FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Levine, RA Ryan, SM AF Levine, Robert A. Ryan, Sean M. TI Determining the Effect of Calcium Cations on Acrylamide Formation in Cooked Wheat Products Using a Model System SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Acrylamide; cereal; wheat; flour; baking; calcium chloride; divalent cations; GC-MS ID CEREAL PRODUCTS; POTATO CRISPS; PH; REDUCTION; KINETICS; IMPACT; DOUGH; FERMENTATION; TEMPERATURE; SOLUBILITY AB A model system was used to cook wheat flour and water dough pieces in sealed pressure tubes under controlled pH conditions and with various additives in the recipe water to determine acrylamide (AA) formation and elimination. The potential effectiveness of calcium as CaCl(2) or CaCO(3) salts to reduce the formation of AA in wheat based food products was assessed. Since the divalent Ca(2+) was capable of inducing significant pH reduction in the dough, and pH lowering is known to reduce AA formation, it was necessary in some cases to adjust the pH before cooking or use a pH matched control. For comparison, the effect of NaCl on AA formation was also determined. It was found that AA reduction up to 36% was obtained by adding CaCl(2) to the recipe water at a 0.04 M concentration, compared to 23% for 0.04 M NaCl, and there was no reduction when CaCO(3) was added to simulate a calcium enriched flour. C1 [Levine, Robert A.; Ryan, Sean M.] US FDA, Total Diet & Pesticide Res Ctr, Lenexa, KS 66214 USA. RP Levine, RA (reprint author), US FDA, Total Diet & Pesticide Res Ctr, 11510 W 80th St, Lenexa, KS 66214 USA. EM robert.levine@fda.hhs.gov NR 39 TC 19 Z9 20 U1 3 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD AUG 12 PY 2009 VL 57 IS 15 BP 6823 EP 6829 DI 10.1021/jf901120m PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 477RW UT WOS:000268537300047 PM 19603807 ER PT J AU Stone, M Laughren, T Jones, ML Levenson, M Holland, PC Hughes, A Hammad, TA Temple, R Rochester, G AF Stone, Marc Laughren, Thomas Jones, M. Lisa Levenson, Mark Holland, P. Chris Hughes, Alice Hammad, Tarek A. Temple, Robert Rochester, George TI Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; RANDOMIZED CONTROLLED-TRIALS; PLACEBO; METAANALYSIS; DEPRESSION; RATES AB Objective To examine the risk of suicidal behaviour within clinical trials of antidepressants in adults. Design Meta-analysis of 372 double blind randomised placebo controlled trials. Setting Drug development programmes for any indication in adults. Participants 99 231 adults assigned to antidepressants or placebo. Median age was 42 and 63.1% were women. Indications for treatment were major depression (45.6%), other depression (4.6%), other psychiatric disorders (27.6%), and non-psychiatric disorders (22.2%). Main outcome measures Suicidal behaviour (completed suicide, attempted suicide, or preparatory acts) and ideation. Results For participants with non-psychiatric indications, suicidal behaviour and ideation were extremely rare. For those with psychiatric indications, risk was associated with age. For suicidal behaviour or ideation and for suicidal behaviour only, the respective odds ratios were 1.62 (95% confidence interval 0.97 to 2.71) and 2.30 (1.04 to 5.09) for participants aged <25, 0.79 (0.64 to 0.98) and 0.87 (0.58 to 1.29) for those aged 25-64, and 0.37 (0.18 to 0.76) and 0.06 (0.01 to 0.58) for those aged >= 65. When age was modelled as a continuous variable, the odds ratio for suicidal behaviour or ideation declined at a rate of 2.6% per year of age (-3.9% to -1.3%, P=0.0001) and the odds ratio for suicidal behaviour declined at a rate of 4.6% per year of age (-7.4% to -1.8%, P=0.001). Conclusions Risk of suicidality associated with use of antidepressants is strongly age dependent. Compared with placebo, the increased risk for suicidality and suicidal behaviour among adults under 25 approaches that seen in children and adolescents. The net effect seems to be neutral on suicidal behaviour but possibly protective for suicidal ideation in adults aged 25-64 and to reduce the risk of both suicidality and suicidal behaviour in those aged >= 65. C1 [Stone, Marc; Laughren, Thomas] US FDA, Ctr Drug Evaluat & Res, Div Psychiat Prod, Silver Spring, MD 20993 USA. [Hughes, Alice] US FDA, Ctr Drug Evaluat & Res, Div Neurol Prod, Silver Spring, MD 20993 USA. [Hammad, Tarek A.] US FDA, Ctr Drug Evaluat & Res, Div Epidemiol, Silver Spring, MD 20993 USA. RP Stone, M (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Psychiat Prod, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM marc.stone@fda.hhs.gov NR 18 TC 174 Z9 177 U1 2 U2 19 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD AUG 11 PY 2009 VL 339 AR b2880 DI 10.1136/bmj.b2880 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 485YH UT WOS:000269161800002 PM 19671933 ER PT J AU El Sahly, HM Atmar, RL Patel, SM Wells, JM Cate, T Ho, M Guo, K Pasetti, MF Lewis, DE Sztein, MB Keitel, WA AF El Sahly, H. M. Atmar, R. L. Patel, S. M. Wells, J. M. Cate, T. Ho, M. Guo, K. Pasetti, M. F. Lewis, D. E. Sztein, M. B. Keitel, W. A. TI Safety, reactogenicity and immunogenicity of Francisella tularensis live vaccine strain in humans SO VACCINE LA English DT Article; Proceedings Paper CT 2nd Vaccine Congress CY DEC 07-09, 2008 CL Boston, MA DE Clinical trial; Tularemia vaccine; Live vaccine strain; Safety and immunogenicity ID TULAREMIA VACCINE; PROTECTIVE IMMUNITY; IMMUNIZATION; CHALLENGE; INFECTION; RESPONSES; ANTIBODIES; INNATE; AGENTS; LVS AB We evaluated the safety, reactogenicity and immunogenicity of escalating doses of a new Francisella tularensis Live Vaccine Strain (LVS) lot by scarification (SCAR) or subcutaneously (SQ) in humans. Subjects (N = 10/group) received one dose of LVS via SCAR at 10(5),10(7) or 10(9) cfu/ml or SQ at 10(2), 10(3), 10(4) or 10(5) cfu/ml; 14 subjects received placebo. All doses/routes were well tolerated. When compared to placebo, vaccination with 10(7) SCAR and 10(9) SCAR resulted in significantly higher serologic response frequencies, as measured by ELISA for IgG, IgM, IgA and microagglutination; whereas vaccination with 10(5) SCAR, 10(7) SCAR 10(9) SCAR and 10(5) SQ elicited a significantly higher interferon-gamma response frequency. (C) 2009 Elsevier Ltd. All rights reserved. C1 [El Sahly, H. M.; Atmar, R. L.; Patel, S. M.; Wells, J. M.; Cate, T.; Keitel, W. A.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [El Sahly, H. M.; Atmar, R. L.; Patel, S. M.; Cate, T.; Keitel, W. A.] Baylor Coll Med, Dept Med, Infect Dis Sect, Houston, TX 77030 USA. [Ho, M.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Guo, K.] EMMES Corp, Rockville, MD USA. [Pasetti, M. F.; Sztein, M. B.] Univ Maryland, Dept Pediat, Ctr Vaccine Dev, Baltimore, MD 21201 USA. [Lewis, D. E.] Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. RP El Sahly, HM (reprint author), Baylor Coll Med, Dept Mol Virol & Microbiol, 1 Baylor Plaza,BCM MS280, Houston, TX 77030 USA. EM hanae@bcm.edu FU NIAID NIH HHS [N01AI25465, N01-AI-25465, N01 AI025465, N01-AI-30028, N01AI30028] NR 30 TC 17 Z9 17 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 6 PY 2009 VL 27 IS 36 BP 4905 EP 4911 DI 10.1016/j.vaccine.2009.06.036 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 484UA UT WOS:000269071800006 PM 19567246 ER PT J AU Hanson, MA Brorson, KA Moreira, AR Rao, G AF Hanson, Michael A. Brorson, Kurt A. Moreira, Antonio R. Rao, Govind TI Comparisons of optically monitored small-scale stirred tank vessels to optically controlled disposable bag bioreactors SO MICROBIAL CELL FACTORIES LA English DT Article ID MAMMALIAN-CELL CULTURE; OXYGEN LIMITATION; PH; PROBES; SENSOR AB Background: Upstream bioprocesses are extremely complex since living organisms are used to generate active pharmaceutical ingredients (APIs). Cells in culture behave uniquely in response to their environment, thus culture conditions must be precisely defined and controlled in order for productivity and product quality to be reproducible. Thus, development culturing platforms are needed where many experiments can be carried out at once and pertinent scale-up information can be obtained. Results: Here we have tested a High Throughput Bioreactor (HTBR) as a scale-down model for a lab-scale wave-type bioreactor (CultiBag). Mass transfer was characterized in both systems and scaling based on volumetric oxygen mass transfer coefficient (k(L)a) was sufficient to give similar DO trends. HTBR and CultiBag cell growth and mAb production were highly comparable in the first experiment where DO and pH were allowed to vary freely. In the second experiment, growth and mAb production rates were lower in the HTBR as compared to the CultiBag, where pH was controlled. The differences in magnitude were not considered significant for biological systems. Conclusion: Similar oxygen delivery rates were achieved in both systems, leading to comparable culture performance (growth and mAb production) across scales and mode of mixing. HTBR model was most fitting when neither system was pH-controlled, providing an information-rich alternative to typically non-monitored mL-scale platforms. C1 [Hanson, Michael A.; Moreira, Antonio R.; Rao, Govind] Univ Maryland Baltimore Cty, Dept Chem & Biochem Engn, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Hanson, Michael A.; Brorson, Kurt A.] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. [Hanson, Michael A.] Wyeth Pharmaceut, Mfg Sci & Technol, Pearl River, NY 10965 USA. RP Rao, G (reprint author), Univ Maryland Baltimore Cty, Dept Chem & Biochem Engn, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. EM hansonm@wyeth.com; kurt.brorson@fda.hhs.gov; moreira@umbc.edu; grao@umbc.edu FU PDA Pre-doctoral Fellowship; Sartorius-Stedim Biotech FX While carrying out this work Michael Hanson was partially funded by a PDA Pre-doctoral Fellowship. Funding and equipment donations from Sartorius-Stedim Biotech are gratefully acknowledged. NR 15 TC 12 Z9 12 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1475-2859 J9 MICROB CELL FACT JI Microb. Cell. Fact. PD AUG 5 PY 2009 VL 8 AR 44 DI 10.1186/1475-2859-8-44 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 486DC UT WOS:000269174700001 PM 19656387 ER PT J AU Sauna, ZE Okunji, C Hunt, RC Gupta, T Allen, CE Plum, E Blaisdell, A Grigoryan, V Geetha, S Fathke, R Soejima, K Kimchi-Sarfaty, C AF Sauna, Zuben E. Okunji, Chinyere Hunt, Ryan C. Gupta, Tanvi Allen, Courtni E. Plum, Elizabeth Blaisdell, Adam Grigoryan, Vahan Geetha, S. Fathke, Robert Soejima, Kenji Kimchi-Sarfaty, Chava TI Characterization of Conformation-Sensitive Antibodies to ADAMTS13, the von Willebrand Cleavage Protease SO PLOS ONE LA English DT Article AB Background: The zinc metalloprotease ADAMTS13 is a multidomain protein that cleaves von Willebrand Factor (VWF) and is implicated in Thrombotic Thrombocytopenic Purpura (TTP) pathogenesis. Understanding the mechanism of this protein is an important goal. Conformation sensitive antibodies have been used to monitor protein conformation and to decipher the molecular mechanism of proteins as well as to distinguish functional and non-functional mutants. Methodology/Principal Findings: We have characterized several antibodies against ADAMTS13, both monoclonal and polyclonal. We have used flow cytometry to estimate the binding of these antibodies to ADAMTS13 and demonstrate that antibodies raised against the TSP and disintegrin domains detect conformation changes in the ADAMTS13. Thus for example, increased binding of these antibodies was detected in the presence of the substrate (VWF), mainly at 37 degrees C and not at 4 degrees C. These antibodies could also detect differences between wild-type ADAMTS13 and the catalytically deficient mutant (P475S). The flow cytometry approach also allows us to estimate the reactivity of the antibody as well as its apparent affinity. Conclusions/Significance: Our results suggest that these antibodies may serve as useful reagents to distinguish functional and non-functional ADAMTS13 and analyze conformational transitions to understand the catalytic mechanism. RP Sauna, ZE (reprint author), US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM Zuben.sauna@fda.hhs.gov; Chava.kimchi-sarfaty@fda.hhs.gov NR 45 TC 5 Z9 5 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 5 PY 2009 VL 4 IS 8 AR e6506 DI 10.1371/journal.pone.0006506 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 480MN UT WOS:000268739100007 PM 19654870 ER PT J AU Mackey, AC Green, L St Amand, K Avigan, M AF Mackey, Ann Corken Green, Lanh St Amand, Keith Avigan, Mark TI Sodium Phosphate Tablets and Acute Phosphate Nephropathy SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material ID BOWEL PREPARATIONS; COLONOSCOPY C1 [Mackey, Ann Corken; Green, Lanh; St Amand, Keith; Avigan, Mark] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. RP Mackey, AC (reprint author), US FDA, Off Surveillance & Epidemiol, Bldg 22,Room 3472,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM ann.mackey@fda.hhs.gov NR 15 TC 11 Z9 11 U1 0 U2 0 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 AUG PY 2009 VL 104 IS 8 BP 1903 EP 1906 DI 10.1038/ajg.2009.342 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 483KW UT WOS:000268965300002 PM 19661931 ER PT J AU Gupta, A Ciavarella, AB Rothman, B Faustino, PJ Khan, MA AF Gupta, Abhay Ciavarella, Anthony B. Rothman, Barry Faustino, Patrick J. Khan, Mansoor A. TI Stability of gabapentin 300-mg capsules repackaged in unit dose containers SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE Anticonvulsants; Capsules; Dissolution; Drug distribution systems; Gabapentin; Moisture; Packaging; Stability; Storage; Temperature; Weight ID VALIDATED HPLC METHOD; INFUSION ADMIXTURES; DRUG PRODUCTS; PVC BAGS; INJECTION; SYRUP; COMPATIBILITY; SYRINGES AB Purpose. The stability of a gabapentin 300-mg capsule product in the original bulk containers and repackaged in unit dose blister strips was studied. Methods. Both products were stored for one year under long-term storage conditions (25 degrees C and 60% relative humidity [RH]) and for three months under accelerated storage conditions (40 degrees C and 75% RH) and tested for weight change, potency, and dissolution using validated analytical method. Results. The capsules in the original containers showed no change in weight during the study period. However, the repackaged drug product stored under long-term storage conditions and under accelerated storage conditions showed significant weight increases (p < 0.001) during the study period. No significant differences in potency between the original and repackaged drug products were detected. Potency exceeded 97% for the products stored under the long-term storage conditions and exceeded 95% for the products stored under the accelerated storage conditions. At 13 weeks, samples from the original container and the blister strips stored under the accelerated storage conditions showed quantitative levels of the lactam degradation product; however, these levels were within acceptable limits. No other difference was observed between the original and the repackaged drug products, and both products remained stable throughout the study period. Conclusion. Gabapentin 300-mg capsules in the original containers and repackaged in blister strips were stable up to one year under long-term storage conditions and up to three months under accelerated storage conditions. C1 [Khan, Mansoor A.] US FDA, Div Prod Qual Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Gupta, Abhay; Ciavarella, Anthony B.] OPS, DPQR, OTR, Silver Spring, MD USA. [Rothman, Barry] US FDA, Div Mfg & Prod Qual, Off Compliance, Silver Spring, MD 20993 USA. RP Khan, MA (reprint author), US FDA, Div Prod Qual Res, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Life Sci Bldg 64,Room 107, Silver Spring, MD 20993 USA. EM mansoor.khan@fda.hhs.gov NR 30 TC 5 Z9 5 U1 0 U2 5 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD AUG 1 PY 2009 VL 66 IS 15 BP 1376 EP 1380 DI 10.2146/ajhp080236 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 475LV UT WOS:000268361700010 PM 19635774 ER PT J AU Rafii, F Park, M Carman, RJ AF Rafii, Fatemeh Park, Miseon Carman, Robert J. TI Characterization of an ATP-binding cassette from Clostridium perfringens with homology to an ABC transporter from Clostridium hathewayi SO ANAEROBE LA English DT Article DE Clostridium perfringens; ABC transporter; Drug resistance ID FLUOROQUINOLONE-RESISTANCE; EFFLUX PUMP; STREPTOCOCCUS-PNEUMONIAE; BACTEROIDES-FRAGILIS; MULTIDRUG-RESISTANCE; MUTANTS; CLASSIFICATION; INVOLVEMENT; PROTEINS; GYRASE AB A ciprofloxacin-resistant mutant of Clostridium perfringens, strain VPI-C, which had stable mutations in the topoisomerase genes, accumulated less norfloxacin and ethidium bromide than the wild type, strain VPI. Efflux pump inhibitors both increased the accumulation of ethidium bromide by cells of the mutant and enhanced their sensitivity to this toxic dye. Cloning a gene, which codes for a putative ABC transporter protein (NP_562422) of 527 amino acids, from the mutant strain VPI-C into the wild-type strain VPI not only reduced the accumulation of ethidium bromide by the recombinant strain but also reduced its sensitivity to norfloxacin and ciprofloxacin. Efflux pump inhibitors decreased the rate at which ethidium bromide was removed from the cells of the recombinant strain. It appears that the putative ABC transporter protein (NP_562422) may contribute to extrusion of drugs from C. perfringens. Published by Elsevier Ltd. C1 [Rafii, Fatemeh; Park, Miseon] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Carman, Robert J.] VPI Res Pk, Tech Lab, Blacksburg, VA 24060 USA. RP Rafii, F (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM fatemeh.rafii@fda.hhs.gov NR 21 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1075-9964 J9 ANAEROBE JI Anaerobe PD AUG PY 2009 VL 15 IS 4 BP 116 EP 121 DI 10.1016/j.anaerobe.2009.01.008 PG 6 WC Microbiology SC Microbiology GA 483ND UT WOS:000268972700003 PM 19655423 ER PT J AU Schultheis, LW Nikhar, BM Mellon, RD Doddapaneni, S Christodoulo, DD Roca, R Rappaport, BA AF Schultheis, Lex W. Nikhar, Bindi M. Mellon, R. Daniel Doddapaneni, Suresh Christodoulo, Danae D. Roca, Rigoberto Rappaport, Bob A. TI Clinical Investigation of Neuraxially Administered Drugs: A Regulatory Perspective SO ANESTHESIA AND ANALGESIA LA English DT Editorial Material C1 [Schultheis, Lex W.; Nikhar, Bindi M.; Mellon, R. Daniel; Doddapaneni, Suresh; Christodoulo, Danae D.; Roca, Rigoberto; Rappaport, Bob A.] US FDA, Ctr Drug Evaluat & Res, Div Anesthesia Analgesia & Rheumatol Prod, Silver Spring, MD 20993 USA. RP Schultheis, LW (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Anesthesia Analgesia & Rheumatol Prod, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM lester.schultheis@fda.hhs.gov NR 1 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD AUG PY 2009 VL 109 IS 2 BP 299 EP 300 DI 10.1213/ane.0b013e3181a801b9 PG 2 WC Anesthesiology SC Anesthesiology GA 474QH UT WOS:000268298600003 PM 19608794 ER PT J AU Jia, YP Alayash, AI AF Jia, Yiping Alayash, Abdu I. TI Effects of cross-linking and zero-link polymerization on oxygen transport and redox chemistry of bovine hemoglobin SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Article DE Hemoglobin; Zero-link; Rapid kinetics; Stopped-flow; Oxygen affinity ID HEME DEGRADATION-PRODUCTS; CHLORIDE-BINDING SITES; BLOOD SUBSTITUTES; FUNCTIONAL CONSEQUENCES; NITRIC-OXIDE; OXIDATION; CARRIERS; GLUTARALDEHYDE; DISSOCIATION; AFFINITY AB Cross-linked hemoglobins (Hbs) were found to have enhanced oxidative reactions which compromise the ability of cell-free Hb to carry oxygen. Zero-link bovine Hb (ZL-HbBv). also known as OxyVita(TM), a large polymer held together by pseudopeptide bonds on the surface of adjacent tetramers, provides a model in which these reactions can be evaluated. The oxygen affinity of ZL-HbBv was greatly increased, whereas the oxygen binding cooperativity (n(50)) as well as the regulatory responses to pH and chloride ions was diminished. Rapid mixing kinetic studies revealed faster carbon monoxide (CO) and nitric oxide (NO) binding to ZL-HbBv. consistent with a more accessible heme pocket conformation. The rate of autoxidation of ferrous ZL-HbBv was 3 folds faster than the unmodified HbBv (control) but only slightly suppressed by the presence of superoxide dismutase and catalase enzymes. The peroxide (H(2)O(2)) reaction rates of ferric ZL-HbBv and its degradation were comparable to that of the control. The rate of heme loss from ZL-HbBv to a mutant apomyoglobin (H64Y/V68F) was also very close to that of the control. Taken together, allosteric and redox reactions of this protein are altered due to heme accessibility to solvent. however, the compact tetramer to tetramer interaction of the ZL-HbBv polymer appears to restrict heme loss even in the presence of excess H(2)O(2). Published by Elsevier B.V. C1 [Jia, Yiping; Alayash, Abdu I.] US FDA, LBVB, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Jia, YP (reprint author), Natl Inst Hlth NIH Campus,8800 Rockville Pike,Bld, Bethesda, MD 20892 USA. EM yiping.jia@fda.hhs.gov NR 47 TC 13 Z9 13 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD AUG PY 2009 VL 1794 IS 8 BP 1234 EP 1242 DI 10.1016/j.bbapap.2009.04.008 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 467VV UT WOS:000267772100017 PM 19409516 ER PT J AU Sheng-Fowler, L Lewis, AM Peden, K AF Sheng-Fowler, Li Lewis, Andrew M., Jr. Peden, Keith TI Quantitative determination of the infectivity of the proviral DNA of a retrovirus in vitro: Evaluation of methods for DNA inactivation SO BIOLOGICALS LA English DT Article DE DNA infectivity; DNA inactivation; Vaccine cell substrates ID RABBIT PAPILLOMAVIRUS DNA; BOVINE LEUKEMIA-VIRUS; SIMIAN IMMUNODEFICIENCY VIRUS; VIRAL-DNA; MOLECULAR CLONE; BETA-PROPIOLACTONE; DEOXYRIBONUCLEIC-ACID; BIOLOGICAL-ACTIVITY; MAMMALIAN-CELLS; POLYOMA-VIRUS AB All viral vaccines contain contaminating residual DNA derived from the production cell substrate. The potential risk of this DNA, particularly when derived from tumorigenic cells, has been debated for over 40 years. While the major risk has been considered to be the oncogenicity of the DNA, another potential risk is that a genome of an infectious virus is present in this DNA. Such a genome might generate an infectious agent that could establish an infection in vaccine recipients. To determine the quantity of a retroviral provirus in cellular DNA that can establish a productive infection in vitro, we developed a transfection/co-culture system capable of recovering infectious virus from 1 pg of cloned HIV DNA and from 2 pg of cellular DNA from HIV-infected cells. We demonstrate that infectivity can be reduced to below detectable levels either by lowering the median size of the DNA to 350 base pairs or by treatment with beta-propiolactone. From the amount of reduction of infectivity, we calculate that clearance values in excess of 10 7 are attainable with respect to the infectivity associated with residual cell-substrate DNA. Thus, the potential fisk associated with DNA can be substantially reduced by degradation or by chemical inactivation. Published by Elsevier Ltd on behalf of The International Association for Biologicals. C1 [Sheng-Fowler, Li; Peden, Keith] US FDA, CBER, Div Viral Prod, Lab Retrovirus Res, Bethesda, MD 20892 USA. [Lewis, Andrew M., Jr.] US FDA, CBER, Div Viral Prod, Lab DNA Viruses, Bethesda, MD 20892 USA. RP Peden, K (reprint author), US FDA, CBER, Div Viral Prod, Lab Retrovirus Res, Bldg 29A,Room 3D08,29 Lincoln Dr, Bethesda, MD 20892 USA. EM keith.peden@fda.hhs.gov FU National Vaccine Program Office.; National Vaccine Program Office FX This work was supported in part by a grant from the National Vaccine Program Office. L.S. was initially supported by a fellowship funded by the National Vaccine Program Office. We thank Phil Krause, Hana Golding, Phoebe Mounts, Arifa Khan, Jerry Weir, and Erik Henchal for discussions and/or comments on the manuscript. NR 83 TC 8 Z9 9 U1 0 U2 3 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 AUG PY 2009 VL 37 IS 4 BP 259 EP 269 DI 10.1016/j.biologicals.2009.04.002 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 495ZO UT WOS:000269936400009 PM 19457682 ER PT J AU Zhang, ZW AF Zhang, Zhiwei TI Interpreting Statistical Evidence with Empirical Likelihood Functions SO BIOMETRICAL JOURNAL LA English DT Article DE Consistency; Evidential analysis; Law of likelihood; Local asymptotic normality; Robust adjusted likelihood ID TRIALS; MODELS AB There has been growing interest in the likelihood paradigm of statistics, where statistical evidence is represented by the likelihood function and its strength is measured by likelihood ratios. The available literature in this area has so far focused on parametric likelihood functions, though in some cases a parametric likelihood can be robustified. This focused discussion on parametric models, while insightful and productive, may have left the impression that the likelihood paradigm is best suited to parametric situations. This article discusses the use of empirical likelihood functions, a well-developed methodology in the frequentist paradigm, to interpret statistical evidence in nonparametric and semiparametric situations. A comparative review of literature shows that, while an empirical likelihood is not a true probability density, it has the essential properties, namely consistency and local asymptotic normality that unify and justify the various parametric likelihood methods for evidential analysis. Real examples are presented to illustrate and compare the empirical likelihood method and the parametric likelihood methods. These methods are also compared in terms of asymptotic efficiency by combining relevant results from different areas. It is seen that a parametric likelihood based on a correctly specified model is generally more efficient than an empirical likelihood for the same parameter. However, when the working model fails, a parametric likelihood either breaks down or, if a robust version exists, becomes less efficient than the corresponding empirical likelihood. C1 Ctr Devices & Radiol Hlth Food & Drug Adm, Silver Spring, MD USA. RP Zhang, ZW (reprint author), Ctr Devices & Radiol Hlth Food & Drug Adm, Silver Spring, MD USA. EM zhiwei.zhang@fda.hhs.gov NR 18 TC 2 Z9 2 U1 0 U2 9 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD AUG PY 2009 VL 51 IS 4 BP 710 EP 720 DI 10.1002/bimj.200800209 PG 11 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 493EY UT WOS:000269718300013 PM 19650056 ER PT J AU Riordan, W Heilmann, S Brorson, K Seshadri, K He, Y Etzel, M AF Riordan, William Heilmann, Steve Brorson, Kurt Seshadri, Kannan He, Yi Etzel, Mark TI Design of Salt-Tolerant Membrane Adsorbers for Viral Clearance SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE membrane adsorbers; viral clearance; anion exchange chromatography; salt tolerant ligands; monoclonal antibodies; Phi X174 ID SCALE ANTIBODY PURIFICATION; ION-EXCHANGE CHROMATOGRAPHY; PLASMID DNA; PROTEIN; PERFORMANCE; VIRUS; RETENTION; BEHAVIOR; CAPTURE; FILTERS AB Strong anion exchange chromatography has frequently been employed as a viral clearance step during downstream processing of biological therapeutics. When challenged with viruses having only slightly acidic isoelectric points, the performance of the anion exchange operation becomes highly dependent on the buffer salt concentration, with the virus log reduction value (LRV) dropping dramatically in buffers with 50-150 mM salt. In this work, a series of anion exchange membrane adsorbers utilizing alternative ligand chemistries instead of the traditional quaternary amine (Q) ligand have been developed that overcome this limitation. Four different ligands (agmatine, tris-2-aminoethyl amine, polyhexamethylene biguanide, and polyethyleneimine) achieved >5 LRV of bacteriophage Phi X174 (pI similar to 6.7) at PH 7.5 and up to 150 mM salt, compared to 0 LRV for the Q ligand. By evaluating structural derivatives of the successful ligands, three factors were identified that contributed to ligand salt tolerance: ligand net charge, ligand immobilization density on the membrane, and molecular structure of the ligand-binding group. Based on the results of this study, membrane adsorbers that incorporate alternative ligands provide a more robust and salt tolerant viral clearance-processing step compared to traditional strong anion exchange membrane adsorbers. Biotechnol. Bioeng. 2009;103: 920-929. (C) 2009 Wiley Periodicals, Inc. C1 [Riordan, William; Etzel, Mark] Univ Wisconsin, Dept Chem & Biol Engn, Madison, WI 53706 USA. [Heilmann, Steve; Seshadri, Kannan; He, Yi] 3M Corp, Mat Res Lab, 3M Ctr, St Paul, MN USA. [Brorson, Kurt] US FDA, CDER, Div Monoclonal Antibodies, Silver Spring, MD USA. RP Etzel, M (reprint author), Univ Wisconsin, Dept Chem & Biol Engn, 1605 Linden Dr, Madison, WI 53706 USA. EM etzel@engr.wisc.edu NR 32 TC 32 Z9 32 U1 2 U2 12 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 AUG 1 PY 2009 VL 103 IS 5 BP 920 EP 929 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 469BG UT WOS:000267869300008 PM 19370771 ER PT J AU Hubert, KC Singh, M Zhou, EH Delos Santos, G Stovsky, MD AF Hubert, Katherine C. Singh, Mandeep Zhou, Esther H. Delos Santos, Grace Stovsky, Mark D. TI Charlson comorbidity index and success of extracorporeal shock wave lithotripsy SO CANADIAN JOURNAL OF UROLOGY LA English DT Article DE treatment outcome; comorbidity; lithotripsy ID LOCALIZED PROSTATE-CANCER; CO-MORBIDITY; VALIDATION; MEN AB Introduction/objective: We examined the potential correlation between Charlson comorbidity index (CCI) and stone free rate after extracorporeal shock wave lithotripsy (ESWL). Materials and methods: Two hundred twenty-six adult patients were treated with 241 ESWL procedures for a renal or ureteral stone(s) over a 3 year period. Age, race, comorbidities, CCI, stone size and location, number of shocks and power level were determined. Treatment efficacies were evaluated at a mean of 56.1 days after each ESWL with computed tomography, abdominal x-ray, intravenous pyleography and/or renal ultrasound. Multivariate logistic regression analysis was performed. Results: There was no correlation between CCI and any of the following: stone burden, number of shocks, or power level. There was no difference in stone burden, number of shocks or power level between those who were and were not stone free. Stone free rates for patients with CCI of zero, one, and two or greater were 44.7% (71/159), 27% (13/48) and 41.2% (14/34) respectively. Patients with an index of one were 2.1 times more likely to have a residual stone burden than patients with an index of zero (95% CI 0.99-4.42, p = 0.05). Patients with one comorbidity were 2.4 times more likely to have a residual stone burden than patients with none (95% CI 1.04-5.72, p = 0.04). Patients with upper ureteral stones were less likely to have a residual stone burden than patients with renal stones (RR = 0.52, 95% CI 0.27-0.98, p = 0.04). Those with lower ureteral stones were less likely to have a residual stone burden than those with renal stones (RR = 0.20, 95% CI 0.09-0.43, p < 0.0001). The only significant predictors of the stone free rate were stone location and number of comorbidities. Conclusions: Stone location and number of comorbidities were significant predictors of ESWL outcome. The CCI may underestimate the magnitude of comorbidities and their effect on stone treatment efficacy. C1 [Hubert, Katherine C.; Singh, Mandeep; Delos Santos, Grace; Stovsky, Mark D.] Case Western Reserve Univ, Sch Med, Univ Hosp Case Med Ctr, Dept Urol, Cleveland, OH 44106 USA. [Zhou, Esther H.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Hubert, KC (reprint author), Case Western Reserve Univ, Sch Med, Univ Hosp Case Med Ctr, Dept Urol, 11100 Euclid Ave, Cleveland, OH 44106 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU CANADIAN J UROLOGY PI ST LAURENT PA 2330 WARD ST, STE 604, ST LAURENT, QUEBEC H4M 2V6, CANADA SN 1195-9479 J9 CAN J UROL JI Can. J. Urol. PD AUG PY 2009 VL 16 IS 4 BP 4733 EP 4735 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 483RI UT WOS:000268985000005 PM 19671224 ER PT J AU Kennedy, R Pankratz, VS Swanson, E Watson, D Golding, H Poland, GA AF Kennedy, Richard Pankratz, V. Shane Swanson, Eric Watson, David Golding, Hana Poland, Gregory A. TI Statistical Approach To Estimate Vaccinia-Specific Neutralizing Antibody Titers Using a High-Throughput Assay SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID GREEN FLUORESCENT PROTEIN; SMALLPOX VACCINE; NONHUMAN-PRIMATES; BIOLOGICAL AGENTS; IMMUNE-RESPONSES; LETHAL MONKEYPOX; VIRUS CHALLENGE; NAIVE ADULTS; CELL MEMORY; REVACCINATION AB Because of the bioterrorism threat posed by agents such as variola virus, considerable time, resources, and effort have been devoted to biodefense preparation. One avenue of this research has been the development of rapid, sensitive, high-throughput assays to validate immune responses to poxviruses. Here we describe the adaptation of a beta-galactosidase reporter-based vaccinia virus neutralization assay to large-scale use in a study that included over 1,000 subjects. We also describe the statistical methods involved in analyzing the large quantity of data generated. The assay and its associated methods should prove useful tools in monitoring immune responses to next-generation smallpox vaccines, studying poxvirus immunity, and evaluating therapeutic agents such as vaccinia virus immune globulin. C1 [Kennedy, Richard; Swanson, Eric; Poland, Gregory A.] Mayo Clin, Mayo Vaccine Res Grp, Rochester, MN 55905 USA. [Pankratz, V. Shane; Watson, David] Mayo Clin, Div Biostat, Rochester, MN 55905 USA. [Golding, Hana] US FDA, CBER, Div Viral Prod, Washington, DC 20204 USA. [Poland, Gregory A.] Mayo Clin, Program Translat Immunovirol & Biodef, Rochester, MN 55905 USA. RP Poland, GA (reprint author), Mayo Clin, Mayo Vaccine Res Grp, Guggenheim 611C,200 1st St SW, Rochester, MN 55905 USA. EM Poland.gregory@mayo.edu FU NIAID though NIH Population Genetics Analysis Program [AI40065] FX This work was supported by the NIAID though NIH Population Genetics Analysis Program grant AI40065. Disclosures and conflicts of interest: G. A. P. has provided consultant advice to Acambis. The other authors do not have any conflicts of interest. NR 53 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD AUG PY 2009 VL 16 IS 8 BP 1105 EP 1112 DI 10.1128/CVI.00109-09 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476PX UT WOS:000268455800002 PM 19535540 ER PT J AU Ning, YM Figg, WD Dahut, WL AF Ning, Yang-min Figg, William D. Dahut, William L. TI Reversal of Docetaxel Resistance With Bevacizumab and Thalidomide SO CLINICAL GENITOURINARY CANCER LA English DT Article DE Antiangiogenesis; Castration-resistant prostate cancer; Reversal of taxane resistance ID REFRACTORY PROSTATE-CANCER; PHASE-2; TUMORS AB Taxane resistance is a common clinical problem in the treatment of many metastatic malignancies. Observational clues or evidence of overcoming such resistance is important for developing treatments that can extend taxane activity. We report a case of the reversal of docetaxel resistance with the addition of antiangiogenic agents bevacizumab and thalidomide to docetaxel and prednisone in a patient with metastatic castration-resistant prostate cancer after PSAWG progression on docetaxel and prednisone. The patient then responded for an additional 7 months. The addition of bevacizumab and thalidomide after progression on docetaxel/prednisone might reverse docetaxel resistance. These or other antiangiogenic agents for overcoming clinical taxane resistance are candidates for further study. C1 [Figg, William D.; Dahut, William L.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Ning, Yang-min] US FDA, DDOP, OODP, CDER, Silver Spring, MD USA. RP Dahut, WL (reprint author), NCI, Med Oncol Branch, NIH, 10 Ctr Dr,Bldg 10,Rm 12N226, Bethesda, MD 20892 USA. EM dahutw@mail.nih.gov RI Figg Sr, William/M-2411-2016 FU National Cancer Institute, Center for Cancer Research, National Institutes of Health FX This project has been supported by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research, National Institutes of Health. The observations discussed herein do not represent the views of the federal agencies nor does mention of the combined antiangiogenic therapy imply approval by these agencies. NR 9 TC 4 Z9 4 U1 1 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD AUG PY 2009 VL 7 IS 2 BP E37 EP E38 DI 10.3816/CGC.2009.n.020 PG 2 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 528PX UT WOS:000272460000008 PM 19692321 ER PT J AU Wang, Y Sung, C Dartois, C Ramchandani, R Booth, BP Rock, E Gobburu, J AF Wang, Y. Sung, C. Dartois, C. Ramchandani, R. Booth, B. P. Rock, E. Gobburu, J. TI Elucidation of Relationship Between Tumor Size and Survival in Non-Small-Cell Lung Cancer Patients Can Aid Early Decision Making in Clinical Drug Development SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID PHASE-II; CHEMOTHERAPY; STAGE; ERLOTINIB; COMBINATION; BEVACIZUMAB; CARBOPLATIN; DOCETAXEL; EFFICACY; APPROVAL AB Four non-small-cell lung cancer (NS CLC) registration trials were utilized to develop models linking survival to risk factors and changes in tumor size during treatment. The purpose was to leverage existing quantitative knowledge to facilitate future development of anti-NSCLC drugs. Eleven risk factors were screened using a Cox model. A mixed exponential decay and linear growth model was utilized for modeling tumor size. Survival times were described in a parametric model. Eastern Cooperative Oncology Group (ECOG) score and baseline tumor size were consistent prognostic factors of survival. Tumor size was well described by the mixed model. The parametric survival model includes ECOG score, baseline tumor size, and week 8 tumor size change as predictors of survival duration. The change in tumor size at week 8 allows early assessment of the activity of an experimental regimen. The survival model and the tumor model will be beneficial for early screening of candidate drugs, simulating NSCLC trials, and optimizing trial designs. C1 [Wang, Y.; Sung, C.; Dartois, C.; Gobburu, J.] US FDA, Off Clin Pharmacol, Div Pharmacometr, Silver Spring, MD USA. [Sung, C.; Ramchandani, R.; Booth, B. P.] US FDA, Off Clin Pharmacol, Div Clin Pharmacol 5, Silver Spring, MD USA. [Rock, E.] US FDA, Off New Drugs, Div Oncol, Silver Spring, MD USA. RP Wang, Y (reprint author), US FDA, Off Clin Pharmacol, Div Pharmacometr, Silver Spring, MD USA. EM yaning.wang@fda.hhs.gov FU Office of Women's Health; Food and Drug Administration (FDA) FX This research was made possible in part by funding provided by the Office of Women's Health, Food and Drug Administration (FDA). We thank Mark Rothmann for valuable statistical input that greatly improved the manuscript. The views expressed in this article are those of the authors and do not necessarily reflect the official views of the NR 24 TC 95 Z9 98 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD AUG PY 2009 VL 86 IS 2 BP 167 EP 174 DI 10.1038/clpt.2009.64 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 478CJ UT WOS:000268565100017 PM 19440187 ER PT J AU Cole, SR Chu, HT Nie, L AF Cole, Stephen R. Chu, Haitao Nie, Lei TI Nonparametric estimator of relative time with application to the Acyclovir Prevention Trial SO CLINICAL TRIALS LA English DT Article ID INVERSE PROBABILITY; SURVIVAL ANALYSIS; MODELS; RATIO AB Background Relative hazard is a central measure of association in randomized clinical trials. Relative time (RT) is a competing measure that is rarely used. Purpose We describe a simple area-based nonparametric estimator of RT and illustrate its use in the Acyclovir Prevention Trial. Methods Let Q(x)(p) be the quantile function for the xth treatment group, defined as the time by which p% of the treatment group experience the event, and p(x) be the maximum event proportion observed. Our consistent estimator is defined as the ratio of the integrals of Q(1)(p) and Q(0)(p) with integration over 0 to pi, where pi = min(p(1), p(0)). Confidence limits (CL) are provided by bootstrap. Results A total of 703 immunocompetent adult men and women (54% male, 79% Caucasian, median age 49 years) with a history of ocular herpes simplex virus (HSV) were enrolled in 1992-1996, randomized to acyclovir or placebo, followed for up to 1 year for the 1st episode of ocular HSV, and 170 events were confirmed by a study-certified ophthalmologist using slit-lamp biomicroscopy. The nonparametric RT comparing acyclovir use with nonuse was 2.6 (bootstrap 95% CL: 1.6, 4.2). For comparison, the best-fitting parametric model was the lognormal (RT = 2.5; 95% CL: 1.5, 3.9). In limited simulations, the average proposed estimate of RT was similar to the true RT with a relative root mean squared error of 1.13 compared to a correctly specified parametric (lognormal) model. Limitations An analytical variance estimator for the proposed RT is lacking. Also, more examples and more extensive simulations are warranted. Conclusions Similar to Cox's relative hazard estimator, the proposed RT does not assume the data are generated from a particular distribution. RTs should be more widely used as a measure of association in clinical trials. Clinical Trials 2009;6:320-328.http://ctj.sagepub.com C1 [Cole, Stephen R.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Chu, Haitao] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. [Nie, Lei] CDER OTS FDA, Off Biometr, Silver Spring, MD 20993 USA. RP Cole, SR (reprint author), Univ N Carolina, Dept Epidemiol, McGavran Greenberg Hall,CB 7435, Chapel Hill, NC 27599 USA. EM cole@unc.edu RI Chu, Haitao /J-7576-2012; OI Chu, Haitao/0000-0003-0932-598X FU NIH; NIAID [R03-AI 071763]; Lineberger Cancer Center Core [CA16086] FX The authors would like to thank Dr Roy Beck for his assistance with the Acyclovir Prevention Trial data, and Dr Alvaro Munoz for expert advice regarding the GG model. NR 26 TC 2 Z9 2 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD AUG PY 2009 VL 6 IS 4 BP 320 EP 328 DI 10.1177/1740774509338231 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 481UD UT WOS:000268836600003 PM 19667028 ER PT J AU Joshi, BH Puri, RK AF Joshi, Bharat H. Puri, Raj K. TI Hot Topic: Tumor Immunology SO CURRENT MOLECULAR MEDICINE LA English DT Editorial Material C1 [Joshi, Bharat H.; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies,Ctr Biol Evaluat &, Off Cellular Tissue & Gene Therapies, Bethesda, MD 20014 USA. RP Joshi, BH (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies,Ctr Biol Evaluat &, Off Cellular Tissue & Gene Therapies, Bethesda, MD 20014 USA. EM bharat.joshi@fda.hhs.gov; Puri@cber.fda.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD AUG PY 2009 VL 9 IS 6 BP 665 EP 666 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 514FW UT WOS:000271380700001 PM 19689292 ER PT J AU Puri, S Puri, S Mahapatra, AK Hussain, E Sarkar, C Sinha, S Joshi, BH AF Puri, Sachin Puri, Surbhi Mahapatra, Ashok K. Hussain, Ejaz Sarkar, Chitra Sinha, Subrata Joshi, Bharat H. TI A Review of Studies on Targeting Interleukin 4 Receptor for Central Nervous System Malignancy SO CURRENT MOLECULAR MEDICINE LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; COLONY-STIMULATING FACTOR; TUMOR-NECROSIS-FACTOR; HUMAN B-CELLS; IL4-PSEUDOMONAS EXOTOXIN NBI-3001; CIRCULARLY PERMUTED INTERLEUKIN-4; CHRONIC MYELOMONOCYTIC LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; KAPOSIS-SARCOMA CELLS; COMMON GAMMA-CHAIN AB Despite advances in biomedical sciences, the prognosis of patients with brain tumors remains poor. Effective treatment is lacking for these central nervous system (CNS) cancers. Targeted immunotoxins are a new class of therapeutic approaches that have emerged for the treatment of human cancers. In this approach, tumor antigen or cell surface receptor is targeted by a chimeric fusion protein consisting of an antibody or a ligand and a suicidal gene or toxin to kill tumor cells. In that regard, receptors for interleukin (IL)-4 (IL-4R) have been identified to be overexpressed on a variety of human CNS tumor cell lines and tissue samples including meningioma. In various studies, high grade brain tumor specimens and malignant brain tumor cell lines have been shown to overexpress high-affinity IL-4R, while normal brain samples or cell lines expressed lower levels of these receptors. The structures of IL-4R on CNS tumors have been studied, which demonstrate that these cells express predominantly type II IL-4R. These receptors are functional as IL-4 can cause signal transduction, inhibit growth of some tumor cell lines and increase expression of major histocompatibility antigens and intracellular adhesion molecular-1 (ICAM-1) on some tumor cells lines. To target IL-4R, a chimeric fusion protein composed of IL-4 and truncated Pseudomonas exotoxin has been developed. This cytotoxin is highly cytotoxic to IL-4R positive tumors in vitro and has been reported to be highly effective in preclinical animal model of human brain cancer. Several Phase I/II clinical trials for treatment of IL-4R positive cancers have been completed. This review article will summarize pre-clinical and clinical development of IL-4PE cytotoxin. C1 [Puri, Sachin; Sinha, Subrata] All India Inst Med Sci, Dept Biochem, New Delhi 110029, India. [Puri, Surbhi] Guru Teg Bahadur Sahib Hosp, Ludhiana 141002, Punjab, India. [Mahapatra, Ashok K.] All India Inst Med Sci, Dept Neurosurg, New Delhi 110029, India. [Puri, Sachin; Hussain, Ejaz] Jamia Millia Islamia, Dept Biosci, New Delhi 110025, India. [Sarkar, Chitra] All India Inst Med Sci, Dept Pathol, New Delhi 110029, India. [Joshi, Bharat H.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular Tissues & Gene Therapies, Off Cellular Tissue & Gene Therapies,Ctr Biol Eva, Bethesda, MD 20014 USA. RP Puri, S (reprint author), All India Inst Med Sci, Dept Biochem, New Delhi 110029, India. EM sachinpuri15@yahoo.com NR 135 TC 12 Z9 12 U1 0 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD AUG PY 2009 VL 9 IS 6 BP 732 EP 739 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 514FW UT WOS:000271380700009 PM 19689300 ER PT J AU Geetha, S Allen, CE Hunt, RC Plum, E Garfield, S Friedman, SL Soejima, K Sauna, ZE Kimchi-Sarfaty, C AF Geetha, S. Allen, Courtni E. Hunt, Ryan C. Plum, Elizabeth Garfield, Susan Friedman, Scott L. Soejima, Kenji Sauna, Zuben E. Kimchi-Sarfaty, Chava TI Detection of Intracellular ADAMTS13, a Secreted Zinc-Metalloprotease, via Flow Cytometry SO CYTOMETRY PART A LA English DT Article DE ADAMTS13; flow cytometry; intracellular protein expression ID VON-WILLEBRAND-FACTOR; FACTOR-CLEAVING PROTEASE; THROMBOTIC THROMBOCYTOPENIC PURPURA; STELLATE CELLS; WESTERN-BLOT; EXPRESSION; CLEAVAGE AB ADAMTS13 is a secreted metalloprotease that cleaves von Willebrand Factor multimers in order to maintain proper homeostasis. A severe deficiency in ADAMTS13 triggers a disorder known as thrombotic thrombocytopenic purpura. At present, ADAMTS13 expression levels are determined by immunoblotting. We established a flow cytometry methodology to detect intracellular ADAMTS13 in liver and kidney cells using a polyclonal antibody, BL154G, and several monoclonal antibodies previously used to detect ADAMTS13 by immunoblotting. The results were validated using confocal microscopy, immunoblotting, and an activity assay (FRETS-VWF73). We show that labeling ADAMTS13 with specific antibodies and detection by flow cytometry yields results that are comparable with previously established methods for ADAMTS13 detection. Specifically, we compared the endogenous expression levels of ADAMTS13 in various liver cell lines using flow cytometry and obtained results that parallel immunoblot analysis. Knockdown of ADAMTS13 expression via targeted siRNA resulted in significantly reduced median signal, displaying the sensitivity of this detection method. A further analysis of reliability and specificity was achieved through plasmid DNA and transfection reagent dose response studies. The flow cytometry method described here is useful in determining the expression of both endogenous and recombinant forms of intracellular ADAMTS13. Flow cytometry is a convenient, efficient, and cost-effective way to measure the expression levels of ADAMTS13. Published 2009 Wiley-Liss, Inc. C1 [Geetha, S.; Allen, Courtni E.; Hunt, Ryan C.; Plum, Elizabeth; Sauna, Zuben E.; Kimchi-Sarfaty, Chava] US FDA, Div Hematol, Lab Hemostasis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Garfield, Susan] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Friedman, Scott L.] Mt Sinai Sch Med, Dept Med, Div Liver Dis, New York, NY USA. [Soejima, Kenji] Chemo Sero Therapeut Res Inst, Dept Res 1, Kumamoto, Japan. RP Kimchi-Sarfaty, C (reprint author), US FDA, Div Hematol, Lab Hemostasis, Ctr Biol Evaluat & Res, 29 Lincoin Dr, Bethesda, MD 20892 USA. EM chava.kimchi-sarfaty@fda.hhs.gov FU Intramural NIH HHS [Z01 BC010858-01] NR 20 TC 3 Z9 3 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD AUG PY 2009 VL 75A IS 8 BP 675 EP 681 DI 10.1002/cyto.a.20748 PG 7 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 474MX UT WOS:000268289300005 PM 19526483 ER PT J AU Stephenson, I Heath, A Major, D Newman, RW Hoschler, K Junzi, W Katz, JM Weir, JP Zambon, MC Wood, JM AF Stephenson, Iain Heath, Alan Major, Diane Newman, Robert W. Hoschler, Katja Junzi, Wang Katz, Jacqueline M. Weir, Jerry P. Zambon, Maria C. Wood, John M. TI Reproducibility of Serologic Assays for Influenza Virus A (H5N1) SO EMERGING INFECTIOUS DISEASES LA English DT Article ID MF59-ADJUVANTED INFLUENZA; HUMAN SERA; ANTIBODY; VACCINE AB Hemagglutination-inhibition (HI) and neutralization are used to evaluate vaccines against influenza virus A (H5N1); however, poor standardization leads to interlaboratory variation of results. A candidate antibody standard (07/150) was prepared from pooled plasma of persons given clade 1 A/Vietnam/1194/2004 vaccine. To test human and sheep antiserum, 15 laboratories used HI and neutralization and reassortant A/Vietnam/1194/2004, A/turkey/Turkey/1/2005 (clade 2.2), and A/Anhui/1/2005 (clade 2.3.4) viruses. Inter-laboratory variation was observed for both assays, but when titers were expressed relative to 07/150, overall percentage geometric coefficient of variation for A/Vietnam/1194/2004 was reduced from 125% to 61% for HI and from 183% to 81% for neutralization. Lack of reduced variability to clade 2 antigens suggested the need for clade-specific standards. Sheep antiserum as a standard did not reliably reduce variability. The World Health Organization has established 07/150 as an international standard for antibody to clade 1 subtype H5 and has an assigned potency of 1,000 IU/ampoule. C1 [Stephenson, Iain] Univ Leicester, Leicester, Leics, England. [Heath, Alan; Major, Diane; Newman, Robert W.; Wood, John M.] Natl Inst Biol Stand & Controls, Potters Bar EN6 3QG, Herts, England. [Hoschler, Katja; Zambon, Maria C.] Hlth Protect Agcy, Colindale, England. [Katz, Jacqueline M.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Weir, Jerry P.] US FDA, Rockville, MD 20857 USA. [Junzi, Wang] Natl Inst Control Pharmaceut & Biol Prod, Beijing, Peoples R China. RP Stephenson, I (reprint author), Leicester Royal Infirm, Infect Dis Unit, Leicester LE1 5WW, Leics, England. EM iain.stephenson@uhl-tr.nhs.uk FU Nobilon; NexBio; CSL Biotherapies; Sanofi-Pasteur; Baxter; Novartis FX Dr Stephenson is a senior lecturer in infectious diseases at the University of Leicester. He has research interests in the extent of respiratory virus infections and their control with vaccines and antiviral drugs. NR 20 TC 21 Z9 21 U1 0 U2 2 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 AUG PY 2009 VL 15 IS 8 BP 1250 EP 1259 DI 10.3201/eid1508.081754 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 481NT UT WOS:000268819100014 PM 19751587 ER PT J AU Lyn-Cook, BD AF Lyn-Cook, B. D. TI Polymorphisms in ATP-Binding Cassette (ABC) Transporters: Tangier Disease and Other High-Density Lipoprotein Deficiencies SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 40th Annual Meeting of the Environment-Mutagen-Society CY OCT 24-28, 2009 CL St Louis, MO SP Environm Mutagen Soc C1 [Lyn-Cook, B. D.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 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 AUG PY 2009 VL 50 IS 7 BP 540 EP 540 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 484LM UT WOS:000269046400027 ER PT J AU Benz, RD AF Benz, R. D. TI Computational Approaches for Predicting Genetic Toxicity/Cancer SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 40th Annual Meeting of the Environment-Mutagen-Society CY OCT 24-28, 2009 CL St Louis, MO SP Environm Mutagen Soc C1 [Benz, R. D.] US FDA, CDER, OPS, SRS,ICSAS, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2009 VL 50 IS 7 BP 543 EP 543 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 484LM UT WOS:000269046400038 ER PT J AU Chen, T Li, Z Mei, N Guo, L AF Chen, T. Li, Z. Mei, N. Guo, L. TI MicroRNA Expression and Genomic Gene Expression, Rather Than DNA Adduct and Mutation Induction, Indicate the Carcinogenic Tissue of Aristolochic Acid in Rat SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 40th Annual Meeting of the Environment-Mutagen-Society CY OCT 24-28, 2009 CL St Louis, MO SP Environm Mutagen Soc C1 [Chen, T.; Li, Z.; Mei, N.; Guo, L.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2009 VL 50 IS 7 BP 547 EP 547 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 484LM UT WOS:000269046400054 ER PT J AU Parsons, BL AF Parsons, B. L. TI Theoretical Implications of Polyclonal Tumor Origin and Tumor-Associated Mutations, Which Are Not Rare Events, in Interpreting Chemical Mode of Action SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 40th Annual Meeting of the Environment-Mutagen-Society CY OCT 24-28, 2009 CL St Louis, MO SP Environm Mutagen Soc C1 [Parsons, B. L.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-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 AUG PY 2009 VL 50 IS 7 BP 547 EP 547 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 484LM UT WOS:000269046400052 ER PT J AU Pogribny, IP AF Pogribny, I. P. TI Nutrition and Carcinogenesis: Epigenomic Approaches to Cancer Prevention SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 40th Annual Meeting of the Environment-Mutagen-Society CY OCT 24-28, 2009 CL St Louis, MO SP Environm Mutagen Soc C1 [Pogribny, I. P.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2009 VL 50 IS 7 BP 551 EP 551 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 484LM UT WOS:000269046400067 ER PT J AU Rice, P AF Rice, P. TI Regulatory Issues Surrounding Nanoparticles SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 40th Annual Meeting of the Environment-Mutagen-Society CY OCT 24-28, 2009 CL St Louis, MO SP Environm Mutagen Soc C1 [Rice, P.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2009 VL 50 IS 7 BP 555 EP 555 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 484LM UT WOS:000269046400081 ER PT J AU Kwekel, JC Melvin, CD Desai, VG Branham, WS Moland, CL Han, T Fuscoe, JC AF Kwekel, J. C. Melvin, C. D. Desai, V. G. Branham, W. S. Moland, C. L. Han, T. Fuscoe, J. C. TI Age and Sex Differences in Hepatic Gene Expression during the Rat Life Cycle SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 40th Annual Meeting of the Environment-Mutagen-Society CY OCT 24-28, 2009 CL St Louis, MO SP Environm Mutagen Soc C1 [Kwekel, J. C.; Melvin, C. D.; Desai, V. G.; Branham, W. S.; Moland, C. L.; Han, T.; Fuscoe, J. C.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2009 VL 50 IS 7 BP 558 EP 558 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 484LM UT WOS:000269046400095 ER PT J AU Li, Z Shi, L Pearce, M Wang, Y Guo, L Branham, WS Chen, T AF Li, Z. Shi, L. Pearce, M. Wang, Y. Guo, L. Branham, W. S. Chen, T. TI Time-Course Study of MicroRNA Gene Expression in Liver of Mice Treated with One Dose of N-ethyl-N-nitrosourea SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 40th Annual Meeting of the Environment-Mutagen-Society CY OCT 24-28, 2009 CL St Louis, MO SP Environm Mutagen Soc C1 [Li, Z.; Shi, L.; Pearce, M.; Guo, L.; Branham, W. S.; Chen, T.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Wang, Y.] SABiosci Corp, Frederick, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2009 VL 50 IS 7 BP 558 EP 558 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 484LM UT WOS:000269046400094 ER PT J AU Mei, N McDaniel, LP Guo, L Dial, SL Manjanatha, MG AF Mei, N. McDaniel, L. P. Guo, L. Dial, S. L. Manjanatha, M. G. TI Liver Gene Expression Changes in Mice Exposed to Acrylamide SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 40th Annual Meeting of the Environment-Mutagen-Society CY OCT 24-28, 2009 CL St Louis, MO SP Environm Mutagen Soc C1 [Mei, N.; McDaniel, L. P.; Guo, L.; Dial, S. L.; Manjanatha, M. G.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 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 AUG PY 2009 VL 50 IS 7 BP 558 EP 558 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 484LM UT WOS:000269046400096 ER PT J AU Dobrovolsky, VN Bigger, CAH Elespuru, RK Robison, TW Heflich, RH AF Dobrovolsky, V. N. Bigger, C. A. H. Elespuru, R. K. Robison, T. W. Heflich, R. H. TI Detecting PIG-A Gene Mutation in Human Red Blood Cells SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 40th Annual Meeting of the Environment-Mutagen-Society CY OCT 24-28, 2009 CL St Louis, MO SP Environm Mutagen Soc C1 [Dobrovolsky, V. N.; Heflich, R. H.] NCTR FDA, Jefferson, AR USA. [Bigger, C. A. H.; Robison, T. W.] CDER FDA, White Oak, MD USA. [Elespuru, R. K.] CDRH FDA, White Oak, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2009 VL 50 IS 7 BP 562 EP 562 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 484LM UT WOS:000269046400112 ER PT J AU Elespuru, RK Agarwal, R Atrakchi, A Bigger, CAH Heflich, RH Jagannath, DR Levy, DD Moore, MM Ouyang, Y Robison, TW Cimino, MC Dearfield, KL AF Elespuru, R. K. Agarwal, R. Atrakchi, A. Bigger, C. A. H. Heflich, R. H. Jagannath, D. R. Levy, D. D. Moore, M. M. Ouyang, Y. Robison, T. W. Cimino, M. C. Dearfield, K. L. TI Future Application of Genetic Toxicity Assays SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 40th Annual Meeting of the Environment-Mutagen-Society CY OCT 24-28, 2009 CL St Louis, MO SP Environm Mutagen Soc C1 [Elespuru, R. K.] FDA Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Agarwal, R.; Atrakchi, A.; Bigger, C. A. H.; Ouyang, Y.; Robison, T. W.] FDA Ctr Drugs, Silver Spring, MD USA. [Heflich, R. H.; Moore, M. M.] FDA Natl Ctr Toxicol Res, Jefferson, AR USA. [Jagannath, D. R.] FDA Ctr Vet Med, Rockville, MD USA. [Levy, D. D.] FDA Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Cimino, M. C.] US EPA, Washington, DC 20460 USA. [Dearfield, K. L.] US DA, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2009 VL 50 IS 7 BP 563 EP 563 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 484LM UT WOS:000269046400114 ER PT J AU Guo, L Shelton, S Moore, M Manjanatha, M AF Guo, L. Shelton, S. Moore, M. Manjanatha, M. TI Acrylamide and Glycidamide Induce cll Gene Mutations in Lung Tissue of Big Blue Mice SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 40th Annual Meeting of the Environment-Mutagen-Society CY OCT 24-28, 2009 CL St Louis, MO SP Environm Mutagen Soc C1 [Guo, L.; Shelton, S.; Moore, M.; Manjanatha, M.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 1 Z9 1 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 AUG PY 2009 VL 50 IS 7 BP 570 EP 570 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 484LM UT WOS:000269046400139 ER PT J AU McDaniel, LP Guo, XQ Doerge, DR Heflich, RH Mei, N AF McDaniel, L. P. Guo, X. Q. Doerge, D. R. Heflich, R. H. Mei, N. TI Mutagenicity of Acrylamide and Glycidamide in Rat Thyroid SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 40th Annual Meeting of the Environment-Mutagen-Society CY OCT 24-28, 2009 CL St Louis, MO SP Environm Mutagen Soc C1 [McDaniel, L. P.; Guo, X. Q.; Doerge, D. R.; Heflich, R. H.; Mei, N.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2009 VL 50 IS 7 BP 570 EP 570 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 484LM UT WOS:000269046400140 ER PT J AU Wang, Y Mei, N Chen, T Parsons, BL AF Wang, Y. Mei, N. Chen, T. Parsons, B. L. TI ACB-PCR Measurement of K-Ras Codon 12 GAT Mutation in Rat Liver and Kidney Exposed to Aristolochic Acid SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 40th Annual Meeting of the Environment-Mutagen-Society CY OCT 24-28, 2009 CL St Louis, MO SP Environm Mutagen Soc C1 [Wang, Y.; Mei, N.; Chen, T.; Parsons, B. L.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-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 AUG PY 2009 VL 50 IS 7 BP 570 EP 570 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 484LM UT WOS:000269046400141 ER PT J AU Bhalli, JA Khan, QM Khalid, ZM AF Bhalli, J. A. Khan, Q. M. Khalid, Z. M. TI Cytogenetic and Molecular Biomonitoring of Sprayers Exposed to Pesticides in Cotton Fields in Pakistan SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 40th Annual Meeting of the Environment-Mutagen-Society CY OCT 24-28, 2009 CL St Louis, MO SP Environm Mutagen Soc C1 [Bhalli, J. A.] Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Bhalli, J. A.; Khan, Q. M.; Khalid, Z. M.] NIBGE, Environm Toxicol Lab, Faisalabad, Pakistan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2009 VL 50 IS 7 BP 573 EP 573 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 484LM UT WOS:000269046400153 ER PT J AU Starlard-Davenport, A Tryndyak, V Beland, F Pogribny, I AF Starlard-Davenport, A. Tryndyak, V Beland, F. Pogribny, I TI Role of Altered Hepatic microRNA Expression in the Pathogenesis of Nonalcoholic Hepatosteatosis in Mice Induced by Methyl-Deficiency SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 40th Annual Meeting of the Environment-Mutagen-Society CY OCT 24-28, 2009 CL St Louis, MO SP Environm Mutagen Soc C1 [Starlard-Davenport, A.; Tryndyak, V; Beland, F.; Pogribny, I] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 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 AUG PY 2009 VL 50 IS 7 BP 575 EP 575 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 484LM UT WOS:000269046400160 ER PT J AU Montgomery, BA Koturbash, I Kovalchuk, O Pogribny, IP AF Montgomery, B. A. Koturbash, I Kovalchuk, O. Pogribny, I. P. TI Radiation-Induced Age-Related Epigenetic Changes in Mouse Liver SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 40th Annual Meeting of the Environment-Mutagen-Society CY OCT 24-28, 2009 CL St Louis, MO SP Environm Mutagen Soc C1 [Montgomery, B. A.; Pogribny, I. P.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Koturbash, I; Kovalchuk, O.] Univ Lethbridge, Lethbridge, AB T1K 3M4, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2009 VL 50 IS 7 BP 576 EP 576 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 484LM UT WOS:000269046400162 ER PT J AU Chen, Y Li, Z Chen, T Moore, MM AF Chen, Y. Li, Z. Chen, T. Moore, M. M. TI Comparison of MicroRNA Expression Profiles from Large and Small Colony Thymidine Kinase Mutants of L5178Y Mouse Lymphoma Cells SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 40th Annual Meeting of the Environment-Mutagen-Society CY OCT 24-28, 2009 CL St Louis, MO SP Environm Mutagen Soc C1 [Chen, Y.; Li, Z.; Chen, T.; Moore, M. M.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2009 VL 50 IS 7 BP 577 EP 577 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 484LM UT WOS:000269046400165 ER PT J AU Kulkarni, R Petibone, DM Chang, CW Morris, SM AF Kulkarni, R. Petibone, D. M. Chang, C. W. Morris, S. M. TI Effect of P53 Genotype on Gene Expression Profile in Murine Testis SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 40th Annual Meeting of the Environment-Mutagen-Society CY OCT 24-28, 2009 CL St Louis, MO SP Environm Mutagen Soc C1 [Kulkarni, R.; Petibone, D. M.; Chang, C. W.; Morris, S. M.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2009 VL 50 IS 7 BP 577 EP 577 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 484LM UT WOS:000269046400167 ER PT J AU Petibone, D Kulkarni, R Chang, CW Morris, S AF Petibone, D. Kulkarni, R. Chang, C-W Morris, S. TI Effect of p53 Genotype on Gene Expression in the Livers of ENU-Exposed Mice SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 40th Annual Meeting of the Environment-Mutagen-Society CY OCT 24-28, 2009 CL St Louis, MO SP Environm Mutagen Soc C1 [Petibone, D.; Kulkarni, R.; Chang, C-W; Morris, S.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2009 VL 50 IS 7 BP 577 EP 577 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 484LM UT WOS:000269046400166 ER PT J AU Ali, T Bhalli, JA Khan, QM AF Ali, T. Bhalli, J. A. Khan, Q. M. TI Appraisal of Comet Tail Length in Pesticide Exposed Cotton Field Females during Picking Season SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 40th Annual Meeting of the Environment-Mutagen-Society CY OCT 24-28, 2009 CL St Louis, MO SP Environm Mutagen Soc C1 [Ali, T.; Khan, Q. M.] NIBGE, Faisalabad, Pakistan. [Bhalli, J. A.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 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 AUG PY 2009 VL 50 IS 7 BP 579 EP 579 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 484LM UT WOS:000269046400174 ER PT J AU Ding, W Manjanatha, M Cook, LL Bishop, M Levy, D Aidoo, A AF Ding, W. Manjanatha, M. Cook, Lyn L. Bishop, M. Levy, D. Aidoo, A. TI Use of the In Vivo Comet Assay to Evaluate Methyleugenol-Induced DNA Damage in Various Tissues of the Rat SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 40th Annual Meeting of the Environment-Mutagen-Society CY OCT 24-28, 2009 CL St Louis, MO SP Environm Mutagen Soc C1 [Ding, W.; Manjanatha, M.; Cook, Lyn L.; Bishop, M.; Aidoo, A.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Levy, D.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RI Ding, Wei/L-1503-2014 NR 0 TC 0 Z9 0 U1 1 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 AUG PY 2009 VL 50 IS 7 BP 579 EP 579 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 484LM UT WOS:000269046400173 ER PT J AU Mittelstaedt, RA Shaddock, JG Heflich, RH AF Mittelstaedt, R. A. Shaddock, J. G. Heflich, R. H. TI Flow Cytometry Analysis of Responses in the In Vitro Micronucleus Assay SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 40th Annual Meeting of the Environment-Mutagen-Society CY OCT 24-28, 2009 CL St Louis, MO SP Environm Mutagen Soc C1 [Mittelstaedt, R. A.; Shaddock, J. G.; Heflich, R. H.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-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 AUG PY 2009 VL 50 IS 7 BP 581 EP 581 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 484LM UT WOS:000269046400183 ER PT J AU Guo, XQ Verkler, TL Mei, N Richter, PA Polzin, GM Moore, MM AF Guo, X. Q. Verkler, T. L. Mei, N. Richter, P. A. Polzin, G. M. Moore, M. M. TI Relative Mutagenicity of Cigarette Smoke Condensates in Mouse Lymphoma Cells SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 40th Annual Meeting of the Environment-Mutagen-Society CY OCT 24-28, 2009 CL St Louis, MO SP Environm Mutagen Soc C1 [Guo, X. Q.; Verkler, T. L.; Mei, N.; Moore, M. M.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Richter, P. A.] Ctr Dis Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. [Polzin, G. M.] Natl Ctr Environm Hlth, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2009 VL 50 IS 7 BP 586 EP 586 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 484LM UT WOS:000269046400197 ER PT J AU Elinos-Calderon, D Robledo-Arratia, Y Perez-De La Cruz, V Pedraza-Chaverri, J Ali, SF Santamaria, A AF Elinos-Calderon, Diana Robledo-Arratia, Yolanda Perez-De La Cruz, Veronica Pedraza-Chaverri, Jose Ali, Syed F. Santamaria, Abel TI Early nerve ending rescue from oxidative damage and energy failure by l-carnitine as post-treatment in two neurotoxic models in rat: recovery of antioxidant and reductive capacities SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE Synaptosomal fractions; Functional recovery; Excitotoxicity; Energy depletion; Oxidative damage; L-carnitine post-treatment ID ACETYL-L-CARNITINE; TOXIN 3-NITROPROPIONIC ACID; MITOCHONDRIAL DYSFUNCTION; HUNTINGTONS-DISEASE; QUINOLINIC ACID; NEURODEGENERATIVE DISORDERS; LIPID-PEROXIDATION; PROTECTIVE ROLE; BRAIN-DAMAGE; LIPOIC ACID AB Cell rescue is a primary need during acute and chronic insults to the central nervous system. Functional preservation during the early stages of toxicity in a given degenerative event may represent a significant amelioration of detrimental processes linked to neuronal cell loss. Excitotoxicity and depleted cellular energy are toxic events leading to cell death in several neurodegenerative disorders. In this work, the effects of the well-known antioxidant and energy precursor, l-carnitine (l-CAR), were tested as a post-treatment in two neurotoxic models under in vitro and in vivo conditions. The experimental models tested included: (1) a typical excitotoxic and pro-oxidant inducer, quinolinic acid (QUIN); and (2) a mitochondrial energy inhibitor, 3-nitropropionic acid (3-NP). For in vitro studies, increasing concentrations of l-CAR (10-1,000 mu M) were added to the isolated brain synaptosomes at different times (1, 3 and 6 h) after the incubation with toxins (100 mu M QUIN and 1 mM 3-NP), and 30 min later, lipid peroxidation (LP) and mitochondrial dysfunction (MD) were evaluated. For in vivo purposes, l-CAR (100 mg/kg, i.p.) was given to rats either as a single administration 120 min after the intrastriatal infusion of QUIN (240 nmol/mu l) or 3-NP (500 nmol/mu l), or for 7 consecutive days (starting 120 min post-lesion). LP and MD were evaluated 4 h and 7 days post-lesions in isolated striatal synaptosomes. Our results show that, despite some variations depending on the toxic model tested, the time of exposure, or the biomarker evaluated, nerve ending protection can be mostly achieved by l-CAR within the first hours after the toxic insults started, suggesting that targeting the ongoing oxidative damage and/or energy depletion during the first stages of neurotoxic events is essential to rescue nerve endings. C1 [Elinos-Calderon, Diana; Robledo-Arratia, Yolanda; Perez-De La Cruz, Veronica; Santamaria, Abel] Inst Nacl Neurol & Neurocirugia Manuel Velasco Su, Lab Aminoacids Excitadores, Mexico City 14269, DF, Mexico. [Pedraza-Chaverri, Jose] Univ Nacl Autonoma Mexico, Fac Quim, Dept Biol, Mexico City 04510, DF, Mexico. [Ali, Syed F.; Santamaria, Abel] US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Santamaria, A (reprint author), Inst Nacl Neurol & Neurocirugia Manuel Velasco Su, Lab Aminoacids Excitadores, Insurgentes 3877,CP 14269, Mexico City 14269, DF, Mexico. EM absada@yahoo.com FU CONACyT-Mexico [48370-Q, 40009]; Fundacion Armstrong-Mexico; PROBEI, S.S.A.-Mexico FX This work was supported by CONACyT-Mexico Grants 48370-Q ( A. S.) and 40009 (J.P-Ch). Diana Elinos-Calderon received scholarships from Fundacion Armstrong-Mexico and PROBEI, S.S.A.-Mexico. NR 46 TC 10 Z9 11 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD AUG PY 2009 VL 197 IS 3 BP 287 EP 296 DI 10.1007/s00221-009-1913-3 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 477UK UT WOS:000268544200009 PM 19565224 ER PT J AU Jung, CM Heinze, TM Schnackenberg, LK Mullis, LB Elkins, SA Elkins, CA Steele, RS Sutherland, JB AF Jung, Carina M. Heinze, Thomas M. Schnackenberg, Laura K. Mullis, Lisa B. Elkins, Stephanie A. Elkins, Christopher A. Steele, Roger S. Sutherland, John B. TI Interaction of dietary resveratrol with animal-associated bacteria SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE dietary supplements; intestinal bacteria; phytochemicals; resveratrol; stilbenes ID RED WINE; MULTIDRUG-RESISTANCE; PHENOLIC-COMPOUNDS; ESCHERICHIA-COLI; EFFLUX PUMPS; INHIBITORS; IDENTIFICATION; ANTIOXIDANT; EXTRACTS; PROTECTS AB Resveratrol (3,5,4'-trihydroxy-trans-stilbene), an antifungal phytoalexin produced by grapes, peanuts, and Japanese knotweeds, is thought to be a beneficial dietary phytochemical in red wine and grape juice. Information on its antibacterial properties and biotransformation, however, is limited. We surveyed the interactions of resveratrol with 43 strains of bacterial species that are often animal- or human-associated. Resveratrol at 50 mg L(-1) reduced the growth rates of most of the bacteria tested, but did not totally prevent growth even at much higher levels. Eleven of the 43 bacteria were capable of transforming at least 20% of the resveratrol. Three major metabolites were identified as resveratroloside, piceid, and dihydroresveratrol, and three other metabolites were partially characterized. C1 [Mullis, Lisa B.; Elkins, Stephanie A.; Steele, Roger S.; Sutherland, John B.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Jung, Carina M.] USA, Engineer Res & Dev Ctr, Vicksburg, MS USA. [Heinze, Thomas M.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Schnackenberg, Laura K.] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. [Elkins, Christopher A.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD USA. RP Sutherland, JB (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM john.sutherland@fda.hhs.gov NR 39 TC 27 Z9 28 U1 2 U2 11 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD AUG PY 2009 VL 297 IS 2 BP 266 EP 273 DI 10.1111/j.1574-6968.2009.01691.x PG 8 WC Microbiology SC Microbiology GA 469FT UT WOS:000267882000018 PM 19566680 ER PT J AU Varadkar, PA Kraman, M McCright, B AF Varadkar, Prajakta A. Kraman, Matthew McCright, Brent TI Generation of Mice That Conditionally Express the Activation Domain of Notch2 SO GENESIS LA English DT Article DE Notch2; Notch transgene; conditional expression; heart development; Notch activation domain ID CELLS; HEART; FATE; CARDIOMYOCYTES; PROLIFERATION; DEFECTS; ORIGIN; MOUSE AB The Notch pathway is an intercellular signaling mechanism frequently used for controlling cell fate during organogenesis. There are four structurally related Notch receptors in mice and humans, and Notch1 and Notch2 are essential genes. In this report we describe the construction of a transgenic mouse strain that expresses the Notch2 intracellular domain in response to cell lineage specific expression of Cre recombinase. This approach bypasses the requirement for ligand-receptor interaction and allows the direct determination of the consequences of Notch2 activation in vivo. Exogenous expression of the Notch2 intracellular domain resulted in the developmental arrest of secondary heart field derived cardiomyocytes during the transition from immature alpha-Smooth Muscle Actin expressing cells to mature alpha-Actinin positive cardiomyocytes. In contrast, a cell nonautonomous mesenchymal expansion was observed in semilunar valves. This new conditionally expressed allele of Notch2 can be used in studies by investigators interested in the effects of Notch2 activation in vivo. genesis 47:573-578, 2009. Published 2009 Wiley-Liss, lnc.(dagger) C1 [Varadkar, Prajakta A.; Kraman, Matthew; McCright, Brent] US FDA, Div Cellular & Gene Therapies, Bethesda, MD 20014 USA. RP McCright, B (reprint author), US FDA, Div Cellular & Gene Therapies, Bethesda, MD 20014 USA. EM brenton.mccright@fda.hhs.gov NR 21 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-954X J9 GENESIS JI Genesis PD AUG PY 2009 VL 47 IS 8 BP 573 EP 578 DI 10.1002/dvg.20537 PG 6 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 488RX UT WOS:000269368600007 PM 19530136 ER PT J AU Fricke, WF Welch, TJ McDermott, PF Mammel, MK LeClerc, JE White, DG Cebula, TA Ravel, J AF Fricke, W. Florian Welch, Timothy J. McDermott, Patrick F. Mammel, Mark K. LeClerc, J. Eugene White, David G. Cebula, Thomas A. Ravel, Jacques TI Comparative Genomics of the IncA/C Multidrug Resistance Plasmid Family SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SALMONICIDA SUBSP SALMONICIDA; ANTIBIOTIC-RESISTANCE; CONJUGAL TRANSFER; ESCHERICHIA-COLI; YERSINIA-PESTIS; UNITED-STATES; FISH-PATHOGEN; VIBRIO-CHOLERAE; REPLICON; SEQUENCE AB Multidrug resistance (MDR) plasmids belonging to the IncA/C plasmid family are widely distributed among Salmonella and other enterobacterial isolates from agricultural sources and have, at least once, also been identified in a drug-resistant Yersinia pestis isolate (IP275) from Madagascar. Here, we present the complete plasmid sequences of the IncA/C reference plasmid pRA1 (143,963 bp), isolated in 1971 from the fish pathogen Aeromonas hydrophila, and of the cryptic IncA/C plasmid pRAx (49,763 bp), isolated from Escherichia coli transconjugant D7-3, which was obtained through pRA1 transfer in 1980. Using comparative sequence analysis of pRA1 and pRAx with recent members of the IncA/C plasmid family, we show that both plasmids provide novel insights into the evolution of the IncA/C MDR plasmid family and the minimal machinery necessary for stable IncA/C plasmid maintenance. Our results indicate that recent members of the IncA/C plasmid family evolved from a common ancestor, similar in composition to pRA1, through stepwise integration of horizontally acquired resistance gene arrays into a conserved plasmid backbone. Phylogenetic comparisons predict type IV secretion-like conjugative transfer operons encoded on the shared plasmid backbones to be closely related to a group of integrating conjugative elements, which use conjugative transfer for horizontal propagation but stably integrate into the host chromosome during vegetative growth. A hipAB toxin-antitoxin gene cluster found on pRA1, which in Escherichia coli is involved in the formation of persister cell subpopulations, suggests persistence as an early broad-spectrum antimicrobial resistance mechanism in the evolution of IncA/C resistance plasmids. C1 [Fricke, W. Florian; Ravel, Jacques] Univ Maryland, Sch Med, IGS, Baltimore, MD 21201 USA. [Welch, Timothy J.] USDA, Natl Ctr Cool & Cold Water Aquaculture, Kearneysville, WV 25430 USA. [McDermott, Patrick F.; White, David G.] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [Mammel, Mark K.; LeClerc, J. Eugene] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Cebula, Thomas A.] Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Ravel, J (reprint author), Univ Maryland, Sch Med, IGS, Baltimore, MD 21201 USA. EM jravel@som.umaryland.edu RI Ravel, Jacques/D-2530-2009; OI Ravel, Jacques/0000-0002-0851-2233 FU National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health; Department of Health and Human Services [N01-AI-30071] FX The sequencing of pRAx was supported with federal funds from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Department of Health and Human Services, under NIAID contract N01-AI-30071. NR 46 TC 107 Z9 109 U1 2 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD AUG PY 2009 VL 191 IS 15 BP 4750 EP 4757 DI 10.1128/JB.00189-09 PG 8 WC Microbiology SC Microbiology GA 469YD UT WOS:000267937000007 PM 19482926 ER PT J AU Kim, CS Saylor, DM McDermott, MK Patwardhan, DV Warren, JA AF Kim, Chang-Soo Saylor, David M. McDermott, Martin K. Patwardhan, Dinesh V. Warren, James A. TI Modeling Solvent Evaporation During the Manufacture of Controlled Drug-Release Coatings and the Impact on Release Kinetics SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE drug delivery/release; stents; microstructure; computer modeling; simulation; controlled release ID DIFFUSION-COEFFICIENTS; MACROPOROUS POLYMERS; ELUTING STENTS; SYSTEMS AB To improve functionality and performance, controlled drug-release coatings comprised of drug and polymer are integrated with traditional medical devices, e.g., drug eluting stents. Depending on manufacturing conditions, these coatings can exhibit complex microstructures. Previously, a thermodynamically consistent model was developed for microstructure evolution in these systems to establish relationships between process variables, microstructure, and the subsequent release kinetics. Calculations based on the model were, in general, consistent with experimental findings. However, because of assumptions regarding the evaporation of solvent during fabrication, the model was unable to capture variations through the coating thickness that are observed experimentally. Here, a straightforward method is introduced to incorporate solvent evaporation explicitly into the model. Calculations are used to probe the impact of solvent evaporation rate and drug loading on the microstructure that forms during manufacturing and subsequent drug release kinetics. The predicted structures and release kinetics are found to be consistent with experimental observations. Further, the calculations demonstrate that solvent evaporation rate can be as critical to device performance as the amount of drug within the coating. For example, changes of a factor of five in the amount of drug released were observed by modifying the rate of solvent evaporation during manufacturing. (C) 2009 Wiley Periodicals. Inc.