CA AB We have demonstrated a simple and effective common-path optical coherence tomography guided fiber probe for optical nerve stimulation which improves the spatial precision and safety of stimulation laser power delivery. (C) 2010 Optical Society of America C1 [Zhang, Kang; Kang, Jin U.] Johns Hopkins Univ, Dept Elect & Comp Engn, 3400 N Charles St, Baltimore, MD 21218 USA. [Katz, Elizabeth; Kim, Do-Hyun; Ilev, Ilko K.] Ctr Devices & Radiol Hlth, US Food & Drug Adm, 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 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-55752-890-2 PY 2010 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BUW45 UT WOS:000290513601351 ER PT J AU Zhang, K Akpek, E Weiblinger, RP Kim, DH Kang, JU Ilev, IK AF Zhang, Kang Akpek, Esen Weiblinger, Richard P. Kim, Do-Hyun Kang, Jin U. Ilev, Ilko K. GP IEEE TI Post-Surgical Volumetric Evaluation of Clear Corneal Incision Quality Using a High-Resolution 3-D Spectral-Domain Optical Coherence Tomography SO 2010 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) AND QUANTUM ELECTRONICS AND LASER SCIENCE CONFERENCE (QELS) LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO)/Quantum Electronics and Laser Science Conference (QELS) CY MAY 16-21, 2010 CL San Jose, CA AB A novel approach for post-surgical volumetric evaluation of the quality of corneal incisions and wound healing is presented. It is based on high-resolution 3-D spectral-domain optical coherence tomography providing both multiple-cross-sectional and volumetric images. (C)2010 Optical Society of America C1 [Zhang, Kang; Kang, Jin U.] Johns Hopkins Univ, Dept Elect & Comp Engn, 3400 N Charles St, Baltimore, MD 21218 USA. [Zhang, Kang; Weiblinger, Richard P.; Kim, Do-Hyun; Ilev, Ilko K.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Akpek, Esen] Johns Hopkins Univ Hosp, Wilmer Eye Inst \, Baltimore, MD 21287 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 3 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-55752-890-2 PY 2010 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BUW45 UT WOS:000290513600010 ER PT S AU Wang, SJ Petrick, N Van Uitert, RL Periaswamy, S Summers, RM AF Wang, Shijun Petrick, Nicholas Van Uitert, Robert L. Periaswamy, Senthil Summers, Ronald M. GP IEEE TI GRAPH MATCHING BASED ON MEAN FIELD THEORY SO 2010 IEEE INTERNATIONAL CONFERENCE ON IMAGE PROCESSING SE IEEE International Conference on Image Processing ICIP LA English DT Proceedings Paper CT IEEE International Conference on Image Processing CY SEP 26-29, 2010 CL Hong Kong, PEOPLES R CHINA SP IEEE, IEEE Signal Proc Soc DE graph matching; spin model; mean field theory; Computed tomographic colonography ID ALGORITHM AB In this paper, we propose a new graph matching algorithm based on mean field theory. We first convert the original graph matching problem which is a quadratic integer programming problem to a spin model with quadratic interaction by dropping the matching constraints. Then the matching constraints are added to the system iteratively after each round of mean field calculation. Prominent matching pairs found in previous iterations will guide the mean field calculation in the next round. Experiments on the CMU house dataset and a CTC dataset show promising matching results. C1 [Wang, Shijun; Summers, Ronald M.] Hlth Clin Ctr, Imaging Biomarkers & Comp Aided Diag Lab, Natl Inst, Bldg 10 Room 1C368X MSC 1182, Bethesda, MD 20892 USA. [Petrick, Nicholas] Ctr Devices & Radiol Health, US Food & Drug Adm, Silver Spring, MD 20993 USA. [Van Uitert, Robert L.; Periaswamy, Senthil] ICAD Inc, Nashua, NH 03062 USA. RP Summers, RM (reprint author), Hlth Clin Ctr, Imaging Biomarkers & Comp Aided Diag Lab, Natl Inst, Bldg 10 Room 1C368X MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov FU NIH Clinical Center; U.S. Food and Drug Administration (NP) FX This research was supported by the Intramural Research Programs of the NIH Clinical Center and the U.S. Food and Drug Administration (NP). We thank Drs. Perry Pickhardt,J. Richard Choi and William Schindler for providing CT colonography data. NR 10 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1522-4880 BN 978-1-4244-7994-8 J9 IEEE IMAGE PROC PY 2010 BP 1893 EP 1896 DI 10.1109/ICIP.2010.5652432 PG 4 WC Engineering, Electrical & Electronic; Imaging Science & Photographic Technology SC Engineering; Imaging Science & Photographic Technology GA BTP82 UT WOS:000287728001244 ER PT S AU Popescu, LM AF Popescu, Lucretiu M. GP IEEE TI Image quality evaluation using automatic image scanning and a novel nonparametric free-response data analysis method. Application to PET energy based scatter correction evaluation SO 2010 IEEE NUCLEAR SCIENCE SYMPOSIUM CONFERENCE RECORD (NSS/MIC) SE IEEE Nuclear Science Symposium Conference Record LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium (NSS)/Medical Imaging Conference (MIC)/17th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors CY OCT 30-NOV 06, 2010 CL Knoxville, TN SP Inst Elect & Elect Engineers, Nucl & Plasma Sci Soc, IEEE ID LOCALIZATION AB We present the application of a task-based image quality evaluation procedure that combines an automatic signal detection technique with a novel nonparametric free-response data analysis method. The procedure delivers an index measuring the detectability of signals at unknown locations, in a manner that requires only a small number of image samples, thus making it convenient for practical applications. We are using the free-response methodology, which allows for multiple marks to be retrieved from an image. An overall signal detectability metric is obtained by using an exponential transformation of the free-response operating characteristic (EFROC) curve. A nonparametric estimator with expressions for its variance calculations are presented. The procedure allows for scaling of the detectability index to any given image size, a property that makes it advantageous for application to phantom experiments in which multiple signals can be inserted, or have relatively large background volumes that can be scanned for false signals. Such experiments can provide substantial signal detectability information with only a few images. We apply this technique to evaluate an energy-based scatter estimation method for PET, which is used in conjunction with an image reconstruction algorithm that incorporates energy-dependent corrections for scatter and random coincidences [Phys. Med. Biol. 51 (2006) 2919-2937]. A comparison of PET time-of-flight (TOF) performance versus no-TOF is also presented. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Imaging & Appl Math, Silver Spring, MD 20993 USA. RP Popescu, LM (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Imaging & Appl Math, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM lucretiu.popescu@fda.hhs.gov NR 7 TC 0 Z9 0 U1 3 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 978-1-4244-9106-3 J9 IEEE NUCL SCI CONF R PY 2010 BP 3009 EP 3014 PG 6 WC Engineering, Electrical & Electronic; Nuclear Science & Technology; Physics, Applied SC Engineering; Nuclear Science & Technology; Physics GA BBB94 UT WOS:000306402903038 ER PT S AU Das, SS Schwerin, M Walsh, D Tack, C Richardson, DC AF Das, Srilekha Sarkar Schwerin, Matthew Walsh, Donna Tack, Charles Richardson, D. Coleman BE Herold, KE Bentley, WE Vossoughi, J TI Changes in Viscoelastic Properties of Latex Condoms Due to Personal Lubricants SO 26TH SOUTHERN BIOMEDICAL ENGINEERING CONFERENCE: SBEC 2010 SE IFMBE Proceedings LA English DT Proceedings Paper CT 26th Southern Biomedical Engineering Conference, SBEC 2010 CY APR 30-MAY 02, 2010 CL Univ Maryland, College Park, MD SP Natl Sci Fdn, Biomed Engn Soc Chongqing, Natl Canc Inst (NCI) HO Univ Maryland DE Latex condoms; lubricants; slippage; swelling; stress relaxation AB Changes in the viscoelastic properties of the latex membrane due to personal lubricant application may be a potential cause of condom slippage during use. In this study, swelling and stress relaxation were studied for natural rubber latex condoms in the presence of personal lubricants. Neither swelling nor stress relaxation occurred in the presence of a water-based lubricant. Marginal swelling occurred due to a silicone-based lubricant compared to the positive control, mineral oil. However, no relaxation was observed when a stress relaxation test was performed after the swelling reached completion. Considerable relaxation occurred when the test was performed during the ongoing swelling process. These results suggest that stress relaxation may increase the risk of condom slippage due to the presence of a personal lubricant that induces swelling. C1 [Das, Srilekha Sarkar; Schwerin, Matthew; Walsh, Donna; Richardson, D. Coleman] US FDA, CDRH, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. [Tack, Charles] Marquette Univ, Biomed Engn, Milwaukee, WI 53233 USA. RP Das, SS (reprint author), US FDA, CDRH, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. EM Srilekha.Das@fda.hhs.gov NR 1 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1680-0737 BN 978-3-642-14997-9 J9 IFMBE PROC PY 2010 VL 32 BP 89 EP 91 PG 3 WC Engineering, Biomedical SC Engineering GA BBO72 UT WOS:000307744700024 ER PT S AU Karanian, JW Lopez, O Rad, D McDowell, B Kreitz, M Esparza, J Vossoughi, J Chiesa, OA Pritchard, WF AF Karanian, J. W. Lopez, O. Rad, D. McDowell, B. Kreitz, M. Esparza, J. Vossoughi, J. Chiesa, O. A. Pritchard, W. F. BE Herold, KE Bentley, WE Vossoughi, J TI Quantitative Mapping of Vascular Geometry for Implant Sites SO 26TH SOUTHERN BIOMEDICAL ENGINEERING CONFERENCE: SBEC 2010 SE IFMBE Proceedings LA English DT Proceedings Paper CT 26th Southern Biomedical Engineering Conference, SBEC 2010 CY APR 30-MAY 02, 2010 CL Univ Maryland, College Park, MD SP Natl Sci Fdn, Biomedical Engn Soc, Natl Canc Inst HO Univ Maryland DE Vascular biomechanics; vascular characterization; interventional device safety; imaging-based modeling; preclinical evaluation ID ELUTING STENT IMPLANTATION; FRACTURE AB In vivo characterization of the complex dynamic forces and repetitive deformations experienced by pelvic and leg vasculature is important to improve the evaluation of safety and effectiveness of implantable interventional devices such as stents [1]. The goal of this study was to use image based geometric modeling and analytical techniques to characterize the vascular deformations that occur with pelvic-hind limb motion in swine. Geometric changes in the ilio-femoral vessels were evaluated across a full range of motion in anesthetized swine. Computed tomography angiograms were obtained at each position and processed for model construction and geometric analysis of vascular segment length, curvature and twist. Local geometric changes between positions were evaluated and compared for each arterial segment over the full length of the iliac-femoral-popliteal artery. The greatest changes in axial length, twist and curvature were observed in the femoral segments between positions of hip extension to flexion. The total change in iliac-femoral-popliteal artery axial length and twist between the positions were -5.4cm and 112 degrees, respectively. Similarly, the maximum change in curvature along the artery was 0.46 cm(-1). Reported device failures in the ilio-femoral-popliteal vessels of human may be due in part to the wide range of physical forces and deformations imposed on these vessels during normal motion. Improved knowledge of the biomechanical behavior of the sites of vascular implants will make bench and preclinical testing more predictive for these devices, improving early evaluation of safety and effectiveness. C1 [Karanian, J. W.; Lopez, O.; Rad, D.; McDowell, B.; Kreitz, M.; Esparza, J.; Vossoughi, J.; Chiesa, O. A.; Pritchard, W. F.] FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Lab Cardiovasc & Intervent Therapeut,Div Biol, Laurel, MD 20708 USA. RP Karanian, JW (reprint author), FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Lab Cardiovasc & Intervent Therapeut,Div Biol, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1680-0737 BN 978-3-642-14997-9 J9 IFMBE PROC PY 2010 VL 32 BP 150 EP 153 PG 4 WC Engineering, Biomedical SC Engineering GA BBO72 UT WOS:000307744700039 ER PT S AU Das, SS McDermott, MK Lucas, AD Cargal, TE Patel, L Saylor, DM Patwardhan, DV AF Das, S. Sarkar McDermott, M. K. Lucas, A. D. Cargal, T. E. Patel, L. Saylor, D. M. Patwardhan, D. V. BE Herold, KE Bentley, WE Vossoughi, J TI Absorbable Coatings: Structure and Drug Elution SO 26TH SOUTHERN BIOMEDICAL ENGINEERING CONFERENCE: SBEC 2010 SE IFMBE Proceedings LA English DT Proceedings Paper CT 26th Southern Biomedical Engineering Conference, SBEC 2010 CY APR 30-MAY 02, 2010 CL Univ Maryland, College Park, MD SP Natl Sci Fdn, Biomed Engn Soc Chongqing, Natl Canc Inst (NCI) HO Univ Maryland DE PLGA; tetracycline; drug elution; release rate; matrix structure; matrix morphology ID TETRACYCLINE AB Drug delivery from biodegradable polymer coatings is becoming an important area of research for applications including medical devices. In this work, we probe the impact of polymer chemistry and solvent evaporation rate on drug morphology and the subsequent elution from biodegradable polymer. systems. Two different formulations of poly(lactic-glycolic-acid) (PLGA) polymers are used in combination with tetracycline (TC) to fabricate coatings using two different solvent evaporation rates. We have conducted elution studies to quantify the release behavior of tetracycline (TC) at the first 2-3 days of dissolution. Significantly we have correlated the drug release kinetics with the drug microstructure of TC/PLGA coating using atomic force microscopy (AFM) and laser scanning confocal microscopy (LSCM). These results suggest that polymer chemistry affects the rate of water absorption and drug dissolution which in turn alters the rate of TC release during the early stages of drug elution. C1 [Das, S. Sarkar; McDermott, M. K.; Lucas, A. D.; Cargal, T. E.; Patel, L.; Saylor, D. M.; Patwardhan, D. V.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, 10903 New Hampshire Ave Bldg 64, Silver Spring, MD 20993 USA. RP Das, SS (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, 10903 New Hampshire Ave Bldg 64, Silver Spring, MD 20993 USA. EM srilekha.das@fda.hhs.gov FU Department of Bioengineering, Rice University; Biomedical Engineering, John Hopkins University FX These authors are indebted to Ms. Deidra Johns, Department of Bioengineering, Rice University, and Ms. Rachel Casas, Biomedical Engineering, John Hopkins University, for their initial trial experiment. NR 6 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1680-0737 BN 978-3-642-14997-9 J9 IFMBE PROC PY 2010 VL 32 BP 240 EP 242 PG 3 WC Engineering, Biomedical SC Engineering GA BBO72 UT WOS:000307744700061 ER PT S AU Stohlman, J Aguel, F Calcagnini, G Mattei, E Triventi, M Censi, F Bartolini, P Krauthamer, V AF Stohlman, J. Aguel, F. Calcagnini, G. Mattei, E. Triventi, M. Censi, F. Bartolini, P. Krauthamer, V. BE Herold, KE Bentley, WE Vossoughi, J TI Effect of Waveform Shape and Duration on Defibrillation Threshold in Rabbit Hearts SO 26TH SOUTHERN BIOMEDICAL ENGINEERING CONFERENCE: SBEC 2010 SE IFMBE Proceedings LA English DT Proceedings Paper CT 26th Southern Biomedical Engineering Conference, SBEC 2010 CY APR 30-MAY 02, 2010 CL Univ Maryland, College Park, MD SP Natl Sci Fdn, Biomed Engn Soc Chongqing, Natl Canc Inst (NCI) HO Univ Maryland DE defibrillation; ventricular fibrillation; cardiac electrophysiology ID EFFICACY AB We compared the energy threshold (EDFT) for termination of ventricular fibrillation (VF) with shocks of different duration and waveform shape using an arbitrary waveform amplifier. Isolated rabbit hearts were Langendorf-perfused with Tyrode's solution and submerged in a 37 degrees C bath of Tyrode's solution. VF was induced by rapidly pacing the epicardium with a bipolar electrode. Once arrhythmic activity was identified via ECG, the rapid stimulus was terminated, and in most cases VF persisted. Two conventional waveform shapes were chosen for comparison: Monophasic Damped Sinusoid (MDS) and Biphasic Truncated Exponential (BTE). These waveforms, with varying duration and amplitude, were delivered to the fibrillating heart through titanium mesh 2x2cm electrodes positioned similar to 1cm on either side of the ventricles. A short duration BTE waveform (10ms) was used as a control, to compare with a long duration BTE waveform (45 ms) and a long duration MDS waveform (40ms). To determine the EDFT for each waveform, a step-up protocol was used. The delivered energy of the initial shock was set to similar to 0.2J; if this shock failed to defibrillate, the energy of the subsequent shock was increased 0.5-1J. The process of incrementally increasing the shock amplitude was continued until VF was terminated or the limit of our arbitrary waveform amplifier was reached. The short duration BTE waveform consistently terminated VF with an EDFT of 0.5-3J for all hearts. The long duration MDS waveform failed to terminate VF in a number of heart preparations, but successfully terminated VF in some hearts at an average EDFT 23 times higher than that of the short duration BTE for the same heart. The long duration BTE waveform failed to defibrillate arrhythmias for all hearts. Preliminary results demonstrate a method for comparing defibrillation shocks with waveforms that have customizable shapes, as well as selectable duration and delivered energy characteristics. C1 [Stohlman, J.; Aguel, F.; Krauthamer, V.] US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave WO62-1129, Silver Spring, MD 20903 USA. [Calcagnini, G.; Mattei, E.; Triventi, M.; Censi, F.; Bartolini, P.] Italian Inst Hlth, Rome, Italy. RP Stohlman, J (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave WO62-1129, Silver Spring, MD 20903 USA. EM Jayna.Stohlman@fda.hhs.gov RI MATTEI, EUGENIO/E-4623-2015 OI MATTEI, EUGENIO/0000-0002-6494-9456 NR 10 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1680-0737 BN 978-3-642-14997-9 J9 IFMBE PROC PY 2010 VL 32 BP 254 EP + PG 2 WC Engineering, Biomedical SC Engineering GA BBO72 UT WOS:000307744700065 ER PT S AU Pritchard, WF Kreitz, M Lopez, O Rad, D McDowell, B Nagaraja, S Dreher, ML Esparza, J Vossoughi, J Chiesa, OA Karanian, JW AF Pritchard, W. F. Kreitz, M. Lopez, O. Rad, D. McDowell, B. Nagaraja, S. Dreher, M. L. Esparza, J. Vossoughi, J. Chiesa, O. A. Karanian, J. W. BE Herold, KE Bentley, WE Vossoughi, J TI The Role of Imaging Tools in Biomedical Research: Preclinical Stent Implant Study SO 26TH SOUTHERN BIOMEDICAL ENGINEERING CONFERENCE: SBEC 2010 SE IFMBE Proceedings LA English DT Proceedings Paper CT 26th Southern Biomedical Engineering Conference, SBEC 2010 CY APR 30-MAY 02, 2010 CL Univ Maryland, College Park, MD SP Natl Sci Fdn, Biomedical Engn Soc, Natl Canc Inst HO Univ Maryland DE medical imaging; implant safety; predictive models ID KNEE FLEXION; FRACTURE; HIP AB Imaging tools are used at the bedside for diagnostic and interventional procedures. The use of more than one modality (including fused modalities) can provide information from diverse sources during different stages of image-guided interventional procedures such as diagnosis, delivery of a stent to treat vascular disease and subsequent evaluation. Multi-modality interventions use an array of tools including ultrasound, fluoroscopy, angiography, endoscopy, electromagnetic tracking, robotics and computed tomographic (CT) imaging, alone or in combination, together with analytical tools during preclinical vascular and therapeutic procedures. Explant analysis includes specimen radiography (Faxitron) and scanning electron microscopy (SEM)). In the case presented, swine underwent implantation of peripheral and coronary stents. Image acquisition tools included CT imaging and angiography (CTA), diagnostic angiography, fluoroscopy and specimen radiography. Image management and three-dimensional reconstructions were accomplished using OsiriX. Following delivery and deployment of stainless steel stents (Guidant Multi Link) and nitinol stents (Boston Scientific Radius), fluoroscopic and CT images were obtained at 30 day intervals for up to six months to define stent integrity. 3D reconstructions of CT scans using OsiriX were compared to explant specimen radiographs of each stent. Ex-planted stents were processed for SEM analysis. Stent integrity was evaluated in vivo and ex vivo demonstrating the development of stent fracture. Use of multi-modality imaging tools enhances the performance of pre-clinical device trials and the information generated by those studies. This may lead to improved safety evaluations and produce more reliable data for quantitative analysis. These imaging tools are available in clinical practice and are used to determine procedural success and short term and long term effectiveness of cardiovascular implants such as stents. The application of these clinical tools in pre-clinical trials, together with imaging procedures and analytic techniques that cannot be used clinically, represents a dynamic and rapidly emerging component of the device development and evaluation process. C1 [Pritchard, W. F.; Kreitz, M.; Lopez, O.; Rad, D.; McDowell, B.; Nagaraja, S.; Dreher, M. L.; Esparza, J.; Vossoughi, J.; Chiesa, O. A.; Karanian, J. W.] US FDA, Lab Cardiovasc & Intervent Therapeut, Div Biol, Off Sci & Engn Labs,Ctr Devices & Radiol Hlth, Laurel, MD 20708 USA. RP Pritchard, WF (reprint author), US FDA, Lab Cardiovasc & Intervent Therapeut, Div Biol, Off Sci & Engn Labs,Ctr Devices & Radiol Hlth, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 7 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1680-0737 BN 978-3-642-14997-9 J9 IFMBE PROC PY 2010 VL 32 BP 512 EP 515 PG 4 WC Engineering, Biomedical SC Engineering GA BBO72 UT WOS:000307744700131 ER PT S AU Harris, GR Herman, BA Myers, MR AF Harris, Gerald R. Herman, Bruce A. Myers, Matthew R. BE Hynynen, K Souquet, J TI An Analytical Comparison of the Thermal Dose Equation and the Intensity-Time Product, It(m), for Predicting Tissue Damage Thresholds SO 9TH INTERNATIONAL SYMPOSIUM ON THERAPEUTIC ULTRASOUND SE AIP Conference Proceedings LA English DT Proceedings Paper CT 9th International Symposium on Therapeutic Ultrasound CY SEP 24-26, 2009 CL Aix en Provence, FRANCE SP SuperSonic Imagine, Philips Healthcare, EDAP TMS, Focused Ultrasound Surg Fdn, Imasonic, EyeTechCare, InSightec, JJ&A Instruments, Siemens DE HIFU; thermal dose; thermal damage threshold ID FOCUSED ULTRASOUND; SURGERY; DOSAGES AB Thermal dose is the most generally accepted concept for estimating temperature-related tissue damage thresholds. However, another approach based on the intensity-time product of the form D = It(m) has been used, where D is a tissue-dependent damage threshold, I is the spatial-peak, temporal-average intensity, t is time, and m is an exponent not greater than one. In this study these two relationships were compared analytically by substituting a well-known soft tissue solution for temperature vs. time into the thermal dose equation. The commonly accepted value for t(43) of 240 minutes was used as a thermal dose threshold for necrosis. Then power law fits were found for I vs. t for various frequencies and beam diameters. Using published values for soft tissue acoustic and thermal properties, typical high intensity focused ultrasound (HIFU) frequencies and beam diameters, and exposure times from 1-20 s, the exponent m was found to fall between about 0.3 and 0.8. The value for m increased with increasing diameter but was independent of frequency. Thus, for the parameters examined, the intensity-time product relationship is equivalent to the thermal dose formulation over certain practical ranges of HIFU exposure duration. C1 [Harris, Gerald R.; Herman, Bruce A.; Myers, Matthew 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, Silver Spring, MD 20993 USA. NR 13 TC 1 Z9 1 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0758-9 J9 AIP CONF PROC PY 2010 VL 1215 BP 136 EP 139 DI 10.1063/1.3367124 PG 4 WC Acoustics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BQE66 UT WOS:000280794100030 ER PT S AU Soneson, JE AF Soneson, Joshua E. BE Hynynen, K Souquet, J TI Effects of dose-dependent absorption on heating and lesion formation SO 9TH INTERNATIONAL SYMPOSIUM ON THERAPEUTIC ULTRASOUND SE AIP Conference Proceedings LA English DT Proceedings Paper CT 9th International Symposium on Therapeutic Ultrasound CY SEP 24-26, 2009 CL Aix en Provence, FRANCE SP SuperSonic Imagine, Philips Healthcare, EDAP TMS, Focused Ultrasound Surg Fdn, Imasonic, EyeTechCare, InSightec, JJ&A Instruments, Siemens DE HIFU modeling; dynamic absorption; numerical methods AB A mathematical model for studying the effects of dose-dependent tissue absorption on high intensity focused ultrasound (HIFU) treatments is presented and a numerical solution method is discussed. An example HIFU system is considered and comparisons are made between including and neglecting dynamic absorption. Simulations show that neglecting dynamic absorption can result in highly underpredicted focal temperature, hotspot size, and lesion volume. C1 US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Soneson, JE (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0758-9 J9 AIP CONF PROC PY 2010 VL 1215 BP 164 EP 167 DI 10.1063/1.3367132 PG 4 WC Acoustics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BQE66 UT WOS:000280794100037 ER PT S AU Maruvada, S Liu, YB Herman, BA Harris, GR AF Maruvada, Subha Liu, Yunbo Herman, Bruce A. Harris, Gerald R. BE Hynynen, K Souquet, J TI Multiple Cavitation Detection Methods for Evaluating Tissue Mimicking Materials during HIFU Exposure SO 9TH INTERNATIONAL SYMPOSIUM ON THERAPEUTIC ULTRASOUND SE AIP Conference Proceedings LA English DT Proceedings Paper CT 9th International Symposium on Therapeutic Ultrasound CY SEP 24-26, 2009 CL Aix en Provence, FRANCE SP SuperSonic Imagine, Philips Healthcare, EDAP TMS, Focused Ultrasound Surg Fdn, Imasonic, EyeTechCare, InSightec, JJ&A Instruments, Siemens DE HIFU; Cavitation; Tissue-mimicking material AB Temperature rise during HIFU procedures and the possibility of cavitation activity during heating are important to quantify in planning a safe and effective treatment. Therefore, in pre-clinical testing it is essential to characterize clinical HIFU devices using tissue-mimicking materials (TMMs) with well known characteristics, including cavitation properties. The purpose of this study was to monitor cavitation behavior and determine its effect on temperature rise in a HIFU TMM containing an embedded thermocouple. A 50 mu m fine wire thermocouple was embedded in a hydrogel-based TMM previously developed for HIFU. HIFU at 1.1 MHz was focused at the thermocouple junction. HIFU focal pressures from 1-5 MPa were applied and the temperature rise and decay were recorded. Three hydrophones were used to monitor cavitation activity during sonication. A hydrophone confocal with the HIFU transducer and a cylindrical hydrophone lateral to the HIFU beam were used as passive cavitation detectors for spectral analysis of cavitation signals, and a needle hydrophone