* J Biomed Mater Res Part B: Appl Biomater 90B: 688-699, 2009 C1 [Kim, Chang-Soo; Saylor, David M.; McDermott, Martin K.; Patwardhan, Dinesh V.] US FDA, Div Chem & Mat Sci, Off Sci & Engn Labs, Ctr Device & Radiol Hlth, Silver Spring, MD 20903 USA. [Warren, James A.] NIST, Mat Sci & Engn Labs, Div Met, Gaithersburg, MD 20899 USA. RP Kim, CS (reprint author), US FDA, Div Chem & Mat Sci, Off Sci & Engn Labs, Ctr Device & Radiol Hlth, Silver Spring, MD 20903 USA. EM chang-soo.kim@fda.hhs.gov RI Warren, James/B-1698-2008 OI Warren, James/0000-0001-6887-1206 NR 26 TC 13 Z9 13 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4973 EI 1552-4981 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD AUG PY 2009 VL 90B IS 2 BP 688 EP 699 DI 10.1002/jbm.b.31336 PG 12 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 472FD UT WOS:000268114200026 PM 19213052 ER PT J AU Sosnik, J Miranda, PV Spiridonov, NA Yoon, SY Fissore, RA Johnson, GR Visconti, PE AF Sosnik, Julian Miranda, Patricia V. Spiridonov, Nikolay A. Yoon, Sook-Young Fissore, Rafael A. Johnson, Gibbes R. Visconti, Pablo E. TI Tssk6 is required for Izumo relocalization and gamete fusion in the mouse SO JOURNAL OF CELL SCIENCE LA English DT Article DE Tssk6 (Sstk); Gamete fusion; Izumo; Fertilization; Acrosome reaction ID PROTEIN-KINASE 1; SERINE/THREONINE KINASE; SPERM CAPACITATION; ACROSOME REACTION; MAMMALIAN FERTILIZATION; ACTIN POLYMERIZATION; SURFACE-ANTIGENS; BOAR SPERMATOZOA; MALE-FERTILITY; BOVINE SPERM AB One of the most important processes in fertilization is the fusion of egg and sperm; however, the molecular mechanisms involved in this process are not well understood. So far, using genetic approaches, only two proteins have been demonstrated to be necessary for this process: Izumo in sperm and CD9 in the egg. Here we demonstrate that sperm produced by Tssk6 (Sstk)-null mice present defects that prevent the successful fertilization of eggs in vitro and the fusion to zona-pellucida-free eggs. Tssk6 is a member of the testis-specific serine kinase family of proteins and is expressed postmeiotically in male germ cells. In order for fusion to occur, during the process known as acrosome reaction Izumo needs to relocate from the anterior head to other regions, including the postacrosomal compartment. Tssk6-null sperm fails to relocate Izumo during the acrosome reaction. Agents that interfere with actin dynamics blocked the acrosome-reaction-associated translocation of Izumo that is required for fusion in wild-type sperm. Additionally, actin polymerization was compromised in Tssk6-null sperm. Taken together, our results indicate that Tssk6 is involved in sperm-egg fusion through the regulation of actin polymerization and changes in Izumo localization. C1 [Sosnik, Julian; Miranda, Patricia V.; Yoon, Sook-Young; Fissore, Rafael A.; Visconti, Pablo E.] Univ Massachusetts, Dept Vet & Anim Sci, Amherst, MA 01003 USA. [Sosnik, Julian; Fissore, Rafael A.; Visconti, Pablo E.] Univ Massachusetts, Mol & Cellular Biol Grad Program, Amherst, MA 01003 USA. [Miranda, Patricia V.] Consejo Nacl Invest Cient & Tecn, Inst Biol & Med Expt, RA-1428 Buenos Aires, DF, Argentina. [Spiridonov, Nikolay A.; Johnson, Gibbes R.] US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Visconti, PE (reprint author), Univ Massachusetts, Dept Vet & Anim Sci, Amherst, MA 01003 USA. EM pvisconti@vasci.umass.edu RI Sosnik, Julian/A-8310-2010; Spiridonov, Nikolay/B-6287-2014 OI Sosnik, Julian/0000-0002-0528-9929; FU NIH [HD038082, HD044044, HD050341, F31HD049324] FX We thank Masaru Okabe ( Osaka University, Japan) for his generous contribution of anti-Izumo antibodies. We also thank Dominique Alfandari and Anna Maria Salicioni ( University of Massachusetts, Amherst) for their input. This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development through grants NIH HD038082, NIH HD044044 and NIH HD050341 ( to P. E. V.) and NIH F31HD049324 (to J.S.). Deposited in PMC for release after 12 months. NR 51 TC 56 Z9 61 U1 0 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 EI 1477-9137 J9 J CELL SCI JI J. Cell Sci. PD AUG PY 2009 VL 122 IS 15 BP 2741 EP 2749 DI 10.1242/jcs.047225 PG 9 WC Cell Biology SC Cell Biology GA 473BM UT WOS:000268179400018 PM 19596796 ER PT J AU Lai, EW Joshi, BH Martiniova, L Dogra, R Fujisawa, T Leland, P de Krijger, RR Lubensky, IA Elkahloun, AG Morris, JC Puri, RK Pacak, K AF Lai, Edwin W. Joshi, Bharat H. Martiniova, Lucia Dogra, Ritika Fujisawa, Toshio Leland, Pamela de Krijger, Ronald R. Lubensky, Irina A. Elkahloun, Abdel G. Morris, John C. Puri, Raj K. Pacak, Karel TI Overexpression of Interleukin-13 Receptor-alpha 2 in Neuroendocrine Malignant Pheochromocytoma: A Novel Target for Receptor Directed Anti-Cancer Therapy SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CHIMERIC FUSION PROTEINS; IL-13 RECEPTOR; ANTITUMOR-ACTIVITY; PSEUDOMONAS EXOTOXIN; GLIOMA THERAPY; ALPHA-2 CHAIN; CYTOTOXIN; CANCER; EXPRESSION; MODEL AB Context: Pheochromocytomas and paragangliomas are rare catecholamine-secreting neuroendocrine tumors arising from the adrenal medulla and sympathetic tissues. When complete surgical resection is not an option, the treatment of pheochromocytoma is limited. Objective: The objective of the study was to identify and characterize overexpression of IL-13 receptor-alpha 2 (IL-13R alpha 2) gene expression in human and murine tumors and verify xenograft mouse pheochromocytoma cell (MPC)-derived tumor's response to a selective cytotoxin. Design/Setting/Patients: Expression of IL-13R alpha 2 was evaluated in a panel of 25 human pheochromocytoma clinical samples by RT-PCR and eight MPC tumors by indirect immunofluorescence assay and RT-PCR. Intervention: The function of IL-13R alpha 2 in these tumor cells was examined by evaluating tumor sensitivity to a recombinant IL-13-Pseudomonas exotoxin (IL-13PE). Subcutaneous small and large MPC tumors in athymic nude mice (n = 10) were treated intratumorally with IL-13PE (100 mu g/kg). Main Outcome Measures: IC(50) and tumor size were measured. Results: IL-13PE immunotoxin was highly cytotoxic to IL-13R alpha 2-overexpressing MPC cells (IC(50) < 2.5 ng/ml) in vitro. Furthermore, IL-13PE was highly cytotoxic to sc tumors. Our results showed a statistically significant decrease in tumor size as early as 3 d after initial treatment and further suppressed growth of MPC tumors. All tumors displayed a histological evidence of necrosis in response to IL-13 immunotoxin without any adverse effects in host at this dose. Conclusions: Human and murine neuroendocrine pheochromocytoma overexpress the IL-13R alpha 2 chain, and an IL-13PE-based receptor-directed anticancer approach may prove useful in treatment for metastatic pheochromocytoma patients. (J Clin Endocrinol Metab 94: 2952-2957, 2009) C1 [Lai, Edwin W.; Martiniova, Lucia; Pacak, Karel] NCI, Sect Med Neuroendocrinol, Ctr Canc Res, Bethesda, MD 20892 USA. [Joshi, Bharat H.; Dogra, Ritika; Fujisawa, Toshio; Leland, Pamela; Puri, Raj K.] NCI, Eunice Kennedy Shriver Natl Inst Child & Human De, NIH, Tumor Vaccines & Biotechnol Branch,Ctr Canc Res, Bethesda, MD 20892 USA. [Lubensky, Irina A.] NCI, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, US FDA,Canc Diag Program,Ctr Canc Res, Bethesda, MD 20892 USA. [Elkahloun, Abdel G.] NCI, NHGRI, Ctr Canc Res, Bethesda, MD 20892 USA. [Morris, John C.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [de Krijger, Ronald R.] Univ Med Ctr, Erasmus Med Ctr, Josephine Nefkens Inst, Dept Pathol, NL-3000 DR Rotterdam, Netherlands. RP Pacak, K (reprint author), NICHHD, Sect Med Neuroendocrinol, Reprod & Adult Endocrinol Program, CRC,NIH, Bldg 10,Room 1-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM raj.puri@fda.hhs.gov; karel@mail.nih.gov FU Intramural NIH HHS NR 26 TC 6 Z9 7 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2009 VL 94 IS 8 BP 2952 EP 2957 DI 10.1210/jc.2009-0309 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 479UW UT WOS:000268687700040 PM 19491224 ER PT J AU Boretti, FS Buehler, PW D'Agnillo, F Kluge, K Glaus, T Butt, OI Jia, YP Goede, J Pereira, CP Maggiorini, M Schoedon, G Alayash, AI Schaer, DJ AF Boretti, Felicitas S. Buehler, Paul W. D'Agnillo, Felice Kluge, Katharina Glaus, Tony Butt, Omer I. Jia, Yiping Goede, Jeroen Pereira, Claudia P. Maggiorini, Marco Schoedon, Gabrielle Alayash, Abdu I. Schaer, Dominik J. TI Sequestration of extracellular hemoglobin within a haptoglobin complex decreases its hypertensive and oxidative effects in dogs and guinea pigs SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CELL-FREE HEMOGLOBIN; NITRIC-OXIDE BIOAVAILABILITY; ACUTE-PHASE PROTEINS; ACUTE CHEST SYNDROME; SCAVENGER RECEPTOR; BLOOD SUBSTITUTES; PULMONARY-HYPERTENSION; CEREBRAL MALARIA; ACUTE HEMOLYSIS; PLASMA-PROTEIN AB Release of hemoglobin (Hb) into the circulation is a central pathophysiologic event that contributes to morbidity and mortality in chronic hemolytic anemias and severe malaria. These toxicities arise from Hb-mediated vasoactivity, possibly due to NO scavenging and localized tissue oxidative processes. Currently, there is no established treatment that targets circulating extracellular Hb. Here, we assessed the role of haptoglobin (Hp), the primary scavenger of Hb in the circulation, in limiting the toxicity of cell-free Hb infusion. Using a canine model, we found that glucocorticoid stimulation of endogenous Hp synthesis prevented Hb-induced hemodynamic responses. Furthermore, guinea pigs administered exogenous Hp displayed decreased Hb-induced hypertension and oxidative toxicity to extravascular environments, such as the proximal tubules of the kidney. The ability of Hp to both attenuate hypertensive responses during Hb exposure and prevent peroxidative toxicity in extravascular compartments was dependent on Hb-Hp complex formation, which likely acts through sequestration of Hb rather than modulation of its NO- and O(2)-binding characteristics. Our data therefore suggest that therapies involving supplementation of endogenous Hb scavengers may be able to treat complications of acute and chronic hemolysis, as well as counter the adverse effects associated with Hb-based oxygen therapeutics. C1 [Goede, Jeroen; Pereira, Claudia P.; Maggiorini, Marco; Schoedon, Gabrielle; Schaer, Dominik J.] Univ Zurich Hosp, Dept Internal Med, CH-8091 Zurich, Switzerland. [Buehler, Paul W.; D'Agnillo, Felice; Butt, Omer I.; Jia, Yiping; Alayash, Abdu I.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Boretti, Felicitas S.; Kluge, Katharina; Glaus, Tony] Univ Zurich, Vetsuisse Fac, Clin Small Anim, Zurich, Switzerland. RP Schaer, DJ (reprint author), Univ Zurich Hosp, Dept Internal Med, CH-8091 Zurich, Switzerland. EM abdu.alayash@fda.hhs.gov; dominik.schaer@usz.ch FU Swiss National Science Foundation [31-120658]; Helmut Horten Foundation; Gianni Rubatto Foundation; FDA/CBER Critical Patti Funds FX We are indebted to the Institute of Parasicology, Vetsuisse Faculty, Zurich for generously Supporting the beagle dog Studies and providing access to their animal research facility. We are particularly grateful to Armin Rudemarin and Andrea Perreren for excellent technical help. This study was Supported by the Swiss National Science Foundation (grant 31-120658), the Helmut Horten Foundation, and the Gianni Rubatto Foundation (all to D.J. Schaer) and by FDA/CBER Critical Patti Funds (to A.I. Alayash). The findings and conclusions in this article have not been formally disserninated by the FDA and should not be construed to represent any agency determination or policy. NR 63 TC 90 Z9 91 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 2009 VL 119 IS 8 BP 2271 EP 2280 DI 10.1172/JCI39115 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 478NW UT WOS:000268596000018 PM 19620788 ER PT J AU Brehm-Stecher, B Young, C Jaykus, LA Tortorello, ML AF Brehm-Stecher, Byron Young, Crarles Jaykus, Lee-Ann Tortorello, Mary Lou TI Sample Preparation: The Forgotten Beginning SO JOURNAL OF FOOD PROTECTION LA English DT Review ID REAL-TIME PCR; ESCHERICHIA-COLI O157-H7; ALTERNATIVE BINDING-PROTEINS; SUPERCRITICAL-FLUID EXTRACTION; IN-SITU HYBRIDIZATION; TO-AIR TRANSFER; LISTERIA-MONOCYTOGENES; ONE-STEP; CAPILLARY-ELECTROPHORESIS; ENHANCED DETECTION AB Advances in molecular technologies and automated instrumentation have provided many opportunities for improved detection and identification of microorganisms; however, the upstream sample preparation steps needed to apply these advances to foods have not been adequately researched or developed. Thus, the extent to which these advances have improved food microbiology has been limited. The purpose of this review is to present the current state of sample preparation, to identify knowledge gaps and opportunities for improvement, and to recognize the need to support greater research and development efforts on preparative methods in food microbiology. The discussion focuses on the need to push technological developments toward methods that do not rely on enrichment culture. Among the four functional components of microbiological analysis (i.e., sampling, separation, concentration, detection), the separation and concentration components need to be researched more extensively to achieve rapid, direct, and quantitative methods. The usefulness of borrowing concepts of separation and concentration from other disciplines and the need to regard the microorganism as a physicochemical analyte that may be directly extracted from the food matrix are discussed. The development of next-generation systems that holistically integrate sample preparation with rapid, automated detection will require interdisciplinary collaboration and substantially increased funding. C1 [Tortorello, Mary Lou] US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. [Jaykus, Lee-Ann] N Carolina State Univ, Dept Food Bioproc & Nutr Sci, Raleigh, NC 27695 USA. [Young, Crarles] Johns Hopkins Univ, Appl Phys Lab, Natl Secur & Technol Dept, Laurel, MD 20723 USA. [Brehm-Stecher, Byron] Iowa State Univ, Dept Food Sci & Human Nutr, Ames, IA 50011 USA. RP Tortorello, ML (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM mary.tortorello@fda.hhs.gov FU International Association for Food Protection; Sample Prep Working Group FX The authors gratefully acknowledge the International Association for Food Protection for their financial and organizational support of the Sample Prep Working Group, which provided the structure for discussions that resulted in this review. NR 98 TC 57 Z9 60 U1 4 U2 35 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD AUG PY 2009 VL 72 IS 8 BP 1774 EP 1789 PG 16 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 483DH UT WOS:000268941700031 PM 19722419 ER PT J AU Tournas, VH AF Tournas, Valerie H. TI MICROBIAL CONTAMINATION OF SELECT DIETARY SUPPLEMENTS SO JOURNAL OF FOOD SAFETY LA English DT Article ID ANTIMICROBIAL ACTIVITY; FUNGAL CONTAMINATION; ESSENTIAL OILS; OCHRATOXIN-A; HERBAL DRUGS; ASPERGILLUS; GROWTH; HYPERCHOLESTEROLEMIA; CORIANDER; ECHINACEA AB One hundred thirty-eight dietary supplement samples comprised of alfalfa, Circu-Care, coriander, cumin, echinacea, garlic, ginger, ginkgo, horse chestnut extract, juniper berries, licorice, psyllium, saw palmetto, St. John's wort, valerian, white willow bark, and various vitamins and minerals were obtained from local supermarkets and dietary supplement companies and analyzed for fungal contamination and the presence of aerobic mesophilic bacteria. Results indicated that the highest mold and yeast counts of 5.6 x 10(6) colony forming units (cfu) per gram product were found in alfalfa and the lowest (1.0 x 10(2) cfu/g) were present in ginger supplements. Potentially toxigenic molds were found in alfalfa, coriander, echinacea, garlic, ginkgo, juniper, licorice, psyllium and St. John's wort supplements. The most common fungi were aspergilli, followed by eurotia, penicillia and yeasts. Alternaria alternata, Fusarium, Cladosporium, Rhizopus and Phoma spp. were isolated less frequently. No molds or yeasts were found in synthetic vitamins, minerals, Circu-Care and valerian. Aerobic mesophilic bacteria were isolated from all commodities tested. The highest aerobic plate count numbers (5.2 x 10(6)-3.8 x 10(7) cfu/g) were recovered from alfalfa, whereas the lowest (< 100-5.5 x 10(2) cfu/g) were found in vitamins and minerals. PRACTICAL APPLICATIONS With an ever-increasing population utilizing dietary supplements in order to improve and sustain health and vitality, it is essential that these products are safe for human consumption. A very critical indicator of safety is the bacteriological and mycological quality of these commodities. The results of this investigation constitute an indicator of mycological/bacteriological contamination of a variety of dietary supplements. Similar testing has not been reported for several of the studied commodities. Therefore, our findings can serve as a basis for future mycological and mycotoxin testing of dietary supplements and eventually for developing guidelines in order to achieve and maintain safe microbial levels in these products. C1 Food & Drug Adm, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Tournas, VH (reprint author), Food & Drug Adm, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM valerie.tournas@fda.hhs.gov NR 39 TC 2 Z9 2 U1 2 U2 6 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 AUG PY 2009 VL 29 IS 3 BP 430 EP 442 DI 10.1111/j.1745-4565.2009.00167.x PG 13 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 479MK UT WOS:000268663400008 ER PT J AU Burnham, VE Janes, ME Jakus, LA Supan, J DePaola, A Bell, J AF Burnham, V. E. Janes, M. E. Jakus, L. A. Supan, J. DePaola, A. Bell, J. TI Growth and Survival Differences of Vibrio vulnificus and Vibrio parahaemolyticus Strains during Cold Storage SO JOURNAL OF FOOD SCIENCE LA English DT Article DE cold storage; strains; Vibrio parahaemolyticus; Vibrio vulnificus ID CRASSOSTREA-VIRGINICA; NONCULTURABLE STATE; RAW OYSTERS; TEMPERATURE; RECOVERY; CELLS; SHELLSTOCK; SALINITY; BACTERIA AB Vibrio vulnificus and Vibrio parahaemolyticus are the most common Vibrio species associated with seafood illness in the United States. Our study was conducted to determine if strain-to-strain differences exist in the growth and survival of 8 different V. vulnificus and V. parahaemolyticus strains at low temperatures. By day 10, V. vulnificus strain 515-4C2 had significantly higher counts (P < 0.05) (1.97 log CFU/g) compared with strains 3315, 1007, 29306 at 5 degrees C, which reached nondetectable levels. At 8 degrees C, strain 515-4C2 had significantly higher counts (P < 0.05) (2.23 log CFU/mL) compared with 1007, 33815, 541(O) 49C, which reached nondetectable levels. At 10 degrees C, only V. vulnificus strain 33815 reached nondetectable levels. At 5 degrees C, V. parahaemolyticus strain 541(O) 57C had the highest counts (5.28 log CFU/g) by day 10 while strain 33847 had significantly lower counts (3.46 log CFU/g). After 10 d at 8 degrees C, V. parahaemolyticus strain M350A had the highest counts (7.97 log CFU/mL) while strain 541(O) 57C had the lowest counts (4.80 log CFU/mL). At 10 degrees C, V. parahaemolyticus strain NY477 had significantly higher counts (P < 0.05) with 8.31 log CFU/mL compared with strain 33847, which had the lowest counts (6.77 log CFU/mL). Our research has shown that various V. vulnificus and V. parahaemolyticus strains vary in their ability to survive and grow at refrigeration temperatures. C1 [Burnham, V. E.; Janes, M. E.; Bell, J.] Louisiana State Univ, Ctr Agr, Dept Food Sci, Baton Rouge, LA 70803 USA. [Supan, J.] Louisiana State Univ, Ctr Agr, LA Sea Grant Coll Pr, Baton Rouge, LA 70803 USA. [Jakus, L. A.] N Carolina State Univ, Dept Food Sci, Raleigh, NC 27695 USA. [DePaola, A.] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36538 USA. RP Janes, ME (reprint author), Louisiana State Univ, Ctr Agr, Dept Food Sci, Baton Rouge, LA 70803 USA. EM mjanes@agcenter.lsu.edu FU U.S. Dept. of Agriculture; Natl. Research Initiative; Competitive Grants Program, Epidemiological Approaches to Food Safety, [2004-3521214882] FX This study was supported by a grant from the U.S. Dept. of Agriculture, Natl. Research Initiative, Competitive Grants Program, Epidemiological Approaches to Food Safety, project nr 2004-3521214882. NR 25 TC 10 Z9 11 U1 1 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD AUG PY 2009 VL 74 IS 6 BP M314 EP M318 DI 10.1111/j.1750-3841.2009.01227.x PG 5 WC Food Science & Technology SC Food Science & Technology GA 479BS UT WOS:000268634400043 PM 19723217 ER PT J AU Colino, J Chattopadhyay, G Sen, G Chen, QY Lees, A Canaday, DH Rubtsov, A Torres, R Snapper, CM AF Colino, Jesus Chattopadhyay, Gouri Sen, Goutam Chen, Quanyi Lees, Andrew Canaday, David H. Rubtsov, Anatoly Torres, Raul Snapper, Clifford M. TI Parameters Underlying Distinct T Cell-Dependent Polysaccharide-Specific IgG Responses to an Intact Gram-Positive Bacterium versus a Soluble Conjugate Vaccine SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ZONE B-CELLS; STREPTOCOCCUS-PNEUMONIAE ELICIT; INDEPENDENT TYPE-2 ANTIGENS; MARGINAL-ZONE; IN-VIVO; CAPSULAR POLYSACCHARIDE; PARTICULATE ANTIGENS; DENDRITIC CELLS; DIFFERENTIAL REGULATION; ANTIBODY-RESPONSES AB IgG anti-polysaccharide (PS) responses to both intact Streptococcus pneumoniae (Pn) and PS conjugate vaccines are dependent on CD4(+) T cells, B7-dependent costimulation, and CD40-CD40-ligand interactions. Nevertheless, the former response, in contrast to the latter, is mediated by an ICOS-independent, a poptosis-prone, extrafollicular pathway that fails to generate PS-specific memory. We show that pre-existing PS-specific Igs, the bacterial surface or particulation, selective recruitment of B cell subsets, or activation and recruitment of Pn protein-specific CD4(+) T cells do not account for the failure of Put to generate PS-specific IgG memory. Rather, the data suggest that the critical factor may be the lack of covalent attachment of PS to protein in intact Pn, highlighting the potential importance of the physicochemical relationship of PS capsule with the underlying bacterial structure for in vivo induction of PS-specific Igs. The Journal of Immunology, 2009, 183: 1551-1559. C1 [Colino, Jesus; Chattopadhyay, Gouri; Chen, Quanyi; Snapper, Clifford M.] Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. [Sen, Goutam] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Lees, Andrew] Fina Biosolut, Rockville, MD 20850 USA. [Canaday, David H.] Ctr Geriatr Res Educ & Clin, Cleveland, OH 44106 USA. [Rubtsov, Anatoly; Torres, Raul] Univ Colorado & Natl Jewish Hlth, Integrated Dept Immunol, Denver, CO 80206 USA. RP Snapper, CM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pathol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM csnapper@usuhs.mil FU National Institutes of Health [2ROI A149192] FX This study was supported by National Institutes of Health Grant 2ROI A149192 and the United States Uniformed Services University of the Health Sciences Dean's Research and Education Endowment Fund. NR 34 TC 20 Z9 20 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2009 VL 183 IS 3 BP 1551 EP 1559 DI 10.4049/jimmunol.0900238 PG 9 WC Immunology SC Immunology GA 477LB UT WOS:000268519500010 PM 19570830 ER PT J AU Selvapandiyan, A Dey, R Nylen, S Duncan, R Sacks, D Nakhasi, HL AF Selvapandiyan, Angamuthu Dey, Ranadhir Nylen, Susanne Duncan, Robert Sacks, David Nakhasi, Hira L. TI Intracellular Replication-Deficient Leishmania donovani Induces Long Lasting Protective Immunity against Visceral Leishmaniasis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELLS; TH1 RESPONSE; NITRIC-OXIDE; BALB/C MICE; INFECTION; VACCINATION; DISEASE; MODEL; PARASITES; MEXICANA AB No vaccine is currently available for visceral leishmaniasis (VL) caused by Leishmania donovani. This study addresses whether a live attenuated centrin gene-deleted L. donovani (LdCen1(-/-)) parasite can persist and be both safe and protective in animals. LdCen1(-/-) has a defect in amastigote replication both in vitro and ex vivo in human macrophages. Safety was shown by the lack of parasites in spleen and liver in susceptible BALB/c mice, immune compromised SCID mice, and human VL, model hamsters 10 wk after infection. Mice immunized with LdCen1(-/-) showed early clearance of virulent parasite challenge not seen in mice immunized with heat killed parasites. Upon virulent challenge, the immunized mice displayed in the CD4(+) T cell population a significant increase of single and multiple cytokine (IFN-gamma, IL-2, and TNF) producing cells and IFN-gamma/IL10 ratio. Immunized mice also showed increased IgG2a immunoglobulins and NO production in macrophages. These features indicated a protective Th1-type immune response. The Th1 response correlated with a significantly reduced parasite burden in the spleen and no parasites in the liver compared with naive mice 10 wk post challenge. Protection was observed, when challenged even after 16 wk post immunization, signifying a sustained immunity. Protection by immunization with attenuated parasites was also seen in hamsters. Immunization with LdCen1(-/-) also cross-protected mice against infection with L. braziliensis that causes mucocutaneous leishmaniasis. Results indicate that LdCen1(-/-) can be a safe and effective vaccine candidate against VL as well as mucocutaneous leishmaniasis causing parasites. The Journal of Immunology, 2009, 183: 1813-1820. C1 [Selvapandiyan, Angamuthu; Dey, Ranadhir; Duncan, Robert; Nakhasi, Hira L.] US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Nylen, Susanne; Sacks, David] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Nakhasi, HL (reprint author), US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM hira.nakhasi@fda.hhs.gov RI Duncan, Robert/I-8168-2015; OI Duncan, Robert/0000-0001-8409-2501; Nylen, Susanne/0000-0002-3875-3353 NR 42 TC 57 Z9 57 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2009 VL 183 IS 3 BP 1813 EP 1820 DI 10.4049/jimmunol.0900276 PG 8 WC Immunology SC Immunology GA 477LB UT WOS:000268519500038 PM 19592661 ER PT J AU Coelho, SG Choi, W Brenner, M Miyamura, Y Yamaguchi, Y Wolber, R Smuda, C Batzer, J Kolbe, L Ito, S Wakamatsu, K Zmudzka, BZ Beer, JZ Miller, SA Hearing, VJ AF Coelho, Sergio G. Choi, Wonseon Brenner, Michaela Miyamura, Yoshinori Yamaguchi, Yuji Wolber, Rainer Smuda, Christoph Batzer, Jan Kolbe, Ludger Ito, Shosuke Wakamatsu, Kazumasa Zmudzka, Barbara Z. Beer, Janusz Z. Miller, Sharon A. Hearing, Vincent J. TI Short- and Long-Term Effects of UV Radiation on the Pigmentation of Human Skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS LA English DT Article CT 9th Annual Meeting of the Society-of-Japanese-Photo-Aging-Research CY MAY 13, 2008 CL Kyoto, JAPAN SP Soc Japanese Photo Aging Res ID ULTRAVIOLET-RADIATION; MELANIN PIGMENTATION; DNA-DAMAGE; MECHANISMS; IRRADIATION; APOPTOSIS; RESPONSES; EPIDERMIS; CANCER AB The incidence of skin cancer, including cutaneous melanoma, has risen substantially in recent years, and epidemiological and laboratory studies show that UV radiation is a major causative factor of this increase. UV damage also underlies photoaging of the skin, and these deleterious effects of UV can be, in part, prevented in skin with higher levels of constitutive pigmentation. We review the clinical studies we have made in recent years regarding the rapid and the long-term responses of the pigmentary system in human skin to UV exposure. C1 [Coelho, Sergio G.; Choi, Wonseon; Brenner, Michaela; Miyamura, Yoshinori; Yamaguchi, Yuji; Hearing, Vincent J.] NCI, Pigment Cell Biol Sect, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Wolber, Rainer; Smuda, Christoph; Batzer, Jan; Kolbe, Ludger] Beiersdorf AG, R&D Skin Res, Hamburg, Germany. [Ito, Shosuke; Wakamatsu, Kazumasa] Fujita Hlth Univ, Sch Hlth Sci, Dept Chem, Aichi, Japan. [Zmudzka, Barbara Z.; Beer, Janusz Z.; Miller, Sharon A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Hearing, VJ (reprint author), NCI, Pigment Cell Biol Sect, Cell Biol Lab, NIH, Bldg 37,Room 2132,MSC 4256, Bethesda, MD 20892 USA. EM hearingv@nih.gov OI Wakamatsu, Kazumasa/0000-0003-1748-9001; Ito, Shosuke/0000-0001-9182-5144 FU Intramural NIH HHS [ZIA BC010784-03] NR 29 TC 8 Z9 10 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0024 J9 J INVEST DERM SYMP P JI J. Invest. Dermatol. Symp. Proc. PD AUG PY 2009 VL 14 IS 1 BP 32 EP 35 DI 10.1038/jidsymp.2009.10 PG 4 WC Dermatology SC Dermatology GA 483LD UT WOS:000268967100007 PM 19675550 ER PT J AU Sharma, HS Ali, S Tian, ZR Patnaik, R Patnaik, S Lek, P Sharma, A Lundstedt, T AF Sharma, Hari S. Ali, Syed Tian, Z. Ryan Patnaik, Ranjana Patnaik, S. Lek, Per Sharma, Aruna Lundstedt, Torbjorn TI Nano-Drug Delivery and Neuroprotection in Spinal Cord Injury SO JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY LA English DT Article; Proceedings Paper CT 1st International Symposium on Nanoneuroscience - Nanoeuroprotection and Nanoeurotoxicity CY AUG 20-26, 2007 CL Killithea, GREECE DE Nanowiring; Nano-Drug Delivery; Spinal Cord Injury; Neuroprotection; Blood-Spinal Cord Barrier; Functional Paralysis; Myelin Damage; Titanium Dioxide ID CENTRAL-NERVOUS-SYSTEM; TITANIUM-DIOXIDE NANOPARTICLES; SEROTONIN SYNTHESIS INHIBITOR; FINE PARTICULATE MATTER; PARTICLE-SIZE; IN-VIVO; ELECTRON-MICROSCOPY; TISSUE DISTRIBUTION; BARRIER DISRUPTION; SURFACE-PROPERTIES AB Recently nano-drug delivery to the central nervous system (CNS) has been shown to be more effective than the parent compound by itself. An increased availability of the drug for longer periods to the brain or spinal cord and/or a decrease in the drug metabolism altogether could lead to potentiation of the pharmacological activity of the nano-delivered compounds. However, it is still unclear whether the nanocarriers used to deliver the drugs may itself has any potential neurotoxic activity. Although, nanodrug-delivery appears to be a quite promising therapeutic tool for the future clinical therapy, its advantages and limitations for the routine use of patients still needs to be elucidated. Our laboratory is engaged to study a plethora of potential neuroprotective novel compounds delivered to the CNS using nanowiring techniques following brain or spinal cord trauma. Our investigations show that nanowired drugs, if delivered locally following spinal cord injury achieve better neuroprotection than the parent compounds. This effect of nano-drug delivery appears to be very selective in nature. Thus, a clear differentiation based on the compounds used for nano-drug delivery can be seen on various pathological parameters in spinal cord injury. These observations suggest that nanowiring may itself do not induce neuroprotection, but enhance the neuroprotective ability of compounds after trauma. This review describes some recent advances in nano-drug delivery to the CNS in relation to novel neuroprotective strategies with special emphasis on spinal cord trauma based on our own observations and recent findings from our laboratory investigations. C1 [Sharma, Hari S.; Sharma, Aruna] Uppsala Univ, Univ Hosp, Dept Surg Sci Anaesthesiol & Intens Care Med, Lab Cerebrovasc Res, SE-75185 Uppsala, Sweden. [Lek, Per; Lundstedt, Torbjorn] AcurePharma AB, SE-75643 Uppsala, Sweden. [Ali, Syed] US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Tian, Z. Ryan] Univ Arkansas, Dept Chem & Biochem, Fayetteville, AR 72701 USA. [Patnaik, Ranjana; Patnaik, S.] Banaras Hindu Univ, Inst Technol, Dept Pharm, Varanasi 221005, Uttar Pradesh, India. [Lundstedt, Torbjorn] Uppsala Univ, Div Organ Chem, Dept Med Chem, SE-75105 Uppsala, Sweden. RP Lundstedt, T (reprint author), Uppsala Univ, Univ Hosp, Dept Surg Sci Anaesthesiol & Intens Care Med, Lab Cerebrovasc Res, SE-75185 Uppsala, Sweden. RI Sharma, Aruna/D-4430-2011; Sharma, Hari/G-4508-2016; Tian, Z. Ryan /R-6671-2016; OI Tian, Z. Ryan /0000-0002-5644-8483; Patnaik, Ranjana/0000-0002-8131-177X NR 94 TC 31 Z9 31 U1 1 U2 16 PU AMER SCIENTIFIC PUBLISHERS PI STEVENSON RANCH PA 25650 NORTH LEWIS WAY, STEVENSON RANCH, CA 91381-1439 USA SN 1533-4880 J9 J NANOSCI NANOTECHNO JI J. Nanosci. Nanotechnol. PD AUG PY 2009 VL 9 IS 8 BP 5014 EP 5037 DI 10.1166/jnn.2009.GR04 PG 24 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 470QO UT WOS:000267994100068 PM 19928182 ER PT J AU Sharma, HS Ali, SF Hussain, SM Schlager, JJ Sharma, A AF Sharma, Hari S. Ali, Syed F. Hussain, Saber M. Schlager, John J. Sharma, Aruna TI Influence of Engineered Nanoparticles from Metals on the Blood-Brain Barrier Permeability, Cerebral Blood Flow, Brain Edema and Neurotoxicity. An Experimental Study in the Rat and Mice Using Biochemical and Morphological Approaches SO JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY LA English DT Article; Proceedings Paper CT 1st International Symposium on Nanoneuroscience - Nanoeuroprotection and Nanoeurotoxicity CY AUG 20-26, 2007 CL Killithea, GREECE DE Engineered Nanoparticles; Silver; Copper; Aluminum; Blood-Brain Barrier; Brain Edema; Cerebral Blood Flow; Neuropathology; Astrocytes; Myelin; Evans Blue ID SPINAL CORD BARRIER; CARBON-NANOTUBES; TRAUMATIC INJURY; OXIDATIVE STRESS; HEAT-STRESS; METHAMPHETAMINE INTOXICATION; TISSUE DISTRIBUTION; PYROLYSIS PRODUCTS; DRUG-DELIVERY; HEALTH-RISKS AB Influence of nanoparticles on brain function following in vivo exposures is not well known. Depending on the magnitude and intensity of nanoparticle exposure from the environment, food and/or water source, neuronal function could be affected and may lead to neurotoxicity and neuropathology. This hypothesis was examined in present investigation using systemic or intracerebroventricular administration of engineered nanoparticles from metals, i.e., Al, Ag and Cu (approximate to 50 to 60 nm) on neurotoxicity in rats and mice. Intraperitoneal (50 mg/kg), intravenous (30 mg/kg), intracarotid (2.5 mg/kg) or intracerebroventricular administration (20 mu g) of nanoparticles significantly altered the blood-brain barrier (BBB) function to Evans blue and radioiodine in several regions of the brain and spinal cord at 24 h after their administration. Marked decreases in local cerebral blood flow (CBF) and pronounced brain edema was seen in regional areas associated with BBB leakage. Neuronal cell injuries, glial cell activation, heat shock protein (HSP) upregulation and loss of myelinated fibers are quite common in effected brain areas. The observed pathological changes were most pronounced in mice compared to rats. Exposures to Cu and Ag nanoparticles showed most marked effects on brain pathology when administered into systemic circulation or into the brain ventricular spaces as compared to Al nanoparticles. Our results are the first to show that nanoparticles from metals are able to induce selective and specific neurotoxicity that depends on the type of metals, route of administration and the species used. C1 [Sharma, Hari S.; Sharma, Aruna] Uppsala Univ, Univ Hosp, Lab Cerebrovasc Res Anesthesiol & Intens Care, SE-75185 Uppsala, Sweden. [Ali, Syed F.] US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Hussain, Saber M.; Schlager, John J.] USAF, Res Lab, Appl Biotechnol Branch, Human Effectiveness Directorate, Wright Patterson AFB, OH 45433 USA. RP Sharma, HS (reprint author), Uppsala Univ, Univ Hosp, Lab Cerebrovasc Res Anesthesiol & Intens Care, SE-75185 Uppsala, Sweden. RI Sharma, Aruna/D-4430-2011; Sharma, Hari/G-4508-2016 NR 64 TC 69 Z9 70 U1 1 U2 21 PU AMER SCIENTIFIC PUBLISHERS PI STEVENSON RANCH PA 25650 NORTH LEWIS WAY, STEVENSON RANCH, CA 91381-1439 USA SN 1533-4880 J9 J NANOSCI NANOTECHNO JI J. Nanosci. Nanotechnol. PD AUG PY 2009 VL 9 IS 8 BP 5055 EP 5072 DI 10.1166/jnn.2009.GR09 PG 18 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 470QO UT WOS:000267994100071 PM 19928185 ER PT J AU Sharma, HS Ali, SF Tian, ZR Hussain, SM Schlager, JJ Sjoquist, PO Sharma, A Muresanu, DF AF Sharma, Hari Shanker Ali, Syed F. Tian, Z. Ryan Hussain, Saber M. Schlager, John J. Sjoquist, Per-Ove Sharma, Aruna Muresanu, Datin F. TI Chronic Treatment with Nanoparticles Exacerbate Hyperthermia Induced Blood-Brain Barrier Breakdown, Cognitive Dysfunction and Brain Pathology in the Rat. Neuroprotective Effects of Nanowired-Antioxidant Compound H-290/51 SO JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY LA English DT Article; Proceedings Paper CT 1st International Symposium on Nanoneuroscience - Nanoeuroprotection and Nanoeurotoxicity CY AUG 20-26, 2007 CL Killithea, GREECE DE Nanoparticles; Hyperthermia; Heat Stress; Antioxidants; H-290/51; Blood-Brain Barrier; Brain Edema; Brain Pathology; Nanowiring; Nano-Drug Delivery ID NORMOTENSIVE YOUNG-RATS; CENTRAL-NERVOUS-SYSTEM; POLIOMYELITIS VIRUS; OXIDATIVE STRESS; DRUG-DELIVERY; AIR-POLLUTION; HEAT-STRESS; NASAL-MUCOSA; SPINAL-CORD; INFLAMMATION AB The possibility that chronic exposure of nanoparticles may alter stress reaction and brain pathology following hyperthermia was examined in a rat model. Engineered nanoparticles from Ag or M Cu (approximate to 50-60 nm) were administered (30 mg/kg, i.p.) once daily for 1 week in young male rats. M On the 8th day these animals were subjected to 4 h heat stress at 38 degrees C in a BOD incubator. In these animals stress symptoms, blood-brain barrier (BBB) permeability, cognitive and motor functions and brain pathology were examined. Subjection of nanoparticle treated rats to heat stress showed exacerbation of stress symptoms i.e., hyperthermia, salivation and prostration and exhibited greater BBB disruption, brain edema formation, impairment of cognitive and motor functions M and brain damage compared to normal animals. This enhanced brain pathology in heat stress was most marked in animals that received Ag nanoparticles compared to Cu treatment. Treatment with antioxidant compound H-290/51 either 30 min or 60 min after heat stress did not alter hyperthermia M induce brain pathology in nanoparticle treated rats. Whereas, administration of nanowired-H-290/51 after 30 min or 60 min heat stress markedly attenuated BBB disruption, sensory motor function and brain pathology. These results suggest that chronic nanoparticles treatment exacerbate hyperthermia induced brain pathology that is significantly attenuated by nanowired but not normal H-290/51 compound. Taken together, our observations suggest that nano-wired drug delivery of H-290/51 is a promising approach to induce neuroprotection in hyperthermia induced brain pathology, not reported earlier. C1 [Sharma, Hari Shanker; Sharma, Aruna] Uppsala Univ, Univ Hosp, Dept Surg Sci Anaesthesiol & Intens Care Med, Lab Cerebrovasc Res, SE-75185 Uppsala, Sweden. [Ali, Syed F.] US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Tian, Z. Ryan] Univ Arkansas, Dept Chem & Biochem, Fayetteville, AR 72701 USA. [Hussain, Saber M.; Schlager, John J.] USAF, Res Lab, Appl Biotechnol Branch, Human Effectiveness Directorate, Wright Patterson AFB, OH 45433 USA. [Sjoquist, Per-Ove] Astra Zeneca, Dept Biosci, SE-43183 Molndal, Sweden. [Muresanu, Datin F.] Univ Med & Pharm Iuliu Hatieganu, Dept Neurol, RO-400011 Cluj Napoca, Romania. RP Sharma, HS (reprint author), Uppsala Univ, Univ Hosp, Dept Surg Sci Anaesthesiol & Intens Care Med, Lab Cerebrovasc Res, SE-75185 Uppsala, Sweden. RI Muresanu, Dafin Fior/C-4092-2011; Sharma, Aruna/D-4430-2011; Sharma, Hari/G-4508-2016; Tian, Z. Ryan /R-6671-2016 OI Tian, Z. Ryan /0000-0002-5644-8483 NR 64 TC 45 Z9 45 U1 2 U2 11 PU AMER SCIENTIFIC PUBLISHERS PI STEVENSON RANCH PA 25650 NORTH LEWIS WAY, STEVENSON RANCH, CA 91381-1439 USA SN 1533-4880 J9 J NANOSCI NANOTECHNO JI J. Nanosci. Nanotechnol. PD AUG PY 2009 VL 9 IS 8 BP 5073 EP 5090 DI 10.1160/jnn.2009.GR10 PG 18 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 470QO UT WOS:000267994100072 PM 19928186 ER PT J AU Gulmann, C Sheehan, KM Conroy, RM Wulfkuhie, JD Espina, V Mullarkey, MJ Kay, EW Liotta, LA Petricoin, EF AF Gulmann, Christian Sheehan, Katherine M. Conroy, Ronan M. Wulfkuhie, Julia D. Espina, Virginia Mullarkey, Michelle J. Kay, Elaine W. Liotta, Lance A. Petricoin, Emanuel F., III TI Quantitative cell signalling analysis reveals down-regulation of MAPK pathway activation in colorectal cancer SO JOURNAL OF PATHOLOGY LA English DT Article DE colorectal cancer; MAPK; Erk; p38; phosphorylation; proteomics ID PHASE PROTEIN MICROARRAYS; DIFFERENTIAL REGULATION; KINASE; CARCINOMA; EXPRESSION AB Mitogen-activated protein kinases (MAPK) are considered to play significant roles in colonic carcinogenesis and kinase inhibitor therapy has been proposed as a potential tool in the treatment of this disease. Reverse-phase microarray assays using phospho-specific antibodies can directly measure levels of phosphorylated protein isoforms. In the current study, samples from 35 cases of untreated colorectal cancer colectomies were laser capture-microdissected to isolate epithelium and stroma from cancer as well as normal (i.e. uninvolved) mucosa. Lysates generated from these four tissue types were spotted onto reverse-phase protein microarrays and probed with a panel of antibodies to ERK, p-ERK, p38, p-p38, p-JNK, MEK and p-MEK. Whereas total protein levels were unchanged, or slightly elevated (p38, p = 0.0025) in cancers, activated isoforms, including p-ERK, p-p38 and p-JNK, were decreased two- to four-fold in cancers compared with uninvolved mucosa (p < 0.0023 in all cases except for p-JNK in epithelium, where decrement was non-significant). This was backed up by western blotting. Dukes' stage B and C cancers displayed lower p-ERK and p-p38 expression than Dukes' stage A cancers, although this was not statistically significant. It is concluded that MAPK activity may be down-regulated in colorectal cancer and that further exploration of inhibitory therapy in this system should be carefully evaluated if this finding is confirmed in larger series. Copyright (C) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Gulmann, Christian; Sheehan, Katherine M.; Kay, Elaine W.] Beaumont Hosp, Dept Pathol, Dublin 9, Ireland. [Sheehan, Katherine M.; Mullarkey, Michelle J.; Kay, Elaine W.] Royal Coll Surgeons Ireland, Dept Pathol, Dublin 2, Ireland. [Gulmann, Christian; Sheehan, Katherine M.; Espina, Virginia; Liotta, Lance A.] NCI, FDA Clin Prote Program, Pathol Lab, Bethesda, MD USA. [Conroy, Ronan M.] Royal Coll Surgeons Ireland, Dept Epidemiol, Dublin 2, Ireland. [Wulfkuhie, Julia D.; Espina, Virginia; Liotta, Lance A.; Petricoin, Emanuel F., III] George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA USA. [Wulfkuhie, Julia D.; Petricoin, Emanuel F., III] NCI, FDA Clin Prote Program, US FDA, Bethesda, MD 20892 USA. RP Gulmann, C (reprint author), Beaumont Hosp, Dept Pathol, Beaumont Rd, Dublin 9, Ireland. EM christiangulmann@beaumont.ie OI Espina, Virginia/0000-0001-5080-5972; Conroy, Ronan/0000-0001-5983-8682 FU Pathological Society of Great Britain and Ireland; Laboratory of Molecular Pharmacology, Center for Cancer Research, NIH Bethesda, MD, USA FX The Pathological Society of Great Britain and Ireland is gratefully acknowledged for financial support (to CG and KS). Gabriel S. Eichler, Laboratory of Molecular Pharmacology, Center for Cancer Research, NIH Bethesda, MD, USA, is gratefully acknowledged for his help with standardization of data. NR 20 TC 34 Z9 36 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD AUG PY 2009 VL 218 IS 4 BP 514 EP 519 DI 10.1002/path.2561 PG 6 WC Oncology; Pathology SC Oncology; Pathology GA 477IA UT WOS:000268511400012 PM 19396842 ER PT J AU Wu, HQ Khan, MA AF Wu, Huiquan Khan, Mansoor A. TI Quality-By-Design (QbD): An Integrated Approach for Evaluation of Powder Blending Process Kinetics and Determination of Powder Blending End-point SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE quality-by-design (QbD); process analytical technology (PAT); design of experiments; multivariate statistical data analysis; powder blending; process monitoring; blending end-point determination; moving block standard deviation; process dynamics ID NEAR-INFRARED SPECTROSCOPY; AUTOMATED-SYSTEM; REAL-TIME; HOMOGENEITY; FLOW AB The objective of this study was to develop an integrated process monitoring approach for evaluating powder blending process kinetics and determining blending process end-point. A mixture design was created to include 26 powder formulations consisting of ibuprofen as the model drug and three excipients (HPMC, MCC, and Eudragit L100-55). The mixer was stopped at Various time points to enable near-infrared spectroscopy scan of the powder mixture for obtaining the time course of the blending process. The evaluation of the blending process kinetics and process end-point was studied through three quantitative approaches: (1) Spectra linear superposition method; (2) Characteristic peak method; (3) Moving block standard deviation method. It was found that the powder blending experienced an initial rapid process to reach a quasi-end point within the first few minutes. Afterwards, a demixing occurred. Then, a real blending end-point was reached as characterized by an inflection point. ANOVA shows that the compositions of ibuprofen and MCC are the most statistically significant variables that impact the time required to reach the blending end-point. This highlighted the critical importance of developing quantitative chemometric approaches to extract critical process information and generate essential process knowledge to enable real-time release of the blending process. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2784-2798, 2009 C1 [Wu, Huiquan; Khan, Mansoor A.] US FDA, CDER, OPS, OTR,DPQR,HRD 940, Silver Spring, MD 20993 USA. RP Khan, MA (reprint author), US FDA, CDER, OPS, OTR,DPQR,HRD 940, FDA White Oak Campus Life Sci Bldg 64,10903 New H, Silver Spring, MD 20993 USA. EM mansoor.khan@fda.hhs.gov NR 32 TC 32 Z9 34 U1 2 U2 12 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD AUG PY 2009 VL 98 IS 8 BP 2784 EP 2798 DI 10.1002/jps.21646 PG 15 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 478PN UT WOS:000268600300021 PM 19116952 ER PT J AU Guo, CN Ye, W Kauffman, J Doub, WH AF Guo, Changning Ye, Wei Kauffman, John Doub, William H. TI Evaluation of Impaction Force of Nasal Sprays and Metered-Dose Inhalers Using the Texture Analyser SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE impaction force; nasal spray; MDI; Texture Analyser; design of experiment ID PARAMETERS AB The impaction force from an inhalation product is an important characteristics by which to characterize the spray plume. It is one of the plume characteristics that can be perceived by a patient, and is expected to be good measures of local delivery equivalence for inhalation drugs. A Stable Micro Systems TA-XT.plus Texture Analyser equipped with 750 g load cell was used to measure the impaction force of several nasal sprays and metered-dose inhalers (MDIs). A survey of several commercial nasal spray and MDI products shows that impaction forces of these products varies from 1.5 to 6.5 g force and are significantly different from each other. A 3-level, 4-factor Box-Behnken design was applied to the study of impaction force of nasal sprays using placebo solutions. The influences of four factors: actuation stroke length, actuation velocity, concentration of gelling agent, and concentration of surfactant, were investigated. Of those factors examined here, actuation velocity exerts the greatest effect on impaction force. Impaction force is a discriminative parameter for in vitro testing of nasal spray and MDI products. Since impaction force is more directly related to patient sensation and aerosol deposition in the nasal mucus than other, more traditional parameters, it may provide a better way to evaluate in vitro equivalence in support of abbreviated new drug applications (ANDAS) for orally inhaled and nasal drug products. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2799-2806, 2009 C1 [Guo, Changning; Ye, Wei; Kauffman, John; Doub, William H.] 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 NR 11 TC 5 Z9 5 U1 1 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD AUG PY 2009 VL 98 IS 8 BP 2799 EP 2806 DI 10.1002/jps.21648 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 478PN UT WOS:000268600300022 PM 19097159 ER PT J AU Biancani, PJ Camichael, R Aven, A Calci, K Burkhardt, W Daskin, JH AF Biancani, Peter J. Camichael, Ruth Aven, Allen Calci, Kevin Burkhardt, William, III Daskin, Joshua H. TI AN INNOVATIVE APPROACH TO DETECTING WASTEWATER INFLUENCE ON OYSTERS SO JOURNAL OF SHELLFISH RESEARCH LA English DT Meeting Abstract C1 [Biancani, Peter J.; Camichael, Ruth; Aven, Allen] Univ S Alabama, Dauphin Isl Sea Lab, Dauphin Isl, AL 36528 USA. [Calci, Kevin; Burkhardt, William, III] US FDA, Dauphin Isl, AL 36528 USA. [Daskin, Joshua H.] Brandeis Univ, Waltham, MA 02454 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATL SHELLFISHERIES ASSOC PI GROTON PA C/O DR. SANDRA E. SHUMWAY, UNIV CONNECTICUT, 1080 SHENNECOSSETT RD, GROTON, CT 06340 USA SN 0730-8000 J9 J SHELLFISH RES JI J. Shellfish Res. PD AUG PY 2009 VL 28 IS 3 BP 683 EP 683 PG 1 WC Fisheries; Marine & Freshwater Biology SC Fisheries; Marine & Freshwater Biology GA 546HK UT WOS:000273801700089 ER PT J AU Martinez, MN AF Martinez, M. N. TI Upcoming workshop: exploring complex bioequivalence (BE) issues in veterinary medicine SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Meeting Abstract C1 [Martinez, M. N.] US FDA, Ctr Vet Med, Rockville, MD 20857 USA. NR 1 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 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD AUG PY 2009 VL 32 BP 48 EP 48 PG 1 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 472AI UT WOS:000268100600028 ER PT J AU Grajkowska, LT Pedras-Vasconcelos, JA Sauder, C Verthelyi, D Puig, M AF Grajkowska, Lucja T. Pedras-Vasconcelos, Joao A. Sauder, Christian Verthelyi, Daniela Puig, Montserrat TI High-throughput real-time PCR for early detection and quantitation of arenavirus Tacaribe SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE Tacaribe; Arenavirus; qRT-PCR; Viral hemorrhagic fever; Diagnosis ID MULTIPLE-SCLEROSIS; VIRUS; PATHOGENESIS; ANTIBODIES; DISEASE; HIV AB Arenaviruses merit significant attention both as causative agents of endemic hemorrhagic fevers and as model systems to study the immune response to acute and persistent viral infections. Development of highly sensitive quantitative screening methods to detect arenavirus is critical for early diagnosis of patients, to screen the rodent population in endemic areas, and as a research tool to confirm effective tissue clearance during the development of anti-viral strategies. This study describes a novel sensitive and reproducible method to quantify prototypic new world arenavirus Tacaribe RNA in cell cultures and tissues using a real-time TaqMan PCR-based detection system. The method has a sensitivity of 100 RNA copies per 200 ng of total RNA, making it 2 logs more sensitive than the currently utilized TCID(50) method, and a linear range from 10(2) to 10(9) copies/reaction. The qRT-PCR method is high-throughput and screening can be achieved in <2 h allowing for diagnosis of infected patients before the onset of symptoms. This new method is a powerful tool to screen populations for infection and monitor the clearance achieved by available therapies, and serves as a model diagnostic tool for other arenaviruses. (C) Published by Elsevier B.V. C1 [Grajkowska, Lucja T.; Pedras-Vasconcelos, Joao A.; Verthelyi, Daniela; Puig, Montserrat] US FDA, Div Therapeut Prot, Off Biotechnol Prod, CDER, Bethesda, MD 20892 USA. [Sauder, Christian] US FDA, Div Viral Prod, Off Vaccines Res & Review, CDER, Bethesda, MD 20892 USA. RP Verthelyi, D (reprint author), Bldg 29A,Rm 3B19,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Daniela.verthelyi@fda.hhs.gov NR 20 TC 1 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD AUG PY 2009 VL 159 IS 2 BP 239 EP 243 DI 10.1016/j.jviromet.2009.04.001 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 463TC UT WOS:000267454000016 PM 19490980 ER PT J AU Abdallah, AM Verboom, T Weerdenburg, EM Gey van Pittius, NC Mahasha, PW Jimenez, C Parra, M Cadieux, N Brennan, MJ Appelmelk, B Bitter, W AF Abdallah, Abdallah M. Verboom, Theo Weerdenburg, Eveline M. Gey van Pittius, Nicolaas C. Mahasha, Phetole W. Jimenez, Connie Parra, Marcela Cadieux, Nathalie Brennan, Michael J. Appelmelk, Ben J. Bitter, Wilbert TI PPE and PE_PGRS proteins of Mycobacterium marinum are transported via the type VII secretion system ESX-5 SO MOLECULAR MICROBIOLOGY LA English DT Article ID BACILLE CALMETTE-GUERIN; COMPARATIVE PROTEOME ANALYSIS; COMPLETE GENOME SEQUENCE; BOVIS BCG; PHAGOSOME MATURATION; PROTECTIVE IMMUNITY; EXPRESSION CLONING; ESAT-6 SECRETION; GENE-CLUSTER; TUBERCULOSIS AB ESX-5 is one of the five type VII secretion systems found in mycobacteria. These secretion systems are also known as ESAT-6-like secretion systems. Here, we have determined the secretome of ESX-5 by a proteomic approach in two different strains of Mycobacterium marinum. Comparison of the secretion profile of wild-type strains and their ESX-5 mutants showed that a number of PE_PGRS and PPE-MPTR proteins are dependent on ESX-5 for transport. The PE and PPE protein families are unique to mycobacteria, are highly expanded in several pathogenic species, such as Mycobacterium tuberculosis and M. marinum, and certain family members are cell surface antigens associated with virulence. Using a monoclonal antibody directed against the PGRS domain we showed that nearly all PE_PGRS proteins that are recognized by this antibody are missing in the supernatant of ESX-5 mutants. In addition to PE_PGRS and PPE proteins, the ESX-5 secretion system is responsible for the secretion of a ESAT-6-like proteins. Together, these data show that ESX-5 is probably a major secretion pathway for mycobacteria and that this system is responsible for the secretion of recently evolved PE_PGRS and PPE proteins. C1 [Abdallah, Abdallah M.; Verboom, Theo; Weerdenburg, Eveline M.; Appelmelk, Ben J.; Bitter, Wilbert] Vrije Univ Amsterdam Med Ctr, Dept Med Microbiol & Infect Control, Vumc Canc Ctr Amsterdam, Amsterdam, Netherlands. [Jimenez, Connie] Vrije Univ Amsterdam Med Ctr, OncoProte Lab, Vumc Canc Ctr Amsterdam, Amsterdam, Netherlands. [Gey van Pittius, Nicolaas C.; Mahasha, Phetole W.] Univ Stellenbosch, DST NRF Ctr Excellence Biomed TB Res, Dept Biomed Sci,MRC Ctr Mol & Cellular Biol, Div Mol Biol & Human Genet,Fac Hlth Sci, ZA-7505 Tygerberg, South Africa. [Parra, Marcela; Cadieux, Nathalie; Brennan, Michael J.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Bitter, W (reprint author), Vrije Univ Amsterdam Med Ctr, Dept Med Microbiol & Infect Control, Vumc Canc Ctr Amsterdam, Amsterdam, Netherlands. EM w.bitter@vumc.nl RI Gey van Pittius, Nicolaas/D-3434-2015 OI Gey van Pittius, Nicolaas/0000-0002-8807-4105 FU European Community [201762] FX We acknowledge Mark Alderson (Corixa Corporation, Seattle, USA) and Bryan McLaughlin (UCSF, San Francisco, USA) for the Mtb9.9a and Rv3881c antibodies respectively. We also thank Jaco Knol for help with MS. This work was supported by European Community's Seventh Framework Programme Grant No. 201762 ( to E. M. W. and W. B.). NR 55 TC 104 Z9 114 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD AUG PY 2009 VL 73 IS 3 BP 329 EP 340 DI 10.1111/j.1365-2958.2009.06783.x PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 481FL UT WOS:000268792700002 PM 19602152 ER PT J AU Rudick, RA Polman, CH Cohen, JA Walton, MK Miller, AE Confavreux, C Lublin, FD Hutchinson, M O'Connor, PW Schwid, SR Balcer, LJ Lynn, F Panzara, MA Sandrock, AW AF Rudick, R. A. Polman, C. H. Cohen, J. A. Walton, M. K. Miller, A. E. Confavreux, C. Lublin, F. D. Hutchinson, M. O'Connor, P. W. Schwid, S. R. Balcer, L. J. Lynn, F. Panzara, M. A. Sandrock, A. W. TI Assessing disability progression with the Multiple Sclerosis Functional Composite SO MULTIPLE SCLEROSIS LA English DT Article DE clinical end points; disability progression; multiple sclerosis; Multiple Sclerosis Functional Composite; natalizumab; relapsing-remitting ID PLACEBO-CONTROLLED TRIAL; QUALITY-OF-LIFE; CLINICAL-OUTCOMES ASSESSMENT; TIMED 25-FOOT WALK; DOUBLE-BLIND; REFERENCE POPULATION; INTERFERON BETA-1A; RELIABLE CHANGE; STATUS SCALE; MS AB Background The initial Multiple Sclerosis Functional Composite (MSFC) proposal was a three-part composite of quantitative measures of ambulation, upper extremity function, and cognitive function expressed as a single composite Z-score. However, the clinical meaning of an MSFC Z-score change is not obvious. This study instead used MSFC component data to define a patient-specific disease progression event. Objective Evaluate a new method for analyzing disability progression using the MSFC. Methods MSFC progression was defined as worsening from baseline on scores of at least one MSFC component by 20% (MSFC Progression-20) or 15% (MSFC Progression-15), sustained for >= 3 months. Progression rates were determined using data from natalizumab clinical studies (Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis [AFFIRM] and Safety and Efficacy of Natalizumab in Combination With Interferon Beta-1a in Patients With Relapsing Remitting Multiple Sclerosis [SENTINEL]). Correlations between MSFC progression and other clinical measures were determined, as was sensitivity to treatment effects. Results Substantial numbers of patients met MSFC progression criteria, with MSFC Progression-15 being more sensitive than MSFC Progression-20, at both 1 and 2 years. MSFC Progression-20 and MSFC Progression-15 were related significantly to Expanded Disability Status Scale (EDSS) score change, relapse rate, and the SF-36 Physical Component Summary (PCS) score change. MSFC Progression-20 and MSFC Progression-15 at 1 year were predictive of EDSS progression at 2 years. Both MSFC progression end points demonstrated treatment effects in AFFIRM, and results were replicated in SENTINEL. Conclusion MSFC Progression-20 and MSFC Progression-15 are sensitive measures of disability progression; correlate with EDSS, relapse rates, and SF-36 PCS; and are capable of demonstrating therapeutic effects in randomized, controlled clinical studies. Multiple Sclerosis 2009; 15: 984-997. http://msj.sagepub.com C1 [Rudick, R. A.] Cleveland Clin, Mellen Ctr Multiple Sclerosis Treatment & Res, Neurol Inst, Cleveland, OH 44106 USA. [Polman, C. H.] Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Amsterdam, Netherlands. [Walton, M. K.] US FDA, Ctr Drug Evaluat & Res, Washington, DC 20204 USA. [Miller, A. E.; Lublin, F. D.] Mt Sinai Sch Med, Corinne Goldsmith Dickinson Ctr Multiple Scleros, New York, NY USA. [Confavreux, C.] Hop Neurol, Lyon, France. [Hutchinson, M.] St Vincents Univ Hosp, Dublin 4, Ireland. [O'Connor, P. W.] St Michaels Hosp, Toronto, ON M5B 1W8, Canada. [Schwid, S. R.] Univ Rochester, Med Ctr, Rochester Multiple Sclerosis Ctr, New York, NY USA. [Balcer, L. J.] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Lynn, F.; Panzara, M. A.; Sandrock, A. W.] Biogen Idec Inc, Cambridge, MA USA. RP Rudick, RA (reprint author), Cleveland Clin, Mellen Ctr Multiple Sclerosis Treatment & Res, Neurol Inst, 9500 Euclid Ave, Cleveland, OH 44106 USA. EM rudickr@ccf.org OI hutchinson, michael/0000-0002-8675-1723 FU Biogen Idec; Elan Pharmaceuticals, Inc. FX Meetings of the MSFC Working Group were supported by Biogen Idec and Elan Pharmaceuticals, Inc. The views expressed within this manuscript do not necessarily represent those of the United States Food and Drug Administration. Biogen Idec performed the statistical analyses, and the corresponding author had full access to the data. Hema Gowda, Paul Benfield, and Matthew Hasson of Scientific Connexions, Newtown, Pennsylvania, USA provided editorial assistance in the preparation of this manuscript. Their activities were funded by Biogen Idec and Elan Pharmaceuticals, Inc. NR 31 TC 45 Z9 46 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 JI Mult. Scler. PD AUG PY 2009 VL 15 IS 8 BP 984 EP 997 DI 10.1177/1352458509106212 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 481IC UT WOS:000268800000014 PM 19667023 ER PT J AU Tawakkul, MA Shah, RB Zidan, A Sayeed, VA Khan, MA AF Tawakkul, Mobin A. Shah, Rakhi B. Zidan, Ahmed Sayeed, Vilayat A. Khan, Mansoor A. TI Complexation of risperidone with a taste-masking resin: Novel application of near infra-red and chemical imaging to evaluate complexes SO PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY LA English DT Article DE Polacrilex; amberlite; complexation; characterization; drug release; chemical imaging; calorimetry (DSC); FTIR; near infra-red spectroscopy; raman spectroscopy; x-ray diffractometry ID BETA-CYCLODEXTRIN; BITTER TASTE AB The purpose of the study was to investigate the complexation between a weakly basic drug (risperidone) and an ion exchange resin (amberlite IRP-64) used as a taste-masking agent via two preparation methods: physical mixture and solvent evaporation. Both methods were prepared in different drug-to-resin ratios by weight (1:1, 1:2, 1:4, 1:6). Physicochemical characterizations were performed using differential scanning calorimetry, x-ray diffraction, infra-red spectroscopy, Raman spectroscopy, near infra-red spectroscopy, chemical imaging and drug release studies. These physicochemical techniques revealed that risperidone formed complex with the resin via the solvent evaporation method where enhanced dissolution occurred but not with the physical mixtures. C1 [Tawakkul, Mobin A.; Shah, Rakhi B.; Zidan, Ahmed; Khan, Mansoor A.] US FDA, Div Prod Qual Res, Off Testing & Res, Ctr Drug Evaluat & Res,Off Pharmaceut Sci, Silver Spring, MD 20993 USA. [Sayeed, Vilayat A.] US FDA, Off Gener Drugs, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Khan, MA (reprint author), US FDA, Div Prod Qual Res, Off Testing & Res, Ctr Drug Evaluat & Res,Off Pharmaceut Sci, 10903 New Hampshire Ave,LS Bldg 64, Silver Spring, MD 20993 USA. EM Mansoor.khan@fda.hhs.gov RI Zidan, Ahmed/I-1147-2012 NR 19 TC 13 Z9 13 U1 0 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1083-7450 J9 PHARM DEV TECHNOL JI Pharm. Dev. Technol. PD AUG PY 2009 VL 14 IS 4 BP 409 EP 421 DI 10.1080/10837450802712666 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 487FU UT WOS:000269257100010 PM 19630698 ER PT J AU Ahmad, SR Swann, J AF Ahmad, Syed Rizwanuddin Swann, Joslyn TI Reporting Rates of Hemorrhagic/Necrotizing Pancreatitis (HNP) in Association with Selected Newer Antidiabetics SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Ahmad, Syed Rizwanuddin] FDA CDER, OSE, Div Epidemiol, Silver Spring, MD USA. [Swann, Joslyn] FDA CDER, OSE, Div Pharmacovigilance, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S79 EP S80 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900182 ER PT J AU Alshammari, TM Ahmad, SR Swartz, L Hammad, TA AF Alshammari, Thamir M. Ahmad, Syed Rizwanuddin Swartz, Lynette Hammad, Tarek A. TI Comparison of Adverse Drug Reaction (ADR) Reports Submitted to the FDA by Consumers and Healthcare Professionals (HCPs) SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Alshammari, Thamir M.] Univ Rhode Isl, Kingston, RI 02881 USA. [Ahmad, Syed Rizwanuddin; Swartz, Lynette; Hammad, Tarek A.] US FDA, CDER, Off Surveillance & Epidemiol, Silver Spring, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S4 EP S5 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900010 ER PT J AU Colvin, L Hernandez-Diaz, S Andrews, E Mitchell, A Chambers, T Scott, PE Hill, R AF Colvin, Lyn Hernandez-Diaz, Sonia Andrews, Elizabeth Mitchell, Allen Chambers, Tina Scott, Pamela E. Hill, Richard . TI Assessment of Prenatal Exposure to Medications SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Colvin, Lyn] Telethon Ctr Child Hlth Res, Perth, WA, Australia. [Hernandez-Diaz, Sonia] Harvard SPH, Program Pharmacoepidemiol, Boston, MA USA. [Andrews, Elizabeth] RTI Hlth Solut, Res Triangle Pk, NC USA. [Mitchell, Allen] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. [Chambers, Tina] Univ Calif San Diego, La Jolla, CA 92093 USA. [Scott, Pamela E.] US FDA, OSE, Silver Spring, MD USA. [Hill, Richard .] WHO Collaborating Ctr Int Drug Monitoring, Uppsala, Sweden. RI Colvin, Lyn/F-6886-2012 OI Colvin, Lyn/0000-0002-8492-9954 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S203 EP S203 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900463 ER PT J AU Gagne, JJ Hammad, TA Iyasu, S AF Gagne, Joshua J. Hammad, Tarek A. Iyasu, Solomon TI Individual-Level Time Series Analysis of Antidepressant and Antipsychotic Drug Use Around Varenicline Initiation SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Gagne, Joshua J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hammad, Tarek A.; Iyasu, Solomon] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 0 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 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S41 EP S41 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900094 ER PT J AU Gagne, JJ Hammad, TA Iyasu, S AF Gagne, Joshua J. Hammad, Tarek A. Iyasu, Solomon TI Incident Anticoagulant Use among Users of Extended-Cycle Versus Conventional Oral Contraceptives SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Gagne, Joshua J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hammad, Tarek A.; Iyasu, Solomon] US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S9 EP S10 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900022 ER PT J AU Geier, J Juhaeri, J Mines, D Mosholder, A Trivedi, M Eng, S Skovron, ML Stang, P Volkova, N AF Geier, Jamie Juhaeri, Juhaeri Mines, Daniel Mosholder, Andrew Trivedi, Madhukar Eng, Sybil Skovron, Mary Lou Stang, Paul Volkova, Nataliya TI Assessing the Association of Pharmacotherapeutics and Suicidal Behavior: Lessons from the Front SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Geier, Jamie; Eng, Sybil; Volkova, Nataliya] Pfizer Inc, New York, NY USA. [Juhaeri, Juhaeri] Sanofi Aventis, Bridgewater, NJ USA. [Mines, Daniel] Wyeth Res, Collegeville, PA USA. [Mosholder, Andrew] FDA CDER, Silver Spring, MD USA. [Trivedi, Madhukar] UT SW, Dallas, TX USA. [Skovron, Mary Lou] Bristol Myers Squibb Co, Plainsboro, NJ USA. [Stang, Paul] Johnson & Johnson PRD, Titusville, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S125 EP S125 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900285 ER PT J AU Greene, P Governale, L Borders-Hemphill, V Mehta, H Moeny, D AF Greene, Patty Governale, Laura Borders-Hemphill, Vicky Mehta, Hina Moeny, David TI Trends in Outpatient Drug Utilization Patterns in the US Pediatric Population: Y2002-Y2008 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Greene, Patty; Governale, Laura; Borders-Hemphill, Vicky; Mehta, Hina; Moeny, David] US FDA, Div Epidemiol, OSE, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S57 EP S57 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900130 ER PT J AU Hammad, TA Pamer, C McCune, S Kaplan, S Aly, H Yap, J Iyasu, S AF Hammad, Tarek A. Pamer, Carol McCune, Susan Kaplan, Sigal Aly, Hany Yap, John Iyasu, Solomon TI Association between Maternal Exposure to Antidepressant Drugs and Persistent Pulmonary Hypertension of the Newborn (PPHN) in the Mother-Baby Linked Records in the UK-Based General Practice Research Database (GPRD): Preliminary Results SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Hammad, Tarek A.; Pamer, Carol; McCune, Susan; Kaplan, Sigal; Yap, John; Iyasu, Solomon] US FDA, Silver Spring, MD USA. [Aly, Hany] George Washington Univ, Washington, DC USA. RI Research Datalink, Clinical Practice/H-2477-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S91 EP S92 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900209 ER PT J AU Hammad, TA Pamer, C McCune, S Kaplan, S Aly, H Iyasu, S AF Hammad, Tarek A. Pamer, Carol McCune, Susan Kaplan, Sigal Aly, Hany Iyasu, Solomon TI Validation of Persistent Pulmonary Hypertension in the Newborn (PPHN) within the UK-Based General Practice Research Database (GPRD): Comparing Two Approaches SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Hammad, Tarek A.; Pamer, Carol; McCune, Susan; Kaplan, Sigal; Iyasu, Solomon] US FDA, Silver Spring, MD USA. [Aly, Hany] George Washington Univ, Washington, DC USA. RI Research Datalink, Clinical Practice/H-2477-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S21 EP S22 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900049 ER PT J AU Iyasu, S Hammad, TA Dal Pan, GJ Staff, JA AF Iyasu, Solomon Hammad, Tarek A. Dal Pan, Gerald J. Staff, Judy A. TI The Past, Present and Future of Pharmacoepidemiology at CDER, FDA SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Iyasu, Solomon; Hammad, Tarek A.; Dal Pan, Gerald J.; Staff, Judy A.] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S29 EP S30 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900067 ER PT J AU Kaplan, S La Grenade, L Pamer, C Mackey, AC AF Kaplan, Sigal La Grenade, Lois Pamer, Carol Mackey, Ann Corken TI Evaluation of Current Practices in Drug Adverse Event Reporting Rates: A Methodological Approach for Estimating the Denominator SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Kaplan, Sigal; La Grenade, Lois; Pamer, Carol; Mackey, Ann Corken] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S65 EP S65 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900148 ER PT J AU Kaplan, S Ding, YL Mosholder, A AF Kaplan, Sigal Ding, Yulan Mosholder, Andrew TI Drug Concurrency Patterns among Asthma Patients Using Single-Ingredient LABA: A Claims Data Study SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Kaplan, Sigal; Ding, Yulan; Mosholder, Andrew] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S59 EP S59 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900135 ER PT J AU M'ikanatha, NM Bodeis-Jones, S Lautenbach, E Zhao, SH Folster, JP Medalla, FM Localio, AR Russo, AT Reynolds, S McDermott, PF AF M'ikanatha, Nkuchia M. Bodeis-Jones, Sonya Lautenbach, Ebbing Zhao, Shaohua Folster, Jason P. Medalla, Felicita M. Localio, A. Russell Russo, Anthony T. Reynolds, Stanley McDermott, Patrick F. TI Comparison of Fluoroquinolone and Macrolide Resistance in Campylobacter from Retail Chicken Meat in Pennsylvania with National Data SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [M'ikanatha, Nkuchia M.] Penn Dept Hlth, Harrisburg, PA 17108 USA. [M'ikanatha, Nkuchia M.; Lautenbach, Ebbing; Localio, A. Russell] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Bodeis-Jones, Sonya; Zhao, Shaohua; McDermott, Patrick F.] US FDA, Ctr Vet Med, Laurel, MD USA. [Folster, Jason P.; Medalla, Felicita M.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Localio, A. Russell] Penn Dept Agr, Harrisburg, PA USA. [Reynolds, Stanley] Penn Dept Hlth, Bur Labs, Exton, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 AUG PY 2009 VL 18 BP S215 EP S216 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900492 ER PT J AU Moeny, D La Grenade, L Brinker, A AF Moeny, David La Grenade, Lois Brinker, Allen TI Changes in Topical Calcineurin Use Following Regulatory Actions in the US SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Moeny, David; La Grenade, Lois; Brinker, Allen] US FDA, Silver Spring, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S180 EP S181 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900412 ER PT J AU Raine, JM Dal Pan, G Hauben, M Shibata, A AF Raine, June M. Dal Pan, Gerald Hauben, Manfred Shibata, Atsuko TI Practical Aspects of Signal Detection in Pharmacovigilance-The CIOMS VIII Report SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Raine, June M.] Vigilance & Risk Management Med & Healthcare Prod, London, England. [Dal Pan, Gerald] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. [Shibata, Atsuko] Amgen Inc, Global Regulatory Affairs & Safety, Thousand Oaks, CA 91320 USA. [Hauben, Manfred] Pfizer Inc, Risk Management Strategy, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S204 EP S205 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900466 ER PT J AU Ritchey, M Funk, MJ Marshall, S Marinac-Dabic, D Rutala, W Weber, D AF Ritchey, Mary Funk, Michele Jonsson Marshall, Stephen Marinac-Dabic, Danica Rutala, William Weber, David TI Changing Rate of Blood-Stream Infection across Duration of Central Venous Access SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Ritchey, Mary; Funk, Michele Jonsson; Marshall, Stephen; Weber, David] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Marinac-Dabic, Danica] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Rutala, William; Weber, David] Univ N Carolina Hosp, Hosp Epidemiol, Chapel Hill, NC USA. RI Jonsson Funk, Michele/F-6885-2011 OI Jonsson Funk, Michele/0000-0002-3756-7540 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S117 EP S118 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900268 ER PT J AU Rothman, K Dal Pan, G Evans, S Stang, P Jones, J Sturmer, T AF Rothman, Ken Dal Pan, Gerald Evans, Stephen Stang, Paul Jones, Judith Sturmer, Til TI The Future of Epidemiology SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Rothman, Ken] Newton Ctr, RTI, Newton, MA USA. [Dal Pan, Gerald] US FDA, Silver Spring, MD USA. [Evans, Stephen] LSHTM, London, England. [Stang, Paul] J&J, Titusville, NJ USA. [Jones, Judith] Degge Grp, Arlington, VA USA. [Sturmer, Til] UNC, Chapel Hill, NC USA. NR 0 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 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S205 EP S205 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900468 ER PT J AU Saddier, P Perez-Gutthann, S Stem-hagen, A Garg, R Blackburn, S Dal Pan, G AF Saddier, Patricia Perez-Gutthann, Susana Stem-hagen, Annette Garg, Rekha Blackburn, Stella Dal Pan, Gerald TI RMP, RiskMAP and REMS: The Challenges of Epidemiology SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Saddier, Patricia] Merck Res Labs, N Wales, PA USA. [Perez-Gutthann, Susana] RTI Hlth Solut, Barcelona, Spain. [Stem-hagen, Annette] United BioSource Corp, Blue Bell, PA USA. [Garg, Rekha] Amgen Inc, Thousand Oaks, CA USA. [Blackburn, Stella] EMEA, London, England. [Dal Pan, Gerald] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S203 EP S204 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900464 ER PT J AU Sandhu, SK Burwen, D MaCurdy, T Gibbs, J Rusev, E Garcia, B Sholley, C Marston, D Elmo, K Izurieta, H Ball, R AF Sandhu, S. K. Burwen, D. MaCurdy, T. Gibbs, J. Rusev, E. Garcia, B. Sholley, C. Marston, D. Elmo, K. Izurieta, H. Ball, R. TI Comparison of Alpha-Spending Plans for Influenza Vaccine Safety Surveillance SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Sandhu, S. K.; Burwen, D.; Izurieta, H.; Ball, R.] US FDA, Rockville, MD 20857 USA. [MaCurdy, T.; Gibbs, J.; Rusev, E.; Garcia, B.; Sholley, C.] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. [Marston, D.; Elmo, K.] Acumen LLC, Burlingame, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S35 EP S35 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900080 ER PT J AU Zhang, HT Hammad, TA Christiani, D Giovannuci, E AF Zhang, Hui-Talia Hammad, Tarek A. Christiani, David Giovannuci, Edward TI The Risk of Cancer Associated with Anti-Diabetic Agents SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Zhang, Hui-Talia; Christiani, David; Giovannuci, Edward] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Zhang, Hui-Talia; Hammad, Tarek A.] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2009 VL 18 BP S39 EP S39 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 483YQ UT WOS:000269009900090 ER PT J AU Miller, SA Beer, JZ Savalia, V AF Miller, Sharon A. Beer, Janusz Z. Savalia, Varsha TI Commentary on 'Indoor tanning injuries: an evaluation of FDA adverse event reporting data' SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE LA English DT Editorial Material ID FACILITIES; STATE C1 [Miller, Sharon A.; Beer, Janusz Z.; Savalia, Varsha] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Miller, SA (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62,Rm 114, Silver Spring, MD 20993 USA. EM SharonA.Miller@fda.hhs.gov NR 6 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0905-4383 J9 PHOTODERMATOL PHOTO JI Photodermatol. Photoimmunol. Photomed. PD AUG PY 2009 VL 25 IS 4 BP 223 EP 224 PG 2 WC Dermatology SC Dermatology GA 469GU UT WOS:000267885200010 PM 19614903 ER PT J AU Getie-Kebtie, M Chen, D Eichelberger, M Alterman, M AF Getie-Kebtie, Melkamu Chen, David Eichelberger, Maryna Alterman, Michail TI Proteomics-based characterization of hemagglutinins in different strains of influenza virus SO PROTEOMICS CLINICAL APPLICATIONS LA English DT Article DE Antigenic drift; Hemagglutinin; Influenza; Unique peptides; Vaccine ID SINGLE-RADIAL-IMMUNODIFFUSION; MASS-SPECTROMETRY; VACCINE STRAINS; QUANTIFICATION; IDENTIFICATION; ASSAY AB Infection with influenza A (subtypes H1N1 and H3N2) or B viruses results in over half a million deaths worldwide every year. Frequent antigenic changes (drift) in two major viral surface proteins hemagglutinin (HA) and neuraminidase lead to the constant emergence of antigenically distinct virus strains against which there is sub-optimal immunity in the population. Consequently the suitability of the viral strains included in the trivalent influenza vaccine (TIV) has to be re-evaluated annually. While virus seeds selected for vaccine manufacture are very well characterized, there is no assay in place to identify the source of HA in the formulated trivalent vaccine. Our study describes a proteomics-based method to identify the HA strain (not just subtype) and more fully characterize the final vaccine product. Unique and shared tryptic peptides of HAs were predicted by in silico tryptic digest of different influenza A and B virus strains. Recombinant HA and whole virus preparations of selected strains were then digested to identify the peptides detected by MS. Both subtype and strain-specific peptides were observed. The feasibility of this method to accurately identify HA strains in an inactivated TIV was tested using a 2006/2007 formulation. Each of the three HAs in the vaccine was identified in addition to a number of other viral and non-viral proteins. In summary, MS is a powerful method that is both specific and inclusive; in a single analysis, HAs of individual virus strains can be identified and the composition of the TIV fully characterized. C1 [Getie-Kebtie, Melkamu; Alterman, Michail] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Chen, David; Eichelberger, Maryna] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Alterman, M (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bldg 29A,Room 2D12,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Michail.Alterman@fda.hhs.gov FU CB ER Pandemic Influenza Unmet Needs; Biomedical Advanced Research and Development Authority FX This project was supported by funding provided by the CB ER Pandemic Influenza Unmet Needs and by the Biomedical Advanced Research and Development Authority. NR 24 TC 8 Z9 9 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1862-8346 J9 PROTEOM CLIN APPL JI Proteom. Clin. Appl. PD AUG PY 2009 VL 3 IS 8 BP 979 EP 988 DI 10.1002/prca.200800219 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 493HS UT WOS:000269728000009 PM 21137000 ER PT J AU Gendel, SM AF Gendel, Steven M. TI Allergen databases and allergen semantics SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT International Workshop on Current and Future Methods for Evaluating the Allergenic Potential of Proteins CY OCT 23-25, 2007 CL Nice, FRANCE SP Health & Environ Sci Inst, Protein Allergenic Tech Committ DE Food allergy; Food safety; Informatics; Allergen sequences; Database; Semantic web ID POTENTIAL ALLERGENICITY; SEQUENCE DATABASES; ONTOLOGY; PROTEINS AB The efficacy of any specific bioinformatic analysis of the potential allergenicity of new food proteins depends directly on the nature and content of the databases that are used in the analysis. A number of different allergen-related databases have been developed, each designed to meet a different need. These databases differ in content, organization, and accessibility. These differences create barriers for users and prevent data sharing and integration. The development and application of appropriate semantic web technologies, (for example, a food allergen ontology) could help to overcome these barriers and promote the development of more advanced analytic capabilities. Published by Elsevier Inc. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Gendel, SM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM steven.gendel@fda.hhs.gov NR 16 TC 7 Z9 7 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 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD AUG PY 2009 VL 54 IS 3 BP S7 EP S10 DI 10.1016/j.yrtph.2008.10.011 PG 4 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 476TZ UT WOS:000268470100003 PM 19095034 ER PT J AU Chiesa, OA von Bredow, J Smith, M Thomas, M AF Chiesa, Oscar Alberto von Bredow, Jurgen Smith, Michelle Thomas, Michael TI One-port video assisted laparoscopic kidney biopsy in standing steers SO RESEARCH IN VETERINARY SCIENCE LA English DT Article DE One-port; Kidney; Biopsy; Laparoscopy; Cattle; Standing ID RENAL BIOPSY; CATTLE AB The purpose of this study was to simplify the two-port laparoscopic renal biopsy technique used in support of pharmacokinetic studies through the application of a one-port system. Twelve Holstein steers were fasted for 24 h and sedated with acepromazine and xylaxine in preparation for laparoscopic surgery in standing stocks. Lidocaine 2% was injected to provide local anesthesia for introduction of the trocar-cannula assembly. The operating endoscope was inserted and the abdomen was insufflated with CO(2). A biopsy forceps was introduced into the channel of the operating endoscope to obtain a 100 mg kidney cortex sample. Eighteen laparoscopic procedures provided 18 kidney samples suitable for pharmacokinetic studies. No complications were encountered. The one-port laparoscopic kidney biopsy is feasible and safe, and advanced skill required for triangulation is not necessary for its performance. Published by Elsevier Ltd. C1 [Chiesa, Oscar Alberto; von Bredow, Jurgen; Smith, Michelle; Thomas, Michael] US FDA, Ctr Vet Med, Res Off, Div Residue Chem, Laurel, MD 20708 USA. RP Chiesa, OA (reprint author), US FDA, Ctr Vet Med, Res Off, Div Residue Chem, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM oscar.chiesa@fda.hhs.gov NR 10 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0034-5288 J9 RES VET SCI JI Res. Vet. Sci. PD AUG PY 2009 VL 87 IS 1 BP 133 EP 134 DI 10.1016/j.rvsc.2008.10.016 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA 455HC UT WOS:000266748200028 PM 19081120 ER PT J AU Zhang, ZW AF Zhang, Zhiwei TI Covariate-Adjusted Putative Placebo Analysis in Active-Controlled Clinical Trials SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH LA English DT Article DE Causal inference; Conditional effect; Constancy; Discounting; Noninferiority; Potential outcome AB Even though an active-controlled trial provides no information about placebo, investigators and regulators often wonder how the experimental treatment would compare to placebo should a placebo arm be included in the study. A putative placebo analysis attempts to address this question by combining information from previous studies comparing the active control with placebo. Such an analysis often requires a constancy assumption, namely that the control effect relative to placebo is constant across studies. When the constancy assumption is in doubt, there are ad hoc methods that "discount" the historical data in conservative ways. This article presents a different approach that does not require constancy or involve discounting, but rather attempts to adjust for any imbalances in covariates between the current and historical studies. This covariate-adjusted approach is valid under a conditional constancy assumption which requires only that the control effect be constant within each subpopulation characterized by the observed covariates. Simulation results show that the proposed method performs reasonably well in moderate-sized samples. The method is illustrated with an example concerning benign prostate hyperplasia. C1 US FDA, Div Biostat, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Zhang, ZW (reprint author), US FDA, Div Biostat, Ctr Devices & Radiol Hlth, 1350 Piccard Dr,HFZ-550, Rockville, MD 20850 USA. EM zhiwei.zhang@fda.hhs.gov NR 21 TC 6 Z9 6 U1 0 U2 2 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 1946-6315 J9 STAT BIOPHARM RES JI Stat. Biopharm. Res. PD AUG PY 2009 VL 1 IS 3 BP 279 EP 290 DI 10.1198/sbr.2009.0034 PG 12 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA V17ZK UT WOS:000207974900006 ER PT J AU Zhang, J Goering, PL Espandiari, P Shaw, M Bonventre, JV Vaidya, VS Brown, RP Keenan, J Kilty, CG Sadrieh, N Hanig, JP AF Zhang, Jun Goering, Peter L. Espandiari, Parvaneh Shaw, Martin Bonventre, Joseph V. Vaidya, Vishal S. Brown, Ronald P. Keenan, Joe Kilty, Cormac G. Sadrieh, Nakissa Hanig, Joseph P. TI Differences in Immunolocalization of Kim-1, RPA-1, and RPA-2 in Kidneys of Gentamicin-, Cisplatin-, and Valproic Acid-Treated Rats: Potential Role of iNOS and Nitrotyrosine SO TOXICOLOGIC PATHOLOGY LA English DT Article DE cisplatin; gentamicin; Kim-1; nitrotyrosine; RPA-1; RPA-2 ID RENAL ISCHEMIA/REPERFUSION INJURY; PROXIMAL TUBULE CELLS; NITRIC-OXIDE; MONOCLONAL-ANTIBODIES; DIFFERENT FIXATIVES; PAPILLARY ANTIGENS; URINARY ANTIGENS; NEPHROTOXICITY; PEROXYNITRITE; INHIBITION AB The present study compared the immunolocalization of Kim-1, renal papillary antigen (RPA)-1, and RPA-2 with that of inducible nitric oxide synthase (iNOS) and nitrotyrosine in kidneys of gentamicin sulfate (Gen)- and cisplatin (Cis)- treated rats. The specificity of acute kidney injury (AKI) biomarkers, iNOS, and nitrotyrosine was evaluated by dosing rats with valproic acid (VPA). Sprague-Dawley (SD) rats were injected subcutaneously (sc) with 100 mg/kg/day of Gen for six or fourteen days; a single intraperitoneal (ip) dose of 1, 3, or 6 mg/kg of Cis; or 650 mg/kg/day of VPA (ip) for four days. In Gen-treated rats, Kim-1 was expressed in the epithelial cells, mainly in the S1/S2 segments but less so in the S3 segment, and RPA-1 was increased in the epithelial cells of collecting ducts (CD) in the cortex. Spatial expression of iNOS or nitrotyrosine with Kim-1 or RPA-1 was detected. In Cis-treated rats, Kim-1 was expressed only in the S3 segment cells, and RPA-1 and RPA-2 were increased in the epithelial cells of medullary CD or medullary loop of Henle (LH), respectively. Spatial expression of iNOS or nitrotyrosine with RPA-1 or RPA-2 was also identified. These findings suggest that peroxynitrite formation may be involved in the pathogenesis of Gen and Cis nephrotoxicity and that Kim-1, RPA-1, and RPA-2 have the potential to serve as site-specific biomarkers for Gen or Cis AKI. C1 [Zhang, Jun; Espandiari, Parvaneh; Sadrieh, Nakissa; Hanig, Joseph P.] Food & Drug Adm, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Goering, Peter L.; Brown, Ronald P.] Food & Drug Adm, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Shaw, Martin; Keenan, Joe; Kilty, Cormac G.] Argutus Med Ltd, Dublin, Ireland. [Bonventre, Joseph V.; Vaidya, Vishal S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Renal Div,Harvard Inst Med, Boston, MA 02115 USA. RP Zhang, J (reprint author), Food & Drug Adm HFD 910, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM jun.zhang@fda.hhs.gov FU NIDDK NIH HHS [R01 DK072381]; NIEHS NIH HHS [R00 ES016723, R00 ES016723-02] NR 38 TC 22 Z9 24 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD AUG PY 2009 VL 37 IS 5 BP 629 EP 643 DI 10.1177/0192623309339605 PG 15 WC Pathology; Toxicology SC Pathology; Toxicology GA 476WF UT WOS:000268476400007 PM 19535489 ER PT J AU Keenan, C Elmore, S Francke-Carroll, S Kerlin, R Peddada, S Pletcher, J Rinke, M Schmidt, SP Taylor, I Wolf, DC AF Keenan, Charlotte Elmore, Susan Francke-Carroll, Sabine Kerlin, Roy Peddada, Shyamal Pletcher, John Rinke, Matthias Schmidt, Stephen Peter Taylor, Ian Wolf, Douglas C. TI Potential for a Global Historical Control Database for Proliferative Rodent Lesions SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material C1 [Keenan, Charlotte] GlaxoSmithKline Inc, King Of Prussia, PA 19406 USA. [Elmore, Susan] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Francke-Carroll, Sabine] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Pletcher, John] Charles River, Frederick, MD 21701 USA. [Rinke, Matthias] Bayer Schering Pharma AG, Wuppertal, Germany. [Kerlin, Roy; Schmidt, Stephen Peter] Pfizer Inc, Groton, CT 06340 USA. [Taylor, Ian] Huntingdon Life Sci, Eye IP23 7PX, Suffolk, England. [Wolf, Douglas C.] US EPA, Res Triangle Pk, NC 27711 USA. RP Keenan, C (reprint author), GlaxoSmithKline Inc, 709 Swedeland Rd,UE0360, King Of Prussia, PA 19406 USA. EM charlotte.m.keenan@gsk.com RI Peddada, Shyamal/D-1278-2012 FU Intramural NIH HHS NR 3 TC 3 Z9 3 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD AUG PY 2009 VL 37 IS 5 BP 677 EP 678 DI 10.1177/0192623309336155 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 476WF UT WOS:000268476400012 PM 19638441 ER PT J AU Keenan, C Elmore, S Francke-Carroll, S Kemp, R Kerlin, R Peddada, S Pletcher, J Rinke, M Schmidt, SP Taylor, I Wolf, DC AF Keenan, Charlotte Elmore, Susan Francke-Carroll, Sabine Kemp, Ramon Kerlin, Roy Peddada, Shyamal Pletcher, John Rinke, Matthias Schmidt, Stephen Peter Taylor, Ian Wolf, Douglas C. TI Best Practices for Use of Historical Control Data of Proliferative Rodent Lesions SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material DE historical control data; rodent tumors; carcinogenicity studies; best practices ID NATIONAL TOXICOLOGY PROGRAM; SPRAGUE-DAWLEY RATS; DUAL CONTROL-GROUPS; WISTAR RATS; BODY-WEIGHT; SPONTANEOUS TUMORS; B6C3F1 MICE; JOINT PUBLICATION; REVISED GUIDES; NACAD GROUPS C1 [Keenan, Charlotte] GlaxoSmithKline Inc, King Of Prussia, PA 19406 USA. [Elmore, Susan] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Francke-Carroll, Sabine] US FDA, CFSAN, College Pk, MD USA. [Kemp, Ramon] Merck Res Labs, Riom, France. [Kerlin, Roy; Schmidt, Stephen Peter] Pfizer Inc, Groton, CT 06340 USA. [Pletcher, John] Charles River, Frederick, MD USA. [Rinke, Matthias] Bayer Schering Pharma AG, Wuppertal, Germany. [Wolf, Douglas C.] US EPA, Res Triangle Pk, NC 27711 USA. RP Keenan, C (reprint author), GlaxoSmithKline Inc, 79 Swedeland Rd,UE0360, King Of Prussia, PA 19406 USA. EM charlotte.m.keenan@gsk.com RI Peddada, Shyamal/D-1278-2012 FU Intramural NIH HHS NR 114 TC 43 Z9 44 U1 0 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD AUG PY 2009 VL 37 IS 5 BP 679 EP 693 DI 10.1177/0192623309336154 PG 15 WC Pathology; Toxicology SC Pathology; Toxicology GA 476WF UT WOS:000268476400013 PM 19454599 ER PT J AU Tournas, VH Memon, SU AF Tournas, V. H. Memon, S. Uppal TI Internal contamination and spoilage of harvested apples by patulin-producing and other toxigenic fungi SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE Toxigenic moulds; Apples; Internal contamination ID PENICILLIUM-EXPANSUM; MYCOTOXIN PATULIN; CELLS; POPULATIONS; FRUITS; TOXINS AB A total of 424 apple samples comprised of six varieties (Gala. Red Delicious, Golden Delicious, Fuji, Granny Smith. and Braeburn) were analyzed for internal fungal contamination. Two hundred sixteen apples were incubated intact for 2-4 weeks at room temperature. The cores of the remaining 208 apples were aseptically removed and incubated without supplemental media at room temperature for 3 weeks. After the incubation period was over, the mycological profiles of the analyzed samples were determined. Twelve per cent of the intact apples showed visible growth after 2-4 weeks of incubation at room temperature. Penicillia (including the patulin producer, Penicillium expansum) were the most frequent. found in 8% of the samples followed by Fusarium and Alternaria spp. (each found in 3% of the samples tested). The highest mould incidence was observed in the Red Delicious and Fuji and the lowest in the Granny Smith variety. A variety of microfungi including members of the toxigenic genera Alternaria, Penicillium and Fusarium were isolated from the apple cores. The predominant moulds were Alternaria, Cladosporium, Penicillium and Fusarium spp. recovered from 50, 22, 33 and 23% of the analyzed samples, respectively. Less common were Ulocladium spp., Botrytis cinerea and Aureobasidium pullulans found in less than 4% of the samples. Yeasts were found only in 2% of the samples. Apple cores from all varieties tested showed a high degree of mould contamination. Published by Elsevier B.V. C1 [Tournas, V. H.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Memon, S. Uppal] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20740 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 FU FDA funds FX We are grateful to our colleagues Eugenia Katsouclas and Jeffrey Kohn (FDA) for their constructive comments during the preparation of the manuscript. This research was solely supported by FDA funds. NR 31 TC 15 Z9 15 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD JUL 31 PY 2009 VL 133 IS 1-2 BP 206 EP 209 DI 10.1016/j.ijfoodmicro.2009.05.025 PG 4 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 473PK UT WOS:000268219600028 PM 19524316 ER PT J AU Millet, C Yamashita, M Heller, M Yu, LR Veenstra, TD Zhang, YE AF Millet, Caroline Yamashita, Motozo Heller, Mary Yu, Li-Rong Veenstra, Timothy D. Zhang, Ying E. TI A Negative Feedback Control of Transforming Growth Factor-beta Signaling by Glycogen Synthase Kinase 3-mediated Smad3 Linker Phosphorylation at Ser-204 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TGF-BETA; UBIQUITIN LIGASE; TRANSCRIPTIONAL ACTIVATION; CRYSTAL-STRUCTURE; BMP; DEGRADATION; PATHWAYS; DOMAIN; PROTEIN; IDENTIFICATION AB Through the action of its membrane-bound type I receptor, transforming growth factor-beta (TGF-beta) elicits a wide range of cellular responses that regulate cell proliferation, differentiation, and apoptosis. Many of these signaling responses are mediated by Smad proteins. As such, controlling Smad activity is crucial for proper signaling by TGF-beta and its related factors. Here, we show that TGF-beta induces phosphorylation at three sites in the Smad3 linker region in addition to the two C-terminal residues, and glycogen synthase kinase 3 is responsible for phosphorylation at one of these sites, namely Ser-204. Alanine substitution at Ser-204 and/or the neighboring Ser-208, the priming site for glycogen synthase kinase 3 in vivo activity, strengthened the affinity of Smad3 to CREB-binding protein, suggesting that linker phosphorylation may be part of a negative feedback loop that modulates Smad3 transcriptional activity. Thus, our findings reveal a novel aspect of the Smad3 signaling mechanism that controls the final amplitude of cellular responses to TGF-beta. C1 [Millet, Caroline; Yamashita, Motozo; Heller, Mary; Zhang, Ying E.] NCI, Ctr Canc Res, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Yu, Li-Rong] US FDA, Natl Ctr Toxicol Res, Ctr Prote, Div Syst Toxicol, Jefferson, AR 72079 USA. [Veenstra, Timothy D.] SAIC Frederick Inc, Lab Prote & Analyt Technol, Adv Technol Program, Frederick, MD 21702 USA. [Veenstra, Timothy D.] NCI, NIH, Frederick, MD 21702 USA. RP Zhang, YE (reprint author), NCI, Ctr Canc Res, Cellular & Mol Biol Lab, NIH, 37 Convent Dr,Bldg 37,Rm 2056B, Bethesda, MD 20892 USA. EM yingz@helix.nih.gov RI Zhang, Ying/G-3657-2015 OI Zhang, Ying/0000-0003-2753-7601 FU National Institutes of Health, NCI, Center for Cancer Research, Intramural Research Program; NCI [N01-CO-12400] FX This work was supported, in whole or in part, by the National Institutes of Health, NCI, Center for Cancer Research, Intramural Research Program and is funded in part by National Institutes of Health Contract N01-CO-12400 from NCI. NR 39 TC 40 Z9 42 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 24 PY 2009 VL 284 IS 30 BP 19808 EP 19816 DI 10.1074/jbc.M109.016667 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 471ZO UT WOS:000268097400007 PM 19458083 ER PT J AU Sun, L Haun, S Jones, RC Edmondson, RD Machaca, K AF Sun, Lu Haun, Shirley Jones, Richard C. Edmondson, Ricky D. Machaca, Khaled TI Kinase-dependent Regulation of Inositol 1,4,5-Trisphosphate-dependent Ca2+ Release during Oocyte Maturation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNALING DIFFERENTIATION; CALCIUM-RELEASE; PROTEIN-KINASE; XENOPUS-LAEVIS; ENDOPLASMIC-RETICULUM; STATISTICAL-MODEL; EGG ACTIVATION; CELL-CYCLE; RECEPTOR; PHOSPHORYLATION AB Fertilization induces a species-specific Ca2+ transient with specialized spatial and temporal dynamics, which are essential to temporally encode egg activation events such as the block to polyspermy and resumption of meiosis. Eggs acquire the competence to produce the fertilization-specific Ca2+ transient during oocyte maturation, which encompasses dramatic potentiation of inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ release. Here we show that increased IP3 receptor (IP3R) sensitivity is initiated at the germinal vesicle breakdown stage of maturation, which correlates with maturation promoting factor (MPF) activation. Extensive phosphopeptide mapping of the IP3R resulted in similar to 70% coverage and identified three residues, Thr-931, Thr-1136, and Ser-114, which are specifically phosphorylated during maturation. Phospho-specific antibody analyses show that Thr-1136 phosphorylation requires MPF activation. Activation of either MPF or the mitogen-activated protein kinase cascade independently, functionally sensitizes IP3-dependent Ca2+ release. Collectively, these data argue that the kinase cascades driving meiotic maturation potentiates IP3-dependent Ca2+ release, possibly trough direct phosphorylation of the IP3R. C1 [Sun, Lu; Haun, Shirley; Machaca, Khaled] Univ Arkansas Med Sci, Dept Physiol & Biophys, Little Rock, AR 72205 USA. [Jones, Richard C.; Edmondson, Ricky D.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Machaca, Khaled] Qatar Fdn, Weill Cornell Med Coll, Doha, Qatar. RP Machaca, K (reprint author), POB 24144, Doha, Qatar. EM khm2002@qatar-med.cornell.edu OI Machaca, Khaled/0000-0001-6215-2411 FU National Institutes of Health, NIGMS [GM61829] FX This work was supported, in whole or in part, by National Institutes of Health Grant GM61829 from NIGMS. NR 42 TC 20 Z9 20 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 24 PY 2009 VL 284 IS 30 BP 20184 EP 20196 DI 10.1074/jbc.M109.004515 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 471ZO UT WOS:000268097400046 PM 19473987 ER PT J AU Cole, KD Pease, LF Tsai, DH Singh, T Lute, S Brorson, KA Wang, LL AF Cole, Kenneth D. Pease, Leonard F., III Tsai, De-Hao Singh, Tania Lute, Scott Brorson, Kurt A. Wang, Lili TI Particle concentration measurement of virus samples using electrospray differential mobility analysis and quantitative amino acid analysis SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Electrospray; Differential mobility analysis; Amino acid analysis; Virus concentration ID FIELD-FLOW FRACTIONATION; MEMBRANE-FILTER; BACTERIOPHAGE-MS2; PCR; PROTEIN; ELECTROPHORESIS; MICROSCOPY; FILTRATION; SCATTERING; COMPLEXES AB Virus reference materials are needed to develop and calibrate detection devices and instruments. We used electrospray differential mobility analysis (ES-DMA) and quantitative amino acid analysis (AAA) to determine the particle concentration of three small model viruses (bacteriophages MS2, PP7, and phi X174). The biological activity, purity, and aggregation of the virus samples were measured using plaque assays, denaturing gel electrophoresis, and size-exclusion chromatography. ES-DMA was developed to count the virus particles using gold nanoparticles as internal standards. ES-DMA additionally provides quantitative measurement of the size and extent of aggregation in the virus samples. Quantitative AAA was also used to determine the mass of the viral proteins in the pure virus samples. The samples were hydrolyzed and the masses of the well-recovered amino acids were used to calculate the equivalent concentration of vital particles in the samples. The concentration of the virus samples determined by ES-DMA was in good agreement with the concentration predicted by AAA for these purified samples. The advantages and limitations of ES-DMA and AAA to characterize virus reference materials are discussed. Published by Elsevier B.V. C1 [Cole, Kenneth D.; Tsai, De-Hao; Singh, Tania; Wang, Lili] NIST, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA. [Pease, Leonard F., III] Univ Utah, Dept Chem Engn, Salt Lake City, UT 84112 USA. [Lute, Scott; Brorson, Kurt A.] FDA, CDER, Div Monoclonal Antibodies, Silver Spring, MD 20903 USA. RP Cole, KD (reprint author), NIST, Chem Sci & Technol Lab, Mailstop 8312,100 Bur Dr, Gaithersburg, MD 20899 USA. EM Kenneth.Cole@nist.gov RI Zhou, Feng/E-9510-2011; Tsai, De-Hao/K-6702-2012 OI Tsai, De-Hao/0000-0002-2669-3007 FU U.S. Department of Homeland Security FX We wish to thank Dr. Bert Coursey (U.S. Department of Homeland Security) for support of this project. NR 51 TC 13 Z9 13 U1 2 U2 10 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 JUL 24 PY 2009 VL 1216 IS 30 BP 5715 EP 5722 DI 10.1016/j.chroma.2009.05.083 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 471RA UT WOS:000268074800013 PM 19545873 ER PT J AU Sainathrao, S Mohan, KVK Atreya, C AF Sainathrao, Shilpakala Mohan, Ketha V. Krishna Atreya, Chintamani TI Gamma-phage lysin PlyG sequence-based synthetic peptides coupled with Qdot-nanocrystals are useful for developing detection methods for Bacillus anthracis by using its surrogates, B. anthracis-Sterne and B. cereus-4342 SO BMC BIOTECHNOLOGY LA English DT Article ID INHALATIONAL ANTHRAX; BINDING; IDENTIFICATION; INFECTIONS; ENZYMES AB Background: Previous reports of site-directed deletion analysis on gamma (gamma)-phage lysin protein (PlyG) have demonstrated that removal of a short amino acid sequence in the C-terminal region encompassing a 10-amino acid motif (190LKMTADFILQ199) abrogates its binding activity specific to the cell wall of Bacillus anthracis. Whether short synthetic peptides representing the 10-amino acid PlyG putative binding motif flanked by surrounding N- and C-terminal residues also selectively bind to the bacterial cell wall has not been evaluated. If such peptides do demonstrate selective binding to the cell wall, they could serve as bio-probes towards developing detection technologies for B. anthracis. Furthermore, by using B. anthracis (Sterne, 34F2), an animal vaccine and B. cereus-4342, a gamma-phage susceptible rare strain as surrogates of B. anthracis, development of proof-of-concepts for B. anthracis are feasible. Results: Using four different methods, we evaluated six synthetic peptides representing the putative binding motif including flanking sequences (PlyG-P1 through P6) for the bacterial cell wall binding capacity. Our analysis identified PlyG-P1, PlyG-P3 and PlyG-P5 to have binding capability to both B. anthracis (Sterne, 34F2) and B. cereus-4342. The peptides however did not bind to B. cereus-11778, B. thuringiensis, and B. cereus-10876 suggesting their specificity for B. anthracis-Sterne and B. cereus-4342. PlyG-P3 in combination with fluorescent light microscopy detected even a single bacterium in plasma spiked with the bacteria. Conclusion: Overall, these studies illustrate that the short 10-amino acid sequence 'LKMTADFILQ' in fact is a stand-alone bacterial cell wall-binding motif of PlyG. In principle, synthetic peptides PlyG-P1, PlyG-P3 and PlyG-P5, especially PlyG-P3 coupled with Qdot-nanocrystals are useful as high-sensitivity bio-probes in developing detection technologies for B. anthracis. C1 [Sainathrao, Shilpakala; Mohan, Ketha V. Krishna; Atreya, Chintamani] US FDA, Sect Cell Biol, Lab Cellular Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Atreya, C (reprint author), US FDA, Sect Cell Biol, Lab Cellular Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM shilpakala.sainathrao@fda.hhs.gov; krishna.ketha@fda.hhs.gov; chintamani.atreya@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 CA. SS is a recipient of a postdoctoral fellowship at the Center for Biologics Evaluation and Research (CBER) administered by the Oak Ridge Institute for Science and Education (ORISE) through an intra agency agreement between the U. S. Department of Energy and the U. S. Food and Drug Administration. Authors wish to thank Kannan Meghanathan and Sandhya Kulkarni, CBER for their review of the manuscript. The findings and conclusions in this report have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy. NR 25 TC 18 Z9 19 U1 0 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1472-6750 J9 BMC BIOTECHNOL JI BMC Biotechnol. PD JUL 22 PY 2009 VL 9 AR 67 DI 10.1186/1472-6750-9-67 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 488NG UT WOS:000269355900001 PM 19624851 ER PT J AU Tareke, E Lyn-Cook, BD Duhart, H Newport, G Ali, S AF Tareke, Eden Lyn-Cook, Beverly D. Duhart, Helen Newport, Glenn Ali, Syed TI Acrylamide decreased dopamine levels and increased 3-nitrotyrosine (3-NT) levels in PC 12 cells SO NEUROSCIENCE LETTERS LA English DT Article DE Acrylamide; PC 12 cells; Dopamine; 3-Nitrotyrosine ID IN-VITRO NEUROTOXICITY; HEMOGLOBIN ADDUCTS; NITRIC-OXIDE; NEUROTRANSMITTER RECEPTORS; OCCUPATIONAL-EXPOSURE; BRAIN-REGIONS; TREATED RATS; L-CARNITINE; SUPEROXIDE; CARCINOGEN AB Acrylamide is a chemical known to produce neurotoxicity in animals, as well as in humans. The mechanism of acrylamide-induced neurotoxicity is not fully known. However, recent studies have revealed that acrylamide affects the dopaminergic system. Therefore, the aim of this study was to investigate the effect of acrylamide on dopamine (DA) and the metabolites, 3,4-dihydroxy phenylacetic acid (DOPAC) and homovanillicacid (HVA), levels in Pheochromocytoma (PC 12) cells. In addition, the generation of peroxynitrite (ONOO(-)), measured by 3-nitrotyrosine (3-NT), was investigated as a possible mechanism in acrylamide-induced neurotoxicity. HPLC-coupled to electrochemical detection (ECD) was used to determine DA, DOPAC, HVA and 3-NT levels. Acrylamide (0.01-5 mM) exposure produced a dose- and time (1-42 h)-dependent decrease in DA levels. The decrease (P<0.05) in DA levels was noted at 24h after exposure to acrylamide. The study also revealed that 3-NT levels in PC 12 increased as a result of treatment with acrylamide. Thus, these data suggest that acrylamide-induced decrease in DA levels in PC 12 cells may be associated with peroxynitrite formation, measured as 3-NT levels. (c) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Tareke, Eden; Duhart, Helen; Newport, Glenn; Ali, Syed] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. [Lyn-Cook, Beverly D.] US FDA, Natl Ctr Toxicol Res, Off Regulatory Act, Jefferson, AR 72079 USA. RP Tareke, E (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. EM edunatar@hotmail.com FU Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS); U.S. FDA/NCfR FX This work is supported by the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS) and U.S. FDA/NCfR.The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration. NR 32 TC 12 Z9 15 U1 3 U2 16 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 JUL 17 PY 2009 VL 458 IS 2 BP 89 EP 92 DI 10.1016/j.neulet.2009.04.016 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 454CF UT WOS:000266658500010 PM 19442880 ER PT J AU Sun, R Skeiky, YAW Izzo, A Dheenadhayalan, V Imam, Z Penn, E Stagliano, K Haddock, S Mueller, S Fulkerson, J Scanga, C Grover, A Derrick, SC Morris, S Hone, DM Horwitz, MA Kaufmann, SHE Sadoff, JC AF Sun, Ronggai Skeiky, Yasir A. W. Izzo, Angelo Dheenadhayalan, Veerabadran Imam, Zakaria Penn, Erica Stagliano, Katherine Haddock, Scott Mueller, Stefanie Fulkerson, John Scanga, Charles Grover, Ajay Derrick, Steven C. Morris, Sheldon Hone, David M. Horwitz, Marcus A. Kaufmann, Stefan H. E. Sadoff, Jerald C. TI Novel recombinant BCG expressing perfringolysin O and the over-expression of key immunodominant antigens; pre-clinical characterization, safety and protection against challenge with Mycobacterium tuberculosis SO VACCINE LA English DT Article DE Recombinant BCG; Endosome lysis; Antigen over-expression; Ad35; Prime-boost; Tuberculosis; Vaccination; T-cell; Protection ID GUINEA-PIG MODEL; IMMUNODEFICIENCY-VIRUS-INFECTION; MAJOR SECRETORY PROTEIN; CD8(+) T-CELLS; PULMONARY TUBERCULOSIS; IMMUNE-RESPONSES; SUBUNIT VACCINE; INTERFERON-GAMMA; BOVIS BCG; EXTRACELLULAR PROTEINS AB Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), has infected approximately two billion individuals worldwide with approximately 9.2 million new cases and 1.6 million deaths annually. Current efforts are focused on making better BCG priming vaccines designed to induce a comprehensive and balanced immunity followed by booster(s) targeting a specific set of relevant antigens in common with the BCG prime. We describe the generation and immunological characterization of recombinant BCG strains with properties associated with lysis of the endosome compartment and over-expression of key Mtb antigens. The endosome lysis strain, a derivative of BCG SSI-1331 (BCG(1331)) expresses a mutant form of perfringolysin O (PfoA(G137Q)), a cytolysin normally secreted by Clostridium perfringens. Integration of the PfoA(G137Q) gene into the BCG genome was accomplished using an allelic exchange plasmid to replace ureC with PfoA(G137Q) under the control of the Ag85B promoter. The resultant BCG construct, designated AERAS-401 (BCG(1331) Delta ureC::Omega pfoA(G137Q)) secreted biologically active Pfo, was well tolerated with a good safety profile in immunocompromised SCID mice. A second rBCG strain, designated AFRO-1, was generated by incorporating an expression plasmid encoding three mycobacterial antigens, Ag85A, Ag85B and TB10.4, into AERAS-401. Compared to the parental BCG strain, vaccination of mice and guinea pigs with AFRO-1 resulted in enhanced immune responses. Mice vaccinated with AFRO-1 and challenged with the hypervirulent Mtb strain HN878 also survived longer than mice vaccinated with the parental BCG. Thus, we have generated improved rBCG vaccine candidates that address many of the shortcomings of the currently licensed BCG vaccine strains. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Sun, Ronggai; Skeiky, Yasir A. W.; Dheenadhayalan, Veerabadran; Imam, Zakaria; Penn, Erica; Stagliano, Katherine; Haddock, Scott; Mueller, Stefanie; Fulkerson, John; Scanga, Charles; Hone, David M.; Sadoff, Jerald C.] Aeras Global TB Vaccine Fdn, Rockville, MD 20850 USA. [Izzo, Angelo; Grover, Ajay] Colorado State Univ, Ft Collins, CO 80523 USA. [Derrick, Steven C.; Morris, Sheldon] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Kaufmann, Stefan H. E.] Max Planck Inst Infect Biol, Berlin, Germany. [Horwitz, Marcus A.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. RP Skeiky, YAW (reprint author), Aeras Global TB Vaccine Fdn, 1405 Res Blvd,Suite 300, Rockville, MD 20850 USA. EM yskeiky@aeras.org RI Izzo, Angelo/F-1229-2017; Kaufmann, Stefan HE/I-5454-2014 OI Izzo, Angelo/0000-0003-3208-2330; Kaufmann, Stefan HE/0000-0001-9866-8268 FU Bill and Melinda Gates Foundation; Netherlands Ministry of Foreign Affairs (DGIS); Colorado State University [N01-Al-400091] FX This study was supported by grants awarded to the Aeras Global TB Vaccine Foundation by the Bill and Melinda Gates Foundation and The Netherlands Ministry of Foreign Affairs (DGIS). Native Ag85 complex, Ag85A, Ag85B, CFP and whole cell lysate derived from Mtb were produced and provided by Drs. John Belisle and Karen Dobos at the Colorado State University under the TB Vaccine Testing and Research Material contract N01-Al-400091. We are grateful to Margaret Ann Goetz and James Zhou for statistical analysis, Dr. Lewellys Barker for critical review of the manuscriptand Dr. Barbara Shepherd for editorial assistance. NR 74 TC 93 Z9 101 U1 1 U2 17 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 JUL 16 PY 2009 VL 27 IS 33 BP 4412 EP 4423 DI 10.1016/j.vaccine.2009.05.048 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 473OR UT WOS:000268217600005 PM 19500523 ER PT J AU Parreiras, PM Sirota, LA Wagner, LD Menzies, SL Arciniega, JL AF Parreiras, P. M. Sirota, L. A. Wagner, L. D. Menzies, S. L. Arciniega, J. L. TI Comparability of ELISA and toxin neutralization to measure immunogenicity of Protective Antigen in mice, as part of a potency test for anthrax vaccines SO VACCINE LA English DT Article DE Anthrax; Vaccine; Potency ID BIOTERRORISM; IMMUNIZATION; ADJUVANTS; ASSAY; VALIDATION; RESPONSES; EFFICACY; SAFETY AB Complexities of lethal challenge models have prompted the investigation of immunogenicity assays as potency tests of anthrax vaccines. An ELISA and a lethal toxin neutralization assay (TNA) were used to measure antibody response to Protective Antigen (PA) in mice immunized once with either a commercial or a recombinant PA (rPA) vaccine formulated in-house. Even though ELISA and TNA results showed correlation, ELISA results may not be able to accurately predict TNA results in this single immunization model. Published by Elsevier Ltd. C1 [Parreiras, P. M.; Sirota, L. A.; Wagner, L. D.; Menzies, S. L.; Arciniega, J. L.] US FDA, Ctr Biol Evaluat & Res, DBPAP, HFM 443, Rockville, MD 20852 USA. [Parreiras, P. M.] Fundacao Oswaldo Cruz, Res Ctr Rene Rachou, BR-30190002 Belo Horizonte, MG, Brazil. RP Arciniega, JL (reprint author), US FDA, Ctr Biol Evaluat & Res, DBPAP, HFM 443, 1401 Rockville Pike, Rockville, MD 20852 USA. EM juan.arciniega@fda.hhs.gov FU PAHO FX This research was performed while P. Parreiras was an ORISE/IRTA Research Fellow. Dr. Parreiras received additional funding from PAHO. The authors wish to thank H. Hsu, R. Levis and J. Castelan for their critical reading of the manuscript. NR 31 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUL 16 PY 2009 VL 27 IS 33 BP 4537 EP 4542 DI 10.1016/j.vaccine.2009.05.045 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 473OR UT WOS:000268217600021 PM 19501205 ER PT J AU Hayward, DG Wong, JW AF Hayward, Douglas G. Wong, Jon W. TI Organohalogen and Organophosphorous Pesticide Method for Ginseng Root - A Comparison of Gas Chromatography-Single Quadrupole Mass Spectrometry with High Resolution Time-of-Flight Mass Spectrometry SO ANALYTICAL CHEMISTRY LA English DT Article ID SOLID-PHASE EXTRACTION; GC-MS DETERMINATION; ORGANOCHLORINE PESTICIDES; LIQUID-CHROMATOGRAPHY; MEDICINAL-PLANTS; RESIDUE ANALYSIS; POLYCHLORINATED-BIPHENYLS; MULTIRESIDUE ANALYSIS; FOOD; CLEANUP AB A method has been developed for the analysis of 170 organohalogen and organophosphorous pesticides, isomers, and metabolites in dried ground ginseng root. Pesticides were extracted with ethyl acetate and purified with gel permeation chromatography (GPC) and primary/secondary amine modified silica (PSA)/graphitized carbon black (GCB) combination SPE column. Each purified pesticide extract was determined by both gas chromatography single quadrupole mass spectrometry using selected ion monitoring (GC-qMS-SIM) and by gas chromatography high resolution time-of-flight mass spectrometry (GC-HR-TOFMS). The geometric mean LOQs using the qMS and TOFMS were 4 and 3 ng/g ginseng, respectively. Mean recoveries from ginseng were 83, 79, and 75% with standard deviations of 4, 5, and 3%, respectively, for 25, 100, and 500 ng/g using GC-qMS-SIM. Mean recoveries using GC-HR-TOFMS were 93, 85, and 81% with mean standard deviations of 7, 7, and 8% for 25, 100, and 500 ng/g, respectively. Seven dried ginseng root products were found to contain combinations of the following pesticides: dacthal, diazinon, DDT, hexachlorobenzene, iprodione, lindane, procymidone, and quintozene (1-460 ng/g). No significant differences were found in the concentrations measured for these pesticides on commercial ginsengs using either of the two GC/MS techniques. C1 [Hayward, Douglas G.; Wong, Jon W.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. RP Hayward, DG (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, 5100 Paint Branch Pkwy,HFS-706, College Pk, MD 20740 USA. EM douglas.hayward@fda.hhs.gov FU National Institutes of Health (NIH) [Y1-OD-6412-01] FX We thank the U.S. EPA Pesticide Repository, Ft. Meade, MD, and in particular, Ms. Terry Cole, for providing the majority of the organohalogen standards used in this study; Ms. Gail Parker; and the State of Florida Department of Agriculture and Consumer Services for providing documentation on identification criteria for pesticides. This work was financially supported by an interagency agreement with the National Institutes of Health (NIH), Office of Dietary Supplements (ODS), Y1-OD-6412-01, and we acknowledge the unwavering support of Dr. Joseph M. Betz, Director, ODS, NIH. NR 41 TC 44 Z9 49 U1 0 U2 28 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 JUL 15 PY 2009 VL 81 IS 14 BP 5716 EP 5723 DI 10.1021/ac900494a PG 8 WC Chemistry, Analytical SC Chemistry GA 472MF UT WOS:000268135000018 PM 19548696 ER PT J AU Johnson, JR McCabe, JS White, DG Johnston, B Kuskowski, MA McDermott, P AF Johnson, James R. McCabe, James S. White, David G. Johnston, Brian Kuskowski, Michael A. McDermott, Patrick TI Molecular Analysis of Escherichia coli from Retail Meats (2002-2004) from the United States National Antimicrobial Resistance Monitoring System SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ANTIBIOTIC-RESISTANCE; PHYLOGENETIC ORIGIN; VIRULENCE GENOTYPE; STRAINS; FOOD; POULTRY; GENES; FLUOROQUINOLONES; AEROBACTIN; MINNESOTA AB Background. The origins and virulence potential of meat product-associated Escherichia coli are undefined. Methods. Two hundred eighty-seven E. coli isolates (145 resistant and 142 susceptible to trimethoprim-sulfamethoxazole, nalidixic acid, and/or ceftiofur), recovered by the United States National Antimicrobial Monitoring System from retail beef, pork, chicken, and turkey products (from Oregon, Tennessee, Georgia, and Maryland, 2002-2004) underwent polymerase chain reaction testing for phylogenetic groupings and 59 virulence-associated genes. Results. However analyzed, resistant and susceptible isolates differed minimally according to the assessed characteristics. In contrast, the 4 meat types differed greatly for multiple individual traits and aggregate virulence scores. Poultry isolates exhibited virulence genes associated with avian pathogenic E. coli; beef isolates exhibited traits associated with E. coli from diseased cattle. Overall, 20% of isolates qualified as extraintestinal pathogenic E. coli, with poultry isolates exhibiting significantly higher virulence scores than beef and pork isolates (P < .001). Conclusions. Within this systematically collected, geographically distributed sample of recent retail meat isolates, the carriage of extraintestinal pathogenic E. coli virulence genes in antimicrobial-resistant and antimicrobial-susceptible E. coli appeared similar, whereas isolates from different types of meat differed, consistent with on-farm acquisition of resistance within host species-specific E. coli populations. A substantial minority of meat-source E. coli (whether susceptible or resistant) may represent potential human pathogens. C1 [Johnson, James R.; McCabe, James S.; Johnston, Brian; Kuskowski, Michael A.] Vet Affairs Med Ctr, Minneapolis, MN 55417 USA. [Johnson, James R.; McCabe, James S.; Johnston, Brian] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Kuskowski, Michael A.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [White, David G.; McDermott, Patrick] US FDA, Ctr Vet Med, Laurel, MD USA. RP Johnson, JR (reprint author), Vet Affairs Med Ctr, Infect Dis 111F,1 Vet Dr, Minneapolis, MN 55417 USA. EM johns007@umn.edu FU Office of Research and Development, Medical Research Service, Department of Veterans Affairs, and the Center for Veterinary Medicine; US Food and Drug Administration FX This study is based on work supported by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, and the Center for Veterinary Medicine, US Food and Drug Administration. We acknowledge Sonya Bodies-Jones, Stuart Gaines, Shawn McDermott, and Sherry Ayers for microbiological support. NR 34 TC 29 Z9 29 U1 0 U2 10 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 15 PY 2009 VL 49 IS 2 BP 195 EP 201 DI 10.1086/599830 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 460XU UT WOS:000267226900005 PM 19508167 ER PT J AU Kashimshetty, R Desai, VG Kate, VM Lee, T Moland, CL Branham, WS New, LS Chan, ECY Younis, H Boelsterli, UA AF Kashimshetty, Rohini Desai, Varsha G. Kate, Vijay M. Lee, Taewon Moland, Carrie L. Branham, William S. New, Lee S. Chan, Eric C. Y. Younis, Husam Boelsterli, Urs A. TI Underlying mitochondrial dysfunction triggers flutamide-induced oxidative liver injury in a mouse model of idiosyncratic drug toxicity SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Flutamide; Drug-induced liver injury (DILI); Superoxide dismutase; Sod2(+/-) mice; Hepatotoxicity; Mitochondria; Idiosyncratic drug toxicity; Bicalutamide ID HETEROZYGOUS SOD2(+/-) MICE; IN-VITRO; SUPEROXIDE-DISMUTASE; PROSTATE-CANCER; ANIMAL-MODEL; CYANO ANALOG; HEPATOTOXICITY; METABOLITES; BIOACTIVATION; MICROSOMES AB Flutamide, a widely used nonsteroidal anti-androgen, but not its bioisostere bicalutamide, has been associated with idiosyncratic drug-induced liver injury. Although the susceptibility factors are unknown, mitochondrial injury has emerged as a putative hazard of flutamide. To explore the role of mitochondrial sensitization in flutamide hepatotoxicity, we determined the effects of superimposed drug stress in a murine model of underlying mitochondrial abnormalities. Male wild-type or heterozygous Sod2(+/-) mice were injected intraperitoneously with flutamide (0, 30 or 100 mg/kg/day) for 28 days. A kinetic pilot study revealed that flutamide (100 mg/kg/day) caused approximately 10-fold greater exposure than the reported therapeutic mean plasma levels. Mutant (5/10), but not wild-type, mice in the high-dose group exhibited small foci of hepatocellular necrosis and an increased number of apoptotic hepatocytes. Hepatic GSSG/GSH, protein carbonyl levels, and serum lactate levels were significantly increased, suggesting oxidant stress and mitochondrial dysfunction. Measurement of mitochondrial superoxide in cultured hepatocytes demonstrated that mitochondria were a significant source of flutamide-enhanced oxidant stress. Indeed, mitochondria isolated from flutamide-treated Sod2(+/-) mice exhibited decreased aconitase activity as compared to vehicle controls. A transcriptomics analysis using MitoChips revealed that flutamide-treated Sod2(+/-) mice exhibited a selective decrease in the expression of all complexes I and III subunits encoded by mitochondrial DNA. In contrast, Sod2(+/-) mice receiving bicalutamide (50 mg/kg/day) did not reveal any hepatic changes. These results are compatible with our concept that flutamide targets hepatic mitochondria and exerts oxidant stress that can lead to overt hepatic injury in the presence of an underlying mitochondrial abnormality. (C) 2009 Elsevier Inc. All rights reserved. C1 [Kashimshetty, Rohini; Kate, Vijay M.; Boelsterli, Urs A.] Univ Connecticut, Sch Pharm, Dept Pharmaceut Sci, Storrs, CT 06269 USA. [Desai, Varsha G.; Moland, Carrie L.; Branham, William S.] US FDA, Natl Ctr Toxicol Res, Ctr Funct Genom, Div Syst Toxicol, Jefferson, AR 72079 USA. [Lee, Taewon] Korea Univ, Dept Math & Informat, Jochiwon 339700, South Korea. [New, Lee S.; Chan, Eric C. Y.] Natl Univ Singapore, Dept Pharm, Singapore 117543, Singapore. [Younis, Husam] Pfizer Global Res & Dev, San Diego, CA 92121 USA. RP Boelsterli, UA (reprint author), Univ Connecticut, Sch Pharm, Dept Pharmaceut Sci, Storrs, CT 06269 USA. EM urs.boelsterli@uconn.edu RI Kale, Vijay/D-8603-2011; Chan , Eric Chun Yong/E-7101-2013 FU Boehringer Ingelheim Endowed Chair in Mechanistic Toxicology; Pfizer, Inc [634841]; NUS startup grant [R-148-050-088-101/133] FX This work was supported in part by the Boehringer Ingelheim Endowed Chair in Mechanistic Toxicology at the University of Connecticut, and by research grants from Pfizer, Inc. (634841, to U.A.B.) and a NUS startup grant (R-148-050-088-101/133, to E.C.Y.C.). NR 50 TC 46 Z9 47 U1 1 U2 8 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 JUL 15 PY 2009 VL 238 IS 2 BP 150 EP 159 DI 10.1016/j.taap.2009.05.007 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 465KV UT WOS:000267584200006 PM 19442681 ER PT J AU Kakhi, M AF Kakhi, Maziar TI Classification of the flow regimes in the flow-through cell SO EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE Dissolution; Flow-through cell; USP 4; Laminar; Turbulent; Transitional; Pulsating flow; Open column; Packed column ID COLLABORATIVE INVITRO DISSOLUTION; REYNOLDS-NUMBER; APPARATUS; METHODOLOGY; TRANSITION; TURBULENCE; TABLETS; JET AB This paper examines the dissolution apparatus referred to as the flow-through cell from an engineering fluid mechanics viewpoint. The analysis demonstrates that laminar now predominantly occurs in the standard operation of this apparatus. It is argued that fully turbulent conditions are unlikely. Consequently. the phrases 'open column' and 'packed column' are suggested as technically more accurate terms for its operational characteristics than the conventionally referenced 'turbulent mode' and 'laminar mode'. Examples of flow profiles are given to show that the criterion of a "sinusoidal" input flow profile required by USP is not a sufficiently accurate characterization at the inlet as numerous profiles can be conceived which have the same average flow rate. The rationale of pulsating flows Versus constant, steady flows is discussed. Examples of how references to turbulence in the dissolution-related literature can lead to ambiguities and/or inconsistencies are highlighted. Published by Elsevier B.V. C1 US FDA, Div Pharmaceut Anal, Silver Spring, MD 20993 USA. RP Kakhi, M (reprint author), US FDA, Div Pharmaceut Anal, Bldg 22,Rm 2147,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Maziar.Kakhi@fda.hhs.gov NR 60 TC 16 Z9 16 U1 1 U2 5 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 JUL 12 PY 2009 VL 37 IS 5 BP 531 EP 544 DI 10.1016/j.ejps.2009.04.003 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 471KV UT WOS:000268057500001 PM 19379811 ER PT J AU Thomas, JT Canelos, P Luyten, FP Moos, M AF Thomas, J. Terrig Canelos, Paola Luyten, Frank P. Moos, Malcolm, Jr. TI Xenopus SMOC-1 Inhibits Bone Morphogenetic Protein Signaling Downstream of Receptor Binding and Is Essential for Postgastrulation Development in Xenopus. SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INTEGRIN-LINKED KINASE; GROWTH-FACTOR; NEURAL INDUCTION; EMBRYONIC-DEVELOPMENT; SPEMANN ORGANIZER; ENDOTHELIAL-CELLS; EXPRESSION; LAEVIS; BMP; FAMILY AB The bone morphogenetic protein (BMP) family of signaling molecules and their antagonists are involved in patterning of the body axis and numerous aspects of organogenesis. Classical biochemical purification and protein sequencing of highly purified fractions containing potent bone forming activity from bovine cartilage identified several BMPs together with a number of other proteins. One such protein was SMOC-2 (secreted modular calcium-binding protein-2), classified as belonging to the BM-40 family of modular extracellular proteins. Data regarding the biological function of SMOC-2 and closely related SMOC-1 remain limited, and their expression or function during embryological development is unknown. We therefore isolated the Xenopus ortholog of human SMOC-1 (XSMOC-1) and explored its function in Xenopus embryos. In gain-of-function assays, XSMOC-1 acted similarly to a BMP antagonist. However, in contrast to known extracellular ligand-binding BMP antagonists, such as noggin, SMOC antagonizes BMP activity in the presence of a constitutively active BMP receptor, indicating a mechanism of action downstream of the receptor. We provide several lines of evidence to suggest that SMOC acts downstream of the BMP receptor via MAPK-mediated phosphorylation of the Smad linker region. Loss-of-function studies, using antisense morpholino oligonucleotides, revealed XSMOC-1 to be essential for postgastrulation development. The catastrophic developmental failure observed following XSMOC knockdown resembles that observed following simultaneous depletion of three ligand-binding BMP antagonists described in prior studies. These findings provide a direct link between the extracellular matrix-associated protein SMOC and a signaling pathway of general importance in anatomic patterning and cell or tissue fate specification. C1 [Thomas, J. Terrig; Canelos, Paola; Moos, Malcolm, Jr.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Luyten, Frank P.] Katholieke Univ Leuven, Dept Musculoskeletal Sci, Div Rheumatol, Lab Skeletal Dev & Joint Disorders, B-3000 Louvain, Belgium. RP Thomas, JT (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM john.thomas@fda.hhs.gov; malcolm.moos@fda.hhs.gov RI Moos, Malcolm/F-3673-2011 OI Moos, Malcolm/0000-0002-9575-9938 NR 48 TC 22 Z9 23 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 10 PY 2009 VL 284 IS 28 BP 18994 EP 19005 DI 10.1074/jbc.M807759200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 467BP UT WOS:000267711500049 PM 19414592 ER PT J AU Rosenberg, M Sparks, R McMahon, A Iskander, J Campbell, JD Edwards, KM AF Rosenberg, Melissa Sparks, Robert McMahon, Ann Iskander, John Campbell, James D. Edwards, Kathryn M. TI Serious adverse events rarely reported after trivalent inactivated influenza vaccine (TIV) in children 6-23 months of age SO VACCINE LA English DT Article DE Trivalent influenza vaccine; Vaccine Adverse Event Reporting System; Advisory Committee on Immunization; Practices; Serious adverse event; Causality ID YOUNG-CHILDREN; ANTHRAX VACCINE; SYSTEM VAERS; SAFETY; BURDEN; COMMITTEE; ILLNESS; SEASON; AVEC AB In October 2003 the Advisory Committee on Immunization Practices (ACIP) recommended influenza vaccination for all children ages 6-23 months. We evaluated the safety of this recommendation by querying the Vaccine Adverse Events Reporting System (VAERS) for serious adverse events (SAE) reported between July 1, 2003 and June 30, 2006 in 6-23 month old infants after trivalent inactivated influenza vaccine (TIV). Cases were reviewed and the causal relationship with vaccine assessed. One hundred and four SAE were reported: median time from vaccination to SAE onset was one day. The two most commonly reported SAE disease categories were fever (N=52) and seizure (N=35). Causality assessment revealed that none of the SAE was definitely related to TIV. Although the number of SAE increased over time, the most common types of events remained unchanged with no new or unexpected safety concerns identified with expanded TIV use. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Campbell, James D.] Univ Maryland, Ctr Vaccine Dev, Sch Med, Dept Pediat, Baltimore, MD 21201 USA. [Edwards, Kathryn M.] Vanderbilt Univ, Vanderbilt Vaccine Res Program, Sarah H Sell Chair Pediat, Nashville, TN 37232 USA. [McMahon, Ann] US FDA, Div Adverse Event Anal 2, Off Surveillance & Epidemiol, CDER, Silver Spring, MD USA. [Iskander, John] Ctr Dis Control & Prevent, Immunizat Safety Off, Off Chief Sci Officer, Atlanta, GA USA. RP Rosenberg, M (reprint author), Michigan State Univ, Coll Osteopath Med, Dept Pediat, 547B W Fee Hall, E Lansing, MI 48824 USA. EM melissa.rosenberg@ht.msu.edu; robert.c.sparks@vanderbilt.edu; ann.mcmahon@fda.hhs.gov; jxi0@cdc.gov; campbellj@ug.cdc.gov; kathryn.edwards@vanderbilt.edu NR 31 TC 27 Z9 28 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 JUL 9 PY 2009 VL 27 IS 32 BP 4278 EP 4283 DI 10.1016/j.vaccine.2009.05.023 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 470UD UT WOS:000268005400006 PM 19450636 ER PT J AU Kakhi, M AF Kakhi, Maziar TI Mathematical modeling of the fluid dynamics in the flow-through cell SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE Dissolution; Flow-through cell (USP 4); Computational fluid dynamics (CFD); Flow separation; Velocity boundary layer; Adverse pressure gradient; Open/packed column modes ID DISSOLUTION APPARATUS; HYDRODYNAMICS; VARIABILITY; TABLETS AB The fluid dynamics in the flow-through cell (USP apparatus 4) has been predicted using the mathematical modeling approach of computational fluid dynamics (CFD). The degree to which flow structures in this apparatus can be qualified as 'ideal' both spatially and temporally has been assessed. The simulations predict the development of the velocity field in this apparatus for configurations with and without beads during the discharge stroke of the pump. When the cell is operated only with the red ruby bead ('open column' mode), highly non-uniform flow is predicted just downstream of the bead in the latter stages of the pump's pulse. In contrast, a strong degree of profile uniformity and symmetry is predicted throughout the entire pulse in the region of the tablet holder for both standard configurations involving beads. However, noticeable differences in the tablet shear stress distribution are predicted at times when the same instantaneous inlet flow rates are being pumped through the apparatus. This effect is caused by flow separation in the velocity boundary layer formed around the tablet under the influence of an adverse pressure gradient, an effect not predicted with constant (non-pulsating) flow. While the degree of tablet erosion correlates with the average flow rate, during a particular pulse both the free-stream velocity and the boundary layer thickness are also influential. Published by Elsevier B.V. C1 US FDA, Div Pharmaceut Anal, Silver Spring, MD 20993 USA. RP Kakhi, M (reprint author), US FDA, Div Pharmaceut Anal, Bldg 22,Rm 2147,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Maziar.Kakhi@fda.hhs.gov NR 42 TC 14 Z9 14 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARMACEUT JI Int. J. Pharm. PD JUL 6 PY 2009 VL 376 IS 1-2 BP 22 EP 40 DI 10.1016/j.ijpharm.2009.04.012 PG 19 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 468CI UT WOS:000267790800004 PM 19375490 ER PT J AU Abu-Ali, GS Lacher, DW Wick, LM Qi, WH Whittam, TS AF Abu-Ali, Galeb S. Lacher, David W. Wick, Lukas M. Qi, Weihong Whittam, Thomas S. TI Genomic diversity of pathogenic Escherichia coli of the EHEC 2 clonal complex SO BMC GENOMICS LA English DT Article ID HEMOLYTIC-UREMIC-SYNDROME; SHIGA TOXIN; ENTEROCYTE EFFACEMENT; MOLECULAR EVOLUTION; EFFACING LESIONS; HUMAN INFECTIONS; DIARRHEAGENIC STRAINS; VIRULENCE PROPERTIES; NUCLEOTIDE-SEQUENCE; GENETIC-STRUCTURE AB Background:Evolutionary analyses of enterohemorrhagic Escherichia coli (EHEC) have identified two distantly related clonal groups:EHEC 1, including serotype O157:H7 and its inferred ancestor O55:H7; and EHEC 2, comprised of several serogroups (O26, O111, O118, etc.). These two clonal groups differ in their virulence and global distribution. Although several fully annotated genomic sequences exist for strains of serotype O157:H7, much less is known about the genomic composition of EHEC 2. In this study, we analyzed a set of 24 clinical EHEC 2 strains representing serotypes O26:H11, O111:H8/H11, O118:H16, O153:H11 and O15:H11 from humans and animals by comparative genomic hybridization (CGH) on an oligoarray based on the O157:H7 Sakai genome. Results: Backbone genes, defined as genes shared by Sakai and K-12, were highly conserved in EHEC 2. The proportion of Sakai phage genes in EHEC 2 was substantially greater than that of Sakai-specific bacterial (non-phage) genes. This proportion was inverted in O55:H7, reiterating that a subset of Sakai bacterial genes is specific to EHEC 1. Split decomposition analysis of gene content revealed that O111:H8 was more genetically uniform and distinct from other EHEC 2 strains, with respect to the Sakai O157:H7 gene distribution. Serotype O26:H11 was the most heterogeneous EHEC 2 subpopulation, comprised of strains with the highest as well as the lowest levels of Sakai gene content conservation. Of the 979 parsimoniously informative genes, 15% were found to be compatible and their distribution in EHEC 2 clustered O111:H8 and O118:H16 strains by serotype. CGH data suggested divergence of the LEE island from the LEE1 to the LEE4 operon, and also between animal and human isolates irrespective of serotype. No correlation was found between gene contents and geographic locations of EHEC 2 strains. Conclusion: The gene content variation of phage-related genes in EHEC 2 strains supports the hypothesis that extensive modular shuffling of mobile DNA elements has occurred among EHEC strains. These results suggest that EHEC 2 is a multiform pathogenic clonal complex, characterized by substantial intra-serotype genetic variation. The heterogeneous distribution of mobile elements has impacted the diversification of O26:H11 more than other EHEC 2 serotypes. C1 [Abu-Ali, Galeb S.; Whittam, Thomas S.] 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 20708 USA. [Wick, Lukas M.] Biosynth AG, CH-9422 Staad, Switzerland. [Qi, Weihong] Univ Zurich, Funct Genom Ctr Zurich, CH-8057 Zurich, Switzerland. [Qi, Weihong] Swiss Fed Inst Technol, CH-8057 Zurich, Switzerland. RP Abu-Ali, GS (reprint author), Michigan State Univ, Natl Food Safety & Toxicol Ctr, Microbial Evolut Lab, 165 Food Safety & Toxicol Bldg, E Lansing, MI 48824 USA. EM abualiga@cvm.msu.edu; David.Lacher@fda.hhs.gov; lukas.wick@biosynth.ch; weihong.qi@fgcz.ethz.ch; abualiga@cvm.msu.edu FU MSU foundation; NIAID; NIH [N01-AI-30058]; DHHS FX The authors thank Shannon Manning, James Riordan, Sivapriya Kailasan Vanaja, Linda Mansfield, Martha Mulks, and Jillian Tietjen for critically reviewing earlier versions of the manuscript; Lindsey Ouellette for technical assistance with MLST; and those investigators who supplied strains for use in the study. This project was funded in part by the MSU foundation and the NIAID, NIH, DHHS, under NIH research contract N01-AI-30058 (TSW), which supports the STEC Center. The authors wish to dedicate this work to the memory of Dr. Thomas S. Whittam. NR 96 TC 10 Z9 10 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD JUL 3 PY 2009 VL 10 AR 296 DI 10.1186/1471-2164-10-296 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 480RS UT WOS:000268755100001 PM 19575794 ER PT J AU Berridge, BR Pettit, S Walker, DB Jaffe, AS Schultze, AE Herman, E Reagan, WJ Lipshultz, SE Apple, FS York, MJ AF Berridge, Brian R. Pettit, Syril Walker, Dana B. Jaffe, Alan S. Schultze, Albert E. Herman, Eugene Reagan, William J. Lipshultz, Steven E. Apple, Fred S. York, Malcolm J. TI A translational approach to detecting drug-induced cardiac injury with cardiac troponins: Consensus and recommendations from the Cardiac Troponins Biomarker Working Group of the Health and Environmental Sciences Institute SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CORONARY SYNDROMES; MYOCARDIAL INJURY; HISTOLOGICAL-FINDINGS; NATRIURETIC PEPTIDE; SAFETY BIOMARKER; RATS; INFARCTION; DAMAGE; CARDIOTOXICITY; ISOPROTERENOL AB Cardiac troponins (cTns) are established biomarkers of ischemic heart disease in humans. However, their value as biomarkers of cardiac injury from causes other than ischemic heart disease is now being explored, particularly in drug development. In a workshop sponsored by the Cardiac Troponin Biomarker Working Group of the Health and Environmental Sciences Institute, preclinical, clinical, and regulatory scientists discussed the application of cTns in their respective environments, issues in translating the preclinical application of cTn to clinical studies, and gaps in our understanding of cTn biology and pathobiology. Evidence indicates that cTns are sensitive and specific biomarkers of cardiac injury from varying causes in both animals and humans. Accordingly, monitoring cTns can help ensure patient safety during the clinical evaluation of new drugs. In addition, preclinical characterization of cardiac risk and cTns as biomarkers of that risk can guide relevant clinical application and interpretation. We summarize here the outcomes of the workshop which included consensus statements, recommendations for further research, and a proposal for a cross-disciplinary group of clinical, regulatory, and drug development scientists to collaborate in such research. (Am Heart J 2009; 158:21-9.) C1 [Berridge, Brian R.] GlaxoSmithKline Safety Assessment, Res Triangle Pk, NC USA. [Pettit, Syril] ILSI Hlth & Environm Sci Inst, Washington, DC USA. [Walker, Dana B.] Bristol Myers Squibb Co, E Syracuse, NY USA. [Jaffe, Alan S.] Mayo Clin, Rochester, MN USA. [Schultze, Albert E.] Eli Lilly & Co, Dept Pathol, Indianapolis, IN 46285 USA. [Herman, Eugene] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Reagan, William J.] Pfizer Inc, Drug Safety Evaluat, Groton, CT 06340 USA. [Lipshultz, Steven E.] Univ Miami, Dept Pediat, Miller Sch Med, Miami, FL 33152 USA. [Apple, Fred S.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. RP Berridge, BR (reprint author), GlaxoSmithKline Safety Assessment, 5 Moore Dr,RD9-3005, Res Triangle Pk, NC USA. EM brian.x.berridge@gsk.com NR 29 TC 28 Z9 29 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUL PY 2009 VL 158 IS 1 BP 21 EP 29 DI 10.1016/j.ahj.2009.04.020 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 465ZU UT WOS:000267630600004 PM 19540388 ER PT J AU Ali, SF Patnaik, R Sharma, HS AF Ali, Syed F. Patnaik, Ranjana Sharma, Hari Shanker TI Nanodrug delivery alters heat shock protein expression in drug dependence and induces neuroprotection SO AMINO ACIDS LA English DT Meeting Abstract C1 [Ali, Syed F.; Sharma, Hari Shanker] Food & Drug Adm Labs, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR USA. [Patnaik, Ranjana; Sharma, Hari Shanker] Uppsala Univ, Univ Hosp, Lab Cerebrovasc Res, Dept Surg Sci Anaesthesiol & Intens Care Med, Uppsala, Sweden. [Patnaik, Ranjana] Banaras Hindu Univ, Inst Technol, Sch Biomed Engn, Dept Biomat, Varanasi 221005, Uttar Pradesh, India. RI Sharma, Hari/G-4508-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0939-4451 EI 1438-2199 J9 AMINO ACIDS JI Amino Acids PD JUL PY 2009 VL 37 IS 1 SU S BP 26 EP 26 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 468MN UT WOS:000267823800084 ER PT J AU Kodell, RL Pearce, BA Baek, S Moon, H Ahn, H Young, JF Chen, JJ AF Kodell, Ralph L. Pearce, Bruce A. Baek, Songjoon Moon, Hojin Ahn, Hongshik Young, John F. Chen, James J. TI A model-free ensemble method for class prediction with application to biomedical decision making SO ARTIFICIAL INTELLIGENCE IN MEDICINE LA English DT Article DE Cancer; Disease classification; Convex hull; Gene imprinting; Genomics; k-Nearest-neighbor; Medical screening ID HIGH-DIMENSIONAL DATA; GENE-EXPRESSION; CLASSIFICATION; CANCER AB Objective: A classification algorithm that utilizes two-dimensional convex hulls of training-set samples is presented. Methods and material: For each pair of predictor variables, separate convex hulls of positive and negative samples in the training set are formed, and these convex hulls are used to classify test points according to a nearest-neighbor criterion. An ensemble of these two-dimensional convex-hull classifiers is formed by trimming the (m)C(2) possible classifiers derived from the m predictors to a set of classifiers comprised of only unique predictor variables. Because only two-dimensional spaces are required to be populated by training-set samples, the "curse of dimensionality" is not an issue. At the same time, the power of ensemble voting is exploited by combining the classifications of the unique two-dimensional classifiers to reach a final classification. Results: The algorithm is illustrated by application to three publicly available biomedical data sets with genomic predictors and is shown to have prediction accuracy that is competitive with a number of published classification procedures. Conclusion: Because of its superior performance in terms of sensitivity and negative predictive value compared to its competitors, the convex-hull ensemble classifier demonstrates good potential for medical screening, where often the major emphasis is placed on having reliable negative predictions. (C) 2008 Elsevier B.V. All rights reserved. C1 [Kodell, Ralph L.] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. [Pearce, Bruce A.] Natl Ctr Toxicol Res, Informat Technol Staff, Jefferson, AR 72079 USA. [Baek, Songjoon; Young, John F.; Chen, James J.] Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. [Moon, Hojin] Calif State Univ Long Beach, Dept Math & Stat, Long Beach, CA 90840 USA. [Ahn, Hongshik] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. RP Kodell, RL (reprint author), Univ Arkansas Med Sci, Dept Biostat, 781,4301 W Markham St,COPH 3218, Little Rock, AR 72205 USA. EM rlkodell@uams.edu NR 39 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0933-3657 J9 ARTIF INTELL MED JI Artif. Intell. Med. PD JUL PY 2009 VL 46 IS 3 BP 267 EP 276 DI 10.1016/j.artmed.2008.11.001 PG 10 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA 471GC UT WOS:000268043000006 PM 19081231 ER PT J AU Strauss, DM Lute, S Brorson, K Blank, GS Chen, Q Yang, B AF Strauss, Daniel M. Lute, Scott Brorson, Kurt Blank, Gregory S. Chen, Qi Yang, Bin TI Removal of Endogenous Retrovirus-Like Particles from CHO-Cell Derived Products Using Q Sepharose Fast Flow Chromatography SO BIOTECHNOLOGY PROGRESS LA English DT Article DE endogenous retrovirus-like particle (RVLP); anion exchange chromatography (AEX); Q sepharose fast flow (QSFF); viral safety; monoclonal antibody production ID REVERSE-TRANSCRIPTASE ASSAY; TIME QUANTITATIVE PCR; MONITOR RETROVIRUS; VIRUS REMOVAL; CULTURE; CLEARANCE AB Retrovirus-like particles (RVLPs) that are expressed during the production of monoclonal antibodies in Chinese hamster ovary (CHO) cell cultures must be removed during product recovery. Anion exchange chromatography (AEX) performed in product flow-through mode, a common, component in the purification of monoclonal antibodies, has beet? shown to provide robust removal of a related retrovirus model, but it's ability to remove the actual RVLP impurities has not been directly investigated. We have determined the ability of a typical Q sepharose process to remove actual CHO RVLP impurities. Using small scale experiments with three model antibodies, we observe that this AEX process is capable of effectively removing both in-process and spiked RVLPs from? different feedstocks containing different mAb products. In addition, we show that this AEX process also achieves a similarly high degree of RVLP removal during large scale manufacturing operations. (C) 2009 American Institute of Chemical Engineers Biotechnol. Prog., 25: 1194-1197, 2009 C1 [Strauss, Daniel M.; Blank, Gregory S.; Chen, Qi; Yang, Bin] Genentech Inc, Proc Res & Dev, Late Stage Purificat, San Francisco, CA 94080 USA. [Lute, Scott; Brorson, Kurt] Food & Drug Adm, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. RP Yang, B (reprint author), Genentech Inc, Proc Res & Dev, Late Stage Purificat, 1 DNA Way, San Francisco, CA 94080 USA. EM yang.bin@gene.com NR 21 TC 8 Z9 9 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD JUL-AUG PY 2009 VL 25 IS 4 BP 1194 EP 1197 DI 10.1002/btpr.249 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 489EO UT WOS:000269403000036 PM 19452543 ER PT J AU Pogribny, IP AF Pogribny, Igor P. TI Genomic instability induced by heat-inactivated bacteria Implication to tumorigenesis SO CELL CYCLE LA English DT News Item ID DOUBLE-STRAND BREAKS; MECHANISMS; PATHOGENS; CANCER; CELLS 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 10 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUL 1 PY 2009 VL 8 IS 13 BP 1983 EP 1983 PG 1 WC Cell Biology SC Cell Biology GA 465RG UT WOS:000267603900010 PM 19550153 ER PT J AU Pogribny, IP Beland, FA AF Pogribny, Igor P. Beland, Frederick A. TI DNA hypomethylation in the origin and pathogenesis of human diseases SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE DNA hypomethylation; G-specific hypomethylation; Cancer; Atherosclerosis; Alzheimer's disease; Psychiatric disorders ID PANCREATIC DUCTAL ADENOCARCINOMA; CANCER/TESTIS ANTIGEN GENE; SQUAMOUS-CELL CARCINOMA; PRECURSOR PROTEIN GENE; HEMI-METHYLATED DNA; DE-NOVO METHYLATION; PROMOTER HYPOMETHYLATION; BREAST-CANCER; CPG ISLAND; 5-METHYLCYTOSINE CONTENT AB The pathogenesis of any given human disease is a complex multifactorial process characterized by many biologically significant and interdependent alterations. One of these changes, specific to a wide range of human pathologies, is DNA hypomethylation. DNA hypomethylation signifies one of the major DNA methylation states that refers to a relative decrease from the "normal" methylation level. It is clear that disease by itself can induce hypomethylation of DNA; however, a decrease in DNA methylation can also have an impact on the predisposition to pathological states and disease development. This review presents evidence suggesting the involvement of DNA hypomethylation in the pathogenesis of several major human pathologies, including cancer, atherosclerosis, Alzheimer's disease, and psychiatric disorders. C1 [Pogribny, Igor P.; Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov NR 194 TC 94 Z9 105 U1 5 U2 22 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD JUL PY 2009 VL 66 IS 14 BP 2249 EP 2261 DI 10.1007/s00018-009-0015-5 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 469HG UT WOS:000267886500004 PM 19326048 ER PT J AU Atrakchi, AH AF Atrakchi, Aisar H. TI Interpretation and Considerations on the Safety Evaluation of Human Drug Metabolites SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Review ID GLUCURONIDATION; TOXICITY AB The final Food and Drug Administration guidance on the safety testing of drug metabolites was published in February 2008. Discussions of the role and applications of this guidance were addressed at several public scientific meetings over the past year. One of the main differences between the draft and the finalized guidance is that in the latter, the human metabolite level was correlated to the parent drug level in plasma, whereas this parameter was considered in relationship to administered dose or total exposure in the draft guidance. The parent drug concentration in plasma has traditionally been the parameter commonly measured in animals during drug development and the one used to estimate drug clinical levels and to assess human risk. Moreover, circulating parent drug in general is the molecule with the intended therapeutic and pharmacologic effect. Therefore, it is appropriate to compare metabolite concentration to that of the parent drug. This report elaborates on this issue and supports other alternative rational and scientific approaches on the design of nonclinical studies that may be needed to test a human drug metabolite. C1 US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Silver Spring, MD 20993 USA. RP Atrakchi, AH (reprint author), US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Silver Spring, MD 20993 USA. EM aisar.atrakchi@fda.hhs.gov NR 35 TC 32 Z9 32 U1 0 U2 2 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 JUL PY 2009 VL 22 IS 7 BP 1217 EP 1220 DI 10.1021/tx900124j PG 4 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 473AJ UT WOS:000268175100001 PM 19563206 ER PT J AU Findlow, H Plikaytis, BD Aase, A Bash, MC Chadha, H Elie, C Laher, G Martinez, J Herstad, T Newton, E Viviani, S Papaspyridis, C Kulkarni, P Wilding, M Preziosi, MP Marchetti, E Hassan-King, M La Force, FM Carlone, G Borrow, R AF Findlow, H. Plikaytis, B. D. Aase, A. Bash, M. C. Chadha, H. Elie, C. Laher, G. Martinez, J. Herstad, T. Newton, E. Viviani, S. Papaspyridis, C. Kulkarni, P. Wilding, M. Preziosi, M. P. Marchetti, E. Hassan-King, M. La Force, F. M. Carlone, G. Borrow, R. TI Investigation of Different Group A Immunoassays following One Dose of Meningococcal Group A Conjugate Vaccine or A/C Polysaccharide Vaccine in Adults SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID MENINGITIDIS SEROGROUP-A; LINKED-IMMUNOSORBENT-ASSAY; ANTIBODY-RESPONSES; HUMAN IMMUNITY; CHILDREN; IMMUNOGENICITY; PERSISTENCE; PROTECTION; EFFICACY; AFRICA AB A double-blind, randomized, controlled phase I study to assess the safety, immunogenicity, and antibody persistence of a new group A conjugate vaccine (PsA-TT) in volunteers aged 18 to 35 years was previously performed. Subjects received one dose of either the PsA-TT conjugate vaccine, meningococcal A/C polysaccharide vaccine (PsA/C), or tetanus toxoid vaccine. The conjugate vaccine was shown to be safe and immunogenic as demonstrated by a standardized group A-specific immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and by a serum bactericidal antibody (SBA) assay using rabbit complement (rSBA). This report details further analysis of the sera using four additional immunologic assays to investigate the relationship between the different immunoassays. The immunoassays used were an SBA assay that used human complement (hSBA), a group A-specific IgG multiplexed bead assay, and two opsonophagocytic antibody (OPA) assays which used two different methodologies. For each vaccine group, geometric mean concentrations or geometric mean titers were determined for all assays before and 4, 24, and 48 weeks after vaccination. Pearson's correlation coefficients were used to assess the relationship between the six assays using data from all available visits. An excellent correlation was observed between the group A-specific IgG concentrations obtained by ELISA and those obtained by the multiplexed bead assay. hSBA and rSBA titers correlated moderately, although proportions of subjects with putatively protective titers and those demonstrating a >= 4-fold rise were similar. The two OPA methods correlated weakly and achieved only a low correlation with the other immunoassays. The correlation between hSBA and group A-specific IgG was higher for the PsA-TT group than for the PsA/C group. C1 [Findlow, H.] Manchester Royal Infirm, Vaccine Evaluat Unit, Hlth Protect Agcy NW, Manchester Lab, Manchester M13 9WL, Lancs, England. [Plikaytis, B. D.; Elie, C.; Martinez, J.; Carlone, G.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Aase, A.; Herstad, T.] Norwegian Inst Publ Hlth, Div Infect Dis Control, NO-0403 Oslo, Norway. [Bash, M. C.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Viviani, S.; Marchetti, E.; Hassan-King, M.; La Force, F. M.] PATH, Meningitis Vaccine Project, F-01210 Ferney Voltaire, France. [Kulkarni, P.] Serum Inst India Ltd, Pune, Maharashtra, India. [Preziosi, M. P.] WHO, Initiat Vaccine Res, Meningitis Vaccine Project, CH-1211 Geneva, Switzerland. RP Findlow, H (reprint author), Manchester Royal Infirm, Vaccine Evaluat Unit, Hlth Protect Agcy NW, Manchester Lab, POB 209,Clin Sci Bldg, Manchester M13 9WL, Lancs, England. EM Helen.findlow@hpa.org.uk NR 27 TC 17 Z9 17 U1 0 U2 1 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 JUL 1 PY 2009 VL 16 IS 7 BP 969 EP 977 DI 10.1128/CVI.00068-09 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 467OH UT WOS:000267747700002 PM 19474264 ER PT J AU Parra, M Yang, AL Lim, J Kolibab, K Derrick, S Cadieux, N Perera, LP Jacobs, WR Brennan, M Morris, SL AF Parra, Marcela Yang, Amy L. Lim, JaeHyun Kolibab, Kristopher Derrick, Steven Cadieux, Nathalie Perera, Liyanage P. Jacobs, William R. Brennan, Michael Morris, Sheldon L. TI Development of a Murine Mycobacterial Growth Inhibition Assay for Evaluating Vaccines against Mycobacterium tuberculosis SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; CD4(+) T-CELLS; IN-VITRO; INTRACELLULAR GROWTH; PROTECTIVE IMMUNITY; INTERFERON-GAMMA; CALMETTE-GUERIN; INFECTION; MICE; BCG AB The development and characterization of new tuberculosis (TB) vaccines has been impeded by the lack of reproducible and reliable in vitro assays for measuring vaccine activity. In this study, we developed a murine in vitro mycobacterial growth inhibition assay for evaluating TB vaccines that directly assesses the capacity of immune splenocytes to control the growth of Mycobacterium tuberculosis within infected macrophages. Using this in vitro assay, protective immune responses induced by immunization with five different types of TB vaccine preparations (Mycobacterium bovis BCG, an attenuated M. tuberculosis mutant strain, a DNA vaccine, a modified vaccinia virus strain Ankara [MVA] construct expressing four TB antigens, and a TB fusion protein formulated in adjuvant) can be detected. Importantly, the levels of vaccine-induced mycobacterial growth-inhibitory responses seen in vitro after 1 week of coculture correlated with the protective immune responses detected in vivo at 28 days postchallenge in a mouse model of pulmonary tuberculosis. In addition, similar patterns of cytokine expression were evoked at day 7 of the in vitro culture by immune splenocytes taken from animals immunized with the different TB vaccines. Among the consistently upregulated cytokines detected in the immune cocultures are gamma interferon, growth differentiation factor 15, interleukin-21 (IL-21), IL-27, and tumor necrosis factor alpha. Overall, we have developed an in vitro functional assay that may be useful for screening and comparing new TB vaccine preparations, investigating vaccine-induced protective mechanisms, and assessing manufacturing issues, including product potency and stability. C1 [Parra, Marcela; Yang, Amy L.; Lim, JaeHyun; Kolibab, Kristopher; Derrick, Steven; Cadieux, Nathalie; Brennan, Michael; Morris, Sheldon L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Perera, Liyanage P.] Ctr Canc Res, Metab Branch, Natl Canc Inst, Bethesda, MD USA. [Jacobs, William R.] Albert Einstein Coll Med, Howard Hughes Med Inst, Dept Microbiol & Immunol, Bronx, NY 10467 USA. [Brennan, Michael] Aeras Global TB Vaccine Fdn, Rockville, MD USA. RP Morris, SL (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 29,Room 502,29 Lincoln Dr, Bethesda, MD 20892 USA. EM sheldon.morris@fda.hhs.gov FU National Institute of Allergy and Infectious Diseases; National Institutes of Health; Department of Health and Human Services [IAA 224-06-1322] FX This project has been funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under IAA 224-06-1322. NR 36 TC 32 Z9 33 U1 0 U2 0 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 JUL 1 PY 2009 VL 16 IS 7 BP 1025 EP 1032 DI 10.1128/CVI.00067-09 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 467OH UT WOS:000267747700010 PM 19458207 ER PT J AU Gubernot, DM Wise, RP Spinola, SM AF Gubernot, Diane M. Wise, Robert P. Spinola, Stanley M. TI Fatality Despite Appropriate Treatment for Babesiosis SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 [Gubernot, Diane M.; Wise, Robert P.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Spinola, Stanley M.] Indiana Univ, Dept Med, Indianapolis, IN USA. RP Gubernot, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 1 PY 2009 VL 49 IS 1 BP 166 EP 167 DI 10.1086/599621 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 455ND UT WOS:000266766500026 PM 19500034 ER PT J AU Woodcock, J AF Woodcock, J. TI Chutes and Ladders on the Critical Path: Comparative Effectiveness, Product Value, and the Use of Biomarkers in 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 18 Z9 20 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 JUL PY 2009 VL 86 IS 1 BP 12 EP 14 DI 10.1038/clpt.2009.33 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 460XJ UT WOS:000267225200002 PM 19536116 ER PT J AU Gobburu, JVS AF Gobburu, J. V. S. TI Biomarkers in Clinical Drug Development SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material AB The primary purpose of this Commentary is to complement the description of biomarkers given in this issue in the Pharmaceutical Research and Manufacturers of America report by Lathia et al. I offer several examples of the use of biomarkers that highlight their value in drug development and regulatory decision making. C1 US FDA, Div Pharmacometr, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Gobburu, JVS (reprint author), US FDA, Div Pharmacometr, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM jogarao.gobburu@fda.hhs.gov NR 9 TC 13 Z9 13 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 JUL PY 2009 VL 86 IS 1 BP 26 EP 27 DI 10.1038/clpt.2009.57 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 460XJ UT WOS:000267225200007 PM 19536121 ER PT J AU Dzanis, DA AF Dzanis, David A. TI Regulation of Pet Foods in the United States SO COMPENDIUM-CONTINUING EDUCATION FOR VETERINARIANS LA English DT Article AB In the United States, pet foods (including treats, edible chews, and supplements) are subject to regulation at both federal and state levels. Products found to be adulterated or misbranded are subject to enforcement action. Veterinarians play a key role in helping ensure pet food safety by reporting possible adverse effects to authorities in a timely manner. C1 [Dzanis, David A.] Dzanis Consulting & Collaborat, Santa Clarita, CA USA. [Dzanis, David A.] US FDA, Rockville, MD 20857 USA. RP Dzanis, DA (reprint author), Dzanis Consulting & Collaborat, Santa Clarita, CA USA. NR 6 TC 1 Z9 1 U1 1 U2 3 PU VETERINARY LEARNING SYSTEMS PI YARDLEY PA 780 TOWNSHIP LINE RD, YARDLEY, PA 19067-4200 USA SN 1940-8307 J9 COMPENDIUM JI Compendium PD JUL PY 2009 VL 31 IS 7 BP 324 EP 328 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA 476GX UT WOS:000268428100003 PM 19746351 ER PT J AU Permutt, T Pinheiro, J AF Permutt, Thomas Pinheiro, Jose TI Dealing With the Missing Data Challenge in Clinical Trials SO DRUG INFORMATION JOURNAL LA English DT Editorial Material C1 [Permutt, Thomas] US FDA, CDER, Rockville, MD 20857 USA. [Pinheiro, Jose] Novartis Pharmaceut, E Hanover, NJ USA. RP Permutt, T (reprint author), 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Thomas.Permutt@fda.hhs.gov NR 0 TC 3 Z9 3 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 JUL PY 2009 VL 43 IS 4 BP 403 EP 408 PG 6 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 469EC UT WOS:000267877500003 ER PT J AU Soon, G AF Soon, Guoxing (Greg) TI Minimizing Missing Data in Clinical Trials: Design, Operation, and Regulatory Considerations SO DRUG INFORMATION JOURNAL LA English DT Article DE Clinical trial; Benefit/risk, Minimizing missing data; MCAR; MAR; Off-treatment follow-up; Sensitivity analysis; Labeling; Statistical methods AB The ultimate question to be answered in a clinical trial is "What benefit/risk has the drug caused to the patient?" To answer this question, it is critical to avoid missing data on outcome that measures benefit and risk from the beginning. This article emphasizes that when a patient discontinues the study treatment, instead of trying to impute the missing outcome values, effort should be made to follow the patient until the endpoint or the end of the trial. The information in the follow-up period can be used to describe the benefit/risk to those patients who would discontinue treatment in the actual clinical practice, while imputing values that are not observed, yet may never exist, can only answer the unrealistic question, "What would have happened had the subject not discontinued?" Minimizing missing data is possible through the joint efforts of drug companies and regulatory agencies. Drug companies can improve their efforts in study design and operation, including off-treatment follow-up, prioritization of information collection, endpoint selection, and detailed documentation of reasons for missing data. Regulatory agencies can provide general guidance and convey specific comments for improvement through protocol review regarding missing data; and can ensure proper labeling language that reflects the extent of missing data and the reliability of conclusions. C1 US FDA, Div Biometr 4, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Soon, G (reprint author), US FDA, Div Biometr 4, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Bldg 21,10993 New Hampshire Ave, Silver Spring, MD 20993 USA. EM guoxing.soon@fda.hhs.gov FU US Food and Drug Administration FX -The author would like to thank Dr. Mohammad Huque and Dr. Robert O'Neill for their valuable comments. The views expressed in this article are those of the author and do not necessarily represent those of the US Food and Drug Administration. NR 11 TC 1 Z9 1 U1 0 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 JUL PY 2009 VL 43 IS 4 BP 485 EP 492 PG 8 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 469EC UT WOS:000267877500014 ER PT J AU Ehrenfeld, E Modlin, J Chumakov, K AF Ehrenfeld, Ellie Modlin, John Chumakov, Konstantin TI Future of polio vaccines SO EXPERT REVIEW OF VACCINES LA English DT Review DE eradication; global vaccination program; immunization; inactivated polio vaccine; infectious disease control; oral polio vaccine ID PARALYTIC POLIOMYELITIS; ENHANCED-POTENCY; NERVOUS-SYSTEM; ERADICATION; ELIMINATION; INFECTION; MICE; EPIDEMIOLOGY; IMMUNIZATION; VACCINATION AB Over the past half-century, global use of highly effective vaccines against poliomyelitis brought this disease to the brink of elimination. Mounting evidence supports the argument that a high level of population immunity must be maintained after wild poliovirus circulation is stopped to preserve a polio-free status worldwide. Shifting factors in the risk-benefit-cost equation favor the creation of new poliovirus vaccines for use in the foreseeable future. Genetically stable attenuated virus strains could be developed for an improved oral poliovirus vaccine, but proving their safety and efficacy would be impractical owing to the enormous size of the clinical trials required. Novel versions of inactivated poliovirus vaccine that could be used globally should be developed. An improved inactivated poliovirus vaccine must be efficacious, inexpensive, safe to manufacture and easy to administer. Combination products containing inactivated poliovirus vaccine and other protective antigens should become part of routine childhood immunizations around the world. C1 [Ehrenfeld, Ellie] NIAID, NIH, Bethesda, MD 20892 USA. [Modlin, John] Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Lebanon, NH 03766 USA. [Chumakov, Konstantin] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Ehrenfeld, E (reprint author), NIAID, NIH, 50 South Dr, Bethesda, MD 20892 USA. EM eehrenfeld@niaid.nih.gov; john.modlin@dartmouth.edu; konstantin.chumakov@fda.hhs.gov FU NIAID; NIH; FDA; DHHS FX This work was supported in part by the intramural research programs of the NIAID, NIH and the FDA, DHHS. 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 45 TC 28 Z9 28 U1 1 U2 12 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD JUL PY 2009 VL 8 IS 7 BP 899 EP 905 DI 10.1586/ERV.09.49 PG 7 WC Immunology SC Immunology GA 471KM UT WOS:000268056500013 PM 19545205 ER PT J AU Johnson, TJ Logue, CM Wannemuehler, Y Kariyawasam, S Doetkott, C DebRoy, C White, DG Nolan, LK AF Johnson, Timothy J. Logue, Catherine M. Wannemuehler, Yvonne Kariyawasam, Subhashinie Doetkott, Curt DebRoy, Chitrita White, David G. Nolan, Lisa K. TI Examination of the Source and Extended Virulence Genotypes of Escherichia coli Contaminating Retail Poultry Meat SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID URINARY-TRACT-INFECTION; ANTIMICROBIAL-RESISTANT; CAMPYLOBACTER CONTAMINATION; PHYLOGENETIC DISTRIBUTION; MOLECULAR EPIDEMIOLOGY; NEONATAL MENINGITIS; GREATER WASHINGTON; DNA-SEQUENCE; RAW CHICKEN; SALMONELLA AB Extraintestinal pathogenic Escherichia coli (ExPEC) are major players in human urinary tract infections, neonatal bacterial meningitis, and sepsis. Recently, it has been suggested that there might be a zoonotic component to these infections. To determine whether the E. coli contaminating retail poultry are possible extraintestinal pathogens, and to ascertain the source of these contaminants, they were assessed for their genetic similarities to E. coli incriminated in colibacillosis (avian pathogenic E. coli [APEC]), E. coli isolated from multiple locations of apparently healthy birds at slaughter, and human ExPEC. It was anticipated that the retail poultry isolates would most closely resemble avian fecal E. coli since only apparently healthy birds are slaughtered, and fecal contamination of carcasses is the presumed source of meat contamination. Surprisingly, this supposition proved incorrect, as the retail poultry isolates exhibited gene profiles more similar to APEC than to fecal isolates. These isolates contained a number of ExPEC-associated genes, including those associated with ColV virulence plasmids, and many belonged to the B2 phylogenetic group, known to be virulent in human hosts. Additionally, E. coli isolated from the crops and gizzards of apparently healthy birds at slaughter also contained a higher proportion of ExPEC-associated genes than did the avian fecal isolates examined. Such similarities suggest that the widely held beliefs about the sources of poultry contamination may need to be reassessed. Also, the presence of ExPEC-like clones on retail poultry meat means that we cannot yet rule out poultry as a source of ExPEC human disease. C1 [Nolan, Lisa K.] Iowa State Univ, Coll Vet Med, Dept Vet Microbiol & Prevent Med, Ames, IA 50011 USA. [Johnson, Timothy J.] Univ Minnesota, Dept Vet & Biomed Sci, St Paul, MN 55108 USA. [Logue, Catherine M.] N Dakota State Univ, Dept Vet & Microbiol Sci, Fargo, ND 58105 USA. [Kariyawasam, Subhashinie] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. [Doetkott, Curt] N Dakota State Univ, Informat Technol Serv, Fargo, ND 58105 USA. [DebRoy, Chitrita] Penn State Univ, E Coli Reference Ctr, University Pk, PA 16802 USA. [White, David G.] US FDA, Ctr Vet Med, Res Off, Laurel, MD USA. RP Nolan, LK (reprint author), Iowa State Univ, Coll Vet Med, Dept Vet Microbiol & Prevent Med, 1802 Univ Blvd,VMRI 2, Ames, IA 50011 USA. EM lknolan@iastate.edu FU Iowa State University's College of Veterinary Medicine; Prudent Use of Antibiotics (APUA) NIH [U24 AI 50139] FX The authors are grateful to Dr. Paul Carson (Meritcare Medical Center, Fargo, ND), Dr. James R. Johnson (VA Medical Center and University of Minnesota, Minneapolis, MN), Dr. Lodewijk Spanjaard (Academic Medical Center, Amsterdam, The Netherlands), and Dr. Kwang Sik Kim (Johns Hopkins University, Baltimore, MD) for providing some of the human isolates used in this study. This project was funded by Iowa State University's College of Veterinary Medicine and The Alliance for the Prudent Use of Antibiotics (APUA) NIH Grant No. U24 AI 50139. NR 53 TC 32 Z9 33 U1 0 U2 5 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 JUL PY 2009 VL 6 IS 6 BP 657 EP 667 DI 10.1089/fpd.2009.0266 PG 11 WC Food Science & Technology SC Food Science & Technology GA 471ZS UT WOS:000268097900003 PM 19580453 ER PT J AU Sacks, LV Behrman, RE AF Sacks, Leonard V. Behrman, Rachel E. TI Challenges, successes and hopes in the development of novel TB therapeutics SO FUTURE MEDICINAL CHEMISTRY LA English DT Review ID MULTIDRUG-RESISTANT TUBERCULOSIS; MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; DRUG CANDIDATE; IN-VITRO; PERSISTENCE; DISCOVERY; GROWTH; MODEL; VIVO AB Despite efficacious drugs for treatment, TB continues to affect enormous numbers of patients throughout the world. Failure to control TB may be related to the biological characteristics of Mycobacterium tuberculosis, the nature of susceptible hosts often impoverished and poorly supported by healthcare infrastructure and the complex treatment regimens that must be used. Challenges to anti-TB drug development include the organism's slow replication, the ability of M. tuberculosis to survive in a dormant state and to persist despite therapy, its impregnable cell wall and its capacity to develop resistance to drugs. The need for extended therapy using combinations of drugs remains a practical obstacle to effective control in poor, malnourished and diseased communities most susceptible to TB. High-throughput screening of candidate agents and investigation of drugs already in use for other infections are yielding promising new candidates for TB treatment. New families of drugs entering clinical trials include 5-nitroimidazoles, diarylquinolines and ethylene diamines. Increasing funding initiatives, advances in the biology of TB and strategies for drug discovery have rejuvenated the pipeline of new drugs for TB, promising an expanding armamentarium of effective drugs with improved tolerability and potential to treat drug-resistant cases. C1 [Sacks, Leonard V.; Behrman, Rachel E.] US FDA, Off Crit Path Programs, Rockville, MD 20857 USA. RP Sacks, LV (reprint author), US FDA, Off Crit Path Programs, Room 14B 45,5600 Fishers Lane, Rockville, MD 20857 USA. EM leonard.sacks@fda.hhs.gov NR 44 TC 7 Z9 7 U1 0 U2 4 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1756-8919 J9 FUTURE MED CHEM JI Future Med. Chem. PD JUL PY 2009 VL 1 IS 4 BP 749 EP 756 DI 10.4155/FMC.09.53 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 575LJ UT WOS:000276068200017 PM 21426037 ER PT J AU Motakis, E Ivshina, AV Kuznetsov, VA AF Motakis, Efthimios Ivshina, Anna V. Kuznetsov, Vladimir A. TI Data-Driven Approach to Predict Survival of Cancer Patients Estimation of Microarray Genes' Prediction Significance by Cox Proportional Hazard Regression Model SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Article ID BREAST-CANCER; VITAMIN-D; CELLS C1 [Motakis, Efthimios; Kuznetsov, Vladimir A.] ASTAR, BioInformat Inst, Singapore, Singapore. [Ivshina, Anna V.] Genome Inst Singapore, Lab Microarrays & Express Genom, Singapore, Singapore. [Ivshina, Anna V.; Kuznetsov, Vladimir A.] US FDA, Rockville, MD 20857 USA. [Kuznetsov, Vladimir A.] Russian Acad Sci, Inst Chem Phys, Lab Math Immunobiophys, Moscow 117901, Russia. [Kuznetsov, Vladimir A.] NCI, NICHD, NIH, Bethesda, MD 20892 USA. [Kuznetsov, Vladimir A.] ASTAR, Genome Inst Singapore, Lab Computat Genom & Syst Biol, Singapore, Singapore. RP Kuznetsov, VA (reprint author), ASTAR, BioInformat Inst, Singapore, Singapore. EM vladimirk@bii.a-star.edu.sg NR 23 TC 20 Z9 21 U1 1 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD JUL-AUG PY 2009 VL 28 IS 4 BP 58 EP 66 DI 10.1109/MEMB.2009.932937 PG 9 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA 474KJ UT WOS:000268281900015 PM 19622426 ER PT J AU Chattopadhyay, R Kumar, S AF Chattopadhyay, Rana Kumar, Sanjai TI Malaria vaccine: Latest update and challenges ahead SO INDIAN JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Review DE Malaria; Plasmodium spp; Vaccine ID PLASMODIUM-FALCIPARUM MALARIA; CD8(+) T-CELLS; CIRCUMSPOROZOITE PROTEIN VACCINE; SPOROZOITE SURFACE PROTEIN-2; RANDOMIZED CONTROLLED-TRIAL; RECEPTOR-BINDING DOMAIN; PROTECTIVE IMMUNITY; LYMPHOCYTE RESPONSES; MOZAMBICAN CHILDREN; INTERFERON-GAMMA AB Development of an effective malaria vaccine remains one of the biggest challenges faced by modem science. Although in the last decade tremendous advances have taken place in the design, construction and testing of malaria vaccines, many questions still remained unanswered. This review highlights exclusively some of the exciting and most recent progress in the development and clinical testing of candidate malaria vaccines and points out some of the outstanding scientific issues and technological challenges that must be met to develop a successful vaccine. C1 [Chattopadhyay, Rana; Kumar, Sanjai] US FDA, Malaria Res Program, Div Emerging & Transfus Transmitted Dis, Off Blood & Res Review,Ctr Biol Evaluat & Res, Kensington, MD 20895 USA. RP Kumar, S (reprint author), US FDA, Malaria Res Program, Div Emerging & Transfus Transmitted Dis, Off Blood & Res Review,Ctr Biol Evaluat & Res, 5516 Nicholson Lane, Kensington, MD 20895 USA. EM sanjai.kumar@fda.hhs.gov NR 80 TC 5 Z9 6 U1 1 U2 2 PU NATL INST SCIENCE COMMUNICATION PI NEW DELHI PA DR K S KRISHNAN MARG, NEW DELHI 110 012, INDIA SN 0019-5189 J9 INDIAN J EXP BIOL JI Indian J. Exp. Biol. PD JUL PY 2009 VL 47 IS 7 BP 527 EP 536 PG 10 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 468CG UT WOS:000267790500001 PM 19761036 ER PT J AU Foley, SL Lynne, AM Nayak, R AF Foley, Steven L. Lynne, Aaron M. Nayak, Rajesh TI Molecular typing methodologies for microbial source tracking and epidemiological investigations of Gram-negative bacterial foodborne pathogens SO INFECTION GENETICS AND EVOLUTION LA English DT Review DE Gram-negative bacterial typing methods; Restriction-based typing; Sequencing-based typing; Amplification-based typing methods ID FIELD GEL-ELECTROPHORESIS; TANDEM-REPEAT ANALYSIS; FRAGMENT-LENGTH-POLYMORPHISM; ESCHERICHIA-COLI O157-H7; ENTERICA SEROVAR TYPHIMURIUM; SINGLE-NUCLEOTIDE POLYMORPHISMS; INSERTION-SEQUENCE IS200; ANTIMICROBIAL RESISTANCE GENES; SHIGELLA-DYSENTERIAE TYPE-1; REPETITIVE DNA-SEQUENCES AB Gram-negative bacterial foodborne pathogens are a worldwide cause of morbidity and mortality. The ability to carry out epidemiological investigations to determine the primary sources of bacterial contamination is important to improve public health. Multiple methods are available for bacterial source tracking and to determine the distribution of pathogens isolated from sick patients. The molecular based typing methods available fall into three general categories: those based on restriction analysis of the bacterial DNA; those based on polymerase chain reaction (PCR) amplification of particular genetic targets; and those based on the identification of DNA sequence polymorphisms. The techniques that are examined in this review include: plasmid analysis, restriction fragment length polymorphism methods, pulsed-field gel electrophoresis, amplified fragment length polymorphism analysis, PCR-based genotyping, variable number of tandem repeat analysis, multilocus sequence typing, and single nucleotide polymorphism analysis. These methods are described along with a discussion of the strengths and weaknesses of the techniques for genotyping the major Gram-negative foodborne pathogens-Campylobacter spp., Salmonella enterica, Shigella spp., Escherichia coli, and Yersinia enterocolitica. (C) 2009 Elsevier B.V. All rights reserved. C1 [Foley, Steven L.] Marshfield Clin Fdn Med Res & Educ, Natl Farm Med Ctr, Marshfield, WI 54449 USA. [Lynne, Aaron M.] Sam Houston State Univ, Dept Biol Sci, Huntsville, TX 77340 USA. [Nayak, Rajesh] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Foley, SL (reprint author), Marshfield Clin Fdn Med Res & Educ, Natl Farm Med Ctr, Marshfield, WI 54449 USA. EM foleysteven@yahoo.com NR 158 TC 96 Z9 104 U1 0 U2 21 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1348 J9 INFECT GENET EVOL JI Infect. Genet. Evol. PD JUL PY 2009 VL 9 IS 4 BP 430 EP 440 DI 10.1016/j.meegid.2009.03.004 PG 11 WC Infectious Diseases SC Infectious Diseases GA 458SW UT WOS:000267044800005 PM 19460308 ER PT J AU Holloway, K Fearon, M Scalia, V Dawood, M Mamiya, H Van Caeseele, P Khurana, V Appleyard, G Pabbaraju, K Fox, J Grinev, A Rios, M Barker, I Drebot, M AF Holloway, K. Fearon, M. Scalia, V. Dawood, M. Mamiya, H. Van Caeseele, P. Khurana, V. Appleyard, G. Pabbaraju, K. Fox, J. Grinev, A. Rios, M. Barker, I. Drebot, M. TI Identification and characterization of West Nile virus genetic variants collected from Canadian samples 2006-2008 SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Meeting Abstract CT 26th International Congress of Chemotherapy and Infection CY JUN 18-21, 2009 CL Toronto, CANADA C1 [Holloway, K.; Drebot, M.] Publ Hlth Agcy Canada, Winnipeg, MB, Canada. [Fearon, M.; Scalia, V.] Canadian Blood Serv, Toronto, ON, Canada. [Dawood, M.; Mamiya, H.; Van Caeseele, P.] Cadham Prov Lab, Winnipeg, MB, Canada. [Khurana, V.; Appleyard, G.; Pabbaraju, K.; Fox, J.] Prov Lab Publ Hlth, Calgary, AB, Canada. [Grinev, A.; Rios, M.] US FDA, Bethesda, MD 20014 USA. [Barker, I.] Univ Guelph, Guelph, ON N1G 2W1, Canada. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-8579 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD JUL PY 2009 VL 34 MA O52 BP S18 EP S19 PG 5 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 470DR UT WOS:000267955200053 ER PT J AU McMullen, SE Schenck, FJ Vega, VA AF McMullen, Sarah E. Schenck, Frank J. Vega, Victor A. TI Rapid Method for the Determination and Confirmation of Fluoroquinolone Residues in Catfish Using Liquid Chromatography/Fluorescence Detection and Liquid Chromatography-Tandem Mass Spectrometry SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MULTIRESIDUE DETERMINATION; FLUORESCENCE DETECTION; ANTIBIOTICS; CAMPYLOBACTER; SHRIMP AB A simplified method for the extraction and determination of four fluoroquinolone (FQ) residues (ciprofloxacin, enrofloxacin, sarafloxacin, and difloxacin) in catfish is presented. In this method, the FQ residues were extracted with acidified acetonitrile, and the extract was defatted with dispersive C(18) solid-phase extraction (SPE) sorbent or hexane. A portion of the extract was evaporated and reconstituted in the mobile phase. The quantitative determination was accomplished with LC-fluorescence detection (FLD), and the confirmation was by LC-MS/MS. Fortifications of catfish tissue were carried out at 0.5x, x, 2x, and 4x, where x = 5 ppb (U.S. Food and Drug Administration current regulatory target level). Recoveries for the LC/FLD determination of five replicates (for both cleanup routes) at each level ranged from 64 to 98%, with RSD values <8%. The method quantitation limits for all residues were <1 ng/g. The LC-MS/MS analysis of the same extracts confirmed all FQ residues at all levels. This method is an improvement over existing methodologies since additional cleanup steps, such as cation exchange SPE column cleanup, are not utilized. The C(18) dispersive SPE method represents a novel cleanup approach for FQs in fish tissue. C1 [McMullen, Sarah E.; Schenck, Frank J.] US FDA, SE Reg Lab, Atlanta, GA 30309 USA. [Vega, Victor A.] Food Safety & Inspect Serv, USDA, Russell Res Ctr, Athens, GA 30605 USA. RP McMullen, SE (reprint author), US FDA, SE Reg Lab, 60 8th St NE, Atlanta, GA 30309 USA. EM sarah.mcmullen@fda.hhs.gov NR 14 TC 17 Z9 19 U1 0 U2 4 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 2009 VL 92 IS 4 BP 1233 EP 1240 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 487CP UT WOS:000269248500032 PM 19714995 ER PT J AU Nochetto, CB Reimschuessel, R Gieseker, C Cheely, CS Carson, MC AF Nochetto, Cristina B. Reimschuessel, Renate Gieseker, Charles Cheely, Christie-Sue Carson, Mary C. TI Determination of Tricaine Residues in Fish by Liquid Chromatography SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID BENZOCAINE AB Tricaine methanesulfonate (MS-222) is approved by the U.S. Food and Drug Administration, Center for Veterinary Medicine (CVM), as an anesthetic drug for select aquaculture species. It was approved for use as a handling aid with a 3 week withdrawal time. The drug is rapidly metabolized and excreted; therefore, CVM approved its use without requiring a regulatory method for drug residues in tissues. However, there are concerns that the drug may be used to sedate fish during transport to slaughter. A regulatory method will enable monitoring for unsafe residues of this drug resulting from extralabel use. We present a quantitative method, using LC at a target level of 0.1 mg/kg (ppm), for three different farmed species: salmon (Salmo salar); tilapia (Oreochromis spp.); and catfish (Ictalurus punctatus). The assay begins with an acetonitrile extraction, followed by filtration and mixed-mode cation-exchange solid-phase extraction cleanup. The extracts are analyzed by reversed-phase LC with UV detection at 320 nm. The method was validated by using fish fillets with incurred residues, control fish fillets, and fish fillets fortified at half the target level, the target level, and twice the target level (0.05, 0.1, and 0.2 ppm, respectively). For all species, accuracy is >= 80% and the RSD is <= 10%. The method complies with CVM performance criteria for the determination of veterinary drug residues. C1 [Nochetto, Cristina B.; Reimschuessel, Renate; Gieseker, Charles; Cheely, Christie-Sue; Carson, Mary C.] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP Nochetto, CB (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM cristina.nochetto@fda.hhs.gov NR 11 TC 5 Z9 5 U1 1 U2 5 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 2009 VL 92 IS 4 BP 1241 EP 1247 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 487CP UT WOS:000269248500033 PM 19714996 ER PT J AU Lyle, DB Shallcross, JC Durfor, CN Hitchins, VM Breger, JC Langone, JJ AF Lyle, Daniel B. Shallcross, Jonathan C. Durfor, Charles N. Hitchins, Victoria M. Breger, Joyce C. Langone, John J. TI Screening biomaterials for stimulation of nitric oxide-mediated inflammation SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE biomaterials; nitric oxide; inflammation; macrophage; hyaluronic acid ID MACROPHAGE CELL-LINES; NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; INTERFERON-GAMMA; RAW 264.7; ACID; HYALURONAN; ACTIVATION; EXPRESSION; ENDOTOXIN AB Inflammatory reactions to biomaterials may include macrophage-mediated generation of nitric oxide (NO), which may harm patient tissue or potentially interfere with proper function of an implanted device. RAW 264.7 cells were grown in culture and treated at various times with lipopolysaccharide (LPS, endotoxin), murine recombinant gamma-interferon (mrIFN-gamma), and different preparation of hyaluronic acid (HA). Increase ill fluorescence of 2,3-diaminonaphthalene (DAN) allowed for detection of initial (24 h or less) NO inflammatory responses of. RAW 264.7 to LPS from E. coli O26:B6. By looking at early time points, mrIFN-gamma augmentation of the LPS effect was observed, simulating a complex immune reaction. Activation through nuclear factor-kappa B (NF-kappa B), was confirmed in this system by parthenolide inhibition of LPS stimulation. C1 [Lyle, Daniel B.; Shallcross, Jonathan C.; Durfor, Charles N.; Hitchins, Victoria M.; Breger, Joyce C.; Langone, John J.] US FDA, Div Biol, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Lyle, DB (reprint author), US FDA, Div Biol, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM dan.lyle@fda.hhs.gov NR 49 TC 3 Z9 3 U1 2 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1549-3296 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD JUL PY 2009 VL 90A IS 1 BP 82 EP 93 DI 10.1002/jbm.a.32060 PG 12 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 453YL UT WOS:000266648700008 PM 18481787 ER PT J AU Hepp, NM Mindak, WR Cheng, J AF Hepp, Nancy M. Mindak, William R. Cheng, John TI Determination of total lead in lipstick: Development and validation of a microwave-assisted digestion, inductively coupled plasma-mass spectrometric method SO JOURNAL OF COSMETIC SCIENCE LA English DT Article ID ACID-DIGESTION AB Recent reports describing the presence of lead (Pb) in lipsticks have suggested that, under ordinary, use, the potential amount of Pb exposure is harmful. To permit independent assessment of the Pb contamination, a method for determining total Ph in lipstick using microwave-assisted digestion and analysis employing inductively Coupled plasma-mass spectrometry (ICP-MS) was developed and validated. Since lipsticks may contain fats, oils, pigments, dyes, and minerals, several reference materials (RM) were analyzed, including coal, wear metals in oil, organic Pb in oil, milk powder, and estuarine sediment. With the exception of the RM with mineral content (estuarine sediment), complete recovery of Pb from the RMs was obtained by simple nitric acid (HNO(3)) digestion. Complete recovery of Ph from estuarine sediment was achieved only when hydrofluoric acid (HF) was added to the digestion mix, followed by treatment with excess boric acid (H(3)BO(3)) to neutralize the HF and to dissolve insoluble fluorides. Commercial lipsticks were tested for total Pb by the validated method. The detection limit was estimated to be 0.04 mu g Pb/g. The average value obtained for the lipsticks was 1.07 mu g/g. Undigested material was present in some lipstick digests when only HNO(3) Was used, and generally lower Pb values were obtained. All of the Pb levels found by the U.S. Food and Drug Administration (FDA) were within the range the agency would expect to find in lipsticks formulated with permitted color additives and other ingredients prepared under good manufacturing practice (GMP) conditions. This method will be useful for the FDA and industry in helping to ensure the safety of cosmetic products. C1 [Hepp, Nancy M.] US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, College Pk, MD 20740 USA. [Mindak, William R.; Cheng, John] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. RP Hepp, NM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, College Pk, MD 20740 USA. NR 11 TC 29 Z9 30 U1 8 U2 31 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 JUL-AUG PY 2009 VL 60 IS 4 BP 405 EP 414 PG 10 WC Chemistry, Applied; Dermatology SC Chemistry; Dermatology GA 489AG UT WOS:000269391100002 PM 19691936 ER PT J AU Kornhauser, A Wei, RR Yamaguchi, Y Coelho, SG Kaidbey, K Barton, C Takahashi, K Beer, JZ Miller, SA Hearing, VJ AF Kornhauser, Andrija Wei, Rong-Rong Yamaguchi, Yuji Coelho, Sergio G. Kaidbey, Kays Barton, Curtis Takahashi, Kaoruko Beer, Janusz Z. Miller, Sharon A. Hearing, Vincent J. TI The effects of topically applied glycolic acid and salicylic acid on ultraviolet radiation-induced erythema, DNA damage and sunburn cell formation in human skin SO JOURNAL OF DERMATOLOGICAL SCIENCE LA English DT Article DE Hydroxyacids; Glycolic acid; Salicylic acid; UV-damage; Erythema; DNA damage; Sunburn cells; Cosmetics ID ALPHA-HYDROXY ACIDS; SODIUM-SALICYLATE; XERODERMA-PIGMENTOSUM; PYRIMIDINE DIMER; UV-RADIATION; LIGHT; PIGMENTATION; MUTATIONS; SUNLIGHT; CANCER AB Background: alpha-Hydroxy acids (alpha HAs) are reported to reduce signs of aging in the skin and are widely used cosmetic ingredients. Several studies suggest that alpha HA can increase the sensitivity of skin to ultraviolet radiation. More recently, beta-hydroxy acids (beta HAs), or combinations of alpha HA and beta HA have also been incorporated into antiaging skin care products. Concerns have also arisen about increased sensitivity to ultraviolet radiation following use of skin care products containing beta-HA. Objective: To determine whether topical treatment with glycolic acid, a representative aHA, or with salicylic acid, a beta HA modifies the short-term effects of solar simulated radiation (SSR) in human skin. Methods: Fourteen subjects participated in this study. Three of the four test sites on the mid-back of each subject were treated daily Monday-Friday, for a total of 3.5 weeks, with glycolic acid (10%), salicylic acid (2%), or vehicle (control). The fourth site received no treatment. After the last treatment, each site was exposed to SSR, and shave biopsies from all four sites were obtained. The endpoints evaluated in this study were erythema (assessed visually and instrumentally), DNA damage and sunburn cell formation. Results: Treatment with glycolic acid resulted in increased sensitivity of human skin to SSR, measured as an increase in erythema, DNA damage and sunburn cell formation. Salicylic acid did not produce significant changes in any of these biomarkers. Conclusions: Short-term topical application of glycolic acid in a cosmetic formulation increased the sensitivity of human skin to SSR, while a comparable treatment with salicylic acid did not. Published by Elsevier Ireland Ltd on behalf of Japanese Society for Investigative Dermatology. C1 [Kornhauser, Andrija; Wei, Rong-Rong; Barton, Curtis] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Yamaguchi, Yuji; Coelho, Sergio G.; Takahashi, Kaoruko; Hearing, Vincent J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Kaidbey, Kays] KGL Inc, Ivy Labs, Broomall, PA 19008 USA. [Beer, Janusz Z.; Miller, Sharon A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Kornhauser, A (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM akornhause@aol.com FU U.S. FDA Office of Science and Health Coordination FX This research was supported by the U.S. FDA Office of Science and Health Coordination and in part by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. The authors wish to thank K. Korossy, MD and C. Tock, MD for the dermatological support and for obtaining biopsies from all subjects; J. Kniskern, RN for excellent handling of human subjects' records; W. Warner for useful input to the manuscript; D. Lowther for her skillful technical and editorial assistance in preparing this manuscript; J. Hubinger for analysis of test products. NR 44 TC 16 Z9 16 U1 4 U2 15 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0923-1811 J9 J DERMATOL SCI JI J. Dermatol. Sci. PD JUL PY 2009 VL 55 IS 1 BP 10 EP 17 DI 10.1016/j.jdermsci.2009.03.011 PG 8 WC Dermatology SC Dermatology GA 459FJ UT WOS:000267086100002 PM 19411163 ER PT J AU Malik, TH Wolbert, C Nerret, L Sauder, C Rubin, S AF Malik, Tahir H. Wolbert, Candie Nerret, Laura Sauder, Christian Rubin, Steven TI Single amino acid changes in the mumps virus haemagglutinin-neuraminidase and polymerase proteins are associated with neuroattenuation SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID GENE; NEUROVIRULENCE; REPLICATION; MENINGITIS; SEQUENCE; HUMANS AB It has previously been shown that three amino acid changes, one each in the fusion (F; Ala/Thr-91 -> Thr), haemagglutinin-neuraminidase (HN; Ser-466 -> Asn) and polymerase (L; Ile-736 -> Val) proteins, are associated with attenuation of a neurovirulent clinical isolate of mumps virus (88-1961) following serial passage in vitro. Here, using full-length cDNA plasmid clones and site-directed mutagenesis, it was shown that the single amino acid change in the HN protein and to a lesser extent, the change in the L protein, resulted in neuroattenuation, as assessed in rats. The combination of both amino acid changes caused neuroattenuation of the virus to levels previously reported for the clinical isolate following attenuation in vitro. The amino acid change in the F protein, despite having a dramatic effect on protein function in vitro, was previously shown to not be involved in the observed neuroattenuation, highlighting the importance of conducting confirmatory in vivo studies. This report provides additional supporting evidence for the role of the HN protein as a virulence factor and, as far as is known, is the first report to associate an amino acid change in the L protein with mumps virus neuroattenuation. C1 [Malik, Tahir H.; Wolbert, Candie; Nerret, Laura; Sauder, Christian; Rubin, Steven] US FDA, Ctr Biol Evaluat & Res, DVP Off Vaccines Res & Review, Bethesda, MD 20892 USA. RP Malik, TH (reprint author), US FDA, Ctr Biol Evaluat & Res, DVP Off Vaccines Res & Review, Bethesda, MD 20892 USA. EM tahir.malik@fda.hhs.gov NR 16 TC 10 Z9 11 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD JUL PY 2009 VL 90 BP 1741 EP 1747 DI 10.1099/vir.0.009449-0 PG 7 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 470DX UT WOS:000267955900023 PM 19282431 ER PT J AU Pogribny, IP Tryndyak, VP Bagnyukova, TV Melnyk, S Montgomery, B Ross, SA Latendresse, JR Rusyn, I Beland, FA AF Pogribny, Igor P. Tryndyak, Volodymyr P. Bagnyukova, Tetyana V. Melnyk, Stepan Montgomery, Beverly Ross, Sharon A. Latendresse, John R. Rusyn, Ivan Beland, Frederick A. TI Hepatic epigenetic phenotype predetermines individual susceptibility to hepatic steatosis in mice fed a lipogenic methyl-deficient diet SO JOURNAL OF HEPATOLOGY LA English DT Article DE Hepatic steatosis; Non-alcoholic steatohepatitis; DNA methylation; Histone modifications; Disease susceptibility ID HISTONE LYSINE METHYLATION; FATTY LIVER-DISEASE; NONALCOHOLIC STEATOHEPATITIS; DNA; HYPOMETHYLATION; MECHANISMS; PATTERNS; EXPOSURE; ELEMENTS; GENES AB Background/Aims: The importance of epigenetic changes in etiology and pathogenesis of disease has been increasingly recognized. However, the role of epigenetic alterations in the genesis of hepatic steatosis and cause of individual susceptibilities to this pathological state are largely unknown. Methods: Male inbred C57BL/6J and DBA/2J mice were fed a lipogenic methyl-deficient diet (MDD) that causes liver injury similar to human non-alcoholic steatohepatitis (NASH) for 6, 12, or 18 weeks, and the status of global and repetitive elements cytosine methylation, histone modifications, and expression of proteins responsible for those epigenetic modifications in livers was determined. Results: The development of hepatic steatosis in inbred C57BL/6J and DBA/2J mice was accompanied by prominent epigenetic abnormalities. This was evidenced by pronounced loss of genomic and repetitive sequences cytosine methylation, especially at major and minor satellites, accompanied by increased levels of repeat-associated transcripts, aberrant histone modifications, and alterations in expression of the maintenance DNA methyltransferase 1 (DNMT1) and de novo DNMT3A proteins in the livers of both mouse strains. However, the DBA/2J mice, which were characterized by an initially lower degree of methylation of repetitive elements and lower extent of histone H3 lysine 9 (H3K9) and H3 lysine 27 (H3K27) trimethylation in the normal livers, as compared to those in the C57BL/6J mice, developed more prominent NASH-specific pathomorphological changes. Conclusions: These results mechanistically link epigenetic alterations to the pathogenesis of hepatic steatosis and strongly suggest that differences in the cellular epigenetic status may be a predetermining factor to individual susceptibilities to hepatic steatosis. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver. C1 [Pogribny, Igor P.; Tryndyak, Volodymyr P.; Bagnyukova, Tetyana V.; Montgomery, Beverly; Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Melnyk, Stepan] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. [Ross, Sharon A.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov RI Rusyn, Ivan/S-2426-2016 FU NIAAA NIH HHS [R01 AA016258-04, R01 AA016258]; NIEHS NIH HHS [P42 ES005948, P42 ES005948-170010, R01 ES015241, R01 ES015241-02] NR 31 TC 67 Z9 67 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD JUL PY 2009 VL 51 IS 1 BP 176 EP 186 DI 10.1016/j.jhep.2009.03.021 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 467CF UT WOS:000267713400021 PM 19450891 ER PT J AU Abou-Zeid, KA Oscar, TP Schwarz, JG Hashem, FM Whiting, RC Yoon, K AF Abou-Zeid, Khaled A. Oscar, Thomas P. Schwarz, Jurgen G. Hashem, Fawzy M. Whiting, Richard C. Yoon, Kisun TI Development and Validation of a Predictive Model for Listeria monocytogenes Scott A as a Function of Temperature, pH, and Commercial Mixture of Potassium Lactate and Sodium Diacetate SO JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article DE L. monocytogenes Scott A; polynomial model; model validation; potassium lactate/diacetate mixture; temperature ID COOKED MEAT-PRODUCTS; MICROBIAL-GROWTH; SMOKED SALMON; NA-LACTATE; SURVIVAL; BROTH; ATMOSPHERE; MOISTURE; CHLORIDE; BOLOGNA AB The objective of this study was to develop and validate secondary models that can predict growth parameters of L. monocytogenes Scott A as a function of concentrations (0-3%) of a commercial potassium lactate (PL) and sodium diacetate (SDA) mixture, pH (5.5-7.0), and temperature (4-37 degrees C). A total of 120 growth curves were fitted to the Baranyi primary model that directly estimates lag time (LT) and specific growth rate (SGR). The effects of the variables on L. monocytogenes Scott A growth kinetics were modeled by response surface analysis using quadratic and cubic polynomial models of the natural logarithm transformation of both LT and SGR. Model performance was evaluated with dependent data and independent data using the prediction bias (B(f)) and accuracy factors (A(f)) as well as the acceptable prediction zone method [percentage of relative errors (%RE)]. Comparison of predicted versus observed values of SGR indicated that the cubic model fits better than the quadratic model, particularly at 4 and 10 degrees C. The B(f) and A(f) for independent SGR were 1.00 and 1.08 for the cubic model and 1.08 and 1.16 for the quadratic model, respectively. For cubic and quadratic models, the %REs for the independent SGR data were 92.6 and 85.7, respectively. Both quadratic and cubic polynomial models for SGR and LT provided acceptable predictions of L. monocytogenes Scott A growth in the matrix of conditions described in the present study. Model performance can be more accurately evaluated with B(f) and A(f) and % RE together. C1 [Abou-Zeid, Khaled A.; Schwarz, Jurgen G.; Hashem, Fawzy M.; Yoon, Kisun] Univ Maryland Eastern Shore, Ctr Food Sci & Technol, USDA ARS, Princess Anne, MD 21853 USA. [Oscar, Thomas P.] Univ Maryland Eastern Shore, Microbial Food Safety Res Unit, USDA ARS, Princess Anne, MD 21853 USA. [Yoon, Kisun] Kyung Hee Univ, Dept Food & Nutr, Seoul 130701, South Korea. [Whiting, Richard C.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Yoon, K (reprint author), Univ Maryland Eastern Shore, Ctr Food Sci & Technol, USDA ARS, Princess Anne, MD 21853 USA. EM ksyoon@khu.ac.kr FU JIFSAN (Joint Institute of Food Safety and Nutrition) FX Funding for this study was provided by the JIFSAN (Joint Institute of Food Safety and Nutrition). Thanks are extended to PURAC America Inc. for providing PURASAL P Opti. Form 4 for this study. NR 28 TC 8 Z9 8 U1 0 U2 5 PU KOREAN SOC MICROBIOLOGY & BIOTECHNOLOGY PI SEOUL PA KOREA SCI TECHNOL CENTER #507, 635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1017-7825 J9 J MICROBIOL BIOTECHN JI J. Microbiol. Biotechnol. PD JUL PY 2009 VL 19 IS 7 BP 718 EP 726 DI 10.4014/jmb.0809.534 PG 9 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 476OV UT WOS:000268452800013 PM 19652521 ER PT J AU Mahmood, I AF Mahmood, Iftekhar TI Role of Fixed Coefficients and Exponents in the Prediction of Human Drug Clearance: How Accurate Are the Predictions from One or Two Species? SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Review DE allometric scaling; clearance; bioavailability; biliary excretion ID MODIFIED ANTISENSE OLIGONUCLEOTIDE; WEIGHT THROMBIN INHIBITOR; RECOMBINANT FACTOR-IX; NECROSIS-FACTOR-ALPHA; IN-VITRO DATA; COMPARATIVE PHARMACOKINETICS; PLASMINOGEN-ACTIVATOR; LABORATORY-ANIMALS; HEALTHY-VOLUNTEERS; CLINICAL PHARMACOKINETICS AB Pharmacokinetic (PK) interspecies scaling is generally conducted using PK data from at least three animal species but three animal species may not be always available. In a recent manuscript, Tang et al. have described the methods to predict human drug clearance using one or two animal species. The authors claim that their proposed methods are better than the rule of exponents (ROE) which uses at least three animal species for the prediction of human drug clearance. A thorough examination of Tang et al.'s manuscript indicates that the data analysis may not be accurate. Considering that Tang et al.'s method may be of value, the objective of this study was to extend Tang et al.'s proposed methods for drugs given both intravenously and orally. The results of this study indicate that human drug clearance cannot be predicted with reasonable accuracy for most of the drugs by Tang et al.'s proposed methods and the accuracy of the prediction obtained from the ROE remains more accurate (based on average fold-error) than the one or two-species methods. This manuscript also clarifies some incorrect views regarding ROE presented by Tang et al. in their manuscript. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2472-2493, 2009 C1 US FDA, OBRR, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Mahmood, I (reprint author), US FDA, OBRR, Ctr Biol Evaluat & Res, 1451 Rockville Pike, Rockville, MD 20857 USA. EM iftekhar.mahmood@fda.hhs.gov NR 120 TC 21 Z9 21 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD JUL PY 2009 VL 98 IS 7 BP 2472 EP 2493 DI 10.1002/jps.21597 PG 22 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 465GJ UT WOS:000267570400019 PM 19025899 ER PT J AU Myers, MR Soneson, JE AF Myers, Matthew R. Soneson, Joshua E. TI Temperature modes for nonlinear Gaussian beams SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article DE bioacoustics; biological effects of acoustic radiation; biothermics; finite difference methods; nonlinear acoustics; ultrasonic propagation ID INTENSITY FOCUSED ULTRASOUND; HEAT TRANSFER EQUATION; TISSUE; ACOUSTICS AB In assessing the influence of nonlinear acoustic propagation on thermal bioeffects, approximate methods for quickly estimating the temperature rise as operational parameters are varied can be very useful. This paper provides a formula for the transient temperature rise associated with nonlinear propagation of Gaussian beams. The pressure amplitudes for the Gaussian modes can be obtained rapidly using a method previously published for simulating nonlinear propagation of Gaussian beams. The temperature-mode series shows that the nth temperature mode generated by nonlinear propagation, when normalized by the fundamental, is weaker than the nth heat-rate mode (also normalized by the fundamental in the heat-rate series) by a factor of log(n)/n, where n is the mode number. Predictions of temperature rise and thermal dose were found to be in close agreement with full, finite-difference calculations of the pressure fields, temperature rise, and thermal dose. Applications to non-Gaussian beams were made by fitting the main lobe of the significant modes to Gaussian functions. C1 [Myers, Matthew R.; Soneson, Joshua E.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Myers, MR (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. NR 15 TC 8 Z9 8 U1 0 U2 2 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JUL PY 2009 VL 126 IS 1 BP 425 EP 433 DI 10.1121/1.3148204 PG 9 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 471NL UT WOS:000268065100053 PM 19603899 ER PT J AU Smith, ME Gopee, NV Ferguson, SA AF Smith, Melody E. Gopee, Neera V. Ferguson, Sherry A. TI Preferences of Minipigs for Environmental Enrichment Objects SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID PIGS; SWINE AB The minipig is an increasingly popular species for use in behavioral and toxicologic studies. As a result, quantification of environmental enrichment preferences for this species is especially important. We exposed 6 individually housed prepubertal female Yucatan minipigs to 1 of 3 different objects on a rotating schedule: 2 sessions with a hard plastic ball (diameter, 21.0 cm), and 3 sessions each with a large plastic apple (diameter, 22.5 cm) and a soft rubber cone (height, 48.0 cm). Objects were changed every 4 to 5 d. The initial 15 min after each object change was recorded, and duration of object interaction and other behaviors (activity and interaction with the food bowl) were measured. Results indicated significantly longer interactions with the cone (mean +/- SE, 282 +/- 54 s) than the ball (14 +/- 3 s). Interactions with the apple (66 +/- 18 s) and ball did not differ significantly. Interactions with the apple decreased across the 3 sessions, whereas interaction with the cone remained high for most minipigs over the 3 sessions. Duration of activity appeared to be inversely correlated with duration of object interaction (that is, the longer the subject interacted with the object, the less it engaged in nonobject activity). These results provide valuable and practical information on the features of objects that minipigs appear to prefer and offer suggestions for future studies evaluating environmental enrichment paradigms with individually housed minipigs. C1 [Smith, Melody E.; Ferguson, Sherry A.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Gopee, Neera V.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Ferguson, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. EM Sherry.Ferguson@fda.hhs.gov NR 18 TC 3 Z9 4 U1 1 U2 4 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD JUL PY 2009 VL 48 IS 4 BP 391 EP 394 PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 478SR UT WOS:000268609100009 PM 19653948 ER PT J AU Meysick, KC Seidman, J Falconio, JR AF Meysick, Karen C. Seidman, Jessica Falconio, Jason R. TI The Yersinia pseudotuberculosis YplA phospholipase differs in its activity, regulation and secretion from that of the Yersinia enterocolitica YplA SO MICROBIAL PATHOGENESIS LA English DT Article DE Phospholipases; Yersinia; Enzyme activity; Accessory protein; Secretion; Expression ID SERRATIA-MARCESCENS METALLOPROTEASE; ESCHERICHIA-COLI; ERWINIA-CHRYSANTHEMI; BACTERIAL PHOSPHOLIPASES; EXTRACELLULAR PROTEASES; MEMBRANE PHOSPHOLIPASE; GENOME SEQUENCE; ANKYRIN REPEAT; EXPRESSION; GENE AB Analysis of the Yersinia pseudotuberculosis and Yersinia pestis genomes indicates that both species carry an identical copy of a gene that is predicted to encode a protein which shares 80% similarity to the Yersinia enterocolitica YplA, a secreted phospholipase that has been shown to contribute to virulence. In contrast to well tolerated production of the Y. enterocolitica YplA in Escherichia coli, Y. pseudotuberculosis YplA expression was found to be toxic; however, cell viability could be restored if the Y. pseudotuberculosis YplA was expressed in the presence of its accessory protein YplB. In vitro, Y. pseudotuberculosis YplB was shown to reduce the activity of its cognate phospholipase in a dose-dependent manner. To determine whether the Y. pseudotuberculosis and Y. enterocolitica YplAs were secreted and regulated in a similar manner, secretion and promoter activity assays were performed. Unlike the situation apparent in Y. enterocolitica, expression of the Y. pseudotuberculosis yplA gene did not appear to be controlled by the flagellar regulon, nor did the phospholipase appear to be efficiently exported through the flagellar apparatus. These results indicate that the Yersinia YplAs vary in many of their attributes despite their high degree of amino acid homology. Published by Elsevier Ltd C1 [Meysick, Karen C.; Falconio, Jason R.] US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Lab Resp & Special Pathogens, Bethesda, MD 20892 USA. [Seidman, Jessica] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Meysick, KC (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Lab Resp & Special Pathogens, HFM 434,8800 Rockville Pike,Bldg 29,Room 430, Bethesda, MD 20892 USA. EM karen.meysick@fda.hhs.gov NR 53 TC 1 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0882-4010 J9 MICROB PATHOGENESIS JI Microb. Pathog. PD JUL PY 2009 VL 47 IS 1 BP 24 EP 32 DI 10.1016/j.micpath.2009.04.008 PG 9 WC Immunology; Microbiology SC Immunology; Microbiology GA 467ZZ UT WOS:000267784100004 PM 19397992 ER PT J AU Platek, SF Crowe, JB Ranieri, N Witkowski, M AF Platek, S. Frank Crowe, John B. Ranieri, Nicola Witkowski, Mark TI Applications of Microscopy and Microanalysis in US FDA Forensic Cases SO MICROSCOPY AND MICROANALYSIS LA English DT Meeting Abstract C1 [Platek, S. Frank; Crowe, John B.; Ranieri, Nicola; Witkowski, Mark] US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Platek, SF (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1431-9276 J9 MICROSC MICROANAL JI Microsc. microanal. PD JUL PY 2009 VL 15 SU 2 BP 796 EP 797 DI 10.1017/S1431927609099644 PG 2 WC Materials Science, Multidisciplinary; Microscopy SC Materials Science; Microscopy GA V20CW UT WOS:000208119100395 ER PT J AU van Ommen, B Keijer, J Heil, SG Kaput, J AF van Ommen, Ben Keijer, Jaap Heil, Sandra G. Kaput, Jim TI Challenging homeostasis to define biomarkers for nutrition related health SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Article; Proceedings Paper CT Symposium on Quantifying the Healthy Phenotype CY MAY, 2007 CL Cork, IRELAND SP European Nutrigen Org DE Biomarker; Challenge; Health; Homeostasis; Nutrition ID SURROGATE END-POINTS; MOLECULAR DIAGNOSTICS APPLICATIONS; GENE-EXPRESSION DATA; C-REACTIVE PROTEIN; INSULIN-RESISTANCE; NONFASTING TRIGLYCERIDES; CARDIOVASCULAR EVENTS; METABOLOMIC PROFILES; INFLAMMATORY MARKERS; MULTIPLE BIOMARKERS AB A primary goal of nutrition research is to optimize health and prevent or delay disease. Biomarkers to quantify health optimization are needed since many if not most biomarkers are developed for diseases. Quantifying "normal homeostasis" and developing validated biomarkers are formidable tasks because of the robustness of homeostasis and of inter-individual diversity. In this paper, we discuss the science, strategies, and technologies for measuring parameters that define individual health. The following concepts are central to define the physiology of the healthy individual: (i) responses to a challenge of homeostasis will be more informative than static homeostatic rneasures; (ii) processes involved in maintaining homeostasis usually are multi-factorial and require quantitative analyses of the many individual components involved; (iii) health includes a large variation in "normality" and the effects of nutritional interventions may remain hidden in this "diversity of robustness," if incompletely analyzed. Specifically, comprehensive multi-parameter ("omics") analysis may identify key parameters (biomarkers) and lead to a greater understanding of health supporting processes. Perturbation tests that accurately target aspects of the overarching drivers of health (metabolism, oxidation, inflammation, and psychological stress) may be instrumental in creating knowledge for maintaining health and preventing disease through nutrition. C1 [van Ommen, Ben] TNO Qual Life, NL-3700 AJ Zeist, Netherlands. [Keijer, Jaap; Heil, Sandra G.] Univ Wageningen & Res Ctr, RIKILT Inst Food Safety, Wageningen, Netherlands. [Kaput, Jim] US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. RP van Ommen, B (reprint author), TNO Qual Life, POB 360, NL-3700 AJ Zeist, Netherlands. EM ben.vanommen@tno.nl NR 100 TC 68 Z9 69 U1 0 U2 15 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1613-4125 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD JUL PY 2009 VL 53 IS 7 BP 795 EP 804 DI 10.1002/mnfr.200800390 PG 10 WC Food Science & Technology SC Food Science & Technology GA 478IO UT WOS:000268581200001 PM 19517455 ER PT J AU Dobrovolskaia, MA Germolec, DR Weaver, JL AF Dobrovolskaia, Marina A. Germolec, Dori R. Weaver, James L. TI Evaluation of nanoparticle immunotoxicity SO NATURE NANOTECHNOLOGY LA English DT Review ID VACCINES; ISSUES; SIZE AB The pharmaceutical industry is developing increasing numbers of drugs and diagnostics based on nanoparticles, and evaluating the immune response to these diverse formulations has become a challenge for scientists and regulatory agencies alike. An international panel of scientists and representatives from various agencies and companies reviewed the limitations of current tests at a workshop held at the National Cancer Institute in Frederick, Maryland. This article outlines practical strategies for identifying and controlling interferences in common evaluation methods and the implications for regulation. C1 [Dobrovolskaia, Marina A.] NCI, SAIC Frederick Inc, Nanotechnol Characterizat Lab, Frederick, MD 21702 USA. [Germolec, Dori R.] Natl Inst Environm Hlth Sci, Toxicol Branch, Natl Toxicol Program, NIH,DHHS, Res Triangle Pk, NC 27709 USA. [Weaver, James L.] US FDA, CDER, Div Appl Pharmacol Res, Silver Spring, MD 20993 USA. RP Dobrovolskaia, MA (reprint author), NCI, SAIC Frederick Inc, Nanotechnol Characterizat Lab, Frederick, MD 21702 USA. EM marina@mail.nih.gov RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU PHS HHS [HHSN261200800001E] NR 12 TC 157 Z9 158 U1 3 U2 73 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1748-3387 J9 NAT NANOTECHNOL JI Nat. Nanotechnol. PD JUL PY 2009 VL 4 IS 7 BP 411 EP 414 DI 10.1038/NNANO.2009.175 PG 4 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Science & Technology - Other Topics; Materials Science GA 478OJ UT WOS:000268597300009 PM 19581891 ER PT J AU Ferguson, SA Boctor, SY AF Ferguson, Sherry A. Boctor, Sherin Y. TI Adolescent methylphenidate treatment does not alter adult levels of hedonia in male and female Sprague-Dawley rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting of the Neurobehavioral-Teratology-Society/49th Annual Meeting of the Teratology-Society/22nd Annual Meeting of the Organization-of-Teratology-Information-Specialists CY JUN 28-JUL 01, 2009 CL Rio Grande, PR SP Neurobehav Teratol Soc, Teratol Soc, Org Teratol Informat Specialists C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. UAMS, Dept Interdisciplinary Biomed Sci, Little Rock, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-SEP PY 2009 VL 31 IS 4 MA NBTS27 BP 243 EP 243 DI 10.1016/j.ntt.2009.04.031 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 461GY UT WOS:000267253900034 ER PT J AU Chelonis, JJ Gravelin, CR AF Chelonis, John J. Gravelin, Claire R. TI An examination of the relationship between time estimation and time production SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting of the Neurobehavioral-Teratology-Society/49th Annual Meeting of the Teratology-Society/22nd Annual Meeting of the Organization-of-Teratology-Information-Specialists CY JUN 28-JUL 01, 2009 CL Rio Grande, PR SP Neurobehav Teratol Soc, Teratol Soc, Org Teratol Informat Specialists C1 [Chelonis, John J.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Chelonis, John J.; Gravelin, Claire R.] SUNY Coll Brockport, Brockport, NY 14420 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-SEP PY 2009 VL 31 IS 4 MA NBTS33 BP 245 EP 245 DI 10.1016/j.ntt.2009.04.037 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 461GY UT WOS:000267253900040 ER PT J AU Boctor, S Wang, C Ferguson, S AF Boctor, Sherin Wang, Cheng Ferguson, Sherry TI Neonatal PCP is more potent than ketamine at modifying preweaning behaviors of Sprague-Dawley rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting of the Neurobehavioral-Teratology-Society/49th Annual Meeting of the Teratology-Society/22nd Annual Meeting of the Organization-of-Teratology-Information-Specialists CY JUN 28-JUL 01, 2009 CL Rio Grande, PR SP Neurobehav Teratol Soc, Teratol Soc, Org Teratol Informat Specialists C1 [Boctor, Sherin; Wang, Cheng; Ferguson, Sherry] Univ Arkansas Med Sci, Dept Interdisciplinary Biomed Sci, Little Rock, AR 72205 USA. [Wang, Cheng; Ferguson, Sherry] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-SEP PY 2009 VL 31 IS 4 MA NBTS42 BP 247 EP 247 DI 10.1016/j.ntt.2009.04.046 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 461GY UT WOS:000267253900049 ER PT J AU Patterson, T Li, M Morris, S Rodriguez, J Slikker, W Mattison, D Paule, M AF Patterson, Tucker Li, Mi Morris, Suzanne Rodriguez, Jesse Slikker, William Mattison, Donald, Jr. Paule, Merle TI The effects of chronic methylphenidate treatment on the performance of rhesus monkeys in the NCTR operant test battery SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting of the Neurobehavioral-Teratology-Society/49th Annual Meeting of the Teratology-Society/22nd Annual Meeting of the Organization-of-Teratology-Information-Specialists CY JUN 28-JUL 01, 2009 CL Rio Grande, PR SP Neurobehav Teratol Soc, Teratol Soc, Org Teratol Informat Specialists C1 [Patterson, Tucker; Li, Mi; Rodriguez, Jesse; Paule, Merle] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Morris, Suzanne] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Slikker, William] US FDA, Natl Ctr Toxicol Res, Off Director, Jefferson, AR 72079 USA. [Mattison, Donald, Jr.] NICHHD, Rockville, MD USA. RI Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-SEP PY 2009 VL 31 IS 4 MA NBTS45 BP 248 EP 248 DI 10.1016/j.ntt.2009.04.049 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 461GY UT WOS:000267253900052 ER PT J AU Paule, M AF Paule, Merle TI Alteration in nonhuman primate brain function as a consequence of developmental exposure to drugs of abuse SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting of the Neurobehavioral-Teratology-Society/49th Annual Meeting of the Teratology-Society/22nd Annual Meeting of the Organization-of-Teratology-Information-Specialists CY JUN 28-JUL 01, 2009 CL Rio Grande, PR SP Neurobehav Teratol Soc, Teratol Soc, Org Teratol Informat Specialists C1 [Paule, Merle] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-SEP PY 2009 VL 31 IS 4 MA NBTS57 BP 251 EP 251 DI 10.1016/j.ntt.2009.04.061 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 461GY UT WOS:000267253900064 ER PT J AU Jamali, F Lemery, S Ayalew, K Robottom, S Robie-Suh, K Rieves, D Pazdur, R AF Jamali, Faranak Lemery, Steven Ayalew, Kassa Robottom, Suzanne Robie-Suh, Kathy Rieves, Dwaine Pazdur, Richard TI Romiplostim for the Treatment of Chronic Immune (Idiopathic) Thrombocytopenic Purpura SO ONCOLOGY-NEW YORK LA English DT Article AB Purpose: On August 22, 2008, Romiplostim (Nplate for Injection) received approval from the US Food and Drug Administration (FDA) for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. This report summarizes the FDA analyses of the clinical data supporting this approval. Experimental Design: The FDA reviewed data from two double-blind, placebo-controlled clinical studies, an uncontrolled extension study, and supportive studies. In the controlled studies, enrolled patients had completed at least one prior treatment for chronic ITP and had a platelet count <= 30 x 10(9)/L. One study enrolled patients who had undergone splenectomy; the other enrolled patients who had not undergone splenectomy. The primary endpoint in both controlled studies was durable platelet response. Results: Overall, 125 patients were randomized in the controlled studies. A durable platelet response was observed in 61% of nonsplenectomized patients and 38% of patients who had undergone splenectomy. One placebo group patient achieved a durable platelet response. Serious hemorrhage events were reported in 10% of placebo recipients and 6% of romiplostim recipients. In the extension study, patients received romiplostim for a median of 60 weeks and a maximum of 96 weeks; the majority of patients maintained platelet counts >= 50 x 10(9)/L throughout the study. Major safety findings pertained to a risk for bone marrow reticulin formation and worsened thrombocytopenia following romiplostim discontinuation. Conclusions: The FDA approved romiplostim for use among certain patients with chronic ITP. This approval included a Risk Evaluation and Mitigation Strategy to ensure that the benefits of the drug outweigh its risks. C1 [Jamali, Faranak; Lemery, Steven; Ayalew, Kassa; Robottom, Suzanne; Robie-Suh, Kathy; Rieves, Dwaine; Pazdur, Richard] US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Rieves, D (reprint author), US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Rm 2354,Bldg 22,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Rafael.Rieves@fda.hhs.gov NR 9 TC 8 Z9 9 U1 0 U2 0 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUL PY 2009 VL 23 IS 8 BP 704 EP 709 PG 6 WC Oncology SC Oncology GA V18PR UT WOS:000208017200007 PM 19711585 ER PT J AU Dworkin, RH Turk, DC Revicki, DA Harding, G Coyne, KS Peirce-Sandner, S Bhagwat, D Everton, D Burke, LB Cowan, P Farrar, JT Hertz, S Max, MB Rappaport, BA Melzack, R AF Dworkin, Robert H. Turk, Dennis C. Revicki, Dennis A. Harding, Gale Coyne, Karin S. Peirce-Sandner, Sarah Bhagwat, Dileep Everton, Dennis Burke, Laurie B. Cowan, Penney Farrar, John T. Hertz, Sharon Max, Mitchell B. Rappaport, Bob A. Melzack, Ronald TI Development and initial validation of an expanded and revised version of the Short-form McGill Pain Questionnaire (SF-MPQ-2) SO PAIN LA English DT Article DE Pain; Pain quality; Short-form McGill Pain Questionnaire; Neuropathic pain; Non-neuropathic pain; Assessment; Outcome measures; Painful diabetic peripheral neuropathy ID QUALITY-OF-LIFE; PREDOMINANTLY NEUROPATHIC ORIGIN; RANDOMIZED CONTROLLED-TRIAL; CLINICAL-TRIALS; IMMPACT RECOMMENDATIONS; SCREENING QUESTIONNAIRE; MULTIDIMENSIONAL AFFECT; POSTHERPETIC NEURALGIA; OUTCOME MEASURES; ASSESSMENT SCALE AB The objective of the present research was to develop a single measure of the major symptoms of both neuropathic and non-neuropathic pain that can be used in Studies of epidemiology, natural history, pathophysiologic mechanisms, and treatment response. We expanded and revised the Short-form McGill Pain Questionnaire(1) (SF-MPQ) pain descriptors by adding symptoms relevant to neuropathic pain and by modifying the response format to a 0-10 numerical rating scale to provide increased responsiveness in longitudinal studies and clinical trials. The reliability, validity, and subscale structure of the revised SF-MPQ (SF-MPQ-2(1)) were examined in responses from 882 individuals with diverse chronic pain syndromes and in 226 patients with painful diabetic peripheral neuropathy who participated in a randomized clinical trial. The data Suggest that the SF-MPQ-2 has excellent reliability and validity, and the results of both exploratory and Confirmatory factor analyses provided Support for four readily interpretable subscales-continuous pain, intermittent pain, predominantly neuropathic pain, and affective descriptors. These results provide a basis for use of the SF-MPQ-2 in future clinical research, including clinical trials of treatments for neuropathic and non-neuropathic pain conditions. (C) 2009 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Dworkin, Robert H.] Univ Rochester, Sch Med, Dept Anesthesiol, Rochester, NY 14642 USA. [Dworkin, Robert H.] Univ Rochester, Sch Med, Dept Neurol, Rochester, NY 14642 USA. [Turk, Dennis C.] Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. [Revicki, Dennis A.; Harding, Gale; Coyne, Karin S.] United Biosource Corp, Bethesda, MD USA. [Peirce-Sandner, Sarah] Univ Rochester, Dept Anesthesiol, Rochester, NY USA. [Bhagwat, Dileep; Everton, Dennis] EpiCept Corp, Tarrytown, NY USA. [Burke, Laurie B.; Hertz, Sharon; Rappaport, Bob A.] US FDA, Bethesda, MD 20014 USA. [Cowan, Penney] Amer Chron Pain Assoc, Rocklin, CA USA. [Farrar, John T.] Univ Penn, Dept Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Max, Mitchell B.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA USA. [Melzack, Ronald] McGill Univ, Dept Psychol, Montreal, PQ, Canada. RP Dworkin, RH (reprint author), Univ Rochester, Sch Med, Dept Anesthesiol, 601 Elmwood Ave,Box 604, Rochester, NY 14642 USA. EM robert_dworkin@urmc.rochester.edu RI Farrar, John/A-1037-2007 OI Farrar, John/0000-0001-8656-5157 FU United BioSource Corporation; IMMPACT; EpiCept Corporation FX The web Survey was funded by a grant to United BioSource Corporation (formerly known as The MEDTAP Institute at UBC) from IMMPACT, and the clinical trial was sponsored and funded by the EpiCept Corporation. The authors Would like to thank the American Chronic Pain Association for cooperation and Support for the web survey, and all of the individuals ill the focus groups, web Survey, and clinical trial for their participation. NR 53 TC 127 Z9 134 U1 4 U2 38 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUL PY 2009 VL 144 IS 1-2 BP 35 EP 42 DI 10.1016/j.pain.2009.02.007 PG 8 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 470GL UT WOS:000267963100012 PM 19356853 ER PT J AU Zineh, I Lesko, LJ AF Zineh, Issam Lesko, Lawrence J. TI Pharmacogenetics in medicine: barriers, critical factors and a framework for dialogue SO PERSONALIZED MEDICINE LA English DT Editorial Material C1 [Zineh, Issam] US FDA, Off Clin Pharmacol, CDER, Silver Spring, MD 20993 USA. RP Zineh, I (reprint author), US FDA, Off Clin Pharmacol, CDER, 10903 New Hampshire Ave,White Oak Bldg 51,Room 31, Silver Spring, MD 20993 USA. EM issam.zineh@fda.hhs.gov NR 3 TC 11 Z9 11 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 J9 PERS MED JI Pers. Med. PD JUL PY 2009 VL 6 IS 4 BP 359 EP 361 DI 10.2217/PME.09.27 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 481BC UT WOS:000268780500001 ER PT J AU Jadhav, PR Zhang, JL Gobburu, JVS AF Jadhav, Pravin R. Zhang, Jialu Gobburu, Jogarao V. S. TI Leveraging prior quantitative knowledge in guiding pediatric drug development: a case study SO PHARMACEUTICAL STATISTICS LA English DT Article DE pediatrics; exclusivity; FDAAA; BPCA; PREA; trial design; clinical trial simulations; power ID CHILDREN; EXCLUSIVITY AB The manuscript presents the FDA's focus on leveraging prior knowledge in designing informative pediatric trial through this case study. In developing written request for Drug X, an anti-hypertensive for immediate blood pressure (BP) control, the sponsor and FDA conducted clinical trial simulations (CTS) to design trial with proper sample size and support the choice of dose range. The objective was to effectively use prior knowledge from adult patients for drug X, pediatric data from Corlopam (approved for a similar indication) trial and general experience in developing antihypertensive agents. Different scenarios governing the exposure response relationship in the pediatric population were simulated to perturb model assumptions. The choice of scenarios was based on the past observation that pediatric population is less responsive and sensitive compared with adults. The conceptual framework presented here should serve as an example on how the industry and FDA scientists can collaborate in designing the pediatric exclusivity trial. Using CTS, inter-disciplinary scientists with the sponsor and FDA can objectively discuss the choice of dose range, sample size, endpoints and other design elements. These efforts are believed to yield plausible trial design, qrational dosing recommendations and useful labeling information in pediatrics. Published in (C) 2009 by John Wiley & Sons, Ltd. C1 [Jadhav, Pravin R.] US FDA, Div Pharmacometr, OCP, OTS,CDER, Silver Spring, MD 20993 USA. [Zhang, Jialu; Gobburu, Jogarao V. S.] US FDA, Off Biostat, OTS, CDER, Silver Spring, MD 20993 USA. RP Jadhav, PR (reprint author), US FDA, Div Pharmacometr, OCP, OTS,CDER, Rm 3117,White Oak Bldg 51, Silver Spring, MD 20993 USA. EM Pravin.Jadhav@fda.hhs.gov NR 13 TC 26 Z9 27 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1539-1604 J9 PHARM STAT JI Pharm. Stat. PD JUL-SEP PY 2009 VL 8 IS 3 BP 216 EP 224 DI 10.1002/pst.394 PG 9 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 501YH UT WOS:000270419900005 PM 19610013 ER PT J AU Saver, JL Albers, GW Dunn, B Johnston, KC Fisher, M AF Saver, Jeffrey L. Albers, Gregory W. Dunn, Billy Johnston, Karen C. Fisher, Marc CA STAIR VI Consortium TI Stroke Therapy Academic Industry Roundtable (STAIR) Recommendations for Extended Window Acute Stroke Therapy Trials SO STROKE LA English DT Article DE stroke; therapy; clinical trials ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN-ACTIVATOR; RANDOMIZED CONTROLLED-TRIAL; MERCI TRIAL; THROMBOLYSIS; RECANALIZATION; REPERFUSION; ALTEPLASE; PENUMBRA; CLOT AB The Stroke Therapy Academic Industry Roundtable (STAIR) meetings focus on helping to advance the development of acute stroke therapies. Further extending the time window for acute stroke therapies is an important endeavor for increasing the number of stroke patients who might benefit from treatment. The STAIR group recommends that future extended time window trials initially should focus on selected patient groups most likely to respond to investigational therapies and that penumbral imaging is one tool that may identify such patients. The control group in these trials should receive best locally available medical care; if regulatory approval for intravenous (i.v.) tPA is extended to 4.5 hours, then tPA will become the most appropriate comparator in trials conducted within this time window. In future well-designed extended window clinical trials randomization is appropriate and should not be precluded by using unproven treatment with intraarterial (i.a.) thrombolysis or mechanical devices. For proof of concept, extended time window, phase II trials of i.v. thrombolysis, or mechanical devices in which early recanalization/ reperfusion is the primary end point, rescue therapy/bailout treatment with i.a. thrombolysis or devices may be acceptable. Statistical considerations and definitions of successful recanalization/ reperfusion are suggested for these trials. (Stroke. 2009; 40: 2594-2600.) C1 [Albers, Gregory W.] Stanford Univ, Sch Med, Dept Neurol, Stanford, CA 94305 USA. [Albers, Gregory W.] Stanford Univ, Sch Med, Dept Neurol Sci, Stanford, CA 94305 USA. [Johnston, Karen C.] Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA. [Dunn, Billy] US FDA, Silver Spring, MD USA. [Saver, Jeffrey L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Fisher, Marc] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01605 USA. RP Fisher, M (reprint author), Univ Massachusetts, Sch Med, Dept Neurol, 119 Belmont St, Worcester, MA 01605 USA. EM fisherm@ummhc.org RI Macleod, Malcolm/B-2052-2010; Chen, Christopher/E-7023-2013; OI Saver, Jeffrey/0000-0001-9141-2251; Macleod, Malcolm Robert/0000-0001-9187-9839 FU NIH; Sygnis FX This study was in part supported by NIH grants ( to G. W. A. and K. C. J). M. F. received support from Sygnis. NR 42 TC 67 Z9 69 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD JUL PY 2009 VL 40 IS 7 BP 2594 EP 2600 DI 10.1161/STROKEAHA.109.552554 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 463XR UT WOS:000267467900056 PM 19478212 ER PT J AU Kelly, W Arellano, F Barnes, J Bergman, U Edwards, R Fernandez, A Freedman, S Goldsmith, D Huang, K Jones, J McLeay, R Moore, N Stather, R Trenque, T Troutman, W van Puijenbroek, E Williams, F Wise, R AF Kelly, William Arellano, Felix Barnes, Joanne Bergman, Ulf Edwards, Ralph Fernandez, Alina Freedman, Stephen Goldsmith, David Huang, Kui Jones, Judith McLeay, Rachel Moore, Nicholas Stather, Rosie Trenque, Thierry Troutman, William van Puijenbroek, Eugene Williams, Frank Wise, Robert TI Guidelines for Submitting Adverse Event Reports for Publication SO THERAPIE LA English DT Article DE guidelines; adverse; event; report ID DRUG-REACTIONS; PHARMACOVIGILANCE; ANECDOTES; STANDARDS; CRITERIA; QUALITY AB Publication of case reports describing suspected adverse effects of drugs and medical products that include herbal and complementary medicines, vaccines and other biologicals and devices is important for postmarketing surveillance. Publication lends credence to important signals raised in these adverse event reports. Unfortunately, deficiencies in vital information in published cases can often limit the value of such reports by failing to provide enough details for either (i) a differential diagnosis or provisional assessment of cause-effect association, or (ii) a reasonable pharmacological or biological explanation. Properly described, a published report of one or more adverse events can provide a useful signal of possible risks associated with the use of a drug or medical product which might warrant further exploration. A review conducted by the Task Force authors found that many major journals have minimal requirements for publishing adverse event reports and some have none at all. Based on a literature review and our collective experience in reviewing adverse event case reports in regulatory, academic and industry settings, we have identified information that we propose should always be considered for inclusion in a report submitted for publication. These guidelines have been endorsed by the International Society for Pharmacoepidemiology (ISPE) and the International Society of Pharmacovigilance (ISoP) and are freely available on the societies' web sites. Their widespread distribution is encouraged. ISPE and ISoP urge biomedical journals to adopt these guidelines and apply them to case reports submitted for publication. They also encourage schools of medicine, pharmacy, and nursing to incorporate them into the relevant curricula that address the detection, evaluation and reporting of suspected drug or other medical product adverse events. C1 [Trenque, Thierry] Ctr Hosp Univ, Ctr Reg Pharmacovigilance Reims Champagne Ardenne, F-51092 Reims, France. [Kelly, William] William N Kelly Consulting Inc, Oldsmar, FL USA. [Arellano, Felix] Risk Management Resources, Dip Pharm Med, Bridgewater, NJ USA. [Arellano, Felix] Risk Management Resources, Dip Pharm Med, Zaragoza, Spain. [Barnes, Joanne] Univ Auckland, Auckland 1, New Zealand. [Bergman, Ulf] Karolinska Inst, Stockholm, Sweden. [Edwards, Ralph] Uppsala Monitoring Ctr, Uppsala, Sweden. [Fernandez, Alina] TAP Pharmaceut Prod Inc, Lake Forest, IL USA. [Freedman, Stephen] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Goldsmith, David] Goldsmith Pharmacovigilance & Syst, New York, NY USA. [Huang, Kui] Pfizer Pharmaceut Inc, New York, NY USA. [Jones, Judith] Dedge Grp Ltd, Arlington, VA USA. [McLeay, Rachel; Stather, Rosie] Wolters Kluwer Hlth, Auckland, New Zealand. [Moore, Nicholas] Univ Victor Segalen, Bordeaux, France. [Troutman, William] Univ New Mexico, Albuquerque, NM 87131 USA. [van Puijenbroek, Eugene] Netherlands Pharmacovigilance Ctr, sHertogenbosch, Netherlands. [Williams, Frank] USN, Bethesda, MD 20084 USA. [Wise, Robert] US FDA, Rockville, MD USA. RP Trenque, T (reprint author), Ctr Hosp Univ, Ctr Reg Pharmacovigilance Reims Champagne Ardenne, Ave Gen Koening, F-51092 Reims, France. EM ttrenque@chu-reims.fr OI Bergman, Ulf/0000-0003-4654-2211 NR 21 TC 13 Z9 13 U1 0 U2 0 PU EDP SCIENCES S A PI LES ULIS CEDEX A PA 17, AVE DU HOGGAR, PA COURTABOEUF, BP 112, F-91944 LES ULIS CEDEX A, FRANCE SN 0040-5957 J9 THERAPIE JI Therapie PD JUL-AUG PY 2009 VL 64 IS 4 BP 289 EP 294 DI 10.2515/therapie/2009041 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 514JM UT WOS:000271390500007 PM 19804709 ER PT J AU Kannan, M Mohan, KVK Kulkarni, S Atreya, C AF Kannan, Meganathan Mohan, Ketha V. Krishna Kulkarni, Sandhya Atreya, Chintamani TI Membrane array-based differential profiling of platelets during storage for 52 miRNAs associated with apoptosis SO TRANSFUSION LA English DT Article ID MICRORNAS; ACTIVATION; CANCER; CELL; TRANSFUSION; EXPRESSION; MECHANISM; SEQUENCE; MARKERS; STRESS AB BACKGROUND: Enucleated platelets (PLTs) utilize posttranscriptional gene (mRNA) regulation (PTGR) for their normal morphologic and physiologic functions, which are altered in their ex vivo storage, also collectively referred to as storage lesions. While cellular micro-RNAs (miRNAs) play a significant role in posttranscriptional gene (mRNA) regulation by binding to their target mRNAs, comprehensive analysis of apoptosis-associated miRNAs and global changes in their profiles during PLT storage have not been evaluated to date. STUDY DESIGN AND METHODS: In this report room temperature-stored PLTs of Days 0, 2, and 9 were analyzed by differential profiling for 52 apoptosis-associated human miRNAs. After total RNA extraction from the samples, a membrane array-based miRNA analysis was carried out. Prediction of target genes was performed by bioinformatics-based approaches. RESULTS: Our analysis revealed that during storage, Let-7a, -7c, -7e, -7f, -7g, and -7i miRNA profiles of the PLTs were barely detectable, while levels of miR-150, -151, -152, -184, -188, -196a, -197, and -202 remained at high levels in PLTs. The rest of the miRNA levels were in between. However, two miRNAs, Let-7b and miR-16, distinctly demonstrated an increasing trend while miR-7 and miR-145 showed a decreasing profile during PLT storage. For these four miRNAs, we also identified their potential target mRNAs. CONCLUSIONS: Overall, these results confirm the fact that miRNAs do exist in PLTs, and among 52 apoptosis-specific miRNAs studied, only a few selected miRNAs did perturb during PLT storage. Future experimental evaluation of these miRNA-target mRNA interactions will provide new insights into the molecular mechanisms of PLT storage-associated lesions. C1 [Kannan, Meganathan; Mohan, Ketha V. Krishna; Kulkarni, Sandhya; Atreya, Chintamani] US FDA, Sect Cell Biol, Lab Cellular Hematol, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Atreya, C (reprint author), Bldg 29A,Room 2C-11,NIH Campus,8800 Rockville Pik, Bethesda, MD 20892 USA. EM chintamani.atreya@fda.hhs.gov FU FDA; CBER Critical Path Research Initiative; Oak Ridge Institute for Science and Engineering fellowship FX This work in part was supported by the FDA, CBER Critical Path Research Initiative funds to CDA. MK is a recipient of Oak Ridge Institute for Science and Engineering fellowship. NR 30 TC 29 Z9 31 U1 0 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL PY 2009 VL 49 IS 7 BP 1443 EP 1450 DI 10.1111/j.1537-2995.2009.02140.x PG 8 WC Hematology SC Hematology GA 467CX UT WOS:000267715300025 PM 19389023 ER PT J AU Girnita, DM Webber, SA Brooks, MM Ferrell, R Girnita, AL Burckart, GJ Chinnock, R Canter, C Addonizio, L Bernstein, D Kirklin, JK Naftel, D Zeevi, A AF Girnita, Diana M. Webber, Steven A. Brooks, Maria M. Ferrell, Robert Girnita, Alin L. Burckart, Gilbert J. Chinnock, Richard Canter, Charles Addonizio, Linda Bernstein, Daniel Kirklin, James K. Naftel, David Zeevi, Adriana TI Genotypic Variation and Phenotypic Characterization of Granzyme B Gene Polymorphisms SO TRANSPLANTATION LA English DT Article DE Granzyme B; Gene polymorphism; Transplantation; Pediatric; Heart ID ACUTE REJECTION; TRANSPLANT RECIPIENTS; HEART-TRANSPLANTATION; LUNG TRANSPLANTATION; PREDICTIVE MARKERS; PERFORIN; ALLELE; CYTOKINE; CELLS; EXPRESSION AB Background. Granzyme B has been associated with allograft rejection in solid organ transplantation. Single nucleotide polymorphisms (SNPs) in the granzyme B gene might impact its expression. The aims of this study were (1) to establish the frequency of two granzyme B SNPs (A-295G; Q-55R) in pediatric heart transplant (PHTx) recipients and (2) to determine their phenotypic expression in healthy individuals. Methods. Three hundred ninety-six PHTx patients (245 white non-Hispanic, 49 black non-Hispanic, 82 Hispanics, and 20 others) and 52 healthy controls were screened for Q-55R and A-295G. For the control samples, we assessed the frequency of granzyme B positive cells by ELISPOT assay after mitogen stimulation. Results. Among the PHTx recipients, 57% percent of the population carried the Q/Q genotype, whereas 6% were R/R homozygotes. Seven of 49 (14%) black non-Hispanics were R/R homozygotes, whereas 13 of 245 (5%) of white non-Hispanics and 5 of 82 (6%) Hispanics carried the R/R genotype (P=0.02). The A allele frequency of granzyme B A-295G (49.6%) was similar to that of the G allele (50.4%). However, 80% of Black non-Hispanics were A allele carriers compared with 68% of White non-Hispanics (P<0.0001). After mitogen stimulation, the frequency of granzyme B positive cells was higher in the Q/Q homozygotes compared with R/R carriers (P=0.006), whereas a similar frequency of granzyme B positive cells was noticed among the genotypes of A-295G SNP. Conclusions. These data indicate that 55 Q/Q genotype is associated with increased in vitro expression of granzyme B. C1 [Girnita, Diana M.; Girnita, Alin L.; Zeevi, Adriana] Univ Pittsburgh, Dept Pathol, Thomas E Starzl Transplant Inst, Pittsburgh, PA USA. [Webber, Steven A.] Univ Pittsburgh, Dept Pediat, Div Cardiol, Pittsburgh, PA 15260 USA. [Brooks, Maria M.