placed beyond the HIFU focus was used to record changes in the pressure amplitude due to blockage by bubbles at or near the focus. B-mode imaging scans were employed to visualize bubble presence during. sonication. Forward and reverse electrical powers also were measured. Temperature traces obtained at various pressure levels demonstrated a wide range of heating profiles in the TMM due to the occurrence of cavitation. Hydrophone and reflected power signals varied with focal pressure, and the signals could be correlated with suspected cavitation-induced anomalies of the temperature profile as well as B-mode images. Of the several methods studied for detecting cavitation, both the needle hydrophone and electrical power measurements were convenient adjuncts to spectral analysis for evaluating cavitation activity in the TMM. C1 [Maruvada, Subha; Liu, Yunbo; Herman, Bruce A.; Harris, Gerald R.] Ctr Devices & Radiol Hlth, US FDA, Silver Spring, MD 20993 USA. RP Maruvada, S (reprint author), Ctr Devices & Radiol Hlth, US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. NR 5 TC 1 Z9 1 U1 0 U2 4 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0758-9 J9 AIP CONF PROC PY 2010 VL 1215 BP 345 EP 348 DI 10.1063/1.3367177 PG 4 WC Acoustics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BQE66 UT WOS:000280794100078 ER PT S AU Khokhlova, VA Bessonova, OV Soneson, JE Canney, MS Bailey, MR Crum, LA AF Khokhlova, V. A. Bessonova, O. V. Soneson, J. E. Canney, M. S. Bailey, M. R. Crum, L. A. BE Hynynen, K Souquet, J TI Bandwidth Limitations in Characterization of High Intensity Focused Ultrasound Fields in the Presence of Shocks SO 9TH INTERNATIONAL SYMPOSIUM ON THERAPEUTIC ULTRASOUND SE AIP Conference Proceedings LA English DT Proceedings Paper CT 9th International Symposium on Therapeutic Ultrasound CY SEP 24-26, 2009 CL Aix en Provence, FRANCE SP SuperSonic Imagine, Philips Healthcare, EDAP TMS, Focused Ultrasound Surg Fdn, Imasonic, EyeTechCare, InSightec, JJ&A Instruments, Siemens DE HIFU; fiber optic hydrophone; KZK; nonlinear acoustics AB Nonlinear propagation effects result in the formation of weak shocks in high intensity focused ultrasound (HIFU) fields. When shocks are present, the wave spectrum consists of hundreds of harmonics. In practice, shock waves are modeled using a finite number of harmonics and measured with hydrophones that have limited bandwidths. The goal of this work was to determine how many harmonics are necessary to model or measure peak pressures, intensity, and heat deposition rates of the HIFU fields. Numerical solutions of the Khokhlov-Zabolotskaya-Kuznctzov-type (KZK) nonlinear parabolic equation were obtained using two independent algorithms, compared, and analyzed for nonlinear propagation in water, in gel phantom, and in tissue. Measurements were performed in the focus of the HIFU field in the same media using fiber optic probe hydrophones of various bandwidths. Experimental data were compared to the simulation results. C1 [Khokhlova, V. A.; Canney, M. S.; Bailey, M. R.; Crum, L. A.] Univ Washington, Ctr Ind & Med Ultrasound, Appl Phys Lab, 1013 NE 40th St, Seattle, WA 98105 USA. [Khokhlova, V. A.; Bessonova, O. V.] Moscow MV Lomonosov State Univ, Fac Phys, Dept Acoustics, Moscow R-119991, Russia. [Soneson, J. E.] US FDA, Silver Spring, MD 20993 USA. RP Khokhlova, VA (reprint author), Univ Washington, Ctr Ind & Med Ultrasound, Appl Phys Lab, 1013 NE 40th St, Seattle, WA 98105 USA. RI Khokhlova, Vera/A-2813-2012 FU NIH [EB007643]; NSBRI [SMS00402]; ISTC [3691]; RFBR [09-02-01530] FX The work was supported in parts by NIH EB007643, NSBRI SMS00402, ISTC 3691 and RFBR 09-02-01530 grants. Numerical simulations were performed on the supercomputer center Skif-MSU. NR 5 TC 2 Z9 2 U1 0 U2 2 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0758-9 J9 AIP CONF PROC PY 2010 VL 1215 BP 363 EP + DI 10.1063/1.3367181 PG 2 WC Acoustics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BQE66 UT WOS:000280794100082 ER PT J AU Lacerda, SHD Park, JJ Meuse, C Pristinski, D Becker, ML Karim, A Douglas, JF AF Lacerda, Silvia H. De Paoli Park, Jung Jin Meuse, Curt Pristinski, Denis Becker, Matthew L. Karim, Alamgir Douglas, Jack F. TI Interaction of Gold Nanoparticles with Common Human Blood Proteins SO ACS NANO LA English DT Article DE gold nanoparticles; fluorescence quenching; protein-nanoparticle interaction; binding affinity; conformational change; nanotoxicology; biocompatibility; protein adsorption ID HUMAN CARBONIC-ANHYDRASE; INDUCED CONFORMATIONAL-CHANGES; TRYPTOPHAN FLUORESCENCE; SILICA NANOPARTICLES; SERUM-ALBUMIN; COLLOIDAL GOLD; TYROSINE FLUORESCENCE; CANCER-THERAPY; QUANTUM DOTS; AMINO-ACID AB In order to better understand the physical basis of the biological activity of nanoparticles (NPs) in nanomedicine applications and under conditions of environmental exposure, we performed an array of photophysical measurements to quantify the interaction of model gold NPs having a wide range of NP diameters with common blood proteins, In particular, absorbance, fluorescence quenching, circular dichroism, dynamic light scattering, and electron microscopy measurements were performed on surface-functionalized water-soluble gold NPs having a diameter range from 5 to 100 nm in the presence of common human blood proteins: albumin, fibrinogen, gamma-globulin, histone, and insulin, We find that the gold NPs strongly associate with these essential blood proteins where the binding constant, K, as well as the degree of cooperativity of particle-protein binding (Hill constant, n), depends on particle size and the native protein structure. We also find tentative evidence that the model proteins undergo conformational change upon association with the NPs and that the thickness of the adsorbed protein layer (bare NO diameter <50 nm) progressively increases with NP size, effects that have potential general importance for understanding NP aggregation in biological media and the interaction of NP with biological materials broadly. C1 [Lacerda, Silvia H. De Paoli] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Park, Jung Jin] Univ Maryland, Dept Aerosp Engn, College Pk, MD 20742 USA. [Meuse, Curt; Pristinski, Denis; Douglas, Jack F.] Natl Inst Stand & Technol, Div Polymers, Gaithersburg, MD 20899 USA. [Becker, Matthew L.; Karim, Alamgir] Univ Akron, Dept Polymer Sci, Akron, OH 44325 USA. RP Lacerda, SHD (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM silvia.lacerda@fda.hhs.gov; jack.douglas@nist.gov RI Park, Jung Jin/C-7627-2011 FU National Institute of Standards and Technology; Polymers Division FX SHDPL thanks the National Institute of Standards and Technology and the Polymers Division in particular for its support of this research. NR 71 TC 318 Z9 322 U1 35 U2 254 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 JAN PY 2010 VL 4 IS 1 BP 365 EP 379 DI 10.1021/nn9011187 PG 15 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 547CP UT WOS:000273863400047 PM 20020753 ER PT J AU Wanner, T Fuller, ER Saylor, DM AF Wanner, Thomas Fuller, Edwin R., Jr. Saylor, David M. TI Homology metrics for microstructure response fields in polycrystals SO ACTA MATERIALIA LA English DT Article DE Homology metrics; Microstructures; Polycrystals; Finite element simulations; Thermal expansion anisotropy ID FE-CR ALLOYS; SPINODAL DECOMPOSITION; COMPUTER-MODELS; ATOMIC-LEVEL; ORIENTATION; COMPLEXITY; EVOLUTION; MARBLE AB Quantitative homology metrics are proposed for characterizing the thermal-elastic response of polycrystalline materials. Simulations for a calcite-based polycrystal, marble, are used as an illustrative example. The homology metrics are based on topological measurements, such as the number of components and the number of handles of the thermal-elastic response fields for a complex microstructure. These homology metrics are applied to characterize not only the elastic energy density and maximum principal stress response fields in a polycrystal but also the correlated grain-boundary misorientation distributions that influenced the formation of these response fields. It is demonstrated that the topological analysis can quantitatively distinguish between different types of grain-boundary misorientations, as well as between differences in the resulting response fields. Published by Elsevier Ltd. on behalf of Acta Materialia Inc. C1 [Wanner, Thomas] George Mason Univ, Dept Math Sci, Fairfax, VA 22030 USA. [Fuller, Edwin R., Jr.] Natl Inst Stand & Technol, Mat Sci & Engn Labs, Div Ceram, Gaithersburg, MD 20899 USA. [Saylor, David M.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20903 USA. RP Wanner, T (reprint author), George Mason Univ, Dept Math Sci, Fairfax, VA 22030 USA. EM twanner@gmu.edu; edwin.fuller@nist.gov; david.saylor@fda.hhs.gov FU NSF [DMS-0406231]; US Department of Energy [DE-FG02-05ER25712] FX Thomas Wanner was partially supported by NSF Grant DMS-0406231 and the US Department of Energy under Contract DE-FG02-05ER25712. NR 22 TC 19 Z9 19 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6454 J9 ACTA MATER JI Acta Mater. PD JAN PY 2010 VL 58 IS 1 BP 102 EP 110 DI 10.1016/j.actamat.2009.08.061 PG 9 WC Materials Science, Multidisciplinary; Metallurgy & Metallurgical Engineering SC Materials Science; Metallurgy & Metallurgical Engineering GA 527XW UT WOS:000272405600012 ER PT S AU Hong, HX Xu, L Tong, WD AF Hong, Huixiao Xu, Lei Tong, Weida BE Arabnia, HR TI Assessing Consistency Between Versions of Genotype-Calling Algorithm Birdseed for the Genome-Wide Human SNP Array 6.0 Using HapMap Samples SO ADVANCES IN COMPUTATIONAL BIOLOGY SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE Algorithm; Association; Genotype calling; HapMap; Reproducibility ID DISEASE AB Highly accurate and reproducible genotype calling is a key to success of genome-wide association studies (GWAS) since errors introduced by calling algorithms can lead to inflation of false associations between genotype and phenotype. The Affymetrix Genome-Wide Human SNP Array 6.0 is widely utilized and was used in the current GWAS. Birdseed, a genotype-calling algorithm for this chip, is available in two versions. It is important to know the reproducibility between the two versions. We assessed the inconsistency in genotypes called by the two versions of Birdseed and examined the propagation of the genotype inconsistency to the downstream association analysis by using the 270 HapMap samples. Our results revealed that genotypes called from version-1 and version-2 of Birdseed were slightly different and the inconsistency in genotypes propagated to the downstream association analysis. C1 [Hong, Huixiao] US FDA, Ctr Toxicoinformat, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Hong, HX (reprint author), US FDA, Ctr Toxicoinformat, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM Huixiao.Hong@fda.hhs.gov NR 9 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4419-5912-6 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2010 VL 680 BP 355 EP 360 DI 10.1007/978-1-4419-5913-3_40 D2 10.1007/978-1-4419-5913-3 PG 6 WC Mathematical & Computational Biology; Medicine, Research & Experimental SC Mathematical & Computational Biology; Research & Experimental Medicine GA BRL22 UT WOS:000283006100040 PM 20865519 ER PT B AU Lahiri, DK Ghosh, C Rogers, JT Bondy, S Greig, NH AF Lahiri, Debomoy K. Ghosh, Chandramallika Rogers, Jack T. Bondy, Stephen Greig, Nigel H. BE Bondy, S Maiese, K TI Role of Nitric Oxide in Neurodegeneration and Vulnerability of Neuronal Cells to Nitric Oxide Metabolites and Reactive Oxygen Species SO AGING AND AGE-RELATED DISORDERS SE Oxidative Stress in Applied Basic Research and Clinical Practice LA English DT Article; Book Chapter DE Alzheimer; Antioxidants; Chemical insults; Melatonin; Oxidative damage; Neuronal culture; Pineal hormone; Reactive nitrogen species; RNS; Tissue culture ID AMYLOID PRECURSOR PROTEIN; VASCULAR SMOOTH-MUSCLE; AGE-RELATED-CHANGES; ALZHEIMERS-DISEASE; SODIUM-NITROPRUSSIDE; MEDIATED TOXICITY; OXIDATIVE STRESS; GENE-EXPRESSION; GLIAL-CELLS; MELATONIN AB Nitric oxide (NO) is produced during the oxidative deamination catalyzed by nitric oxide synthase (NOS) that converts L-arginine to L-citrulline. NO can also be released chemically from a group of compounds called NO donors, such as sodium nitroprusside (SNP). NO directly or through its metabolites is believed to be involved in several disorders, including Alzheimer's disease (AD). This chapter summarizes the role of NO and oxidative stress in neurodegeneration and describes the experimental evidence of increased vulnerability of neuronal cells to NO metabolites and other reactive oxygen species (ROS). As NO is a highly labile, unstable free gas, levels of the stable end products, such as nitrite and nitrate (NOx), were measured. When different cell types were treated with SNP, a significant level of NOx was detected in a time- and dose-dependent manner, which was more than the spontaneous release by SNP. Astrocytic, glial, and epithelial cell lines released significantly higher levels of NOx compared with neuronal cell lines after SNP treatment. Neuronal cells were more sensitive to SNP-induced cytotoxicity, as determined by lactate dehydrogenase assay. SNP-mediated toxicity is known to be due, in large part, to the accumulation of cyanide ions, and the ability of cells to protect themselves against this toxicity depends upon their levels of NO metabolites. Cell lines that generate more NOx, such as astrocytic and epithelial, are better protected against the SNP-induced toxicity than are less NOx-protecting neuronal cell lines. Our results suggest that various cell types metabolize SNP differently and that neuronal cell lines are more vulnerable than other cell types to SNP treatment. As neuronal cell lines lack an NO-generated protective mechanism, these cells are potentially primary targets for neurodegeneration by toxic agents including the free radicals and peroxynitrites. C1 [Lahiri, Debomoy K.] Inst Psychiat Res, Mol Neurogenet Lab, Dept Psychiat, Indianapolis, IN USA. [Lahiri, Debomoy K.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Bondy, Stephen] Univ Calif Irvine, Dept Med Community & Environm Med, Ctr Occupat & Environm Hlth, Irvine, CA 92697 USA. [Ghosh, Chandramallika] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Greig, Nigel H.] NIA, Intramural Res Program, Neurosci Lab, NIH, Baltimore, MD 21224 USA. [Rogers, Jack T.] Harvard Univ, Sch Med, Dept Psychiat Neurosci, Massachusetts Gen Hosp E, Charlestown, MA USA. RP Lahiri, DK (reprint author), Inst Psychiat Res, Mol Neurogenet Lab, Dept Psychiat, Indianapolis, IN USA. EM dlahiri@iupui.edu NR 44 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-60761-601-6 J9 OXID STRESS APPL BAS JI Oxid. Stress Appl. Basic Res. Clin. Pract. PY 2010 BP 399 EP 415 DI 10.1007/978-1-60761-602-3_20 D2 10.1007/978-1-60761-602-3 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA BQX53 UT WOS:000282063600020 ER PT J AU Al-Khatib, SM Calkins, H Eloff, BC Packer, DL Ellenbogen, KA Hammill, SC Natale, A Page, RL Prystowsky, E Jackman, WM Stevenson, WG Waldo, AL Wilber, D Kowey, P Yaross, MS Mark, DB Reiffel, J Finkle, JK Marinac-Dabic, D Pinnow, E Sager, P Sedrakyan, A Canos, D Gross, T Berliner, E Krucoff, MW AF Al-Khatib, Sana M. Calkins, Hugh Eloff, Benjamin C. Packer, Douglas L. Ellenbogen, Kenneth A. Hammill, Stephen C. Natale, Andrea Page, Richard L. Prystowsky, Eric Jackman, Warren M. Stevenson, William G. Waldo, Albert L. Wilber, David Kowey, Peter Yaross, Marcia S. Mark, Daniel B. Reiffel, James Finkle, John K. Marinac-Dabic, Danica Pinnow, Ellen Sager, Phillip Sedrakyan, Art Canos, Daniel Gross, Thomas Berliner, Elise Krucoff, Mitchell W. TI Planning 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 PULMONARY-VEIN ABLATION; RADIOFREQUENCY ABLATION; ANTIARRHYTHMIC-DRUGS; CATHETER ABLATION; RANDOMIZED-TRIAL; GUIDED ABLATION; CURE AB Atrial fibrillation (AF) is a major public health problem in the United States that is associated with increased mortality and morbidity. Of the therapeutic modalities available to treat AF, the use of percutaneous catheter ablation of AF is expanding rapidly. Randomized clinical trials examining the efficacy and safety of AF ablation are currently underway; however, such trials can only partially determine the safety and durability of the effect of the procedure in routine clinical practice, in more complex patients, and over a broader range of techniques and operator experience. These limitations of randomized trials of AF ablation, particularly with regard to safety issues, could be addressed using a synergistically structured national registry, which is the intention of the SAFARI. To facilitate discussions about objectives, challenges, and steps for such a registry, the Cardiac Safety Research Consortium and the Duke Clinical Research Institute, Durham, NC, in collaboration with the US Food and Drug Administration, the American College of Cardiology, and the Heart Rhythm Society, organized a Think Tank meeting of experts in the field. 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 Society of Thoracic Surgeons, the AdvaMed AF working group, and additional industry representatives. The meeting took place on April 27 to 28, 2009, at the US Food and Drug Administration headquarters in Silver Spring, MD. This article summarizes the issues and directions presented and discussed at the meeting. (Am Heart J 2010; 159: 17-24. e1.) C1 [Al-Khatib, Sana M.; Mark, Daniel B.; Krucoff, Mitchell W.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27715 USA. [Calkins, Hugh] Johns Hopkins Univ, Baltimore, MD USA. [Eloff, Benjamin C.; Marinac-Dabic, Danica; Pinnow, Ellen; Sedrakyan, Art; Canos, Daniel; Gross, Thomas] US FDA, Silver Spring, MD USA. [Packer, Douglas L.; Hammill, Stephen C.] Mayo Clin, Rochester, MN USA. [Ellenbogen, Kenneth A.] Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. [Natale, Andrea] St Davids Med Ctr, Texas Cardiac Arrhythmia Inst, Austin, TX USA. [Page, Richard L.] Univ Washington, Seattle, WA 98195 USA. [Prystowsky, Eric] Care Grp, Indianapolis, IN USA. [Jackman, Warren M.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Stevenson, William G.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Waldo, Albert L.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Wilber, David] Loyola Univ, Chicago, IL 60611 USA. [Kowey, Peter] Lankenau Inst Med Res, Diamond Bar, CA USA. Main Line Heart Ctr, Diamond Bar, CA USA. [Yaross, Marcia S.] Biosense Webster, Diamond Bar, CA USA. [Reiffel, James] Columbia Univ, New York, NY USA. [Finkle, John K.] GlaxoSmithKline Inc, Collegeville, PA USA. [Sager, Phillip] Gilead Sci Inc, Palo Alto, CA USA. [Berliner, Elise] Agcy Healthcare Res & Qual, Rockville, MD USA. RP Al-Khatib, SM (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM alkha001@mc.duke.edu RI Page, Richard/L-5501-2014 OI Page, Richard/0000-0001-5603-1330 FU CSRC; DCRI; ACC; HRS FX This conference was funded by CSRC, DCRI, ACC, and HRS; registration fees and in- kind support from FDA and AdvaMed.; Views expressed in this article reflect the opinions of the authors only and not the official policy of the Food and Drug Administration, the Agency for Healthcare Research and Quality, the Department of Human Services, or the remaining authors' affiliated organizations. NR 17 TC 14 Z9 14 U1 0 U2 1 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 JAN PY 2010 VL 159 IS 1 BP 17 EP U34 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 536NO UT WOS:000273051300003 PM 20102862 ER PT J AU Rossi, J AF Rossi, John TI International Research and Positive Obligations: Are They "Transaction Specific"? SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 US FDA, Off Pediat Therapeut, Silver Spring, MD 20993 USA. RP Rossi, J (reprint author), US FDA, Off Pediat Therapeut, 10903 New Hampshire Ave,Bldg 32,Room 5165, Silver Spring, MD 20993 USA. EM John.Rossi@fda.hhs.gov NR 7 TC 1 Z9 1 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2010 VL 10 IS 6 BP 49 EP 51 PG 4 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 606SJ UT WOS:000278447300019 PM 20526974 ER PT J AU Li, J Liu, HP Ramachandran, S Waypa, GB Yin, JJ Li, CQ Han, M Huang, HH Sillard, WW Hoek, TLV Shao, ZH AF Li, Jing Liu, Huiping Ramachandran, Srinivasan Waypa, Gregory B. Yin, Jun-Jie Li, Chang-Qing Han, Mei Huang, Hsien-Hao Sillard, Willard W. Hoek, Terry L. Vanden Shao, Zuo-Hui TI Grape Seed Proanthocyanidins Ameliorate Doxorubicin-Induced Cardiotoxicity SO AMERICAN JOURNAL OF CHINESE MEDICINE LA English DT Article DE Grape Seed Proanthocyanidin Extract; Doxorubicin; Reactive Oxygen Species; Cardiomyocyte; Cardiotoxicity ID INDUCED OXIDATIVE STRESS; REPERFUSION INJURY; INDUCED APOPTOSIS; CARDIOMYOCYTE APOPTOSIS; CARDIAC MYOCYTES; RAT HEARTS; IN-VIVO; MITOCHONDRIAL; EXTRACT; CELLS AB Doxorubicin (Dox) is one of the most widely used and successful chemotherapeutic antitumor drugs. Its clinical application is highly limited due to its cumulative dose-related cardiotoxicity. Proposed mechanisms include the generation of reactive oxygen species (ROS)-mediated oxidative stress. Therefore, reducing oxidative stress should be protective against Dox-induced cardiotoxicity. To determine whether antioxidant, grape seed proanthocyanidin extract (GSPE) attenuates Dox-induced ROS generation and protects cardiomyocytes from Dox-induced oxidant injury, cultured primary cardiomyocytes were treated with doxorubicin (Dox, 10 mu M) alone or GSPE (50 mu g/ml) with Dox (10 mu M) for 24 hours. Dox increased intracellular ROS production as measured by 6-carboxy-2',7'-dichlorodihydrofluorescein diacetate, induced significant cell death as assessed by propidium iodide, and declined the redox ratio of reduced glutathione (GSH)/oxidized glutathione (GSSG) and disrupted mitochondrial membrane potential as determined by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethlbenzimidazole-carbocyanide iodine (JC-1). Analysis of agarose gel electrophoresis revealed Dox-induced nuclear DNA damage with the ladder like fragmentation. GSPE treatment suppressed those alterations. Electron Spin Resonance (ESR) spectroscopy data also showed that GSPE strongly scavenged hydroxyl radical, superoxide and DPPH radicals. Together, these findings indicate that GSPE in combination with Dox has protective effect against Dox-induced toxicity in cardiomyocytes, which may be in part attributed to its antioxidative activity. Importantly, flow cytometric analysis demonstrated that co-treatment of Dox and GSPE did not decrease the proliferation-inhibitory effect of Dox in MCF-7 human breast carcinoma cells. Thus, GSPE may be a promising adjuvant to prevent cardiotoxicity without interfering with antineoplastic activity during chemotherapeutic treatment with Dox. C1 [Li, Jing; Li, Chang-Qing; Han, Mei; Huang, Hsien-Hao; Sillard, Willard W.; Hoek, Terry L. Vanden; Shao, Zuo-Hui] Univ Chicago, Dept Med, Sect Emergency Med, Emergency Resuscitat Ctr, Chicago, IL 60637 USA. [Liu, Huiping] Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA. [Ramachandran, Srinivasan] Univ Chicago, Ctr Nanomed, Chicago, IL 60637 USA. [Waypa, Gregory B.] Northwestern Univ, Dept Pediat, Chicago, IL 60611 USA. [Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Huang, Hsien-Hao] Natl Yang Ming Univ, Coll Med, Taipei Vet Gen Hosp & Emergency Med, Dept Emergency Med, Taipei 112, Taiwan. RP Shao, ZH (reprint author), Univ Chicago, Dept Med, Sect Emergency Med, Emergency Resuscitat Ctr, 5841 S Maryland Ave,MC 6854, Chicago, IL 60637 USA. EM zshao@medicine.bsd.uchicago.edu RI Ramachandran, Srinivasan/G-5300-2010; Yin, Jun Jie /E-5619-2014; OI Ramachandran, Srinivasan/0000-0002-4912-0279; Sharp, Willard/0000-0002-7175-3523; Waypa, Gregory/0000-0002-6179-4209 FU NIH [AT01575, AT003441]; US, Department of Defense Office of Naval Research. [N00014-04-1-0796] FX This work was supported by the NIH grants AT01575, AT003441 and MURI (Multi-University Research Initiative) award N00014-04-1-0796 from the US, Department of Defense Office of Naval Research. The authors thank Prof. C.S. Yuan (Tang Center for Herbal Medicine Research, University of Chicago) for his generous gift of GSPE and Prof. B. Kalyanaraman (Department of Biophysics and Free Radical Research Center, Medical College of Wisconsin) for his generous gift of BMPO. NR 51 TC 27 Z9 28 U1 0 U2 8 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 0192-415X J9 AM J CHINESE MED JI Am. J. Chin. Med. PY 2010 VL 38 IS 3 BP 569 EP 584 DI 10.1142/S0192415X10008068 PG 16 WC Integrative & Complementary Medicine; Medicine, General & Internal SC Integrative & Complementary Medicine; General & Internal Medicine GA 600TH UT WOS:000278011200012 PM 20503473 ER PT J AU Civelek, M Grant, GR Irolla, CR Shi, CZ Riley, RJ Chiesa, OA Stoeckert, CJ Karanian, JW Pritchard, WF Davies, PF AF Civelek, Mete Grant, Gregory R. Irolla, Chrysta R. Shi, Congzhu Riley, Rebecca J. Chiesa, Oscar A. Stoeckert, Christian J., Jr. Karanian, John W. Pritchard, William F. Davies, Peter F. TI Prelesional arterial endothelial phenotypes in hypercholesterolemia: universal ABCA1 upregulation contrasts with region-specific gene expression in vivo SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE microarray; hypercholesterolemia; Oil Red O; endoplasmic reticulum stress; unfolded protein response ID BINDING CASSETTE TRANSPORTER-1; UNFOLDED PROTEIN RESPONSE; LOW-DENSITY-LIPOPROTEIN; LIVER-X-RECEPTOR; TANGIER-DISEASE; EXPERIMENTAL ATHEROSCLEROSIS; CORONARY ATHEROSCLEROSIS; CHOLESTEROL-METABOLISM; TRANSCRIPTION PROFILES; ENDOPLASMIC-RETICULUM AB Civelek M, Grant GR, Irolla CR, Shi C, Riley RJ, Chiesa OA, Stoeckert CJ Jr, Karanian JW, Pritchard WF, Davies PF. Prelesional arterial endothelial phenotypes in hypercholesterolemia: universal ABCA1 upregulation contrasts with region-specific gene expression in vivo. Am J Physiol Heart Circ Physiol 298: H163-H170, 2010. First published November 6, 2009; doi:10.1152/ajpheart.00652.2009.-Atherosclerosis originates as focal arterial lesions having a predictable distribution to regions of bifurcations, branches, and inner curvatures where blood flow characteristics are complex. Distinct endothelial phenotypes correlate with regional hemodynamics. We propose that systemic risk factors modify regional endothelial phenotype to influence focal susceptibility to atherosclerosis. Transcript profiles of freshly isolated endothelial cells from three atherosusceptible and three atheroprotected arterial regions in adult swine were analyzed to determine the initial prelesional effects of hypercholesterolemia on endothelial phenotypes in vivo. Cholesterol efflux transporter ATP-binding cassette transporter A1 (ABCA1) was upregulated at all sites in response to short-term high-fat diet. Proinflammatory and antioxidative endothelial gene expression profiles were induced in atherosusceptible and atheroprotected regions, respectively. However, markers for endoplasmic reticulum stress, a signature of susceptible endothelial phenotype, were not further enhanced by brief hypercholesterolemia. Both region-specific and ubiquitous (ABCA1) phenotype changes were identified as early prelesional responses of the endothelium to hypercholesterolemia. C1 [Civelek, Mete; Shi, Congzhu; Riley, Rebecca J.; Davies, Peter F.] Univ Penn, Inst Med & Engn, Philadelphia, PA 19104 USA. [Civelek, Mete; Irolla, Chrysta R.; Davies, Peter F.] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. [Grant, Gregory R.; Stoeckert, Christian J., Jr.] Univ Penn, Ctr Bioinformat, Philadelphia, PA 19104 USA. [Grant, Gregory R.; Stoeckert, Christian J., Jr.] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. [Davies, Peter F.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Chiesa, Oscar A.; Karanian, John W.; Pritchard, William F.] US FDA, Lab Cardiovasc & Intervent Therapeut, Ctr Devices & Radiol Hlth, Laurel, MD USA. RP Davies, PF (reprint author), Univ Penn, Inst Med & Engn, 1010 Vagelos Labs,3340 Smith Walk, Philadelphia, PA 19104 USA. EM pfd@pobox.upenn.edu RI Civelek, Mete/C-8058-2011; OI Civelek, Mete/0000-0002-8141-0284 FU American Heart Association [0315286U]; National Institutes of Health [HL-062250, HG-004521] FX This work was supported by an American Heart Association predoctoral fellowship (0315286U) and National Institutes of Health Grants HL-062250 and HG-004521. NR 61 TC 10 Z9 11 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JAN PY 2010 VL 298 IS 1 BP H163 EP H170 DI 10.1152/ajpheart.0652.2009 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 533NT UT WOS:000272831600020 PM 19897713 ER PT J AU Knapik, JJ Brosch, LC Venuto, M Swedler, DI Bullock, SH Gaines, LS Murphy, RJ Tchandja, J Jones, BH AF Knapik, Joseph J. Brosch, Lorie C. Venuto, Margaret Swedler, David I. Bullock, Steven H. Gaines, Lorraine S. Murphy, Ryan J. Tchandja, Juste Jones, Bruce H. TI Effect on Injuries of Assigning Shoes Based on Foot Shape in Air Force Basic Training SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID PHYSICAL-ACTIVITY; RISK-FACTORS; STRESS-FRACTURES; LOWER-EXTREMITY; YOUNG MEN; RUNNING INJURIES; FEMALE RECRUITS; ARMY RECRUITS; US ARMY; FITNESS AB Background: This study examined whether assigning running shoes based on the shape of the bottom of the foot (plantar surface) influenced injury risk in Air Force Basic Military Training (BMT) and examined risk factors for injury in BMT. Methods: Data were collected from BMT recruits during 2007; analysis took place during 2008. After foot examinations, recruits were randomly consigned to either an experimental group (E, n=1042 men, 375 women) or a control group (C, n=913 men, 346 women). Experimental group recruits were assigned motion control, stability, or cushioned shoes for plantar shapes indicative of low, medium, or high arches, respectively. Control group recruits received a stability shoe regardless of plantar shape. Injuries during BMT were determined from Outpatient visits provided from the Defense Medical Surveillance System. Other injury risk factors (fitness, smoking, physical activity, prior injury, menstrual history, and demographics) were obtained from a questionnaire, existing databases, or BMT units. Results: Multivariate Cox regression controlling for other risk factors showed little difference in injury risk between the groups among men (hazard ratio [E/C]= 1.11, 95%CI=0.89-1.38) or women (hazard ratio [E/C] = 1.20, 95% CI=0.90-1.60). Independent injury risk factors among both men and women included low aerobic fitness and cigarette smoking. Conclusions: This prospective study demonstrated that assigning running shoes based on the shape of the plantar Surface had little influence on injury risk in BMT even after controlling for other injury risk factors. (Am J Prev Med 2010;38(1S):S197-S211) Published by Elsevier Inc. on behalf of American journal of Preventive Medicine C1 [Knapik, Joseph J.] USA, Ctr Hlth Promot & Prevent Med, Directorate Epidemiol & Dis Surveillance, Aberdeen Proving Ground, MD 21010 USA. [Venuto, Margaret] US FDA, Dept Hlth & Human Serv, College Pk, MD USA. [Brosch, Lorie C.; Tchandja, Juste] USAF, Med Grp 37, Lackland AFB, TX USA. [Murphy, Ryan J.] USA, Med Dept Ctr & Sch, Ft Sam Houston, TX USA. RP Knapik, JJ (reprint author), USA, Ctr Hlth Promot & Prevent Med, Directorate Epidemiol & Dis Surveillance, 1570 Stark Rd, Aberdeen Proving Ground, MD 21010 USA. EM joseph.knapik@us.army.mil NR 64 TC 35 Z9 35 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 JAN PY 2010 VL 38 IS 1 BP S197 EP S211 DI 10.1016/j.amepre.2009.10.013 PG 15 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 541KM UT WOS:000273413900020 PM 20117594 ER PT J AU Kramer, DB Mallis, E Zuckerman, BD Zimmerman, BA Maisel, WH AF Kramer, Daniel B. Mallis, Elias Zuckerman, Bram D. Zimmerman, Barbara A. Maisel, William H. TI Premarket Clinical Evaluation of Novel Cardiovascular Devices: Quality Analysis of Premarket Clinical Studies Submitted to the Food and Drug Administration 2000-2007 SO AMERICAN JOURNAL OF THERAPEUTICS LA English DT Article DE medical device; clinical trials; regulatory affairs; cardiovascular AB The quality of clinical data submitted by manufacturers to support Food and Drug Administration cardiovascular device premarket approval (PMA) applications varies widely and formal quality assessment has not been previously performed. This study evaluated all original cardiovascular device PMAs with Food and Drug Administration decisions between January 1, 2000, and December 31, 2007, to assess the quality of chemical investigations submitted by manufacturers. Effectiveness and safety end points were judged high quality if they were clearly defined and associated with a specific time point for analysis. Subject accounting was high quality if 90% or greater of the original cohort was accounted for at study conclusion. In total, 88 cardiovascular device PMAs (77.3% permanent implants), 132 clinical studies, 37,328 study subjects (age 61.0 +/- 14.5 years, 33.9% women, 86.3% white), and 29,408 device recipients were analyzed. All PMAs contained chemical data. Primary effectiveness end points, primary safety end points, and subject accounting were deemed high quality in 81.8%, 60.2%, and 77.3% of pivotal studies, respectively. Key cardiovascular comorbidities (coronary artery disease 51.1%, diabetes 36.6%, hypertension 35.2%, heart failure 37.5%, tobacco use 31.8%) and race (14.8%) were infrequently reported, and studies rarely included patients younger than 18 years of age (10.2% of studies). Poorly defined safety and effectiveness end points, poor patient accounting, and incomplete collection of important patient comorbidities make device safety and effectiveness assessments more challenging. Women, pediatric, and nonwhite populations are underrepresented in premarket cardiovascular chemical trials. Manufacturers, regulators, and the clinical community should collaborate to address these study shortcomings to ensure that patients are treated with reliable, safe, and clinically useful medical devices. C1 [Maisel, William H.] Beth Israel Deaconess Med Ctr, Med Device Safety Inst, Boston, MA 02215 USA. [Kramer, Daniel B.; Maisel, William H.] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA. [Mallis, Elias; Zuckerman, Bram D.; Zimmerman, Barbara A.] US FDA, Div Cardiovasc Devices, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Maisel, WH (reprint author), Beth Israel Deaconess Med Ctr, Med Device Safety Inst, 185 Pilgrim Rd,Baker 4, Boston, MA 02215 USA. EM wmaisel@bidmc.harvard.edu FU FDA; U.S. Food and Drug Administration FX No author has any conflict of interest or financial disclosure to report. This study was funded by the U.S. Food and Drug Administration. They participated in the design and conduct of the study, data collection, management, analysis, and interpretation of the data, and in the preparation, review, and approval of the manuscript. All authors had complete access to all data in the manuscript. Dr. Maisel takes responsibility for the integrity of the data and accuracy of the data analysis. NR 7 TC 24 Z9 24 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1075-2765 J9 AM J THER JI Am. J. Ther. PD JAN-FEB PY 2010 VL 17 IS 1 BP 2 EP 7 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 546XR UT WOS:000273849000002 PM 20038828 ER PT J AU McCance-Katz, EF Sullivan, LE Nallani, S AF McCance-Katz, Elinore F. Sullivan, Lynn E. Nallani, Srikanth TI Drug Interactions of Clinical Importance among the Opioids, Methadone and Buprenorphine, and Other Frequently Prescribed Medications: A Review SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID HUMAN LIVER-MICROSOMES; HEPATITIS-C VIRUS; P4503A CYP3A ACTIVITY; TORSADE-DE-POINTES; DEPENDENT PATIENTS; CYTOCHROME-P450 3A4; ZIDOVUDINE DISPOSITION; ANTIRETROVIRAL AGENTS; MAINTENANCE PATIENTS; LOPINAVIR-RITONAVIR AB Drug interactions are a leading cause of morbidity and mortality. Methadone and buprenorphine are frequently prescribed for the treatment of opioid addiction. Patients needing treatment with these medications often have co-occurring medical and mental illnesses that require medication treatment. The abuse of illicit substances is also common in opioid-addicted individuals. These clinical realities place patients being treated with methadone and buprenorphine at risk for potentially toxic drug interactions. A substantial literature has accumulated on drug interactions between either methadone or buprenorphine with other medications when ingested concomitantly by humans. This review summarizes current literature in this area. (Am J Addict 2009;19:4-16). C1 [McCance-Katz, Elinore F.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Sullivan, Lynn E.] Yale Univ, Dept Internal Med, New Haven, CT USA. [Nallani, Srikanth] US FDA, Off Clin Pharmacol, CDER, Silver Spring, MD USA. RP McCance-Katz, EF (reprint author), San Francisco Gen Hosp, 1001 Potrero Ave,Suite 7M-WD93, San Francisco, CA 94110 USA. EM elinore.mccance-katz@ucsf.edu FU NIDA NIH HHS [R01 DA013004, K24 DA 023359, K24 DA023359, K24 DA023359-04, R01 DA 13004, R01 DA013004-09S1] NR 92 TC 77 Z9 80 U1 1 U2 12 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JAN-FEB PY 2010 VL 19 IS 1 BP 4 EP 16 DI 10.1111/j.1521-0391.2009.00005.x PG 13 WC Substance Abuse SC Substance Abuse GA 533ZE UT WOS:000272864300003 PM 20132117 ER PT J AU Li, F Nandy, P Chien, S Noel, GJ Tornoe, CW AF Li, Fang Nandy, Partha Chien, Shuchean Noel, Gary J. Tornoe, Christoffer W. TI Pharmacometrics-Based Dose Selection of Levofloxacin as a Treatment for Postexposure Inhalational Anthrax in Children SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID LABELING DECISIONS; DRUG APPLICATIONS; APPROVAL; IMPACT AB Levofloxacin was recently (May 2008) approved by the U. S. Food and Drug Administration as a treatment for children following inhalational exposure to anthrax. Given that no clinical trials to assess the efficacy of a chosen dose was conducted, the basis for the dose recommendation was based upon pharmacometric analyses. The objective of this paper is to describe the basis of the chosen pediatric dose recommended for the label. Pharmacokinetic (PK) data from 90 pediatric patients receiving 7 mg/kg of body weight levofloxacin and two studies of 47 healthy adults receiving 500 and 750 mg/kg levofloxacin were used for the pharmacometric analyses. Body weight was found to be a significant covariate for levofloxacin clearance and the volume of distribution. Consistently with developmental physiology, clearance also was found to be reduced in pediatric patients under 2 years of age due to immature renal function. Different dosing regimens were simulated to match adult exposure (area under the concentration-time curve from 0 to 24 h at steady state, maximum concentration of drug in serum at steady state, and minimum concentration of drug in serum at steady state) following the approved adult dose of 500 mg once a day. The recommended dose of 8 mg/kg twice a day was found to match the exposure of the dose approved for adults in a manner that permitted confidence that this dose in children would achieve efficacy comparable to that of adults. C1 [Li, Fang; Tornoe, Christoffer W.] US FDA, Div Pharmacometr, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Nandy, Partha] Johnson & Johnson Pharmaceut Res & Dev, Adv PK PD Modeling & Simulat, Raritan, NJ USA. [Chien, Shuchean] Johnson & Johnson Pharmaceut Res & Dev, Early Res & Dev, Raritan, NJ USA. [Noel, Gary J.] Johnson & Johnson Pharmaceut Res & Dev, Antiinfect Res & Dev, Raritan, NJ USA. RP Li, F (reprint author), 10903 New Hampshire Ave,WO51 Rm 3169, Silver Spring, MD 20993 USA. EM fang.li@fda.hhs.gov NR 11 TC 27 Z9 28 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 2010 VL 54 IS 1 BP 375 EP 379 DI 10.1128/AAC.00667-09 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 534XQ UT WOS:000272931200049 PM 19858256 ER PT J AU Schaer, DJ Alayash, AI AF Schaer, Dominik J. Alayash, Abdu I. TI Clearance and Control Mechanisms of Hemoglobin from Cradle to Grave SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Editorial Material ID SCAVENGER RECEPTOR; MACROPHAGES; CD163; PEROXIDE; PATHWAY; DISEASE AB Hemoglobin is a highly reactive molecule, and besides its oxygen-carrying capacity, it has multiple enzymatic and ligand-binding activities that have only recently been explored as fundamental pathophysiologic mechanisms. Nitric oxide neutralization, generation of potentially toxic radical species, and heme-mediated inflammation are among the most extensively studied mechanisms of Hb-mediated pathology. Extracellular Hb has an established role in sickle cell disease and other hemolytic disorders. However, extracellular Hb seems also to have relevant disease-modifying activities in many other important pathologic conditions, such as malaria and atherosclerosis. In this Forum, we summarize the current knowledge of mechanisms of Hb toxicity. Special emphasis is given to the highly efficient endogenous scavenger and detoxification pathways, such as alpha-hemoglobin stabilizing protein (AHSP), haptoglobin, hemopexin, CD163, and heme oxygenase. Systemic and local activity of these pathways finally determines the impact of extracellular Hb on physiology and tissue homeostasis. Antioxid. Redox Signal. 12, 181-184. C1 [Schaer, Dominik J.] Univ Hosp, Div Internal Med, CH-8091 Zurich, Switzerland. [Alayash, Abdu I.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Schaer, DJ (reprint author), Univ Hosp, Div Internal Med, CH-8091 Zurich, Switzerland. EM dominik.schaer@hotmail.com NR 13 TC 27 Z9 29 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JAN PY 2010 VL 12 IS 2 BP 181 EP 184 DI 10.1089/ars.2009.2923 PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 538JY UT WOS:000273181600001 PM 19788393 ER PT J AU Widmer, CC Pereira, CP Gehrig, P Vallelian, F Schoedon, G Buehler, PW Schaer, DJ AF Widmer, Corinne C. Pereira, Claudia P. Gehrig, Peter Vallelian, Florence Schoedon, Gabriele Buehler, Paul W. Schaer, Dominik J. TI Hemoglobin Can Attenuate Hydrogen Peroxide-Induced Oxidative Stress by Acting as an Antioxidative Peroxidase SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID NITRIC-OXIDE BIOAVAILABILITY; LOW-DENSITY-LIPOPROTEIN; ENDOTHELIAL-CELLS; HEME DEGRADATION; HORSERADISH-PEROXIDASE; INTRAPLAQUE HEMORRHAGE; FERRYL INTERMEDIATE; SCAVENGER RECEPTOR; PROSTHETIC HEME; CROSS-LINKING AB Hemoglobin is considered a potentially toxic molecule when released from erythrocytes during hemolysis, inflammation, or tissue injury. The mechanisms of toxicity involve reduced nitric oxide bioavailability and oxidative processes both occurring at the heme prosthetic groups. When the endogenous oxidant H2O2 reacts with Hb, transient radicals are generated during the peroxidative consumption of H2O2. If not neutralized, these radicals can lead to tissue toxicity. The net biologic effect of extracellular Hb in an H2O2-rich environment will therefore be determined by the balance of H2O2 decomposition (potential protective effect) and radical generation (potential damaging effect). Here we show that Hb can protect different cell types from H2O2-mediated cell death and the associated depletion of intracellular glutathione and ATP. Importantly, Hb blunts the transcriptional oxidative-stress response induced by H2O2 in human vascular smooth muscle cells (VSMCs). Based on spectrophotometric and quantitative mass spectrometry analysis, we suggested a novel mechanism in which Hb redox-cycles H2O2 and simultaneously internalizes the radical burden, with irreversible structural globin changes starting with specific amino acid oxidation involving the heme proximate beta Cys93 and ultimately ending with protein precipitation. Our results suggest that complex interactions determine whether extracellular Hb, under certain circumstances, acts a protective or a damaging factor during peroxidative stress conditions. Antioxid. Redox Signal. 12, 185-198. C1 [Schaer, Dominik J.] Univ Hosp, Dept Internal Med, Div Internal Med, CH-8091 Zurich, Switzerland. [Gehrig, Peter] Univ Zurich, Funct Genom Ctr Zurich, Zurich, Switzerland. [Gehrig, Peter] Swiss Fed Inst Technol, Zurich, Switzerland. [Buehler, Paul W.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Schaer, DJ (reprint author), Univ Hosp, Dept Internal Med, Div Internal Med, CH-8091 Zurich, Switzerland. EM dominik.schaer@usz.ch FU Swiss National Science Foundation [31-120658]; Gianni Rubatto Foundation; Helmut Horten Foundation FX The study was supported by the Swiss National Science Foundation (grant 31-120658), the Gianni Rubatto Foundation, and the Helmut Horten Foundation (all to D. J. S.). NR 43 TC 33 Z9 33 U1 0 U2 13 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JAN PY 2010 VL 12 IS 2 BP 185 EP 198 DI 10.1089/ars.2009.2826 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 538JY UT WOS:000273181600002 PM 19702440 ER PT J AU Butt, OI Buehler, PW D'Agnillo, F AF Butt, Omer I. Buehler, Paul W. D'Agnillo, Felice TI Differential Induction of Renal Heme Oxygenase and Ferritin in Ascorbate and Nonascorbate Producing Species Transfused with Modified Cell-Free Hemoglobin SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID POLYMERIZED BOVINE HEMOGLOBIN; EXCHANGE-TRANSFUSION; IN-VIVO; IRON; RAT; MODEL; TRANSLATION; EXPRESSION; OXIDATION; DISEASE AB Heme catabolism and iron sequestration systems play an important role in regulating the response to extracellular hemoglobin (Hb). We previously reported that extracellular Hb oxidizes more readily in the circulation of guinea pigs, a nonascorbate (AA)-producing species with similar plasma and tissue antioxidant status to humans, compared to rats, an AA-producing species. To determine whether these two species exhibit differences in heme catabolism and iron sequestration at the level of the kidney, we examined heme oxygenase (HO), H- and L-ferritin expression, nonheme iron deposition, and renal AA content following transfusion with polymerized bovine hemoglobin (HbG). Both species showed similar rates of hemoglobinuria but urinary HbG was significantly more oxidized in guinea pigs. HbG enhanced HO activity in both species but appeared greater and more sustained in guinea pigs. Conversely, rats showed a greater and more rapid induction of H- and L-ferritin as well as greater iron accumulation and AA content. Furthermore, ferrous and ferric iron deposits were detected in rats while only ferric iron was observed in guinea pigs. These findings suggest significant differences in the renal handling of HbG which may be important for understanding how endogenous antioxidant defenses may modulate the renal response to extracellular Hb. Antioxid. Redox Signal. 12, 199-208. C1 [Butt, Omer I.; Buehler, Paul W.; D'Agnillo, Felice] US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP D'Agnillo, F (reprint author), US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, 29 Lincoln Dr,Bldg 29,Rm 129, Bethesda, MD 20892 USA. EM felice.dagnillo@fda.hhs.gov FU CBER/FDA FX This work was supported by a Critical Path Initiative award from CBER/FDA. NR 35 TC 17 Z9 18 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JAN PY 2010 VL 12 IS 2 BP 199 EP 208 DI 10.1089/ars.2009.2798 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 538JY UT WOS:000273181600003 PM 19659432 ER PT J AU Buehler, PW D'Agnillo, F AF Buehler, Paul W. D'Agnillo, Felice TI Toxicological Consequences of Extracellular Hemoglobin: Biochemical and Physiological Perspectives SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID CROSS-LINKED HEMOGLOBIN; SICKLE-CELL-DISEASE; STROMA-FREE HEMOGLOBIN; INHALED NITRIC-OXIDE; EXPERIMENTAL INTRACEREBRAL HEMORRHAGE; EXPERIMENTAL SUBARACHNOID HEMORRHAGE; POLYMERIZED BOVINE HEMOGLOBIN; CULTURED ENDOTHELIAL-CELLS; MEDIATED OXIDATIVE INJURY; TRANSGENIC KNOCKOUT MICE AB Under normal physiology, human red blood cells (RBCs) demonstrate a circulating lifespan of similar to 100-120 days with efficient removal of senescent RBCs taking place via the reticuloendothelial system, spleen, and bone marrow phagocytosis. Within this time frame, hemoglobin (Hb) is effectively protected by efficient RBC enzymatic systems designed to allow for interaction between Hb and diffusible ligands while preventing direct contact between Hb and the external environment. Under normal resting conditions, the concentration of extracellular Hb in circulation is therefore minimal and controlled by specific plasma and cellular (monocyte/macrophage) binding proteins (haptoglobin) and receptors (CD163), respectively. However, during pathological conditions leading to hemolysis, extracellular Hb concentrations exceed normal plasma and cellular binding capacities, allowing Hb to become a biologically relevant vasoactive and redox active protein within the circulation and at extravascular sites. Under conditions of genetic, drug-induced, and autoimmune hemolytic anemias, large quantities of Hb are introduced into the circulation and often lead to acute renal failure and vascular dysfunction. Interestingly, the study of chemically modified Hb for use as oxygen therapeutics has allowed for some basic understanding of extracellular Hb toxicity, particularly in the absence of functional clearance mechanisms and in circulatory antioxidant depleted states. Antioxid. Redox Signal. 12, 275-291. C1 [Buehler, Paul W.; D'Agnillo, Felice] NIH, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res,FDA, Bethesda, MD 20892 USA. RP Buehler, PW (reprint author), NIH, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res,FDA, Campus 8800 Rockville Pike,Bldg 29,Rm 129, Bethesda, MD 20892 USA. EM paul.buehler@fda.hhs.gov FU CBER/FDA FX The work described was supported by a Critical Path Initiative award from CBER/FDA. We would like to thank Dr. Bindu Abraham for assistance in preparation of Fig. 3. NR 161 TC 44 Z9 45 U1 1 U2 19 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JAN PY 2010 VL 12 IS 2 BP 275 EP 291 DI 10.1089/ars.2009.2799 PG 17 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 538JY UT WOS:000273181600009 PM 19659434 ER PT J AU Naeger, LK Struble, KA Muffay, JS Birnkrant, DB AF Naeger, Lisa K. Struble, Kimberly A. Muffay, Jeffrey S. Birnkrant, Debra B. TI Running a tightrope: Regulatory challenges in the development of antiretrovirals SO ANTIVIRAL RESEARCH LA English DT Review DE HIV-1; Drug regulations; Accelerated approval; Surrogate endpoint; Fast track; Clinical trial designs; Resistance; PEPFAR; Expanded access ID EXPERIENCED HIV-1-INFECTED PATIENTS; IMMUNODEFICIENCY-VIRUS-INFECTION; RESISTANT HIV-1 INFECTION; PLACEBO-CONTROLLED TRIAL; CD4 CELL COUNTS; CUBIC MILLIMETER; DOUBLE-BLIND; TMC125 ETRAVIRINE; RANDOMIZED TRIAL; THERAPY AB Since the approval of Retrovir, (zidovudine, AZT) in 1987 by the Food and Drug Administration, a number of regulatory initiatives were codified into regulation which contributed to the rapid development of new treatments for HIV-1 infection. These initiatives are a testament to the efforts of AIDS activists and regulators to improve access to drugs for serious and life-threatening diseases. Currently, 28 antiretroviral drugs and combinations of antiretrovirals are available to treat HIV-1 infection. The broadening armamentarium of approved antiretroviral drugs provides new options and more choices for physicians and HIV patients. Importantly, the introduction of these newly approved HIV drugs has shown that the majority of HIV-1-infected treatment-naive and treatment-experienced patients can achieve maximal virologic suppression (less than 50 copies/mL HIV-1 RNA). This article describes the past and current regulatory challenges in the development of new HIV treatments and provides an overview of the drug regulations that were required for the approval of HIV drugs. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010. Published by Elsevier B.V. C1 [Naeger, Lisa K.; Struble, Kimberly A.; Muffay, Jeffrey S.; Birnkrant, Debra B.] US FDA, Div Antiviral Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Naeger, LK (reprint author), US FDA, Div Antiviral Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM lisa.naeger@fda.hhs.gov NR 37 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JAN PY 2010 VL 85 IS 1 SI SI BP 232 EP 240 DI 10.1016/j.antiviral.2009.07.016 PG 9 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 561LH UT WOS:000274978200017 PM 19665489 ER PT J AU Rosenzweig, JA Abogunde, O Thomas, K Lawal, A Nguyen, YU Sodipe, A Jejelowo, O AF Rosenzweig, Jason A. Abogunde, Ohunene Thomas, Kayama Lawal, Abidat Nguyen, Y-Uyen Sodipe, Ayodotun Jejelowo, Olufisayo TI Spaceflight and modeled microgravity effects on microbial growth and virulence SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Review DE Space microbiology; Microgravity; Low-shear modeled microgravity; Virulence; Bacteria ID BACTERIAL GENE-EXPRESSION; ESCHERICHIA-COLI BIOFILMS; POLYNUCLEOTIDE PHOSPHORYLASE; SALMONELLA-ENTERICA; SACCHAROMYCES-CEREVISIAE; GLOBAL REGULATOR; SHEAR-STRESS; TYPHIMURIUM; YERSINIA; HFQ AB For unsuspecting bacteria, the difference between life and death depends upon efficient and specific responses to various stressors. Facing a much larger world, microbes are invariably challenged with ever-changing environments where temperature, pH, chemicals, and nutrients are in a constant state of flux. Only those that are able to rapidly reprogram themselves and express subsets of genes needed to overcome the stress will survive and outcompete neighboring microbes. Recently, low shear stress, emulating microgravity (MG) experienced in space, has been characterized in a number of microorganisms including fungi and prokaryotes ranging from harmless surrogate organisms to bona fide pathogens. Interestingly, MG appears to induce a plethora of effects ranging from enhanced pathogenicity in several Gram-negative enterics to enhanced biofilm formation. Furthermore, MG-exposed bacteria appeared better able to handle subsequent stressors including: osmolarity, pH, temperature, and antimicrobial challenge while yeast exhibited aberrant budding post-MG-exposure. This review will focus on MG-induced alterations of virulence in various microbes with the emphasis placed on bacteria. C1 [Rosenzweig, Jason A.; Abogunde, Ohunene; Nguyen, Y-Uyen; Sodipe, Ayodotun; Jejelowo, Olufisayo] CBER, Houston, TX 77004 USA. [Rosenzweig, Jason A.; Abogunde, Ohunene; Thomas, Kayama; Lawal, Abidat; Nguyen, Y-Uyen; Sodipe, Ayodotun; Jejelowo, Olufisayo] Texas So Univ, Dept Biol Houston, Houston, TX 77004 USA. RP Rosenzweig, JA (reprint author), CBER, 3100 Cleburne St, Houston, TX 77004 USA. EM rosenzweigja@tsu.edu FU National Aeronautics and Space Administration (NASA) [NNX08B4A47A]; Texas Southern University [Sg0609] FX We would like to thank Duane L. Pierson, C. Mark Ott, and Ashok K. Chopra for discussion and guidance in our pursuit of space microbiology knowledge. We would also like to thank Dieter Haas, Shishir Shishodia, and Hector Miranda for valuable feedback and criticism. Work on this manuscript was supported by the National Aeronautics and Space Administration (NASA) cooperative agreement NNX08B4A47A, and Texas Southern University Start-Up Grant Sg0609. NR 24 TC 30 Z9 36 U1 3 U2 29 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0175-7598 J9 APPL MICROBIOL BIOT JI Appl. Microbiol. Biotechnol. PD JAN PY 2010 VL 85 IS 4 BP 885 EP 891 DI 10.1007/s00253-009-2237-8 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 543EW UT WOS:000273554900006 PM 19847423 ER PT J AU Savoie, N Garofolo, F van Amsterdam, P Booth, BP Fast, DM Lindsay, M Lowes, S Masse, R Mawee, L Ormsby, E Phull, R Rocci, ML Vallanou, PT Yin, X AF Savoie, Natasha Garofolo, Fabio van Amsterdam, Peter Booth, Brian P. Fast, Douglas M. Lindsay, Michael Lowes, Steve Masse, Robert Mawee, Louise Ormsby, Eric Phull, Rupinder Rocci, Mario L., Jr. Vallanou, Patrick T. Yin, Xia TI 2009 White Paper on Recent Issues in Regulated Bioanalysis from The 3rd Calibration and Validation Group Workshop SO BIOANALYSIS LA English DT Article ID ASSAYS AB The 3rd Calibration and Validation Group Workshop on Recent Issues in Regulated Bioanalysis was organized by the Calibration and Validation Group as a I.5-day full immersion workshop for contract research organizations, pharmaceutical companies and regulatory agencies to discuss several 'hot' topics concerning bioanalytical issues and regulatory challenges. A consensus was reached among panelists and attendees on many points regarding method validation of small molecules. C1 [Savoie, Natasha; Garofolo, Fabio] Algorithme Pharma Inc, Montreal, PQ H7V 4B3, Canada. [van Amsterdam, Peter] Solvay Pharmaceut, Weesp, Netherlands. [Booth, Brian P.] US FDA, CDER, Silver Spring, MD USA. [Fast, Douglas M.] Pfizer Global Res & Dev, Groton, CT USA. [Lindsay, Michael; Yin, Xia] Apotex Inc, Toronto, ON, Canada. [Lowes, Steve] Adv BioServ Inc, Ithaca, NY USA. [Masse, Robert] Anapharm Inc, Quebec City, PQ, Canada. [Mawee, Louise] Med & Healthcare Prod Regulatory Agcy MHRA, London, England. [Ormsby, Eric] Hlth Canada TPD, Ottawa, ON, Canada. [Phull, Rupinder] Barr Pharmaceut Inc, Montvale, NJ USA. [Rocci, Mario L., Jr.] Prevalere Life Sci Inc, Whitesboro, NY USA. [Vallanou, Patrick T.] Mylan Pharmaceut Inc, Morgantown, WV USA. RP Garofolo, F (reprint author), Algorithme Pharma Inc, 575 Armand Frappier Blvd, Montreal, PQ H7V 4B3, Canada. EM f.garofolo@algopharm.com FU US FDA; Health Canada TPD; UK MHRA; European Bioanalysis Forum (EBF); Workshop sustaining sponsors: Acanthus Research; Agilent Technologies; Algorithme Pharma; Anapharm; Cantest; CEDRA; Chemtos; Lachman Consultants; MDS Pharma Services; PPD; Prevalere Life Sciences; Synfine Research; Waters; Media Partner: Future Science Group FX On behalf of the Calibration and Validation Group, Dr Garofalo would like to thank: the US FDA, Health Canada TPD and UK MHRA for supporting this Workshop; all the workshop attendees and CVG members who have sent comments and suggestions to complete this report; speakers/panelists: Peter van Amsterdam (Solvay/EBF), Brian Booth (FDA), Douglas M Fast (Pfizer), Michael Lindsay (Apotex), Steve Lowes (Advion), Robert Masse (Anapharm), Louise Mawer (MHRA), Eric Ormsby (Health Canada), Rupinder Phull (Barr Laboratories), Mario L Rocci Jr (Prevalere), Patrick T Vallano (Mylan) and Xia Yin (Apotex); Natasha Savoie (Algorithme Pharma) for collecting the Workshop minutes and preparing the first draft of this White Paper; Wei Garofalo (Database Director, CVG) for the logistic organization of the event; Louis Caille (President, Algorithme Pharma) for supporting Dr Garofolo's initiative in organizing this event as part of the educational & didactic activities of CVG; Supporting Group: European Bioanalysis Forum (EBF); Workshop sustaining sponsors: Acanthus Research; Agilent Technologies; Algorithme Pharma; Anapharm; Cantest; CEDRA; Chemtos; Lachman Consultants; MDS Pharma Services; PPD; Prevalere Life Sciences; Synfine Research; Waters; Media Partner: Future Science Group. NR 16 TC 46 Z9 47 U1 0 U2 1 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 J9 BIOANALYSIS JI Bioanalysis PD JAN PY 2010 VL 2 IS 1 BP 53 EP 68 DI 10.4155/BIO.09.134 PG 16 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 644VP UT WOS:000281410100014 PM 21083120 ER PT J AU Mosley, SL Rancy, PC Peterson, DC Vionnet, J Saksena, R Vann, WF AF Mosley, Sylvester L. Rancy, Pumtiwitt C. Peterson, Dwight C. Vionnet, Justine Saksena, Rina Vann, Willie F. TI Chemoenzymatic synthesis of conjugatable oligosialic acids SO BIOCATALYSIS AND BIOTRANSFORMATION LA English DT Article; Proceedings Paper CT 8th Carbohydrate Bioengineering Meeting CY MAY 10-13, 2009 CL Ischia, ITALY DE Oligosialic acids; conjugatable oligosaccharides; fluorescent oligosialic acids; fluorogenic click reaction ID COLI K92 POLYSIALYLTRANSFERASE; ESCHERICHIA-COLI; CAMPYLOBACTER-JEJUNI; CAPSULAR POLYSACCHARIDE; NEISSERIA-MENINGITIDIS; GANGLIOSIDE MIMICS; BIOSYNTHESIS; VACCINE; OLIGOSACCHARIDE; CYCLOADDITION AB Bacterial polysaccharides are components of glycoconjugate vaccines against encapsulated bacterial pathogens. Because these vaccines are prepared by random coupling methods the structure of the immunogens is difficult to characterize. As a model for the development of well-defined glycoconjugates we have devised a chemoenzymatic method for preparation of conjugatable oligosialic acids. In this scheme, chemically synthesized azide or alkyne derivatives of lactosides are sialylated by bacterial sialyltransferases. An HPLC method to follow the progress of the enzymatic reaction was developed based on fluorogenic coupling partners of the Huisgen 1,3-cycloaddition reaction, since the azide and alkyne aglycons are not convenient chromaphores. We have used this chemoenzymatic scheme to synthesize oligosialic acids of Neisseria meningitidis group C polysaccharide with a conjugatable aglycon. The chemoenzymatically synthesized oligosialic acids were coupled to bovine serum albumin with the 1,3-cycloaddition reaction. The resulting glycoconjugate was reactive with N. meningitidis group C-specific monoclonal antibody, thus confirming this as a possible pathway to glycoconjugate antigens. C1 [Mosley, Sylvester L.; Rancy, Pumtiwitt C.; Peterson, Dwight C.; Vionnet, Justine; Saksena, Rina; Vann, Willie F.] US FDA, Lab Bacterial Polysaccharides, Div Bacterial Parasit & Allergen Prod, CBER, Bethesda, MD 20892 USA. RP Vann, WF (reprint author), US FDA, Lab Bacterial Polysaccharides, Div Bacterial Parasit & Allergen Prod, CBER, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM wvann@helix.nih.gov NR 29 TC 5 Z9 5 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1024-2422 J9 BIOCATAL BIOTRANSFOR JI Biocatal. Biotransform. PD JAN-FEB PY 2010 VL 28 IS 1 BP 41 EP 50 DI 10.3109/10242420903388694 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 555MM UT WOS:000274514900006 ER PT J AU Epstein, JS AF Epstein, Jay S. TI Alternative strategies in assuring blood safety: An Overview SO BIOLOGICALS LA English DT Article DE Blood safety; Pathogen reduction; Emerging pathogen; Nanoparticle; Microarray; Aptamer ID PATHOGEN INACTIVATION; VIRAL-INFECTIONS; THERAPEUTIC-EFFICACY; SPRINT TRIAL; PREVALENCE; PLATELETS; COMPONENTS; DONORS; RISK AB Assuring transfusion safety is an essential element of health care in all countries, requiring government commitment, national policy and a legal framework. Fundamental safety strategies include selection of low risk donors, Good Manufacturing Practices in preparation of blood components, and appropriate clinical use including avoidance of unnecessary transfusions Hemovigilance, including surveillance for known adverse events and sentinel reporting of unexpected adverse events, enhances safety through bench-marking to promote best practices and by enabling rapid responses to new threats. Preventing transmission of infectious diseases is a principal safety concern Selection of low risk donors includes use of screening questions to elicit risk factors known to be associated with transmissible infections. Laboratory testing for specific infectious disease markers is an established strategy for interdicting contaminated donations The sensitivity, specificity, and operational convenience of laboratory testing have improved over time and newer technologies are imminent. Donor screening and laboratory testing, while highly effective in reducing risk, cannot eliminate all risk from known agents and must be developed de novo to address emerging infections. In contrast, pathogen reduction technologies offer the possibility for robust inactivation of a broad spectrum of blood transmissible agents and provide an added safeguard against newly emerging infectious threats of most types. Current pathogen reduction methods also inactivate leukocytes, adding safety benefits similar to leukocyte removal and product irradiation. However, to date, concerns about the safety and efficacy of cellular blood components treated by pathogen reduction have prevented approval of these technologies in the U.S and Canada. FDA is promoting clinical and basic scientific studies to clarify these issues and would consider alternative approaches to assuring blood safety if pathogen reduction technologies are proven to be safe and effective (C) 2009 Published by Elsevier Ltd on behalf of The International Association for Biologicals. C1 US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Rockville, MD 20852 USA. RP Epstein, JS (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, HFM-300,1401 Rockville Pike, Rockville, MD 20852 USA. NR 19 TC 14 Z9 14 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD JAN PY 2010 VL 38 IS 1 BP 31 EP 35 DI 10.1016/j.biologicals.2009.10.009 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 580CX UT WOS:000276425600006 PM 20110174 ER PT S AU Chan, YP Bouaynaya, N Chowdhury, P Leszczynska, D Patterson, TA Tarasenko, O AF Chan, Yupo Bouaynaya, Nidhal Chowdhury, Parimal Leszczynska, Danuta Patterson, Tucker A. Tarasenko, Olga BA Alusta, P BF Alusta, P BE Tarasenko, O Chowdhury, P Mehta, R Kohdakovskaya, M Milanova, M Ali, N TI PREDICTIVE MODELS OF COGNITIVE OUTCOMES OF DEVELOPMENTAL INSULTS SO BIOLOGY, NANOTECHNOLOGY, TOXICOLOGY, AND APPLICATIONS SE AIP Conference Proceedings LA English DT Proceedings Paper CT 4th BioNanoTox & Applications Research Conference CY OCT 21-22, 2009 CL Little Rock, AR SP Dept Health & Human Serv, Food & Drug Adm, Natl Ctr Toxicol Res, Univ Arkansas, Coll Sci & Math, Univ Arkansas, Dept Biol, Univ Arkansas, Chancellor Off, Univ Arkansas, Graduate Sch, Univ Arkansas, Graduate Inst Technol, Univ Arkansas, Coll Engn & Info Technol, Univ Arkansas Med Sci, Arkansas Biosci Inst, BioNanoTox Intl (BNT) DE developmental perturbations; neurological consequences; predictive model; evoked potential; mammalian species AB Representatives of Arkansas medical, research and educational institutions have gathered over the past four years to discuss the relationship between functional developmental perturbations and their neurological consequences. We wish to track the effect on the nervous system by developmental perturbations over time and across species. Except for perturbations, the sequence of events that occur during neural development was found to be remarkably conserved across mammalian species. The tracking includes consequences on anatomical regions and behavioral changes. The ultimate goal is to develop a predictive model of long-term genotypic and phenotypic outcomes that includes developmental insults. Such a model can subsequently be fostered into an educated intervention for therapeutic purposes. Several datasets were identified to test plausible hypotheses, ranging from evoked potential datasets to sleep-disorder datasets. An initial model may be mathematical and conceptual. However, we expect to see rapid progress as large-scale gene expression studies in the mammalian brain permit genome-wide searches to discover genes that are uniquely expressed in brain circuits and regions. These genes ultimately control behavior. By using a validated model we endeavor to make useful predictions. C1 [Chan, Yupo; Bouaynaya, Nidhal] Univ Arkansas, Dept Syst Engn, Little Rock, AR 72204 USA. [Chowdhury, Parimal] Univ Arkansas Med Sci, Dept Physiol & Biophys, Little Rock, AR 72204 USA. [Leszczynska, Danuta] Jackson State Univ, Interdisciplin Nanotox Ctr, Dept Civil & Environm Engn, Jackson, MS USA. [Patterson, Tucker A.] Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR USA. [Tarasenko, Olga] Univ Arkansas Little Rock, Dept Biol, Little Rock, AR USA. RP Chan, YP (reprint author), Univ Arkansas, Dept Syst Engn, Little Rock, AR 72204 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0773-2 J9 AIP CONF PROC PY 2010 VL 1229 BP 87 EP + PG 3 WC Nanoscience & Nanotechnology; Physics, Applied SC Science & Technology - Other Topics; Physics GA BRM21 UT WOS:000283090100014 ER PT J AU Anchoori, RK Harikumar, KB Batchu, VR Aggarwal, BB Khan, SR AF Anchoori, Ravi Kumar Harikumar, Kuzhuvelil B. Batchu, Venkateswara Rao Aggarwal, Bharat B. Khan, Saeed R. TI Inhibition of IkB kinase and NF-kappa B by a novel synthetic compound SK 2009 SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE Novel chemical entities; TNF; NF-kappa B; IKK; KBM-5 cells; Simplactones ID ACTIVATION; APOPTOSIS AB The NF-kappa B family of transcription factors plays an important role in determining cell survival during immune, inflammatory, and stress responses. NF-kappa B activity is frequently deregulated in human cancers and is implicated in the resistance of tumor cells to diverse anticancer agents. We studied the effects of novel analogs of precursors of the natural product simplactone (A) on the activity of IkB kinase and NF-kappa B. Screening of six compounds for the ability to inhibit TNF-induced NF-kappa B activity revealed that compound SK2009 was the most potent of these compounds in suppressing NF-kappa B activation in KBM-5 leukemic cells. Further characterization of SK2009 indicates that this newly synthesized molecule can suppress TNF-induced I kappa B alpha kinase activation and inhibit the expression of three NF-kappa B-dependent gene products, cyclin D1, Bcl-2, and VEGF, in these cells. Published by Elsevier Ltd. C1 [Anchoori, Ravi Kumar; Khan, Saeed R.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Div Chem Therapeut, Baltimore, MD USA. [Harikumar, Kuzhuvelil B.; Aggarwal, Bharat B.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Cytokine Res Lab, Houston, TX 77030 USA. [Batchu, Venkateswara Rao] Indian Inst Chem Technol, Div Organ Chem 3, Hyderabad 500007, Andhra Pradesh, India. [Khan, Saeed R.] FDA CDER, Silver Spring, MD USA. RP Khan, SR (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Div Chem Therapeut, Baltimore, MD USA. EM khansa@jhmi.edu RI Aggarwal, Bharat/G-3388-2013; venkateswararao, batchu/H-7114-2014; OI Harikumar, KB/0000-0002-1763-4179 FU FAMRI; Clayton Foundation for Research FX We gratefully acknowledge the financial support of FAMRI grant (to S. R. K). Dr. Aggarwal is Ransom Horne, Jr., Professor of Cancer Research. This work was supported by a grant from the Clayton Foundation for Research (to B. B. A.). NR 14 TC 12 Z9 12 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JAN 1 PY 2010 VL 18 IS 1 BP 229 EP 235 DI 10.1016/j.bmc.2009.10.065 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 534JJ UT WOS:000272892100026 PM 19962318 ER PT B AU Volpe, DA AF Volpe, Donna A. BE Mossillo, P Pinzini, J TI METHOD SUITABILITY FOR MODELS OF INTESTINAL DRUG PERMEABILITY SO BIOPHARMACEUTICS AND DRUG HYPERSENSITIVITY SE Pharmacology Research Safety Testing and Regulation LA English DT Article; Book Chapter ID MEMBRANE PERMEATION ASSAY; IN-VITRO PERMEABILITY; CACO-2 CELL MONOLAYERS; EVERTED GUT SAC; ARTIFICIAL MEMBRANE; GASTROINTESTINAL-TRACT; ABSORPTION MODELS; PASSIVE DIFFUSION; USSING CHAMBER; TRANSPORT AB Permeability is one of several factors influencing the intestinal absorption of oral drug products. As such, it is the focus of in situ, ex vivo and in vitro experimental models in animals, excised tissues, cell monolayers and artificial membranes. The reliability and validity of these models is demonstrated by their capacity to correctly predict a drug's in vivo intestinal absorption. Differences in the performance of the assays, along with variability in animal species, tissue sources and cell types, have lead to different effective (P(eff)) or apparent (P(app)) permeability values for the same drug between laboratories. A solution to this complication is method suitability which provides a generalized approach to standardize and validate a permeability model within a laboratory. The assay's methodology is first optimized and validated for its various assay parameters (e.g., tissue/cell source, transport conditions, data analysis). Then the suitability of the model is demonstrated by a correlative rank-order relationship between experimental permeability values and in vivo human extent of absorption for a set of model compounds. Finally, reference standards and assay acceptance criteria are utilized to classify or rank-order a drug's intestinal permeability. The advantages of this system are that it accounts for intra- and inter-laboratory variability, allows for improvement in assay technology, and is applicable to animal, tissue and cell permeability models. This review will provide examples of the use of method suitability in in situ (intestinal perfusions), ex vivo (gut sacs, diffusion chambers) and in vitro (cell monolayers, artificial membranes) experimental models. Method suitability, with its reliance on assay standardization, reference standards and acceptance criteria, ensures the reliability of experimental data to predict a drug's intestinal permeability during its discovery, development and regulatory application phases. C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Volpe, DA (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. NR 94 TC 0 Z9 0 U1 1 U2 3 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60741-830-6 J9 PHARM RES SAF TEST PY 2010 BP 99 EP 127 PG 29 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BPO34 UT WOS:000279533100003 ER PT J AU Pogribny, IP AF Pogribny, Igor P. TI Ferroportin and hepcidin: a new hope in diagnosis, prognosis, and therapy for breast cancer SO BREAST CANCER RESEARCH LA English DT Article ID IRON-METABOLISM; NEOPLASTIC-CELLS AB Breast cancer is the most prevalent malignancy in women. The success of breast cancer treatment relies on the ability to detect the disease and correct molecular abnormalities at an early stage of disease development. A recent article describes a marked decrease in the levels of ferroportin in breast cancer. More importantly, the presented results demonstrate convincingly the incredible diagnostic and prognostic value of ferroportin and hepcidin gene expression in breast cancer and suggest that determination of these two molecular markers may be used as guidance toward individualized therapy for breast cancer patients. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov NR 14 TC 6 Z9 8 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2010 VL 12 IS 5 AR 314 DI 10.1186/bcr2641 PG 2 WC Oncology SC Oncology GA 697IG UT WOS:000285506100031 PM 21062518 ER PT J AU Popovici, V Chen, WJ Gallas, BG Hatzis, C Shi, WW Samuelson, FW Nikolsky, Y Tsyganova, M Ishkin, A Nikolskaya, T Hess, KR Valero, V Booser, D Delorenzi, M Hortobagyi, GN Shi, LM Symmans, WF Pusztai, L AF Popovici, Vlad Chen, Weijie Gallas, Brandon G. Hatzis, Christos Shi, Weiwei Samuelson, Frank W. Nikolsky, Yuri Tsyganova, Marina Ishkin, Alex Nikolskaya, Tatiana Hess, Kenneth R. Valero, Vicente Booser, Daniel Delorenzi, Mauro Hortobagyi, Gabriel N. Shi, Leming Symmans, W. Fraser Pusztai, Lajos TI Effect of training-sample size and classification difficulty on the accuracy of genomic predictors SO BREAST CANCER RESEARCH LA English DT Article ID GENE-EXPRESSION PROFILES; NEGATIVE BREAST-CANCER; PREOPERATIVE CHEMOTHERAPY; TUMORS; CYCLOPHOSPHAMIDE; FLUOROURACIL; CLASSIFIERS; DOXORUBICIN; UNIVARIATE; PACLITAXEL AB Introduction: As part of the MicroArray Quality Control (MAQC)-II project, this analysis examines how the choice of univariate feature-selection methods and classification algorithms may influence the performance of genomic predictors under varying degrees of prediction difficulty represented by three clinically relevant endpoints. Methods: We used gene-expression data from 230 breast cancers (grouped into training and independent validation sets), and we examined 40 predictors (five univariate feature-selection methods combined with eight different classifiers) for each of the three endpoints. Their classification performance was estimated on the training set by using two different resampling methods and compared with the accuracy observed in the independent validation set. Results: A ranking of the three classification problems was obtained, and the performance of 120 models was estimated and assessed on an independent validation set. The bootstrapping estimates were closer to the validation performance than were the cross-validation estimates. The required sample size for each endpoint was estimated, and both gene-level and pathway-level analyses were performed on the obtained models. Conclusions: We showed that genomic predictor accuracy is determined largely by an interplay between sample size and classification difficulty. Variations on univariate feature-selection methods and choice of classification algorithm have only a modest impact on predictor performance, and several statistically equally good predictors can be developed for any given classification problem. C1 [Valero, Vicente; Booser, Daniel; Hortobagyi, Gabriel N.; Pusztai, Lajos] Dept Breast Med Oncol, Houston, TX 77230 USA. [Popovici, Vlad; Delorenzi, Mauro] Swiss Inst Bioinformat, Bioinformat Core Facil, CH-1015 Lausanne, Switzerland. [Chen, Weijie; Gallas, Brandon G.; Samuelson, Frank W.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Hatzis, Christos] Nuvera Biosci, Woburn, MA 01801 USA. [Shi, Weiwei; Nikolsky, Yuri; Nikolskaya, Tatiana] GeneGo Inc, St Joseph, MI 49085 USA. [Tsyganova, Marina; Ishkin, Alex; Nikolskaya, Tatiana] Russian Acad Sci, Vavilov Inst Gen Genet, Dept Syst Biol, Moscow 119333, Russia. [Hess, Kenneth R.] Dept Biostat, Houston, TX 77230 USA. [Delorenzi, Mauro] Ecole Polytech Fed Lausanne, Sch Life Sci, ISREC, Swiss NCCR Mol Oncol, CH-1015 Lausanne, Switzerland. [Shi, Leming] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Symmans, W. Fraser] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77230 USA. RP Pusztai, L (reprint author), Dept Breast Med Oncol, POB 301439, Houston, TX 77230 USA. EM lpusztai@mdanderson.org RI Popovici, Vlad/C-2039-2008; Chen, Weijie/A-3712-2012; Nikolskaya, Tatiana/M-5008-2013; Hatzis, Christos/M-3867-2015; OI Popovici, Vlad/0000-0002-1311-9188; Hatzis, Christos/0000-0002-8120-2290; Gallas, Brandon/0000-0001-7332-1620 FU NCI [R-01]; Breast Cancer Research Foundation; MD Anderson Cancer Center; Commonwealth Cancer Fundation; Swiss National Science Foundation NCCR Molecular Oncology FX This research was supported by grants from the NCI R-01 program (LP), The Breast Cancer Research Foundation (LP and WFS), The MD Anderson Cancer Center Faculty Incentive Funds (WFS), and the Commonwealth Cancer Fundation (LP, WFS). VP and MD acknowledge the support of the Swiss National Science Foundation NCCR Molecular Oncology. Certain commercial materials and equipment are identified to specify experimental procedures adequately. In no case does such identification imply recommendation or endorsement by the FDA, nor does it imply that the items identified are necessarily the best available for the purpose. The views presented in this article do not necessarily reflect those of the U. S. Food and Drug Administration. NR 28 TC 72 Z9 75 U1 0 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2010 VL 12 IS 1 AR R5 DI 10.1186/bcr2468 PG 13 WC Oncology SC Oncology GA 587JD UT WOS:000276986300011 PM 20064235 ER PT J AU Chen, JJ Roberson, PK Schell, MJ AF Chen, James J. Roberson, Paula K. Schell, Michael J. TI The False Discovery Rate: A Key Concept in Large-Scale Genetic Studies SO CANCER CONTROL LA English DT Article AB Background: In experimental research, a statistical test is often used for making decisions on a null hypothesis such as that the means of gene expression in the normal and tumor groups are equal. Typically, a test statistic and its corresponding P value are calculated to measure the extent of the difference between the two groups. The null hypothesis is rejected and a discovery is declared when the P value is less than a prespecified significance level. When more than one test is conducted, use of a significance level intended for use by a single test typically leads to a large chance of false-positive findings. Methods: This paper presents an overview of the multiple testing framework and describes the false discovery rate (FDR) approach to determining the significance cutoff when a large number of tests are conducted. Results: The FDR is the expected proportion of the null hypotheses that are falsely rejected divided by the total number of rejections. An FDR-controlling procedure is described and illustrated with a numerical example. Conclusions: In multiple testing, a classical "family-wise error rate" (FWE) approach is commonly used when the number of tests is small. When a study involves a large number of tests, the FDR error measure is a more useful approach to determining a significance cutoff, as the FWE approach is too stringent. The FDR approach allows more claims of significant differences to be made, provided the investigator is willing to accept a small fraction of false-positive findings. C1 [Chen, James J.] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Roberson, Paula K.] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. [Schell, Michael J.