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Ferrell, Robert] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15260 USA. [Burckart, Gilbert J.] US FDA, Off Clin Pharmacol, Off Translat Sci, Silver Spring, MD USA. [Chinnock, Richard] Loma Linda Univ, Dept Pediat, Loma Linda, CA 92350 USA. [Canter, Charles] Washington Univ, Sch Med, Dept Pediat, St Louis Childrens Hosp,Div Cardiol, St Louis, MO 63110 USA. [Addonizio, Linda] Columbia Univ, Dept Pediat, Div Cardiol, Childrens Hosp New York, New York, NY 10027 USA. [Bernstein, Daniel] Stanford Univ, Lucile Packard Childrens Hosp, Div Cardiol, Dept Pediat, Palo Alto, CA 94304 USA. [Kirklin, James K.; Naftel, David] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. RP Zeevi, A (reprint author), 200 Lothrop St,W1551,Thomas E Starzl Biomed Sci T, Pittsburgh, PA 15261 USA. EM zeevi@pitt.edu OI Chinnock, Richard/0000-0002-9814-1762; Brooks, Maria/0000-0002-2030-7873 FU National Heart Lung and Blood Institute, National Institutes of Health [5P50 HL 074 732-03] FX This work was supported by National Heart Lung and Blood Institute, National Institutes of Health (5P50 HL 074 732-03). NR 26 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUN 27 PY 2009 VL 87 IS 12 BP 1801 EP 1806 DI 10.1097/TP.0b013e3181a755a4 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 462NO UT WOS:000267361000007 PM 19543056 ER PT J AU Fink, DW AF Fink, Donald W., Jr. TI FDA Regulation of Stem Cell-Based Products SO SCIENCE LA English DT Editorial Material AB Cell self-renewal and the capacity to differentiate into multiple cell types (pluripotency) are biological attributes casting stem cells as attractive candidates for development of therapies targeting indications that involve functional restoration of damaged tissues. In the United States, clinical trials designed to demonstrate the safety and effectiveness of stem cell-based products are regulated by the U. S. Food and Drug Administration (FDA). To ensure that subjects enrolled in a clinical study involving stem cell-based products are not exposed to significant and unreasonable risk, the FDA reviews medical and scientific information that encompasses delineation of product-specific characteristics and preclinical testing to determine whether there is sufficient safety assurance to permit initiation of human clinical studies. C1 US FDA, Cell Therapy Branch,Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Fink, DW (reprint author), US FDA, Cell Therapy Branch,Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, 1401 Rockville Pike,Suite 200N,Mail Code HFM 720, Rockville, MD 20852 USA. EM donald.fink@fda.hhs.gov NR 10 TC 66 Z9 67 U1 1 U2 12 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 26 PY 2009 VL 324 IS 5935 BP 1662 EP 1663 DI 10.1126/science.1173712 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 462GE UT WOS:000267338200025 PM 19556496 ER PT J AU Shankavaram, UT Varma, S Kane, D Sunshine, M Chary, KK Reinhold, WC Pommier, Y Weinstein, JN AF Shankavaram, Uma T. Varma, Sudhir Kane, David Sunshine, Margot Chary, Krishna K. Reinhold, William C. Pommier, Yves Weinstein, John N. TI CellMiner: a relational database and query tool for the NCI-60 cancer cell lines SO BMC GENOMICS LA English DT Article ID GENE-EXPRESSION DATABASE; MOLECULAR PHARMACOLOGY; DRUG SCREEN; PANEL; MICROARRAY; PROFILES; SET AB Background: Advances in the high-throughput omic technologies have made it possible to profile cells in a large number of ways at the DNA, RNA, protein, chromosomal, functional, and pharmacological levels. A persistent problem is that some classes of molecular data are labeled with gene identifiers, others with transcript or protein identifiers, and still others with chromosomal locations. What has lagged behind is the ability to integrate the resulting data to uncover complex relationships and patterns. Those issues are reflected in full form by molecular profile data on the panel of 60 diverse human cancer cell lines ( the NCI-60) used since 1990 by the U. S. National Cancer Institute to screen compounds for anticancer activity. To our knowledge, CellMiner is the first online database resource for integration of the diverse molecular types of NCI-60 and related meta data. Description: CellMiner enables scientists to perform advanced querying of molecular information on NCI-60 ( and additional types) through a single web interface. CellMiner is a freely available tool that organizes and stores raw and normalized data that represent multiple types of molecular characterizations at the DNA, RNA, protein, and pharmacological levels. Annotations for each project, along with associated metadata on the samples and datasets, are stored in a MySQL database and linked to the molecular profile data. Data can be queried and downloaded along with comprehensive information on experimental and analytic methods for each data set. A Data Intersection tool allows selection of a list of genes ( proteins) in common between two or more data sets and outputs the data for those genes ( proteins) in the respective sets. In addition to its role as an integrative resource for the NCI-60, the CellMiner package also serves as a shell for incorporation of molecular profile data on other cell or tissue sample types. Conclusion: CellMiner is a relational database tool for storing, querying, integrating, and downloading molecular profile data on the NCI-60 and other cancer cell types. More broadly, it provides a template to use in providing such functionality for other molecular profile data generated by academic institutions, public projects, or the private sector. CellMiner is available online at http://discover.nci.nih.gov/cellminer/. C1 [Kane, David; Sunshine, Margot] SRA Int, Fairfax, VA USA. [Chary, Krishna K.] US FDA, Off Informat Technol, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Weinstein, John N.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. [Shankavaram, Uma T.; Varma, Sudhir; Reinhold, William C.; Pommier, Yves; Weinstein, John N.] NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Shankavaram, UT (reprint author), NCI, Radiat Oncol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM Uma.Shankavaram@nih.hhs.gov; varmas@mail.nih.gov; David_Kane@sra.com; Margot.Sunshine@hhs.nih.gov; Krishna.Chary@fda.hhs.gov; William.Reinhold@nih.hhs.gov; Yves.Pommier@nih.hhs.gov; jweinste@mdanderson.org RI Varma, Sudhir/N-8763-2014 OI Varma, Sudhir/0000-0002-4096-4782 NR 25 TC 67 Z9 69 U1 3 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD JUN 23 PY 2009 VL 10 AR 277 DI 10.1186/1471-2164-10-277 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 480RH UT WOS:000268754000001 PM 19549304 ER PT J AU Zolnik, BS Sadrieh, N AF Zolnik, Banu S. Sadrieh, Nakissa TI Regulatory perspective on the importance of ADME assessment of nanoscale material containing drugs SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE Nanomaterials; Regulatory; Biodistribution; Physico-chemical characterization ID TUMOR-NECROSIS-FACTOR; COLLOIDAL GOLD NANOPARTICLES; I CLINICAL-TRIAL; PHASE-I; PARTICLE-SIZE; PHARMACOKINETICS; BIODISTRIBUTION; DENDRIMERS; DELIVERY; NANOTECHNOLOGY AB The promise of nanoscale material containing drug products to treat complex diseases is mounting. According to the literature, in addition to the liposomes, micelles, emulsions, there are novel drug delivery systems such as dendrimers and metal colloids at different stages of pre-clinical and clinical development. With the anticipation that more nanoscale material containing drug products will be submitted to the Food and Drug Administration (FDA) for approval in the future, FDA formed a Nanotechnology Task Force in 2006 to determine the critical regulatory issues regarding nanomaterials. As a result, all centers within the FDA are considering the development of guidance documents to address nanomaterial specific issues. It is well established in the literature that physico-chemical characterization (PCC) studies are crucial for nanomaterial containing drug products. However, this paper addresses the equally important topic of Absorption, Distribution, Metabolism and Excretion (ADME) studies for nanomaterials and provides examples of how physical properties affect biodistribution (i.e. the state of agglomeration, or aggregation, surface characteristics, stability of PEG). This paper also attempts to highlight some of the ADME study design issues related to nanomaterials such as the need for conducting biodistribution studies on each moiety of the multifunctional nanoparticles, dual labeled pharmacokinetic (PK) studies, and comparative PK studies on the free versus encapsulated drugs. In addition, this paper underlines the importance of long-term biodistribution and mass balance studies to understand the nanoparticle accumulation profile which may help to assess the safety and efficacy of the nanomaterial containing drug products. This review also lists some of the pre-clinical guidance documents that may help sponsors get started in developing data for inclusion in an initial investigational new drug application package for nanoscale material containing drug products. Published by Elsevier B.V. C1 [Zolnik, Banu S.; Sadrieh, Nakissa] US FDA, Ctr Drug Evaluat & Res, Off Phartnaceut Sci, Silver Spring, MD 20993 USA. RP Sadrieh, N (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Phartnaceut Sci, 10903 New Hampshire Ave,WO 51,HFD-003, Silver Spring, MD 20993 USA. EM nakissa.sadrieh@fda.hhs.gov NR 32 TC 55 Z9 57 U1 3 U2 27 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD JUN 21 PY 2009 VL 61 IS 6 BP 422 EP 427 DI 10.1016/j.addr.2009.03.006 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 464AN UT WOS:000267476600002 PM 19389437 ER PT J AU Nanga, RPR Brender, JR Xu, JD Hartman, K Subramanian, V Ramamoorthy, A AF Nanga, Ravi Prakash Reddy Brender, Jeffrey R. Xu, Jiadi Hartman, Kevin Subramanian, Vivekanandan Ramamoorthy, Ayyalusamy TI Three-Dimensional Structure and Orientation of Rat Islet Amyloid Polypeptide Protein in a Membrane Environment by Solution NMR Spectroscopy SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID GENE-RELATED PEPTIDE; DODECYL-SULFATE MICELLES; HUMAN ALPHA-SYNUCLEIN; SOLID-STATE NMR; HUMAN CALCITONIN; MOLECULAR-DYNAMICS; HUMAN AMYLIN; SALMON-CALCITONIN; LIPID-BILAYERS; CONFORMATIONAL PREFERENCES AB Islet amyloid-polypeptine (IAPP or amylin) is a 37-residue peptide hormone associated with glucose metabolism that is cosecreted with insulin by beta-cells in the pancreas. Since human IAPP is a highly amyloidogenic peptide, it has been suggested that the formation of IAPP amyloid fibers is responsible for the death of beta-cells during the early stages of type II diabetes. It has been hypothesized that transient membrane-bound alpha-helical structures of human IAPP are precursors to the formation of these amyloid deposits. On the other hand, rat IAPP forms transient a-helical structures but does not progress further to form amyloid fibrils. To understand the nature of this intermediate state and the difference in toxicity between the rat and human versions of IAPP, we have solved the high-resolution structure of rat IAPP in the membrane-mimicking detergent micelles composed of dodecylphosphocholine. The structure is characterized by a helical region spanning the residues A5 to S23 and a disordered C-terminus. A distortion in the helix is seen at R18 and S19 that may be involved in receptor binding. Paramagnetic quenching NMR experiments indicate that rat IAPP is bound on the surface of the micelle, in agreement with other nontoxic forms of IAPP. A comparison to the detergent-bound structures of other IAPP variants indicates that the N-terminal region may play a crucial role in the self-association and toxicity of IAPP by controlling access to the putative dimerization interface on the hydrophobic face of the amphipathic helix. C1 [Nanga, Ravi Prakash Reddy; Brender, Jeffrey R.; Xu, Jiadi; Hartman, Kevin; Ramamoorthy, Ayyalusamy] Univ Michigan, Dept Chem & Biophys, Ann Arbor, MI 48109 USA. [Subramanian, Vivekanandan] US FDA, Struct Biol NMR Spect, Bethesda, MD 20892 USA. RP Ramamoorthy, A (reprint author), Univ Michigan, Dept Chem & Biophys, Ann Arbor, MI 48109 USA. EM ramamoor@umich.edu RI Xu, jiadi/E-3163-2010; OI brender, jeffrey/0000-0001-7487-6169; Ramamoorthy, Ayyalusamy/0000-0003-1964-1900 FU NIH [DK078885]; Michigan Diabetes Research Training Center at the University of Michigan FX This study was supported by research funds from NIH (DK078885 to A.R.) and Michigan Diabetes Research Training Center at the University of Michigan. NR 79 TC 92 Z9 95 U1 3 U2 37 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUN 17 PY 2009 VL 131 IS 23 BP 8252 EP 8261 DI 10.1021/ja9010095 PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA 465XL UT WOS:000267623100046 PM 19456151 ER PT J AU Zhang, J Sattler, M Tonon, G Grabher, C Lababidi, S Zimmerhackl, A Raab, MS Vallet, S Zhou, YM Cartron, MA Hideshima, T Tai, YT Chauhan, D Anderson, KC Podar, K AF Zhang, Jing Sattler, Martin Tonon, Giovanni Grabher, Clemens Lababidi, Samir Zimmerhackl, Alexander Raab, Marc S. Vallet, Sonia Zhou, Yiming Cartron, Marie-Astrid Hideshima, Teru Tai, Yu-Tzu Chauhan, Dharminder Anderson, Kenneth C. Podar, Klaus TI Targeting Angiogenesis via a c-Myc/Hypoxia-Inducible Factor-1 alpha-Dependent Pathway in Multiple Myeloma SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; IN-VIVO; TUMOR PROGRESSION; KINASE INHIBITOR; TRANSGENIC ZEBRAFISH; FACTOR 1-ALPHA; MYC; HYPOXIA; CANCER; CELLS AB Bone marrow angiogenesis is associated with multiple myeloma (MM) progression. Here, we report high constitutive hypoxia-inducible factor-1 alpha (Hif-1 alpha) expression in MM cells, which is associated with oncogenic c-Myc. A drug screen for anti-MM agents that decrease Hif-1 alpha and c-Myc levels identified a variety of compounds, including bortezomib, lenalidomide, enzastaurin, and adaphostin. Functionally, based on transient knockdowns and overexpression, our data delineate a c-Myc/Hif-1 alpha-dependent pathway mediating vascular endothelial growth factor production and secretion. The antiangiogenic activity of our tool compound, adaphostin, was subsequently shown in a zebrafish model and translated into a preclinical in vitro and in vivo model of MM in the bone marrow milieu. Our data, therefore, identify Hif-1 alpha as a novel molecular target in MM and add another facet to anti-MM drug activity. [Cancer Res 2009;69(12):5082-90] C1 [Podar, Klaus] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Tonon, Giovanni] Dana Farber Canc Inst, Ctr Appl Canc Sci, Boston, MA 02115 USA. [Grabher, Clemens] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Vallet, Sonia] Harvard Univ, Sch Med, Boston, MA USA. [Vallet, Sonia] Massachusetts Gen Hosp, Ctr Multiple Myeloma, Boston, MA 02114 USA. [Lababidi, Samir] US FDA, Div Biostat, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Zhou, Yiming; Cartron, Marie-Astrid] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. [Tonon, Giovanni] Ist Sci San Raffaele, I-20132 Milan, Italy. [Podar, Klaus] Univ Heidelberg, Natl Ctr Tumor Dis NCT, Heidelberg, Germany. RP Podar, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, LeBow Inst Myeloma Therapeut, 44 Binney St, Boston, MA 02115 USA. EM klaus_podar@dfci.harvard.edu RI Grabher, Clemens/H-2064-2013 FU Multiple Myeloma Research Foundation Senior Research Grant Award; Dunkin' Donuts Rising Star Award; NIH [1P50 CA 1 00707, RO-1 CA 50947, PO-1 78378, CA134660-01]; LeBow Family Fund to Cure Myeloma FX Multiple Myeloma Research Foundation Senior Research Grant Award and Dunkin' Donuts Rising Star Award (K. Podar); NIH grants 1P50 CA 1 00707, RO-1 CA 50947, and PO-1 78378 and LeBow Family Fund to Cure Myeloma (K.C. Anderson); and NIH grant CA134660-01 (M. Sattler) NR 49 TC 43 Z9 46 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 2009 VL 69 IS 12 BP 5082 EP 5090 DI 10.1158/0008-5472.CAN-08-4603 PG 9 WC Oncology SC Oncology GA 464LM UT WOS:000267506400022 PM 19509231 ER PT J AU Hamburg, MA Sharfstein, JM AF Hamburg, Margaret A. Sharfstein, Joshua M. TI The FDA as a Public Health Agency SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Hamburg, Margaret A.; Sharfstein, Joshua M.] US FDA, Silver Spring, MD USA. RP Hamburg, MA (reprint author), US FDA, Silver Spring, MD USA. NR 0 TC 40 Z9 40 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 JUN 11 PY 2009 VL 360 IS 24 BP 2493 EP 2495 DI 10.1056/NEJMp0903764 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 456BS UT WOS:000266813800001 PM 19470577 ER PT J AU Albillos, SM Menhart, N Fu, TJ AF Albillos, Silvia M. Menhart, Nicholas Fu, Tong-Jen TI Structural Stability of Amandin, a Major Allergen from Almond (Prunus dulcis), and Its Acidic and Basic Polypeptides SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Amandin; circular dichroism (CD); almond proteins; prunin; secondary structure ID PROTEIN SECONDARY STRUCTURE; CIRCULAR-DICHROISM SPECTRA; PLANT FOOD ALLERGENS; STORAGE PROTEINS; 11S GLOBULIN; 2S ALBUMIN; EVOLUTIONARY RELATIONSHIPS; BETA-CONGLYCININ; PEANUT ALLERGEN; GLYCINE-MAX AB Information relating to the resistance of food allergens to thermal and/or chemical denaturation is critical if a reduction in protein allergenicity is to be achieved through food-processing means. This study examined the changes in the secondary structure of an almond allergen, amandin, and its acidic and basic polypeptides as a result of thermal and chemical denaturation. Amandin (similar to 370 kDa) was purified by cryoprecipitation followed by gel filtration chromatography and subjected to thermal (13-96 degrees C) and chemical (urea and dithiothreitol) treatments. Changes in the secondary structure of the protein were followed using circular dichroism spectroscopy. The secondary structure of the hexameric amandin did not undergo remarkable changes at temperatures up to 90 degrees C, although protein aggregation was observed. In the presence of a reducing agent, irreversible denaturation occurred with the following experimental values: T(m) = 72.53 degrees C (transition temperature), Delta H = 87.40 kcal/mol (unfolding enthalpy), and C(p) = 2.48 kcal/(mol degrees C) (heat capacity). The concentration of urea needed to achieve 50% denaturation was 2.59 M, and the Gibbs free energy of chemical denaturation was calculated to be Delta G = 3.82 kcal/mol. The basic and acidic polypeptides of amandin had lower thermal stabilities than the multimeric protein. C1 [Menhart, Nicholas] IIT, Dept Biol, Chicago, IL 60616 USA. [Fu, Tong-Jen] US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. [Albillos, Silvia M.] IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Albillos, SM (reprint author), Inst Biotechnol INBIOTEC, Av Real 1, Leon 24006, Spain. EM smalbg@unileon.es; tong.fu@fda.hhs.gov RI Albillos, Silvia/D-1276-2016 OI Albillos, Silvia/0000-0002-3273-0126 FU FDA HHS [5U01 FD000431] NR 52 TC 15 Z9 16 U1 1 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUN 10 PY 2009 VL 57 IS 11 BP 4698 EP 4705 DI 10.1021/jf803977z PG 8 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 453YW UT WOS:000266649800034 PM 19374443 ER PT J AU Fleming, TR Rothmann, MD Lu, HL AF Fleming, Thomas R. Rothmann, Mark D. Lu, Hong Laura TI Issues in Using Progression-Free Survival When Evaluating Oncology Products SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SURROGATE END-POINTS; METASTATIC COLORECTAL-CANCER; CLINICAL-TRIALS; RANDOMIZED-TRIALS; DESIGN AB Several challenging and often controversial issues arise in oncology trials with the use of the end point progression-free survival (PFS),defined to be the time to detection of progressive disease or death. While this end point does not directly measure how a patient feels, functions, or survives, it does provide insights about whether an intervention affects the tumor burden process, the intended mechanism through which it is hoped that most anticancer agents will provide benefit. However, simply achieving statistically significant effects on PFS is insufficient to obtaining reliable evidence of important clinical benefit, and even is insufficient to justifying the conclusion that the experimental intervention is "reasonably likely to provide clinical benefit." The magnitude of the effect on PFS in addition to the statistical strength of evidence is of great importance in interpreting the reliability of the evidence regarding clinical efficacy. PFS has several important properties, including being a direct measure of the effect of treatment on the tumor burden process, being sensitive to cytostatic as well as cytotoxic mechanisms of interventions, and incorporating the clinically relevant event of death, increasing its sensitivity to influential harmful mechanisms and avoiding substantial bias that arises when deaths are censored. To obtain reliable evidence about the effect of an intervention on PFS and patient survival, randomized trials should be conducted where all patients are followed to progression and death, and where patients in a control arm do not cross-in at progression unless the experimental regimen has already been established to be effective rescue treatment. C1 [Fleming, Thomas R.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. US FDA, Div Biometr 5, Silver Spring, MD USA. RP Fleming, TR (reprint author), Univ Washington, Dept Biostat, Box 357232, Seattle, WA 98195 USA. EM tfleming@u.washington.edu FU National Institutes of Health/NIAID [R37 AI 29168]; Statistical Issues in AIDS Research; US Food and Drug Administration [RSR 05-07, RSR 06-11] FX Supported by National Institutes of Health/NIAID Grant No. R37 AI 29168 entitled the Statistical Issues in AIDS Research (T.R.F.); and US Food and Drug Administration internal Grants No. RSR 05-07 and RSR 06-11 (M.D.R.). NR 29 TC 95 Z9 95 U1 0 U2 7 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 JUN 10 PY 2009 VL 27 IS 17 BP 2874 EP 2880 DI 10.1200/JCO.2008.20.4107 PG 7 WC Oncology SC Oncology GA 455RO UT WOS:000266782100021 PM 19414672 ER PT J AU Dessailly, BH Nair, R Jaroszewski, L Fajardo, JE Kouranov, A Lee, D Fiser, A Godzik, A Rost, B Orengo, C AF Dessailly, Benoit H. Nair, Rajesh Jaroszewski, Lukasz Fajardo, J. Eduardo Kouranov, Andrei Lee, David Fiser, Andras Godzik, Adam Rost, Burkhard Orengo, Christine TI PSI-2: Structural Genomics to Cover Protein Domain Family Space SO STRUCTURE LA English DT Article ID COMPLETED GENOMES; DATABASE; EVOLUTION; ALIGNMENT; SUPERFAMILIES; SEQUENCES; RESOURCE; CLASSIFICATION; METAGENOMICS; PREDICTION AB One major objective of structural genomics efforts, including the NIH-funded Protein Structure Initiative (PSI), has been to increase the structural coverage of protein sequence space. Here, we present the target selection strategy used during the second phase of PSI (PSI-2). This strategy, jointly devised by the bioinformatics groups associated with the PSI-2 large-scale production centers, targets representatives from large, structurally uncharacterized protein domain families, and from structurally uncharacterized subfamilies in very large and diverse families with incomplete structural coverage. These very large families are extremely diverse both structurally and functionally, and are highly overrepresented in known proteomes. On the basis of several metrics, we then discuss to what extent PSI-2, during its first 3 years, has increased the structural coverage of genomes, and contributed structural and functional novelty. Together, the results presented here suggest that PSI-2 is successfully meeting its objectives and provides useful insights into structural and functional space. C1 [Dessailly, Benoit H.; Lee, David; Orengo, Christine] UCL, Dept Biol Mol & Struct, London WC1E 6BT, England. [Nair, Rajesh] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. [Jaroszewski, Lukasz; Godzik, Adam] Burnham Inst, La Jolla, CA 92037 USA. [Fajardo, J. Eduardo; Fiser, Andras] Albert Einstein Coll Med, Dept Syst & Computat Biol, Bronx, NY 10461 USA. [Kouranov, Andrei] Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA. [Rost, Burkhard] Columbia Univ, Ctr Computat Biol & Bioinformat C2B2, Dept Biochem & Mol Biophys, New York, NY 10032 USA. [Rost, Burkhard] Columbia Univ, NE Struct Genom Consortium NESG, New York, NY 10032 USA. RP Dessailly, BH (reprint author), UCL, Dept Biol Mol & Struct, Mortimer St, London WC1E 6BT, England. EM benoit@biochem.ucl.ac.uk RI Godzik, Adam/A-7279-2009 OI Godzik, Adam/0000-0002-2425-852X FU National Institute for General Medicine at the National Institutes of Health FX This work was supported by a grant from the Protein Structure Initiative of the National Institute for General Medicine at the National Institutes of Health. NR 51 TC 74 Z9 85 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 J9 STRUCTURE JI Structure PD JUN 10 PY 2009 VL 17 IS 6 BP 869 EP 881 DI 10.1016/j.str.2009.03.015 PG 13 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 458QZ UT WOS:000267039900012 PM 19523904 ER PT J AU Huang, WL Lee, SL Yu, LX AF Huang, Weili Lee, Sau Lawrence Yu, Lawrence X. TI Mechanistic Approaches to Predicting Oral Drug Absorption SO AAPS JOURNAL LA English DT Review DE advanced compartmental absorption and transit (ACAT) model; advanced dissolution, absorption, and metabolism (ADAM) model; compartmental model; dispersion model; oral drug absorption ID BETA-LACTAM ANTIBIOTICS; INTESTINAL-ABSORPTION; PHARMACOKINETIC SIMULATION; GASTROINTESTINAL-TRANSIT; PHYSIOLOGICAL MODEL; MATHEMATICAL-MODEL; P-GLYCOPROTEIN; SOLUBLE DRUG; DISSOLUTION; FRACTION AB Modeling and simulation of oral drug absorption have been widely used in drug discovery, development, and regulation. Predictive absorption models are used to determine the rate and extent of oral drug absorption, facilitate lead drug candidate selection, establish formulation development strategy, and support the development of regulatory policies. This review highlights the development of recent drug absorption models including dispersion and compartmental models. The compartmental models include the compartmental absorption and transit model; Grass model; gastrointestinal transit absorption model; advanced compartmental absorption and transit model; and advanced dissolution, absorption, and metabolism model. Compared to the early absorption models, the above models developed or extended since the mid-1990s have demonstrated greatly improved predictive performance by accounting for multiple factors such as drug degradation, gastric emptying, intestinal transit, first-pass metabolism, and intestinal transport. For future model development, more heterogeneous features of the gastrointestinal tract (villous blood flow, metabolizing enzymes, and transporters), food effects, and drug-drug interactions should be fully characterized and taken into consideration. Moreover, predicting population inter- and intravariability in oral drug absorption can be useful and important for the evaluation of clinical safety and efficacy of drugs. Establishing databases and libraries that contain accurate pharmaceutical and pharmacokinetic information for commercialized and uncommercialized drugs may also be helpful for model development and validation. C1 [Huang, Weili; Lee, Sau Lawrence; Yu, Lawrence X.] US FDA, Off Gener Drugs, Rockville, MD 20855 USA. RP Yu, LX (reprint author), US FDA, Off Gener Drugs, 7519 Standish Pl, Rockville, MD 20855 USA. EM lawrence.yu@fda.hhs.gov NR 67 TC 50 Z9 52 U1 6 U2 27 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD JUN PY 2009 VL 11 IS 2 BP 217 EP 224 DI 10.1208/s12248-009-9098-z PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 496AS UT WOS:000269940800002 PM 19381841 ER PT J AU Zhang, L Zhang, YC Zhao, P Huang, SM AF Zhang, Lei Zhang, Yuanchao (Derek) Zhao, Ping Huang, Shiew-Mei TI Predicting Drug-Drug Interactions: An FDA Perspective SO AAPS JOURNAL LA English DT Article DE drug development; drug-drug interaction; new drug application; prediction; regulatory and guidance ID IN-VITRO DATA; QUANTITATIVE PREDICTION; GENETIC-VARIATION; P-GLYCOPROTEIN; VIVO; PHARMACOKINETICS; INHIBITION; METABOLISM; KETOCONAZOLE; INACTIVATION AB Pharmacokinetic drug interactions can lead to serious adverse events, and the evaluation of a new molecular entity's drug-drug interaction potential is an integral part of drug development and regulatory review prior to its market approval. Alteration of enzyme and/or transporter activities involved in the absorption, distribution, metabolism, or excretion of a new molecular entity by other concomitant drugs may lead to a change in exposure leading to altered response (safety or efficacy). Over the years, various in vitro methodologies have been developed to predict drug interaction potential in vivo. In vitro study has become a critical first step in the assessment of drug interactions. Well-executed in vitro studies can be used as a screening tool for the need for further in vivo assessment and can provide the basis for the design of subsequent in vivo drug interaction studies. Besides in vitro experiments, in silico modeling and simulation may also assist in the prediction of drug interactions. The recent FDA draft drug interaction guidance highlighted the in vitro models and criteria that may be used to guide further in vivo drug interaction studies and to construct informative labeling. This report summarizes critical elements in the in vitro evaluation of drug interaction potential during drug development and uses a case study to highlight the impact of in vitro information on drug labeling. C1 [Zhang, Lei; Zhang, Yuanchao (Derek); 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, Rm 3188,Bldg 51,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM shiewmei.huang@fda.hhs.gov NR 48 TC 98 Z9 107 U1 4 U2 18 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD JUN PY 2009 VL 11 IS 2 BP 300 EP 306 DI 10.1208/s12248-009-9106-3 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 496AS UT WOS:000269940800009 PM 19418230 ER PT J AU Gupta, A Hunt, RL Shah, RB Sayeed, VA Khan, MA AF Gupta, Abhay Hunt, Robert L. Shah, Rakhi B. Sayeed, Vilayat A. Khan, Mansoor A. TI Disintegration of Highly Soluble Immediate Release Tablets: A Surrogate for Dissolution SO AAPS PHARMSCITECH LA English DT Article DE disintegration test; dissolution test; ICH Q6A; specification AB The purpose of the work was to investigate correlation between disintegration and dissolution for immediate release tablets containing a high solubility drug and to identify formulations where disintegration test, instead of the dissolution test, may be used as the acceptance criteria based on International Conference on Harmonization Q6A guidelines. A statistical design of experiments was used to study the effect of filler, binder, disintegrating agent, and tablet hardness on the disintegration and dissolution of verapamil hydrochloride tablets. All formulation variables, i.e., filler, binder, and disintegrating agent, were found to influence tablet dissolution and disintegration, with the filler and disintegrating agent exerting the most significant influence. Slower dissolution was observed with increasing disintegration time when either the filler or the disintegrating agent was kept constant. However, no direct corelationship was observed between the disintegration and dissolution across all formulations due to the interactions between different formulation components. Although all tablets containing sodium carboxymethyl cellulose as the disintegrating agent, disintegrated in less than 3 min, half of them failed to meet the US Pharmacopeia 30 dissolution criteria for the verapamil hydrochloride tablets highlighting the dependence of dissolution process on the formulation components other than the disintegrating agent. The results identified only one formulation as suitable for using the disintegration test, instead of the dissolution test, as drug product acceptance criteria and highlight the need for systematic studies before using the disintegration test, instead of the dissolution test as the drug acceptance criteria. C1 [Gupta, Abhay; Hunt, Robert L.; Shah, Rakhi B.; Khan, Mansoor A.] US FDA, Div Prod Qual Res, Off Testing & Res, Off Pharmaceut Sci, Silver Spring, MD 20993 USA. [Sayeed, Vilayat A.] US FDA, Div Chem 3, Off Gener Drugs, Rockville, MD 20855 USA. RP Khan, MA (reprint author), US FDA, Div Prod Qual Res, Off Testing & Res, Off Pharmaceut Sci, 10903 New Hampshire Ave,LS Bldg 64, Silver Spring, MD 20993 USA. EM Mansoor.khan@fda.hhs.gov NR 6 TC 12 Z9 12 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PD JUN PY 2009 VL 10 IS 2 BP 495 EP 499 DI 10.1208/s12249-009-9227-0 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 453VK UT WOS:000266640800023 PM 19387843 ER PT J AU Gupta, A Hamad, ML Tawakkul, M Sayeed, VA Khan, MA AF Gupta, Abhay Hamad, Mazen L. Tawakkul, Mobin Sayeed, Vilayat A. Khan, Mansoor A. TI Difference in the Lubrication Efficiency of Bovine and Vegetable-Derived Magnesium Stearate During Tabletting SO AAPS PHARMSCITECH LA English DT Article DE characterization; fluid bed granulation; functionality testing; high-shear granulation; lubricant efficiency; magnesium stearate AB The purpose of this work was to evaluate and compare the functionality of bovine fatty acids-derived (MgSt-B) and vegetable fatty acids-derived (MgSt-V) magnesium stearate powders when used for the lubrication of granules prepared by high-shear (HSG) and fluid bed (FBG) wet granulation methods. The work included evaluation of tablet compression and ejection forces during tabletting and dissolution testing of the compressed tablets. Granules prepared by both granulation methods required significantly lower ejection force (p < 0.01) when lubricated with the MgSt-V powder as compared to those lubricated with the MgSt-B powder. Granules prepared by the HSG method and lubricated with the MgSt-V powder also required significantly lower compression force (p < 0.01) to produce tablets of similar weight and hardness as compared to those lubricated with the MgSt-B powder. The dissolution profiles were not affected by these differences and were the same for tablets prepared by same granulation method and lubricated with either magnesium stearate powder. The results indicate significant differences (p < 0.01) between lubrication efficiency of the MgSt-B and the MgSt-V powders and emphasize the importance of functionality testing of the MgSt powders to understand the impact of these differences. C1 [Gupta, Abhay; Hamad, Mazen L.; Tawakkul, Mobin; Khan, Mansoor A.] US FDA, Div Prod Qual Res, Off Testing & Res, Off Pharmaceut Sci, Silver Spring, MD 20993 USA. [Sayeed, Vilayat A.] US FDA, Div Chem 3, Off Gener Drugs, Rockville, MD 20855 USA. [Hamad, Mazen L.] Univ Hawaii, Coll Arts & Sci, Hilo, HI 96720 USA. RP Khan, MA (reprint author), US FDA, Div Prod Qual Res, Off Testing & Res, Off Pharmaceut Sci, 10903 New Hampshire Ave,LS Bldg 64, Silver Spring, MD 20993 USA. EM Mansoor.khan@fda.hhs.gov NR 10 TC 5 Z9 5 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PD JUN PY 2009 VL 10 IS 2 BP 500 EP 504 DI 10.1208/s12249-009-9229-y PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 453VK UT WOS:000266640800024 PM 19390976 ER PT J AU Gheorghiade, M Adams, KF Cleland, JGF Cotter, G Felker, GM Filippatos, GS Fonarow, GC Greenberg, BH Hernandez, AF Khan, S Komajda, M Konstam, MA Liu, PP Maggioni, AP Massie, BM McMurray, JJ Mehra, M Metra, M O'Connell, J O'Connor, CM Pang, PS Pina, IL Sabbah, HN Teerlink, JR Udelson, JE Yancy, CW Zannad, F Stockbridge, N AF Gheorghiade, Mihai Adams, Kirkwood F. Cleland, John G. F. Cotter, Gad Felker, G. Michael Filippatos, Gerasimos S. Fonarow, Gregg C. Greenberg, Barry H. Hernandez, Adrian F. Khan, Sadiya Komajda, Michel Konstam, Marvin A. Liu, Peter P. Maggioni, Aldo P. Massie, Barry M. McMurray, John J. Mehra, Mandeep Metra, Marco O'Connell, John O'Connor, Christopher M. Pang, Peter S. Pina, Ileana L. Sabbah, Hani N. Teerlink, John R. Udelson, James E. Yancy, Clyde W. Zannad, Faiez Stockbridge, Norman CA Acute Heart Failure Syndromes Int TI Phase III clinical trial end points in acute heart failure syndromes: A virtual roundtable with the acute heart failure syndromes international working group SO AMERICAN HEART JOURNAL LA English DT Editorial Material C1 [Gheorghiade, Mihai; Khan, Sadiya; O'Connell, John; Pang, Peter S.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Adams, Kirkwood F.] Univ N Carolina, Chapel Hill, NC USA. [Cleland, John G. F.] Univ Hull, Castle Hill Hosp, Kingston Upon Hull, Yorks, England. [Cotter, Gad] Momentum Res Inc, Durham, NC USA. [Felker, G. Michael; Hernandez, Adrian F.; O'Connor, Christopher M.] Duke Univ, Med Ctr, Durham, NC USA. [Filippatos, Gerasimos S.] Univ Athens, Athens, Greece. [Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles Med Ctr, Los Angeles, CA USA. [Greenberg, Barry H.] Univ Calif San Diego, San Diego, CA 92103 USA. [Komajda, Michel] Univ Paris 06, Paris, France. [Komajda, Michel] Hosp Pitie Salpetriere, Paris, France. [Konstam, Marvin A.] Tufts Med Ctr, Boston, MA USA. [Liu, Peter P.] UHN, Toronto Gen Hosp, Toronto, ON, Canada. [Maggioni, Aldo P.] Assoc Nazl Med Cardiol Osped, Florence, Italy. [Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. [McMurray, John J.] Univ Glasgow, British Heart Fdn, Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Mehra, Mandeep] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. [Metra, Marco] Univ Brescia, Brescia, Italy. [Pina, Ileana L.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Sabbah, Hani N.] Henry Ford Hosp, Henry Ford Heart & Vasc Inst, Detroit, MI 48202 USA. [Teerlink, John R.] Univ Calif San Francisco, Vet Adm Med Ctr, San Francisco, CA USA. [Yancy, Clyde W.] Baylor Heart & Vasc Inst, Dallas, TX USA. [Zannad, Faiez] INSERM, Nancy, France. [Stockbridge, Norman] US FDA, Silver Spring, MD USA. RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, 676 N St Clair St,Suite 600, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu RI Teerlink, John/D-2986-2012; Lainscak, Mitja/F-3237-2015; Hernandez, Adrian F./A-7818-2016; OI Mehra, Mandeep/0000-0001-8683-7044; Hernandez, Adrian F./0000-0003-3387-9616; Cleland, John/0000-0002-1471-7016; Metra, Marco/0000-0001-6691-8568; mcmurray, john/0000-0002-6317-3975 NR 0 TC 37 Z9 37 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 2009 VL 157 IS 6 BP 957 EP 970 DI 10.1016/j.ahj.2009.04.010 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 454GD UT WOS:000266669500002 PM 19464405 ER PT J AU Pinheiro, SP Tworoger, SS Cramer, DW Rosner, BA Hankinson, SE AF Pinheiro, Simone P. Tworoger, Shelley S. Cramer, Daniel W. Rosner, Bernard A. Hankinson, Susan E. TI Use of Nonsteroidal Antiinflammatory Agents and Incidence of Ovarian Cancer in 2 Large Prospective Cohorts SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE anti-inflammatory agents; non-steroidal; ovarian neoplasms ID NATIONAL DEATH INDEX; COLORECTAL ADENOMAS; SEROUS CARCINOMA; RANDOMIZED-TRIAL; UNITED-STATES; ANALGESIC USE; RISK; ASPIRIN; DRUGS; EXPRESSION AB Epidemiologic data on the association between nonsteroidal antiinflammatory drugs (NSAIDs) and ovarian cancer risk have been inconsistent. The authors prospectively examined the association between regular use of aspirin and nonaspirin NSAIDs and ovarian cancer incidence among 197,486 participants of the Nurses' Health Study (NHS) and the Nurses' Health Study-II (NHS-II) over 24 and 16 years of follow-up, respectively. Information on aspirin was initially assessed in 1980 (NHS) and 1989 (NHS-II) and on nonaspirin NSAIDs and acetaminophen in 1990 (NHS) and 1989 (NHS-II) and updated throughout follow-up. The authors used Cox proportional hazards models adjusting for ovarian cancer risk factors. A total of 666 confirmed cases of epithelial ovarian cancer were identified over 2,790,986 person-years of follow-up. The hazard ratios associated with regular use of aspirin, nonaspirin NSAIDs, and acetaminophen were 1.11 (95% confidence interval (CI): 0.92, 1.33), 0.81 (95% CI: 0.64, 1.01), and 1.14 (95% CI: 0.92, 1.43), respectively. The authors did not observe a dose-response relation with increased frequency or duration of regular use of any of these medications and ovarian cancer incidence. The results did not differ substantially by tumor histology. In this large prospective study, the authors found no compelling evidence to support an association between regular use of aspirin, nonaspirin NSAIDs, or acetaminophen and ovarian cancer incidence. C1 [Pinheiro, Simone P.; Tworoger, Shelley S.; Rosner, Bernard A.; Hankinson, Susan E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Pinheiro, Simone P.; Tworoger, Shelley S.; Rosner, Bernard A.; Hankinson, Susan E.] Harvard Univ, Sch Med, Boston, MA USA. [Pinheiro, Simone P.; Tworoger, Shelley S.; Cramer, Daniel W.; Hankinson, Susan E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Pinheiro, Simone P.; Cramer, Daniel W.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. [Rosner, Bernard A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Pinheiro, SP (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Room 2471, Silver Spring, MD 20993 USA. EM spinheir@hsph.harvard.edu OI Tworoger, Shelley/0000-0002-6986-7046 FU National Institutes of Health [P50 CA105009, CA 50385, P01 CA87969] FX The funding source had no role in the study design, data collection, data analysis, or interpretation of the findings. NR 52 TC 22 Z9 22 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2009 VL 169 IS 11 BP 1378 EP 1387 DI 10.1093/aje/kwp062 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 446GF UT WOS:000266109400014 PM 19342401 ER PT J AU Nichols, WL Rick, ME Ortel, TL Montgomery, RR Sadler, JE Yawn, BP James, AH Hultin, MB Manco-Johnson, MJ Weinstein, M AF Nichols, William L. Rick, Margaret E. Ortel, Thomas L. Montgomery, Robert R. Sadler, J. Evan Yawn, Barbara P. James, Andra H. Hultin, Mae B. Manco-Johnson, Marilyn J. Weinstein, Mark TI Clinical and laboratory diagnosis of von Willebrand disease: A synopsis of the 2008 NHLBI/NIH guidelines SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID CARDIOMYOPATHY AB Von Willebrand factor (VWF) mediates blood platelet adhesion and accumulation at sites of blood vessel injury, and also carries coagulation factor VIII (FVIII) that is important for generating procoagulant activity. Von Willebrand disease (VWD), the most common inherited bleeding disorder, affects males and females, and reflects deficiency or defects of VWF that may also cause decreased FVIII. It may also occur less commonly as an acquired disorder (acquired von Willebrand syndrome). This article briefly summarizes selected features of the March 2008 evidence-based clinical and laboratory diagnostic recommendations from the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel for assessment for VWD or other bleeding disorders or risks. Management of VWD is also addressed in the NHLBI guidelines, but is not summarized here. The VWD guidelines are available at the NHLBI Web site (http://www.nhlbi.nih.gov/guidelines/ vwd). Am. J. Hematol. 84:366-370, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Nichols, William L.] Mayo Clin, Special Coagulat Lab, Coll Med, Dept Lab Med & Pathol,Div Hematopathol, Rochester, MN 55905 USA. [Nichols, William L.] Mayo Clin, Coll Med, Div Hematol & Internal Med, Coagulat Clin, Rochester, MN 55905 USA. [Nichols, William L.] Mayo Clin, Coll Med, Div Hematol & Internal Med, Comprehens Hemophilia Ctr, Rochester, MN 55905 USA. [Rick, Margaret E.] NIH, Hematol Serv, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Ortel, Thomas L.] Duke Univ, Med Ctr, Dept Med, Div Hematol, Durham, NC 27710 USA. [Ortel, Thomas L.] Duke Univ, Med Ctr, Dept Pathol, Clin Coagulat Lab, Durham, NC 27710 USA. [Montgomery, Robert R.] Med Coll Wisconsin, Blood Ctr Wisconsin, Blood Res Inst, Milwaukee, WI 53226 USA. [Montgomery, Robert R.] Med Coll Wisconsin, Dept Pediat, Sect Pediat Hematol, Milwaukee, WI 53226 USA. [Sadler, J. Evan] Washington Univ, Dept Med, St Louis, MO USA. [Yawn, Barbara P.] Olmsted Med Ctr, Dept Res, Rochester, MN USA. [Yawn, Barbara P.] Univ Minnesota, Dept Family & Community Med, Minneapolis, MN USA. [James, Andra H.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. [Hultin, Mae B.] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. [Manco-Johnson, Marilyn J.] Univ Colorado Denver, Dept Pediat, Aurora, CO USA. [Manco-Johnson, Marilyn J.] Childrens Hosp, Ctr Canc & Blood Disorders, Denver, CO 80218 USA. [Weinstein, Mark] US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Rockville, MD 20857 USA. RP Nichols, WL (reprint author), Mayo Clin, Special Coagulat Lab, Coll Med, Dept Lab Med & Pathol,Div Hematopathol, Hilton 200,200 1st St SW, Rochester, MN 55905 USA. EM nichols.william@mayo.edu RI Sadler, Evan/D-8556-2011 NR 11 TC 34 Z9 34 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2009 VL 84 IS 6 BP 366 EP 370 DI 10.1002/ajh.21405 PG 5 WC Hematology SC Hematology GA 452VW UT WOS:000266570300011 PM 19415721 ER PT J AU Gonzalez-Escalona, N Hammack, TS Russell, M Jacobson, AP De Jesus, AJ Brown, EW Lampel, KA AF Gonzalez-Escalona, Narjol Hammack, Thomas S. Russell, Mindi Jacobson, Andrew P. De Jesus, Antonio J. Brown, Eric W. Lampel, Keith A. TI Detection of Live Salmonella sp Cells in Produce by a TaqMan-Based Quantitative Reverse Transcriptase Real-Time PCR Targeting invA mRNA SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; MAMMALIAN-CELLS; VIBRIO-CHOLERAE; RT-PCR; AMPLIFICATION; QUANTIFICATION; GENE; TYPHIMURIUM; SEQUENCE; FOOD AB Salmonella enterica contamination in foods is a significant concern for public health. When DNA detection methods are used for analysis of foods, one of the major concerns is false-positive results from the detection of dead cells. To circumvent this crucial issue, a TaqMan quantitative real-time RT-PCR (qRT-PCR) assay with an RNA internal control was developed. invA RNA standards were used to determine the detection limit of this assay as well as to determine invA mRNA levels in mid-exponential-, late-exponential-, and stationary-phase cells. This assay has a detection limit of 40 copies of invA mRNA per reaction. The levels of invA mRNA in mid-exponential-, late-exponential-, and stationary-phase S. enterica cells was approximately 1 copy per 3 CFU, 1 copy per CFU, and 4 copies per 10(3) CFU, respectively. Spinach, tomatoes, jalapeno peppers, and serrano peppers were artificially contaminated with four different Salmonella serovars at levels of 10(5) and less than 10 CFU. These foods were analyzed with qRT-PCR and with the FDA's Bacteriological Analytical Manual Salmonella culture method (W. A. Andrews and T. S. Hammack, in G. J. Jackson et al., ed., Bacteriological analytical manual online, http://www.cfsan.fda.gov/similar to ebam/bam-5.html, 2007). Comparable results were obtained by both methods. Only live Salmonella cells could be detected by this qRT-PCR assay, thus avoiding the dangers of false-positive results from nonviable cells. False negatives (inhibition of the PCR) were also ruled out through the use of an RNA internal control. This assay allows for the fast and accurate detection of viable Salmonella spp. in spinach, tomatoes, and in both jalapeno and serrano peppers. C1 [Gonzalez-Escalona, Narjol; Hammack, Thomas S.; Russell, Mindi; Jacobson, Andrew P.; De Jesus, Antonio J.; Brown, Eric W.; Lampel, Keith A.] FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Gonzalez-Escalona, N (reprint author), FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy HFS 712, 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 41 TC 60 Z9 62 U1 2 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JUN 1 PY 2009 VL 75 IS 11 BP 3714 EP 3720 DI 10.1128/AEM.02686-08 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 449QT UT WOS:000266345800042 PM 19376910 ER PT J AU Sheng-Fowler, L Lewis, AM Peden, K AF Sheng-Fowler, Li Lewis, Andrew M., Jr. Peden, Keith TI Issues associated with residual cell-substrate DNA in viral vaccines SO BIOLOGICALS LA English DT Article; Proceedings Paper CT Conference on New Cells for New Vaccines III CY SEP 28-OCT 01, 2008 CL Wilmington, DE DE Oncogenic DNA; Infectious DNA; Risk evaluation ID COTTONTAIL RABBIT PAPILLOMAVIRUS; INFECTIOUS MOLECULAR CLONE; BOVINE LEUKEMIA-VIRUS; ILLEGITIMATE RECOMBINATION EVENTS; SIMIAN IMMUNODEFICIENCY VIRUS; OPEN READING FRAME; PLASMID DNA; BIOLOGICAL-ACTIVITY; IN-VIVO; DEOXYRIBONUCLEIC ACID AB The presence of some residual cellular DNA derived from the production-cell substrate in viral vaccines is inevitable. Whether this DNA represents a safety concern, particularly if the cell substrate is derived from a tumor or is tumorigenic, is unknown. DNA has two biological activities that need to be considered. First, DNA can be oncogenic; second, DNA can be infectious. As part of our studies to assess the risk of residual cell-substrate DNA in viral vaccines, we have established assays that can quantify the biological activities of DNA. From data obtained using these assays, we have estimated the risk of an oncogenic or an infectious event from DNA. Because these estimates were derived from the most sensitive assays identified so far, they likely represent worst-case estimates. In addition, methods that inactivate the biological activities of DNA can be assessed and estimations of risk reduction by these treatments can be made. In this paper, we discuss our approaches to address potential safety issues associated with residual cellular DNA from neoplastic cell substrates in viral vaccines, summarize the development of assays to quantify the oncogenic and infectivity activities of DNA, and discuss methods to reduce the biological activities of DNA. Published by Elsevier Ltd on behalf of The International Association for Biologicals. C1 [Sheng-Fowler, Li; Lewis, Andrew M., Jr.; Peden, Keith] US FDA, Div Viral Prod, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Peden, K (reprint author), US FDA, Div Viral Prod, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bldg 29A,Room 3D08,CBER,FDA,29 Lincoln Dr, Bethesda, MD 20892 USA. EM keith.peden@fda.hhs.gov NR 83 TC 20 Z9 23 U1 0 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD JUN PY 2009 VL 37 IS 3 BP 190 EP 195 DI 10.1016/j.biologicals.2009.02.015 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 461GX UT WOS:000267253800015 PM 19285882 ER PT J AU Khan, AS Ma, WB Ma, YK Kumar, A Williams, DK Muller, J Ma, HL Galvin, TA AF Khan, Arifa S. Ma, Wenbin Ma, Yunkun Kumar, Anita Williams, Dhanya K. Muller, Jacqueline Ma, Hailun Galvin, Teresa A. TI Proposed algorithm to investigate latent and occult viruses in vaccine cell substrates by chemical induction SO BIOLOGICALS LA English DT Article; Proceedings Paper CT Conference on New Cells for New Vaccines III CY SEP 28-OCT 01, 2008 CL Wilmington, DE DE Vaccine cell substrates; Latent viruses; Chemical inducers; Virus activation ID REVERSE-TRANSCRIPTASE ASSAY; SIGNALS AB The recent urgency to develop new vaccines for emerging and re-emerging diseases, such as pandemic influenza, has necessitated the use of cell substrates not previously used in the manufacture of licensed vaccines. A major safety concern in the use of novel cell substrates is the presence of potential adventitious agents, such as latent and occult viruses, that may not be detected by currently used conventional assays. In cases where the novel cell substrate is known to be tumorigenic, there are additional safety issues related to tumorigenicity of intact cells and oncogenicity of residual cellular DNA. We have developed a strategy for evaluating vaccine cell substrates for the presence of latent/occult viruses, including endogenous retroviruses, latent RNA viruses and oncogenic DNA viruses, by optimizing conditions for chemical induction of viruses and using a combination of broad and specific assays to enable detection of known and novel viruses. Published by Elsevier Ltd on behalf of The International Association for Biologicals. C1 [Khan, Arifa S.; Ma, Wenbin; Ma, Yunkun; Kumar, Anita; Williams, Dhanya K.; Ma, Hailun; Galvin, Teresa A.] US FDA, Lab Retrovirus Res, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Muller, Jacqueline] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Khan, AS (reprint author), US FDA, Lab Retrovirus Res, Ctr Biol Evaluat & Res, 8800 Rockville Pike HFM-454,Bldg 29B,Room 4NN10, Bethesda, MD 20892 USA. EM arifa.khan@fda.hhs.gov FU PHS HHS [Y1-A1-4893-02] NR 19 TC 8 Z9 8 U1 0 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD JUN PY 2009 VL 37 IS 3 BP 196 EP 201 DI 10.1016/j.biologicals.2009.02.016 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 461GX UT WOS:000267253800016 PM 19299169 ER PT J AU Maher, C Lushniak, BD AF Maher, C. Lushniak, B. D. TI Availability of Medical Countermeasures for Bioterrorism Events: US Legal and Regulatory Options SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article AB Plans for mass distribution of medical countermeasures raise challenging problems, including legal and regulatory issues. Many in the distribution chain have expressed concerns over the potential for liability when countermeasures are distributed in accordance with large-scale response plans. This is of particular concern if the medical countermeasure involved has not been approved, cleared, or licensed by the US Food and Drug Administration (FDA). This article discusses legal and regulatory options for countermeasure distribution that address liability concerns and access to unapproved countermeasures during an emergency. C1 [Maher, C.; Lushniak, B. D.] US FDA, Off Counterterrorism & Emerging Threats, US Dept Hlth & Human Serv, Rockville, MD 20857 USA. RP Maher, C (reprint author), US FDA, Off Counterterrorism & Emerging Threats, US Dept Hlth & Human Serv, Rockville, MD 20857 USA. EM carmen.maher@fda.hhs.gov NR 6 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 JUN PY 2009 VL 85 IS 6 BP 669 EP 671 DI 10.1038/clpt.2009.55 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 448VL UT WOS:000266290000024 PM 19387435 ER PT J AU Lorenz, BD Smith, TD Laessig, K Chambers, W Nambiar, S AF Lorenz, Benjamin D. Smith, Thomas D. Laessig, Katherine Chambers, Wiley Nambiar, Sumati TI Recombinant activated protein C and risk of bleeding Reply SO CRITICAL CARE MEDICINE LA English DT Letter C1 [Lorenz, Benjamin D.; Smith, Thomas D.; Laessig, Katherine; Chambers, Wiley; Nambiar, Sumati] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Lorenz, BD (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 2009 VL 37 IS 6 BP 2141 EP 2142 DI 10.1097/CCM.0b013e3181a5c415 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 448ZK UT WOS:000266300300070 PM 19448483 ER PT J AU Kim, SJ Kweon, O Cerniglia, CE AF Kim, Seong-Jae Kweon, Ohgew Cerniglia, Carl E. TI Proteomic applications to elucidate bacterial aromatic hydrocarbon metabolic pathways SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID MYCOBACTERIUM-VANBAALENII PYR-1; BURKHOLDERIA-XENOVORANS LB400; RING-HYDROXYLATING DIOXYGENASES; ACINETOBACTER-LWOFFII K24; BETA-KETOADIPATE PATHWAY; SP STRAIN PYR-1; PSEUDOMONAS-PUTIDA; GEL-ELECTROPHORESIS; CATABOLIC PATHWAYS; MASS-SPECTROMETRY AB The growing availability of genome sequences and advancement of high-throughput omics and analytical chemistry technologies have reinvigorated the study of biodegradation processes in aromatic hydrocarbon catabolism. In particular, proteomics approaches globally have identified and quantified bacterial enzymes responsible for aromatic hydrocarbon metabolism, which significantly assists in determining strategies for the biodegradation of aromatic hydrocarbons with applications in environmental bioremediation. C1 [Kim, Seong-Jae; Kweon, Ohgew; Cerniglia, Carl E.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Cerniglia, CE (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM carl.cerniglia@fda.hhs.gov NR 56 TC 25 Z9 26 U1 4 U2 27 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD JUN PY 2009 VL 12 IS 3 BP 301 EP 309 DI 10.1016/j.mib.2009.03.006 PG 9 WC Microbiology SC Microbiology GA 469US UT WOS:000267926800012 PM 19414279 ER PT J AU Billal, DS Hotomi, M Yan, SS Fedorko, DP Shimada, J Fujihara, K Yamanaka, N AF Billal, Dewan Sakhawat Hotomi, Muneki Yan, Steve S. Fedorko, Daniel P. Shimada, Jun Fujihara, Keiji Yamanaka, Noboru TI Loss of erythromycin resistance genes from strains of Streptococcus pyogenes that have developed resistance to levofloxacin SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE Streptococcus pyogenes; Fluoroquinolone resistance; Erythromycin resistance; Transconjugation ID GROUP-A STREPTOCOCCI; UROPATHOGENIC ESCHERICHIA-COLI; MACROLIDE RESISTANCE; ANTIMICROBIAL SUSCEPTIBILITY; STAPHYLOCOCCUS-AUREUS; VANCOMYCIN; INDUCTION; JAPAN AB In the past 2 to 3 decades, erythromycin resistance in Streptococcus pyogenes has been decreasing, whereas fluoroquinolone resistance (or reduction in its susceptibility) has been reported often. Although a shift of M-type prevalence and decreased pressure from macrolides have been suggested for the decrease in erythromycin resistance, we hypothesized that this might also be a result of increased antimicrobial pressure from fluoroquinolone use. Levofloxacin resistance for 4 erythromycin-resistant parent strains was induced in vitro. Their mutants became highly resistant to the fluoroquinolones but lost their erythromycin resistance trait. Erythromycin resistance was fully restored by transconjugation with respective parent strains with either mefA- or ermTR-mediated mechanisms. (C) 2009 Published by Elsevier Inc. C1 [Billal, Dewan Sakhawat; Hotomi, Muneki; Shimada, Jun; Fujihara, Keiji; Yamanaka, Noboru] Wakayama Med Univ, Dept Otolaryngol, Wakayama 6418509, Japan. [Yan, Steve S.] US FDA, Dept Hlth & Human Serv, Rockville, MD 20855 USA. [Fedorko, Daniel P.] NIH, Dept Hlth & Human Serv, Ctr Clin, Bethesda, MD 20892 USA. RP Yamanaka, N (reprint author), Wakayama Med Univ, Dept Otolaryngol, Wakayama 6418509, Japan. EM ynobi@wakayama-med.ac.jp NR 20 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD JUN PY 2009 VL 64 IS 2 BP 225 EP 228 DI 10.1016/j.diagmicrobio.2009.01.034 PG 4 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 455WZ UT WOS:000266800600017 PM 19345038 ER PT J AU Khan, AS AF Khan, Arifa S. TI Simian foamy virus infection in humans: prevalence and management SO EXPERT REVIEW OF ANTI-INFECTIVE THERAPY LA English DT Review DE cross-species retrovirus; nonhuman primate; persistent human infection; simian foamy virus; transmission ID HUMAN SYNCYTIAL VIRUS; NATURALLY-OCCURRING ANTIBODIES; ENDOGENOUS RETROVIRUSES; NONHUMAN-PRIMATES; TRANSCRIPTIONAL TRANSACTIVATOR; INDUCED IMMUNOSUPPRESSION; NASOPHARYNGEAL CARCINOMA; MOLECULAR EPIDEMIOLOGY; HUMAN SPUMARETROVIRUS; PERSISTENT INFECTION AB Simian foamy viruses (SFVs) are highly prevalent in all nonhuman primate species and can infect humans following occupational and non-occupational exposure to infected animals and their tissues, blood or body fluids. Virus transmission results in a stable, persistent infection that seems to be latent. SFV infections are thus far nonpathogenic, with no evidence of adverse clinical outcome in their natural nonhuman primate hosts or by experimental injection in animals and upon cross-species transmission in humans. Since the emergence of pathogenic viruses from nonpathogenic viruses upon cross-species infection is well-documented for several retroviruses, it is prudent to take necessary precautions to deter SFV infections in humans. These steps will help prevent the emergence of a novel pathogen and reduce the risk of transmission of another potential pathogenic human retrovirus. C1 US FDA, Lab Retrovirus Res, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Khan, AS (reprint author), US FDA, Lab Retrovirus Res, Div Viral Prod, Ctr Biol Evaluat & Res, 8800 Rockville Pike,HFM 454,Bldg 29B,Room 4NN10, Bethesda, MD 20892 USA. EM arifa.khan@fda.hhs.gov NR 129 TC 32 Z9 33 U1 0 U2 2 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-7210 J9 EXPERT REV ANTI-INFE JI Expert Rev. Anti-Infect. Ther. PD JUN PY 2009 VL 7 IS 5 BP 569 EP 580 DI 10.1586/ERI.09.39 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 460HS UT WOS:000267179400015 PM 19485797 ER PT J AU Autran, B Asturias, EJ Evans, S Harrigan-Go, K Hussey, G John, TJ Lambert, PH Law, B Midthun, K Nohynek, H Salmaso, S Smith, PG Zuber, PLF Bentsi-Enchill, A Caric, A Pfeifer, D Duclos, P Wood, D AF Autran, Brigitte Asturias, Edwin J. Evans, Stephen Harrigan-Go, Kenneth Hussey, Gregory John, T. Jacob Lambert, Paul-Henri Law, Barbara Midthun, Karen Nohynek, Hanna Salmaso, Stefania Smith, Peter G. Zuber, Patrick L. F. Bentsi-Enchill, Adwoa Caric, Alecksandra Pfeifer, Dina Duclos, Philippe Wood, David CA Global Advisory Committee Vaccine WHO Secretariat TI Global safety of vaccines: strengthening systems for monitoring, management and the role of GACVS SO EXPERT REVIEW OF VACCINES LA English DT Article DE adverse event; immunization program; monitoring signal; pharmacovigilance; safety; vaccine; WHO ID IMMUNIZATION PRACTICES ACIP; EVENT REPORTING SYSTEM; THIMEROSAL-CONTAINING VACCINE; STANDARDIZED CASE DEFINITIONS; ANTIVACCINATION WEB SITES; HEPATITIS-B-VACCINE; ADVISORY-COMMITTEE; DEVELOPING-COUNTRIES; INFLUENZA VACCINE; PUBLIC-HEALTH AB Vaccines have contributed enormously in reducing the impact of many infectious diseases, and the expanded use of new and existing vaccines provides unprecedented potential for further reducing the global burden of infectious diseases. Yet, as with the deployment of other technologies, their use may also sometimes be associated with undesirable effects that need to be identified rapidly, understood and minimized. In this article, we review the models and systems that have been developed to monitor and respond to concerns regarding vaccine safety and we give illustrative examples of real or perceived vaccine safety issues. The Global Advisory Committee on Vaccine Safety (GACVS) was set up 10 years ago and charged to provide the WHO with independent advice on vaccine safety issues. The role of the GACVS is both to analyze and to interpret reports of the adverse effects of vaccines that impact on global vaccination programs and strategies, and to foster the development of improved surveillance systems to detect any adverse effects of vaccines, particularly in low- and middle-income countries. It also monitors the development of new vaccines during clinical testing and advises on the safe use of vaccines in immunization programs. As success is achieved with reducing the burden of vaccine-preventable diseases, there will be increasing attention focused on potential adverse effects, on the development of effective surveillance systems to detect adverse effects, and on improved methods to manage and control any harmful consequences of vaccination. C1 [Zuber, Patrick L. F.] WHO, Dept Immunizat Vaccines & Biol, Qual Safety & Stand Team, CH-1211 Geneva 27, Switzerland. [Autran, Brigitte] Univ Paris 06, Fac Med Pitie Salpetriere, Lab Immunol Cellulaire & Tissulaire, F-75252 Paris, France. [Asturias, Edwin J.] Univ Valle Guatemala, Guatemala City, Guatemala. [Asturias, Edwin J.] Johns Hopkins Sch Publ Hlth, Guatemala City, Guatemala. [Evans, Stephen] London Sch Hyg & Trop Med, Med Stat Unit, London WC1, England. [Harrigan-Go, Kenneth] Zuellig Fdn, Manila, Philippines. [Hussey, Gregory] Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7700 Rondebosch, South Africa. [John, T. Jacob] Christian Med Coll & Hosp, Vellore, Tamil Nadu, India. [Lambert, Paul-Henri] Ctr Med Univ Geneva, Ctr Vaccinol, Geneva, Switzerland. [Law, Barbara] Publ Hlth Agcy Canada, Ottawa, ON, Canada. [Midthun, Karen] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Nohynek, Hanna] KTL Natl Publ Hlth Inst, Dept Vaccines, Helsinki, Finland. [Salmaso, Stefania] Ist Super Sanita, Natl Ctr Epidemiol, I-00161 Rome, Italy. [Smith, Peter G.] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1, England. RP Zuber, PLF (reprint author), WHO, Dept Immunizat Vaccines & Biol, Qual Safety & Stand Team, CH-1211 Geneva 27, Switzerland. EM zuberp@who.int NR 88 TC 25 Z9 25 U1 0 U2 11 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD JUN PY 2009 VL 8 IS 6 BP 705 EP 716 DI 10.1586/ERV.09.40 PG 12 WC Immunology SC Immunology GA 457TV UT WOS:000266957500013 ER PT J AU Olekhnovich, IN Goodwin, A Hoffman, PS AF Olekhnovich, Igor N. Goodwin, Avery Hoffman, Paul S. TI Characterization of the NAD(P)H oxidase and metronidazole reductase activities of the RdxA nitroreductase of Helicobacter pylori SO FEBS JOURNAL LA English DT Article DE flavoprotein; Helicobacter; metronidazole; NAD(P)H oxidase; nitroreductase ID ENZYME PRODRUG THERAPY; ESCHERICHIA-COLI-NITROREDUCTASE; GLUCOSE OXIDASE; RESISTANCE; GENE; OXYGEN; ACTIVATION; CANCER; OXIDOREDUCTASE; IDENTIFICATION AB Metronidazole (MTZ) is widely used in combination therapies against the human gastric pathogen Helicobacter pylori. Resistance to this drug is common among clinical isolates and results from loss-of-function mutations in rdxA, which encodes an oxygen-insensitive nitroreductase. The RdxA-associated MTZ-reductase activity of H. pylori is lost upon cell disruption. Here we provide a mechanistic explanation for this phenomenon. Under aerobic conditions, His6-tagged RdxA protein (purified from Escherichia coli), catalyzed NAD(P)H-dependent reductions of nitroaromatic and quinone substrates including nitrofurazone, nitrofurantoin, furazolidone, CB1954 and 1,4-benzoquinone, but not MTZ. Unlike other nitroreductases, His6-RdxA exhibited potent NAD(P)H-oxidase activity (k(cat) = 2.8 s(-1)) which suggested two possible explanations for the role of oxygen in MTZ reduction: (a) NAD(P)H-oxidase activity promotes cellular hypoxia (nonspecific reduction of MTZ), and (b) molecular oxygen out-competes MTZ for reducing equivalents. The first hypothesis was eliminated upon finding that rdxA expression, although increasing MTZ toxicity in both E. coli and H. pylori constructs, did not increase paraquat toxicity, even though both are of similar redox potential. The second hypothesis was confirmed by demonstrating NAD(P)H-dependent MTZ-reductase activity (apparent K(m) = 122 +/- 58 mu m, k(cat) = 0.24 s(-1)) under strictly anaerobic conditions. The MTZ-reductase activity of RdxA was 60 times greater than for NfsB (E. coli NTR), but 10 times lower than the NADPH-oxidase activity. Whether molecular oxygen directly competes with MTZ or alters the redox state of the FMN cofactors is discussed. C1 [Olekhnovich, Igor N.; Hoffman, Paul S.] Univ Virginia, Sch Med, Dept Microbiol, Charlottesville, VA 22908 USA. [Goodwin, Avery] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Olekhnovich, Igor N.; Hoffman, Paul S.] Univ Virginia, Sch Med, Dept Med, Charlottesville, VA 22908 USA. RP Hoffman, PS (reprint author), Univ Virginia Hlth Syst, Div Infect Dis & Int Hlth, Room 2146 MR-4 Bldg,409 Lane Rd, Charlottesville, VA 22908 USA. EM psh2n@virginia.edu RI Olekhnovich, Igor/N-4058-2014 OI Olekhnovich, Igor/0000-0003-1648-8509 FU NIH [5U01AI075520, 5R01DK073823] FX We thank Douglas Berg for lively discussions and critical review of the manuscript and Syargey Gilevich for helpful discussions. This work was supported by NIH grants 5U01AI075520 and 5R01DK073823 to PSH. NR 43 TC 28 Z9 29 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1742-464X J9 FEBS J JI FEBS J. PD JUN PY 2009 VL 276 IS 12 BP 3354 EP 3364 DI 10.1111/j.1742-4658.2009.07060.x PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 448MX UT WOS:000266267800015 PM 19438716 ER PT J AU Blodgett, RJ AF Blodgett, Robert J. TI Planning a serial dilution test with multiple dilutions SO FOOD MICROBIOLOGY LA English DT Article DE MPN, most probable number; Microbial concentration; Test design ID BACTERIOLOGY AB The dilutions used ill a serial dilution test determine which concentrations it call estimate well. Two criteria help to select how many and which dilutions to Use. The first Criterion is a low probability of Outcomes with either all growth or all non-growth tubes at the concentrations of interest. The second criterion considers how far the estimated concentration (MPN) is likely to be from the actual concentration. Published by Elsevier Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Blodgett, RJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM robert.blodgett@fda.hhs.gov NR 5 TC 2 Z9 2 U1 3 U2 10 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD JUN PY 2009 VL 26 IS 4 BP 421 EP 424 DI 10.1016/j.fm.2009.02.001 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 445CY UT WOS:000266028500009 PM 19376465 ER PT J AU Nawaz, M Khan, AA Khan, S Sung, K Kerdahi, K Steele, R AF Nawaz, Mohamed Khan, Ashraf A. Khan, Saeed Sung, Kidon Kerdahi, Khalil Steele, Roger TI Molecular Characterization of Tetracycline-Resistant Genes and Integrons from Avirulent Strains of Escherichia coli Isolated from Catfish SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID FOODBORNE DISEASES; SEAFOOD; FISH; SUSCEPTIBILITY; DETERMINANTS; PREVALENCE; PRODUCTS; BACTERIA; REGION AB A study was undertaken to investigate the occurrence of tetracycline-resistant genes and to characterize the integrons present in Escherichia coli isolated from catfish. Sixty-three tetracycline-resistant E. coli strains were isolated from the intestinal contents of 407 farm-raised catfish. All strains were resistant to multiple antibiotics. A polymerase chain reaction (PCR) assay detected tetA in the DNA of 15 of 63 (25.0%) isolates by amplifying a PCR amplicon measuring 957 bp. Oligonucleotide primers targeting a 436-bp region of tetB successfully amplified a PCR amplicon from 47 of 63 (77.0%) isolates, indicating that tetB was predominant. Oligonucleotide primers specific for tetC amplified a 589-bp PCR amplicon from 3 of 63 (5%) isolates. Eleven (17.0%) of the isolates contained both tetA and tetB genes. Class I integrons amplified from the genomic DNA of 14 of 63 (22.0%) isolates measured 1.6 and 1.8 kb. Sequence analysis of the 1.6 kb integrons indicated the presence of three different gene cassettes: a dfrA12, conferring resistance to trimethoprim; an open reading frame, orfF, a hypothetical protein of unknown function; and aadA2, conferring resistance to aminoglycosides. Sequence analysis of the 1.8-kb integron indicated the presence of dfrA17 and aadA5. PCR assays for the detection of the six predominant virulence genes failed to amplify any genes from the genomic DNA. Pulsed-field gel electrophoresis using XbaI identified 16 distinct macro restriction patterns among the 63 isolates. The dendrogram analysis indicated that the DNA from 4 of 16 isolates had a similarity index of 90.0%. Our results indicate that the use of oxytetracycline and Romet 30 (sulfadimethoxine and ormetoprim) in farm-raised catfish may select for multiple antibiotic-resistant E. coli that could serve as a reservoir of tetracycline, trimethoprim, and aminoglycoside resistance genes. C1 [Nawaz, Mohamed; Khan, Ashraf A.; Khan, Saeed; Sung, Kidon; Steele, Roger] Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Kerdahi, Khalil] Arkansas Reg Lab, Jefferson, AR USA. RP Nawaz, M (reprint author), Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM mohamed.nawaz@fda.hhs.gov RI Khan, Ashraf/E-8133-2013 FU National Center for Toxicological Research, U.S. Food and Drug Administration FX We thank Drs. Carl E. Cerniglia, J.B. Sutherland, and Carina M. Jung for critical review of the manuscript. Views presented here do not necessarily reflect those of the U. S. Food and Drug Administration. This work was supported by the National Center for Toxicological Research, U.S. Food and Drug Administration. NR 25 TC 19 Z9 21 U1 1 U2 14 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1535-3141 J9 FOODBORNE PATHOG DIS JI Foodborne Pathog. Dis. PD JUN PY 2009 VL 6 IS 5 BP 553 EP 559 DI 10.1089/fpd.2008.0204 PG 7 WC Food Science & Technology SC Food Science & Technology GA 459GR UT WOS:000267090100006 PM 19388830 ER PT J AU Taylor, DR Silberstein, E AF Taylor, Deborah R. Silberstein, Erica TI Innate immunity and hepatitis C virus: eluding the host cell defense SO FRONTIERS IN BIOSCIENCE LA English DT Article DE Interferon; Hepatitis; Signaling; Liver; Genotypes; Innate Immunity; Review ID NONSTRUCTURAL 5A PROTEIN; BLOOD MONONUCLEAR-CELLS; RECEPTOR MESSENGER-RNA; NITRIC-OXIDE SYNTHASE; DOUBLE-STRANDED-RNA; SENSITIVITY-DETERMINING REGION; INTERFERON-ALPHA THERAPY; CHRONIC LIVER-DISEASES; RIBOSOME ENTRY SITE; E2 ENVELOPE PROTEIN AB Interferon-alpha (IFN-alpha) mono-therapy is largely ineffective for most of the hepatitis C virus (HCV)-infected patients that receive it. The addition of ribavirin to IFN therapy has increased the response rate dramatically. While many factors are implicated in determining the success rate for IFN therapy, viral genotype seems to play a crucial role. Examining differences in viral gene sequences has and will continue to advance our understanding as to how HCV and other viruses circumvent the IFN response. Here we review the different ways that HCV evades the immune response elicited by IFN. C1 [Taylor, Deborah R.; Silberstein, Erica] CBER FDA, Off Blood Res & Review, Div Emerging & Transfus Transmitted Dis, Lab Hepatitis & Related Emerging Agents, Bethesda, MD 20892 USA. RP Taylor, DR (reprint author), CBER FDA, Off Blood Res & Review, Div Emerging & Transfus Transmitted Dis, Lab Hepatitis & Related Emerging Agents, 8800 Rockville Pike,HFM-310,NIH Bldg 29,131, Bethesda, MD 20892 USA. EM Deborah.Taylor@FDA.HHS.gov NR 100 TC 7 Z9 7 U1 0 U2 2 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JUN PY 2009 VL 14 BP 4950 EP 4961 DI 10.2741/3579 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 497LP UT WOS:000270061300010 PM 19482597 ER PT J AU Lartigue, J Jester, ELE Dickey, RW Villareal, TA AF Lartigue, J. Jester, Edward L. E. Dickey, R. W. Villareal, T. A. TI Nitrogen source effects on the growth and toxicity of two strains of the ciguatera-causing dinoflagellate Gambierdiscus toxicus SO HARMFUL ALGAE LA English DT Article DE Ciguatoxin; Gambierdiscus toxicus; Nitrogen; Strain 1651; Strain 1655; Toxicity ID CORAL-REEF; MARINE-PHYTOPLANKTON; FLORIDA KEYS; FOOD-CHAIN; DINOPHYCEAE; SALINITY; FUKUYO; ADACHI; TEMPERATURE; SEASONALITY AB Two Caribbean strains (1651 and 1655) of the ciguatera-causing dinoflagellate Gambierdiscus toxicus were grown in xenic, batch culture under defined, measured nutrient conditions with nitrate, ammonium, urea, a mix of free amino acids (FAA), or putrescine as the nitrogen source. Cultures were maintained at 27 degrees C, salinity 35, 110 mu mol m-(2) s(-1) (12 h:12 h light:dark cycle) on L2 medium at an initial nitrogen concentration of 50 mu M N. Toxicity was determined using a ouabain/veratridine dependent cytotoxicity assay (N2A assay) standardized to a ciguatoxin standard. Nitrate, ammonium, FAA, and putrescine supported growth, but urea did not. The appearance of ammonium in the organic nitrogen cultures indicated that G. toxicus and/or associated bacteria remineralized the available organic nitrogen. Both strains were exposed to nitrogen-limiting conditions as evidenced by chlorophyll a content per cell, nitrogen content, and nitrogen (N) to phosphorus (P) (N:P) ratio significantly declining once nitrogen was no longer available in the medium and cells entered stationary phase. Strain 1651 grew significantly faster than strain 1655 when nitrate, FAA, and putrescine was the nitrogen source, but not ammonium. Nitrogen source had no effect on growth rate (similar to 0.14 d(-1)) in strain 1651. The growth rate of strain 1655 (0.10-0.13 d(-1)) was significantly faster on ammonium than the other nitrogen sources. Strain 1655 was significantly more toxic (similar to 10-fold) than strain 1651 except when growing on ammonium at exponential phase. Toxicity ranged from 1.3 to 8.7 fg C-CTX1-Eq cell(-1) in strain 1651 and from 30.7 to 54.3 fg; C-CTX1-Eq cell(-1) in strain 1655. Nitrogen source had no significant affect on toxicity. Toxicity was greater in stationary versus exponential phase cells for strain 1651 when grown on nitrate and strain 1655 regardless of nitrogen source. The difference in toxicity between growth phases may result from an increase in ciguatoxin and/or maitotoxin. Our results suggest that some strains of G. toxicus when associated with bacteria are able to take advantage of organic as well as inorganic nitrogen sources on short time scales to support future growth. The uncoupling of total nitrogen and phosphorus pools from conditions in the water column suggest that instantaneous growth rates can be supported by nutrients acquired hours to days earlier. (C) 2009 Elsevier B.V. All rights reserved. C1 [Lartigue, J.; Villareal, T. A.] Univ Texas Austin, Inst Marine Sci, Port Aransas, TX 78373 USA. [Jester, Edward L. E.; Dickey, R. W.] US FDA, Gulf Coast Seafood Lab, Chem Hazards Sci Branch, Dauphin Isl, AL 36528 USA. RP Villareal, TA (reprint author), Univ Texas Austin, Inst Marine Sci, 750 Channel View Dr, Port Aransas, TX 78373 USA. EM t.villareal@mail.utexas.edu RI Villareal, Tracy/I-9462-2012 NR 55 TC 28 Z9 29 U1 2 U2 28 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-9883 J9 HARMFUL ALGAE JI Harmful Algae PD JUN PY 2009 VL 8 IS 5 BP 781 EP 791 DI 10.1016/j.hal.2008.05.006 PG 11 WC Marine & Freshwater Biology SC Marine & Freshwater Biology GA 459ZW UT WOS:000267153900020 ER PT J AU Masmoudi, H Hewitt, SA Petrick, N Myers, KJ Gavrielides, MA AF Masmoudi, Hela Hewitt, Stephen M. Petrick, Nicholas Myers, Kyle J. Gavrielides, Marios A. TI Automated Quantitative Assessment of HER-2/neu Immunohistochemical Expression in Breast Cancer SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Biomarker; breast cancer; computer-aided immunohistochemistry; digital microscopy; HER2/neu; pathology ID IN-SITU HYBRIDIZATION; TRIAL COMPARING DOXORUBICIN; RANDOMIZED CLINICAL-TRIALS; COLOR PIXEL CLASSIFICATION; SURGICAL ADJUVANT BREAST; CELLULAR IMAGING-SYSTEM; TISSUE MICROARRAYS; PROGNOSTIC-SIGNIFICANCE; PROTEIN OVEREXPRESSION; CARDIAC DYSFUNCTION AB The expression of the HER-2/neu (HER2) gene, a member of the epidermal growth factor receptor family, has been shown to be a valuable prognostic indicator for breast cancer. However, interobserver variability has been reported in the evaluation of HER2 with immunohistochemistry. It has been suggested that automated computer-based evaluation can provide a consistent and objective evaluation of HER2 expression. In this manuscript, we present an automated method for the quantitative assessment of HER2 using digital microscopy. The method processes microscopy images from tissue slides with a multistage algorithm, including steps of color pixel classification, nuclei segmentation, and cell membrane modeling, and extracts quantitative, continuous measures of cell membrane staining intensity and completeness. A minimum cluster distance classifier merges the features to classify the slides into HER2 categories. An evaluation based on agreement analysis with pathologist-derived HER2 scores, showed good agreement with the provided truth. Agreement varied within the different classes with highest agreement (up to 90%) for positive (3+) slides, and lowest agreement (72%-78%) for equivocal (2+) slides which contained ambiguous scoring. The developed automated method has the potential to be used as a computer aid for the immunohistochemical evaluation of HER2 expression with the objective of increasing observer reproducibility. C1 [Petrick, Nicholas; Myers, Kyle J.; Gavrielides, Marios A.] NIBIB, CDRH, Lab Assessment Med Imaging Syst, US FDA, Silver Spring, MD 20903 USA. [Masmoudi, Hela] George Washington Univ, Dept Elect & Comp Engn, Washington, DC 20052 USA. [Hewitt, Stephen M.] NCI, Tissue Array Res Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Gavrielides, MA (reprint author), NIBIB, CDRH, Lab Assessment Med Imaging Syst, US FDA, Silver Spring, MD 20903 USA. EM marios.gavrielides@fda.gov OI Hewitt, Stephen/0000-0001-8283-1788 NR 67 TC 41 Z9 42 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 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD JUN PY 2009 VL 28 IS 6 BP 916 EP 925 DI 10.1109/TMI.2009.2012901 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 454IV UT WOS:000266676500012 PM 19164073 ER PT J AU Babu, U Wiesenfeld, P Gaines, D Raybourne, RB AF Babu, Uma Wiesenfeld, Paddy Gaines, Dennis Raybourne, Richard B. TI Effect of long chain fatty acids on Salmonella killing, superoxide and nitric oxide production by chicken macrophages SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE Fatty acid uptake; Chicken macrophage functions; S. typhimurium ID ENTERICA SEROVAR TYPHIMURIUM; TUMOR-NECROSIS-FACTOR; DIETARY LIPIDS; IN-VIVO; LISTERIA-MONOCYTOGENES; PERITONEAL-MACROPHAGES; IMMUNE-RESPONSES; CELL-LINES; N-3; EXPRESSION AB The objective of this study was to investigate the effect of uptake of different commonly consumed long chain fatty acids on superoxide (O(2)(-)), nitric oxide (NO) production, and ability to kill Salmonella enterica serotype typhimurium (S. typhimurium) by chicken macrophages (HD11 cells). All the fatty acids were taken up by HD11 cells with stearic acid uptake higher than polyunsaturated fatty acids. Uptake of green fluorescent protein-labeled bacteria and the viability of HD11 cells(measured by flow cytometry) was not affected by any of the fatty acids tested. Bacterial clearance (measured by the plating of sorted viable infected cells) was significantly higher with n - 3 fatty acids alpha-linolenic acid (ALA) and docosahexanoic acid (DHA). However, stearic acid (SA) and the n - 6 fatty acid, arachidonic acid (ARA) did not influence S. typhimurium killing by HD11 cells. The improved S. typhimurium clearance by ALA and DHA was not associated with increased NO or O(2)(-) production by HD11 cells. These results suggest a role for n - 3 polyunsaturated fatty acids in Salmonella clearance by chicken macrophages however in vivo studies are essential to confirm their efficacy in controlling Salmonella infection in chickens and contamination in shell eggs. Published by Elsevier B.V. C1 [Babu, Uma] US FDA, MOD 1, Immunobiol Branch, Laurel, MD 20708 USA. [Wiesenfeld, Paddy] US FDA, Neurotoxicol & In Vitro Toxicol Branch, Laurel, MD 20708 USA. RP Babu, U (reprint author), US FDA, MOD 1, Immunobiol Branch, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM uma.babu@fda.hhs.gov NR 56 TC 4 Z9 4 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD JUN 1 PY 2009 VL 132 IS 1 BP 67 EP 72 DI 10.1016/j.ijfoodmicro.2009.03.017 PG 6 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 454WC UT WOS:000266713300010 PM 19375809 ER PT J AU Chen, EA Patel-Raman, SM O'Callaghan, K Hillebrenner, MG AF Chen, Eric A. Patel-Raman, Sonna M. O'Callaghan, Kathryn Hillebrenner, Matthew G. TI FDA'S Perspectives on Cardiovascular Devices SO JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH LA English DT Article DE FDA; Cardiovascular Devices; Medical Devices AB The Food and Drug Administration (FDA) decision process for approving or clearing medical devices is often determined by a review of robust clinical data and extensive preclinical testing of the device. The mission statement for the Center for Devices and Radiological Health (CDRH) is to review the information provided by manufacturers so that it can promote and protect the health of the public by ensuring the safety and effectiveness of medical devices deemed appropriate for human use (Food, Drug & Cosmetic Act, 903(b)(1, 2(C)), December 31, 2004; accessed December 17, 2008 http://www.fda.gov/opacom/laws/fdcact/fdctoc.htm). For high-risk devices, such as ventricular assist devices (VADs), mechanical heart valves, stents, cardiac resynchronization therapy (CRT) devices, pacemakers, and defibrillators, the determination is based on FDA's review of extensive preclinical bench and animal testing followed by use of the device in a clinical trial in humans. These clinical trials allow the manufacturer to evaluate a device in the intended use population. FDA reviews the data from the clinical trial to determine if the device performed as predicted and the clinical benefits outweigh the risks. This article reviews the regulatory framework for different marketing applications related to cardiovascular devices and describes the process of obtaining approval to study a cardiovascular device in a U. S. clinical trial. C1 [Chen, Eric A.; Patel-Raman, Sonna M.; O'Callaghan, Kathryn; Hillebrenner, Matthew G.