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Biostat, Tampa, FL 33612 USA. RP Chen, JJ (reprint author), US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, HFT 20, Jefferson, AR 72079 USA. EM JamesJ.Chen@fda.hhs.gov NR 29 TC 18 Z9 20 U1 1 U2 4 PU H LEE MOFFITT CANCER CENTER & RESEARCH INST PI TAMPA PA 12902 MAGNOLIA DR, TAMPA, FL 33612 USA SN 1073-2748 J9 CANCER CONTROL JI Cancer Control PD JAN PY 2010 VL 17 IS 1 BP 58 EP 62 PG 5 WC Oncology SC Oncology GA V24TW UT WOS:000208433700008 PM 20010520 ER PT J AU Reimschuessel, R Mayer, T Hasbrouck, N Gieseker, C AF Reimschuessel, Renate Mayer, Tamara Hasbrouck, Nicholas Gieseker, Charles TI Fish: A Nonmammalian Model for Determining a "No Observable Effect Level" (NOEL) for Crystal Formation in Kidneys after Exposure to Melamine and Cyanuric Acid SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT 238th American-Chemical-Society National Meeting CY AUG 16-20, 2009 CL Washington, DC SP Amer Chem Soc, Div Chem Toxicol, Amer Chem Soc, Env Chem Inc C1 [Reimschuessel, Renate; Mayer, Tamara; Hasbrouck, Nicholas; Gieseker, Charles] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. EM renate.reimschuessel@fda.hhs.gov; tamara.mayer@fda.hhs.gov; nicholas.hasbrouck@fda.hhs.gov; charles.gieseker@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN PY 2010 VL 23 IS 1 MA 7 BP 265 EP 265 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 543YU UT WOS:000273618500038 ER PT J AU Atrakchi, A AF Atrakchi, Aisar TI FDA Guidance on the Safety Testing of Drug Metabolites: Scientific Recommendations with Flexible Interpretation SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT 238th American-Chemical-Society National Meeting CY AUG 16-20, 2009 CL Washington, DC SP Amer Chem Soc, Div Chem Toxicol, Amer Chem Soc, Env Chem Inc C1 [Atrakchi, Aisar] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM Aisar.atrakchi@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN PY 2010 VL 23 IS 1 MA 40 BP 273 EP 273 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 543YU UT WOS:000273618500071 ER PT J AU Cobb, J Lee, A Tran-Son-Tay, R Sarntinoranont, M Luu, HMD AF Cobb, Jessica Lee, Alexandra Tran-Son-Tay, Roger Sarntinoranont, Malisa Luu, Hoan-My D. TI Evaluation of Hyaluronic Acid-Based Ocular Viscosurgical Devices (OVDs) Using an in Vitro Human Corneal Epithelial Cell Line Model SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT 238th American-Chemical-Society National Meeting CY AUG 16-20, 2009 CL Washington, DC SP Amer Chem Soc, Div Chem Toxicol, Amer Chem Soc, Env Chem Inc C1 [Cobb, Jessica] Univ Florida, Dept Biomed Engn, Gainesville, FL 32611 USA. [Lee, Alexandra] Univ Florida, Dept Agr & Biol Engn, Gainesville, FL 32611 USA. [Tran-Son-Tay, Roger; Sarntinoranont, Malisa] Univ Florida, Dept Bioengn, Gainesville, FL 32611 USA. [Tran-Son-Tay, Roger; Sarntinoranont, Malisa] Univ Florida, Dept Mech & Aerosp Engn, Gainesville, FL 32611 USA. [Luu, Hoan-My D.] US FDA, Off Sci & Engn Labs, Div Chem & Mat Sci, Silver Spring, MD 20903 USA. EM Hoan-My.Luu@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN PY 2010 VL 23 IS 1 MA 50 BP 276 EP 276 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 543YU UT WOS:000273618500081 ER PT J AU Tareke, E Gamboa, G Heinz, T Ali, S AF Tareke, Eden Gamboa, Goncalo Heinz, Thomas Ali, Syed TI Formation of Acrylamide at 37C: Role of Oxidative Stress SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT 238th American-Chemical-Society National Meeting CY AUG 16-20, 2009 CL Washington, DC SP Amer Chem Soc, Div Chem Toxicol, Amer Chem Soc, Env Chem Inc C1 [Tareke, Eden] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Gamboa, Goncalo; Heinz, Thomas] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Ali, Syed] US FDA, Natl Ctr Toxicol Res, Div Neurotox, Jefferson, AR 72079 USA. EM edunatar@hotmail.com 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 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN PY 2010 VL 23 IS 1 MA 70 BP 280 EP 281 PG 2 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 543YU UT WOS:000273618500101 ER PT J AU Antunes, AMM Sidarus, MC Beland, FA Marques, MM AF Antunes, Alexandra M. M. Sidarus, Muna C. Beland, Frederick A. Marques, M. Matilde TI Synthesis and Oxidation of 2-Hydroxynevirapine, a Metabolite of the HIV-1 Reverse Transcriptase Inhibitor Nevirapine SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT 238th National Meeting of the American-Chemical-Society (ACS)/American-Chemical-Society (ACS) Symposium on Emerging Contaminants, Pharmaceuticals and Personal Care Products (PPCPs), and Organohalogens in Wastewater and Municipal Biosolids CY AUG 16-20, 2009 CL Washington, DC SP Amer Chem Soc, Div Chem Toxicol, Amer Chem Soc, Env Chem Inc C1 [Antunes, Alexandra M. M.; Sidarus, Muna C.; Marques, M. Matilde] Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, P-1049001 Lisbon, Portugal. [Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM alexandra.antunes@ist.utl.pt; msidarus@gmail.com; frederick.beland@fda.hhs.gov; matilde.marques@ist.utl.pt RI Marques, M. Matilde/E-2535-2012; PTMS, RNEM/C-1589-2014; Antunes, Alexandra/B-7871-2009 OI Marques, M. Matilde/0000-0002-7526-4962; Antunes, Alexandra/0000-0003-1827-7369 NR 0 TC 0 Z9 0 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN PY 2010 VL 23 IS 1 MA 87 BP 284 EP 285 PG 2 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 543YU UT WOS:000273618500118 ER PT J AU Pos, Z Thomas, J Selleri, S Spivey, T Wang, J Liu, H Worschech, A Sabatino, M Monaco, A Alter, H Falus, A Wang, E Marincola, F AF Pos, Zoltan Thomas, Jaime Selleri, Silvia Spivey, Tara Wang, Jeanne Liu, Hui Worschech, Andrea Sabatino, Marianna Monaco, Alessandro Alter, Harvey Falus, Andras Wang, Ena Marincola, Francesco TI The Impact of Race on Interferon-alpha Responsiveness: A Genome-wide Study SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Pos, Zoltan; Thomas, Jaime; Spivey, Tara; Liu, Hui; Sabatino, Marianna; Monaco, Alessandro; Alter, Harvey; Wang, Ena; Marincola, Francesco] Natl Inst Hlth, Bethesda, MD USA. [Selleri, Silvia] Ist Sci San Raffaele, Milan, Italy. [Wang, Jeanne] US FDA, Silver Spring, MD USA. [Worschech, Andrea] Univ Wurzburg, Wurzburg, Germany. [Falus, Andras] Semmelweis Univ, Budapest, Hungary. RI Worschech, Andrea/I-3919-2012; Monaco, Alessandro/O-5338-2015 OI Worschech, Andrea/0000-0002-4303-8653; Monaco, Alessandro/0000-0002-9941-7003 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S45 EP S45 DI 10.1016/j.clim.2010.03.138 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700122 ER PT J AU Lee, JI Zhang, L Men, AY Kenna, LA Huang, SM AF Lee, Jang-Ik Zhang, Lei Men, Angela Y. Kenna, Leslie A. Huang, Shiew-Mei TI CYP-Mediated Therapeutic Protein-Drug Interactions Clinical Findings, Proposed Mechanisms and Regulatory Implications SO CLINICAL PHARMACOKINETICS LA English DT Review ID TUMOR-NECROSIS-FACTOR; HEPATIC CYTOCHROME-P450 ACTIVITY; CONGESTIVE-HEART-FAILURE; GROWTH-HORMONE; TRANSPLANT RECIPIENTS; THEOPHYLLINE PHARMACOKINETICS; MONOCLONAL-ANTIBODIES; METABOLIZING-ENZYMES; INTERFERON-ALPHA; IN-VIVO AB Therapeutic proteins (TPs) may affect the disposition of drugs that are metabolized by cytochrome P450 (CYP) enzymes, as is evident from a review of data in recently published literature and approved Biologic License Applications. Many TPs belonging to the cytokine class appear to differentially affect CYP activities. Cytokine modulators may affect CYP enzyme activities by altering cytokine effects on CYP enzymes. The alteration in CYP enzyme activities seems to result from changes in transcription factor activity for CYP enzyme expression or changes in CYP enzyme stability, which have been observed during altered immunological states such as infection and inflammation. Human growth hormone also appears to differentially affect CYP activities through unknown mechanisms. Because TP-drug interaction research is an evolving area, limited information is available during drug development on TP-drug interactions mediated by CYP inhibition or induction. The authors of this review suggest that effort be made to understand TP-drug interactions for the safe and effective use of TPs in combination with small-molecule drugs. C1 [Lee, Jang-Ik; Zhang, Lei; Men, Angela Y.; Huang, Shiew-Mei] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Kenna, Leslie A.] US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Lee, JI (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM jangik.lee@fda.hhs.gov NR 60 TC 39 Z9 41 U1 1 U2 7 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0312-5963 EI 1179-1926 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PY 2010 VL 49 IS 5 BP 295 EP 310 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 596EZ UT WOS:000277669000002 PM 20384392 ER PT J AU Mahmood, I AF Mahmood, Iftekhar TI Interspecies Scaling for the Prediction of Drug Clearance in Children SO CLINICAL PHARMACOKINETICS LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; SINGLE-DOSE PHARMACOKINETICS; HUMAN-IMMUNODEFICIENCY-VIRUS; PEDIATRIC-PATIENTS; AMPHOTERICIN-B; CLINICAL PHARMACOKINETICS; KETOROLAC TROMETHAMINE; HEALTHY-SUBJECTS; BODY-WEIGHT; INFANTS AB Background and Objective: lnterspecies pharmacokinetic scaling is widely used to predict pharmacokinetic parameters in adult humans but has not been used for the prediction of pharmacokinetic parameters in children. The current study was undertaken to evaluate whether or not drug clearance in children from adult rat, dog and human clearance values could be predicted allometrically. Methods: Four methods (simple allometry, maximum lifespan potential [MLP], MLP with an empirical correction factor and a fixed exponent of 0.75 in association with adult data) were used for the prediction of drug clearance in children. The first three methods included adult animal (rat and dog) data and human data, whereas the fixed exponent of 0.75 included only adult human data. Results: The results of this study indicated that simple allometry would systematically overpredict drug clearance in children, whereas application of MLP would underpredict drug clearance in children. Therefore, an empirical correction factor was introduced into MLP, which substantially improved the prediction of drug clearance in children. Prediction based on a fixed exponent of 0.75 and adult human clearance was highly erratic and inferior to the prediction of drug clearance in children from MLP or MLP with an empirical correction factor. Conclusions: Overall, the results of the study indicated that interspecies scaling using adult rat, dog and human clearance values could be useful to predict drug clearance in children in different age groups. C1 US FDA, Div Hematol, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Div Hematol, Off Blood Res & Review, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM iftekhar.mahmood@fda.hhs.gov NR 106 TC 11 Z9 11 U1 0 U2 3 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0312-5963 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PY 2010 VL 49 IS 7 BP 479 EP 492 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 620CY UT WOS:000279477800006 PM 20528008 ER PT J AU Huang, SM Zhang, L Giacomini, KM AF Huang, S-M Zhang, L. Giacomini, K. M. TI The International Transporter Consortium: A Collaborative Group of Scientists From Academia, Industry, and the FDA SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article; Proceedings Paper CT FDA Critical Path Transporter Workshop CY OCT 02-03, 2008 CL Bethesda, MD ID DRUG-DRUG INTERACTIONS; EFFLUX TRANSPORTERS; KIDNEY; IMPACT; LIVER; OATP AB The US Food and Drug Administration-led Critical Path Initiative, launched in 2004, has resulted in an array of activities focused on the sciences that support the development of human medical products.(1) These activities include the development of new scientific tools, such as in vitro testing, qualified biomarkers of drug safety, and innovative new methods in study design and data analysis.(2) As a result of the Critical Path Initiative and enormous advances in the field of membrane transporters, the International Transporter Consortium was formed. C1 [Giacomini, K. M.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. [Huang, S-M; Zhang, L.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Giacomini, KM (reprint author), Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. EM kathy.giacomini@ucsf.edu NR 15 TC 34 Z9 34 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 JAN PY 2010 VL 87 IS 1 BP 32 EP 36 DI 10.1038/clpt.2009.236 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 537VA UT WOS:000273141100013 PM 20019700 ER PT S AU Martinez, M Silley, P AF Martinez, Marilyn Silley, Peter BE Cunningham, F Elliott, J Lees, P TI Antimicrobial Drug Resistance SO COMPARATIVE AND VETERINARY PHARMACOLOGY SE Handbook of Experimental Pharmacology LA English DT Article; Book Chapter DE Antimicrobial resistance; PK/PD; Dose selection; Antimicrobial tolerance ID FOOD ANIMALS POSE; MUTANT PREVENTION CONCENTRATION; URINARY BACTERICIDAL ACTIVITY; GROWTH-PROMOTING ANTIBIOTICS; DIFFERENT EUROPEAN COUNTRIES; STAPHYLOCOCCUS-AUREUS; ESCHERICHIA-COLI; HUMAN HEALTH; IN-VITRO; PSEUDOMONAS-AERUGINOSA AB This chapter provides an overview of our current understanding of the mechanisms associated with the development of antimicrobial drug resistance, international differences in definitions of resistance, ongoing efforts to track shifts in drug susceptibility, and factors that can influence the selection of therapeutic intervention. The latter presents a matrix of complex variables that includes the mechanism of drug action, the pharmacokinetics (PK) of the antimicrobial agent in the targeted patient population, the pharmacodynamics (PD) of the bacterial response to the antimicrobial agent, the PK/PD relationship that will influence dose selection, and the integrity of the host immune system. Finally, the differences between bacterial tolerance and bacterial resistance are considered, and the potential for non-traditional anti-infective therapies is discussed. C1 [Martinez, Marilyn] US FDA, Off New Anim Drug Evaluat HFV 130, Ctr Vet Med, Rockville, MD 20855 USA. [Silley, Peter] MB Consult Ltd, Southampton SO14 3XB, Hants, England. RP Martinez, M (reprint author), US FDA, Off New Anim Drug Evaluat HFV 130, Ctr Vet Med, 7500 Standish Pl, Rockville, MD 20855 USA. EM marilyn.martinez@fda.hhs.gov; p-s@mbconsult.co.uk NR 145 TC 17 Z9 19 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0171-2004 BN 978-3-642-10323-0 J9 HANDB EXP PHARMACOL JI Handb. Exp. Pharmacol. PY 2010 VL 199 BP 227 EP 264 DI 10.1007/978-3-642-10324-7_10 D2 10.1007/978-3-642-10324-7 PG 38 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BOZ45 UT WOS:000278106500010 ER PT J AU Hansen, DK AF Hansen, D. K. BE McQueen, CA TI Developmental Toxicity of Antiepileptic Drugs SO COMPREHENSIVE TOXICOLOGY, VOL 12: DEVELOPMENTAL TOXICOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID NEURAL-TUBE DEFECTS; MURINE EMBRYO CULTURE; ACID-INDUCED EMBRYOTOXICITY; ENHANCED OXIDATIVE STRESS; VALPROIC ACID; PHENYTOIN TERATOGENICITY; IN-VIVO; PREGNANCY OUTCOMES; FOLIC-ACID; CONGENITAL-MALFORMATIONS C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Hansen, DK (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 119 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046884-6 PY 2010 BP 177 EP 187 PG 11 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA BA2HH UT WOS:000333408300013 ER PT J AU Singh, AV Kavlock, RJ Richard, AM Yang, C AF Singh, A. V. Kavlock, R. J. Richard, A. M. Yang, C. BE McQueen, CA TI Computational Toxicology SO COMPREHENSIVE TOXICOLOGY, VOL 12: DEVELOPMENTAL TOXICOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID TOXICITY HAZARD IDENTIFICATION; DEFECTS SYSTEMS MANAGER; DEVELOPMENTAL TOXICITY; ENVIRONMENTAL CHEMICALS; EXPRESSION PROFILES; COMPREHENSIVE MODEL; NCBI GEO; DATABASE; ARRAYEXPRESS; RESOURCES C1 [Singh, A. V.] Natl Ctr Computat Toxicol B205 01, Res Triangle Pk, NC 27711 USA. [Kavlock, R. J.; Richard, A. M.] Natl Ctr Computat Toxicol, Res Triangle Pk, NC USA. [Yang, C.] Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Singh, AV (reprint author), Natl Ctr Computat Toxicol B205 01, Res Triangle Pk, NC 27711 USA. NR 68 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046884-6 PY 2010 BP 307 EP 337 PG 31 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA BA2HH UT WOS:000333408300021 ER PT J AU Slikker, W AF Slikker, W. BE McQueen, CA TI The Developing Nervous System SO COMPREHENSIVE TOXICOLOGY, VOL 13: NERVOUS SYSTEM AND BEHAVIORAL TOXICOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID BLOOD-BRAIN-BARRIER; TRYPTOPHAN-HYDROXYLASE-ACTIVITY; RAT-BRAIN; PLACENTAL-TRANSFER; METHYLENEDIOXYMETHAMPHETAMINE MDMA; PARA-CHLOROAMPHETAMINE; CIRCUMVENTRICULAR ORGANS; DEVELOPMENTAL ASPECTS; POSTNATAL-DEVELOPMENT; SUBFORNICAL ORGAN C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Slikker, W (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 125 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046884-6 PY 2010 BP 277 EP 288 PG 12 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA BA2JT UT WOS:000333465100016 ER PT J AU Zhang, X Paule, MG AF Zhang, X. Paule, M. G. BE McQueen, CA TI In Vivo Systems: Animal Models of Neurodegeneration SO COMPREHENSIVE TOXICOLOGY, VOL 13: NERVOUS SYSTEM AND BEHAVIORAL TOXICOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID PRENATAL COCAINE EXPOSURE; RAT FOREBRAIN CULTURE; FETAL RHESUS-MONKEY; EXTRADIMENSIONAL SHIFT TASKS; ALPHA-SYNUCLEIN AGGREGATION; NMDA RECEPTOR ANTAGONISTS; MESSENGER-RNA EXPRESSION; PARKINSONIAN TOXIN MPTP; D-ASPARTATE RECEPTOR; OPERANT TEST BATTERY C1 [Zhang, X.; Paule, M. G.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Zhang, X (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 145 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046884-6 PY 2010 BP 399 EP 413 PG 15 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA BA2JT UT WOS:000333465100023 ER PT J AU Arasappan, D Fang, H Perkins, R Tong, W AF Arasappan, D. Fang, H. Perkins, R. Tong, W. BE McQueen, CA TI Interpretation of Toxicogenomics Data SO COMPREHENSIVE TOXICOLOGY, VOL 2: CELLULAR AND MOLECULAR TOXICOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID GENE-EXPRESSION PROFILES; FALSE DISCOVERY RATE; MICROARRAY DATA; TOXICOLOGICAL-RESEARCH; QUANTITATIVE TRAITS; STATISTICAL-METHODS; PROTEOMIC DATA; HUMAN GENOME; PATHWAY; TOXICITY C1 [Arasappan, D.; Fang, H.; Perkins, R.] US FDA, Z Tech, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Tong, W.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Arasappan, D (reprint author), US FDA, Z Tech, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 81 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046884-6 PY 2010 BP 663 EP 683 PG 21 WC Toxicology SC Toxicology GA BA2JD UT WOS:000333458300034 ER PT J AU Goering, PL Barber, DS AF Goering, P. L. Barber, D. S. BE McQueen, CA TI Hepatotoxicity of Copper, Iron, Cadmium, and Arsenic SO COMPREHENSIVE TOXICOLOGY, VOL 9: HEPATIC TOXICOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID ISOLATED RAT HEPATOCYTES; CHLORIDE-INDUCED HEPATOTOXICITY; TUMOR-NECROSIS-FACTOR; IDIOPATHIC PORTAL-HYPERTENSION; INDUCED OXIDATIVE STRESS; SPRAGUE-DAWLEY RATS; EVANS CINNAMON RATS; DNA STRAND BREAKS; LIPID-PEROXIDATION; VITAMIN-E C1 [Goering, P. L.] US FDA, Silver Spring, MD 20993 USA. [Barber, D. S.] Univ Florida, Gainesville, FL USA. RP Goering, PL (reprint author), US FDA, Silver Spring, MD 20993 USA. NR 207 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046884-6 PY 2010 BP 501 EP 526 PG 26 WC Gastroenterology & Hepatology; Toxicology SC Gastroenterology & Hepatology; Toxicology GA BA2JW UT WOS:000333465800023 ER PT S AU DeGrasse, JA Devos, D AF DeGrasse, Jeffrey A. Devos, Damien BE Fenyo, D TI A Functional Proteomic Study of the Trypanosoma brucei Nuclear Pore Complex: An Informatic Strategy SO COMPUTATIONAL BIOLOGY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Trypanosoma brucei; Functional proteomics; Functional annotation; Informatics; Evolution; Nuclear pore complex; Structure prediction ID PROTEIN FAMILIES DATABASE; STRUCTURE PREDICTION; ARCHITECTURE; IDENTIFICATION; SERVER AB The nuclear pore complex (NPC) is the sole mediator of transport between the nucleus and the cytoplasm. The NPC is composed of about 30 distinct proteins, termed nucleoporins or nups. The yeast (Rout et al., J Cell Biol 148:635-651, 2000) and mammalian (Cronshaw et al., J Cell Biol 158:915-927, 2002) NPC have been extensively studied. However, the two species arc relatively closely related. Thus, to reveal details about NPC evolution, we chose to characterize the NPC of a distantly related organism, Trypanosoma brucei. We took a subcellular proteomic approach and used several complementary strategies to identify 865 proteins associated with the nuclear envelope. Over 50% of similar to 8,100 open reading frames of T. brucei have little or no known function because T brucei is distantly related to model meta-zoa and fungi (Berriman et al., Science 309:416-422, 2005). By sequence similarity alone, we could identify only five nucleoporins. This chapter outlines our strategy to identify 17 additional nucleoporins as well as contribute functional annotation data to the T. brucei genome database. C1 [DeGrasse, Jeffrey A.] US FDA, College Pk, MD USA. [Devos, Damien] European Mol Biol Lab, Heidelberg, Germany. RP DeGrasse, JA (reprint author), US FDA, College Pk, MD USA. OI devos, damien/0000-0002-9453-4753 NR 23 TC 3 Z9 3 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-841-6 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 673 BP 231 EP 238 DI 10.1007/978-1-60761-842-3_15 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA BRE95 UT WOS:000282535500015 PM 20835803 ER PT S AU Kelly, RJ Smith, JA Kardiat, SLR AF Kelly, Reagan J. Smith, Jennifer A. Kardiat, Sharon L. R. BE Dunlap, JC Moore, JH TI Providing Context and Interpretability to Genetic Association Analysis Results Using the KGraph SO COMPUTATIONAL METHODS FOR GENETICS OF COMPLEX TRAITS SE Advances in Genetics LA English DT Review; Book Chapter ID HUMAN-DISEASES; ARCHITECTURE AB The KGraph is a data visualization system that has been developed to display the complex relationships between the univariate and bivariate associations among an outcome of interest, a set of covariates, and a set of genetic variations such as single-nucleotide polymorphisms (SNPs). It allows for easy simultaneous viewing and interpretation of genetic associations, correlations among covariates and SNPs, and information about the replication and cross-validation of these associations. The KGraph allows the user to more easily investigate multicollinearity and confounding through visualization of the multidimensional correlation structure underlying genetic associations. It emphasizes gene environment interactions, gene gene interactions, and correlations, all important components of the complex genetic architecture of most human traits. The KGraph was designed for use in gene-centric studies, but can be integrated into association analysis workflows as well. The software is available at http://www.epidkardia.sph.umich.edu/software/kgrapher (C) 2010, Elsevier Inc. C1 [Kelly, Reagan J.] US FDA, Div Bioinformat, ICF Int, Natl Ctr Toxicol Res, Jefferson, AR USA. [Smith, Jennifer A.; Kardiat, Sharon L. R.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. RP Kelly, RJ (reprint author), US FDA, Div Bioinformat, ICF Int, Natl Ctr Toxicol Res, Jefferson, AR USA. NR 15 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2660 BN 978-0-12-380862-2 J9 ADV GENET JI Adv. Genet. PY 2010 VL 72 BP 181 EP 193 DI 10.1016/S0065-2660(10)72008-3 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA BAD32 UT WOS:000303839100008 PM 21029853 ER PT B AU Alvandi, F Ayache, S Drum, ET Herman, JH AF Alvandi, Firoozeh Ayache, Saleh Drum, Elizabeth T. Herman, Jay H. BE Criner, GJ Barnette, RE DAlonzo, GE TI Use of Blood Components SO CRITICAL CARE STUDY GUIDE: TEXT AND REVIEW, SECOND EDITION LA English DT Article; Book Chapter ID PROPHYLACTIC PLATELET TRANSFUSIONS; ACUTE MYELOID-LEUKEMIA; ACTIVATED FACTOR-VII; FRESH-FROZEN PLASMA; ACUTE LUNG INJURY; CLINICAL-PRACTICE; AMERICAN-SOCIETY; THERAPEUTIC APHERESIS; PRACTICE GUIDELINES; CELL TRANSFUSION C1 [Alvandi, Firoozeh; Ayache, Saleh] US FDA, Silver Spring, MD 20903 USA. [Drum, Elizabeth T.] Temple Univ, Sch Med, Dept Anesthesiol, Philadelphia, PA 19140 USA. [Herman, Jay H.] Thomas Jefferson Univ Hosp, Dept Pathol & Med, Philadelphia, PA 19140 USA. RP Alvandi, F (reprint author), US FDA, Silver Spring, MD 20903 USA. NR 53 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-77327-8 PY 2010 BP 1091 EP 1111 DI 10.1007/978-0-387-77452-7_55 D2 10.1007/978-0-387-77452-7 PG 21 WC Critical Care Medicine SC General & Internal Medicine GA BQC04 UT WOS:000280605100055 ER PT J AU Schneeman, BO AF Schneeman, Barbara O. TI Application of Epidemiological Data for Decision Making: Health Claims SO CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION LA English DT Editorial Material AB The Nutrition Labeling and Education Act (NLEA), which amended the Federal Food, Drug, and Cosmetic Act in 1990, authorized the use of health claims that are based on significant scientific agreement in food labeling. In 1994, the Dietary Supplement Health and Education Act (DSHEA) defined dietary supplements and created a legal framework for use of claims that is similar to the regulation of foods. Health claims describe the relationship between a substance (food or food component) and reduction of the risk of a disease or health-related condition; they are not intended as claims to cure, treat, mitigate, or prevent disease, which are considered drug claims. Since the enactment of the NLEA, the FDA has developed a process to evaluate scientific evidence in support of health claims. In 1999, the FDA published Guidance for Industry: Significant Scientific Agreement in the Review of Health Claims for Conventional Foods and Dietary Supplements. As a result of a series of court cases, the agency developed a process for qualified health claims that characterizes the quality and strength of scientific evidence because these claims are not based on significant scientific agreement. Since 2003, the FDA has published several letters of enforcement discretion for qualified health claims that illustrate the agency's approach to evaluating the scientific literature when the strength of the evidence is not consistent with significant scientific agreement. In 2007, the agency published the draft Guidance for Industry: Evidence-Based Review System for the Scientific Evaluation of Health Claims that further outlined the FDA's approach to evaluating scientific evidence for health claims. In January 2009, the final guidance was posted and replaced the 1999 guidance document as well as the interim guidance related to qualified health claims. The final guidance specifically addresses the use of observational data in the evaluation of health claims and describes the criteria used by the agency in the evaluation of such data. A copy of the guidance can be found on the FDA Web site (http://www.fda.gov/Food/GuidanceComplianceRegulatoryInformation/GuidanceDocuments/FoodLabelingNutrition/ucm073332.htm). The guidance highlights some of the challenges that must be considered for the agency to use observational data to draw scientific conclusions on the relationship between a specific substance and disease or health-related condition for the health claim under review. This article is not subject to US copyright law. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Schneeman, BO (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-8398 J9 CRIT REV FOOD SCI JI Crit. Rev. Food Sci. Nutr. PY 2010 VL 50 SU 1 BP 19 EP 19 AR PII 930704474 DI 10.1080/10408398.2010.526850 PG 1 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 689UL UT WOS:000284955300006 ER PT J AU Caporaso, NE Marti, GE Vogt, RF Shim, YK Middleton, D Landgren, O AF Caporaso, Neil E. Marti, Gerald E. Vogt, Robert F., Jr. Shim, Youn K. Middleton, Dan Landgren, Ola CA Int MBL Study Grp TI Evolution of a Precursor SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Editorial Material ID CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELL LYMPHOCYTOSIS; SUSCEPTIBILITY LOCI; NATURAL-HISTORY; CLASSIFICATION; FAMILIES; CLONES; COUNT C1 [Caporaso, Neil E.] NCI, Pharmacogenet Sect, Genet Epidemiol Branch, Div Canc Epidemiol & Genet,NIH, Bethesda, MD 20892 USA. [Marti, Gerald E.] NIH, Flow & Image Cytometry Sect, CBER, US FDA, Bethesda, MD 20892 USA. [Vogt, Robert F., Jr.] Ctr Dis Control & Prevent, Newborn Screening Branch, Div Sci Lab, Atlanta, GA USA. [Shim, Youn K.; Middleton, Dan] ATSDR, Div Hlth Studies, Chamblee, GA 30341 USA. [Landgren, Ola] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Caporaso, NE (reprint author), NCI, Pharmacogenet Sect, Genet Epidemiol Branch, Div Canc Epidemiol & Genet,NIH, EPS 7116,6120 Execut Blvd, Bethesda, MD 20892 USA. EM caporaso@nih.gov NR 22 TC 1 Z9 1 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 JAN PY 2010 VL 78B IS 1 BP 1 EP 2 DI 10.1002/cyto.b.20508 PG 2 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 538EW UT WOS:000273168100001 PM 20014321 ER PT J AU Caporaso, NE Marti, GE Landgren, O Azzato, E Weinberg, JB Goldin, L Shanafelt, T AF Caporaso, Neil E. Marti, Gerald E. Landgren, Ola Azzato, Elizabeth Weinberg, J. Brice Goldin, Lynn Shanafelt, Tait TI Monoclonal B Cell Lymphocytosis: Clinical and Population Perspectives SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Review DE chronic lymphocytic leukemia; monoclonal B cell lymphocytosis; population; lymphocytosis ID NATURAL-HISTORY; DIAGNOSTIC-CRITERIA; SUSCEPTIBILITY LOCI; FLOW-CYTOMETRY; LEUKEMIA; TRANSPLANTATION; CLASSIFICATION; FAMILIES; RISK; CLL AB Monoclonal B Cell Lymphocytosis (MBL) refers to clones of CLL-like cells that exhibit CLL characteristics that fall short of the numbers required for CLL diagnosis. Data from large CLL kindreds document increased prevalence of MBL suggesting a genetic contribution to its etiology. The molecular features that favor progression of MBL to CLL are poorly understood but an elevated B-cell count is a risk factor for progression. An important consideration when evaluating volunteers from CLL families who are willing to donate bone marrow is that MBL be ruled out since the MBL donor clone could result in a second CLL in the recipient. Further studies of MBL are needed to identify the molecular features and how they evolve during progression. Published 2010 Wiley-Liss, Inc.(dagger) C1 [Caporaso, Neil E.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, EPS 7116, Bethesda, MD 20892 USA. [Marti, Gerald E.] US FDA, Off Cellular Tissue & Gene Therapies, Ctr Biol Res & Evaluat, Bethesda, MD 20892 USA. [Landgren, Ola] Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA. [Weinberg, J. Brice] Duke Univ, Durham, NC 27705 USA. [Weinberg, J. Brice] VA Med Ctr, Durham, NC 27705 USA. [Shanafelt, Tait] Mayo Clin, Dept Med, Rochester, MN 55905 USA. RP Caporaso, NE (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, EPS 7116, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM caporaso@nih.gov NR 44 TC 5 Z9 5 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. PY 2010 VL 78B SU 1 BP S115 EP S119 DI 10.1002/cyto.b.20555 PG 5 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 647BM UT WOS:000281590700016 PM 20839332 ER PT J AU Marti, GE Shim, YK Albitar, M Middleton, D Abbasi, F Anderson, A Vogt, RF AF Marti, Gerald E. Shim, Youn K. Albitar, Maher Middleton, Dan Abbasi, Fatima Anderson, Ayana Vogt, Robert F. TI Long-Term Follow-Up of Monoclonal B-cell Lymphocytosis Detected in Environmental Health Studies SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE monoclonal B-cell lymphocytosis; follow-up; case report ID NATURAL-HISTORY; LEUKEMIA; BLOOD; CLONES AB Background: Four individuals in whom Monoclonal B cell Lymphocytosis (MBL) had been previously detected were evaluated for the fourth time after 15-18 years since initial testing. All four were environmental health study participants without hematologic malignancies who had elevated absolute B cell counts at initial testing. Methods: The current laboratory evaluation included complete blood counts, lymphocyte immunophenotypes, immunoglobulin heavy-chain variable (IGHV) gene mutation status, and serum tests for monoclonal immunoglobulins and free light chains. Results from this evaluation were compared with those from the three previous evaluations. Clinical status was assessed by reviewing medical records. Results: B-cell clones with phenotypic characteristics of the original MBL clone were detected in three of the four individuals. Since the last evaluation in 2003, one participant who had a clinical diagnosis of Waldenstrom's Macroglobulinemia had developed a diffuse large cell lymphoma and was treated. Another participant continued to show a decline in lymphocyte and B cell counts, reaching clinical lymphocytopenia and B cell lymphopenia. The MBL clone was still detectable. The remaining two participants had stable blood counts and MBL phenotypes. Neither had been diagnosed with a hematologic malignancy. However, molecular analysis revealed clonal changes in both: one showed a marked decline in the percentage of somatically-mutated B cells, and the other showed a clonal transition from IGHV3-13 to IGHV4-34. Conclusions: A diversity of clonal evolution was observed in these MBL cases. These observations suggest that long-term follow-up studies using standardized MBL subcategories are essential to understanding B-cell pathobiology and optimizing clinical management. Published 2010 Wiley-Liss, Inc.(dagger) C1 [Shim, Youn K.; Middleton, Dan; Anderson, Ayana] ATSDR, Div Hlth Studies, Atlanta, GA 30341 USA. [Marti, Gerald E.; Abbasi, Fatima] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Albitar, Maher] Nichols Inst, San Juan Capistrano, CA USA. [Vogt, Robert F.] Ctr Dis Control & Prevent, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA USA. RP Shim, YK (reprint author), ATSDR, Div Hlth Studies, 4770 Buford Hwy,Mailstop F-57, Atlanta, GA 30341 USA. EM yshim@cdc.gov NR 19 TC 2 Z9 3 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. PY 2010 VL 78B SU 1 BP S83 EP S90 DI 10.1002/cyto.b.20522 PG 8 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 647BM UT WOS:000281590700012 PM 20839341 ER PT J AU Nieto, WG Almeida, J Teodosio, C Abbasi, F Allgood, SD Connors, F Rachel, JM Ghia, P Lanasa, MC Rawstron, AC Orfao, A Caporaso, NE Hanson, CA Shim, YK Vogt, RF Marti, GE AF Nieto, Wendy G. Almeida, Julia Teodosio, Cristina Abbasi, Fatima Allgood, Sallie D. Connors, Fiona Rachel, Jane M. Ghia, Paolo Lanasa, Mark C. Rawstron, Andy C. Orfao, Alberto Caporaso, Neil E. Hanson, Curt A. Shim, Youn K. Vogt, Robert F. Marti, Gerald E. TI Commentary: Comparison of Current Flow Cytometry Methods for Monoclonal B Cell Lymphocytosis Detection SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Editorial Material DE chronic lymphocytic leukemia; immunophenotyping; lymphocyte gating ID CHRONIC LYMPHOPROLIFERATIVE DISORDERS; MINIMAL RESIDUAL DISEASE; LEUKEMIA; CLONES; COUNT AB Monoclonal B cell lymphocytosis (MBL) is now recognized as the B-lymphocyte analogue of a monoclonal gammopathy of unknown significance. MBL can be the precursor of chronic lymphocytic leukemia or associated with non-Hodgkin's lymphoma. It may be associated with an autoimmune abnormality or be related to aging (immunosenescence). The combination of available new fluorochrome-conjugated monoclonal antibody reagents, multilaser instrumentation, and improved software tools have led to a new level of multicolor analysis of MBL. Presently, several centers, including the University of Salamanca (Spain), Duke University (Durham, NC), Mayo Clinic (Rochester, MN), and the National Cancer Institute (Bethesda, MD) in conjunction with the Genetics and Epidemiology of Familial chronic lymphocytic leukemia Consortium, the Food and Drug Administration (Bethesda, MD), and the Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry (Atlanta, GA) in collaboration with Saint Luke's Hospital (Kansas City, MO), the Universita Vita-Salute San Raffaele in Milan (Italy), and Leeds Teaching Hospital (UK) are all actively conducting studies on MBL. This commentary is an updated summary of the current methods used in these centers. It is important to note the diversity of use in reagents, instruments, and methods of analysis. Despite this diversity, there is a consensus in what constitutes the diagnosis of MBL and its subtypes. There is also an emerging consensus on what the next investigative steps should be. Published 2010 Wiley-Liss, Inc.(dagger) C1 [Abbasi, Fatima; Marti, Gerald E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Nieto, Wendy G.; Almeida, Julia; Teodosio, Cristina; Orfao, Alberto] Univ Salamanca, Serv Gen Citometria, CSIC, Ctr Invest Canc,IBMCC,USAL, E-37008 Salamanca, Spain. [Nieto, Wendy G.; Almeida, Julia; Teodosio, Cristina; Orfao, Alberto] Univ Salamanca, Dept Med, E-37008 Salamanca, Spain. [Allgood, Sallie D.; Lanasa, Mark C.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Connors, Fiona; Rawstron, Andy C.] Leeds Teaching Hosp, St Jamess Inst Oncol, Hematol Malignancy Diagnost Serv, Leeds, W Yorkshire, England. [Rachel, Jane M.] St Lukes Hosp, Mol Diagnost & Flow Cytometry Lab, Kansas City, MO USA. [Ghia, Paolo] Univ Vita Salute San Raffaele, Dept Oncol, Div Mol Oncol, Lab Cell Neoplasia B, Milan, Italy. [Ghia, Paolo] Univ Vita Salute San Raffaele, Dept Oncol, Lymphoma Unit, Milan, Italy. [Caporaso, Neil E.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Hanson, Curt A.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Shim, Youn K.] Agcy Tox Subst & Dis Registry, Div Hlth Studies, Atlanta, GA USA. [Vogt, Robert F.] Ctr Dis Control & Prevent, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA USA. [Ghia, Paolo] Ist Sci San Raffaele, Milan, Italy. RP Marti, GE (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. EM gemarti@mac.com RI Ghia, Paolo/K-7138-2016; OI Ghia, Paolo/0000-0003-3750-7342; Allgood, Sallie/0000-0002-0329-4572; Rawstron, Andy/0000-0003-0798-9790 NR 15 TC 5 Z9 5 U1 0 U2 5 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. PY 2010 VL 78B SU 1 BP S4 EP S9 DI 10.1002/cyto.b.20556 PG 6 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 647BM UT WOS:000281590700003 PM 20839336 ER PT J AU Perez-Andres, M Paiva, B Nieto, WG Caraux, A Schmitz, A Almeida, J Vogt, RF Marti, GE Rawstron, AC Van Zelm, MC Van Dongen, JJM Johnsen, HE Klein, B Orfao, A AF Perez-Andres, M. Paiva, B. Nieto, W. G. Caraux, A. Schmitz, A. Almeida, J. Vogt, R. F., Jr. Marti, G. E. Rawstron, A. C. Van Zelm, M. C. Van Dongen, J. J. M. Johnsen, H. E. Klein, B. Orfao, A. CA Study MBL TI Human Peripheral Blood B-Cell Compartments: A Crossroad in B-Cell Traffic SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Review DE B-cell; peripheral blood; circulating; differentiation; subsets ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CHRONIC LYMPHOCYTIC-LEUKEMIA; HEMATOPOIETIC STEM-CELLS; TOLL-LIKE RECEPTORS; BONE-MARROW; PLASMA-CELLS; RHEUMATOID-ARTHRITIS; SEROLOGICAL MEMORY; HUMORAL IMMUNITY; FLOW-CYTOMETRY AB A relatively high number of different subsets of B-cells are generated through the differentiation of early B-cell precursors into mature B-lymphocytes in the bone marrow (BM) and antigen-triggered maturation of germinal center B-cells into memory B-lymphocytes and plasmablasts in lymphoid tissues. These B-cell subpopulations, which are produced in the BM and lymphoid tissues, recirculate through peripheral blood (PB), into different tissues including mucosa and the BM, where long-living plasma cells produce antibodies. These circulating PB B-cells can be classified according to their maturation stage into i) immature/transitional, ii) naive, and iii) memory B-lymphocytes, and iv) plasmablasts/plasma cells. Additionally, unique subsets of memory B-lymphocytes and plasmablasts/plasma cells can be identified based on their differential expression of unique Ig-heavy chain isotypes (e.g.: IgM, IgD, IgG, IgA). In the present paper, we review recent data reported in the literature about the distribution, immunophenotypic and functional characteristics of these cell subpopulations, as well as their distribution in PB according to age and seasonal changes. Additional information is also provided in this regard based on the study of a population-based cohort of 600 healthy adults aged from 20 to 80 years, recruited in the Salamanca area in western Spain. Detailed knowledge of the distribution and traffic of B-cell subsets through PB mirrors the immune status of an individual subject and it may also contribute to a better understanding of B-cell disorders related to B-cell biology and homeostasis, such as monoclonal B-cell lymphocytosis (MBL). (C) 2010 International Clinical Cytometry Society C1 [Perez-Andres, M.; Paiva, B.; Nieto, W. G.; Almeida, J.; Orfao, A.] Univ Salamanca, CSIC, Ctr Invest Canc, Salamanca 37007, Spain. [Perez-Andres, M.; Nieto, W. G.; Almeida, J.; Orfao, A.] Univ Salamanca, Dept Med, Serv Cytometry, Salamanca 37007, Spain. [Paiva, B.] Hosp Univ Salamanca, Serv Hematol, Salamanca, Spain. [Caraux, A.] INSERM, U847, F-34295 Montpellier, France. [Schmitz, A.; Johnsen, H. E.] Aarhus Univ Hosp, Aalborg Hosp, Serv Hematol, Aalborg, Denmark. [Vogt, R. F., Jr.] Ctr Dis Control & Prevent, Div Sci Lab, Atlanta, GA USA. [Marti, G. E.] CBER FDA, Flow & Image Cytometry Sect, Bethesda, MD USA. [Rawstron, A. C.] St Jamess Inst Oncol, HMDS, Leeds, W Yorkshire, England. [Rawstron, A. C.] St Jamess Inst Oncol, Dept Haematol, Leeds, W Yorkshire, England. [Van Zelm, M. C.; Van Dongen, J. J. M.] Univ Med Ctr, Erasmus MC, Dept Immunol, Rotterdam, Netherlands. [Klein, B.] CHU Montpellier, Inst Res Biotherapy, F-34295 Montpellier, France. [Klein, B.] Univ Montpellier 1, F-34967 Montpellier, France. RP Orfao, A (reprint author), Univ Salamanca, CSIC, Ctr Invest Canc, Univ Coimbra S-N,Campus Miguel de Unamuno, Salamanca 37007, Spain. EM orfao@usal.es RI IBSAL, Secretaria/H-3719-2011; van Dongen, Jacques/F-8537-2015; van Zelm, Menno/O-4404-2015; OI van Dongen, Jacques/0000-0001-7686-0021; van Zelm, Menno/0000-0003-4161-1919; Lourenco Paiva, Bruno David/0000-0003-1977-3815; Rawstron, Andy/0000-0003-0798-9790 FU MSCNet European strep [E06005FF]; Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Madrid, Spain [RTICC RD06/0020/0035, PI06/0824, PS09/02430]; Gerencia Regional de Salud de castilla y Leon [GRS206/A/08]; Ayuda GR37 de Excelencia de Castilla y Leon, Consejeria de Educacion, Junta de Castilla y Leon, Valladolid, Spain; Fundacion Samuel Solorzano, Salamanca, Spain [FS/16-2008] FX Grant sponsor: MSCNet European strep; Grant number: No E06005FF; Grant sponsor: Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Madrid, Spain; Grant numbers: RTICC RD06/0020/0035, PI06/0824, PS09/02430; Grant sponsor: Gerencia Regional de Salud de castilla y Leon; Grant number: GRS206/A/08; Grant sponsor: Ayuda GR37 de Excelencia de Castilla y Leon, Consejeria de Educacion, Junta de Castilla y Leon, Valladolid, Spain; Fundacion Samuel Solorzano, Salamanca, Spain; Grant number: FS/16-2008. NR 111 TC 74 Z9 77 U1 1 U2 26 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. PY 2010 VL 78B SU 1 BP S47 EP S60 DI 10.1002/cyto.b.20547 PG 14 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 647BM UT WOS:000281590700009 PM 20839338 ER PT J AU Salerno, E Yuan, Y Scaglione, BJ Marti, G Jankovic, A Mazzella, F Laurindo, MF Despres, D Baskar, S Rader, C Raveche, E AF Salerno, Erica Yuan, Yao Scaglione, Brian J. Marti, Gerald Jankovic, Alexander Mazzella, Fermina Laurindo, Maria Fernanda Despres, Daryl Baskar, Sivasubramanian Rader, Christoph Raveche, Elizabeth TI The New Zealand Black Mouse as a Model for the Development and Progression of Chronic Lymphocytic Leukemia SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE chronic lymphocytic leukemia; monoclonal B cell lymphocytosis; miR-16; murine model of CLL; New Zealand Black; side population ID B-CELL LYMPHOCYTOSIS; SIDE POPULATION; STEM-CELLS; CLL; GENES; CANCER; 13Q14; RNA; IDENTIFICATION; MICRORNA-16 AB Background: Similar to a subset of human patients who progress from monoclonal B lymphocytosis (MBL) to chronic lymphocytic leukemia (CLL), New Zealand Black (NZB) mice have an age-associated progression to CLL. The murine disease is linked to a genetic abnormality in microRNA mir-15a/16-1 locus, resulting in decreased mature miR-15a/16. Methods: Spleens of aging NZB were analyzed for the presence of B-1 cells via flow cytometry and for the presence of a side population (SP) via the ability of cells to exclude Hoechst 33342 dye. The SP was assayed for the presence of hyperdiploid B-1 clones and for the ability to differentiate into B-1 cells in vitro and transfer disease in vivo. In addition, enhanced apoptosis of chemoresistant NZB B-1 cells was examined by restoring miR-16 levels in nutlin-treated cells. Results: Aging NZB mice develop a B-1 expansion and clonal development that evolves from MBL into CLL. An expansion in SP is also seen. Although the SP did contain increased cells with stem cell markers, they lacked malignant B-1 cells and did not transfer disease in vivo. Similar to B-1 cells, splenic NZB SP also has decreased miR-15a/16 when compared with C57BI/6. Exogenous addition of miR15a/16 to NZB B-1 cells resulted in increased sensitivity to nutlin. Conclusion: NZB serve as an excellent model for studying the development and progression of age-associated CLL. NZB SP cells do not seem to contain cancer stem cells, but rather the B-1 stem cell. NZB B-1 chemoresistance may be related to reduced miR-15a/16 expression. (C) 2010 International Clinical Cytometry Society C1 [Salerno, Erica; Yuan, Yao; Scaglione, Brian J.; Mazzella, Fermina; Laurindo, Maria Fernanda; Raveche, Elizabeth] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Lab Med & Pathol, Newark, NJ 07103 USA. [Scaglione, Brian J.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA. [Marti, Gerald; Jankovic, Alexander] US FDA, Ctr Biol Evaluat & Res, NIH, Bethesda, MD 20892 USA. [Despres, Daryl] NINDS, Mouse Imaging Facil, NIH, Bethesda, MD 20892 USA. [Baskar, Sivasubramanian; Rader, Christoph] NCI, NIH, Bethesda, MD 20892 USA. RP Raveche, E (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Lab Med & Pathol, MSB C512,185 S Orange Ave, Newark, NJ 07103 USA. EM raveches@umdnj.edu FU NIH NCI [R01CA129826]; NJCCR [09-1255-CCR-E0] FX The authors thank Brian D. Brown, Alessia Baccarini, Sukwinder Singh, and Howard S. Mostowski. This research was in part funded by NIH NCI R01CA129826 granted to E. Raveche and NJCCR pre-doctoral fellowship 09-1255-CCR-E0 awarded to E. Salerno. NR 50 TC 8 Z9 8 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. PY 2010 VL 78B SU 1 BP S98 EP S109 DI 10.1002/cyto.b.20544 PG 12 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 647BM UT WOS:000281590700014 PM 20839343 ER PT J AU Shim, YK Middleton, DC Caporaso, NE Rachel, JM Landgren, O Abbasi, F Raveche, ES Rawstron, AC Orfao, A Marti, GE Vogt, RF AF Shim, Youn K. Middleton, Dannie C. Caporaso, Neil E. Rachel, Jane M. Landgren, Ola Abbasi, Fatima Raveche, Elizabeth S. Rawstron, Andy C. Orfao, Alberto Marti, Gerald E. Vogt, Robert F. TI Prevalence of Monoclonal B-Cell Lymphocytosis: A Systematic Review SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Review DE monoclonal B-cell lymphocytosis; MBL; chronic lymphocytic leukemia; CLL; prevalence; epidemiology ID NATURAL-HISTORY; FLOW-CYTOMETRY; LEUKEMIA; BLOOD; DISEASE; BURDEN; CLONES AB Background: Individuals with monoclonal B-cell lymphocytosis (MBL) have been identified in clinic outpatients, in unaffected relatives of patients with chronic lymphocytic leukemia (CLL), and in general populations. MBL and its relationship with CLL have been actively investigated over the last decade. This report systematically reviews the prevalence of MBL in the context of the populations studied and the evolution of laboratory methods used to define MBL. Methods: To identify published studies that have assessed the prevalence of MBL, we systematically searched the MEDLINE (R) databases and consulted with members of the International MBL Study Group. We reviewed the 10 articles that were identified by this process. We abstracted information on study populations, laboratory tests, criteria for designating MBL, and the reported frequencies. Results: Three of the ten studies were published in 2009, three between 2007 and 2008, and four between 2002 and 2004. Reported prevalences varied widely, ranging from 0.12 to 18.2%. This variability was clearly associated with both the laboratory methods and the populations studied. MBL was more common among older individuals and kindred of persons with CLL. The most common MBL subtype was CLL-like MBL. Conclusions: Large population-based studies of MBL that employ standardized laboratory methods with a consensus case definition are needed to assess prevalence and establish risk factors. These studies should include prospective follow-up of MBL cases to determine the relationship between MBL and CLL. Data from original studies should be reported in sufficient detail to allow future synthesis of information from multiple studies, such as meta-analysis. Published 2010 Wiley-Liss, Inc.(dagger) C1 [Shim, Youn K.; Middleton, Dannie C.] Agcy Tox Subst & Dis Registry, Div Hlth Studies, Atlanta, GA USA. [Caporaso, Neil E.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Rachel, Jane M.] St Lukes Hosp, Kansas City, MO USA. [Landgren, Ola] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Abbasi, Fatima; Marti, Gerald E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Raveche, Elizabeth S.] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. [Rawstron, Andy C.] Leeds Teaching Hosp, St Jamess Inst Oncol, Hematol Malignancy Diagnost Serv, Leeds, W Yorkshire, England. [Orfao, Alberto] Univ Hosp, Dept Med, Cytometry Serv, Canc Res Ctr,IBMCC,CSIC,USAL, Salamanca, Spain. [Orfao, Alberto] Univ Salamanca, E-37008 Salamanca, Spain. [Vogt, Robert F.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, Atlanta, GA USA. RP Shim, YK (reprint author), Agcy Tox Subst & Dis Registry, Div Hlth Studies, Atlanta, GA USA. EM yshim@cdc.gov RI IBSAL, Secretaria/H-3719-2011; OI Rawstron, Andy/0000-0003-0798-9790 FU NCI NIH HHS [R01 CA129826-01A2, R01 CA129826] NR 30 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 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PY 2010 VL 78B SU 1 BP S10 EP S18 DI 10.1002/cyto.b.20538 PG 9 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 647BM UT WOS:000281590700004 PM 20839330 ER PT S AU Wang, QZ Pfefer, TJ AF Wang, Quanzeng Pfefer, T. Joshua BE Raghavachari, R Liang, R TI In situ optical property measurement in layered tissue: Theoretical and experimental assessment of an unconstrained approach SO DESIGN AND QUALITY FOR BIOMEDICAL TECHNOLOGIES III SE Proceedings of SPIE-The International Society for Optical Engineering LA English DT Proceedings Paper CT Conference on Design and Quality for Biomedical Technologies III CY JAN 25-26, 2010 CL San Francisco, CA SP SPIE DE fiberoptic; optical properties; neural network; Monte Carlo; reflectance; multi-layer tissue ID DIFFUSE-REFLECTANCE SPECTRA; MONTE-CARLO SIMULATIONS; 2-LAYER TURBID MEDIA; EPITHELIAL TISSUE; SCATTERING SPECTROSCOPY; BARRETTS-ESOPHAGUS; LIGHT TRANSPORT; MODEL; FLUORESCENCE; ULTRAVIOLET AB We have investigated a potential technique based on spatially resolved reflectance to determine optical properties (OPs) in two-layer turbid media. Reflectance from two-layer tissue was simulated for a wide range of OP combinations (mu(a) = 1-22.5, mu(s)' = 5-42.5 cm(-1)) using a condensed Monte Carlo (MC) model and utilized to train neural network (NN) inverse models. Experimental data from two-layer tissue phantoms with top layer thicknesses (D) ranging from 0.22 to 0.66 mm were collected at three UV-Vis wavelengths. Estimation accuracy was compared to simulated results with added noise. The mean error in experimental determination of mu(a) ranged from 1.5 to 5.9 cm(-1) and mean error for mu(s)' ranged from 2.1 to 12.1 cm(-1) as a function of D. Although numerous realistic challenges remain, this initial experimental study of an unconstrained two-layer diffuse reflectance based OP estimation approach provides support that such a technique has a strong potential to provide accurate in situ measurements in layered tissues. C1 [Wang, Quanzeng; Pfefer, T. Joshua] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Wang, QZ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. NR 26 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7952-5 J9 P SOC PHOTO-OPT INS PY 2010 VL 7556 AR 75560J DI 10.1117/12.842412 PG 7 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSS12 UT WOS:000285579000012 ER PT S AU Hillebrenner, MG Chen, EA Faris, OP O'Callaghan, KM AF Hillebrenner, Matthew G. Chen, Eric A. Faris, Owen P. O'Callaghan, Kathryn M. BE Maisel, WH TI The FDA Perspective on Heart Failure Devices SO DEVICE THERAPY IN HEART FAILURE SE Contemporary Cardiology LA English DT Article; Book Chapter ID EXERCISE OXYGEN-CONSUMPTION; VENTRICULAR ASSIST DEVICE; 6-MINUTE WALK TEST; HEALTH-STATUS; CARDIAC TRANSPLANTATION; CONTROLLED-TRIAL; QUESTIONNAIRE; SUPPORT; MORBIDITY; NOVACOR AB The Food and Drug Administration's Center for Devices and Radiological Health (CDRH) is charged with ensuring that manufacturers of new medical devices demonstrate a reasonable assurance that their devices are safe and effective prior to approval for commercial distribution in the United States. C1 [Hillebrenner, Matthew G.] US FDA, Div Cardiovasc Devices, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Hillebrenner, MG (reprint author), US FDA, Div Cardiovasc Devices, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 57 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1191-7601 BN 978-1-58829-994-9 J9 CONTEMP CARDIOL JI Contemp. Cardiol. PY 2010 BP 89 EP 117 DI 10.1007/978-1-59745-424-7_4 PG 29 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BMH72 UT WOS:000272396900004 ER PT J AU Johannsson, B Taylor, J Clark, CR Shamsuddin, H Beelcrnann, SE Polgreen, P AF Johannsson, Birgir Taylor, James Clark, Charles R. Shamsuddin, Hala Beelcrnann, Susan E. Polgreen, Philip CA Infect Dis Soc Amer Emerging Infec TI Treatment approaches to prosthetic joint infections: results of an Emerging Infections Network survey SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE Prosthetic joint; Infection; Treatment; Diagnosis; Antibiotic-impregnated materials; Toxicity ID TOTAL KNEE ARTHROPLASTY; ACUTE-RENAL-FAILURE; REVISION HIP-ARTHROPLASTY; IMPREGNATED BONE-CEMENT; UNITED-STATES; 2-STAGE REVISION; TOBRAMYCIN; DEBRIDEMENT; COMPONENTS; RETENTION AB We report the results of an Emerging Infections Network survey of 994 infectious disease consultants (IDCs) regarding their participation in the medical management of prosthetic joint infections and observations of adverse effects associated with antibiotic-impregnated materials (response rate, 54.8%). There was general agreement about when a prosthesis can be retained, but substantial variability in the duration of suppressive antibiotics was recommended, with 36% supporting life-long suppression. For 2-stage procedures, 95% recommended a minimum of 4 weeks of systemic antibiotics after the first stage. However, there was little agreement regarding the duration of an antibiotic-free period before reimplantation. Eleven percent of IDCs reported adverse events related to antibiotic-impregnated materials, ranging from skin reactions to renal failure. Further studies to address the substantial variability in the duration of antibiotic suppressive therapy for retained joints and for the duration of antibiotic-free period before reimplantation are needed. (C) 2010 Elsevier Inc. All rights reserved. C1 [Johannsson, Birgir; Taylor, James; Beelcrnann, Susan E.; Polgreen, Philip] Univ Iowa, Carver Coll Med, Dept Internal Med, Iowa City, IA 52242 USA. [Clark, Charles R.] Univ Iowa, Dept Orthopaed & Rehabil, Iowa City, IA 52242 USA. [Shamsuddin, Hala] US FDA, Dept Hlth & Human Serv, Silver Spring, MD 20993 USA. [Polgreen, Philip] Univ Iowa, Coll Publ Hlth, Iowa City, IA 52242 USA. RP Johannsson, B (reprint author), Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. EM birgir-johannsson@uiowa.edu FU Centers for Disease Control and Prevention (CDC) [U50 CI00358] FX This publication was supported by Grant/Cooperative Agreement Number U50 CI00358 from the Centers for Disease Control and Prevention (CDC). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of CDC. NR 41 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD JAN PY 2010 VL 66 IS 1 BP 16 EP 23 DI 10.1016/j.diagmicrobio.2009.08.016 PG 8 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 594YH UT WOS:000277576800003 PM 19782494 ER PT B AU Ning, YM Dagher, RN Pazdur, R AF Ning, Yang-Min Dagher, Ramzi N. Pazdur, Richard BE Figg, WD Chau, CH Small, EJ TI FDA Approval of Prostate Cancer Treatments SO DRUG MANAGEMENT OF PROSTATE CANCER LA English DT Article; Book Chapter DE Drug approval; Drug development; Endpoints; FDA; Post-hoc analysis; Prostate cancer; Subgroup analysis; Surrogate endpoints; Survival ID MITOXANTRONE PLUS PREDNISONE; END-POINTS; CLINICAL-TRIALS; ACCELERATED APPROVAL; DOCETAXEL; THERAPY; SURVIVAL AB The United States Food and Drug Administration has approved more than ten drugs for the treatment of prostate cancer, which include hormonal, supportive, and cytotoxic agents. Although these drugs have remarkably improved the management of patients with the disease, new treatments are greatly needed for achieving better clinical outcomes. Regulatory evaluation of newer agents under development is highly challenging, especially for agents intended for patients with advanced metastatic disease resistant to castration and/or docetaxel. Substantial evidence of efficacy and safety must be demonstrated for an agent to receive marketing approval. The evidence must be based on adequate, well-designed, and well-conducted clinical trials that provide quantitative assessments of measured clinical benefits and risks of the agent. Although improvements in survival and/or patient-reported outcomes continue to be valid endpoints for approving new claims or agents, effective surrogates that can reliably measure and predict clinical benefit remain to be established for accelerating drug development for the disease. Furthermore, appropriate utilization of trial results is very important. Subgroup analysis and/or post-hoc analysis results are not acceptable for regulatory action in general. Productive collaboration between all stakeholders and the agency is one of the keys for successful development of prostate cancer treatments. C1 [Ning, Yang-Min; Pazdur, Richard] US FDA, Off Oncol Drug Prod, Silver Spring, MD USA. [Dagher, Ramzi N.] Pfizer Inc, Global Res & Dev, VP Worldwide Regulatory Strategy, New London, CT USA. RP Ning, YM (reprint author), US FDA, Off Oncol Drug Prod, Silver Spring, MD USA. EM ningy@mail.nih.gov NR 27 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-60327-831-7 PY 2010 BP 399 EP 405 DI 10.1007/978-1-60327-829-4_35 D2 10.1007/978-1-60327-829-4 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA BRE85 UT WOS:000282532600035 ER PT J AU Bai, JPF AF Bai, Jane P. F. TI Ongoing Challenges in Drug Interaction Safety: from Exposure to Pharmacogenomics SO DRUG METABOLISM AND PHARMACOKINETICS LA English DT Review DE drug drug interactions; transporters; intravenous drug interaction; maximum tolerable systemic exposure; modeling and simulation; pharmacogenomics; adverse events ID IRINOTECAN-INDUCED NEUTROPENIA; JAPANESE CANCER-PATIENTS; PROTON PUMP INHIBITORS; COLORECTAL-CANCER; LUNG-CANCER; CLOPIDOGREL; POLYMORPHISMS; CYCLOSPORINE; PATIENT; UGT1A1-ASTERISK-6 AB The complex transporter-cytochrome P450 (CYP) enzyme interplay in the disposition of drugs makes it very challenging to address the safety of clinical drug interactions. Thus, two major subjects are discussed herein. First, the concept of an intravenous drug interaction study ( where the perpetrator is administered intravenously or orally while the drug candidate administered intravenously) to facilitate prediction of maximal possible systemic exposure of a substrate drug when oral drug interactions occur is explored. If a substrate drug with oral bioavailability is equal to or less than 80%, an intravenous drug interaction study at low dose along with a few key oral drug interaction studies could be useful for achieving this objective with the aid of modeling and simulations. Along with the clinical safety of the drug, one could then attempt to predict the safety margin when the worst drug interactions occur. Secondly, the efficacy and safety disparity of clopidogrel, statins and irinotecan each among races and genetic variants are discussed to illustrate that pharmacogenetic knowledge is important for the interpretation and prediction of drug interaction-induced adverse events, whereas drug interaction-induced adverse events are equally informative for identifying genes-based mechanisms involved. C1 US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Clin Pharmacol, Silver Spring, MD 20993 USA. RP Bai, JPF (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Clin Pharmacol, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. NR 37 TC 12 Z9 13 U1 0 U2 2 PU JAP SOC STUDY XENOBIOTICS PI TOKYO PA INT MED INF CENTER SHINANOMACHI RENGAKAN, 35 SHINANO-MACHI SHINJUKU-KU, TOKYO, 160-0016, JAPAN SN 1347-4367 J9 DRUG METAB PHARMACOK JI Drug Metab. Pharmacokinet. PY 2010 VL 25 IS 1 SI SI BP 62 EP 71 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 565CZ UT WOS:000275268100006 PM 20208389 ER PT J AU Malik, M Garnett, CE Zhang, J AF Malik, Marek Garnett, Christine E. Zhang, Joanne TI Thorough QT Studies Questions and Quandaries SO DRUG SAFETY LA English DT Article ID T-WAVE MORPHOLOGY; TORSADES-DE-POINTES; CARDIAC REPOLARIZATION; INTERVAL MEASUREMENT; QT/QTC-PROLONGATION; PREDICTIVE-VALUE; HEALTHY-SUBJECTS; DRUG; RISK; MOXIFLOXACIN AB The International Conference on Harmonisation E14 Guidance was successful in largely standardizing the conduct or the so-called thorough QT/QTc studies (TQTS). Nevertheless, there is still a spectrum of frequently encountered problems with details of design, conduct and interpretation of TQTS. Several of these challenges are reviewed here, starting with explaining that the TQTS goal is only to identify drugs for which the proarrhythmic risk might be considered excluded for the purposes of regulatory benefit-risk assessment. Suggestions are made oil flow to categorize and quantify or exclude proarrhythmic risk if the TQTS is positive. There is a conceptual need for TQTS, and this is discussed, together with reasons why restricted clinical registries cannot prove the absence of proarrhythmic liability of any drug. Appropriate drug doses investigated in TQTS should be derived from the maximum clinically tolerable dose rather than from the known or expected therapeutic dose. With the help of concentration-QTc modelling, the standard therapeutic dose can be omitted from TQTS, especially if the study is expected to be negative. Conditions for single-dose TQTS acceptability are reviewed. The role of the so-called positive control is assessed, contrasting the role of a same-class comparator for the investigated drug. A single 400 mg dose of moxifloxacin is advocated as the present 'gold standard' assay sensitivity test. The necessity of careful placebo control is explained and the frequency of ECG assessments is considered. The central tendency and outlier analyses are discussed, together with the correct approaches to baseline adjustment. The review concludes that the design and interpretation of TQTS must not be approached with mechanistic stereotypes, and highlights the importance of relating the QTc changes to drug plasma levels. C1 [Malik, Marek] Univ London, Div Cardiac & Vasc Sci, London, England. [Garnett, Christine E.] US FDA, Pharmacometr Staff, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Zhang, Joanne] US FDA, Div Biometr 6, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Malik, M (reprint author), 16 Verulam Ave, Surrey CR8 3NQ, England. EM marek.malik@btinternet.com NR 54 TC 30 Z9 30 U1 0 U2 1 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2010 VL 33 IS 1 BP 1 EP 14 PG 14 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 542DP UT WOS:000273472100001 PM 20000862 ER PT J AU Jackson, LS Al-Taher, F AF Jackson, Lauren S. Al-Taher, Fadwa BE Boisrobert, CE Stjepanovic, A Oh, S Lelieveld, HLM TI Processing Issues: Acrylamide, Furan and Trans Fatty Acids SO ENSURING GLOBAL FOOD SAFETY: EXPLORING GLOBAL HARMONIZATION LA English DT Article; Book Chapter ID DIETARY ACRYLAMIDE; MAILLARD REACTION; HEATED FOODSTUFFS; MASS-SPECTROMETRY; POTATO PRODUCTS; FRENCH FRIES; MECHANISTIC PATHWAYS; REDUCING ACRYLAMIDE; CELL-PROLIFERATION; GAS CHROMATOGRAPHY C1 [Jackson, Lauren S.] US FDA, Natl Ctr Food Safety & Technol, Summit, NJ USA. [Al-Taher, Fadwa] IIT, Natl Ctr Food Safety & Technol, Summit, NJ USA. RP Jackson, LS (reprint author), US FDA, Natl Ctr Food Safety & Technol, Summit, NJ USA. NR 134 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-088930-6 PY 2010 BP 383 EP 410 DI 10.1016/B978-0-12-374845-4.00023-0 PG 28 WC Agricultural Economics & Policy; Food Science & Technology SC Agriculture; Food Science & Technology GA BGD31 UT WOS:000322393700025 ER PT B AU Zhao, P Zhang, L Huang, SM AF Zhao, Ping Zhang, Lei Huang, Shiew-Mei BE Pang, KS Rodrigues, AD Peter, RM TI Complex Drug Interactions: Significance and Evaluation SO ENZYME- AND TRANSPORTER-BASED DRUG-DRUG INTERACTIONS: PROGRESS AND FUTURE CHALLENGES LA English DT Proceedings Paper CT Annual Meeting of the American-Association-of-Pharmaceutical-Scientists CY NOV, 2007 CL San Diego, CA SP Amer Assoc Pharmaceut ID IN-VITRO DATA; ITRACONAZOLE METABOLITES; QUANTITATIVE PREDICTION; HUMAN-POPULATIONS; GRAPEFRUIT JUICE; HEALTHY-SUBJECTS; INHIBITION; PHARMACOKINETICS; LIVER; VIVO AB Complex drug interactions that result from a multiplicity of factors (e.g., concomitant medications, organ dysfunction, genetic polymorphism of enzyme/transporter) may be accompanied by important clinical relevance. However, it is difficult to properly design and evaluate all possible complex drug interactions during drug development. In this chapter, we review the types of complex drug interactions and recent advances in studying complex drug interactions using modeling and simulation approaches. Challenges in the quantitative evaluation of complex drug interactions include (1) the need to understand metabolism/transport pathways and their interplay, (2) accurate assessment of key parameters (e.g., fractional clearance) at the enzyme/transporter level, and (3) knowledge in how altered physiological conditions (e.g., by disease states) affect drug disposition and response. Additional research will provide confidence in the use of modeling and simulation to guide clinical study design and generate data for the informative labeling and effective use of medications. C1 [Zhao, Ping; Zhang, Lei] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Zhao, P (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM ping.zhao@fda.hhs.gov NR 87 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ARLINGTON PA 2107 WILSON BLVD, STE 700, ARLINGTON, VA 22201 USA BN 978-1-4419-0839-1 PY 2010 BP 667 EP 692 DI 10.1007/978-1-4419-0840-7_26 PG 26 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BXZ80 UT WOS:000297712900026 ER PT B AU Pogribny, IP Vanyushin, BF AF Pogribny, Igor P. Vanyushin, Boris F. BE Tollefsbol, TO TI Age-Related Genomic Hypomethylation SO EPIGENETICS OF AGING LA English DT Article; Book Chapter ID DNA METHYLATION PATTERNS; PRECURSOR PROTEIN GENE; INVITRO LIFE-SPAN; ALZHEIMERS-DISEASE; 5-METHYLCYTOSINE CONTENT; CHROMOSOMAL INSTABILITY; S-ADENOSYLHOMOCYSTEINE; CANCER SUSCEPTIBILITY; EPIGENETIC REGULATION; COLORECTAL CANCERS AB Aging is a multi-factorial process of the progressive gradual decline of cellular functions with the passage of time. It is clear that aging affects the mammalian epigenome, including hypomethylation of DNA. DNA methylation is a crucial biological process that controls maintenance of genomic integrity and an accurate expression of genetic information. The accurate status of DNA methylation is balanced in mature cells, but with age this balance is strongly shifted in favor of DNA demethylation. Therefore, DNA hypomethylation that occurs during normal aging appears to be a critical risk factor contributing to the development of chronic age-related human pathological states. This review describes the involvement of DNA hypomethylation in the pathogenesis of several major age-related human diseases, including cancer, atherosclerosis, Alzheimer's disease, psychiatric disorders, and autoimmune pathologies. C1 [Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Vanyushin, Boris F.] Moscow MV Lomonosov State Univ, Belozersky Inst Phys Chem Biol, Moscow 119899, Russia. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov; vanyush@belozersky.msu.ru NR 147 TC 15 Z9 15 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-0638-0 PY 2010 BP 11 EP 27 DI 10.1007/978-1-4419-0639-7_2 D2 10.1007/978-1-4419-0639-7 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BMQ80 UT WOS:000273356700002 ER PT B AU Woodcock, J AF Woodcock, Janet BE Ginsburg, GS Willard, HF TI Federal Regulation of Genomic Medicine SO ESSENTIALS OF GENOMIC AND PERSONALIZED MEDICINE LA English DT Article; Book Chapter ID PHARMACOGENOMICS; PERSPECTIVE; OVERSIGHT C1 US FDA, Rockville, MD 20857 USA. RP Woodcock, J (reprint author), US FDA, Parklawn Bldg,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-095811-8; 978-0-12-374934-5 PY 2010 BP 223 EP 232 DI 10.1016/B978-0-12-374934-5.00019-2 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA BID62 UT WOS:000327733200020 ER PT J AU Hsu, A Bray, TM Helferich, WG Doerge, DR Ho, E AF Hsu, Anna Bray, Tammy M. Helferich, William G. Doerge, Daniel R. Ho, Emily TI Differential effects of whole soy extract and soy isoflavones on apoptosis in prostate cancer cells SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article DE soy isoflavones; prostate cancer; apoptosis; nuclear factor kappa B ID NF-KAPPA-B; AKT SIGNALING PATHWAY; BREAST-CANCER; JAPANESE MEN; PHYTO-ESTROGENS; G2/M ARREST; IN-VITRO; GENISTEIN; INHIBITION; PHYTOESTROGENS AB Previous studies have suggested that soy isoflavones exert anticarcinogenic effects against prostate cancer. We propose that soy extracts, containing a mixture of soy isoflavones and other bioactive components, would be a more potent chemopreventive agent than individual soy isoflavones. We compared the apoptotic effects of whole soy extracts and individual soy isoflavones, genistein and daidzein, on prostate cancer cells. The soy extract contained 50% w/w of total isoflavones with approximately 1:5.5:3.5 ratios of genistin, daidzin and glycitin, respectively. Benign prostate hyperplasia. (BPH-1), LnCap and PC3 cells were treated with varying concentrations of soy extract, genistein or daidzein and analyzed for cell cycle alterations and induction of apoptosis. At equal concentrations (25 mu mol/L), soy extract induced a significantly higher percentage of cells undergoing apoptosis than genistein or daidzein (P < 0.001). No significant changes in cell cycle arrest or apoptosis were observed in non-cancerous BPH-1 cells treated with soy extract, suggesting that the effects of soy extract may be tumor cell specific. On the contrary, both genistein and claidzein induced apoptosis in BPH-1 cells, suggesting that individual isoflavones may have cytotoxicity in non-cancerous cells. Soy extracts also increased Bax expression in PC3 cells, but no significant changes in nuclear factor kappa B (NF kappa B) activation were detected, suggesting that the induction of apoptosis was independent of the NF kappa B pathway. Food products that bear a combination of active compounds may be more efficacious and safer as chemo-preventive agents than individual compounds. This 'whole-food'-based approach is significant for the development of public health recommendations for prostate cancer prevention. C1 [Hsu, Anna; Bray, Tammy M.; Ho, Emily] Oregon State Univ, Dept Nutr & Exercise Sci, Corvallis, OR 97331 USA. [Bray, Tammy M.; Ho, Emily] Oregon State Univ, Linus Pauling Inst, Corvallis, OR 97331 USA. [Helferich, William G.] Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. [Doerge, Daniel R.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Ho, E (reprint author), Oregon State Univ, Dept Nutr & Exercise Sci, 117 Milam Hall, Corvallis, OR 97331 USA. EM emily.ho@oregonstate.edu FU National Institute of Health (NIH) [CA107693]; Oregon Agriculture Experiment Station [OR00735]; Environmental Health Science Center at Oregon State University (NIEHS) [P30 ES00210]; National Institute on Aging [P01-AG024387]; National Institute for Complementary and Alternative Medicine; Office of Dietary Supplements; Women's Health Initiative FX This work was supported by a National Institute of Health (NIH) grant CA107693, Oregon Agriculture Experiment Station (OR00735) and the Environmental Health Science Center at Oregon State University (NIEHS P30 ES00210). Soy isoflavone 1-fPLC measurements were done supported by P01-AG024387 to WGH and DRD from the National Institute on Aging with additional support from the National Institute for Complementary and Alternative Medicine, Office of Dietary Supplements, and the Women's Health Initiative. We are also grateful to Dr Carmen Wong for critical input in the manuscript. NR 49 TC 36 Z9 39 U1 0 U2 7 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD JAN PY 2010 VL 235 IS 1 BP 90 EP 97 DI 10.1258/ebm.2009.009128 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 555TK UT WOS:000274538200013 PM 20404023 ER PT J AU Engel, E Vasold, R Santarelli, F Maisch, T Gopee, NV Howard, PC Landthaler, M Baumler, W AF Engel, Eva Vasold, Rudolf Santarelli, Francesco Maisch, Tim Gopee, Neera V. Howard, Paul C. Landthaler, Michael Baeumler, Wolfgang TI Tattooing of skin results in transportation and light-induced decomposition of tattoo pigments - a first quantification in vivo using a mouse model SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE animal model; lymph node; quantification; tattoo pigments; transportation ID SENTINEL LYMPH-NODE; CHEMICAL-ANALYSIS; SKH-1 MICE; YAG LASER; MELANOMA; ASSAY; RADIATION AB Millions of people are tattooed with inks that contain azo pigments. The pigments contained in tattoo inks are manufactured for other uses with no established history of safe use in humans and are injected into the skin at high densities (2.5 mg/cm2). Tattoo pigments disseminate after tattooing throughout the human body and although some may photodecompose at the injection site by solar or laser light exposure, the extent of transport or photodecomposition under in vivo conditions remains currently unknown. We investigated the transport and photodecomposition of the widely used tattoo Pigment Red 22 (PR 22) following tattooing into SKH-1 mice. The pigment was extracted quantitatively at different times after tattooing. One day after tattooing, the pigment concentration was 186 mu g/cm2 skin. After 42 days, the amount of PR 22 in the skin has decreased by about 32% of the initial value. Exposure of the tattooed skin, 42 days after tattooing, to laser light reduced the amount of PR 22 by about 51% as compared to skin not exposed to laser light. A part of this reduction is as a result of photodecomposition of PR 22 as shown by the detection of corresponding hazardous aromatic amines. Irradiation with solar radiation simulator for 32 days caused a pigment reduction of about 60% and we again assume pigment decomposition in the skin. This study is the first quantitative estimate of the amount of tattoo pigments transported from the skin into the body or decomposed by solar or laser radiation. C1 [Engel, Eva; Santarelli, Francesco; Maisch, Tim; Landthaler, Michael; Baeumler, Wolfgang] Univ Regensburg, Dept Dermatol, D-93042 Regensburg, Germany. [Vasold, Rudolf] Univ Regensburg, Dept Organ Chem, D-93042 Regensburg, Germany. [Gopee, Neera V.; Howard, Paul C.] US FDA, Natl Toxicol Program, Ctr Phototoxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Baumler, W (reprint author), Univ Regensburg, Dept Dermatol, D-93042 Regensburg, Germany. EM baeumler.wolfgang@klinik.uni-regensburg.de FU Deutsche Forschungsgemeinschaft' (DFG) [BA1741/3-1] FX The work is supported by a grant of the 'Deutsche Forschungsgemeinschaft' (DFG), Grant number BA1741/3-1. NR 33 TC 28 Z9 28 U1 3 U2 18 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD JAN PY 2010 VL 19 IS 1 BP 54 EP 60 DI 10.1111/j.1600-0625.2009.00925.x PG 7 WC Dermatology SC Dermatology GA 533PJ UT WOS:000272836400008 PM 19703227 ER PT J AU Iha, MH Trucksess, MW AF Iha, M. H. Trucksess, M. W. TI Aflatoxins and ochratoxin A in tea prepared from naturally contaminated powdered ginger SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT LA English DT Article DE high-performance liquid chromatography (HPLC); aflatoxins; ochratoxin A; dietary supplements ID COFFEE BEANS AB The migration of several major mycotoxins, aflatoxins B1 (AFB1), B2, G1, and G2 (AFT, total of the aflatoxins) and ochratoxin A (OTA), from naturally contaminated powdered ginger to surrounding liquid (tea) was investigated. The toxins are commonly found in cereal grains and are toxic, carcinogenic and thermostable. Ginger root is widely used for digestive problems. Powdered ginger (2 g) found to contain AFT and OTA was placed in an empty heat sealable tea bag. The tea bag was heat-sealed and used to prepare tea under different conditions: temperature (50 and 100 degrees C), time (5 and 10 min) and volume (100 and 200 ml). The tea bag was placed in hot water and stirred every 1 min for 5 s during the first 5 min of steeping. After steeping, the tea bag was removed and the tea and ginger residue (in the tea bag) were analysed separately for AFT and OTA. After extraction and immunoaffinity column (IAC) clean-up, the isolated AFT and OTA were separated by reversed-phase liquid chromatography and quantified using a fluorescence detector. At 100 degrees C, approximately 30-40% of AFB1 and AFT and 20-30% of OTA in the contaminated ginger were found in the ginger tea; the total amounts of AFT and OTA in tea varied less than 5% under the three conditions of preparation. At 50 degrees C, about 10% of OTA and AFT were found in tea. This is the first study on the migration of AFT from botanicals to tea. It is also the first to study the distribution of AFT and OTA from powdered ginger to tea and ginger residue. C1 [Iha, M. H.] Inst Adolfo Lutz Registro, BR-14090230 Sao Paulo, Brazil. [Trucksess, M. W.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, Div Bioanalyt Chem, College Pk, MD 20740 USA. RP Iha, MH (reprint author), Inst Adolfo Lutz Registro, Rua Minas 877, BR-14090230 Sao Paulo, Brazil. EM mhiha@ial.sp.gov.br FU Office of Dietary Supplements, National Institutes of Health, Bethesda, MD, USA FX This work was supported in part (interagency agreement) by the Office of Dietary Supplements, National Institutes of Health, Bethesda, MD, USA. The equipment used in part of this project was provided by the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo. NR 16 TC 9 Z9 9 U1 4 U2 22 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1944-0049 J9 FOOD ADDIT CONTAM A JI Food Addit. Contam. Part A-Chem. PY 2010 VL 27 IS 8 BP 1142 EP 1147 AR PII 923438591 DI 10.1080/19440041003795319 PG 6 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 618DN UT WOS:000279331700011 PM 20589549 ER PT J AU Karbiwnyk, CM Williams, RR Andersen, WC Turnipseed, SB Madson, MR Miller, KE Reimschuessel, R AF Karbiwnyk, Christine M. Williams, Rodney R. Andersen, Wendy C. Turnipseed, Sherri B. Madson, Mark R. Miller, Keith E. Reimschuessel, Renate TI Bioaccumulation of cyanuric acid in edible tissues of shrimp following experimental feeding SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT LA English DT Article DE LC; MS; exposure; process contaminants; residues; fish and fish products ID MELAMINE CONTAMINATED FEED; LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRY; RESIDUE DEPLETION; RENAL-FAILURE; PIGS; DEPOSITION; CATFISH; URINE; TROUT AB Due to concerns that cyanuric acid (CYA)-contaminated feed had been used in aquaculture and could enter the human food chain, a method to quantify CYA residues in the edible tissues of fish and shrimp was previously developed and validated. This paper provides further data on the deliberate feeding of CYA to shrimp to determine the extent of residue accumulation in edible tissue. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for the analysis of CYA in shrimp tissue. Edible tissue of shrimp fed 1666 or 3333 mg kg-1 CYA in their diet (approximately 55 and 124 mg kg-1 body weight) contained 0.767 and 0.406 mg kg-1 CYA, respectively. The residue levels are below the World Health Organization (WHO) tolerable daily intake level for CYA and are generally considered unlikely to pose a human health risk. C1 [Karbiwnyk, Christine M.; Andersen, Wendy C.; Turnipseed, Sherri B.] US FDA, Anim Drugs Res Ctr, Denver, CO 80225 USA. [Williams, Rodney R.] Univ Arizona, Environm Res Lab, Tucson, AZ 85756 USA. [Madson, Mark R.] US FDA, Denver Dist Lab, Denver, CO 80225 USA. [Miller, Keith E.] Univ Denver, Dept Chem & Biochem, Denver, CO 80208 USA. [Reimschuessel, Renate] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Karbiwnyk, CM (reprint author), US FDA, Anim Drugs Res Ctr, POB 25087, Denver, CO 80225 USA. EM christine.karbiwnyk@fda.hhs.gov NR 44 TC 2 Z9 2 U1 0 U2 8 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1944-0049 J9 FOOD ADDIT CONTAM A JI Food Addit. Contam. Part A-Chem. PY 2010 VL 27 IS 12 BP 1658 EP 1664 AR PII 927852273 DI 10.1080/19440049.2010.517221 PG 7 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 685ML UT WOS:000284632700003 PM 20936555 ER PT J AU Doan, K Bronaugh, RL Yourick, JJ AF Doan, Khanh Bronaugh, Robert L. Yourick, Jeffrey J. TI In vivo and in vitro skin absorption of lipophilic compounds, dibutyl phthalate, farnesol and geraniol in the hairless guinea pig SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE DBP; Farnesol; Geraniol; Percutaneous absorption; Skin; Hairless guinea pig ID N-BUTYL PHTHALATE; PERCUTANEOUS-ABSORPTION; DEVELOPMENTAL TOXICITY; SYSTEMIC ABSORPTION; RATS; METABOLISM; RESERVOIR; DIESTERS; DBP AB The relationship between in vitro and in vivo skin absorption of lipophilic cosmetic ingredients (dibutyl phthalate (DBP, Log K(ow): 4.45), farnesol (Log K(ow): 5.77) and geraniol (Log K(ow): 3.56) from an oil-in-water emulsion was investigated in the hairless guinea pig. In vivo absorption of DBP, farnesol and geraniol 24 h after dermal application was 62.0 +/- 2.0, 39.8 +/- 2.5, and 15.1 +/- 1.8% of the applied dose (%AD), respectively. In vitro absorption was measured at 24 and 72 h by using flow-through diffusion cells (0.64 cm(2)) with a receptor fluid consisting of HHBSS + 4% BSA. In vitro studies of DBP, farnesol and geraniol absorption over 24 h found 27.1 +/- 1.9. 43.5 +/- 3.3 and 45.9 +/- 3.2%AD in receptor fluid, respectively, and over 72 h found 59.9 +/- 3.2, 77.5 +/- 7.1 and 49.0 +/- 6.3%AD, respectively. We found that the amount of DBP absorbed in vivo after 24 h closely agreed with the amount of DBP found in the receptor fluid in vitro after 72 h. In contrast, the amount of topically applied farnesol absorbed in vivo after 24 h was similar to the amount of farnesol found in receptor fluid in vitro after 24 h. A direct comparison between the in vivo absorption of geraniol and the in vitro absorption at 24 and 72 h was not meaningful due to the rapid evaporation of geraniol from the skin. Our in vitro results suggest that lipophilic chemicals initially form a reservoir in skin, and the material in the reservoir may ultimately diffuse out of the skin into the receptor fluid within 72 h. Our results also demonstrate the utility of in vivo studies for resolving questions about the fate of lipophilic chemicals remaining in skin after in vitro absorption studies. Published by Elsevier Ltd. C1 [Doan, Khanh; Yourick, Jeffrey J.] US FDA, Off Regulatory Serv, College Pk, MD 20740 USA. [Bronaugh, Robert L.] US FDA, Off Cosmet & Colors, College Pk, MD 20740 USA. RP Yourick, JJ (reprint author), Def Threat Reduct Agcy, Chem & Biol Technol Directorate, Ft Belvoir, VA 22060 USA. EM jeffrey.yourick@dtra.mil NR 25 TC 14 Z9 16 U1 2 U2 12 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 JAN PY 2010 VL 48 IS 1 BP 18 EP 23 DI 10.1016/j.fct.2009.09.002 PG 6 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 554UJ UT WOS:000274460400004 PM 19747520 ER PT J AU Griffis, LC Twerdok, LE Francke-Carroll, S Biles, RW Schroeder, RE Bolte, H Faust, H Hall, WC Rojko, J AF Griffis, L. C. Twerdok, L. E. Francke-Carroll, S. Biles, R. W. Schroeder, R. E. Bolte, H. Faust, H. Hall, W. C. Rojko, J. TI Comparative 90-day dietary study of paraffin wax in Fischer-344 and Sprague-Dawley rats SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Wax; Mineral hydrocarbon; Liver granuloma; Cell markers; Inflammation; Rat strains ID WHITE MINERAL-OILS; STREPTOCOCCAL CELL-WALLS; HYDROCARBONS; TOXICITY; SPLEEN; LIVER; MACROPHAGES; MORPHOLOGY; MICE; CARCINOGENICITY AB Highly refined mineral hydrocarbons (MHCs) such as low melting point paraffin wax (LMPW) and low viscosity white oils can cause inflammatory changes in the liver and mesenteric lymph nodes (MLNs) of the Fischer-344 (F-344) rat. In contrast, only minimal MLN changes are seen in the Sprague-Dawley (S-D) rat with no changes in the liver. In this study, the response of female F-344 and S-D rats was compared after 90 days dietary treatment with 0%. 0.2% or 2% LMPW. Effects in the F-344 rats were significantly greater than in the S-D rats: increased liver and splenic weights and inflammatory changes (hepatic microgranulomas) in these tissues were observed only in the F-344 rats. Microgranulomas in the MLNs were observed in both strains but the effects were substantially greater in the F-344 rats. Cellular markers of inflammation were examined in a subset of rats from each group using immunohistochemical staining. An increase in staining for CD3 (T-cells), CD8a (suppresser/cytotoxic T-cells) and CD4 (helper T-cells) correlated with an increase in lymphoid cells in the livers of treated F-344 rats. The majority of macrophages in the hepatic microgranulomas of treated F-344 rats were negative for the ED2 marker, indicating a likely origin from non-resident macrophages. Electron microscopy showed Kupffer cell hypertrophy and hyperplasia in treated F-344 rats. However, lysozyme staining (indicating activation of epithelioid macrophages) decreased with increasing granuloma size. Non-ED2 expressing cells may have been recruited but not sufficiently activated to be lysozyme positive. Inflammatory changes in the cardiac mitral valve noted in previous studies of LMPW were also seen in the F-344 rats in this study but not in the S-D rats. Chemical analysis showed that MHC accumulated in livers from treated F-344 but not S-D rats and the concentration was more than 2-fold greater in MLNs from the F-344 than from the S-D rats. The F-344 appears to be more immunologically sensitive to a number of agents than other rat strains and the results of this study suggest that this may contribute, along with pharmacokinetic differences, to the inflammatory response of F-344 rats to dietary MHCs. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Griffis, L. C.] Toxicol Consulting, Martinez, CA 94553 USA. [Twerdok, L. E.] Twerdok Consulting LLC, Silver Spring, MD USA. [Francke-Carroll, S.] US FDA, CFSAN, College Pk, MD USA. [Biles, R. W.] ExxonMobil Biomed Sci, Houston, TX USA. [Schroeder, R. E.] MPI Res, Mattawan, MI USA. [Bolte, H.] Huntingdon Life Sci, E Millstone, NJ USA. [Faust, H.] Calumet Penreco, Karns City, PA USA. [Hall, W. C.] Hall Consulting Inc, Mt Airy, MD USA. [Rojko, J.] Pathol Associates Inc, Frederick, MD USA. RP Griffis, LC (reprint author), Toxicol Consulting, 116 Chalk Creek Ct, Martinez, CA 94553 USA. EM larrygriffis@comcast.net FU American Petroleum Institute White Oils and Waxes Research Group (Washington, DC) FX This research was conducted at Huntingdon Life Sciences (East Millstone, NJ) and at Pathology Associates (Frederick, MD) and was sponsored by the American Petroleum Institute White Oils and Waxes Research Group (Washington, DC). The views expressed in this manuscript are those of the authors and do not necessarily represent the policies, positions or opinions of their respective agencies or organizations. NR 40 TC 11 Z9 11 U1 0 U2 1 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 JAN PY 2010 VL 48 IS 1 BP 363 EP 372 DI 10.1016/j.fct.2009.10.024 PG 10 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 554UJ UT WOS:000274460400054 PM 19853635 ER PT J AU Benford, D DiNovi, M Setzer, RW AF Benford, Diane DiNovi, Michael Setzer, R. Woodrow TI Application of the margin-of-exposure (MoE) approach to substances in food that are genotoxic and carcinogenic e.g.: Benzo[a]pyrene and polycyclic aromatic hydrocarbons SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Benzo[a]pyrene; Polycyclic aromatic hydrocarbons; BaP; PAHs; Margin of exposure; MoE ID RISK-ASSESSMENT; COAL-TAR; TUMORS AB Benzo[a]pyrene (BaP) and a number of other polycyclic aromatic hydrocarbons (PAH) are mutagenic and are also carcinogenic in rodent bioassays. Oral carcinogenicity data are not available for individual PAH other than BaP, and so BaP has been used as a marker of the carcinogenicity of, and exposure to, PAHs. Carcinogenicity studies of coal tar mixtures, considered to be representative of the genotoxic and carcinogenic PAH in food, have been used for dose-response modelling. Modelling the number of tumour-bearing mice resulted in a BMDL(10) of 0.122 mg BaP/kg-bw/day, which was lower than that for any of the individual tumours and was considered to be most appropriate since the different PAH may have different mechanisms of carcinogenicity. An average dietary exposure estimates of 0.008 mu g BaP/kg-bw/day was identified from the range of national estimates. The calculated MoE was 15,000. Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved. C1 [DiNovi, Michael] US FDA, Rockville, MD 20857 USA. RP Benford, D (reprint author), ILSI Europe, Ave E Mounier 83,B6, B-1200 Brussels, Belgium. EM publications@ilsieurope.be NR 14 TC 27 Z9 27 U1 3 U2 15 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 JAN PY 2010 VL 48 SU 1 BP S42 EP S48 DI 10.1016/j.fct.2009.09.039 PG 7 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 561VM UT WOS:000275007900005 PM 19818825 ER PT J AU Benford, D Bolger, PM Carthew, P Coulet, M DiNovi, M Leblanc, JC Renwick, AG Setzer, W Schlatter, J Smith, B Slob, W Williams, G Wildemann, T AF Benford, Diane Bolger, P. Michael Carthew, Philip Coulet, Myriam DiNovi, Michael Leblanc, Jean-Charles Renwick, Andrew G. Setzer, Woodrow Schlatter, Josef Smith, Benjamin Slob, Wout Williams, Gary Wildemann, Tanja TI Application of the Margin of Exposure (MOE) approach to substances in food that are genotoxic and carcinogenic SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Margin of Exposure; MoE; Genotoxic; Carcinogens; Modelling; Exposure ID RESPONSE RISK-ESTIMATION; CANCER-RISK; LEUCOMALACHITE GREEN; LIVER-MICROSOMES; FISCHER-344 RATS; MALACHITE GREEN; TARGET TISSUES; B6C3F(1) MICE; ZYMBAL GLAND; SUDAN-I AB This paper presents the work of an expert group established by the International Life Sciences institute European branch (ILSI Europe) to follow up the recommendations of an international conference on "Risk Assessment of Compounds that are both Genotoxic and Carcinogenic: New Approaches". Twelve genotoxic and carcinogenic chemicals that can be present in food were selected for calculation of a Margin of Exposure (MOE) between a point of departure on the dose-response for oral carcinogenicity in animal studies and estimates of human dietary exposure. The MOE can be used to support prioritisation of risk management action and, if the MOE is very large, on communication of a low level of human health concern. Depending on the approaches taken in determining the point of departure and the estimation of exposure, it is possible to derive very different values for the MOE. It is therefore essential that the selection of the cancer endpoint and mathematical treatment of the data are clearly described and justified if the results of the MOE approach are to be trusted and of value to risk managers. An outline framework for calculating an MOE is proposed in order to help to ensure transparency in the results. (C) 2009 ILSI Europe. Published by Elsevier Ltd. All rights reserved. C1 [Wildemann, Tanja] ILSI Europe, B-1200 Brussels, Belgium. [Bolger, P. Michael; DiNovi, Michael] US FDA, Rockville, MD 20857 USA. [Renwick, Andrew G.] Univ Southampton, Southampton SO9 5NH, Hants, England. [Slob, Wout] Univ Utrecht, IRAS, NL-3508 TC Utrecht, Netherlands. [Williams, Gary] New York Med Coll, Valhalla, NY 10595 USA. RP Wildemann, T (reprint author), ILSI Europe, Ave E Mounier 83,B6, B-1200 Brussels, Belgium. EM publications@ilsieurope.be NR 71 TC 51 Z9 52 U1 3 U2 18 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 JAN PY 2010 VL 48 SU 1 BP S2 EP S24 DI 10.1016/j.fct.2009.11.003 PG 23 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 561VM UT WOS:000275007900002 PM 20113851 ER PT J AU Bolger, PM Leblanc, JC Setzer, RW AF Bolger, P. Michael Leblanc, Jean-Charles Setzer, R. Woodrow TI Application of the Margin of Exposure (MoE) approach to substances in food that are genotoxic and carcinogenic EXAMPLE: Acrylamide (CAS No. 79-06-1) SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Acrylamide; Margin of Exposure (MoE) ID DNA ADDUCT FORMATION; DIETARY ACRYLAMIDE; FISCHER-344 RATS; FRIED POTATOES; BREAST-CANCER; DOSE-RESPONSE; GLYCIDAMIDE; RISK; MICE; TOXICOKINETICS AB Acrylamide (CH(2)=CHCONH(2), CAS Registry No. 79-06-1) is an industrial chemical used since the 1950s as a chemical intermediate in the production Of polyacrylamides, which are used as flocculants for clarifying drinking-water and other industrial applications. The neurotoxicity of acrylamide in humans is well known from occupational and accidental exposures. In addition, experimental studies with acrylamide in animals have shown reproductive, genotoxic and carcinogenic properties. Acrylamide may be formed when foods, particularly those that are high in carbohydrates and low in protein, are subjected to high temperatures during cooking or other thermal processing. (C) 2009 ILSI Europe. Published by Elsevier Ltd. All rights reserved. C1 [Bolger, P. Michael] US FDA, Rockville, MD 20857 USA. RP Bolger, PM (reprint author), ILSI Europe, Ave E Mounier 83,B6, B-1200 Brussels, Belgium. EM publications@ilsieurope.be NR 31 TC 12 Z9 12 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD JAN PY 2010 VL 48 SU 1 BP S25 EP S33 DI 10.1016/j.fct.2009.11.040 PG 9 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 561VM UT WOS:000275007900003 ER PT J AU Carthew, P DiNovi, M Setzer, RW AF Carthew, Philip DiNovi, Michael Setzer, R. Woodrow TI Application of the margin of exposure (MoE) approach to substances in food that are genotoxic and carcinogenic Example: Furan (CAS No. 110-00-9) SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Furan; Margin of exposure; MoE ID METABOLITE AB Furan is commonly found in foods such as coffee, canned and jarred foods, including baby food containing meat, and various vegetables. It is thought to be formed by the thermal decomposition of carbohydrates. Furan is carcinogenic in rodents, although the detailed mechanism of action has not been completely established. for all the turnout types induced. Dose-response modelling of the data for hepatocellular tumours gives a BMDL(10) of 1.23 mg/kg/day, and MOEs of between 750 and 4300 for exposures of infants and adults. (C) 2009 ILSI Europe. Published by Elsevier Ltd. All rights reserved. C1 [DiNovi, Michael] US FDA, Rockville, MD 20857 USA. RP Carthew, P (reprint author), ILSI Europe, Ave E Mounier 83,B6, B-1200 Brussels, Belgium. EM publications@ilsieurope.be NR 18 TC 12 Z9 12 U1 0 U2 5 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 JAN PY 2010 VL 48 SU 1 BP S69 EP S74 DI 10.1016/j.fct.2009.10.017 PG 6 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 561VM UT WOS:000275007900009 PM 20113857 ER PT J AU Carthew, P DiNovi, M Setzer, RW AF Carthew, Philip DiNovi, Michael Setzer, R. Woodrow TI Application of the Margin of Exposure (MOE) approach to substances in food that are genotoxic and carcinogenic Example: CAS No: 105650-23-5 PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE PhIP; 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine; Margin of exposure; MoE ID SPRAGUE-DAWLEY RATS; DNA-ADDUCT LEVELS; HETEROCYCLIC AMINES; COOKED-FOOD; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; CANCER-RISK; MUTAGEN 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE; PROSTATE-CANCER; BREAST-CANCER; MEAT MUTAGENS AB PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) is a heterocyclic amine and genotoxic carcinogen contaminant that occurs during the grilling and frying of meat and fish, through an interaction between sugars and creatine via the Maillard reaction. PhIP causes cancers of the prostate, mammary gland and colon in rodents. Dose-response modelling of the data for these three turnout types gives BMDL10 values of 0.48 mg/kg/day for the prostate tumours, 0.74 mg/kg/day for mammary tumours and 2.71 mg/kg/day for colon tumours. The lowest MOEs for prostate, mammary and colon tumours were 20,000, 40,000 and 150,000, respectively. (C) 2009 ILSI Europe. Published by Elsevier Ltd. All rights reserved. C1 [DiNovi, Michael] US FDA, Rockville, MD 20857 USA. RP Carthew, P (reprint author), ILSI Europe, Ave E Mounier 83,B6, B-1200 Brussels, Belgium. EM publications@ilsieurope.be NR 38 TC 6 Z9 6 U1 1 U2 5 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 JAN PY 2010 VL 48 SU 1 BP S98 EP S105 DI 10.1016/j.fct.2009.10.035 PG 8 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 561VM UT WOS:000275007900013 PM 20113859 ER PT J AU Schlatter, J DiNovi, M Setzer, RW AF Schlatter, Josef DiNovi, Michael Setzer, R. Woodrow TI Application of the margin of exposure (MoE) approach to substances in food that are genotoxic and carcinogenic Example: Ethyl carbamate (CAS 51-79-6) SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Ethyl carbamate; Margin of Exposure; MoE AB Ethyl carbamate is mutagenic and produces DNA-adducts in vivo, and is carcinogenic in rodent bioassays. Dose-response modelling of the data for alveolar and bronchiolar adenoma or carcinoma in male and female mice combined gave a BMDL(10) of 0.25 mg/kg-bw/day. The dietary exposure from consumption of foods and non-alcoholic beverage was estimated to be 1 mu g/person/day (15 ng/kg-bw/day), while the exposure of a high-percentile consumer of alcoholic beverages was estimated to be 5 mu g/person per day (80 ng/kg-bw/day). The corresponding calculated MOEs were 16600 and 3125, respectively. (C) 2009 ILSI Europe. Published by Elsevier Ltd. All rights reserved. C1 [DiNovi, Michael] US FDA, Rockville, MD 20857 USA. RP Schlatter, J (reprint author), ILSI Europe, Ave E Mounier 83,B6, B-1200 Brussels, Belgium. EM publications@ilsieurope.be NR 3 TC 6 Z9 6 U1 3 U2 8 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 JAN PY 2010 VL 48 SU 1 BP S63 EP S68 DI 10.1016/j.fct.2009.10.032 PG 6 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 561VM UT WOS:000275007900008 PM 20113856 ER PT J AU Smith, B Cadby, P DiNovi, M Setzer, RW AF Smith, Benjamin Cadby, Peter DiNovi, Michael Setzer, R. Woodrow TI Application of the Margin of Exposure (MoE) approach to substances in food that are genotoxic and carcinogenic Example: Benzene, CAS: 71-43-2 SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Benzene; Margin of exposure (MoE); Food ID EPIDEMIOLOGIC RISK ASSESSMENT; VOLATILE FLAVOR COMPONENTS; BOLOGNA-INSTITUTE; MULTIPOTENTIAL CARCINOGEN; TRANS,TRANS-MUCONIC ACID; TARGET TISSUES; ZYMBAL GLAND; B6C3F1 MICE; METABOLISM; TOXICITY AB The role of genotoxic events in the aetiology of benzene induced tumours cannot be ruled out. Dose response modelling of the data for benzene gave a BMDL10 for female Zymbal gland carcinoma of 17.6 mg/kg-bw/d following adjustment to daily average doses. The MOEs ranged from 2 x 10(6) to 0.4 x 10(6) depending on the assumptions used in the exposure estimation. (C) 2009 ILSI Europe. Published by Elsevier Ltd. All rights reserved. C1 [DiNovi, Michael] US FDA, Rockville, MD 20857 USA. RP Smith, B (reprint author), ILSI Europe, Ave E Mounier 83,Postbox 6, B-1200 Brussels, Belgium. EM publications@ilsieurope.be NR 62 TC 4 Z9 4 U1 0 U2 5 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 JAN PY 2010 VL 48 SU 1 BP S49 EP S56 DI 10.1016/j.fct.2009.10.015 PG 8 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 561VM UT WOS:000275007900006 PM 20113854 ER PT J AU Brandt, MB Moss, J Ellwood, K Ferguson, M Asefa, A AF Brandt, Mary Bender Moss, Julie Ellwood, Kathleen Ferguson, Martine Asefa, Aden TI TRACKING LABEL CLAIMS SO FOOD TECHNOLOGY LA English DT Article ID NUTRITION FOOD LABEL; HEALTH CLAIMS; PACKAGE SURVEY; PROMISE C1 [Brandt, Mary Bender] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Brandt, MB (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM mary.brandt@fda.hhs.gov; julie.moss@fda.hhs.gov; kathy.ellwood@fda.hhs.gov; martine.ferguson@fda.hhs.gov; aden.asefa@fda.hhs.gov FU Center for Food Safety and Applied Nutrition; U.S. Dept. of Energy; U.S. Food and Drug Administration FX This project was supported in part by an appointment to the Research Participation Program at the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Dept. of Energy and the U.S. Food and Drug Administration. NR 27 TC 10 Z9 10 U1 0 U2 8 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA 525 WEST VAN BUREN, STE 1000, CHICAGO, IL 60607-3814 USA SN 0015-6639 J9 FOOD TECHNOL-CHICAGO JI Food Technol. PD JAN PY 2010 VL 64 IS 1 BP 34 EP 40 PG 7 WC Food Science & Technology SC Food Science & Technology GA 546QD UT WOS:000273824400012 ER PT J AU Drake, SL Whitney, B Levine, JF DePaola, A Jaykus, LA AF Drake, Stephenie L. Whitney, Brooke Levine, Jay F. DePaola, Angelo Jaykus, Lee-Ann TI Correlation of Mannitol Fermentation with Virulence-Associated Genotypic Characteristics in Vibrio vulnificus Isolates from Oysters and Water Samples in the Gulf of Mexico SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID PCR; STRAINS AB Vibrio vulnificus strains (n = 469) isolated from the Gulf of Mexico oysters and waters over a period of 2 years were subjected to phenotypic and genotypic characterizations. Of the strains that could be definitively genotyped (n = 465), 58% were classified as genotype A, 29% as genotype B, and 13% as genotype A/B by 16S rRNA genotyping. When the same strain bank was characterized by virulence-correlated gene (vcg) typing, 65% were genotype E while 35% were genotype C. Further analysis focusing on strains falling into typical genotype categories (i.e., 16S rRNA types A or B, excluding type A/B strains) showed a high degree of concordance (93%) when comparing the two genotyping methods. D-Mannitol fermentation was also predictive of genotype, with an 86% agreement between 16S rRNA genotype and mannitol fermentation patterns, and an 85% agreement between vcg genotype and mannitol fermentation patterns. D-Mannitol fermentation should be considered as a simple and less expensive alternative to screen V. vulnificus isolates for virulence potential, particularly when analyzing large strain banks. C1 [Drake, Stephenie L.; Whitney, Brooke; Jaykus, Lee-Ann] N Carolina State Univ, Dept Food Sci, Raleigh, NC 27695 USA. [Levine, Jay F.] N Carolina State Univ, Dept Populat Hlth & Pathobiol, Aquat Epidemiol & Conservat Lab, Raleigh, NC 27695 USA. [DePaola, Angelo] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL USA. RP Drake, SL (reprint author), N Carolina State Univ, Dept Food Sci, Campus Box 7624, Raleigh, NC 27695 USA. EM sldrake@ncsu.edu FU U.S. Department of Agriculture, Cooperative State Research, Education, and Extension Service (CSREES), National Research Initiative [2004-35212-14882] FX This study was supported by a grant from the U.S. Department of Agriculture, Cooperative State Research, Education, and Extension Service (CSREES), National Research Initiative, Competitive Grants Program, Epidemiological Approaches to Food Safety (project no. 2004-35212-14882). This article is manuscript no. FSR09-21 of the Department of Food Science, North Carolina State University. NR 19 TC 14 Z9 15 U1 0 U2 2 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 JAN PY 2010 VL 7 IS 1 BP 97 EP 101 DI 10.1089/fpd.2009.0362 PG 5 WC Food Science & Technology SC Food Science & Technology GA 540AI UT WOS:000273302100014 PM 19785540 ER PT J AU Chang, CWJ Edirisinghe, I Jablonski, JE Tadapaneni, RK Tulio, AZ Burton-Freeman, B Jackson, L AF Chang, Claire Wei-Ju Edirisinghe, Indika Jablonski, Joseph E. Tadapaneni, Ravi K. Tulio, Artemio Z. Burton-Freeman, Britt Jackson, Lauren TI Polyphenols-rich Fruit Extracts Modulate Endothelial Cell Migration via PI3 Kinase/Akt pathway in vitro in Human Umbilical Vein Endothelial Cells SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Chang, Claire Wei-Ju; Jablonski, Joseph E.; Tulio, Artemio Z.; Jackson, Lauren] US FDA, Rockville, MD 20857 USA. [Edirisinghe, Indika; Tadapaneni, Ravi K.; Burton-Freeman, Britt] IIT, Chicago, IL 60616 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S178 EP S179 DI 10.1016/j.freeradbiomed.2010.10.507 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000516 ER PT J AU Flaherty, NL Mellilo, AA Rashel, M Poole, LB Melendez, JA AF Flaherty, Nicole L. Mellilo, Amanda A. Rashel, Mohammad Poole, Leslie B. Melendez, J. Andres TI Defining the Antioxidant Determinants of Francisella tularensis Virulence SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Flaherty, Nicole L.; Rashel, Mohammad; Melendez, J. Andres] Albany Med Coll, Albany, NY 12208 USA. [Mellilo, Amanda A.] US FDA, Rockville, MD 20857 USA. [Poole, Leslie B.] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S142 EP S142 DI 10.1016/j.freeradbiomed.2010.10.395 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000407 ER PT J AU Shabalina, SA Spiridonov, AN Spiridonov, NA Koonin, EV AF Shabalina, Svetlana A. Spiridonov, Alexey N. Spiridonov, Nikolay A. Koonin, Eugene V. TI Connections between Alternative Transcription and Alternative Splicing in Mammals SO GENOME BIOLOGY AND EVOLUTION LA English DT Article DE alternative splicing; alternative transcription initiation; alternative transcription termination; gene expression factories ID RNA-POLYMERASE-II; C-TERMINAL DOMAIN; MESSENGER-RNA; UNTRANSLATED REGIONS; INITIATION SITES; START SITES; PROMOTERS; EXPRESSION; EVOLUTION; SEQUENCES AB The majority of mammalian genes produce multiple transcripts resulting from alternative splicing (AS) and/or alternative transcription initiation (ATI) and alternative transcription termination (ATT). Comparative analysis of the number of alternative nucleotides, isoforms, and introns per locus in genes with different types of alternative events suggests that ATI and ATT contribute to the diversity of human and mouse transcriptome even more than AS. There is a strong negative correlation between AS and ATI in 5' untranslated regions (UTRs) and AS in coding sequences (CDSs) but an even stronger positive correlation between AS in CDSs and ATT in 3' UTRs. These observations could reflect preferential regulation of distinct, large groups of genes by different mechanisms: 1) regulation at the level of transcription initiation and initiation of translation resulting from ATI and AS in 5' UTRs and 2) posttranslational regulation by different protein isoforms. The tight linkage between AS in CDSs and ATT in 3' UTRs suggests that variability of 3' UTRs mediates differential translational regulation of alternative protein forms. Together, the results imply coordinate evolution of AS and alternative transcription, processes that occur concomitantly within gene expression factories. C1 [Shabalina, Svetlana A.; 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. [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 US Department of Health and Human Services (National Library of Medicine) FX The research of S.A.S. and E.V.K. is supported by the intramural funds of the US Department of Health and Human Services (National Library of Medicine). NR 44 TC 18 Z9 20 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PY 2010 VL 2 BP 791 EP 799 DI 10.1093/gbe/evq058 PG 9 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 775NT UT WOS:000291467300021 PM 20889654 ER EF