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Chen, EA (reprint author), US FDA, Ctr Devices & Radiol Hlth, 9200 Corp Blvd,HFZ-450 Room 220V, Rockville, MD 20850 USA. EM eric.chen@fda.hhs.gov NR 9 TC 2 Z9 2 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1937-5387 J9 J CARDIOVASC TRANSL JI J. Cardiovasc. Transl. Res. PD JUN PY 2009 VL 2 IS 2 BP 143 EP 146 DI 10.1007/s12265-009-9096-7 PG 4 WC Cardiac & Cardiovascular Systems; Medicine, Research & Experimental SC Cardiovascular System & Cardiology; Research & Experimental Medicine GA 686IN UT WOS:000284690100001 PM 20559979 ER PT J AU Dolcimascolo, F AF Dolcimascolo, Francesca TI Pediatric Cardiac Devices-An FDA Pediatrician's Perspective of the Challenges and Potential Solutions SO JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH LA English DT Article DE Pediatric Medical Devices; Pediatric Cardiac Devices; FDA AB The advancement of pediatric medical devices is an important challenge currently facing the Food and Drug Administration and the medical community. In this manuscript, the challenges are described and possible solutions presented. C1 US FDA, Silver Spring, MD USA. RP Dolcimascolo, F (reprint author), US FDA, Silver Spring, MD USA. EM francesca.dolcimascolo@fda.hhs.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1937-5387 J9 J CARDIOVASC TRANSL JI J. Cardiovasc. Transl. Res. PD JUN PY 2009 VL 2 IS 2 BP 147 EP 149 DI 10.1007/s12265-009-9100-2 PG 3 WC Cardiac & Cardiovascular Systems; Medicine, Research & Experimental SC Cardiovascular System & Cardiology; Research & Experimental Medicine GA 686IN UT WOS:000284690100002 PM 20559980 ER PT J AU Schaffer, SD Yoon, S Zadezensky, I AF Schaffer, Susan D. Yoon, Saunjoo Zadezensky, Immo TI A review of smoking cessation: potentially risky effects on prescribed medications SO JOURNAL OF CLINICAL NURSING LA English DT Review DE CYP1A2; cytochrome P 450; drug interaction; nurses; nursing; smoking cessation ID INTERNATIONAL NORMALIZED RATIO; CIGARETTE-SMOKING; DRUG-INTERACTIONS; PLASMA-CONCENTRATIONS; CLOZAPINE; TOBACCO; PHARMACOKINETICS; DISPOSITION; INCREASE; WARFARIN AB To identify prescription drugs that require dosage adjustment or monitoring in patients who quit smoking and to provide recommendations for dosage adjustment based on available evidence. Health care providers are urged to facilitate smoking cessation for patients who smoke, but the effects of smoking cessation on the metabolism of some drugs is not routinely considered. A comprehensive literature review. The review was conducted in 2008 using a computerised drug interaction program and multiple PubMed and CINAHL searches to identify prescription drugs with clinically significant pharmacokinetic or pharmacodynamic changes caused by smoking cessation. Although much of the evidence is case report, dosage adjustments are clearly indicated for warfarin, olanzapine, clozapine and theophylline since they are metabolised by cytochrome P450 CYP1A2 and also have narrow therapeutic ratios. Careful monitoring is recommended for other CYP1A2 metabolised drugs, including those for hypertension and Alzheimer's disease. For many affected drugs, smoking cessation reverses smoking-induced CYP1A2 hepatic enzyme levels to normal, increasing plasma concentrations in patients whose dose was established while smoking. Because the effect on hepatic microsomal enzymes is not related to the nicotine component of tobacco, nicotine replacement will not alter the effect. The effects of smoking cessation on drugs metabolised by CYP1A2 have been under-appreciated by health care providers. Smoking cessation may increase plasma levels of some drugs to potentially toxic levels. Further research is warranted to clarify this effect. When patients stop smoking, providers should carefully review prescribed drug regimens and adjust or monitor drugs whose metabolism is affected by smoking cessation. This is particularly important for patients who abruptly stop smoking due to hospitalisation and for older patients who are likely to be taking multiple medications. C1 [Schaffer, Susan D.; Yoon, Saunjoo] Univ Florida, Coll Nursing, Gainesville, FL 32610 USA. [Zadezensky, Immo] Ctr Drug Evaluat & Res, Off Transplantat Sci, Div Clin Pharmacol, New Hampshire, MO USA. RP Yoon, S (reprint author), Univ Florida, Coll Nursing, HPNP Complex,POB 100187,101 S Newell Dr, Gainesville, FL 32610 USA. EM yoon@ufl.edu NR 45 TC 12 Z9 12 U1 0 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0962-1067 J9 J CLIN NURS JI J. Clin. Nurs. PD JUN PY 2009 VL 18 IS 11 BP 1533 EP 1540 DI 10.1111/j.1365-2702.2008.02724.x PG 8 WC Nursing SC Nursing GA 444LH UT WOS:000265982000003 PM 19490292 ER PT J AU Bone, PF France, KR Aikin, KJ AF Bone, Paula Fitzgerald France, Karen Russo Aikin, Kathryn J. TI On Break-up ClichEs Guiding Health Literacy's Future SO JOURNAL OF CONSUMER AFFAIRS LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; KNOWLEDGE; PERCEPTIONS; CANCER; POLICY; RISK; FAT AB With the recognized need to increase health literacy, some practices have not worked and, therefore, "should be dumped." Herein we present alternative approaches that may increase health literacy. C1 [Bone, Paula Fitzgerald; France, Karen Russo] W Virginia Univ, Morgantown, WV 26506 USA. [Aikin, Kathryn J.] US FDA, Div Drug Mkt Advertising & Commun, Rockville, MD 20857 USA. RP Bone, PF (reprint author), W Virginia Univ, Morgantown, WV 26506 USA. EM paula.bone@mail.wvu.edu; karen.france@mail.wvu.edu; kathryn.aikin@fda.hhs.gov NR 39 TC 8 Z9 8 U1 1 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-0078 J9 J CONSUM AFF JI J. Consum. Aff. PD SUM PY 2009 VL 43 IS 2 BP 185 EP 198 DI 10.1111/j.1745-6606.2009.01136.x PG 14 WC Business; Economics SC Business & Economics GA 453GR UT WOS:000266599400001 ER PT J AU Day, JB Whiting, RC AF Day, J. B. Whiting, R. C. TI Development of a Macrophage Cell Culture Method To Isolate and Enrich Francisella tularensis from Food Matrices for Subsequent Detection by Real-Time PCR SO JOURNAL OF FOOD PROTECTION LA English DT Article ID POLYMERASE CHAIN-REACTION; SAMPLE PREPARATION METHOD; ESCHERICHIA-COLI; IMMUNOMAGNETIC SEPARATION; LISTERIA-MONOCYTOGENES; INTRACELLULAR GROWTH; CAMPYLOBACTER-JEJUNI; BACTERIAL PATHOGENS; RAPID DETECTION; GROUND-BEEF AB Francisella tularensis is a gram-negative bacterium that can cause gastrointestinal or oropharyngeal tularemia in humans from ingestion of contaminated food or water. Despite the potential for accidental or intentional contamination of foods with F. tularensis, there are no techniques currently available to detect this organism in specific food matrices. In this study, a macrophage cell culture system is combined with real-time PCR to identify F tularensis in food matrices. The method utilizes a mouse macrophage cell line (RAW 264.7) as host for the isolation and intracellular replication of F. tularensis. Exposure of macrophages to F. tularensis-contaminated food matrices results in uptake and intracellular replication of the bacteria, which can be subsequently detected by real-time PCR analysis of the DNA released from infected macrophage cell lysates. Macrophage monolayers were exposed to infant formula, liquid egg whites, and lettuce contaminated with varying quantities of F. tularensis. As few as 10 CFU/ml (or CFU per gram) F. tularensis was detected in infant formula and lettuce after 5 h postinfection. As few as 10 CFU/ml F. tularensis was detected in liquid egg whites after 18 h postinfection. Intracellular F. tularensis could also be isolated on Mueller-Hinton medium from lysates of macrophages infected with the bacteria in infant formula, liquid egg whites, and lettuce for subsequent confirmatory identification. This method is the first to successfully identify F. tularensis from select food matrices. C1 [Day, J. B.; Whiting, R. C.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Day, JB (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS 712,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM james.day@fda.hhs.gov NR 65 TC 4 Z9 4 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 2009 VL 72 IS 6 BP 1156 EP 1164 PG 9 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 457TJ UT WOS:000266956000001 PM 19610325 ER PT J AU Cohen, ED AF Cohen, Ethan D. TI Effects of high-level pulse train stimulation on retinal function SO JOURNAL OF NEURAL ENGINEERING LA English DT Article CT Eye and the Chip Meeting 2008 CY JUN 12-14, 2008 CL Detroit, MI SP Detroit Inst Ophthalmol ID SUPRACHOROIDAL-TRANSRETINAL STIMULATION; CHRONIC ELECTRICAL-STIMULATION; HIGH STIMULUS RATES; SQUID GIANT-AXON; GANGLION-CELLS; SPREADING DEPRESSION; PERCEPTUAL THRESHOLDS; RETINITIS-PIGMENTOSA; AUDITORY-NERVE; CHICKEN RETINA AB We examined how stimulation of the local retina by high-level Current pulse trains affected the light-evoked responses of the retinal ganglion cells. The spikes of retinal ganglion cell axons were recorded extracellularly using an in vitro eyecup preparation of the rabbit retina. Epiretinal electrical stimulation was delivered via a 500 mu m inner diameter saline-filled, transparent tube positioned over the retinal surface forming the receptive field center. Spot stimuli were presented periodically to the receptive field center during the experiment. Trains of biphasic 1 ms current pulses were delivered to the retina at 50 Hz for 1 min. Pulse train charge densities of 1.3-442 mu C/cm(2)/phase were examined. After pulse train stimulation with currents >= 300 mu A (133 mu C/cm(2)/phase), the ganglion cell's ability to respond to light was depressed and a significant time was required for recovery of the light-evoked response. During train stimulation. the ganglion cell's ability to spike following each current Pulse fatigued. The current levels evoking train-evoked depression were suprathreshold to those evoking action potentials. Train-evoked depression was stronger touching the retinal surface, and in some cases impaired ganglion cell function for up to 30 min. This overstimulation could cause a transient refractory period for electrically stimulated perception in the retinal region below the electrode. C1 US FDA, Div Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth,White Oak Fed Res Labs, Silver Spring, MD 20993 USA. RP Cohen, ED (reprint author), US FDA, Div Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth,White Oak Fed Res Labs, Rm 1134,Bldg 62, Silver Spring, MD 20993 USA. EM ethan.cohen@fda.hhs.gov OI COHEN, ETHAN/0000-0001-6365-2266 NR 65 TC 9 Z9 9 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 J9 J NEURAL ENG JI J. Neural Eng. PD JUN PY 2009 VL 6 IS 3 AR 035005 DI 10.1088/1741-2560/6/3/035005 PG 11 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA 461AM UT WOS:000267235600006 PM 19458404 ER PT J AU Lepri, BP AF Lepri, Bernard P. TI Is acuity enough? Other considerations in clinical investigations of visual prostheses SO JOURNAL OF NEURAL ENGINEERING LA English DT Article CT Eye and the Chip Meeting 2008 CY JUN 12-14, 2008 CL Detroit, MI SP Detroit Inst Ophthalmol AB Visual impairing eye diseases are the major frontier facing ophthalmic research today in light of our rapidly aging population. The visual skills necessary for improving the quality of daily function and life are inextricably linked to these impairing diseases. Both research and reimbursement programs are emphasizing outcome-based results. Is improvement in Visual acuity alone enough to improve the function and quality of life Of Visually impaired persons? This perspective summarizes the types of effectiveness endpoints for clinical investigations of visual prostheses that go beyond visual acuity. The clinical investigation of visual prostheses should include visual function, functional vision and quality Of life measures. Specifically, they encompass contrast sensitivity, orientation and mobility, activities of daily living and quality of life assessments. The perspective focuses on the design of clinical trials for visual prostheses and the methods of determining effectiveness above and beyond Visual acuity that will yield outcomes that are measured by improved function in the Visual world and quality of life. The visually impaired population is the primary con side rat ion in this presentation with particular emphases on retinitis pigmentosa and age-related macular degeneration. Clinical trials for visual prostheses cannot be isolated from the need for medical rehabilitation in order to obtain measurements of effectiveness that produce outcomes/evidence-based Success. This approach will facilitate improvement in daily function and quality of life of patients with diseases that cause chronic vision impairment. C1 US FDA, Rockville, MD 20852 USA. RP Lepri, BP (reprint author), US FDA, Rockville, MD 20852 USA. NR 7 TC 6 Z9 6 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 J9 J NEURAL ENG JI J. Neural Eng. PD JUN PY 2009 VL 6 IS 3 AR 035003 DI 10.1088/1741-2560/6/3/035003 PG 4 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA 461AM UT WOS:000267235600004 PM 19458402 ER PT J AU Salzer, W Dinndorf, P Dreyer, Z Hilden, J Reaman, GH AF Salzer, Wanda Dinndorf, Patricia Dreyer, ZoAnn Hilden, Joanne Reaman, Gregory H. TI Analysis of Infectious Complications in Infants With Acute Lymphoblastic Leukemia Treated on the Children's Cancer Group Protocol 1953 A Report From the Children's Oncology Group SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE infection; infant acute lymphoblastic leukemia ID PNEUMOCYSTIS-CARINII-PNEUMONIA; INVASIVE FUNGAL-INFECTIONS; IMMUNODEFICIENCY-VIRUS-INFECTION; STEM-CELL TRANSPLANTATION; AEROSOLIZED PENTAMIDINE; PROGNOSTIC-FACTORS; CHILDHOOD-LEUKEMIA; GENE REARRANGEMENT; PROPHYLAXIS; EXPERIENCE AB Infants with acute lymphoblastic leukemia have a poor prognosis. The Children's Cancer Group (CCG) 1953 protocol tested the hypothesis that intensification of therapy would improve outcome for these patients. This intensified therapy resulted in better disease control, but resulted in greater toxicity. In this paper, we report the infectious complications associated with this intensified therapy. We retrospectively analyzed the infectious complications reported on the case report forms of all 115 patients enrolled on CCG 1953. Overall 495 infectious complications were identified in 115 patients. Bacterial infections occurred most frequently (74%), followed by viral (13%), fungal (11%), and protozoan (1%). Infection related mortality disproportionately occurred with viral (31%) and fungal (19%) infections. Twenty-three percent (n = 26) of patients died of infectious complications, with the majority occurring during induction/intensification. Lower respiratory infections contributed to death in 12 patients and were most commonly viral (n = 6) and fungal (n = 3). Intensification of therapy resulted in increased infectious complications and deaths compared with previous studies. Future studies will need to focus on: (1) decreasing intensification during the first month of therapy, (2) developing targeted therapies, and (3) improving measures designed to prevent, quickly diagnose, and appropriately treat infections. C1 [Salzer, Wanda] NCI, NIH, IRB, Bethesda, MD 20892 USA. [Dinndorf, Patricia] US FDA, Silver Spring, MD USA. [Dreyer, ZoAnn] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. [Hilden, Joanne] Peyton Manning Childrens Hosp St Vincent, Indianapolis, IN USA. [Reaman, Gregory H.] Childrens Oncol Grp, Arcata, CA USA. RP Salzer, W (reprint author), NCI, NIH, IRB, 9030 Old Georgetown Rd,Bldg 82,Room 215,MSC 8200, Bethesda, MD 20892 USA. EM salzerw@mail.nih.gov FU National Institutes of Health [CA13539, CA98543]; Children's Cancer Group (CCG); Pediatric Oncology Group (POG) FX Supported by grants from the National Institutes of Health (grants CA13539 and CA98543). A complete listing of grant support for research conducted by Children's Cancer Group (CCG) and Pediatric Oncology Group (POG) before initiation of the COG grant in 2003. NR 45 TC 10 Z9 11 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD JUN PY 2009 VL 31 IS 6 BP 398 EP 405 PG 8 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 455CJ UT WOS:000266733900004 PM 19648788 ER PT J AU Bennett, RW AF Bennett, Reginald W. TI SEROLOGICAL ATTRACTION OF NONTOXIC EGG COMPONENT TO STAPHYLOCOCCAL ANTI-ENTEROTOXIN SO JOURNAL OF RAPID METHODS AND AUTOMATION IN MICROBIOLOGY LA English DT Article ID FOODS AB Raw whole liquid and dried eggs which were purported to contain staphylococcal enterotoxin were analyzed by a number of enzyme-linked immunosorbent assay (ELISA)-based methods. The initial evaluation was to establish whether the purported positive ELISA reactions were a result of toxin-anti-enterotoxin serological activity. A secondary consideration was to determine whether the putative protein occurred in the yolk and/or white portions of the eggs. A manual polyvalent detection system, manual monovalent ELISA and an automated polyvalent enzyme-linked fluorescent immunoassay were used to investigate this component in eggs. The ELISA results were instantaneous and showed strong positive reactions (false positives) with the manual and automated polyvalent systems, suggesting nonspecific binding of the egg-reactive component to one or more staphylococcal enterotoxin antibodies. Further analysis with the monovalent ELISA showed false-positive reactions when egg extracts were tested separately for enterotoxins A-E. The putative protein from fertilized eggs had caused false-positive reactions and the eggs did not contain preformed staphylococcal enterotoxin. C1 US FDA, College Pk, MD 20740 USA. RP Bennett, RW (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM reginald.bennett@fda.hhs.gov NR 9 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1060-3999 J9 J RAPID METH AUT MIC JI J Rapid Methods Autom. Microbiol. PD JUN PY 2009 VL 17 IS 2 BP 223 EP 232 DI 10.1111/j.1745-4581.2009.00168.x PG 10 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 454WO UT WOS:000266714800008 ER PT J AU Ghosh, P Basu, S Tiwari, RC AF Ghosh, Pulak Basu, Sanjib Tiwari, Ram C. TI Bayesian Analysis of Cancer Rates From SEER Program Using Parametric and Semiparametric Joinpoint Regression Models SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Age-adjusted incidence rates; Dirichlet process mixture; Joint modeling; Joinpoints; Markov chain Monte Carlo ID DIRICHLET PROCESS PRIOR; FINITE NORMAL MIXTURES; LIKELIHOOD; SELECTION; PRIORS; AGE AB Cancer is the second leading cause of death in the United States. Cancer incidence and mortality rates measured the progress against cancer: these rates are obtained from the surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI). Lung cancer has the highest mortality rate among all cancers, whereas prostate cancer has the highest number of new cases among males. In this article, we analyze the incidence rates of these two cancers, as well as colon and rectal cancer. The NCI reports trends in cancer age-adjusted mortality and incidence rates in its annual report to the nation and analyzes them using the Joinpoint software. The location of the joinpoints signifies changes in cancer trends, whereas changes in the regression slope measure the degree of change. The Joinpoint software uses a numerical search to detect the joinpoints, fits regression within two consecutive joinpoints by least squares, and finally selects the number of joinpoints by either a series of permutation tests or the Bayesian information criterion. We propose Bayesian joinpoint models and provide statistical estimates of the joinpoints and the regression slopes. While the Joinpoint software and other work in this area assumes that the joinpoints occur on the discrete time grid, we allow a continous prior for the joinpoints induced by the Dirichlet distribution on the spacings in between. This prior further allows the user to impose prespecified minimum Laps in between two consecutive joinpoints. We develop parametric as well as semiparametric Bayesian joinpoint models: the semiparametric framework relaxes parametric distributional assumptions by modeling the distribution of regression slopes and error variances using Dirichlet process mixtures. These Bayesian models provide statistical inference with finite sample validity. Through a simulation study, We demonstrate performance of the proposed parametric and semiparametric Joinpoint models and compare the results with the ones front the Joinpoint software. We analyze age-adjusted cancer incidence rates from the SEER Program using these Bayesian models with different numbers of joinpoints by employing the deviance information criterion and the cross-validated predictive criterion. In addition, we model the lung cancer incidence rates and the smoking rates jointly and explore the relation between the two longitudinal processes. C1 [Ghosh, Pulak] Georgia State Univ, Dept Math & Stat, Atlanta, GA 30303 USA. [Basu, Sanjib] No Illinois Univ, Div Stat, De Kalb, IL 60115 USA. [Tiwari, Ram C.] US FDA, Ctr Drug Evaluat & Res, Off Biostat, Silver Spring, MD 20993 USA. RP Ghosh, P (reprint author), Georgia State Univ, Dept Math & Stat, Atlanta, GA 30303 USA. EM pulakghosh@gmail.com; ram.tiwari@fda.hhs.gov NR 48 TC 14 Z9 14 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD JUN PY 2009 VL 104 IS 486 BP 439 EP 452 DI 10.1198/jasa.2009.0038 PG 14 WC Statistics & Probability SC Mathematics GA 451HN UT WOS:000266461400002 ER PT J AU Norton, JD Niu, XF AF Norton, Jonathan D. Niu, Xu-Feng TI Intrinsically Autoregressive Spatiotemporal Models With Application to Aggregated Birth Outcomes SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Conditional autoregressive; Deviance Information Criterion; Disease mapping; Hierarchical model; Identifiability; Intrinsically autoregressive ID PRETERM BIRTH; DISEASE; SPACE; RESTORATION; CONVERGENCE; STATISTICS; PREGNANCY; FERTILITY; RATES; TIME AB A class of hierarchical Bayesian models is proposed for adverse birth outcomes such as preterm birth, which are conditional binomial distribution. The log-odds of an adverse outcome in a particular county, logit(p(i)), follow a linear model that includes observed covariates and normally-distributed random effects. Spatial dependence between neighboring regions is allowed for by including an intrinsically autoregressive (IAR) prior or air IAR convolution prior in the linear predictor. Temporal dependence is incorporated by including a temporal IAR term also. It is shown that the variance parameters underlying these random effects (IAR, convolution, convolution plus temporal IAR) are identifiable. The Deviance Information Criterion (DIC) is considered as a way to compare spatial hierarchical models. Simulations are performed to test whether the DIC call identify whether binomial outcomes come front a hierarchical model that includes different combinations of random and fixed effects. Having validated the DIC as a means of comparing models, we examine preterm birth and low birth weight counts in the state of Arkansas from 1994-2005. We find that preterm birth and low birth weight have different spatial patterns of risk, and that rates of low birth weight can be fit with a relatively simple model that includes a constant spatial effect for all periods. a linear trend. and three covariates (multiple birth. black mother, smoking). It is also found that the risks of each outcome are increasing over time, even with adjustment for covariate. C1 [Norton, Jonathan D.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Niu, Xu-Feng] Florida State Univ, Dept Stat, Tallahassee, FL 32306 USA. RP Norton, JD (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM jonathan.norton@fda.hhs.gov; niu@stat.fsu.edu NR 30 TC 2 Z9 2 U1 0 U2 1 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD JUN PY 2009 VL 104 IS 486 BP 638 EP 649 DI 10.1198/jasa.2009.0030 PG 12 WC Statistics & Probability SC Mathematics GA 451HN UT WOS:000266461400017 ER PT J AU Joshi, BH Leland, P Calvo, A Green, JE Puri, RK AF Joshi, B. H. Leland, P. Calvo, A. Green, J. E. Puri, R. K. TI Human Adrenomedullin Up-Regulates Interleukin-13 Receptor Alpha2 Chain in Prostate Cancer In Vitro and In Vivo: A Novel Approach to Sensitize Prostate Cancer to Anticancer Therapy Comment SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 [Joshi, B. H.; Leland, P.; Calvo, A.; Green, J. E.; Puri, R. K.] NCI, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,Food & Drug Adm,NIH, Bethesda, MD 20892 USA. RP Joshi, BH (reprint author), NCI, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,Food & Drug Adm,NIH, Bethesda, MD 20892 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 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 2009 VL 181 IS 6 BP 2824 EP 2825 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 444ZX UT WOS:000266020500146 ER PT J AU Tian, J Xu, ZL Smith, JS Hofherr, SE Barry, MA Byrnes, AP AF Tian, Jie Xu, Zhili Smith, Jeffrey S. Hofherr, Sean E. Barry, Michael A. Byrnes, Andrew P. TI Adenovirus Activates Complement by Distinctly Different Mechanisms In Vitro and In Vivo: Indirect Complement Activation by Virions In Vivo SO JOURNAL OF VIROLOGY LA English DT Article ID INNATE IMMUNE-RESPONSES; POLYETHYLENE-GLYCOL MODIFICATION; APOPTOTIC CELL RECOGNITION; AMYLOID-P COMPONENT; KUPFFER CELLS; GENE-EXPRESSION; NECROTIC CELLS; NONHUMAN-PRIMATES; CANCER-PATIENTS; DYING CELLS AB Understanding innate immunity is key to improving the safety of adenovirus (Ad) vectors for systemic gene therapy. Ad has been shown to activate complement in vitro, but activation of complement after Ad injection in vivo has not been directly measured. Using complement protein C3a as a marker of complement activation, we show that types 2 and 5 human Ads cause rapid complement activation after intravenous injection in mice. Unexpectedly, the mechanisms in vivo were different than those in vitro. Antibodies were critical for the activation of complement by Ad in vitro, but antibodies were not required in vivo. The classical pathway was required in vitro, whereas complement activation in vivo involved both classical and nonclassical pathways as well as the reticuloendothelial system. Remarkably, the entry-deficient Ad mutant ts1 was completely unable to activate complement in vivo even though it was fully able to activate complement in vitro. This result demonstrates that the complement system senses intravenously injected Ad primarily by detecting the effects of Ad on cells rather than through direct interaction of complement with virions. Encouragingly, shielding Ad with polyethylene glycol was effective at reducing complement activation both in vitro and in vivo. In summary, intravenously injected Ad rapidly activates complement through multiple pathways, but these pathways are different than those identified by in vitro studies. In vitro studies are poorly predictive of in vivo mechanisms because Ad virions activate complement through indirect mechanisms in vivo. C1 [Tian, Jie; Xu, Zhili; Smith, Jeffrey S.; Byrnes, Andrew P.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Hofherr, Sean E.; Barry, Michael A.] Mayo Clin, Dept Internal Med, Div Infect Dis, Translat Immunovirol Program,Dept Immunol, Rochester, MN USA. [Barry, Michael A.] Mayo Clin, Dept Mol Med, Rochester, MN USA. RP Byrnes, AP (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, HFM-725,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Andrew.Byrnes@fda.hhs.gov RI Byrnes, Andrew/D-2808-2013 OI Byrnes, Andrew/0000-0003-1135-2629 FU Critical Path Program FX We thank Michael Diamond for providing mice and the CBER veterinary staff for their outstanding support. We thank Suzanne Epstein and Jakob Reiser for constructive comments on the manuscript. NR 70 TC 39 Z9 41 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 JUN 1 PY 2009 VL 83 IS 11 BP 5648 EP 5658 DI 10.1128/JVI.00082-09 PG 11 WC Virology SC Virology GA 445EZ UT WOS:000266034100034 PM 19321608 ER PT J AU Kase, JA Correa, MT Sobsey, MD AF Kase, Julie A. Correa, Maria T. Sobsey, Mark D. TI Detection and molecular characterization of swine hepatitis E virus in North Carolina swine herds and their faecal wastes SO JOURNAL OF WATER AND HEALTH LA English DT Article DE disease reservoirs; faecal contamination; hepatitis E virus; public health; water quality; zoonoses ID CROSS-SPECIES INFECTION; UNITED-STATES; BLOOD-DONORS; GENETIC-CHARACTERIZATION; ENTERIC VIRUSES; PIGS; STRAINS; INACTIVATION; PREVALENCE; SEROREACTIVITY AB Recent findings of almost genetically indistinguishable swine and human strains, have suggested swine play a role in the transmission of hepatitis E virus (HEV). The extent to which HEV may be present and persist in the faecal waste generated from intensive swine operations is largely unknown. The fate of swine waste liquid is often land application, possibly resulting in unintentional seepage into groundwater or run-off into surface waters, hence validating concerns of human exposure risks. Freshly passed swine faeces, barn flush liquid waste, and lagoon liquid from production sites in North Carolina were surveyed periodically for HEV using RT-PCR primers located in ORF2. On three farms where HEV RNA was detected in swine faeces, it was also found in stored liquid waste on several occasions. HEV presence was related to swine age but not to animal management and waste management procedures, which varied amongst the farms. Seasonal patterns of HEV prevalence could not be established as viral RNA was isolated at all time points from two farms. Phylogenetic analysis of 212 bases of the genomic RNA indicated that isolates resembled the known US swine and human strains (percentage nucleic acid homology 91 to 94%), with one amino acid substitution. C1 [Kase, Julie A.] US FDA, Microbial Methods Dev Branch, Div Microbiol, Off Regulatory Sci,Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Sobsey, Mark D.] Univ N Carolina, Sch Publ Hlth, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. [Correa, Maria T.] N Carolina State Univ, Coll Vet Med, Dept Farm Anim Hlth & Resource Management, Raleigh, NC 27606 USA. RP Kase, JA (reprint author), US FDA, Microbial Methods Dev Branch, Div Microbiol, Off Regulatory Sci,Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,Rm 3E-017,HFS-711, College Pk, MD 20740 USA. EM julieannkase@gmail.com NR 42 TC 9 Z9 9 U1 0 U2 3 PU I W A PUBLISHING PI LONDON PA ALLIANCE HOUSE, 12 CAXTON ST, LONDON SW1H0QS, ENGLAND SN 1477-8920 J9 J WATER HEALTH JI J. Water Health PD JUN PY 2009 VL 7 IS 2 BP 344 EP 357 DI 10.2166/wh.2009.137 PG 14 WC Environmental Sciences; Public, Environmental & Occupational Health; Microbiology; Water Resources SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Microbiology; Water Resources GA 458VK UT WOS:000267054000014 PM 19240360 ER PT J AU Dokmanovic, M Hirsch, DS Shen, Y Wu, WJ AF Dokmanovic, Milos Hirsch, Dianne S. Shen, Yi Wu, Wen Jin TI Rac1 contributes to trastuzumab resistance of breast cancer cells: Rac1 as a potential therapeutic target for the treatment of trastuzumab-resistant breast cancer SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID GROWTH-FACTOR RECEPTOR; HER2/NEU-OVEREXPRESSING METASTATIC BREAST; RHO-GTPASES; MONOCLONAL-ANTIBODY; PHASE-II; HERCEPTIN-RESISTANT; LAPATINIB GW572016; DOWN-REGULATION; FACTOR-BETA; IN-VIVO AB Although treatment with trastuzumab improves outcomes for women with ErbB2-positive breast cancer, many patients who achieve an initial response to trastuzumab subsequently acquire resistance within 1 year. Rac1, a Ras-like small GTPase, has been implicated in the control of cell growth and morphology and is believed to be associated with breast cancer progression and metastasis. Here, we show that when parental SKBR3 cells become resistant to trastuzumab, Rac1 activity is increased, leading to altered cell morphology, which is accompanied by significant cytoskeleton disorganization. Furthermore, both trastuzumab-mediated down-regulation of ErbB2 and epidermal growth factor-induced down-regulation of epidermal growth factor receptor are impaired in the trastuzumab-resistant SKBR3 cells, indicating that the endocytic down-regulation of ErbB receptors is compromised in the resistant cells. This results in an aberrant accumulation of ErbB2 on the cell surface and enhanced ErbB2 and extracellular signal-regulated kinase activity in trastuzumab-resistant SKBR3 cells. Additionally, overexpression of constitutively active Rac1G12V in parental SKBR3 cells reduces sensitivity to trastuzumab. After reduction of Rac1 activity by NSC23766, a specific Rac1 inhibitor, trastuzumab-resistant SKBR3 cells display a cellular morphology similar to parental SKBR3 cells. Moreover, we show that NSC23766 restores trastuzumab-mediated endocytic down-regulation of ErbB2 and reduces extracellular signal regulated kinase activity in resistant SKBR3 cells. Our findings highlight an important role for Rac1 in trastuzumab resistance of human breast cancer cells and identify the impaired trastuzumab-mediated endocytic down-regulation of ErbB2 as a novel mechanism of trastuzumab resistance. The significant effects of NSC23766 on trastuzumab-resistant SKBR3 cells warrant further study of NSC23766 as a potential treatment of trastuzumab-resistant breast cancers. [Mol Cancer Ther 2009;8(6):1557-69] C1 [Dokmanovic, Milos; Hirsch, Dianne S.; Shen, Yi; Wu, Wen Jin] US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Wu, WJ (reprint author), US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. EM wen.wu@fda.hhs.gov FU U.S. Food and Drug Administration Critical Path Finding [FY2008]; Interagency Oncology Task Force Joint Fellowship Program; U.S. Food and Drug Administration; National Cancer Institute; NIH FX Grant support: U.S. Food and Drug Administration Critical Path Finding for FY2008 and Interagency Oncology Task Force Joint Fellowship Program sponsored by the U.S. Food and Drug Administration and the National Cancer Institute, NIH. NR 50 TC 39 Z9 42 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 2009 VL 8 IS 6 BP 1557 EP 1569 DI 10.1158/1535-7163.MCT-09-0140 PG 13 WC Oncology SC Oncology GA 458SF UT WOS:000267043100016 PM 19509242 ER PT J AU Tryndyak, VP Ross, SA Belland, FA Pogribny, IP AF Tryndyak, Volodymyr P. Ross, Sharon A. Belland, Frederick A. Pogribny, Igor P. TI Down-Regulation of the microRNAs miR-34a, miR-127, and miR-200b in Rat Liver During Hepatocarcinogenesis Induced by a Methyl-Deficient Diet SO MOLECULAR CARCINOGENESIS LA English DT Article DE microRNAs; p53; apoptosis; hepatocarcinogenesis ID HUMAN HEPATOCELLULAR-CARCINOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; TUMOR-SUPPRESSOR; GENE-EXPRESSION; FOLATE/METHYL DEFICIENCY; CELLULAR-TRANSFORMATION; DNA HYPOMETHYLATION; HUMAN CANCERS; CYCLIN G1; PROLIFERATION AB Altered expression of microRNAs (miRNAs) has been reported in diverse human cancers; however, the down-regulation or up-regulation of any particular miRNAs in cancer is not sufficient to address the role of these changes in carcinogenesis. In this study, using the rat model of liver carcinogenesis induced by a methyl-deficient diet, which is relevant to the hepatocarcinogenesis in humans associated with viral hepatitis C and B infections, alcohol exposure and metabolic liver diseases, we showed that the development of hepatocellular carcinoma (HCC) is characterized by prominent early changes in expression of miRNA genes, specifically by inhibition of expression of microRNAs miR-34a, miR-127, miR-200b, and miR-16a involved in the regulation of apoptosis, cell proliferation, cell-to-cell connection, and epithelial-mesenchymal transition. The mechanistic link between these alterations in miRNAs expression and the development of HCC was confirmed by the corresponding changes in the levels of E2F3, NOTCH1, BCL6, ZFHX1B, and BCL2 proteins targeted by these miRNAs. The significance of miRNAs expression dysregulation in respect to hepatocarcinogenesis was confirmed by the persistence of these miRNAs alterations in the livers of methyl-deficient rats re-fed a methyl-adequate diet. Altogether, the early occurrence of alterations in miRNAs expression and their persistence during the entire process of hepatocarcinogenesis indicate that the dysregulation of microRNAs expression may be an important contributing factor in the development of HCC. (C) 2008 Wiley-Liss, Inc. C1 [Tryndyak, Volodymyr P.; Belland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Ross, Sharon A.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. FU Postgraduate Research Program; Interagency Agreement between NIH-NCI and FDA-NCTR FX The authors would like to thank Dr. M.P. Waalkes for providing the rat liver TRL1215 cell line. Dr. V. Tryndyak is supported by the Postgraduate Research Program administered by the Oak Ridge Institute for Science and Education. Supported in part by Interagency Agreement between NIH-NCI and FDA-NCTR. NR 56 TC 88 Z9 98 U1 1 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 JUN PY 2009 VL 48 IS 6 BP 479 EP 487 DI 10.1002/mc.20484 PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 451MF UT WOS:000266473600001 PM 18942116 ER PT J AU Rojas, P Benavides, F Blando, J Perez, C Cardenas, K Richie, E Knudsen, ES Johnson, DG Senderowicz, AM Rodriguez-Puebla, ML Conti, CJ AF Rojas, Paola Benavides, Fernando Blando, Jorge Perez, Carlos Cardenas, Kim Richie, Ellen Knudsen, Erik S. Johnson, David G. Senderowicz, Adrian M. Rodriguez-Puebla, Marcelo L. Conti, Claudio J. TI Enhanced Skin Carcinogenesis and Lack of Thymus Hyperplasia in Transgenic Mice Expressing Human Cyclin D1b (CCND1b) SO MOLECULAR CARCINOGENESIS LA English DT Article DE cyclin D1; skin carcinogenesis; DMBA; TPA; transgenic mouse model ID ANDROGEN RECEPTOR REGULATION; IN-VIVO; EPIDERMAL HYPERPLASIA; ESTROGEN-RECEPTOR; TUMOR-DEVELOPMENT; NUCLEAR EXPORT; CELL CARCINOMA; CANCER; POLYMORPHISM; GENE AB Cyclin D1b is an alternative transcript of the cyclin D1 gene (CCND1) expressed in human tumors. Its abundance is regulated by a single base pair polymorphism at the exon 4/intron 4 boundary (nucleotide 870). Epidemiological studies have shown a correlation between the presence of the G870A allele (that favors the splicing for cyclin D1b) with increased risk and less favorable outcome in several forms of cancer. More recently, it has been shown that, unlike cyclin D1a, the alternative transcript D1b by itself has the capacity to transform fibroblasts in vitro. In order to study the oncogenic potential of cyclin D1b, we developed transgenic mice expressing human cyclin D1b under the control of the bovine K5 promoter (K5D1b mice). Seven founders were obtained and none of them presented any significant phenotype or developed spontaneous tumors. Interestingly, K5D1b mice do not develop the fatal thymic hyperplasia, which is characteristic of the cyclin D1a transgenic mice (K5D1a). Susceptibility to skin carcinogenesis was tested in K5D1b mice using two-stage carcinogenesis protocols. In two independent experiments, K5D1b mice developed higher papilloma multiplicity as compared with wild-type littermates. However, when K5D1b mice were crossed with cyclin D1KO mice, the expression of cyclin D1b was unable to rescue the carcinogenesis-resistant phenotype of the cyclin D1 KO mice. To further explore the role of cyclin D1b in mouse models of carcinogenesis we carried out in silico analysis and in vitro experiments to evaluate the existence of a mouse homologous of the human cyclin D1b transcript. We were unable to find any evidence of an alternatively spliced transcript in mouse Ccnd1. These results show that human cyclin D1b has different biological functions than cyclin D1a and confirm its oncogenic properties. (C) 2008 Wiley-Liss, Inc. C1 [Rojas, Paola; Benavides, Fernando; Blando, Jorge; Perez, Carlos; Cardenas, Kim; Richie, Ellen; Johnson, David G.; Conti, Claudio J.] Univ Texas MD Anderson Canc Ctr, Div Sci Pk Res, Smithville, TX 78957 USA. [Knudsen, Erik S.] Thomas Jefferson Univ, Dept Canc Biol, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. [Senderowicz, Adrian M.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Rodriguez-Puebla, Marcelo L.] N Carolina State Univ, Coll Vet Med, Ctr Comparat Med & Translat Res, Dept Mol Biomed Sci, Raleigh, NC USA. RP Conti, CJ (reprint author), Univ Texas MD Anderson Canc Ctr, Div Sci Pk Res, 1808 Pk Rd 1C,POB 389, Smithville, TX 78957 USA. FU NIH [CA90922, U01 CA105345]; NIEHS [ES007784]; DHHS/NCI Cancer Center [P30 CA16672-30] FX We thank Pamela S. Huskey, April Weiss, Dr Lezlee Coghlan, and Donna Schutz for their assistance with the breeding and maintenance of the mouse strains; and Oscar Contreras for data coordination. We also wish to thank the Histology and Tissue Processing Facility Core for the processing of samples. NIH Grant CA90922 to CJC, Grant U01 CA105345 to DGj and Center Grant NIEHS ES007784 supported this work. This study also made use of the Research Animal Support Facility-Smithville, including Genetic Services, supported by P30 CA16672-30 DHHS/NCI Cancer Center Support Grant (CCSG). NR 49 TC 7 Z9 8 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JUN PY 2009 VL 48 IS 6 BP 508 EP 516 DI 10.1002/mc.20489 PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 451MF UT WOS:000266473600004 PM 18942117 ER PT J AU Miura, D Dobrovolsky, VN Kimoto, T Kasahara, Y Heflich, RH AF Miura, Daishiro Dobrovolsky, Vasily N. Kimoto, Takafumi Kasahara, Yoshinori Heflich, Robert H. TI Accumulation and persistence of Pig-A mutant peripheral red blood cells following treatment of rats with single and split doses of N-ethyl-N-nitrosourea SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Gene mutation; Phosphatidylinositol glycan complementation group A gene; Glycosylphosphaticlyl inositol; N-Ethyl-N-nitrosourea; CD59; Flow cytometry; Erythrocytes ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; AGE-DEPENDENT SELECTION; SPLEEN T-CELLS; IN-VIVO; NORMAL HEMATOPOIESIS; MEMBRANE-PROTEINS; GENETIC-DISEASE; BONE-MARROW; STEM-CELLS; HPRT GENE AB We previously reported the development of an in vivo gene mutation assay using the phosphatidylinositol glycan complementation group A gene (Mg-A) as an endogenous reporter. The assay quantifies Incitation in rat peripheral red blood cells (RBCs) by flow cytometric detection of cells negative for glycosylphosphatidyl mositol (GPI)-anchored protein surface markers. In this Study, we examined the accumulation and persistence of Pig-A mutant RBCs in rats treated with N-ethyl-N-nitrosourea (ENU) using two (losing schedules. Male F344 rats were given single i.p. injections of 8.9, 35.6, or 142.4 mg/kg ENU or four equal weekly doses totaling 35.6 or 142.4 mg/kg ENU (8.9 mg/kg x 4 or 35.6 mg/kg x 4; split-dose groups). Before the treatment and through 26 weeks after the single dose or beginning the split-dose regimen, peripheral RBCs were collected and Pig-A mutant frequencies measured as RBCs negative for the GPI-anchored protein. CD59. Mean CD59-negative RBC frequencies in negative control rats ranged from 3.9 x 10(-6) to 28.7 x 10(-6) and displayed no time-related trend. With single ENU doses, CD59-negative RBC frequencies increased in a time-and dose-related manner. Maximum responses were observed beginning at 6 weeks post-treatment (57.3 x 10(-6) in the 8.9 mg/kg group; 186.9 x 10(-6) in the 35.6 mg/kg group: 759.2 x 10(-6) in the 142.4 mg/kg group), and these elevated mutant frequencies persisted to the last sampling time. In addition, splitting the dose of ENU into four weekly (loses produced nearly the same mutant frequency as when given as a single dose: the maximum responses after four weekly doses of 8.9 OF 35.6 mg/kg were 176.8 x 10(-6) and 683.3 x 10(-6), respectively. These results indicate that ENU-induced Pig-A Mutant RBCs accumulate in a near additive fashion in rats, and once present in the peripheral blood, persist for at least 6 months. These characteristics of Pig-A Mutation Could be important for detecting weak mutagens by repeated or subchronic/chromic closing protocols. Published by Elsevier B.V. C1 [Miura, Daishiro; Kimoto, Takafumi; Kasahara, Yoshinori] TEIJIN Pharma Ltd, Tokyo, Japan. [Dobrovolsky, Vasily N.; Heflich, Robert H.] US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Heflich, RH (reprint author), TEIJIN Pharma Ltd, Tokyo, Japan. EM robert.heflich@fda.hhs.gov FU Cooperative Research and Development Agreement between the U.S. Food and Drug Administration and TEIJIN Pharma Limited FX The authors sincerely thank Martha M. Moore, Suzanne M. Morris, Stephen D. Dertinger, and Richard J. Albertini for helpful discussions. We also are grateful to Our colleagues, Barbara L. Parsons and Mugimane G. Manjanatha, for their critical review of this manuscript. This research was partially funded by a Cooperative Research and Development Agreement between the U.S. Food and Drug Administration and TEIJIN Pharma Limited. The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration. NR 29 TC 59 Z9 63 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD JUN-JUL PY 2009 VL 677 IS 1-2 BP 86 EP 92 DI 10.1016/j.mrgentox.2009.05.014 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 478TW UT WOS:000268612200014 PM 19501187 ER PT J AU Mei, N Chen, T Godar, DE Moore, MM AF Mei, Nan Chen, Tao Godar, Dianne E. Moore, Martha M. TI UVA-induced photomutagenicity of retinyl palmitate SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Letter ID MOUSE LYMPHOMA-CELLS; PHOTOCHEMICAL GENOTOXICITY; INTERNATIONAL WORKSHOP; RADIATION; PHOTODECOMPOSITION; IRRADIATION; OXYGEN; LIGHT C1 [Mei, Nan; Chen, Tao; Moore, Martha M.] Natl Ctr Toxicol Res, Div Genet & Reproduct Toxicol, Jefferson, AR 72079 USA. [Godar, Dianne E.] Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Mei, N (reprint author), Natl Ctr Toxicol Res, Div Genet & Reproduct 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; GODAR, DIANNE/0000-0002-7690-5223 NR 17 TC 2 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD JUN-JUL PY 2009 VL 677 IS 1-2 BP 105 EP 106 DI 10.1016/j.mrgentox.2009.05.012 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 478TW UT WOS:000268612200017 PM 19477293 ER PT J AU Sahin, L Feibus, K AF Sahin, Leyla Feibus, Karen TI Medications in Pregnancy and Lactation SO OBSTETRICS AND GYNECOLOGY LA English DT Letter C1 [Sahin, Leyla; Feibus, Karen] US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Maternal Hlth Team, Silver Spring, MD USA. RP Sahin, L (reprint author), US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Maternal Hlth Team, Silver Spring, MD USA. NR 2 TC 0 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUN PY 2009 VL 113 IS 6 BP 1375 EP 1376 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 450HU UT WOS:000266392400040 PM 19461450 ER PT J AU Prodduturi, S Smith, GJ Wokovich, AM Doub, WH Westenberger, BJ Buhse, L AF Prodduturi, Suneela Smith, Glen J. Wokovich, Anna M. Doub, William H. Westenberger, Benjamin J. Buhse, Lucinda TI Reservoir Based Fentanyl Transdermal Drug Delivery Systems: Effect of Patch Age on Drug Release and Skin Permeation SO PHARMACEUTICAL RESEARCH LA English DT Article DE fentanyl; reservoir systems; skin permeation; stability; transdermal drug delivery AB To understand and evaluate the stability and skin permeation profiles of fentanyl reservoir systems as a function of patch age. Drug release and skin permeation studies were performed using a modified USP apparatus 5 with a novel sample preparation technique. The amount of fentanyl present in the EVA/adhesive layer (EAL) increased from about 17% of label claim (LC) at 5 months to 25% LC at 22 months. The increase in the drug concentration was mainly observed in the peripheral EAL. Simultaneously, the alcohol content of the patch decreased as a function of patch age. A significant effect of patch age on the drug content in the EAL and the drug release from the system was observed; however, skin permeation studies did not indicate an increase in drug delivery rate. Novel sample preparation technique with USP Apparatus 5 allowed determination of in vitro skin permeation rates for fentanyl transdermal patches with different designs. Permeation rates with cadaver skin as substrate were found not to change with patch age despite changing drug concentration in the EAL. C1 [Prodduturi, Suneela; Wokovich, Anna M.; Doub, William H.; Westenberger, Benjamin J.; Buhse, Lucinda] US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. [Smith, Glen J.] US FDA, Off Gener Drugs, Rockville, MD 20857 USA. RP Prodduturi, S (reprint author), US FDA, Div Pharmaceut Anal, 1114 Market St Rm 1002, St Louis, MO 63101 USA. EM suneela.prodduturi@fda.hhs.gov NR 7 TC 5 Z9 6 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORD JI Pharm. Res. PD JUN PY 2009 VL 26 IS 6 BP 1344 EP 1352 DI 10.1007/s11095-009-9843-0 PG 9 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 442IJ UT WOS:000265834600006 PM 19229594 ER PT J AU Rue-Cover, A Iskander, J Lyn, SN Burwen, DR Gargiullo, P Shadomy, S Blostein, J Bridges, CB Haber, P Satzger, RD Ball, R Seward, JF AF Rue-Cover, Alison Iskander, John Lyn, Shauna Burwen, Dale R. Gargiullo, Paul Shadomy, Sean Blostein, Joel Bridges, Carolyn B. Haber, Penina Satzger, R. Duane Ball, Robert Seward, Jane F. TI Death and serious illness following influenza vaccination: a multidisciplinary investigation SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE vaccine; adverse; event; influenza; elderly; investigation ID EVENT-REPORTING-SYSTEM; ACUTE CORONARY SYNDROMES; UNITED-STATES; MYOCARDIAL-INFARCTION; SURVEILLANCE SYSTEM; ROTAVIRUS VACCINE; ELDERLY PERSONS; CUTTER INCIDENT; FLU VACCINATION; VAERS AB Purpose To evaluate a possible association between influenza vaccination and four deaths and four serious illnesses among 114 recent influenza vaccinees in a long-term care facility (LTCF) and two deaths from a nearby physician's office. All had received vaccine from the same lot (Lot A). Methods Field investigation including (1) a retrospective cohort study among LTCF residents who received Lot A or other influenza vaccine, (2) review of medical records of cases of death or serious illness, (3) active surveillance of deaths among 1500 community based Lot A vaccinees and (4) laboratory testing of vaccine from available Lot A vials. Results Medical record reviews showed no common clinical syndrome or cause of death. Laboratory testing of Lot A samples revealed no evidence of tampering and no differences compared to an unrelated lot. The risk of death or hospitalization was not significantly different between persons who received Lot A versus a comparison lot, Lot B (incidence rate ratio (IRR) = 0.9, 95%CI = 0.3-3.3). Conclusions There was no clinical or biological evidence pointing to inherent vaccine safety issues, nor was there a detectable increased risk of death or hospitalization among persons vaccinated with Lot A. Lot specific clustering of adverse events (AEs) may reflect medical events causally unrelated to vaccination. Rapid investigations of potential AEs are important to ensure vaccine safety and to maintain public and healthcare provider confidence in vaccines. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Rue-Cover, Alison; Gargiullo, Paul; Bridges, Carolyn B.; Seward, Jane F.] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. [Rue-Cover, Alison; Lyn, Shauna] Ctr Dis Control & Prevent, Epidem Intelligence Serv, Atlanta, GA 30333 USA. [Iskander, John; Shadomy, Sean; Haber, Penina] Ctr Dis Control & Prevent, ISO, Div Healthcare Qual Promot Proposed, Atlanta, GA 30333 USA. [Ball, Robert] US FDA, Ctr Biol Evaluat & Res, Rockville, MA USA. [Blostein, Joel] MDCH, Lansing, MI USA. [Satzger, R. Duane] US FDA, ORA, Forens Chem Ctr, Cincinnati, OH USA. RP Rue-Cover, A (reprint author), Ctr Dis Control & Prevent, ISO, Div Healthcare Qual Promot, 1600 Clifton Rd NE,Mail Stop D-26, Atlanta, GA 30333 USA. EM bwf8@cdc.gov NR 32 TC 3 Z9 4 U1 1 U2 3 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 JUN PY 2009 VL 18 IS 6 BP 504 EP 511 DI 10.1002/pds.1743 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 462JU UT WOS:000267349300010 PM 19373848 ER PT J AU Mada, SR Metukuri, MR Burugula, L Reddanna, P Krishna, DR AF Mada, Sripal Reddy Metukuri, Mallikarjuna Reddy Burugula, Laxminarayana Reddanna, Pallu Krishna, Devarakonda Rama TI Antiinflammatory and Antinociceptive Activities of Gossypin and Procumbentin - Cyclooxygenase-2 (COX-2) Inhibition Studies SO PHYTOTHERAPY RESEARCH LA English DT Article DE procumbentin; gossypin; antiinflammatory; antinociception ID SELECTIVE-INHIBITION; TRIDAX-PROCUMBENS; FLAVONOIDS; PROSTAGLANDIN; PLANTS; CELLS; ANTIOXIDANT; EXPRESSION; HESPERIDIN; DISCOVERY AB In the present study the antiinflammatory and antinociceptive activities of a few selected flavonoids were investigated. Procumbentin, gossypin, chrysin and methylhespiridin were studied for antiinflammatory and antinociceptive activities using in vitro enzymatic assays and in animal models utilizing acetic acid-induced writhing in mice and hind paw edema in rats. In vitro studies were performed using TMPD (NNN'N'-tetramethyl-p-phenylene diamine) and oxygraphic methods for COX-1 (cyclooxygenase-1), COX-2, 5-LOX (5-lipoxygenase) and 15-LOX. Gossypin and procumbentin showed COX-2 inhibitory activity and exhibited IC50 (COX-2/COX-1) ratios of 0.14 and 0.11, respectively. None of the flavonoids tested in this study showed LOX inhibitory activity. Four groups were studied for each test compound following intraperitoneal (i.p.) administration of doses of 10, 30 and 100 mg/kg. Antiinflammatory activity was measured by the carrageenin-induced rat hind paw edema model and antinociceptive activity by acetic acid-induced writhing. Procumbentin and gossypin showed antinociceptive activity at the 100 mg/kg dose. Gossypin showed antiinflammatory activity at doses of 10, 30, 100 mg/kg. Procumbentin and gossypin exhibited COX-2 inhibitory activity when tested by in vitro methods. Procumbentin and gossypin showed antinociceptive, and gossypin showed antiinflammatory, activities. Copyright (c) 2008 John Wiley & Sons, Ltd. C1 [Mada, Sripal Reddy; Burugula, Laxminarayana; Krishna, Devarakonda Rama] Kakatiya Univ, Univ Coll Pharmaceut Sci, Drug Metab & Clin Pharmacokinet Div, Warangal, Andhra Pradesh, India. [Metukuri, Mallikarjuna Reddy; Reddanna, Pallu] Univ Hyderabad, Sch Life Sci, Dept Anim Sci, Hyderabad 500134, Andhra Pradesh, India. RP Mada, SR (reprint author), US FDA, Bldg 51,Room 2126,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM sripal.mada@fda.hhs.gov FU Council of Scientific and Industrial Research (CSIR); All India Council of Technical Education (AICTE), Government of India, India FX Gossypin was a kind gift from Professor S. Ganapathy, Andhra University, Vizag, and procumbentin from Dr Earla Ravinder. Hamdard University, India. Grant sponsor: Council of Scientific and Industrial Research (CSIR), All India Council of Technical Education (AICTE), Government of India, India. NR 43 TC 9 Z9 9 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0951-418X EI 1099-1573 J9 PHYTOTHER RES JI Phytother. Res. PD JUN PY 2009 VL 23 IS 6 BP 878 EP 884 DI 10.1002/ptr.2727 PG 7 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 459GC UT WOS:000267088400023 PM 19107863 ER PT J AU Duan, YP Sun, X Zhou, LJ Gabriel, DW Benyon, LS Gottwald, T AF Duan, Y. P. Sun, X. Zhou, L. J. Gabriel, D. W. Benyon, L. S. Gottwald, Tim TI Bacterial Brown Leaf Spot of Citrus, a New Disease Caused by Burkholderia andropogonis SO PLANT DISEASE LA English DT Article ID PHASEOLI EX SMITH; XANTHOMONAS-CITRI; PSEUDOMONAS-ANDROPOGONIS; HOST-RANGE; ET-AL.; SP-NOV; RECLASSIFICATION; WOODSII; WINDOWS; HASSE AB A new bacterial disease of citrus was recently identified in Florida and is here named bacterial brown leaf spot (BBLS) of citrus. BBLS-infected citrus leaves from the field displayed circular, brownish, flat lesions with slightly raised and water-soaked margins surrounded by a chlorotic halo. Based on Biolog carbon source metabolic "fingerprinting", fatty acid analysis, and sequence analysis of partial 16S rDNA, gyrB, and rpoD genes, the causal agent of the disease was identified as Burkholderia andropogonis. Pathogenicity of these B. andropogonis isolates taken from multiple citrus leaves with BBLS was tested by various inoculation methods on three species of citrus as well as on carnation, corn, and sorghum. All isolates infected carnation, corn, and sorghum with varying degrees of pathogenicity. Variation among citrus isolates in pathogenicity was also observed in high titer (10(8) CFU/ml) inoculations of citrus leaves, ranging from a hypersensitive-like response to canker-like lesions. When the inoculum concentration was low (10(6) CFU/ml), only necrotic spots or small lesions slowly developed with all strains. Growth of B. andropogonis in citrus was relatively slow, tissue wounding appeared necessary for symptom appearance with many isolates, and field samples were recovered only after severe storms, indicating that this wide-host-range bacterium is a weak, opportunistic pathogen of citrus. C1 [Duan, Y. P.; Benyon, L. S.; Gottwald, Tim] ARS, USDA, USHRL, Ft Pierce, FL 34945 USA. [Sun, X.] FDACS DPI, Gainesville, FL 32610 USA. [Zhou, L. J.; Gabriel, D. W.] Univ Florida, Dept Plant Pathol, Gainesville, FL 32610 USA. RP Duan, YP (reprint author), ARS, USDA, USHRL, Ft Pierce, FL 34945 USA. EM yongping.duan@ars.usda.gov NR 32 TC 2 Z9 2 U1 0 U2 6 PU AMER PHYTOPATHOLOGICAL SOC PI ST PAUL PA 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 USA SN 0191-2917 EI 1943-7692 J9 PLANT DIS JI PLANT DIS. PD JUN PY 2009 VL 93 IS 6 BP 607 EP 614 DI 10.1094/PDIS-93-6-0607 PG 8 WC Plant Sciences SC Plant Sciences GA 446ON UT WOS:000266131000006 ER PT J AU Ursem, CJ Kruhlak, NL Contrera, JF MacLaughlin, PM Benz, RD Matthews, EJ AF Ursem, Carling J. Kruhlak, Naomi L. Contrera, Joseph F. MacLaughlin, Philip M. Benz, R. Daniel Matthews, Edwin J. TI Identification of structure-activity relationships for adverse effects of pharmaceuticals in humans. Part A: Use of FDA post-market reports to create a database of hepatobiliary and urinary tract toxicities SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE AERS; Drug-induced kidney toxicity; Drug-induced liver toxicity; Human adverse effects; Post-market reporting; Quantitative structure-activity relationships; QSAR; SRS ID PHARMACOVIGILANCE; PERFORMANCE; SOFTWARE; RODENTS; DRUGS; QSAR AB The Informatics and Computational Safety Analysis Staff at the US FDA's Center for Drug Evaluation and Research has created a database of pharmaceutical adverse effects (AEs) linked to pharmaceutical chemical structures and estimated population exposures. The database is being used to develop quantitative structure-activity relationship (QSAR) models for the prediction of drug-induced liver and renal injury, as well as to identify relationships among AEs. The post-market observations contained in the database were obtained from FDA's Spontaneous Reporting System (SRS) and the Adverse Event Reporting System (AERS) accessed through Elsevier PharmaPendium (TM) software. The database contains approximately 3100 unique pharmaceutical compounds and 9685 AE endpoints. To account for variations in AE reports due to different patient populations and exposures for each drug, a proportional reporting ratio (PRR) was used. The PRR was applied to all AEs to identify chemicals that could be scored as positive in the training data sets of QSAR models. Additionally, toxicologically similar AEs were grouped into clusters based upon both biological effects and statistical correlation. This clustering created a weight of evidence paradigm for the identification of compounds most likely to cause human harm based upon findings in multiple related AE endpoints. Published by Elsevier Inc. C1 [Ursem, Carling J.; Kruhlak, Naomi L.; Benz, R. Daniel; Matthews, Edwin J.] US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci Informat & Computat Safety Ana, ICSAS, Silver Spring, MD 20993 USA. [Ursem, Carling J.] GlobalNet Serv, Rockville, MD 20852 USA. [Contrera, Joseph F.] Computat Toxicol Serv LLC, Olney, MD 20830 USA. [MacLaughlin, Philip M.] Elsevier, Salem, MA 01907 USA. RP Matthews, EJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci Informat & Computat Safety Ana, ICSAS, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Edwin.Matthews@fda.hhs.gov NR 29 TC 26 Z9 27 U1 1 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD JUN PY 2009 VL 54 IS 1 BP 1 EP 22 DI 10.1016/j.yrtph.2008.12.009 PG 22 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 446LQ UT WOS:000266123500001 PM 19422096 ER PT J AU Matthews, EJ Ursem, CJ Kruhlak, NL Benz, RD Sabate, DA Yang, CH Klopman, G Contrera, JF AF Matthews, Edwin J. Ursem, Carling J. Kruhlak, Naomi L. Benz, R. Daniel Aragones Sabate, David Yang, Chihae Klopman, Gilles Contrera, Joseph F. TI Identification of structure-activity relationships for adverse effects of pharmaceuticals in humans: Part B. Use of (Q)SAR systems for early detection of drug-induced hepatobiliary and urinary tract toxicities SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE AERS; Computational toxicology; Drug adverse effects; Drug-induced liver injury; Drug-induced renal toxicity; In silico; Post-market reporting; Quantitative structure-activity relationships; QSAR software; SAR; SRS ID DEVELOPMENTAL TOXICITY; RODENT CARCINOGENICITY; QSAR MODELS; HAZARD IDENTIFICATION; COMPREHENSIVE MODEL; GENETIC TOXICITY; END-POINTS; MDL-QSAR; PREDICTION; PERFORMANCE AB This report describes the development of quantitative structure-activity relationship (QSAR) models for predicting rare drug-induced liver and urinary tract injury in humans based upon a database of post-marketing adverse effects (AEs) linked to similar to 1600 chemical structures. The models are based upon estimated population exposure using AE proportional reporting ratios. Models were constructed for 5 types of liver injury (liver enzyme disorders, cytotoxic injury, cholestasis and jaundice, bile duct disorders, gall bladder disorders) and 6 types of urinary tract injury (acute renal disorders, nephropathies, bladder disorders, kidney function tests, blood in urine, urolithiases). Identical training data sets were configured for 4 QSAR programs (MC4PC, MDL-QSAR, BioEpisteme, and Predictive Data Miner). Model performance was optimized and was shown to be affected by the AE scoring method and the ratio of the number of active to inactive drugs. The best QSAR models exhibited an overall average 92.4% coverage, 86.5% specificity and 39.3% sensitivity. The 4 QSAR programs were demonstrated to be complementary and enhanced performance was obtained by combining predictions from 2 programs (average 78.4% specificity, 56.2% sensitivity). Consensus predictions resulted in better performance as judged by both internal and external validation experiments. Published by Elsevier Inc. C1 [Matthews, Edwin J.; Ursem, Carling J.; Kruhlak, Naomi L.; Benz, R. Daniel] US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci Informat & Computat Safety Ana, ICSAS, Silver Spring, MD 20993 USA. [Ursem, Carling J.] GlobalNet Serv, Rockville, MD 20852 USA. [Aragones Sabate, David] Prous Inst Biomed Res SA, Barcelona 08025, Spain. [Yang, Chihae] Leadscope Inc, Columbus, OH 43215 USA. [Klopman, Gilles] Multicase Inc, Beachwood, OH 44122 USA. [Contrera, Joseph F.] Computat Toxicol Serv LLC, Olney, MD 20830 USA. RP Matthews, EJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci Informat & Computat Safety Ana, ICSAS, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM edwin.matthews@fda.hhs.gov NR 45 TC 37 Z9 37 U1 2 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD JUN PY 2009 VL 54 IS 1 BP 23 EP 42 DI 10.1016/j.yrtph.2009.01.009 PG 20 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 446LQ UT WOS:000266123500002 PM 19422098 ER PT J AU Matthews, EJ Kruhlak, NL Benz, RD Sabate, DA Marchant, CA Contrera, JF AF Matthews, Edwin J. Kruhlak, Naomi L. Benz, R. Daniel Aragones Sabate, David Marchant, Carol A. Contrera, Joseph F. TI Identification of structure-activity relationships for adverse effects of pharmaceuticals in humans: Part C: Use of QSAR and an expert system for the estimation of the mechanism of action of drug-induced hepatobiliary and urinary tract toxicities SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE Adverse drug effects; AERS; Clinical indication; Computational toxicology; Drug-induced kidney toxicity; Drug-induced liver toxicity; In silico; Mechanism of action; Pharmaceutical patent; Post-market reporting; Quantitative structure-activity relationships; QSAR; SAR; SRS ID IN-SILICO; DEVELOPMENTAL TOXICITY; CARCINOGENICITY DATA; GENETIC TOXICITY; END-POINTS; PHARMACOVIGILANCE; HEPATOTOXICITY; PERFORMANCE; WINDOWS; EVENTS AB This report describes an in silico methodology to predict off-target pharmacologic activities and plausible mechanisms of action (MOAs) associated with serious and unexpected hepatobiliary and urinary tract adverse effects in human patients. The investigation used a database of 8,316,673 adverse event (AE) reports observed after drugs had been marketed and AEs noted in the published literature that were linked to 2124 chemical structures and 1851 approved clinical indications. The Integrity (TM) database of drug patent and literature studies was used to find pharmacologic targets and proposed clinical indications. BioEpisteme (TM) QSAR software was used to predict possible molecular targets of drug molecules and Derek (TM) for Windows expert system software to predict chemical structural alerts and plausible MOAs for the AEs. AEs were clustered into five types of liver injury: liver enzyme disorders, cytotoxic injury, cholestasis and jaundice, bile duct disorders, and gall bladder disorders, and six types of urinary tract injury: acute renal disorders, nephropathies, bladder disorders, kidney function tests, blood in urine, and urolithiasis. Results showed that drug-related AEs were highly correlated with: (1) known drug class warnings, (2) predicted off-target activities of the drugs, and (3) a specific subset of clinical indications for which the drug may or may not have been prescribed. Published by Elsevier Inc. C1 [Matthews, Edwin J.; Kruhlak, Naomi L.; Benz, R. Daniel] US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci Informat & Computat Safety Ana, Silver Spring, MD 20993 USA. [Aragones Sabate, David] Prous Inst Biomed Res SA, Barcelona 08025, Spain. [Marchant, Carol A.] Lhasa Ltd, Leeds LS2 9HD, W Yorkshire, England. [Contrera, Joseph F.] Computat Toxicol Serv LLC, Olney, MD 20830 USA. RP Matthews, EJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci Informat & Computat Safety Ana, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Edwin.Matthews@fda.hhs.gov NR 36 TC 29 Z9 29 U1 1 U2 14 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 JUN PY 2009 VL 54 IS 1 BP 43 EP 65 DI 10.1016/j.yrtph.2009.01.007 PG 23 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 446LQ UT WOS:000266123500003 PM 19422100 ER PT J AU Peden-Adams, MM Stuckey, JE Gaworecki, KM Berger-Ritchie, J Bryant, K Jodice, PG Scott, TR Ferrario, JB Guan, B Vigo, C Boone, JS McGuinn, WD DeWitt, JC Keil, DE AF Peden-Adams, Margie M. Stuckey, Joyce E. Gaworecki, Kristen M. Berger-Ritchie, Jennifer Bryant, Kathy Jodice, Patrick G. Scott, Thomas R. Ferrario, Joseph B. Guan, Bing Vigo, Craig Boone, J. Scott McGuinn, W. David DeWitt, Jamie C. Keil, Deborah E. TI Developmental toxicity in white leghorn chickens following in ovo exposure to perfluorooctane sulfonate (PFOS) SO REPRODUCTIVE TOXICOLOGY LA English DT Article; Proceedings Paper CT Workshop on Perfluorooctanoic Acid Toxicokinetics and Mechanisms of Toxicity CY 2007 CL Res Triangle Pk, NC SP US Environm Protect Agcy DE PFOS; Immune; Developmental; In ovo; Embryonic; Bird; ALT; Cholesterol; Brain asymmetry ID PERFLUORINATED ALKYL SUBSTANCES; AMMONIUM PERFLUOROOCTANOATE; PEROXISOME PROLIFERATOR; POLYFLUOROALKYL COMPOUNDS; IMMUNE-SYSTEM; TRICHLOROETHYLENE TCE; POTENTIAL BIOMARKER; TURSIOPS-TRUNCATUS; CELL-PROLIFERATION; HUMORAL IMMUNITY AB Studies show that perfluorinated compounds cause various toxicological effects; nevertheless. effects on immune function and developmental endpoints have not been addressed at length. This study examined the effects of perfluorooctane sulfonate (PFOS) in white leghorn hatchlings on various developmental, immunological, and clinical health parameters. In addition, serum PFOS concentrations were determined by LC/MS/MS. Embryonic day (ED) 0 eggs were injected with either safflower oil/10% DMSO (control, 0 mg/kg egg wt) or PFOS in safflower oil/10% DMSO at 1, 2.5, or 5 mg/kg egg wt, and the chicks were grown to post-hatch day (PHD) 14. Treatment with PFOS did not affect hatch rate. Following in ovo exposure chicks exhibited increases in spleen mass at all treatment levels, in liver mass at 2.5 and 5 mg/kg egg wt, and in body length (crown-rump length) at the 5 mg/kg treatment. Right wings were shorter in all treatments compared to control. Increases in the frequency of brain asymmetry were evident in all treatment groups. SRBC-specific immunoglobulin (IgM and IgY combined) titers were decreased significantly at all treatment levels, while plasma lysozyme activity was increased at all treatment levels. The PHA skin test response decreased in relation to increasing PFOS dose. Serum concentrations where significant immunological, morphological, and neurological effects were observed at the lowest dose (I mg/kg egg wt) averaged 154ng PFOS/g serum. These concentrations fall within environmental ranges reported in blood samples from wild caught avian species; thereby, verifying that the environmental egg concentrations used for the injections do indeed relate to serum levels in hatchlings that are also environmentally relevant. These data indicate that immune alterations and brain asymmetry can occur in birds following in ovo exposure to environmentally relevant concentrations of PFOS and demonstrates the need for further research on the developmental effects of perfluorinated compounds in various species. (C) 2009 Elsevier Inc. All rights reserved. C1 [Peden-Adams, Margie M.] MUSC, Dept Pediat, Charleston, SC 29412 USA. [Peden-Adams, Margie M.] MUSC, Marine Biomed & Environm Sci Ctr, Charleston, SC 29412 USA. [Peden-Adams, Margie M.; Stuckey, Joyce E.] Coll Charleston, Grice Marine Lab, Charleston, SC 29401 USA. [Gaworecki, Kristen M.; Bryant, Kathy] Clemson Univ, Inst Environm Toxicol, Pendleton, SC USA. [Berger-Ritchie, Jennifer; Keil, Deborah E.] Univ Nevada, Clin Sci Lab, Las Vegas, NY USA. [Jodice, Patrick G.] Clemson Univ, US Geol Survey, S Carolina Cooperat Fish & Wildlife Res Unit, Clemson, SC USA. [Jodice, Patrick G.] Clemson Univ, Dept Forestry & Nat Resources, Clemson, SC USA. [Scott, Thomas R.] Clemson Univ, Dept Anim & Vet Sci, Clemson, SC USA. [McGuinn, W. David] US FDA, Silver Spring, MD USA. [DeWitt, Jamie C.] E Carolina Univ, Brody Sch Med, Dept Pharmacol & Toxicol, Greenville, NC USA. RP Peden-Adams, MM (reprint author), MUSC, Dept Pediat, 221 Ft Johnson Rd, Charleston, SC 29412 USA. EM pedenadams@gmail.com OI DeWitt, Jamie/0000-0002-0440-4059 NR 114 TC 24 Z9 27 U1 6 U2 22 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD JUN PY 2009 VL 27 IS 3-4 BP 307 EP 318 DI 10.1016/j.reprotox.2008.10.009 PG 12 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 445KQ UT WOS:000266050100011 PM 19071210 ER PT J AU Starlard-Davenport, A Lyn-Cook, B Radominska-Pandya, A AF Starlard-Davenport, Athena Lyn-Cook, Beverly Radominska-Pandya, Anna TI Identification of UDP-glucuronosyltransferase 1A10 in non-malignant and malignant human breast tissues (vol 73, pg 611, 2008) SO STEROIDS LA English DT Correction C1 [Starlard-Davenport, Athena; Radominska-Pandya, Anna] Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. [Lyn-Cook, Beverly] Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. RP Radominska-Pandya, A (reprint author), Univ Arkansas Med Sci, Dept Biochem & Mol Biol, 4301 W Markham,Slot 516, Little Rock, AR 72205 USA. EM radominskaanna@uams.edu NR 1 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 0039-128X J9 STEROIDS JI Steroids PD JUN PY 2009 VL 74 IS 6 BP 548 EP 549 DI 10.1016/j.steroids.2008.09.001 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 432JH UT WOS:000265128800009 ER PT J AU Elespuru, RK Agarwal, R Atrakchi, AH Bigger, CAH Heflich, RH Jagannath, DR Levy, DD Moore, MM Ouyang, YL Robison, TW Sotomayor, RE Cimino, MC Dearfield, KL AF Elespuru, Rosalie K. Agarwal, Rajiv Atrakchi, Aisar H. Bigger, C. Anita H. Heflich, Robert H. Jagannath, Devaraya R. Levy, Dan D. Moore, Martha M. Ouyang, Yanli Robison, Timothy W. Sotomayor, Rene E. Cimino, Michael C. Dearfield, Kerry L. TI Current and Future Application of Genetic Toxicity Assays: The Role and Value of In Vitro Mammalian Assays SO TOXICOLOGICAL SCIENCES LA English DT Editorial Material ID HUMAN SAFETY EVALUATION; PREDICTING RODENT CARCINOGENICITY; MOUSE LYMPHOMA-CELLS; MUTATION ASSAY; INTERNATIONAL WORKSHOP; RISK-ASSESSMENT; FOLLOW-UP; GENOTOXICITY TESTS; MUTAGENIC POTENCY; PIG-A AB With the advent of new technologies (e.g., genomics, automated analyses, and in vivo monitoring), new regulations (e.g., the reduction of animal tests by the European REACH), and new approaches to toxicology (e.g., Toxicity Testing in the 21st Century, National Research Council), the field of regulatory genetic toxicology is undergoing a serious re-examination. Within this context, Toxicological Sciences has published a series of articles in its Forum Section on the theme, "Genetic Toxicity Assessment: Employing the Best Science for Human Safety Evaluation" (beginning with Goodman et al.). As a contribution to the Forum discussions, we present current methods for evaluating mutagenic/genotoxic risk using standard genotoxicity test batteries, and suggest ways to address and incorporate new technologies. We recognize that the occurrence of positive results in relation to cancer prediction has led to criticism of in vitro mammalian cell genetic toxicity assays. We address criticism of test results related to weak positives, associated only with considerable toxicity, only seen at high concentrations, not accompanied by positive results in the other tests of standard test batteries, and/or not correlating well with rodent carcinogenicity tests. We suggest that the problems pointed out by others with these assays already have been resolved, to a large extent, by international groups working to update assay protocols, and by changes in data interpretation at regulatory agencies. New guidances at the U.S. Environmental Protection Agency and the U.S. Food and Drug Administration improve data evaluation and help refocus risk assessment. We discuss the results of international groups working together to integrate new technologies and evaluate new tests, including human monitoring. We suggest that strategies for identifying human health risks should naturally change to integrate new technologies; however, changes should be made only when justified by strong scientific evidence of improvement in the risk assessment paradigm. C1 [Elespuru, Rosalie K.] US FDA, CDRH, OSEL, DB, Silver Spring, MD 20993 USA. [Elespuru, Rosalie K.; Atrakchi, Aisar H.; Bigger, C. Anita H.; Heflich, Robert H.; Jagannath, Devaraya R.; Levy, Dan D.; Moore, Martha M.; Robison, Timothy W.; Sotomayor, Rene E.] US FDA, GeneTox Network, Silver Spring, MD 20993 USA. [Elespuru, Rosalie K.; Agarwal, Rajiv; Atrakchi, Aisar H.; Bigger, C. Anita H.; Heflich, Robert H.; Jagannath, Devaraya R.; Levy, Dan D.; Moore, Martha M.; Ouyang, Yanli; Robison, Timothy W.; Sotomayor, Rene E.] CDER, Genet Toxicol Subcomm, Silver Spring, MD 20993 USA. [Agarwal, Rajiv] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Atrakchi, Aisar H.; Bigger, C. Anita H.; Ouyang, Yanli; Robison, Timothy W.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Heflich, Robert H.; Moore, Martha M.] US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Jagannath, Devaraya R.] US FDA, Off New Anim Drug Evaluat, Ctr Vet Med, Rockville, MD 20855 USA. [Levy, Dan D.; Sotomayor, Rene E.] US FDA, Off Nutr Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Cimino, Michael C.] US EPA, Off Pollut Prevent & Tox, Washington, DC 20460 USA. [Dearfield, Kerry L.] US Food Safety & Inspect Serv, Off Publ Hlth Sci, USDA, Washington, DC 20250 USA. RP Elespuru, RK (reprint author), US FDA, CDRH, OSEL, DB, Bldg 64-3020,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM rosalie.elespuru@fda.hhs.gov NR 53 TC 29 Z9 30 U1 2 U2 12 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 2009 VL 109 IS 2 BP 172 EP 179 DI 10.1093/toxsci/kfp067 PG 8 WC Toxicology SC Toxicology GA 449VH UT WOS:000266357900002 PM 19336498 ER PT J AU Gaines, AR Lee-Stroka, H Byrne, K Scott, DE Uhl, L Lazarus, E Stroncek, DF AF Gaines, Ann Reed Lee-Stroka, Hallie Byrne, Karen Scott, Dorothy E. Uhl, Lynne Lazarus, Ellen Stroncek, David F. TI Investigation of whether the acute hemolysis associated with Rh-o(D) immune globulin intravenous (human) administration for treatment of immune thrombocytopenic purpura is consistent with the acute hemolytic transfusion reaction model SO TRANSFUSION LA English DT Article ID ANTI-D TREATMENT; ACUTE-RENAL-FAILURE; INTRAVASCULAR HEMOLYSIS; D IMMUNOGLOBULIN; AUTOIMMUNE THROMBOCYTOPENIA; RANDOMIZED-TRIAL; WINRHO; HEMOGLOBINURIA; CHILDREN; EFFICACY AB Immune thrombocytopenic purpura and secondary thrombocytopenia patients treated with Rh-o(D) immune globulin intravenous (human; anti-D IGIV) have experienced acute hemolysis, which is inconsistent with the typical presentation of extravascular hemolysis-the presumed mechanism of action of anti-D IGIV. Although the mechanism of anti-D-IGIV-associated acute hemolysis has not been established, the onset, signs/symptoms, and complications appear consistent with the intravascular hemolysis of acute hemolytic transfusion reactions (AHTRs). In transfusion medicine, the red blood cell (RBC) antigen-antibody incompatibility(-ies) that precipitate AHTRs can be detected in vitro with compatibility testing. Under the premise that anti-D-IGIV-associated acute hemolysis results from RBC antigen-antibody-mediated complement activation, this study evaluated whether the incompatibility(-ies) could be detected in vitro with a hemolysin assay, which would support the AHTR model as the hemolytic mechanism. Seven anti-D IGIV lots were tested to determine the RBC antibody identities in those lots, including four lots that had been implicated in acute hemolytic episodes. Hemolysin assays were performed that tested each of 73 RBC specimens against each lot, including the RBCs of one patient who had experienced acute hemolysis after anti-D IGIV administration. Only two anti-D IGIV lots contained RBC antibodies beyond those expected. No hemolysis endpoint was observed in any of the hemolysin assays. Although the findings did not support the AHTR model, the results are reported to contribute knowledge about the mechanism of anti-D-IGIV-associated acute hemolysis and to prompt continued investigation into cause(s), prediction, and prevention of this potentially serious adverse event. C1 [Gaines, Ann Reed] US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Off Blood Res & Review, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Off Cellular Tissue & Gene Therapies, Rockville, MD 20852 USA. NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Div Lab & Transfus Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gaines, AR (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Off Blood Res & Review, 1401 Rockville Pike, Rockville, MD 20852 USA. EM ann.gaines@fda.hhs.gov FU Robert Wise and M. Miles Braun, Office of Biostatistics and Epidemiology, and Susan Abbondanzo, Office of Blood Research and Review; Center for Biologics Evaluation and Research, FDA FX The authors express their appreciation to the patient who experienced acute hemolysis after WinRho SDF administration and who agreed to provide us with blood specimens for this study. The authors would also express our appreciation to Robert Wise and M. Miles Braun, Office of Biostatistics and Epidemiology, and Susan Abbondanzo, Office of Blood Research and Review, Center for Biologics Evaluation and Research, FDA, for their review of the manuscript. The authors declare no competing financial interests. NR 51 TC 8 Z9 10 U1 0 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 2009 VL 49 IS 6 BP 1050 EP 1058 DI 10.1111/j.1537-2995.2008.02083.x PG 9 WC Hematology SC Hematology GA 453IB UT WOS:000266603000006 PM 19220820 ER PT J AU Anderson, SA Yang, H Gallagher, LM O'Callaghan, S Forshee, RA Busch, MP McKenna, MT Williams, I Williams, A Kuehnert, MJ Stramer, S Kleinman, S Epstein, J Dayton, AI AF Anderson, Steven A. Yang, Hong Gallagher, Lou M. O'Callaghan, Sharon Forshee, Richard A. Busch, Michael P. McKenna, Matthew T. Williams, Ian Williams, Alan Kuehnert, Matthew J. Stramer, Susan Kleinman, Steve Epstein, Jay Dayton, Andrew I. TI Quantitative estimate of the risks and benefits of possible alternative blood donor deferral strategies for men who have had sex with men SO TRANSFUSION LA English DT Article ID HEPATITIS-B-VIRUS; INJECTION-DRUG USERS; UNITED-STATES; NUCLEIC-ACID; VIRAL-INFECTIONS; HIV PREVALENCE; YOUNG MEN; TRANSFUSION; ANTIGEN; POPULATION AB Implementation of sensitive screening methods for human immunodeficiency virus (HIV) and hepatitis viruses prompts the question of what quantitative risks may result from altered deferral strategies for donation of blood by men who have had sex with men (MSM). Quantitative probabilistic models were developed to assess changes in the residual risk of transfusion-transmitted HIV and hepatitis B virus (HBV) associated with blood testing and quarantine release errors (QREs) in the initial year of two hypothetical policy scenarios that would allow donations from donors who have abstained from MSM behavior for at least 5 years (MSM5) or at least 1 year (MSM1). The MSM5 and MSM1 models, respectively, predicted annual increases in units of HIV-infected blood of 0.5% (0.03 mean additional units; 95% confidence interval [CI], 0-1) and 3.0% (0.18 mean additional units; 95% CI, 0-1) over current estimated HIV residual risk using recent, nationwide biologic product deviation reports to estimate QRE rates. These estimates are approximately 10-fold lower than estimates based on New York State QRE data from the previous decade. The models predicted smaller increases in infectious HBV donations. QREs remain the most significant preventable source of risk. More accurate inputs, including the percentage of MSM in the population, the percentage of MSM who have abstained from MSM activity for 1 or 5 years, the prevalence of HIV and HBV in MSM who have abstained from MSM activity for 1 or 5 years, the rate of self-deferral, and QRE rates, are required before making more precise predictions. C1 [Dayton, Andrew I.] US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Inst Environm Sci & Res Ltd, Kenepuru, New Zealand. Off Australian Safety & Compensat Council, Canberra, ACT, Australia. Univ Calif San Francisco, San Francisco, CA 94143 USA. Blood Ctr Pacific, San Francisco, CA USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Amer Red Cross, Natl Testing & Reference Labs, Gaithersburg, MD USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. RP Dayton, AI (reprint author), US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM andrew.dayton@fda.hhs.gov FU Center for Biologics Evaluation and Research; U. S. Department of Energy and the U. S. Food and Drug Administration; Institute for Environmental Science and Research Limited, Kenepuru, New Zealand FX This project was supported in part by an appointment to the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U. S. Department of Energy and the U. S. Food and Drug Administration ( L. M. G.). Funding for travel and support were provided by the Institute for Environmental Science and Research Limited, Kenepuru, New Zealand ( L. M. G.). NR 59 TC 23 Z9 23 U1 3 U2 15 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 2009 VL 49 IS 6 BP 1102 EP 1114 DI 10.1111/j.1537-2995.2009.02124.x PG 13 WC Hematology SC Hematology GA 453IB UT WOS:000266603000012 PM 19320868 ER PT J AU Menis, M Burwen, DR Holness, L Anderson, SA AF Menis, Mikhail Burwen, Dale R. Holness, Leslie Anderson, Steven A. TI Blood use in the ambulatory setting among elderly in the United States SO TRANSFUSION LA English DT Article ID RED-CELL TRANSFUSION; COHORT AB Our study characterizes blood use in the ambulatory setting by US elderly Medicare beneficiaries during 2001. As the US population ages and delivery of health care in outpatient settings is on the rise, ambulatory blood utilization is expected to increase. There is currently a lack of broad population-based studies detailing ambulatory blood utilization patterns among the US elderly. This descriptive cross-sectional study of ambulatory blood utilization in institutional outpatient settings used Medicare administrative data (5% sample of enrollees) for calendar year 2001. Blood use was identified by either the presence of recorded blood units or the procedure code(s) for transfusion of whole blood or red blood cells. Among 1,368,368 elderly Medicare beneficiaries analyzed, 7054 (0.52%) had blood transfusion in institutional outpatient settings, and 34,186 (2.50%) had blood transfusion in the inpatient setting. Of 10,705 institutional outpatient claims with blood use quantified in this cohort of elderly Medicare beneficiaries, the top 10 principal diagnoses using the largest quantities of blood accounted for 66.3% of total blood units transfused. Nine of these 10 principal diagnoses were either for anemias (51%) or neoplasms (13%) and accounted for 64% of total blood units transfused. Our study suggests that most of the ambulatory blood utilization among US elderly is for diagnoses of anemias and neoplasms rather than procedures. Our population-based study provides valuable information on ambulatory blood utilization patterns which may be used to better understand the reasons for transfusion in the ambulatory setting as blood use is expected to grow. C1 [Menis, Mikhail] US FDA, Analyt Epidemiol Branch, Off Biostatist & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Menis, M (reprint author), US FDA, Analyt Epidemiol Branch, Off Biostatist & Epidemiol, Ctr Biol Evaluat & Res, 1401 Rockville Pike,Suite 266S, Rockville, MD 20852 USA. EM Mikhail.Menis@fda.hhs.gov FU FDA FX The research was supported through internal FDA funds. NR 31 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 2009 VL 49 IS 6 BP 1186 EP 1194 DI 10.1111/j.1537-2995.2009.02114.x PG 9 WC Hematology SC Hematology GA 453IB UT WOS:000266603000021 PM 19309470 ER PT J AU Vugia, D Cronquist, A Cartter, M Tobin-D'Angelo, M Blythe, D Smith, K Lathrop, S Morse, D Cieslak, P Dunn, J Holt, KG Henao, OL Hoekstra, RM Angulo, FJ Griffin, PM Tauxe, RV Trivedi, KK AF Vugia, D. Cronquist, A. Cartter, M. Tobin-D'Angelo, M. Blythe, D. Smith, K. Lathrop, S. Morse, D. Cieslak, P. Dunn, J. Holt, K. G. Henao, O. L. Hoekstra, R. M. Angulo, F. J. Griffin, P. M. Tauxe, R. V. Trivedi, K. K. TI Preliminary FoodNet Data on the Incidence of Infection With Pathogens Transmitted Commonly Through Food-10 States, 2008 (Reprinted from MMWR, vol 58, pg 333-337, 2009) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 [Cronquist, A.] Colorado Dept Publ Hlth & Environm, Denver, CO USA. [Cartter, M.] Connecticut Dept Publ Hlth, Hartford, CT USA. [Blythe, D.] Maryland Dept Hlth & Mental Hyg, Baltimore, MD 21201 USA. [Smith, K.] Minnesota Dept Hlth, Minneapolis, MN 55414 USA. [Morse, D.] New York State Dept Hlth, Albany, NY 12237 USA. [Cieslak, P.] Oregon Publ Hlth Div, Salem, OR USA. [Holt, K. G.] US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. [Trivedi, K. K.] CDC, Atlanta, GA 30333 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 27 PY 2009 VL 301 IS 20 BP 2088 EP 2090 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 449KF UT WOS:000266328800012 ER PT J AU Zhang, K Wong, JW Hayward, DG Sheladia, P Krynitsky, AJ Schenck, FJ Webster, MG Ammann, JA Ebeler, SE AF Zhang, Kai Wong, Jon W. Hayward, Douglas G. Sheladia, Piyush Krynitsky, Alexander J. Schenck, Frank J. Webster, Michael G. Ammann, Jeffrey A. Ebeler, Susan E. TI Multiresidue Pesticide Analysis of Wines by Dispersive Solid-Phase Extraction and Ultrahigh-Performance Liquid Chromatography-Tandem Mass Spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Multiresidue pesticide analysis; wines; UPLC-MS/MS ID CAPILLARY GAS-CHROMATOGRAPHY; MULTI-RESIDUE METHOD; SELECTIVE DETECTION; JUICE; MALT; FOOD; VEGETABLES; PRODUCE; FRUITS; FATE AB A multiresidue pesticide method is described for the determination of 72 pesticides in wines. Pesticides were extracted using acetonitrile saturated with magnesium sulfate and sodium chloride, followed by solid-phase dispersive cleanup using primary-secondary amine and graphitized carbon black sorbents. Analysis is performed by ultraperformance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-MS/MS). The limits of quantitation (LOQs) for most of the pesticides ranged from 0.3 to 3.3 mu g/L with the exception of cyromazine, fenhexamid, and acibenzolar S-methyl (LOQ > 10 mu g/L), and quantitation was determined from calibration curves of standards containing 5.0-2500 mu g/L with r(2) > 0.99. Recovery studies were performed by fortifying wine samples with the pesticides to concentrations of 10, 100, and 1000 mu g/L, resulting in recoveries of >80% for most of the pesticides. Lower (<70%) and higher (>120%) recoveries were most likely from complications of pesticide lability or volatility, matrix interference, or inefficient desorption from the solid-phase sorbents. The method was used to analyze 10 wines collected from a market basket survey, and 19 different pesticides, primarily fungicides, were present at concentrations ranging from <1.0 to 1000 mu g/L. C1 [Zhang, Kai; Wong, Jon W.; Hayward, Douglas G.; Krynitsky, Alexander J.] US FDA, Ctr Food Safety & Appl Nutr, HFS 706, College Pk, MD 20740 USA. [Sheladia, Piyush] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. [Schenck, Frank J.] US FDA, Off Regulatory Affairs, SE Reg Lab, HFR SE660, Atlanta, GA 30309 USA. [Webster, Michael G.; Ammann, Jeffrey A.] Alcohol & Tobacco Tax & Trade Bur, Beverage Alcohol Lab, Beltsville, MD 20705 USA. [Webster, Michael G.; Ammann, Jeffrey A.] Nonbeverage Prod Lab, Beltsville, MD 20705 USA. [Ebeler, Susan E.] Univ Calif Davis, Dept Viticulture & Enol, Davis, CA 95616 USA. 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 OI Ebeler, Susan/0000-0002-8394-6736 NR 35 TC 30 Z9 38 U1 0 U2 16 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 27 PY 2009 VL 57 IS 10 BP 4019 EP 4029 DI 10.1021/jf9000023 PG 11 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 448BU UT WOS:000266237800008 PM 19371141 ER PT J AU Kulka, M Calvo, MS Ngo, DT Wales, SQ Goswami, BB AF Kulka, Michael Calvo, Mona S. Ngo, Diana T. Wales, Samantha Q. Goswami, Biswendu B. TI Activation of the 2-5OAS/RNase L pathway in CVB1 or HAV/18f infected FRhK-4 cells does not require induction of OAS1 or OAS2 expression SO VIROLOGY LA English DT Article DE Coxsackievirus; Hepatitis A virus; RNase L; 2-5A; Oligoadenylate synthetase; Antiviral ID HEPATITIS-A-VIRUS; DOUBLE-STRANDED-RNA; INTERFERON-TREATED CELLS; 2',5'-OLIGOADENYLATE SYNTHETASE; PERSISTENT INFECTION; MESSENGER-RNA; RIBOSOMAL-RNA; HELA-CELLS; ENCEPHALOMYOCARDITIS VIRUS; COXSACKIEVIRUS REPLICATION AB The latent constitutively expressed protein RNase L is activated in coxsackievirus and HAV strain 18f infected FRhK-4 cells. Endogenous oligoadenylate synthetase (OAS) from uninfected and virus infected cell extracts synthesizes active forms of the triphosphorylated 2-5A oligomer (the only known activator of RNase L) in vitro and endogenous 2-5A is detected in infected cell extracts. However, only the largest OAS isoform. OAS3, is readily detected throughout the time course of infection. While IFN beta treatment results in an increase in the level of all three OAS isoforms in FRhK-4 cells, IFN beta pretreatment does not affect the temporal onset or enhancement of RNase L activity nor inhibit virus replication. Our results indicate that CVB1 and HAV/18f activate the 2-5OAS/RNase L pathway in FRhK-4 cells during permissive infection through endogenous levels of OAS, but contrary to that reported for some picornaviruses, CVB1 and HAV/18f replication is insensitive to this activated antiviral pathway. Published by Elsevier Inc. C1 [Kulka, Michael; Ngo, Diana T.; Wales, Samantha Q.; Goswami, Biswendu B.] US FDA, Div Mol Biol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Calvo, Mona S.] US FDA, Div Toxicol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Goswami, BB (reprint author), US FDA, Div Mol Biol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM michael.kulka@fda.hhs.gov; mona.calvo@fda.hhs.gov; diana.ngo@fda.hhs.gov; samantha.wales@fda.hhs.gov; biswendu.goswami@fda.hhs.gov NR 84 TC 10 Z9 10 U1 1 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 MAY 25 PY 2009 VL 388 IS 1 BP 169 EP 184 DI 10.1016/j.virol.2009.03.014 PG 16 WC Virology SC Virology GA 448UY UT WOS:000266288700019 PM 19383565 ER PT J AU Rahman, MF Wang, J Patterson, TA Saini, UT Robinson, BL Newport, GD Murdock, RC Schlager, JJ Hussain, SM Ali, SF AF Rahman, M. F. Wang, J. Patterson, T. A. Saini, U. T. Robinson, B. L. Newport, G. D. Murdock, R. C. Schlager, J. J. Hussain, S. M. Ali, S. F. TI Expression of genes related to oxidative stress in the mouse brain after exposure to silver-25 nanoparticles SO TOXICOLOGY LETTERS LA English DT Article DE Reactive oxygen species; Neurotoxicity; Silver-25 nanoparticles; Free radicals; Arrays; Neurodegeneration ID SPRAGUE-DAWLEY RATS; IN-VITRO TOXICITY; CELLS; POLYMORPHISMS; INHALATION; APOPTOSIS; LUNG AB Nanoparticles are small scale substances (< 100nm) used in biomedical applications, electronics, and energy production. Increased exposure to nanoparticles being produced in large-scale industry facilities elicits concerns for the toxicity of certain classes of nanoparticles. This study evaluated the effects of silver-25 nm (Ag-25) nanoparticles on gene expression in different regions of the mouse brain. Adult-male C57BL/6N mice were administered (i.p.) 100 mg/kg, 500 mg/kg or 1000 mg/kg Ag-25 and sacrificed after 24 h. Regions from the brain were rapidly removed and dissected into caudate nucleus, frontal cortex and hippocampus. Total RNA was isolated from each of the three brain regions collected and real-time RT-PCR analysis was performed using Mouse Oxidative Stress and Antioxidant Defense Arrays. Array data revealed the expression of genes varied in the caudate nucleus, frontal cortex and hippocampus of mice when treated with Ag-25. The data suggest that Ag-25 nanoparticles may produce neurotoxicity by generating free radical-induced oxidative stress and by altering gene expression, producing apoptosis and neurotoxicity. (c) 2009 Published by Elsevier Ireland Ltd. C1 [Murdock, R. C.; Schlager, J. J.; Hussain, S. M.] AFRL HEPB, Appl Biotechnol Branch, Human Effectiveness Directorate, Area B, Dayton, OH 45433 USA. [Rahman, M. F.; Wang, J.; Patterson, T. A.; Saini, U. T.; Newport, G. D.; Ali, S. F.] US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. [Robinson, B. L.] Toxicol Pathol Associates, Jefferson, AR 72079 USA. RP Hussain, SM (reprint author), AFRL HEPB, Appl Biotechnol Branch, Human Effectiveness Directorate, Area B, R St,Bldg 837, Dayton, OH 45433 USA. EM Saber.Hussain@wpafb.af.mil; Syed.Ali@fda.hhs.gov FU Oak Ridge Institute of Science and Education (Oak Ridge, TN); United States Air Force Research Laboratory, Dayton, OH FX The authors would like to thank Drs. William Slikker and Merle Paule for their keen interest and encouragement for this study. This research was supported in part by an appointment (M.F. Rahman) to the Research Participation Program at the National Center for Toxicological Research administered by the Oak Ridge Institute of Science and Education (Oak Ridge, TN) sponsored by the United States Air Force Research Laboratory, Dayton, OH. NR 33 TC 180 Z9 192 U1 5 U2 44 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD MAY 22 PY 2009 VL 187 IS 1 BP 15 EP 21 DI 10.1016/j.toxlet.2009.01.020 PG 7 WC Toxicology SC Toxicology GA 433AM UT WOS:000265175700003 PM 19429238 ER PT J AU Basch, EM Sit, L Fruscione, M Burke, L Kane, R George, D Carducci, MA Matthew, P Beer, TM Scher, HI AF Basch, E. M. Sit, L. Fruscione, M. Burke, L. Kane, R. George, D. Carducci, M. A. Matthew, P. Beer, T. M. Scher, H. I. TI Pain and analgesic use in men with metastatic prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. US FDA, Silver Spring, MD USA. Duke Comprehens Canc Ctr, Durham, NC USA. Johns Hopkins Univ, Baltimore, MD USA. MD Anderson Canc Ctr, Houston, TX USA. OHSU, Inst Canc, Portland, OR USA. NR 0 TC 1 Z9 1 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 20 PY 2009 VL 27 IS 15 SU S MA e20515 PG 1 WC Oncology SC Oncology GA 582OF UT WOS:000276606606272 PM 27960916 ER PT J AU Cortazar, P Johnson, J Justice, R Pazdur, R AF Cortazar, P. Johnson, J. Justice, R. Pazdur, R. TI Adjuvant breast cancer: FDA approval overview SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 [Cortazar, P.; Johnson, J.; Justice, R.; Pazdur, R.] US FDA, Silver Spring, MD USA. NR 0 TC 1 Z9 1 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 20 PY 2009 VL 27 IS 15 SU S MA e11529 PG 2 WC Oncology SC Oncology GA 582OF UT WOS:000276606601373 PM 27964635 ER PT J AU Fedenko, K Cortazar, P Keegan, P Pazdur, R AF Fedenko, K. Cortazar, P. Keegan, P. Pazdur, R. TI Trastuzumab cardiotoxicity: FDA review of four adjuvant breast cancer clinical trials leading to trastuzumab marketing approvals SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 [Fedenko, K.; Cortazar, P.; Keegan, P.; Pazdur, R.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA e11520 PG 1 WC Oncology SC Oncology GA 582OF UT WOS:000276606601364 PM 27964620 ER PT J AU John, CS Madabushi, R Farah, C Lubas, C Williams, G AF John, C. S. Madabushi, R. Farah, C. Lubas, C. Williams, G. TI Can [F-18]FDG PET imaging predict early response to chemotherapy in breast cancer patients? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol C1 [John, C. S.; Madabushi, R.; Farah, C.; Lubas, C.; Williams, G.] 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2009 VL 27 IS 15 SU S MA e14577 PG 1 WC Oncology SC Oncology GA 582OF UT WOS:000276606603025 PM 27963646 ER PT J AU Sapsford, KE Farrell, D Sun, S Rasooly, A Mattoussi, H Medintz, IL AF Sapsford, Kim E. Farrell, Dorothy Sun, Steven Rasooly, Avraham Mattoussi, Hedi Medintz, Igor L. TI Monitoring of enzymatic proteolysis on a electroluminescent-CCD microchip platform using quantum dot-peptide substrates SO SENSORS AND ACTUATORS B-CHEMICAL LA English DT Article; Proceedings Paper CT 9th European Conference on Optical Chemical Sensors and Biosensors (EUROPT(R) ODE 9) CY MAR 30-APR 02, 2008 CL Dublin, IRELAND DE Electroluminescent excitation; CCD; Resonance energy transfer; FRET; Quantum dots; Peptides; Protease sensor; Trypsin; Microfabricated device; Biosensor ID RESONANCE ENERGY-TRANSFER; TRYPSIN INHIBITION; PROTEASES; PROTEIN; KINETICS; DEVICES; NANOCRYSTALLITES; FLUOROPHORES; LIGANDS; SYSTEMS AB Microfabricated devices will have a large impact on many aspects of analytical chemistry from clinical diagnostics to security applications due to their small size, ease of fabrication, portability and low sample volumes. In this report we compare quantum dot (QD)-peptide fluorescence resonance energy transfer (FRET) and Subsequent FRET-based monitoring of enzymatic proteolysis on both a conventional laboratory fluorescent assay plate reader and an electroluminescent-charged-coupled device (EL-CCD) microchip detection platform. The EL-CCD setup combines the spatial detection of CCD with the simple illumination provided by EL strips to measure fluorescence from multi-well credit card-sized sample chips. Data on FRET between a QD donor and a dye-labeled peptide acceptor along with their usage as a substrate for trypsin proteolysis were collected on both platforms and analyzed. Despite a greater than 12-fold reduction in assay volumes in the microchip format and simplification of excitation/emission monitoring, the data reflected a general agreement including an analysis of the QD donor-dye acceptor FRET efficiency and the determination of proteolytic kinetic parameters such as enzymatic velocity V(max) and the Michaelis constant Km. The EL-CCD was further utilized to monitor specific ovomucoid inhibition of trypsin activity. The results suggest that the unique properties inherent to QDs can be combined with the reduced-scale nature of microfabricated devices to make them suitable fora variety of focused bioanalytical applications. including point-of-care diagnostics and global healthcare applications. (C) 2008 Elsevier B.V. All rights reserved. C1 [Sapsford, Kim E.; Sun, Steven; Rasooly, Avraham] US FDA, Div Biol, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. [Farrell, Dorothy; Mattoussi, Hedi] USN, Div Opt Sci Code 5611, Res Lab, Washington, DC 20375 USA. [Sun, Steven] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21227 USA. [Rasooly, Avraham] NCI, Bethesda, MD 20892 USA. [Medintz, Igor L.] USN, Ctr Biol Mol Sci & Engn Code 6900, Res Lab, Washington, DC 20375 USA. RP Sapsford, KE (reprint author), US FDA, Div Biol, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. EM Kim.sapsford@fda.hhs.gov; Igor.Medintz@nrl.navy.mil NR 50 TC 64 Z9 64 U1 3 U2 36 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 MAY 20 PY 2009 VL 139 IS 1 BP 13 EP 21 DI 10.1016/j.snb.2008.07.026 PG 9 WC Chemistry, Analytical; Electrochemistry; Instruments & Instrumentation SC Chemistry; Electrochemistry; Instruments & Instrumentation GA 450VO UT WOS:000266429400004 ER PT J AU Vala, M Etheridge, S Roach, JA Homola, J AF Vala, M. Etheridge, S. Roach, J. A. Homola, J. TI Long-range surface plasmons for sensitive detection of bacterial analytes SO SENSORS AND ACTUATORS B-CHEMICAL LA English DT Article; Proceedings Paper CT 9th European Conference on Optical Chemical Sensors and Biosensors (EUROPT(R) ODE 9) CY MAR 30-APR 02, 2008 CL Dublin, IRELAND DE Biosensor; Surface plasmon resonance; Long-range surface plasmon; Bacterium ID ESCHERICHIA-COLI O157-H7; RESONANCE BIOSENSORS; SENSOR; PATHOGENS AB We report a novel prism-coupled surface plasmon resonance (SPR) biosensor based on special Surface plasmon (SP) mode referred to as long-range Surface plasmon (LRSP). Utilization of LRSP in prism-coupled SPR sensor offers several advantages in comparison with SPR sensors with conventional SPs (cSP) such as extended probe depth of LRSP mode into sensed dielectric and higher sensitivity to the bulk refractive index (RI) changes. The LRSP-supporting multilayer structures and prototype of the sensor setup were prepared. Performance of the LRSP-based sensor was compared to that of the cSP-based sensor in model experiments. LRSP-based sensor was determined to be almost 8 times more sensitive to sample RI changes than the cSP-based sensor. In addition, LRSP-based sensor responses were up to 2.5 and 5.5-fold greater than cSP-based sensor responses for latex beads and the bacterium E. coli HB101P, respectively. (C) 2008 Elsevier B.V. All rights reserved. C1 [Vala, M.; Homola, J.] Inst Photon & Elect ASCR, Prague 18251, Czech Republic. [Etheridge, S.; Roach, J. A.] US FDA, College Pk, MD USA. RP Homola, J (reprint author), Inst Photon & Elect ASCR, Chaberska 57, Prague 18251, Czech Republic. EM homola@ufe.cz RI Vala, Milan/D-4748-2009; Homola, Jiri/F-3683-2014; OI Homola, Jiri/0000-0001-6258-015X; DeGrasse, Stacey/0000-0001-7808-4193 NR 14 TC 60 Z9 61 U1 3 U2 22 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 MAY 20 PY 2009 VL 139 IS 1 SI SI BP 59 EP 63 DI 10.1016/j.snb.2008.08.029 PG 5 WC Chemistry, Analytical; Electrochemistry; Instruments & Instrumentation SC Chemistry; Electrochemistry; Instruments & Instrumentation GA 450VO UT WOS:000266429400011 ER PT J AU Perez-De La Cruz, V Elinos-Calderon, D Robledo-Arratia, Y Medina-Campos, ON Pedraza-Chaverri, J Ali, SF Santamaria, A AF Perez-De La Cruz, Veronica Elinos-Calderon, Diana Robledo-Arratia, Yolanda Medina-Campos, Omar N. Pedraza-Chaverri, Jose Ali, Syed F. Santamaria, Abel TI Targeting oxidative/nitrergic stress ameliorates motor impairment, and attenuates synaptic mitochondrial dysfunction and lipid peroxidation in two models of Huntington's disease SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Motor/kinetic deficits; Peroxynitrite; Huntington's disease models; Oxidative/nitrergic stress; Iron porphyrinate; Antioxidant defense ID ACID-INDUCED NEUROTOXICITY; 3-NITROPROPIONIC ACID; QUINOLINIC ACID; S-ALLYLCYSTEINE; RAT-BRAIN; NEURODEGENERATIVE DISORDERS; DOPAMINERGIC NEUROTOXICITY; ENDOGENOUS ANTIOXIDANTS; SUPEROXIDE-DISMUTASE; OXIDATIVE STRESS AB In this Study, we reproduced two toxic models resembling some motor/kinetic deficits of Huntington's disease induced by bilateral intrastriatal injections of either quinolinic acid (QUIN, 120 nmol/mu l per or 3-nitropropionic acid (3-NP, 250 nmol/mu l per side) to rats. Motor skills (including total distance walked/traveled and total horizontal and vertical activities) were evaluated in a box-field system at 1 and 7 days post-lesion. In order to investigate whether these alterations were associated with the oxidative/nitrergic stress evoked by the nitrogen reactive species peroxynitrite (ONOO(-)) in the striatum, some rats were pretreated with the ONOO(-) decomposition catalyst iron porphyrinate (Fe(TPPS), 10 mg/kg, i.p.) 120 min prior to toxins infusion. With the aim to further characterize some possible mechanisms by which motor tasks were affected and/or preserved, biochemical analysis of peroxidative damage to lipids and mitochondrial dysfunction were both assessed in synaptic membranes isolated from the striata of QUIN-, 3-NP- and/or Fe(TPPS)-treated animals. Our results show that targeting oxidative/nitrergic stress by Fe(TPPS) in these toxic models results in amelioration of motor deficits linked to inhibition of peroxidative damage and recovery of mitochondrial function in synaptic membranes. Based on these findings, we hypothesize that the protection exerted by Fe(TITS) oil the biochemical markers analyzed reflects the possible preservation of the functional status of the nerve tissue by limiting the deleterious actions of ONOO, further accounting for partial recovery of integrative motor functions. (C) 2008 Elsevier B.V. All rights reserved. C1 [Perez-De La Cruz, Veronica; Elinos-Calderon, Diana; Robledo-Arratia, Yolanda; Santamaria, Abel] Inst Nacl Neurol & Neurocirugia Manuel Velasco Su, Lab Aminoacidos Excitadores, Mexico City 14269, DF, Mexico. [Medina-Campos, Omar N.; Pedraza-Chaverri, Jose] Univ Nacl Autonoma Mexico, Fac Quim, Dept Biol, Mexico City 04510, DF, Mexico. [Ali, Syed F.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. 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-Mexico [48370-Q]; DGAPA PAPIIT IN [207007] FX This work was supported by CONACyT-Mexico Grant 48370-Q (AS) and DGAPA PAPIIT IN 207007 (JP). NR 33 TC 25 Z9 26 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD MAY 16 PY 2009 VL 199 IS 2 BP 210 EP 217 DI 10.1016/j.bbr.2008.11.037 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 429XP UT WOS:000264953700006 PM 19100293 ER PT J AU Zhang, YQ Yoshida, T Zhang, BL AF Zhang, Yaqin Yoshida, Tatsushi Zhang, Baolin TI TRAIL induces endocytosis of its death receptors in MDA-MB-231 breast cancer cells SO CANCER BIOLOGY & THERAPY LA English DT Article DE TNF-related apoptosis inducing ligand (TRAIL); death receptor; endocytosis; apoptosis; caspases; cleavage; breast cancer cells ID TUMOR-NECROSIS-FACTOR; INDUCED APOPTOSIS; MEDIATED ENDOCYTOSIS; LIGAND; INTERNALIZATION; APO2L/TRAIL; RESISTANCE; TRANSPORT; PROTEINS; THERAPY AB TNF-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent that selectively induces apoptosis in cancer cells over normal cells. Here, we show that TRAIL undergoes rapid endocytosis with its death receptors DR4, and likely DR5, in MDA-MB-231 human breast cancer cells. The internalized DR4, but not DR5, is cleaved in a caspase-dependent manner. Blockade of receptor internalization does not prevent caspase activation, but rather enhances apoptosis after TRAIL treatment. TRAIL-induced receptor endocytosis appears to undermine its ability in inducing apoptosis. C1 [Zhang, Yaqin; Yoshida, Tatsushi; Zhang, Baolin] US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Zhang, BL (reprint author), CDER FDA, Div Therapeut Prot, Off Biotechnol, 29 Lincoln Dr,Bldg 29A Rm 2AO1,HFD-122, Bethesda, MD 20892 USA. EM Baolin.zhang@fda.hhs.gov FU FDA Critical Path Fund FX The authors thank Dr. Leslie Rivera for critical reading of the manuscript. These studies were supported in part by the FDA Critical Path Fund to Dr. Baolin Zhang. NR 26 TC 20 Z9 21 U1 1 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD MAY 15 PY 2009 VL 8 IS 10 BP 917 EP 922 DI 10.4161/cbt.8.10.8141 PG 6 WC Oncology SC Oncology GA 475WD UT WOS:000268393300010 PM 19270498 ER PT J AU Turnipseed, SB Clark, SB Karbiwnyk, CM Andersen, WC Miller, KE Madson, MR AF Turnipseed, Sherri B. Clark, Susan B. Karbiwnyk, Christine M. Andersen, Wendy C. Miller, Keith E. Madson, Mark R. TI Analysis of aminoglycoside residues in bovine milk by liquid chromatography electrospray ion trap mass spectrometry after derivatization with phenyl isocyanate SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE Aminoglycosides; Milk; Liquid chromatography-mass spectrometry; Derivatization; Phenyl isocyanate ID GENTAMICIN; EXTRACTION; CONFIRMATION; ANTIBIOTICS AB A derivatization procedure Using phenyl isocyanate was adapted to liquid chromatography ion trap, mass spectrometry (LC-MS(n)) for confirmation and quantification of aminoglycoside residues ill milk. Aminoglycoside residues were extracted from milk with acid and isolated from the matrix with a weak cation exchange solid-phase extraction cartridge. After isolating the compounds from the milk, derivatives of gentamicin, neomycin, and tobramycin were formed by reacting the drugs With phenyl isocyanate ill the presence of triethylamine. The analytes were separated using a dilute formic acid/acetonitrile gradient oil a reversed-phase LC column. The derivatized compounds were analyzed using positive ion electrospray LC-MS(n) with ion trap detection. Product ion spectra were generated from the derivatized protonated molecules. Specific ion transitions were evaluated for quantitative determination and qualitative confirmation of residues in milk. Using this procedure, residues were qualitatively confirmed in milk samples fortified with gentamicin and neomycin at levels ranging from 15 to 300 ng mL(-1). Gentamicin has four major components that were successfully separated and confirmed independently; for quantitative determination the peak areas from the four analogs were summed. Tobramycin was added as ail internal standard for quantitation to mitigate the effects of matrix ion suppression and variable recoveries. Overall recoveries for this method ranged from 80% to 120% with relative standard deviations of less than 25%. The method detection limits are 9.8 ng mL(-1) for NEO and 12.8 ng mL(-1) for total GEN residues. Published by Elsevier B.V. C1 [Turnipseed, Sherri B.; Karbiwnyk, Christine M.; Andersen, Wendy C.] US FDA, Anim Drugs Res Ctr, Denver Sci Branch, Denver Fed Ctr, Denver, CO 80225 USA. [Miller, Keith E.] Univ Denver, Dept Chem & Biochem, Denver, CO 80208 USA. RP Turnipseed, SB (reprint author), US FDA, Anim Drugs Res Ctr, Denver Sci Branch, Denver Fed Ctr, Denver, CO 80225 USA. EM sherri.turnipseed@fda.hhs.gov NR 14 TC 27 Z9 27 U1 2 U2 32 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD MAY 15 PY 2009 VL 877 IS 14-15 BP 1487 EP 1493 DI 10.1016/j.jchromb.2009.03.025 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 447RN UT WOS:000266209600010 PM 19345161 ER PT J AU Wu, HQ Tawakkul, M White, M Khan, MA AF Wu, Huiquan Tawakkul, Mobin White, Maury Khan, Mansoor A. TI Quality-by-Design (QbD): An integrated multivariate approach for the component quantification in powder blends SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE Quality-by-Design (QbD); Process analytical technology (PAT); Design of experiments; Multivariate statistical data analysis; Powder blending; Component quantification; Moving block standard deviation; ANOVA; Scale of scrutiny; Modeling ID NEAR-INFRARED SPECTROSCOPY; PROCESS ANALYTICAL TECHNOLOGY; AUTOMATED-SYSTEM; REAL-TIME; HOMOGENEITY; EXCIPIENTS; SIZE AB The objective of this study was to develop an integrated multivariate approach to quantify the constituent concentrations of both drug and excipients of powder blends. A mixture design was created to include 26 powder formulations consisting of ibuprofen as the model drug and three excipients (HPMC, MCC, and Eudragit L100-55). The mixer was stopped at various time points to enable near-infrared (NIR) scan of the powder mixture and sampling for UV assay. Partial least square (PLS), principal component regression (PCR), and multiple linear regression (MLR) models were established to link the formulation concentrations with the Savitzky-Golay 1st derivative NIR spectral data at various characteristic wavelengths of each component. PLS models based on the NIR data and UV data were calibrated and validated. They predicted the main components' concentrations well in the powder blends, although prediction errors were larger for minor components. As expected from the complete random-mixture (CRM) model, the measurement uncertainties were higher for minor components in the powder formulations. The prediction performance differences between the NIR model and UV model were explained in the context of scale of scrutiny and model applicability. The importance of understanding excipient variability in powder blending and its implication for blending homogeneity assessment is highlighted. Published by Elsevier B.V. C1 [Wu, Huiquan; Tawakkul, Mobin; White, Maury; Khan, Mansoor A.] OTR OPS CDER FDA, DPQR, HFD 940, Silver Spring, MD 20993 USA. RP Wu, HQ (reprint author), OTR OPS CDER FDA, DPQR, HFD 940, FDA White Oak Campus Life Sci Bldg 64,10903 New H, Silver Spring, MD 20993 USA. EM huiquan.wu@fda.hhs.gov NR 27 TC 51 Z9 55 U1 1 U2 33 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 MAY 8 PY 2009 VL 372 IS 1-2 BP 39 EP 48 DI 10.1016/j.ijpharm.2009.01.002 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 445BY UT WOS:000266025800006 PM 19437592 ER PT J AU Zhang, YQ Rosado, LAR Moon, SY Zhang, BL AF Zhang, Yaqin Rosado, Leslie A. Rivera Moon, Sun Young Zhang, Baolin TI Silencing of D4-GDI Inhibits Growth and Invasive Behavior in MDA-MB-231 Cells by Activation of Rac-dependent p38 and JNK Signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BREAST-CANCER CELLS; GDP-DISSOCIATION INHIBITOR; N-TERMINAL KINASE; DRUG-INDUCED APOPTOSIS; GTP-BINDING PROTEINS; HUMAN LYMPHOMA-CELLS; RHO-GTPASES; EPITHELIAL-CELLS; GENE-EXPRESSION; OVARIAN-CARCINOMA AB The Rho GDP dissociation inhibitor D4-GDI is overexpressed in some human breast cancer cell lines (Zhang, Y., and Zhang, B. (2006) Cancer Res. 66, 5592-5598). Here, we show that silencing of D4-GDI by RNA interference abrogates tumor growth and lung metastasis of otherwise highly invasive MDA-MB-231 breast cancer cells. Under anchorage-independent culture conditions, D4-GDI-depleted cells undergo rapid apoptosis (anoikis), which is known to hinder metastasis. We also found that D4-GDI associates with Rac1 and Rac3 in breast cancer cells, but not with other Rho GTPases tested (Cdc42, RhoA, RhoC, and TC10). Silencing of D4-GDI results in constitutive Rac1 activation and translocation from the cytosol to cellular membrane compartments and in sustained activation of p38 and JNK kinases. Rac1 blockade inhibits p38/JNK kinase activities and the spontaneous anoikis of D4-GDI knockdown cells. These results suggest that D4-GDI regulates cell function by interacting primarily with Rac GTPases and may play an integral role in breast cancer tumorigenesis. D4-GDI could prove to be a potential new target for therapeutic intervention. C1 [Zhang, Yaqin; Rosado, Leslie A. Rivera; Moon, Sun Young; Zhang, Baolin] US FDA, Ctr Drug Evaluat & Res, Off Biotechnol, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Zhang, BL (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Biotechnol, Div Therapeut Prot, Bldg 29A,Rm 2A01,HFD-122,29 Lincoln Dr, Bethesda, MD 20892 USA. EM Baolin.zhang@fda.hhs.gov NR 60 TC 42 Z9 46 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 8 PY 2009 VL 284 IS 19 BP 12956 EP 12965 DI 10.1074/jbc.M807845200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 440GH UT WOS:000265688300042 PM 19269969 ER PT J AU Weisz, A Mazzola, EP Ito, Y AF Weisz, Adrian Mazzola, Eugene P. Ito, Yoichiro TI Preparative separation of di- and trisulfonated components of Quinoline Yellow using affinity-ligand pH-zone-refining counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 5th International Conference on Countercurrent Chromatography CY JUL 26-29, 2008 CL Rio de Janeiro, BRAZIL DE Counter-current chromatography; pH-zone-refining CCC; Quinoline Yellow; D&C Yellow No. 10; Sulfonic acids; Disulfonic acids; Trisulfonic acid; Isomers; Ligand; Dyes; NMR ID TANDEM MASS-SPECTROMETRY; ACIDS; PURIFICATION AB Four positionally isomeric 2-(2-quinolinyl)-1H-indene-1,3(2H)-dionedisulfonic acids (SA) and one triSA, components of the color additive Quinoline Yellow (QY, Color Index No. 47005), were isolated from the dye mixture by affinity-ligand pH-zone-refining counter-current chromatography (CCC) through complementary use of ion-exchange and ion-pair reagents as the ligand. The added ligands facilitated the partitioning oft lie very polar polysulfonated components into the organic stationary phase of the two-phase solvent systems that consisted of isoamyl alcohol-methyl tert-butyl ether-acetonitrile-water (3:5:1 :7).(3:4: 1:7) or (3:11:5). Thus. separation of a 5-g portion Of QY using Sulfuric acid as the retainer and dodecylanime as the ligand (an ion-exchange reagent, 20% in the stationary phase), resulted in 1.21 g of 6',5-diSA and 1.69 g of 6',8',5-triSA, both of over 99% purity. A minor component, 8',4-diSA, not previously reported was also obtained (4.8 mg of over 94% purity) through a similar separation of a different batch Of QY using hydrochloric acid as the retainer and 10% dodecylamine as the ligand in the stationary phase. Two components that co-eluted (0.55 g) in the 5 g separation were separated when trifluoroacetic acid was used as the retainer and tetrabutylammonium hydroxide (an ion-pair reagent) as the ligand. The separation resulted in 20.7 mg of 6',4-diSA, not previously reported, and 111.8 mg of 8'.5-diSA, both of over 98% purity. The isolated Compounds were characterized by high-resolution mass spectrometry and proton nuclear magnetic resonance with correlated spectroscopy assignments. Published by Elsevier B.V. C1 [Weisz, Adrian] US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Mazzola, Eugene P.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Ito, Yoichiro] NHLBI, Bioseparat Technol Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Weisz, A (reprint author), US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM adrian.weisz@fda.hhs.gov FU Intramural NIH HHS [Z99 HL999999] NR 26 TC 18 Z9 20 U1 5 U2 24 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 MAY 8 PY 2009 VL 1216 IS 19 BP 4161 EP 4168 DI 10.1016/j.chroma.2009.02.064 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 444BU UT WOS:000265955900005 PM 19281993 ER PT J AU Zhang, P Zhong, LL Struble, EB Watanabe, H Kachko, A Mihalik, K Virata-Theimer, ML Alter, HJ Feinstone, S Major, M AF Zhang, Pei Zhong, Lilin Struble, Evi Budo Watanabe, Hisayoshi Kachko, Alla Mihalik, Kathleen Virata-Theimer, Maria Luisa Alter, Harvey J. Feinstone, Stephen Major, Marian TI Depletion of interfering antibodies in chronic hepatitis C patients and vaccinated chimpanzees reveals broad cross-genotype neutralizing activity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VIRUS-LIKE PARTICLES; CD81 BINDING; E2; GLYCOPROTEIN; INFECTION; IDENTIFICATION; REPLICATION; PROTEIN; PLASMA; AP33 AB Using human immune globulins made from antihepatitis C virus (HCV)-positive plasma, we recently identified two antibody epitopes in the E2 protein at residues 412-426 (epitope I) and 434-446 (epitope II). Whereas epitope I is highly conserved among genotypes, epitope II varies. We discovered that epitope I was implicated in HCV neutralization whereas the binding of non-neutralizing antibody to epitope II disrupted virus neutralization mediated by antibody binding at epitope I. These findings suggested that, if this interfering mechanism operates in vivo during HCV infection, a neutralizing antibody against epitope I can be restrained by an interfering antibody, which may account for the persistence of HCV even in the presence of an abundance of neutralizing antibodies. We tested this hypothesis by affinity depletion and peptide-blocking of epitope-II-specific antibodies in plasma of a chronically HCV-infected patient and recombinant E1E2 vaccinated chimpanzees. We demonstrate that, by removing the restraints imposed by the interfering antibodies to epitope-II, neutralizing activity can be revealed in plasma that previously failed to neutralize viral stock in cell culture. Further, cross-genotype neutralization could be generated from monospecific plasma. Our studies contribute to understanding the mechanisms of anti-body-mediated neutralization and interference and provide a practical approach to the development of more potent and broadly reactive hepatitis C immune globulins. C1 [Zhang, Pei; Zhong, Lilin; Struble, Evi Budo; Virata-Theimer, Maria Luisa] US FDA, Div Hematol, Bethesda, MD 20892 USA. [Watanabe, Hisayoshi; Kachko, Alla; Mihalik, Kathleen; Feinstone, Stephen; Major, Marian] US FDA, Div Viral Prod, Bethesda, MD 20892 USA. [Watanabe, Hisayoshi; Kachko, Alla; Mihalik, Kathleen; Feinstone, Stephen; Major, Marian] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Alter, Harvey J.] NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Zhang, P (reprint author), US FDA, Div Hematol, Bethesda, MD 20892 USA. EM pei.zhang@fda.hhs.gov; halter@mail.nih.gov; marian.major@fda.hhs.gov NR 22 TC 86 Z9 88 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 5 PY 2009 VL 106 IS 18 BP 7537 EP 7541 DI 10.1073/pnas.0902749106 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 441QI UT WOS:000265783600050 PM 19380744 ER PT J AU Carrillo, MC Sanders, CA Katz, RG AF Carrillo, Maria C. Sanders, Charles A. Katz, Russell G. TI Maximizing the Alzheimer's Disease Neuroimaging Initiative II SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Biomarkers; Neuroimaging; Early defection; Longitudinal study; Natural history study; Mild cognitive impairment ID PROGRESSION; MRI; AD AB The Alzheimer's Disease Neuroimaging Initiative is the largest public-private partnership on brain research underway at the National Institutes of Health. This 6-year Study tracks cognitive and brain changes in normal subjects, those with mild cognitive impairment, and individuals with Alzheimer's disease. It was designed to provide better tools for performing effective clinical trials, and is slated to run until 2010. While data are being generated and analyzed, researchers involved in the study are developing an extension, i.e., the Alzheimer's Disease Neuroimaging Initiative U. The Foundation for the National Institutes of Health and the Alzheimer's Association convened a meeting to review the progress, evaluate future directions, and obtain the United States Food and Drug Administration's perspective on how the Alzheimer's Disease Neuroimaging Initiative could affect the drug-approval process. (C) 2009 The Alzheimer's Association. All rights reserved. C1 [Carrillo, Maria C.] Alzheimers Assoc, Chicago, IL USA. [Sanders, Charles A.] Fdn Natl Inst Hlth, Bethesda, MD USA. [Katz, Russell G.] US FDA, Washington, DC 20204 USA. RP Carrillo, MC (reprint author), Alzheimers Assoc, Chicago, IL USA. EM Maria.Carrillo@alz.org NR 9 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAY PY 2009 VL 5 IS 3 BP 271 EP 275 DI 10.1016/j.jalz.2009.02.005 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 445HW UT WOS:000266042900006 PM 19362888 ER PT J AU Finkle, J Bloomfield, D Uhl, K Sanhai, W Stockbridge, N Krucoff, MW AF Finkle, John Bloomfield, Daniel Uhl, Kathleen Sanhai, Wendy Stockbridge, Norman Krucoff, Mitchell W. TI New precompetitive paradigms: Focus on cardiac safety SO AMERICAN HEART JOURNAL LA English DT Editorial Material C1 [Finkle, John] GlaxoSmithKline Inc, Global Clin Safety & Pharnacovigilance, Collegeville, PA USA. [Bloomfield, Daniel] Merck & Co Inc, Merck Res Labs, Cardiovasc Clin Res, Rahway, NJ 07065 USA. [Uhl, Kathleen] US FDA, Off Womans Hlth, Rockville, MD 20857 USA. [Sanhai, Wendy] US FDA, Off Commissioner, Rockville, MD 20857 USA. [Stockbridge, Norman] US FDA, Off Cardiovasc & Renal Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Krucoff, Mitchell W.] Univ Med Ctr, Dept Med, Durham, NC USA. RP Finkle, J (reprint author), GlaxoSmithKline Inc, Global Clin Safety & Pharnacovigilance, Collegeville, PA USA. NR 3 TC 11 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 J9 AM HEART J JI Am. Heart J. PD MAY PY 2009 VL 157 IS 5 BP 825 EP 826 DI 10.1016/j.ahj.2009.02.021 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 444NN UT WOS:000265987800013 PM 19376307 ER PT J AU Rock, EP Finkle, J Fingert, HJ Booth, BP Garnett, CE Grant, S Justice, RL Kovacs, RJ Kowey, PR Rodriguez, I Sanhai, WR Strnadova, C Targum, SL Tsong, Y Uhl, K Stockbridge, N AF Rock, Edwin P. Finkle, John Fingert, Howard J. Booth, Brian P. Garnett, Christine E. Grant, Stephen Justice, Robert L. Kovacs, Richard J. Kowey, Peter R. Rodriguez, Ignacio Sanhai, Wendy R. Strnadova, Colette Targum, Shari L. Tsong, Yi Uhl, Kathleen Stockbridge, Norman TI Assessing proarrhythmic potential of drugs when optimal studies are infeasible SO AMERICAN HEART JOURNAL LA English DT Article ID TORSADES-DE-POINTES; QT PROLONGATION; TERFENADINE; INTERVAL; RISK; ARRHYTHMIAS; SAFETY; ONDANSETRON; MANAGEMENT; PRODACT AB Assessing the potential for a new drug to cause life-threatening arrhythmias is now an integral component of premarketing safety assessment. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use Guideline (ICH) E14 recommends the "Thorough QT Study" (TQT) to assess clinical QT risk. Such a study calls for careful evaluation of drug effects on the electrocardiographic QT interval at multiples of therapeutic exposure and with a positive control to confirm assay sensitivity. Yet for some drugs and diseases, elements of the TQT Study may be impractical or unethical. In these instances, alternative approaches to QT risk assessment must be considered. This article presents points to consider for evaluation of QT risk when alternative approaches are needed. (Am Heart J 2009; 157:827-36.) C1 [Rock, Edwin P.; Finkle, John] GlaxoSmithKline R&D, King Of Prussia, PA USA. [Fingert, Howard J.] Pfizer R&D, New London, CT USA. [Booth, Brian P.; Garnett, Christine E.] US FDA, Off Clin Pharmacol, Silver Spring, MD USA. [Grant, Stephen; Targum, Shari L.; Stockbridge, Norman] US FDA, Div Cardiorenal Drug Prod, Indianapolis, IN USA. [Justice, Robert L.] US FDA, Div Drug Oncol Prod, Indianapolis, IN USA. [Kovacs, Richard J.] Indiana Univ, Sch Med, Krannert Inst Cardiol, Indianapolis, IN 46202 USA. [Kowey, Peter R.] Main Line Hlth & Jefferson Med Coll, Wynnewood, PA USA. [Rodriguez, Ignacio] Roche, Palo Alto, CA USA. [Sanhai, Wendy R.; Uhl, Kathleen] US FDA, Off Commissioner, Rockville, MD 20857 USA. [Strnadova, Colette] Hlth Canada, Ottawa, ON K1A 0L2, Canada. [Tsong, Yi] US FDA, Off Biostat, Rockville, MD 20857 USA. RP Rock, EP (reprint author), GlaxoSmithKline Inc, 709 Swedeland Rd,UW 2104,Bldg 21,Room 1096, King Of Prussia, PA 19406 USA. EM edwin.p.rock@gsk.com NR 35 TC 39 Z9 40 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 2009 VL 157 IS 5 BP 827 EP 836 DI 10.1016/j.ahj.2009.02.020 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 444NN UT WOS:000265987800014 PM 19376308 ER PT J AU Rossi, J AF Rossi, John TI Nonhuman Primate Research: The Wrong Way to Understand Needs and Necessity SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 US FDA, Off Pediat Therapeut, Rockville, MD 20857 USA. RP Rossi, J (reprint author), US FDA, Off Pediat Therapeut, 5600 Fishers Lane,Parklawn Bldg, Rockville, MD 20857 USA. EM John.Rossi@fda.hhs.gov NR 7 TC 3 Z9 3 U1 0 U2 3 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. PD MAY PY 2009 VL 9 IS 5 BP 21 EP 23 DI 10.1080/15265160902788728 PG 5 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 446TU UT WOS:000266144900007 PM 19396676 ER PT J AU Furia, AC Lee, RE Strother, ML Huang, TTK AF Furia, Andrea C. Lee, Rebecca E. Strother, Myra L. Huang, Terry T-K TI College Students' Motivation to Achieve and Maintain a Healthy Weight SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article DE weight maintenance; obesity; overweight; motivation; college students ID PHYSICAL-ACTIVITY; UNITED-STATES; HIGH-SCHOOL; OBESITY; EXERCISE; OVERWEIGHT; PREDICTORS; BEHAVIORS; FRESHMAN; DISEASE AB Objectives: To develop and refine a scale of motivational factors related to healthy weight achievement and maintenance and to examine differences by gender and weight status. Methods: A cross-sectional survey of 300,university students aged 18-24 years. Results: Factor analysis yielded 6 factors - Intrinsic (Cronbach's alpha=0.73): affective motivation, self-efficacy/interest; Extrinsic (Cronbach's alpha=0.68): social reward, peer pressure, lack of choice, and authority influence. Males and normal-weight students showed higher affective motivation and overall intrinsic motivation compared to females and overweight students, (P<.001). Conclusion: Intrinsic motivational factors and gender differences should be considered in developing obesity prevention interventions in this age-group. C1 [Huang, Terry T-K] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Furia, Andrea C.] US FDA, Off Special Hlth Issues, Rockville, MD 20857 USA. [Lee, Rebecca E.] Univ Houston, Dept Hlth & Human Performance, Houston, TX USA. [Strother, Myra L.] Univ Kansas, Watkins Mem Hlth Ctr, Lawrence, KS 66045 USA. RP Huang, TTK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, 6100 Execut Blvd,4B11, Bethesda, MD 20892 USA. EM huangter@mail.nih.gov NR 26 TC 12 Z9 12 U1 3 U2 7 PU PNG PUBLICATIONS PI STAR CITY PA PO BOX 4593, STAR CITY, WV 26504-4593 USA SN 1087-3244 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD MAY-JUN PY 2009 VL 33 IS 3 BP 256 EP 263 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 439WE UT WOS:000265657400004 PM 19063647 ER PT J AU Fogelgren, B Yang, SM Sharp, IC Huckstep, OJ Ma, WB Somponpun, SJ Carlson, EC Uyehara, CFT Lozanoff, S AF Fogelgren, Ben Yang, Shiming Sharp, Ian C. Huckstep, Odaro J. Ma, Wenbin Somponpun, S. J. Carlson, Edward C. Uyehara, Catherine F. T. Lozanoff, Scott TI Deficiency in Six2 during prenatal development is associated with reduced nephron number, chronic renal failure, and hypertension in Br/+ adult mice SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Review DE Br mutant mouse; glomerulus ID POLYCYSTIC KIDNEY-DISEASE; ENDOTHELIN-1 TRANSGENIC MICE; BASEMENT-MEMBRANE THICKNESS; ANTERIOR CRANIAL BASE; BLOOD-PRESSURE; REMNANT KIDNEY; GENE-EXPRESSION; FRONTONASAL DYSPLASIA; MIDFACIAL RETRUSION; ELECTRON-MICROSCOPY AB Fogelgren B, Yang S, Sharp IC, Huckstep OJ, Ma W, Somponpun SJ, Carlson EC, Uyehara CFT, Lozanoff S. Deficiency in Six2 during prenatal development is associated with reduced nephron number, chronic renal failure, and hypertension in Br/+ adult mice. Am J Physiol Renal Physiol 296: F1166-F1178, 2009. First published February 4, 2009; doi:10.1152/ajprenal.90550.2008.-The Br/+ mutant mouse displays decreased embryological expression of the homeobox transcription factor Six2, resulting in hertitable renal hypoplasia. The purpose of this study was to characterize the renal physiological consequences of embryonic haploinsuffiency of Six2 by analyzing renal morphology and function in the adult Br heterozygous mutant. Adult Br/+ kidneys weighed 50% less than those from wild-type mice and displayed glomerulopathy. Stereological analysis of renal glomeruli showed that Br/+ kidneys had an average of 88% fewer glomeruli than +/+ kidneys, whereas individual glomeruli in Br/+ mice maintained an average volume increase of 180% compared with normal nephrons. Immunostaining revealed increased levels of endothelin-1 (ET-1), endothelin receptors A (ETA) and B (ETB), and Na-K-ATPase were present in the dilated renal tubules of mutant mice. Physiological features of chronic renal failure (CRF) including elevated mean arterial pressure, increased plasma creatinine, and dilute urine excretion were measured in Br/+ mutant mice. Electron microscopy of the Br/+ glomeruli revealed pathological alterations such as hypercellularity, extracellular matrix accumulation, and a thick irregular glomerular basement membrane. These results indicate that adult Br/+ mice suffer from CRF associated with reduced nephron number and renal hypoplasia, as well as glomerulopathy. Defects are associated with embryological deficiencies of Six2, suggesting that proper levels of this protein during nephrogenesis are critical for normal glomerular development and adult renal function. C1 [Fogelgren, Ben; Yang, Shiming; Sharp, Ian C.; Huckstep, Odaro J.; Lozanoff, Scott] Univ Hawaii, Dept Anat Biochem & Physiol, John A Burns Sch Med, Honolulu, HI 96813 USA. [Somponpun, S. J.; Uyehara, Catherine F. T.] Tripler Army Med Ctr, Dept Clin Invest, Honolulu, HI 96859 USA. [Ma, Wenbin] US FDA, Lab Retrovirus Res, Div Viral Prod, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Carlson, Edward C.] Univ N Dakota, Dept Anat & Cell Biol, Sch Med & Hlth Sci, Grand Forks, ND 58201 USA. RP Lozanoff, S (reprint author), Univ Hawaii, Dept Anat, John A Burns Sch Med, 651 Ilalo St,BSB 110, Honolulu, HI 96813 USA. EM lozanoff@hawaii.edu FU American Heart Association Hawaii [9951133Z, 1R01-DK-064752]; North Dakota Lions Foundation FX This work was supported by American Heart Association Hawaii Affiliate Grant 9951133Z and 1R01-DK-064752 (to S. Lozanoff), as well as by the North Dakota Lions Foundation (to E. C. Carlson). NR 101 TC 17 Z9 17 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAY PY 2009 VL 296 IS 5 BP F1166 EP F1178 DI 10.1152/ajprenal.90550.2008 PG 13 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 438AZ UT WOS:000265529600026 PM 19193724 ER PT J AU Tomita, T Yamada, A Miyakoshi, M Kido, T Sheikh, F Srisodsai, A Miyajima, A Donnelly, RP Kimura, S AF Tomita, Takeshi Yamada, Atsushi Miyakoshi, Masaaki Kido, Taketomo Sheikh, Faruk Srisodsai, Achara Miyajima, Atsushi Donnelly, Raymond P. Kimura, Shioko TI Oncostatin M Regulates Secretoglobin 3A1 and 3A2 Expression in a Bidirectional Manner SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE oncostatin M; gene regulation; secretoglobin 3A1; secretoglobin 3A2; lung ID UTEROGLOBIN-RELATED PROTEIN-1; ALLERGIC AIRWAY INFLAMMATION; MUCIN GENE-EXPRESSION; IN-VITRO; EPITHELIAL-CELLS; MOUSE; HIN-1; MICE; FIBROBLASTS; LUNG AB Secretoglobin (SCGB) 3A1 and 3A2 are members of the small molecular weight secretoglobin gene superfamily. SCGB3A1 is a tumor suppressor gene, whereas SCGB3A2 has anti-inflammatory properties. Both genes are mainly expressed in the lung and trachea in mice. Whether the expression and/or function of these two genes are related is not known. Here we show that the expression of SCGB3A1 and SCGB3A2 are bidirectionally regulated by oncostatin M (OSM) when examined in a mouse transformed Clara cell line (mtCC); SCGB3A1 is up-regulated by OSM, while SCGB3A2 is downregulated in a time- and dose-dependent manner. OSM-activated STAT3/5, through binding to the STAT-binding element located at -201 to -209 by in the mouse Scgb3a1 gene promoter, and the extracellular signal-regulated kinase (ERK)- and p38-mitogen-activated protein kinase (MAPK) pathways are responsible for the OSM-induced up-regulation of SCGB3A1 expression. On the other hand, the -113 to -273 by region in the Scgb3a2 promoter appears to be responsible for the OSM induced down-regulation of the gene. No significant differences in the levels or patterns of specific DNA-binding proteins were found in the -113 to -273 by region as determined by electrophoretic mobility shift assays. Neither the ERK- nor p38-MAPK pathways were involved in the OSM-induced reduction of Scgb3a2 promoter activity. These results suggest that OSM-induced suppression of SCGB3A2 expression is an indirect effect of OSM. Expression of the Clara cell marker, CYP2F2, was markedly decreased upon OSM treatment in parallel with the decrease of SCGB3A2 expression in mtCC cells. The differential regulation of Scgb3a1 and Scgb3a2 gene expression by OSM may explain the unique functions of these genes in the lung. C1 [Tomita, Takeshi; Yamada, Atsushi; Miyakoshi, Masaaki; Kido, Taketomo; Srisodsai, Achara; Kimura, Shioko] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Sheikh, Faruk; Donnelly, Raymond P.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD USA. [Srisodsai, Achara] Khon Kaen Univ, Fac Pharmaceut Sci, Khon Kaen, Thailand. [Miyajima, Atsushi] Univ Tokyo, Inst Mol & Cellular Biosci, Tokyo, Japan. RP Kimura, S (reprint author), NCI, Lab Metab, NIH, Bldg 37,Rm 3118, Bethesda, MD 20892 USA. EM kimuras@mail.nih.gov FU National Cancer Institute FX This research was supported by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research. NR 47 TC 2 Z9 2 U1 0 U2 2 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 MAY PY 2009 VL 40 IS 5 BP 620 EP 630 DI 10.1165/rcmb.2008-0062OC PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 439IH UT WOS:000265620300012 PM 18978304 ER PT J AU Sapsford, KE Francis, J Sun, S Kostov, Y Rasooly, A AF Sapsford, Kim E. Francis, Jesse Sun, Steven Kostov, Yordan Rasooly, Avraham TI Miniaturized 96-well ELISA chips for staphylococcal enterotoxin B detection using portable colorimetric detector SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE Electroluminescent (EL) illumination; CCD; Miniature ELISA; Staphylococcal enterotoxin B (SEB); Food; Colorimetric measurement; Biosensor ID ATOPIC-DERMATITIS; RHEUMATOID-ARTHRITIS; FOOD; IMMUNOASSAY; SEB; SUPERANTIGENS; CHROMATOGRAPHY; CONFIRMATION; PREVALENCE; ANTIBODIES AB A previously developed fluorescence sensing platform, combining spatial illumination using electroluminescence (EL) semiconductor strips with charge coupled device (CCD)-based detection (EL-CCD), was adapted to a new 96-well chip for colorimetric immunological assays, enhancing the capabilities of the EL-CCD platform. The modified system was demonstrated using a colorimetric-based enzyme linked immunosorbent assay (ELISA) for detection of staphylococcal enterotoxin B (SEB). Limits of detection (LODs) of 3.9 ng/mL (+/- 2.4 ng/mL) SEB were determined with the ELISA chip measured using the EL-CCD platform, following a standard 4-h ELISA protocol. The LODs were comparable to those obtained using standard 96-well ELISA plates measured using a standard laboratory 96-well plate reader. The miniature 96-well ELISA chip however required as little as 5-mu L samples, representing a tenfold reduction in sample volume compared to a standard 96-well ELISA plates. The ELISA chip also demonstrated detection of SEB spiked into various food matrices (milk, mushrooms, and mayonnaise) using limited-to-no sample preparation, with LODs ranging from 3.9 to 18.5 ng/mL depending on the matrix. The EL-CCD platform is versatile, capable of multi-mode detection (e. g., fluorescent and colorimetric along with solution and solid phase assays), and could readily be applied to other field portable or point-of-care applications. C1 [Rasooly, Avraham] NCI, NIH, Bethesda, MD 20892 USA. [Sapsford, Kim E.; Francis, Jesse; Sun, Steven; Rasooly, Avraham] US FDA, Div Biol, CDRH, Off Sci & Engn Labs, Silver Spring, MD 20903 USA. [Francis, Jesse; Sun, Steven; Kostov, Yordan] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21227 USA. RP Rasooly, A (reprint author), NCI, NIH, 6130 Executive Blvd EPN,Room 6035A, Bethesda, MD 20892 USA. EM rasoolya@mail.nih.gov FU Office of Public Health emergency Preparedness (OPHEP) [IAG224-05-655, HHSF223200610765P]; CDRH/OSEL/Division of Biology funds FX This work was supported in part by the Office of Public Health emergency Preparedness (OPHEP) IAG224-05-655 (to A. Rasooly and by FDA contract) and HHSF223200610765P (to Dr. Yordan Kostov) and CDRH/OSEL/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 NR 35 TC 26 Z9 27 U1 0 U2 17 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD MAY PY 2009 VL 394 IS 2 BP 499 EP 505 DI 10.1007/s00216-009-2730-z PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 436BU UT WOS:000265388400013 PM 19290511 ER PT J AU Desai, D Goldbach-Mansky, R Milner, JD Rabin, RL Hull, K Pucino, F Colburn, N AF Desai, Ditina Goldbach-Mansky, Raphaela Milner, Joshua D. Rabin, Ronald L. Hull, Keith Pucino, Frank Colburn, Nona TI Anaphylactic Reaction to Anakinra in a Rheumatoid Arthritis Patient Intolerant to Multiple Nonbiologic and Biologic Disease-Modifying Antirheumatic Drugs SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE adverse drug reactions; anakinra; anaphylactic reaction; antirheumatic drugs; biological therapy; rheumatoid arthritis ID NECROSIS-FACTOR-ALPHA; SYSTEMIC-LUPUS-ERYTHEMATOSUS; ANTI-TNF TREATMENT; CUTANEOUS VASCULITIS; LEUKOCYTOCLASTIC VASCULITIS; ETANERCEPT THERAPY; CROHNS-DISEASE; INFLIXIMAB; PHARMACOGENETICS; ADALIMUMAB AB OBJECTIVE: To report a case of probable anaphylaxis due to anakinra in a patient with rheumatoid arthritis and multiple drug allergies. CASE SUMMARY: A 46-year-old Indian female with rheumatoid arthritis demonstrated distinct adverse reactions to all commercially available anti-tumor necrosis factor therapies, sulfasalazine, and hydroxychloroquine. Over a 4-year period her disease remained active during therapy with methotrexate and prednisone. Biologics were added sequentially, with development of intolerable reactions, first to infliximab (urticarial rash, infusion reactions) after 3 doses, and then to etanercept (autoantibodies, worsening Raynaud's phenomenon, digital microinfarcts) after 1 year. Following 2 months of daily injections of anakinra, she experienced an immediate immunoglobulin E-mediated anaphylactic reaction within 20 minutes of an injection, as evidenced by positive testing to both anakinra and histamine with the skin prick method. The patient subsequently started adalimumab therapy, which was discontinued after the fourth dose due to the development of generalized hives. DISCUSSION: The Naranjo probability scale demonstrated a probable relationship between anaphylaxis and anakinra in this patient. Although cases of anakinra-related hypersensitivity have been reported in patients in which therapy was interrupted and then reintroduced, to our knowledge, this is the first report of anaphylaxis with continuous therapy. CONCLUSIONS: This unusual case of a patient with multiple drug allergies presents a difficult clinical scenario, which was unsuccessfully managed with multiple biologic therapies on a trial-and-error basis. In the future, pharmacogenetics may help to better identify individuals at risk for multiple drug reactions and preclude unnecessary exposure to potentially harmful therapeutic options in similar patients. C1 [Goldbach-Mansky, Raphaela; Colburn, Nona] NIAMSD, Autoinflammatory Dis Sect, NIH, Bethesda, MD 20892 USA. [Milner, Joshua D.] NIAID, Immunol Lab, NIH, Bethesda, MD USA. [Rabin, Ronald L.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Pucino, Frank] NIH, Dept Pharm, Bethesda, MD USA. [Desai, Ditina] Warehouse Camden Yards, Baltimore, MD USA. RP Colburn, N (reprint author), NIAMSD, Autoinflammatory Dis Sect, NIH, Bethesda, MD 20892 USA. EM colburnn@mail.nih.gov FU Intramural NIH HHS [ZIA AR041138-07] NR 45 TC 15 Z9 15 U1 1 U2 3 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD MAY PY 2009 VL 43 IS 5 BP 967 EP 972 DI 10.1345/aph.1L573 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 445WR UT WOS:000266082700021 PM 19417117 ER PT J AU Lin, ZC Wu, ZY AF Lin, Zhichao Wu, Zhongyu TI Analysis of polonium-210 in food products and bioassay samples by isotope-dilution alpha spectrometry SO APPLIED RADIATION AND ISOTOPES LA English DT Article; Proceedings Paper CT 5th International Conference on Radionuclide Metrology-Low-Level Radioactivity Measurement Techniques CY SEP 22-26, 2008 CL Braunschweig, GERMANY DE Polonium-210; Food product; Alpha spectrometry; Bioassay; Plating apparatus; Radiochemical purification ID ENVIRONMENTAL MATERIALS; PB-210; RADIONUCLIDES; ECOSYSTEM; CHAINS AB A rapid and reliable radiochemical method coupled with a simple and compact plating apparatus was developed, validated, and applied for the analysis of (210)Po in variety of food products and bioassay samples. The method performance characteristics, including accuracy, precision, robustness, and specificity, were evaluated along with a detailed measurement uncertainty analysis. With high Po recovery, improved energy resolution, and effective removal of interfering elements by chromatographic extraction. the overall method accuracy was determined to be better than 5% with measurement precision of 10%, at 95% confidence level. Published by Elsevier Ltd. C1 [Lin, Zhichao; Wu, Zhongyu] US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. RP Lin, ZC (reprint author), US FDA, Winchester Engn & Analyt Ctr, 109 Holton St, Winchester, MA 01890 USA. EM zhichao.lin@fda.hhs.gov NR 19 TC 8 Z9 10 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0969-8043 J9 APPL RADIAT ISOTOPES JI Appl. Radiat. Isot. PD MAY PY 2009 VL 67 IS 5 BP 907 EP 912 DI 10.1016/j.apradiso.2009.01.055 PG 6 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 446OD UT WOS:000266130000053 PM 19233664 ER PT J AU Pantalos, G Wu, ZJJ Giridharan, G Rinaldi, J Stewart, S Hariharan, P Lu, QJ Berman, M Lukic, B Deutsch, S Leonard, E Manning, K Antaki, J Paden, D Malinauskas, R Smith, W Mockros, L Johnson, G AF Pantalos, George Wu, Zhongjun Jon Giridharan, Guruprasad Rinaldi, Jean Stewart, Sandy Hariharan, Prasanna Lu, Qijin Berman, Michael Lukic, Branka Deutsch, Steve Leonard, Edward Manning, Keefe Antaki, James Paden, Dave Malinauskas, Rich Smith, William Mockros, Lyle Johnson, Greg TI Use of computer and in vitro modeling techniques during the development of pediatric circulatory support devices (vol 55, pg 3, 2009) SO ASAIO JOURNAL LA English DT Correction C1 [Pantalos, George; Giridharan, Guruprasad] Univ Louisville, Louisville, KY 40292 USA. [Wu, Zhongjun Jon] Univ Maryland, College Pk, MD 20742 USA. [Rinaldi, Jean; Stewart, Sandy; Hariharan, Prasanna; Lu, Qijin; Berman, Michael; Malinauskas, Rich] US FDA, Rockville, MD 20857 USA. [Lukic, Branka; Deutsch, Steve; Manning, Keefe] Penn State Univ, University Pk, PA 16802 USA. [Leonard, Edward] Columbia Univ, New York, NY 10027 USA. [Antaki, James] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. [Smith, William] Cleveland Clin Fdn, Cleveland, OH USA. [Mockros, Lyle] Northwestern Univ, Evanston, IL 60208 USA. RP Pantalos, G (reprint author), Univ Louisville, Louisville, KY 40292 USA. RI Wu, Zhongjun /F-1244-2013; Antaki, James/S-3051-2016 OI Wu, Zhongjun /0000-0003-0807-7195; Antaki, James/0000-0002-5430-7353 NR 1 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1058-2916 J9 ASAIO J JI Asaio J. PD MAY-JUN PY 2009 VL 55 IS 3 BP 307 EP 307 PG 1 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 443FH UT WOS:000265895100028 ER PT J AU Webber, SA Wearden, PD Blume, ED Almond, C O'Callaghan, K Chen, E Pearson, G Pemberton, V Baldwin, JT AF Webber, Steven A. Wearden, Peter D. Blume, Elizabeth D. Almond, Christopher O'Callaghan, Kathryn Chen, Eric Pearson, Gail Pemberton, Victoria Baldwin, J. Timothy TI Pediatric Circulatory Support Contractors' Meeting, February 28, 2008. Report of the Clinical Trials Working Group (vol 55, pg 10, 2009) SO ASAIO JOURNAL LA English DT Correction C1 [Webber, Steven A.; Wearden, Peter D.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Webber, Steven A.; Wearden, Peter D.] UPMC, Childrens Hosp Pittsburgh, Pittsburgh, PA USA. [Blume, Elizabeth D.; Almond, Christopher] Childrens Hosp Boston, Boston, MA USA. [Blume, Elizabeth D.; Almond, Christopher] Harvard Univ, Sch Med, Boston, MA USA. [O'Callaghan, Kathryn; Chen, Eric] US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Cardiovasc Devices, Rockville, MD 20857 USA. [Pearson, Gail; Pemberton, Victoria] NHLBI, Heart Dev & Struct Dis Branch, Div Cardiovasc Dis, NIH, Bethesda, MD 20892 USA. [Baldwin, J. Timothy] NHLBI, Adv Technol & Surg Branch, Div Cardiovasc Dis, NIH, Bethesda, MD 20892 USA. RP Webber, SA (reprint author), Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1058-2916 J9 ASAIO J JI Asaio J. PD MAY-JUN PY 2009 VL 55 IS 3 BP 307 EP 307 PG 1 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 443FH UT WOS:000265895100029 ER PT J AU Harrouk, WA AF Harrouk, W. A. TI Regulatory Perspectives and Case Studies SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Harrouk, W. A.] US FDA, CDER, Div Nonprescript Clin Evaluat, Off Nonprescript Prod, Silver Spring, MD USA. EM wafa.harrouk@fda.hhs.gov 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 2009 VL 85 IS 5 BP 390 EP 390 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 454PX UT WOS:000266695900029 ER PT J AU Fisher, JE Feibus, K Jacobs, A Miller, M Reid, L AF Fisher, J. E. Feibus, K. Jacobs, A. Miller, M. Reid, L. TI Nonclinical Risk Assessment in Pregnancy Labeling of Pharmaceutical Products SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Fisher, J. E.; Feibus, K.; Jacobs, A.; Miller, M.; Reid, L.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2009 VL 85 IS 5 BP 448 EP 448 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 454PX UT WOS:000266695900138 ER PT J AU Surfraz, B Marchant, CA Benz, RD Matthews, EJ AF Surfraz, B. Marchant, C. A. Benz, R. D. Matthews, E. J. TI Mechanistic Insights From an In Silico Model for the Prediction of Teratogenicity SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Surfraz, B.; Marchant, C. A.] Lhasa Ltd, Leeds, W Yorkshire, England. [Benz, R. D.; Matthews, E. J.] US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Informat & Computat Safety Anal Staff, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2009 VL 85 IS 5 BP 448 EP 448 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 454PX UT WOS:000266695900137 ER PT J AU Eggers, S Thorne, S Butte, G Cummins, S AF Eggers, S. Thorne, S. Butte, G. Cummins, S. TI The Decision-Making Process during Pregnancy: Impact on Pregnancy Registries SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Eggers, S.; Thorne, S.; Butte, G.] Decis Partners LLC, Pittsburgh, PA USA. [Cummins, S.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2009 VL 85 IS 5 BP 462 EP 462 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 454PX UT WOS:000266695900164 ER PT J AU Cummins, SK AF Cummins, S. K. TI Evaluation of Pregnancy Exposure Registries for Pharmaceuticals SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Cummins, S. K.] US FDA, Ctr Drug Evaluat & Res, Off New Drugs Immediate Off, Pediat & Maternal Hlth Staff, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2009 VL 85 IS 5 BP 464 EP 464 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 454PX UT WOS:000266695900167 ER PT J AU Calvert, R Maciag, A Gupta, M Anderson, L AF Calvert, Richard Maciag, Anna Gupta, Meghana Anderson, Lucy TI Mutant K-ras 4A protein expression shows a strong positive correlation with superoxide production in human lung adenocarcinoma cell lines SO CANCER RESEARCH LA English DT Meeting Abstract C1 US FDA, College Pk, MD USA. SAIC Frederick Inc, Frederick, MD USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. NCI Frederick, Comparat Carcinogenesis Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 437 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801314 ER PT J AU Chow, D Ako, R Ibrahim, FM Lau, J Loewe, P Tu, SM AF Chow, Diana Ako, Roland Ibrahim, Fady Makram Lau, Johnny Loewe, Patricia Tu, Shi-Ming TI Pharmacokinetics and efficacy of oral diethylstilbestrol (DES) in recurrent prostate cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Houston, Pharm, Houston, TX USA. US FDA, Rockville, MD 20857 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4509 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701805358 ER PT J AU Dokmanovic, M Hirsch, D Shen, Y Wu, WJ AF Dokmanovic, Milos Hirsch, Dianne Shen, Yi Wu, Wen Jin TI Rac1 contributes to trastuzumab-resistance of breast cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Dokmanovic, Milos; Hirsch, Dianne; Shen, Yi; Wu, Wen Jin] US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA LB-196 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604356 ER PT J AU Edavana, VK Williams, S Caldwell, D Ning, BT Yu, XF Mercer, K Kadlubar, F Kadlubar, S AF Edavana, Vineetha Koroth Williams, Suzanne Caldwell, David Ning, Baitang Yu, Xinfeng Mercer, Kelly Kadlubar, Fred Kadlubar, Susan TI Interindividual variability in fulvestrant sulfation by human liver cytosols : effect of suit lel genotype on fulvestrant sulfation SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Arkansas Med Sci, COPH, Little Rock, AR 72205 USA. NCTR, Little Rock, AR USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5455 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702701483 ER PT J AU Fang, JL Han, T Beland, FA Chang, CW Fuscoe, JC AF Fang, Jia-Long Han, Tao Beland, Frederick A. Chang, Ching-Wei Fuscoe, James C. TI Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Fang, Jia-Long; Han, Tao; Beland, Frederick A.; Chang, Ching-Wei; Fuscoe, James C.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2440 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801036 ER PT J AU Lyn-Cook, B Edwards, T Starlard-Davenport, A Word, B Hammons, G AF Lyn-Cook, Beverly Edwards, Timesha Starlard-Davenport, Athena Word, Beverly Hammons, George TI Indole-3-carbinol (I3C) increases the expression of UDP-glucuronsyl-transferases in estrogen receptor negative and positive breast cancer cells: role of DNA methylation SO CANCER RESEARCH LA English DT Meeting Abstract C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Philander Smith Coll, Little Rock, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2863 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702802243 ER PT J AU Mishra, P Ha, LA Rieker, J Henrich, C Bennett, D Sviderskaya, E Merlino, G AF Mishra, Prasun Ha, Linan Rieker, Jennifer Henrich, Curtis Bennett, Dorothy Sviderskaya, Elena Merlino, Glenn TI The p53 and Ink4A independent tumor suppressor activity of ARF in melanoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. US FDA, Div Monoclonal Antibody, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. NCI, Mol Targets Dev Program, Frederick, MD 21701 USA. SAIC Fredrick Inc, Frederick, MD USA. Univ London, Div Basic Med Sci, St Georges, London, England. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5515 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803212 ER PT J AU Nakashima, H Husain, S Puri, R AF Nakashima, Hideyuki Husain, Syed Puri, Raj TI IL-13 receptor \#945;2 DNA vaccine induces tumor immunity in murine tumor models SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Nakashima, Hideyuki; Husain, Syed; Puri, Raj] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 353 PG 1 WC Oncology SC Oncology GA V43TB UT WOS:000209702605317 ER PT J AU Podar, K Zhang, J Tonon, G Sattler, M Grabher, C Lababidi, S Zimmerhackl, A Raab, M Vallet, S Zhou, YM Cartron, MA Tai, YT Chauhan, D Anderson, K AF Podar, Klaus Zhang, Jing Tonon, Giovanni Sattler, Martin Grabher, Clemens Lababidi, Samir Zimmerhackl, Alexander Raab, Marc Vallet, Sonia Zhou, Yiming Cartron, Marie-Astrid Tai, Yu-Tzu Chauhan, Dharminder Anderson, Kenneth TI Targeting angiogenesis via a c-Myc/Hif-1\#945;- dependent pathway in MM SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. US FDA, Rockville, MD 20857 USA. Massachussetts Gen Hosp, Boston, MA USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3185 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803478 ER PT J AU Slager, S Goldin, L Strom, S Lanasa, M Spector, L Rassenti, L Leis, J Camp, N Kay, N Vachon, C Weinberg, J Rabe, K Achenbach, S Hanson, C Marti, G Call, T Caporaso, N Cerhan, J AF Slager, Susan Goldin, Lynn Strom, Sara Lanasa, Mark Spector, Logan Rassenti, Laura Leis, Jose Camp, Nicola Kay, Neil Vachon, Celine Weinberg, J. Rabe, Kari Achenbach, Sara Hanson, Curtis Marti, Gerald Call, Timothy Caporaso, Neil Cerhan, James TI Confirmation of a set of genetic susceptibility variants for chronic lymphocytic leukemia (CLL) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. NCI, DCEG, Bethesda, MD 20892 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Minnesota, Minneapolis, MN USA. UCSD, Moores Canc Ctr, La Jolla, CA USA. Mayo Clin, Scottsdale, AZ USA. Univ Utah, Sch Med, Salt Lake City, UT USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 96 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704045 ER PT J AU Starlard-Davenport, A Tryndyak, V Latendresse, J Beland, F Pogribny, I AF Starlard-Davenport, Athena Tryndyak, Volodymyr Latendresse, John Beland, Frederick Pogribny, Igor TI Assessment and role of RASSF1A promoter hypermethylation during estrogen-induced mammary gland carcinogenesis in ACI rats: Implication for early breast cancer detection SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Starlard-Davenport, Athena; Tryndyak, Volodymyr; Latendresse, John; Beland, Frederick; Pogribny, Igor] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5176 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801431 ER PT J AU Tryndyak, V Beland, F Pogribny, I AF Tryndyak, Volodymyr Beland, Frederick Pogribny, Igor TI E-Cadherin inhibition and epithelial-to-mesenchymal transition in breast cancer cells is associated with down-regulation of the miR-200 family, and not with promoter hypermethylation SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Tryndyak, Volodymyr; Beland, Frederick; Pogribny, Igor] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2633 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804058 ER PT J AU Tsai, HT Caporaso, N Kyle, R Katzmann, J Dispenzieri, A Hayes, R Marti, G Albitar, M Ghia, P Rajkumar, V Landgren, O AF Tsai, Huei-Ting Caporaso, Neil Kyle, Robert Katzmann, Jerry Dispenzieri, Angela Hayes, Richard Marti, Gerald Albitar, Maher Ghia, Paolo Rajkumar, Vincent Landgren, Ola TI Evidence of immune disruption up to 9.8 years prior to diagnosis of chronic lymphocytic leukemia: A prospective study SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Mayo Clin, Div Hematol & Internal Med, Rochester, MN USA. Mayo Clin, Div Clin Biochem & Immunol, Rochester, MN USA. Mayo Clin, Lab Med & Pathol, Rochester, MN USA. NIH, Ctr Biol Evaluat & Res, US FDA, Bethesda, MD 20892 USA. Quest Diagnost, Nichols Inst, San Juan Capistrano, CA USA. Univ Vita Salute San Raffaele, Dept Oncol, Unit & Lab Lymphoid Malignancies, Milan, Italy. Ist Sci San Raffaele, Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1680 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702702330 ER PT J AU Zhang, XM Lin, J Wu, XF Kadlubar, S Lin, ZN Ning, BT Kadlubar, F AF Zhang, Xuemei Lin, Jie Wu, Xifeng Kadlubar, Susan Lin, Zhongning Ning, Baitang Kadlubar, Fred TI Genetic variants of GSTM1 and the risk of bladder cancer in Caucasians SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3056 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703264 ER PT J AU Kannan, M Yadav, BK Ahmad, F Biswas, A Saxena, R AF Kannan, Meganathan Yadav, Birendra Kumar Ahmad, Firdos Biswas, Arijit Saxena, Renu TI Modulation of clinical phenotype of Glanzmann's thrombasthenia by thrombogenic mutations SO CLINICA CHIMICA ACTA LA English DT Article DE Glanzmann's thrombasthenia; Clinical phenotype; Modulation; Thrombogenic mutations ID PLASMA PROTHROMBIN LEVELS; FACTOR-V-LEIDEN; VENOUS THROMBOSIS; METHYLENETETRAHYDROFOLATE REDUCTASE; GENE POLYMORPHISM; DISEASE; HYPERHOMOCYSTEINEMIA; PREVALENCE; RISK AB Background: Glanzmann's thrombasthenia (GT) is an autosomal recessive bleeding disorder which is due to a defect in platelet aggregation in response to multiple physiological agonists. It has been demonstrated that the clinical phenotype of various diseases inherited in a classic Mendelian fashion can be modulated by a series of factors, inherited as well as acquired. Methods: A total of 45 GT patients were screened for the thrombogenic polymorphisms, i.e., FV Leiden (R506Q), Prothrombin G20210A, MTHFR C677T and HPA-1 by PCR/RFLP. Results: MTHFR C677T heterozygous was seen in 6 patients. FV Leiden heterozygous in one and Prothrombin G20210A gene variant in none. HPA-1 was seen in 3 patients of whom 1 was homozygous and 2 were heterozygous. Conclusion: Thus the coinheritance of heterozygous FV Leiden alone or homozygous HPA 1b alone or the combined heterozygosity of MTHFR and HPA-1 were predicted to alter the clinical phenotype. Whereas the inheritance of heterozygous MTHFR alone or heterozygous HPA-1 alone did not altered the clinical phenotype significantly. Hence FV Leiden, MTHFR C677T polymorphism along with PLA-1 and homozygous HPA-1 were the probable ameliorating factor in GT mild phenotype. (C) 2009 Elsevier B.V. All rights reserved. C1 [Kannan, Meganathan; Yadav, Birendra Kumar; Ahmad, Firdos; Biswas, Arijit; Saxena, Renu] All India Inst Med Sci, Dept Haematol, New Delhi 110029, India. [Kannan, Meganathan] US FDA, Div Hematol, Bethesda, MD 20892 USA. RP Saxena, R (reprint author), All India Inst Med Sci, Dept Haematol, IRCH Bldg,1st Floor,Ansari Nagar, New Delhi 110029, India. EM profrsaxena@gmail.com RI Biswas, Arijit/B-9673-2011; Ahmad, Firdos/G-6664-2015 NR 17 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD MAY PY 2009 VL 403 IS 1-2 BP 156 EP 158 DI 10.1016/j.cca.2009.02.009 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 447KN UT WOS:000266190100029 PM 19245802 ER PT J AU Smith, B Uhl, K AF Smith, B. Uhl, K. TI Drug Delivery in the Twenty-First Century: A New Paradigm SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID ALZHEIMERS-DISEASE; TRANSDERMAL PATCH C1 [Smith, B.] Amgen Inc, Thousand Oaks, CA USA. [Uhl, K.] US FDA, Off Womens Hlth, Rockville, MD 20857 USA. RP Smith, B (reprint author), Amgen Inc, Thousand Oaks, CA USA. EM brismith@amgen.com NR 15 TC 6 Z9 6 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAY PY 2009 VL 85 IS 5 BP 451 EP 455 DI 10.1038/clpt.2009.31 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 437ZG UT WOS:000265525100001 PM 19381145 ER PT J AU Ferrari, M Philibert, MA Sanhai, WR AF Ferrari, M. Philibert, M. A. Sanhai, W. R. TI Nanomedicine and Society SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID NANOTECHNOLOGY; DELIVERY; CANCER AB Nanomedicine is a reality of medical research and clinical practice, and it offers new and promising approaches to fundamental problems in medicine. Most prominent are the early detection of neoplastic disease and the individualized treatment of metastases. These potentially transformational developments require careful scrutiny of the potential impact of nanomedicine on society, so that the community can guide its deployment in keeping with the fundamental tenets of medical ethics. C1 [Sanhai, W. R.] US FDA, Off Commissioner, Rockville, MD 20857 USA. [Ferrari, M.] Univ Texas Houston, Hlth Sci Ctr, Div Nanomed, Houston, TX USA. [Philibert, M. A.] Univ Michigan, Sch Publ Hlth, Dept Toxicol, Ann Arbor, MI 48109 USA. RP Sanhai, WR (reprint author), US FDA, Off Commissioner, Rockville, MD 20857 USA. EM wendy.sanhai@fda.hhs.gov NR 7 TC 15 Z9 15 U1 0 U2 10 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 2009 VL 85 IS 5 BP 466 EP 467 DI 10.1038/clpt.2008.276 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 437ZG UT WOS:000265525100009 PM 19381150 ER PT J AU Lauritsen, KJ Nguyen, T AF Lauritsen, K. J. Nguyen, T. TI Combination Products Regulation at the FDA SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material AB The US Food and Drug Administration (FDA) is responsible for protecting the public health by assuring the safety, efficacy, and security of drugs, biological products, and medical devices. As single-entity products, drugs are generally regulated by the Center for Drug Evaluation and Research (CDER), devices by the Center for Devices and Radiological Health (CDRH), and biologics by the Center for Biologics Evaluation and Research (CBER). In recent years, technological advances have led to a blurring of the historical lines of separation between the centers. C1 [Lauritsen, K. J.; Nguyen, T.] US FDA, Off Combinat Prod, Rockville, MD 20857 USA. RP Lauritsen, KJ (reprint author), US FDA, Off Combinat Prod, Rockville, MD 20857 USA. EM kristina.lauritsen@fda.hhs.gov NR 3 TC 15 Z9 16 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAY PY 2009 VL 85 IS 5 BP 468 EP 470 DI 10.1038/clpt.2009.28 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 437ZG UT WOS:000265525100010 PM 19381151 ER PT J AU Bhattacharya, B Puri, S Puri, RK AF Bhattacharya, Bhaskar Puri, Sachin Puri, Raj K. TI A Review of Gene Expression Profiling of Human Embryonic Stem Cell Lines and their Differentiated Progeny SO CURRENT STEM CELL RESEARCH & THERAPY LA English DT Review AB One of the key characteristics of human embryonic stem cells (hESC) is their ability to proliferate for an indefinite period of time. Previous studies have shown that a unique network of transcription factors are involved in hESC self renewal. Since hESC lines have the potential to differentiate into cells of all three germ layers, cells derived from hESC may be useful for the treatment of a variety of inherited or acquired diseases. The molecular signal required to differentiate hESC into a particular cell type has not been defined. It is expected that global gene expression profiling of hESC may provide an insight into the critical genes involved in maintaining pluripotency of hESC and genes that are modulated when hESCs differentiate. Several groups have utilized a variety of high throughput techniques and performed gene expression profiling of undifferentiated hESCs and mouse ES cells (mESC) to identify a set of genes uniquely expressed in ES cells but not in mature cells and defined them as "stemness" genes. These molecular techniques include DNA microarray, EST-enumeration, MPSS profiling, and SAGE. Irrespective of the molecular technique used, highly expressed genes showed similar expression pattern in several ES cell lines supporting their importance. A set of approximately 100 genes were identified, which are highly expressed in ES cells and considered to be involved in maintaining pluripotency and self renewal of ES cells. Various studies have also reported on the gene expression profiling of differentiated embryoid bodies (EB) derived from hESCs and mESCs. When hESCs are differentiated, "stemness" genes are down-regulated and a set of genes are up-regulated. Together with down-modulation of "stemness" genes and up-regulation of new genes may provide a new insight into the molecular pathways of hESC differentiation and study of these genes may be useful in the characterization of differentiated cells. C1 [Bhattacharya, Bhaskar; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Puri, Sachin] Providence Portland Med Ctr, Earle A Chiles Res Inst, Lab Mol & Tumor Immunol, Portland, OR 97213 USA. RP Puri, RK (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM raj.puri@fda.hhs.gov NR 75 TC 34 Z9 35 U1 1 U2 10 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1574-888X J9 CURR STEM CELL RES T JI Curr. Stem Cell Res. Ther. PD MAY PY 2009 VL 4 IS 2 BP 98 EP 106 PG 9 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA V22AZ UT WOS:000208249400002 PM 19442194 ER PT J AU Alosh, M Fritsch, K Soukup, M Wilkin, J AF Alosh, Mohamed Fritsch, Kathleen Soukup, Mat Wilkin, Jonathan TI Clinical trials and statistical analyses: what should dermatologists look for in a report? SO DERMATOLOGIC THERAPY LA English DT Article DE baseline factors; bias; missing data; patient population; prespecified and post hoc statistical analyses; study-to-study variability; variability across reports from different drugs AB Clinicians need to evaluate the quality of individual clinical studies and synthesize the information from multiple clinical studies to provide insights in selecting appropriate therapies for patients. Understanding the key statistical principles that underlie a clinical trial and how they may be implemented can help clinicians properly interpret the efficacy and safety findings of clinical trials. Several factors should be considered when evaluating clinical studies reported in the literature, as important differences might exist among reported studies, thereby impacting the reliability of their findings. Studies vary in terms of study design, conduct, analysis, and presentation of findings. The key features to consider when evaluating clinical trials are inferential intent (exploratory versus confirmatory), choice of control group, randomization, extent of blinding, prespecification of analyses, appropriate handling of missing data, and multiple end points. Making comparisons across studies is extremely difficult and rarely statistically justified. However, this article will point out issues to keep in mind when evaluating multiple studies, such as variations in design and study populations. C1 [Alosh, Mohamed; Fritsch, Kathleen; Soukup, Mat] US FDA, Div Biometr 3, Off Biostat, Off Translat Sci,CDER, Silver Spring, MD USA. [Wilkin, Jonathan] Wilkin Consulting LLC, Columbus, OH USA. RP Alosh, M (reprint author), Bldg 21,Room 3626 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Mohamed.Alosh@fda.hhs.gov NR 7 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1396-0296 J9 DERMATOL THER JI Dermatol. Ther. PD MAY-JUN PY 2009 VL 22 IS 3 BP 199 EP 203 DI 10.1111/j.1529-8019.2009.01232.x PG 5 WC Dermatology SC Dermatology GA 441KX UT WOS:000265768900003 PM 19453343 ER PT J AU Weaver, J La Grenade, L Kwon, H Avigan, M AF Weaver, Joyce La Grenade, Lois Kwon, Hyon Avigan, Mark TI Finding, evaluating, and managing drug-related risks: approaches taken by the US Food and Drug Administration (FDA) SO DERMATOLOGIC THERAPY LA English DT Article DE pharmaceutical risk; postmarketing product surveillance ID PHARMACOGENOMIC BIOMARKERS; GENETIC SUSCEPTIBILITY; MANAGEMENT PROGRAM; PUVA; HYPERSENSITIVITY; CARBAMAZEPINE; CYCLOSPORINE; INFLIXIMAB; CARCINOMA; ABACAVIR AB Marketed pharmaceuticals are evaluated for safety by the US Food and Drug Administration (FDA) throughout the life cycle of the products. The FDA uses data from controlled clinical trials, from postmarketing case reports reported to the FDA's Adverse Event Reporting System, from epidemiological studies, and from registries to evaluate the safety of approved products. For some products, including some products used in dermatologic medicine, risks become apparent during the postmarketing period that require additional measures beyond product labeling and routine pharmacovigilance. The FDA continues to seek additional tools to assess risk, including pharmacogenomic biomarkers for adverse drug reactions and the use of large medical record and epidemiological databases for the systematic detection and characterization of drug-associated safety outcomes. C1 [Kwon, Hyon; Avigan, Mark] US FDA, Div Pharmacovigilance 1, CDER, Off Surveillance & Epidemiol, Silver Spring, MD 20933 USA. [Weaver, Joyce] US FDA, Div Risk Management, CDER, Off Surveillance & Epidemiol, Silver Spring, MD 20933 USA. [La Grenade, Lois] US FDA, Div Epidemiol, CDER, Off Surveillance & Epidemiol, Silver Spring, MD 20933 USA. RP Avigan, M (reprint author), US FDA, Div Pharmacovigilance 1, CDER, Off Surveillance & Epidemiol, Bldg 22,Room 3478,10903 New Hampshire Ave, Silver Spring, MD 20933 USA. EM mark.avigan@fda.hhs.gov NR 45 TC 9 Z9 10 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1396-0296 J9 DERMATOL THER JI Dermatol. Ther. PD MAY-JUN PY 2009 VL 22 IS 3 BP 204 EP 215 DI 10.1111/j.1529-8019.2009.01233.x PG 12 WC Dermatology SC Dermatology GA 441KX UT WOS:000265768900004 PM 19453344 ER PT J AU Peters, JR Hixon, DR Conner, DP Davit, BM Catterson, DM Parise, CM AF Peters, John R. Hixon, Dena R. Conner, Dale P. Davit, Barbara M. Catterson, Debra M. Parise, Cecelia M. TI Generic drugs - safe, effective, and affordable SO DERMATOLOGIC THERAPY LA English DT Article DE bioequivalence; FDA; generic; substitution; topical ID BIOEQUIVALENCE; SUBSTITUTION; EQUIVALENCE; PHYSICIAN; ISSUES; ASSAY AB This article discusses the history and evolution of the process for generic drug evaluation and approval in the United States, with emphasis on locally acting dermatologic products. The requirements for in vivo bioequivalence (BE) testing and the statistical criteria for BE are discussed, and an example of a topical antifungal dermatologic product is used to demonstrate the BE determination for locally acting drugs. Other factors in the dispensing of prescription medications that are not within the Food and Drug Administration regulatory authority are also mentioned. C1 [Hixon, Dena R.] US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Rockville, MD 20855 USA. RP Hixon, DR (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, 7520 Standish Pl 2210, Rockville, MD 20855 USA. EM dena.hixon@fda.hhs.gov RI Mendoza, Elvia/A-9361-2012 NR 35 TC 15 Z9 15 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1396-0296 J9 DERMATOL THER JI Dermatol. Ther. PD MAY-JUN PY 2009 VL 22 IS 3 BP 229 EP 240 DI 10.1111/j.1529-8019.2009.01236.x PG 12 WC Dermatology SC Dermatology GA 441KX UT WOS:000265768900007 PM 19453347 ER PT J AU Dang, JM Krause, D Felten, RP Luke, MK AF Dang, Jiyoung M. Krause, David Felten, Richard P. Luke, Markham K. TI Medical device regulation: what a practicing dermatologist should know SO DERMATOLOGIC THERAPY LA English DT Article DE CDRH; dermal filler; FDA; medical device; regulation AB The practicing dermatologist uses many medical devices during his or her day-to-day practice. The authors present a broad overview of how such medical devices are reviewed for safety and reasonable assurance of effectiveness, and evaluated for classification prior to marketing in the United States by the Food and Drug Administration. The specific example of dermal fillers as a class III medical device is discussed together with its regulatory ramifications. This article is written by staff currently employed at the Center for Devices and Radiological Health and should provide information useful to the practicing dermatologist. C1 [Dang, Jiyoung M.; Krause, David; Felten, Richard P.; Luke, Markham K.] US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Rockville, MD 20850 USA. RP Luke, MK (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, 9200 Corp Blvd, Rockville, MD 20850 USA. EM markham.luke@fda.hhs.gov NR 0 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1396-0296 J9 DERMATOL THER JI Dermatol. Ther. PD MAY-JUN PY 2009 VL 22 IS 3 BP 241 EP 245 DI 10.1111/j.1529-8019.2009.01237.x PG 5 WC Dermatology SC Dermatology GA 441KX UT WOS:000265768900008 PM 19453348 ER PT J AU Lindstrom, JA AF Lindstrom, Jill A. TI Sources of drug information: FDA-approved labeling and other official FDA sources SO DERMATOLOGIC THERAPY LA English DT Article DE Food and Drug Administration; labeling; safety AB To protect the public health and facilitate the safe and effective use of prescription drugs, the Food and Drug Administration (FDA) disseminates information through drug labeling, communication of safety issues, and the archiving of scientific reviews. The content and format requirements for professional labeling were revised in 2006 to improve the accessibility and usability of the information. New or emerging safety information is communicated using the formats of public health advisories (PHAs), information for heath care professional sheets, and early communications about ongoing safety reviews. The FDA analyses of approved drug marketing applications and Advisory Committee transcripts are posted on the FDA Web site. Prescribers can utilize these resources to inform the care that they provide to patients. C1 US FDA, Silver Spring, MD 20993 USA. RP Lindstrom, JA (reprint author), US FDA, 10903 New Hampshire Ave,Bldg 22,Rm 5162, Silver Spring, MD 20993 USA. EM jill.lindstrom@fda.hhs.gov NR 23 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1396-0296 J9 DERMATOL THER JI Dermatol. Ther. PD MAY-JUN PY 2009 VL 22 IS 3 BP 246 EP 256 DI 10.1111/j.1529-8019.2009.01238.x PG 11 WC Dermatology SC Dermatology GA 441KX UT WOS:000265768900009 PM 19453349 ER PT J AU Mathis, L Rodriguez, W AF Mathis, Lisa Rodriguez, William TI Drug therapy in pediatrics: a developing field SO DERMATOLOGIC THERAPY LA English DT Article DE dermatologic; pediatrics; therapeutics AB For many years, drug therapies were not explicitly studied in the pediatric population. The lack of data forced clinicians to treat children using empiric therapy, often guessing at the treatment dose. In addition to the lack of dosing information, there was no evidence that a product would be safe and efficacious in this unique population. Because dermatologic conditions are common in children, this lack of information affected dermatologists. In 1998, a new legislation passed that encouraged drug development in pediatrics. Additional legislation followed that allowed the Food and Drug Administration the authority to require studies in pediatrics when it was anticipated that a product would be used in the pediatric population. With the new legislation and a better understanding of differences in the dose effectiveness and safety profiles of drugs in children when compared with adults, evidence-based treatment of pediatric patients is now possible. C1 [Mathis, Lisa] US FDA, Off New Drugs, Silver Spring, MD 20903 USA. [Rodriguez, William] US FDA, Off Pediat Therapeut, Off Commissioner, Rockville, MD 20857 USA. RP Mathis, L (reprint author), US FDA, Off New Drugs, 10903 New Hampshire Ave,Rm 6414, Silver Spring, MD 20903 USA. EM lisa.mathis@fda.hhs.gov NR 11 TC 5 Z9 6 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1396-0296 J9 DERMATOL THER JI Dermatol. Ther. PD MAY-JUN PY 2009 VL 22 IS 3 BP 257 EP 261 DI 10.1111/j.1529-8019.2009.01239.x PG 5 WC Dermatology SC Dermatology GA 441KX UT WOS:000265768900010 PM 19453350 ER PT J AU Beilke, LD Aleksunes, LM Holland, RD Besselsen, DG Beger, RD Klaassen, CD Cherrington, NJ AF Beilke, Lisa D. Aleksunes, Lauren M. Holland, Ricky D. Besselsen, David G. Beger, Rick D. Klaassen, Curtis D. Cherrington, Nathan J. TI Constitutive Androstane Receptor-Mediated Changes in Bile Acid Composition Contributes to Hepatoprotection from Lithocholic Acid-Induced Liver Injury in Mice SO DRUG METABOLISM AND DISPOSITION LA English DT Article; Proceedings Paper CT Annual Meeting of the Mountain West Regional Chapter of the Society-of-Toxicology CY SEP 06-07, 2007 CL Breckenridge, CO SP Soc Toxicol, Mt W Reg Chapter ID PREGNANE-X-RECEPTOR; OBSTRUCTIVE CHOLESTASIS; NUCLEAR RECEPTORS; MOUSE-LIVER; TOXICITY; CAR; PXR; DETOXIFICATION; ENZYMES; SULFOTRANSFERASE AB Pharmacological activation of the constitutive androstane receptor (CAR) protects the liver during cholestasis. The current study evaluates how activation of CAR influences genes involved in bile acid biosynthesis as a mechanism of hepatoprotection during bile acid-induced liver injury. CAR activators phenobarbital (PB) and 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP) or corn oil (CO) were administered to C57BL/6 wild-type (WT) and CAR knockout (CAR-null) mice before and during induction of intrahepatic cholestasis using the secondary bile acid, lithocholic acid (LCA). In LCA-treated WT and all the CAR-null groups (excluding controls), histology revealed severe multifocal necrosis. This pathology was absent in WT mice pretreated with PB and TCPOBOP, indicating CAR-dependent hepatoprotection. Decreases in total hepatic bile acids and hepatic monohydroxy, dihydroxy, and trihydroxy bile acids in PB-and TCPOBOP-pretreated WT mice correlated with hepatoprotection. In comparison, concentrations of monohydroxylated and dihydroxylated bile acids were increased in all the treated CAR-null mice compared with CO controls. Along with several other enzymes (Cyp7b1, Cyp27a1, Cyp39a1), Cyp8b1 expression was increased in hepatoprotected mice, which could be suggestive of a shift in the bile acid biosynthesis pathway toward the formation of less toxic bile acids. In CAR-null mice, these changes in gene expression were not different among treatment groups. These results suggest CAR mediates a shift in bile acid biosynthesis toward the formation of less toxic bile acids, as well as a decrease in hepatic bile acid concentrations. We propose that these combined CAR-mediated effects may contribute to the hepatoprotection observed during LCA-induced liver injury. C1 [Beilke, Lisa D.; Cherrington, Nathan J.] Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA. [Besselsen, David G.] Univ Arizona, Dept Vet Sci Microbiol, Tucson, AZ 85721 USA. [Aleksunes, Lauren M.; Klaassen, Curtis D.] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66103 USA. [Holland, Ricky D.; Beger, Rick D.] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. RP Cherrington, NJ (reprint author), Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, 1703 E Mabel, Tucson, AZ 85721 USA. EM cherrington@pharmacy.arizona.edu FU NIDDK NIH HHS [R01 DK068039, DK068039]; NIEHS NIH HHS [ES011646] NR 36 TC 31 Z9 31 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD MAY PY 2009 VL 37 IS 5 BP 1035 EP 1045 DI 10.1124/dmd.108.023317 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 434JC UT WOS:000265270000014 PM 19196849 ER PT J AU Pogribny, IP Frederick, A AF Pogribny, Igor P. Frederick, A. TI MicroRNAome Dysregulation during Chemical Carcinogenesis SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 11th European Regional ISSX Meeting CY MAY 17-20, 2009 CL Lisbon, PORTUGAL C1 [Pogribny, Igor P.; Frederick, A.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PD MAY PY 2009 VL 41 SU 1 MA 20 BP 9 EP 10 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 628ZW UT WOS:000280164800018 ER PT J AU Wang, J AF Wang, Jian TI CYP3A polymorphisms and immunosuppressive drugs in solid-organ transplantation SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE ciclosporin; CYP3A; immunosuppression; pharmacogenomic; pharmacokinetic; polymorphism; sirolimus; solid-organ transplantation; tacrolimus ID SINGLE-NUCLEOTIDE POLYMORPHISMS; TACROLIMUS DOSE REQUIREMENTS; MDR1 GENETIC POLYMORPHISMS; RENAL-TRANSPLANT; CYCLOSPORINE PHARMACOKINETICS; ABCB1 POLYMORPHISMS; POPULATION PHARMACOKINETICS; KIDNEY-TRANSPLANTATION; TROUGH CONCENTRATIONS; CYTOCHROME P4503A5 AB Most immunosuppressive drugs have a narrow therapeutic index and large interpatient variabilities in their pharmacokinetic and pharmacodynamic profiles. Identification of functional single-nucleotide polymorphisms in genes encoding for drug metabolizing enzymes has great potential to improve the drug efficacy and safety profiles, since these genetic factors may be important biomarkers for individualization of immunosuppressive therapy. This article summarizes current knowledge regarding the impact of CYP3A polymorphisms on immunosuppressive drug pharmacokinetics. Many retrospective studies have shown a clear relationship between CYP3A5*1/*3 polymorphism and tacrolimus pharmacokinetics, while the influence of CYP3A5*1/*3 or CYP3A4*/*1B on ciclosporin and sirolimus exposure are still questionable. CYP3A polymorphisms may partially contribute to the clinical variability of the enzyme-mediated drug interactions. Drug-drug interactions may also influence the phenotypic consequence of CYP3A polymorphisms. Population pharmacodynamic/kinetic/genomic modeling was proposed as an emerging and promising approach to quantitatively explore the contribution of genetic polymorphisms to the large interpatient variability in the pharmacokinetic and pharmacodynamic profiles of immunosuppressive drugs. Prospective, randomized studies in large patient populations are needed to further clarify the genetic effects of CYP3A on immunosuppressive drug exposure and response. C1 US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Wang, J (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51,Room 2155, Silver Spring, MD 20993 USA. EM jian.wang@fda.hhs.gov NR 58 TC 13 Z9 15 U1 1 U2 4 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD MAY PY 2009 VL 9 IS 4 BP 383 EP 390 DI 10.1586/ERM.09.11 PG 8 WC Pathology SC Pathology GA 446SC UT WOS:000266140400009 PM 19435458 ER PT J AU Park, S Witten, JM Myers, KJ AF Park, Subok Witten, Joel M. Myers, Kyle J. TI Singular Vectors of a Linear Imaging System as Efficient Channels for the Bayesian Ideal Observer SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Bayesian ideal observer; efficient channels; image quality; linear imaging system AB The Bayesian ideal observer provides an absolute upper bound for diagnostic performance of an imaging system and hence should be used for the assessment of image quality whenever possible. However, computation of ideal-observer performance in clinical tasks is difficult since the probability density functions of the data required for this observer are often unknown in tasks involving realistic, complex backgrounds. Moreover, the high dimensionality of the integrals that need to be calculated for the observer makes the computation more difficult. The ideal observer constrained to a set of channels, which we call a channelized-ideal observer (CIO), can reduce the dimensionality of the problem. These channels are called efficient if the CIO can approximate ideal-observer performance. In this paper, we propose a method to choose efficient channels for the ideal observer based on a singular value decomposition of a linear imaging system. As a demonstration, we test our method on detection tasks using non-Gaussian lumpy backgrounds and signals of Gaussian and elliptical profiles. Our simulation results show that singular vectors associated with either the background or the signal are highly efficient for the ideal observer for detecting both types of signals. In addition, this CIO outperforms a channelized-Hotelling observer with the same channels. C1 [Park, Subok; Myers, Kyle J.] US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Div Imaging & Appl Math, Ctr Devices & Radiol Hlth, White Oak, MD 20993 USA. [Witten, Joel M.] Univ Maryland, Dept Math, College Pk, MD 20742 USA. RP Park, S (reprint author), US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Div Imaging & Appl Math, Ctr Devices & Radiol Hlth, White Oak, MD 20993 USA. EM subok.park@fda.hhs.gov NR 11 TC 12 Z9 12 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD MAY PY 2009 VL 28 IS 5 BP 657 EP 668 DI 10.1109/TMI.2008.2008967 PG 12 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 441DB UT WOS:000265748400003 PM 19272990 ER PT J AU Badano, A Kyprianou, IS Freed, M Jennings, RJ Sempau, J AF Badano, Aldo Kyprianou, Iacovos S. Freed, Melanie Jennings, Robert J. Sempau, Josep TI Effect of Oblique X-ray Incidence in Flat-Panel Computed Tomography of the Breast SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Breast computed tomography (CT); Cesium Iodide; Monte Carlo simulation; phosphor blur; phosphor screen ID MONTE-CARLO-SIMULATION; ANISOTROPIC IMAGING PERFORMANCE; POINT-SPREAD FUNCTION; CODE PENELOPE; CT SCANNER; ELECTRON; TOMOSYNTHESIS; RESOLUTION; LEKSELL-GAMMA-KNIFE(R); COLLECTION AB We quantify the variation in resolution due to anisotropy caused by oblique X-ray incidence in indirect flat-panel detectors for computed tomography breast imaging systems. We consider a geometry and detector type utilized in breast computed tomography (CT) systems currently being developed. Our methods rely on MANTIS, a combined X-ray, electron, and optical Monte Carlo transport open source code. The physics models are the most accurate available in general-purpose Monte Carlo packages in the diagnostic energy range. We consider maximum-obliquity angles of 10 degrees and 13 degrees at the centers of the 30 and 40 cm detector edges, respectively, and 160 at the corner of the detector. Our results indicate that blur is asymmetric and that the resolution properties vary significantly with the angle (or location) of incidence. Our results suggest that the asymmetry can be as high as a factor of 2.6 between orthogonal directions. Anisotropy maps predicted by MANTIS provide an understanding of the effect that such variations have on the imaging system and allow more accurate modeling and optimization of breast CT systems. These maps of anisotropy across the detector could lead to improved reconstruction and help motivate physics-based strategies for computer detection of breast lesions. C1 [Badano, Aldo; Kyprianou, Iacovos S.; Freed, Melanie; Jennings, Robert J.] US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Div Imaging & Appl Math, Off Sci & Engn Labs,Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Sempau, Josep] Biomat & Nanomed CIBER BBN, Spanish Networking Res Ctr Bioengn, Zaragoza 20018, Spain. RP Badano, A (reprint author), US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Div Imaging & Appl Math, Off Sci & Engn Labs,Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM aldo.badano@fda.hhs.gov RI Sempau, Josep/J-7834-2013; OI Sempau, Josep/0000-0002-2754-7685; badano, aldo/0000-0003-3712-6670 NR 38 TC 8 Z9 8 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD MAY PY 2009 VL 28 IS 5 BP 696 EP 702 DI 10.1109/TMI.2008.2010443 PG 7 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 441DB UT WOS:000265748400007 PM 19272986 ER PT J AU Joshi, BH Puri, RK AF Joshi, Bharat H. Puri, Raj K. TI IL-13 receptor-alpha 2: a novel target for cancer therapy SO IMMUNOTHERAPY LA English DT Editorial Material ID CONVECTION-ENHANCED DELIVERY; RECURRENT MALIGNANT GLIOMA; INTERLEUKIN (IL)-13 BINDING; CHIMERIC FUSION PROTEINS; CARCINOMA CELL-LINES; COMMON GAMMA-CHAIN; SIGNAL-TRANSDUCTION; PSEUDOMONAS EXOTOXIN; ALPHA-2 CHAIN; NECK-CANCER C1 [Joshi, Bharat H.; Puri, Raj K.] US FDA, Ctr Biol Evaluat & Res, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, NIH Bldg 29B,Room 2NN20, Bethesda, MD 20892 USA. EM bharat.joshi@fda.hhs.gov; raj.puri@fda.hhs.gov NR 79 TC 10 Z9 12 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-743X J9 IMMUNOTHERAPY JI Immunotherapy PD MAY PY 2009 VL 1 IS 3 BP 321 EP 327 DI 10.2217/IMT.09.8 PG 7 WC Immunology SC Immunology GA 546RA UT WOS:000273826800001 PM 20635949 ER PT J AU Collazo, CM Meierovics, AI De Pascalis, R Wu, TH Lyons, CR Elkins, KL AF Collazo, Carmen M. Meierovics, Anda I. De Pascalis, Roberto Wu, Terry H. Lyons, C. Rick Elkins, Karen L. TI T Cells from Lungs and Livers of Francisella tularensis-Immune Mice Control the Growth of Intracellular Bacteria SO INFECTION AND IMMUNITY LA English DT Article ID VACCINE STRAIN INFECTION; GAMMA-INTERFERON; PROTECTIVE IMMUNITY; IFN-GAMMA; NK CELLS; INTRANASAL VACCINATION; PULMONARY INFECTION; IN-VIVO; TULAREMIA; LVS AB Parenteral and respiratory vaccinations with the intracellular bacterium Francisella tularensis have been studied using the live vaccine strain (LVS) in a mouse model, and spleen cells from immune mice are often used for immunological studies. However, mechanisms of host immunological responses may be different in non-lymphoid organs that are important sites of infection, such as lung and liver. Using parenteral (intradermal) or respiratory (cloud aerosol) vaccination, here we examine the functions of resulting LVS-immune liver or lung cells, respectively. Surprisingly, LVS was considerably more virulent when administered by cloud aerosol than by intranasal instillation, suggesting method-dependent differences in initial localization and/or dissemination patterns. Only low doses were sublethal, and resolution of sublethal cloud aerosol infection was dependent on gamma interferon (IFN-gamma), tumor necrosis factor alpha, and inducible nitric oxide synthase. Nonetheless, survival of cloud aerosol or parenteral infection resulted in the development of a protective immune response against lethal LVS intraperitoneal or aerosol challenge, reflecting development of systemic secondary immunity in both cases. Such immunity was further detected by directly examining the functions of LVS-immune lung or liver lymphocytes in vitro. Lung lymphocytes primed by respiratory infection, as well as liver lymphocytes primed by parenteral infection, clearly controlled in vitro intracellular bacterial growth primarily via mechanisms that were not dependent on IFN-gamma activity. Thus, our results indicate functional similarities between immune T cells residing in spleens, livers, and lungs of LVS-immune mice. C1 [Collazo, Carmen M.; Meierovics, Anda I.; De Pascalis, Roberto; Elkins, Karen L.] US FDA, Lab Mycobacterial Dis & Cellular Immunol, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Wu, Terry H.; Lyons, C. Rick] Univ New Mexico, Dept Internal Med, Hlth Sci Ctr, Albuquerque, NM 87131 USA. RP Elkins, KL (reprint author), 1401 Rockville Pike,HFM 431, Rockville, MD 20852 USA. EM karen.elkins@fda.hhs.gov FU National Institute of Allergy and Infectious Diseases [Y1-AI-615301/224-06-1322]; NIAID Public Health Service [PO1 AI056295]; NIH, Bethesda FX This work was supported in part by an interagency agreement with the National Institute of Allergy and Infectious Diseases (Y1-AI-615301/224-06-1322) and NIAID Public Health Service Grant PO1 AI056295, NIH, Bethesda, MD. NR 43 TC 12 Z9 12 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 2009 VL 77 IS 5 BP 2010 EP 2021 DI 10.1128/IAI.01322-08 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 434MX UT WOS:000265279900030 PM 19237526 ER PT J AU Von Tungeln, LS Churchwell, MI Doerge, DR Shaddock, JG McGarrity, LJ Heflich, RH da Costa, GG Marques, MM Beland, FA AF Von Tungeln, Linda S. Churchwell, Mona I. Doerge, Daniel R. Shaddock, Joseph G. McGarrity, Lynda J. Heflich, Robert H. da Costa, Goncalo Gamboa Marques, M. Matilde Beland, Frederick A. TI DNA adduct formation and induction of micronuclei and mutations in B6C3F(1)/Tk mice treated neonatally with acrylamide or glycidamide SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE acrylamide; glycidamide; DNA adducts; micronuclei; mutations ID HPRT LYMPHOCYTE MUTANTS; MOUSE TUMORIGENICITY BIOASSAY; BONE-MARROW MICRONUCLEI; ETHYL-N-NITROSOUREA; HEMOGLOBIN ADDUCTS; MAILLARD REACTION; FISCHER-344 RATS; MAMMALIAN-CELLS; DRINKING-WATER; T-LYMPHOCYTES AB Acrylamide, a food contaminant, is carcinogenic in experimental animals, with both genotoxic and nongenotoxic pathways being proposed. To obtain information regarding mechanisms of acrylamide tumorigenesis, we compared the extent of DNA adduct formation and induction of micronuclei and mutations in mice treated neonatally with acrylamide and its electrophilic metabolite glycidamide. Male and female B6C3F(1)/Tk mice were treated intraperitoneally on postnatal days (PNDs) 1, 8 and 15 or PNDs 1-8 with 0.14 or 0.70 mmol acrylamide or glycidamide per kg body weight per day. One day after the final dose, B6C3F(1)/Tk(+/+) mice were killed to measure DNA adduct levels and peripheral blood micronuclei. Three weeks after the last treatment, B6C3F(1)/Tk(+/-) mice were killed to assess the Hprt and Tk mutant frequencies in spleen lymphocytes. The levels of N7-(2-carbamoyl-2-hydroxy- ethyl)guanine, the major glycidamide-DNA adduct, decreased in the order 0.70 mmol glycidamide > 0.70 mmol acrylamide > 0.14 mmol glycidamide - 0.14 mmol acrylamide. Only glycidamide increased the frequency of micronucleated reticulocytes and normochromatic erythrocytes. In mice treated on PNDs 1, 8 and 15, the Hprt mutant frequency was increased by 0.70 mmol glycidamide. In mice dosed on PNDs 1-8, 0.70 mmol glycidamide caused extensive mortality; each of the other treatments increased the Tk mutant frequency, whereas acrylamide increased the Hprt mutant frequency. These data suggest that the mutagenic response in neonatal mice treated on PNDs 1, 8 and 15 is due to glycidamide, whereas mutations resulting from dosing on PNDs 1-8 are due to another mechanism. (C) 2008 Wiley-Liss, Inc. C1 [Von Tungeln, Linda S.; Churchwell, Mona I.; Doerge, Daniel R.; da Costa, Goncalo Gamboa; Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Shaddock, Joseph G.; McGarrity, Lynda J.; Heflich, Robert H.] Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [da Costa, Goncalo Gamboa; Marques, M. Matilde] Univ Tecn Lisboa, Inst Super Tecn, Ctr Quim Estrutural, P-1096 Lisbon, Portugal. RP Beland, FA (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT 110, Jefferson, AR 72079 USA. EM frederick.beland@fda.hhs.gov RI Marques, M. Matilde/E-2535-2012; PTMS, RNEM/C-1589-2014 OI Marques, M. Matilde/0000-0002-7526-4962; FU National Institute for Environmental Health Sciences/National Toxicology Program [224-07-0007]; Fundacao para a Ciencia e a Tecnologia (FCT), Portugal FX Grant sponsor: National Institute for Environmental Health Sciences/National Toxicology Program; IAG number: 224-07-0007. Grant sponsor Fundacao para a Ciencia e a Tecnologia (FCT), Portugal. NR 55 TC 16 Z9 16 U1 1 U2 19 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 1 PY 2009 VL 124 IS 9 BP 2006 EP 2015 DI 10.1002/ijc.24165 PG 10 WC Oncology SC Oncology GA 425OS UT WOS:000264647600002 PM 19123476 ER PT J AU Fein, SB AF Fein, Sara B. TI Exclusive breastfeeding for under-6-month-old children SO JORNAL DE PEDIATRIA LA English DT Editorial Material ID BRAZIL C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Fein, SB (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM sara.fein@fda.hhs.gov NR 12 TC 3 Z9 3 U1 0 U2 0 PU SOC BRASIL PEDIATRIA PI RIO DE JANEIRO, RJ PA RUA SANTA CLARA 292, RIO DE JANEIRO, RJ, CEP 22401-01, BRAZIL SN 0021-7557 J9 J PEDIAT-BRAZIL JI J. Pediatr. PD MAY-JUN PY 2009 VL 85 IS 3 BP 181 EP 182 DI 10.2223/JPED.1905 PG 2 WC Pediatrics SC Pediatrics GA 466ZO UT WOS:000267704900001 PM 19492177 ER PT J AU Wilson, P AF Wilson, Phyllis TI Development and Validation of a Liquid Chromatographic Method for the Simultaneous Determination of Estradiol, Estriol, Estrone, and Progesterone in Pharmaceutical Preparations SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID BREAST-CANCER; STEROID-HORMONES; THERAPY; TEMPERATURE; PROGESTINS; SEPARATION; ESTROGENS; RISK AB Progesterone and estrogens are hormones produced in the human body that are essential for regulating many vital functions. The three major estrogens produced by women are estriol, estradiol, and estrone. Progesterone is a naturally occurring hormone in both men and women. Pharmaceuticals containing estrogens alone or estrogens in combination with progesterone are commonly used in therapy. Patients requiring unique combinations of the drugs rely on pharmacies to compound the ingredients. In order to assess the potency of drugs containing combinations of estrogens and progesterone, a method was developed to determine all four ingredients simultaneously. The liquid chromatographic method utilized a mu Bondapak C18 column with an isocratic mobile phase of acetonitrile-water (50 + 50, v/v) at a flow rate of 1.0 mL/min and temperature of 30 degrees C. Under these conditions, the order of elution was estriol, estradiol, and estrone, followed by progesterone. UV detection was at 205 nm to monitor elution of the estrogens, then switched to 270 nm to monitor progesterone. The method was applied to the analysis of pharmacy-compounded drugs containing combinations of the hormones. Validation studies demonstrated that the method is accurate and precise. C1 US FDA, Jamaica, NY 11433 USA. RP Wilson, P (reprint author), US FDA, 158-15 Liberty Ave, Jamaica, NY 11433 USA. EM phyllis.wilson@fda.hhs.gov FU U.S. Food and Drug Administration, Office of Women's Health FX This report was supported by a grant from the U.S. Food and Drug Administration, Office of Women's Health. I would like to thank Ales Vancura for scientific discussions. NR 17 TC 6 Z9 6 U1 0 U2 5 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 2009 VL 92 IS 3 BP 846 EP 854 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 454LW UT WOS:000266684500023 PM 19610377 ER PT J AU Chen, Y Hammack, TS Song, KY Lampel, KA AF Chen, Yi Hammack, Thomas S. Song, Kwang-Young Lampel, Keith A. TI Evaluation of a Revised US Food and Drug Administration Method for the Detection and Isolation of Enterobacter sakazakii in Powdered Infant Formula: Precollaborative Study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A revised U.S. Food and Drug Administration (FDA) method for the detection and isolation of Enterobacter sakazakii in powdered infant formula was developed based on real-time PCR technology complemented by culture isolation on chromogenic agars. A validation study was conducted to compare the revised FDA method to the reference FDA method. Casein and soy powdered infant formula inoculated with morphologically typical and atypical strains of E sakazakii were analyzed. Valid results were obtained from 360 test portions and controls and showed that the revised FDA method is significantly better (P < 0.05) than the reference FDA method for the detection of typical E. sakazakii strains and the two methods are equivalent for the detection of atypical E. sakazakii strains. C1 [Chen, Yi; Hammack, Thomas S.; Song, Kwang-Young; Lampel, Keith A.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Lampel, KA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM keith.lampel@fda.hhs.gov RI Zhou, Tian/J-7175-2012 NR 10 TC 13 Z9 13 U1 0 U2 3 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 2009 VL 92 IS 3 BP 862 EP 872 PG 11 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 454LW UT WOS:000266684500025 PM 19610379 ER PT J AU Harp, BP Scher, AL Yang, HHW Brodie, DL Sullivan, MP Barrows, JN AF Harp, Bhakti Petigara Scher, Alan L. Yang, Huei-Hsuan W. Brodie, Darlene L. Sullivan, Michael P. Barrows, Julie N. TI Reversed-Phase LC Determination of Two Manufacturing Intermediates, the Unsulfonated Subsidiary Color, and 4-Methyl-Sudan I in D&C Red No. 6, D&C Red No. 7, and Their Lakes SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LIQUID-CHROMATOGRAPHY; SUDAN-I; FOOD; DRUG; DYES AB A reversed-phase liquid chromatographic (LC) method was developed to determine 4 impurities in the monosulfo monoazo color additives D&C Red No. 6, D&C Red No. 7, and their lakes. Manufacturing intermediates determined are 2-amino-5-methylbenzenesulfonic acid (PTMS) and 3-hydroxy-2-naphthalenecarboxylic acid (3-hydroxy-2-naphthoic acid). Subsidiary colors determined are the unsulfonated and uncarboxylated, unsulfonated homologs of the dye (the unsulfonated subsidiary color and 4-methyl-Sudan I). The new method uses lithium oxalate as part of a novel system to dissolve the water-insoluble color additives. The 4 impurities were identified by LC and UV-visible spectrophotometry; the 4-methyl-Sudan I was confirmed by LC/mass spectrometry. LC peak area calibrations were generally linear (R > 0.999), and recoveries ranged from 90 to 105%. The limits of determination used were 0.02% each for PTMS and 3-hydroxy-2-naphthoic acid, 0.1% for the unsulfonated subsidiary color, and 0.002% for 4-methyl-Sudan I. The relative standard deviations at the specification levels ranged from 0.7 to 22.7%. Survey analyses of 26 samples of certified D&C Red Nos. 6 and 7 straight colors and lakes from 11 domestic and foreign manufacturers yielded results that agree with those previously obtained using 3 other methods. C1 [Harp, Bhakti Petigara; Scher, Alan L.; Yang, Huei-Hsuan W.; Brodie, Darlene L.; Sullivan, Michael P.; Barrows, Julie N.] US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, College Pk, MD 20740 USA. RP Harp, BP (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM bhakti.petigara@fda.hhs.gov NR 18 TC 7 Z9 7 U1 0 U2 3 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 2009 VL 92 IS 3 BP 888 EP 895 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 454LW UT WOS:000266684500028 PM 19610382 ER PT J AU Casanova, MF El-Baz, A Mott, M Mannheim, G Hassan, H Fahmi, R Giedd, J Rumsey, JM Switala, AE Farag, A AF Casanova, Manuel F. El-Baz, Ayman Mott, Meghan Mannheim, Glenn Hassan, Hossam Fahmi, Rachid Giedd, Jay Rumsey, Judith M. Switala, Andrew E. Farag, Aly TI Reduced Gyral Window and Corpus Callosum Size in Autism: Possible Macroscopic Correlates of a Minicolumnopathy SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autistic disorder; Corpus callosum; Magnetic resonance imaging; Telencephalon ID MATTER VOLUME INCREASE; CEREBRAL-CORTEX; BRAIN SIZE; WHITE-MATTER; INFANTILE-AUTISM; GYRIFICATION; ABNORMALITIES; EVOLUTION; GROWTH; MRI AB Minicolumnar changes that generalize throughout a significant portion of the cortex have macroscopic structural correlates that may be visualized with modern structural neuroimaging techniques. In magnetic resonance images (MRIs) of fourteen autistic patients and 28 controls, the present study found macroscopic morphological correlates to recent neuropathological findings suggesting a minicolumnopathy in autism. Autistic patients manifested a significant reduction in the aperture for afferent/efferent cortical connections, i.e., gyral window. Furthermore, the size of the gyral window directly correlated to the size of the corpus callosum. A reduced gyral window constrains the possible size of projection fibers and biases connectivity towards shorter corticocortical fibers at the expense of longer association/commisural fibers. The findings may help explain abnormalities in motor skill development, differences in postnatal brain growth, and the regression of acquired functions observed in some autistic patients. C1 [Casanova, Manuel F.; Mott, Meghan; Switala, Andrew E.] Univ Louisville, Dept Psychiat, Louisville, KY 40292 USA. [El-Baz, Ayman] Univ Louisville, Dept Bioengn, Louisville, KY 40292 USA. [Mannheim, Glenn] US FDA, Div Psychiat Prod, Silver Spring, MD USA. [Hassan, Hossam; Fahmi, Rachid; Farag, Aly] Univ Louisville, Dept Elect & Comp Engn, Louisville, KY 40292 USA. [Giedd, Jay] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. [Rumsey, Judith M.] NIMH, Neurodev Disorders Branch, Bethesda, MD 20892 USA. RP Casanova, MF (reprint author), Univ Louisville, Dept Psychiat, 500 S Preston St,Bldg 55A Ste 210, Louisville, KY 40292 USA. EM manuel.casanova@louisville.edu RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; El-Baz, Ayman/0000-0001-7264-1323 FU Intramural NIH HHS [ZIA MH002794-08] NR 92 TC 41 Z9 41 U1 3 U2 8 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD MAY PY 2009 VL 39 IS 5 BP 751 EP 764 DI 10.1007/s10803-008-0681-4 PG 14 WC Psychology, Developmental SC Psychology GA 442DP UT WOS:000265820500006 PM 19148739 ER PT J AU Lute, S Brorson, K AF Lute, Scott Brorson, Kurt TI Bacteriophage and impurity carryover and total organic carbon release during extended protein A chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Protein A media; Virus clearance; Virus carryover; International regulatory guidance; Monoclonal antibodies ID REVERSE-TRANSCRIPTASE ASSAY; MAB CELL-CULTURE; MONITOR RETROVIRUS; INTERNAL MEMBRANE; VIRAL EVOLUTION; VIRUS; CLEARANCE; LIFETIME; SCALE; PRD1 AB In the biopharmaceutical industry, column chromatography residuals are routinely assessed by the direct measurement of mock eluates. In this study, we evaluated virus and other impurity carryover between protein A cycles and the feasibility of using a total organic carbon (TOC) analyzer to monitor for column impurity leakage as a correlate for actual measured carryover in mock eluates. Commercial process intermediates were used in scaled down studies of two protein A media, ProSep A (Millipore, Bedford, MA, USA) and MabSelect SuRe (GE Healthcare, Uppsala, Sweden). The chromatography system was programmed to run up to 200 normal load/elution cycles with periodic blank cycles to measure protein and phage carryover, and water flush cycles to measure TOC release. Sustained phage carryover was evident in each study. Carryover and TOC release was lowest in the case where cleaning was most stringent (50 mM NaOH/0.5M Na(2)SO(4) with MabSelect SuRe). The TOC analysis at this time does not appear to be a viable practical means of measuring impurity carryover; direct measurements in mock eluates appears to be more predictive of column performance. Published by Elsevier B.V. C1 [Lute, Scott; Brorson, Kurt] US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Brorson, K (reprint author), US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM kurt.brorson@fda.hhs.gov NR 39 TC 6 Z9 6 U1 2 U2 5 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 MAY 1 PY 2009 VL 1216 IS 18 BP 3774 EP 3783 DI 10.1016/j.chroma.2009.02.050 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 440KT UT WOS:000265699900012 PM 19285678 ER PT J AU Duan, JZ AF Duan, John Z. TI Two Commonly Used Methods for Exposure-Adverse Events Analysis: Comparisons and Evaluations SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE Exposure-response; adverse events; logistic regression; proportional hazard model; time-to-event analysis ID TOXICITY; DIGOXIN AB The purpose of this study is to compare and evaluate logistic regression and time-to-event analysis, 2 commonly used methods for exposure-adverse event (AE) analyses. An AE data set selected from clinical trials is analyzed by both methods and the results are compared. The parameter estimates, odds ratios for logistic regression, and hazard ratios for time-to-event analysis for each AE are compared and further analyzed. In a data set involving 822 patients, 25 AEs are analyzed. A linear relationship is demonstrated between the parameter estimates from the 2 methods and between the odds ratios and hazard ratios. The small differences between the 2 analyses are related to the lower rate of the events and the weaker effects of the risk factors. Although the 2 methods can make predications for the risks, the severity, duration, and recurrence are not well defined. AE time profiles showing the onset, duration, and offset of AEs are important for risk assessment and management. Both analyses can provide information about exposure-AE relationship, and the results from the 2 analyses are consistent in most cases. One should not use the logistic model when length of follow-up varies because of biased estimates. The application of the 2 methods should be combined with AE profiling. C1 US FDA, CDER, Off Clin Pharmacol, Off Translat Sci, Silver Spring, MD 20993 USA. RP Duan, JZ (reprint author), US FDA, CDER, Off Clin Pharmacol, Off Translat Sci, HFD 860,Bldg 51,Room 2166,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM john.duan@fda.hhs.gov NR 24 TC 2 Z9 2 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD MAY PY 2009 VL 49 IS 5 BP 540 EP 552 DI 10.1177/0091270009333485 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 437UD UT WOS:000265511500004 PM 19318526 ER PT J AU Cheng, CM Van, KT Lin, W Ruby, RM AF Cheng, Chorng-Ming Van, Khanh T. Lin, Wen Ruby, Richard M. TI Interlaboratory Validation of a Real-Time PCR 24-Hour Rapid Method for Detection of Salmonella in Foods SO JOURNAL OF FOOD PROTECTION LA English DT Article ID POLYMERASE-CHAIN-REACTION; CHEMICAL TREATMENTS; ALFALFA SEEDS; TYPHIMURIUM; INVA; PRODUCTS; POULTRY; GENES; CELLS; WATER AB The efficacy of a 24-h Salmonella real-time, or quantitative, PCR (qPCR) detection method was assessed through a collaborative effort involving eight Federal and state laboratories. Eleven foods including mashed potatoes, soft cheese, chili powder, chocolate, eggs, sprouts, apple juice, fish, shrimp, ground beef, and ground chicken were tested. For each food, seven blind samples were distributed to each participant for testing. These included six samples equivalently inoculated with I to 5 CFU/25 g of various serotypes of Salmonella (Gaminara, Weltevreden, Heidelberg, Senftenberg, Enteritidis, Newport, Typhimurium, and Kentucky for each food) and 10 to 50 CFU/25 g of the competitor Enterobacter cloacae. The seventh sample was inoculated with 10 to 50 CFU/25 g of the competitor, E. cloacae, only. These samples were tested for Salmonella by using four methods in parallel: (i) 24-h qPCR method detecting Salmonella from modified buffered peptone water enrichment medium; (ii) 48-h qPCR method detecting Salmonella from a secondary selective enrichment broth; (iii) modified Bacteriological Analytical Manual method; and (iv) VIDAS, an immunoassay system. The results of the statistical analysis showed there was no significant (P >= 0.05) difference between either of the qPCR methods and the modified Bacteriological Analytical Manual method for 10 of 11 foods. For the one exception, sprouts, detection by qPCR required 48 h. Both qPCR methods showed a detection limit of 0.08 to 0.2 CFU/g. These results provide a solid basis for using this 24-h qPCR rapid screening method to detect Salmonella in foods. C1 [Cheng, Chorng-Ming; Van, Khanh T.; Ruby, Richard M.] US FDA, Off Regulatory Affairs, Pacific Reg Lab SW, Irvine, CA 92612 USA. [Lin, Wen] US FDA, Off Regulatory Affairs, Div Field Sci, Rockville, MD 20857 USA. RP Cheng, CM (reprint author), US FDA, Off Regulatory Affairs, Pacific Reg Lab SW, 19701 Fairchild, Irvine, CA 92612 USA. EM chorng-ming.cheng@fda.hhs.gov NR 13 TC 24 Z9 24 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 MAY PY 2009 VL 72 IS 5 BP 945 EP 951 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 444BS UT WOS:000265955600004 PM 19517719 ER PT J AU Mahovic, M Bartz, JA Schneider, KR Tenney, JD AF Mahovic, Michael Bartz, Jerry A. Schneider, Keith R. Tenney, Joel D. TI Chlorine Dioxide Gas from an Aqueous Solution: Reduction of Salmonella in Wounds on Tomato Fruit and Movement to Sinks in a Treatment Chamber SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ESCHERICHIA-COLI O157-H7; CAPSICUM-ANNUUM L.; LISTERIA-MONOCYTOGENES; KILLING SALMONELLA; APPLE SURFACES; SANITIZER; INACTIVATION; STRAWBERRIES; EFFICACY; YEASTS AB Chlorine dioxide (ClO(2)) off-gassed from an aqueous solution and reacted incrementally with potassium iodide solutions (sinks). After 30 min, 45% of the initial dose was detected as chlorite ion in the sink, whereas 35% of the initial dose was still in the source. Aqueous solutions of ClO(2) can be used as a source of ClO(2) gas in various laboratory experiments involving treatment of fruits or vegetables. Movement from source to sink is continuous, which precludes the development of large headspace concentrations and the need for a tight chamber seal. When the source solution has dissipated, the chamber can be opened safely as there is little free ClO(2) remaining in the headspace. In tests with whole, wound-inoculated tomato fruit, at both green and pink stages of ripeness, the control of Salmonella enterica serotype Typhimurium in wounds varied with the weight of gas used. The number of viable cells of Typhimurium recovered was reduced by >5 log units when >= 0.5 mg of ClO(2) was applied to three pieces of fruit during a 2-h treatment. C1 [Bartz, Jerry A.] Univ Florida, Dept Plant Pathol, Gainesville, FL 32611 USA. [Schneider, Keith R.] Univ Florida, Dept Food Sci & Human Nutr, Gainesville, FL 32611 USA. [Tenney, Joel D.] ICA TriNova Corp LLC, Newnan, GA USA. [Mahovic, Michael] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Bartz, JA (reprint author), Univ Florida, Dept Plant Pathol, Gainesville, FL 32611 USA. EM softbart@ufl.edu NR 17 TC 10 Z9 10 U1 0 U2 4 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD MAY PY 2009 VL 72 IS 5 BP 952 EP 958 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 444BS UT WOS:000265955600005 PM 19517720 ER PT J AU Rozand, C Feng, PCH AF Rozand, Christine Feng, Peter C. H. TI Specificity Analysis of a Novel Phage-Derived Ligand in an Enzyme-Linked Fluorescent Assay for the Detection of Escherichia coli O157:H7 SO JOURNAL OF FOOD PROTECTION LA English DT Article ID MULTIPLEX PCR; IDENTIFICATION; O157-H7; ANTIGEN; STRAIN; SEROTYPES AB An assay using a phage-derived ligand to capture Escherichia coli O15TH7 prior to antibody detection was evaluated for assay specificity. Analysis of 200 strains showed that the assay was highly specific for the O157 serogroup. It detected all the O157:H7 strains including Shiga toxin-producing O157 nonmotile strains as well as O157 non-H7 strains. In addition, the assay detected various O157:H7 phenotypic variants that are not easily detected by routine analytical methods, as well as a rough strain that did not express O157 antigen and therefore is undetectable serologically. The phage ligand assay showed no cross-reactivity to the other E. coli serotypes. Isolates of Salmonella group N and a few Citrobacter freundii strains that cross-reacted with anti-O157 sera also showed cross-reactivity with the phage ligand. However, other strains that cross-reacted serologically with anti-O157 sera were correctly identified as negative with the phage ligand assay, including several strains of E. coli that nonspecifically autoagglutinate latex reagents. C1 [Feng, Peter C. H.] US FDA, Div Microbiol, College Pk, MD 20740 USA. [Rozand, Christine] Ecole Vet Lyon, Unite Microbiol Alimentaire & Previs, Lyon, France. RP Feng, PCH (reprint author), US FDA, Div Microbiol, College Pk, MD 20740 USA. EM peter.feng@fda.hhs.gov NR 21 TC 6 Z9 6 U1 0 U2 2 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD MAY PY 2009 VL 72 IS 5 BP 1078 EP 1081 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 444BS UT WOS:000265955600022 PM 19517737 ER PT J AU Tang, XB Narayanan, S Peruzzi, G Apara, A Natarajan, K Margulies, DH Coligan, JE Borrego, F AF Tang, Xiaobin Narayanan, Sriram Peruzzi, Giovanna Apara, Akintomide Natarajan, Kannan Margulies, David H. Coligan, John E. Borrego, Francisco TI A Single Residue, Arginine 65, Is Critical for the Functional Interaction of Leukocyte-Associated Inhibitory Receptor-1 with Collagens SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IG-LIKE RECEPTOR-1; T-CELLS; ACTIVATION; LAIR-1; DIFFERENTIATION; EXPRESSION; RESPONSES; LIGANDS; COMPLEX; BINDING AB ITIM-containing receptors play an essential role in modulating immune responses. Leukocyte-associated inhibitory receptor (LAIR)-1, also known as CD305, is an ITIM-containing inhibitory receptor, expressed by all leukocytes, that binds collagens. In this article, we investigate the effect of a conservative R65K mutation on LAIR-1 ligand binding and function. Compared with LAIR-1 wild-type (wt)-expressing cells, LAIR-1 R65K cells show markedly reduced binding to collagen, which correlates with a reduced level of LAIR-1 polarization to the site of interaction with collagens. Both LAIR-1 wt and R65K cells can generate intracellular signals when ligated by anti-LAIR-1 mAb, but only LAIR-1 wt cells respond to collagens or matrigel. In agreement, surface plasmon resonance analyses showed that LAIR-1 R65K protein has markedly reduced avidity for collagen type I compared with LAIR-I wt. Likewise, LAIR-1 R65K protein has decreased avidity for cells expressing transmembrane collagen XVII. Thus, a single residue, Arg65, is critical for the interaction of LAIR-1 with collagens. The Journal of Immunology, 2009, 182: 5446-5452. C1 [Tang, Xiaobin; Narayanan, Sriram; Peruzzi, Giovanna; Apara, Akintomide; Coligan, John E.; Borrego, Francisco] NIAID, Receptor Cell Biol Sect, Immunogenet Lab, Immunol Lab,NIH, Rockville, MD 20852 USA. [Natarajan, Kannan; Margulies, David H.] NIAID, Mol Biol Sect, Immunol Lab, NIH, Rockville, MD 20852 USA. RP Borrego, F (reprint author), US FDA, CDER, Div Monoclonal Antibodies HFD 123, Lab Mol & Dev Immunol, 29 Lincoln Dr,Bldg 29B,Room 3NN18, Bethesda, MD 20892 USA. EM Francisco.Borrego@fda.hhs.gov RI Margulies, David/H-7089-2013; OI Narayanan, Sriram/0000-0002-6484-2800; Margulies, David/0000-0001-8530-7375; Peruzzi, Giovanna/0000-0002-6517-9107 FU National Institute of Allergy and Infectious Diseases FX This work was supported by the intramural program of the National Institute of Allergy and Infectious Diseases. NR 30 TC 17 Z9 18 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2009 VL 182 IS 9 BP 5446 EP 5452 DI 10.4049/jimmunol.0804052 PG 7 WC Immunology SC Immunology GA 563HQ UT WOS:000275119200039 PM 19380792 ER PT J AU Wang, Q Sun, AY Simonyi, A Miller, DK Smith, RE Luchtefeld, RG Korthuis, RJ Sun, GY AF Wang, Qun Sun, Albert Y. Simonyi, Agnes Miller, Dennis K. Smith, Robert E. Luchtefeld, Ronald G. Korthuis, Ronald J. Sun, Grace Y. TI Oral administration of grape polyphenol extract ameliorates cerebral ischemia/reperfusion-induced neuronal damage and behavioral deficits in gerbils: comparison of pre- and post-ischemic administration SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE Grape polyphenols; Ischemia/reperfusion; Oxidative stress; Neuronal death; Glial cell activation; Locomotor activity ID OXIDATIVE STRESS; RESVERATROL PROTECTS; RED WINE; IN-VIVO; NEURODEGENERATIVE DISEASES; ISCHEMIC-STROKE; EMERGING ROLE; KAINIC ACID; DNA-DAMAGE; MECHANISMS AB Oxidative stress has been regarded as an important underlying cause for the delayed neuronal death (DND) after cerebral ischemia. In this study, the effects of short-term oral administration of grape polyphenol extract (GPE) on ischemia/reperfusion (I/R) injury in a gerbil global ischemia model were determined. Ischemia was induced by occlusion of the common carotid arteries for 5 min. GPE (30 mg/ml)-containing formula or formula without GPE was administered daily via gavage for 4 days prior to and/or for 4 days after I/R. I/R resulted in hyperlocomotion, extensive DND, oxidative and fragmented DNA damage, and an increase in reactive astrocytes and microglial cells in the hippocampal CA1 region. GPE administration for 4 days prior to I/R and for 4 days after I/R attenuated DND, DNA damage and glial cell activation. However, neuroprotection was more pronounced when GPE was administered for 4 days after I/R than when administered for 4 days prior to I/R. GPE administration after I/R attenuated I/R-induced hyperlocomotion. These findings indicate that oral GPE intake may confer protection against I/R injury and emphasize that early intervention may be an effective therapeutic measure for ameliorating brain injury in stroke. (C) 2009 Elsevier Inc. All rights reserved. C1 [Wang, Qun; Simonyi, Agnes; Sun, Grace Y.] Univ Missouri, Dept Biochem, Columbia, MO 65211 USA. [Miller, Dennis K.] Univ Missouri, Dept Psychol Sci, Columbia, MO 65211 USA. [Sun, Albert Y.; Korthuis, Ronald J.] Univ Missouri, Dept Med Pharmacol & Physiol, Columbia, MO 65211 USA. [Sun, Albert Y.; Korthuis, Ronald J.] Univ Missouri, Dalton Cardiovasc Res Ctr, Columbia, MO 65211 USA. [Smith, Robert E.; Luchtefeld, Ronald G.] US FDA, Lenexa, KS 66214 USA. RP Sun, GY (reprint author), Univ Missouri, Dept Biochem, Columbia, MO 65211 USA. EM sung@missouri.edu OI Miller, Dennis/0000-0003-4422-7197 FU NIH [P01 AG018357, DK 43785, 1101, AA14945]; California Table Grape Commission FX This work was supported by NIH P01 AG018357, DK 43785 and 1101 AA14945, and a grant from the California Table Grape Commission. NR 51 TC 22 Z9 23 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0955-2863 EI 1873-4847 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD MAY PY 2009 VL 20 IS 5 BP 369 EP 377 DI 10.1016/j.jnutbio.2008.04.007 PG 9 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 434YQ UT WOS:000265310600005 PM 18602816 ER PT J AU Ferguson, SA Boctor, SY AF Ferguson, Sherry A. Boctor, Sherin Y. TI Use of Food Wafers for Multiple Daily Oral Treatments in Young Rats SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID ESTROGENIC ENDOCRINE DISRUPTORS; DEVELOPMENTAL EXPOSURE; FEMALE RATS; STRESS; MICE; BEHAVIORS; GENISTEIN; MEMORY; BRAIN; ACID AB Many laboratory studies require oral administration of drugs. Dietary administration in food or water is useful, but is not always the best method. Orogastric gavage can be stressful. Here, we describe in detail a relatively stress-free technique that can be applied to multiple daily administrations using a palatable food item. This method was successfully used to administer water or methylphenidate 3 times daily to young pair-housed adolescent rats. C1 [Ferguson, Sherry A.; Boctor, Sherin Y.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Ferguson, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. EM Sherry.Ferguson@fda.hhs.gov NR 21 TC 14 Z9 14 U1 0 U2 3 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD MAY PY 2009 VL 48 IS 3 BP 292 EP 295 PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 450HV UT WOS:000266392500008 PM 19476719 ER PT J AU Flowers, L Wick, J Figg, WD McClelland, RH Shiber, M Britton, JE Ngo, DKH Borders-Hemphill, V Mead, C Zee, J Huntzinger, P AF Flowers, Louis Wick, Jeannette Figg, William Douglas, Sr. McClelland, Robert H. Shiber, Michael Britton, James E. Ngo, Diem-Kieu H. Borders-Hemphill, Vicky Mead, Christina Zee, Jerry Huntzinger, Paul TI US Public Health Service Commissioned Corps pharmacists: Making a difference in advancing the nation's health SO JOURNAL OF THE AMERICAN PHARMACISTS ASSOCIATION LA English DT Article DE Federal pharmacy; US Public Health Service; Commissioned Corps officers; US Department of Health and Human Services AB Objective: To describe how U. S. Public Health Service (PHS) pharmacists serving in jobs that are normal for them, but considerably different than those found in the private sector, are making a difference in advancing the nation's health. Summary: Pharmacists who serve in the Commissioned Corps of PHS fill roles that are considerably different than their counterparts in the private sector. Their work takes them out from behind the counter and into the world. Pharmacy officers advance the health and safety of the nation by their involvement in the delivery of direct patient care to medically underserved people, national security, drug vigilance, research, and policy-making endeavors. PHS pharmacists fill essential public health leadership and service roles throughout the U. S. Department of Health and Human Services (HHS) and certain non-HHS federal agencies and programs. The Health Resources and Services Administration, National Institutes of Health, Federal Bureau of Prisons, Indian Health Service, Food and Drug Administration, and U. S. Coast Guard are among the many federal agencies in which pharmacy officers are assigned. Conclusion: In each setting, PHS pharmacists find traditional roles augmented with assignments and challenges that broaden the scope of their practice. C1 [Flowers, Louis] US FDA, Div Training & Dev, Off Training & Commun, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Wick, Jeannette] NCI, Pharmaceut Management Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Rockville, MD USA. [Figg, William Douglas, Sr.] NCI, Mol Pharmacol Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Figg, William Douglas, Sr.] NCI, Clin Pharmacol Program, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [McClelland, Robert H.] Indian Hlth Serv, Elko, NV USA. [Shiber, Michael] Fed Bur Prisons, Washington, DC USA. [Britton, James E.] Fed Bur Prisons Natl HIV Clin Consultant Pharmaci, Springfield, MO USA. [Ngo, Diem-Kieu H.] US FDA, Off Execut Programs, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Mead, Christina] Indian Hlth Serv, Bloomfield, NM USA. [Zee, Jerry] Indian Hlth Serv, Omak Satellite Clin, Omak, WA USA. [Huntzinger, Paul] US Coast Guard Integrated Support Command Pharm, Alameda, CA USA. RP Flowers, L (reprint author), DTD OTCOM CDER FDA, Bldg 51,Room 2316,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM louis.flowers@fda.hhs.gov RI Figg Sr, William/M-2411-2016 FU Intramural NIH HHS [Z99 CA999999] NR 25 TC 3 Z9 3 U1 0 U2 3 PU AMER PHARMACEUTICAL ASSOC PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 USA SN 1544-3191 J9 J AM PHARM ASSOC JI J. Am. Pharm. Assoc. PD MAY-JUN PY 2009 VL 49 IS 3 BP 446 EP 452 DI 10.1331/JAPhA.2009.08036 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 453LU UT WOS:000266612800016 PM 19443327 ER PT J AU Kuroda, H Kutner, RH Bazan, NG Reiser, J AF Kuroda, Hitoshi Kutner, Robert H. Bazan, Nicolas G. Reiser, Jakob TI Simplified lentivirus vector production in protein-free media using polyethylenimine-mediated transfection SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE Lentiviral vectors; Vector production; Polyethylenimine transfection; Protein-free media ID MESENCHYMAL STEM-CELLS; GENE-TRANSFER; RECOMBINANT PROTEIN; NONDIVIDING CELLS; MAMMALIAN-CELLS; IN-VIVO; TRANSIENT TRANSFECTION; DNA TRANSFECTION; TRANSDUCTION; THERAPY AB During the past 12 years, lentiviral vectors have emerged as valuable tools for transgene delivery because of their ability to transduce nondividing cells and their capacity to sustain long-term transgene expression. Despite significant progress, the production of high-titer high-quality lentiviral vectors is cumbersome and costly. The most commonly used method to produce lentiviral vectors involves transient transfection using calcium phosphate (CaP)-mediated precipitation of plasmid DNAs. However, inconsistencies in pH can cause significant batch-to-batch variations in lentiviral vector titers, making this method unreliable. This study describes optimized protocols for lentiviral vector production based on polyethylenimine (PEI)-mediated transfection, resulting in more consistent lentiviral vector stocks. To achieve this goal, simple production methods for high-titer lentiviral vector production involving transfection of HEK 293T cells immediately after plating were developed. Importantly, high titers were obtained with cell culture media lacking serum or other protein additives altogether. As a consequence, large-scale lentiviral vector stocks can now be generated with fewer batch-to-batch variations and at reduced costs and with less labor compared to the standard protocols. Published by Elsevier B.V. C1 [Kuroda, Hitoshi; Kutner, Robert H.; Reiser, Jakob] Louisiana State Univ, Hlth Sci Ctr, Gene Therapy Program, New Orleans, LA 70112 USA. [Kuroda, Hitoshi; Bazan, Nicolas G.] Louisiana State Univ, Hlth Sci Ctr, Neurosci Ctr Excellence, New Orleans, LA 70112 USA. [Reiser, Jakob] US FDA, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Reiser, J (reprint author), US FDA, CBER, 1401 Rockville Pike,HFM-725, Rockville, MD 20852 USA. EM Jakob.Reiser@fda.hhs.gov FU NIH [R01 NS 044832] FX This work was supported by NIH grant R01 NS 044832 to J. Reiser. We thank Dr. Takele Argaw (FDA/CBER) for his comments on the manuscript. NR 34 TC 34 Z9 37 U1 0 U2 9 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 2009 VL 157 IS 2 BP 113 EP 121 DI 10.1016/j.jviromet.2008.11.021 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 441JH UT WOS:000265764600001 PM 19114057 ER PT J AU Ma, YK Khan, AS AF Ma, Yun Kun Khan, Arifa S. TI Evaluation of different RT enzyme standards for quantitation of retroviruses using the single-tube fluorescent product-enhanced reverse transcriptase assay SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE Retroviruses; STF-PERT assay; Reverse transcriptase ID REPLICATION-COMPETENT RETROVIRUS; PORCINE ENDOGENOUS RETROVIRUSES; HUMAN-IMMUNODEFICIENCY-VIRUS; VACCINES; TRANSMISSION; RECIPIENTS; CULTURES; MEASLES; RNA AB PCR-based reverse transcriptase (RT) assays are highly sensitive for broad detection of retroviruses. These are Currently used for demonstrating the absence of retroviral contamination in vaccines and can also be applied to clinical and laboratory research to investigate low-virus replication. A single-tube fluorescent product-enhanced reverse transcriptase assay (STF-PERT) has been published that was highly sensitive for retrovirus detection (<10 virions), with enhanced reproducibility and increased efficiency [Sears, J.F., Khan, A.S., 2003. Single-tube fluorescent product-enhanced reverse transcriptase assay with AmpliWax (STF-PERT) for retrovirus quantitation. J. Virol. Meth. 108, 139-142]. In this report, the step-by-step setup and performance of the STF-PERT assay is described and sensitivity, reproducibility and specificity of the assay reported using three different RTs as standards: avian myeloblastosis virus (AMV) RT, murine leukemia virus (MMLV) RT, and human immunodeficiency virus type 1 (HIV-1) RT. Evaluation of virus stocks showed about 1-2 logs difference in RT detection and retrovirus quantitation with the different RT enzyme standards; in general, virus determination using HIV-1 RT was comparable to using the relevant virus RT. Published by Elsevier B.V. C1 [Ma, Yun Kun; Khan, Arifa S.] US FDA, Lab Retrovirus Res, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Khan, AS (reprint author), US FDA, Lab Retrovirus Res, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM arifa.khan@fda.hhs.gov FU NIH [IAA Y1-A1-4893-02] FX We thank Anil Choudhary for providing the titered SIV239 virus stock, Teresa Galvin for the SFV-2 virus stock and Dhanya K. Williams for help with data analysis; Keith Peden, Kurt Brorson, Andrew Dayton, Scott Lute, and Dhanya K. Williams for critical review of the manuscript. This work was partially supported by NIH IAA Y1-A1-4893-02. NR 21 TC 6 Z9 11 U1 0 U2 0 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 2009 VL 157 IS 2 BP 133 EP 140 DI 10.1016/j.jviromet.2009.01.002 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 441JH UT WOS:000265764600003 PM 19186191 ER PT J AU Adamo, JE Liu, T Schmeisser, F Ye, ZP AF Adamo, Joan E. Liu, Teresa Schmeisser, Falko Ye, Zhiping TI Optimizing Viral Protein Yield of Influenza Virus Strain A/Vietnam/1203/2004 by Modification of the Neuraminidase Gene SO JOURNAL OF VIROLOGY LA English DT Article ID MATRIX PROTEIN; A VIRUS; MEMBRANE ASSOCIATION; CYTOPLASMIC TAILS; TISSUE-CULTURE; STALK-LENGTH; VACCINES; HEMAGGLUTININ; GROWTH; GLYCOPROTEINS AB The preparation of high-yield prepandemic influenza virus H5N1 strains has presented a challenge to both researchers and vaccine manufacturers. The reasons for the relatively low yield of the H5N1 strains are not fully understood, but it might be partially dependent on the interactions between the hemagglutinin (HA) or neuraminidase (NA) surface glycoprotein and other influenza virus proteins. In this study, we have constructed chimeras between the A/Puerto Rico/8/34 (PR8) NA gene and the A/Vietnam/1203/2004 (VN1203) NA gene that have resulted in an increase in the virus yield of the reassortant viruses without a significant loss of NA activity. By combining the amino terminus of NA from the PR8 strain with the carboxy terminus of NA from VN1203, the surface epitopes unique to the H5N1 VN1203 NA glycoprotein are maintained. This reassortant virus had a higher titer and total protein yield in eggs, grew to a higher titer, produced large plaques on MDCK cells, and retained NA activity. This work describes a novel recombinant technique designed to increase the yields of vaccine candidates for the production of pandemic influenza virus vaccines. The relationship between the infectivity and protein yield of the reassortants also is discussed. C1 [Adamo, Joan E.; Liu, Teresa; Schmeisser, Falko; Ye, Zhiping] US FDA, Div Viral Prod, CBER, Bethesda, MD 20892 USA. RP Ye, ZP (reprint author), US FDA, Div Viral Prod, CBER, 29A-1B11,8800 Rockville Pike, Bethesda, MD 20892 USA. EM zhiping.ye@fda.hhs.gov NR 28 TC 18 Z9 20 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY 1 PY 2009 VL 83 IS 9 BP 4023 EP 4029 DI 10.1128/JVI.02391-08 PG 7 WC Virology SC Virology GA 431DN UT WOS:000265041600003 PM 19224999 ER PT J AU Laddy, DJ Yan, J Khan, AS Andersen, H Cohn, A Greenhouse, J Lewis, M Manischewitz, J King, LR Golding, H Draghia-Akli, R Weiner, DB AF Laddy, Dominick J. Yan, Jian Khan, Amir S. Andersen, Hanne Cohn, Amanda Greenhouse, Jack Lewis, Mark Manischewitz, Jody King, Lisa R. Golding, Hana Draghia-Akli, Ruxandra Weiner, David B. TI Electroporation of Synthetic DNA Antigens Offers Protection in Nonhuman Primates Challenged with Highly Pathogenic Avian Influenza Virus SO JOURNAL OF VIROLOGY LA English DT Article ID A H5N1 VIRUS; LOWER RESPIRATORY-TRACT; HETEROSUBTYPIC VIRUS; CYNOMOLGUS MACAQUES; LETHAL INFECTION; VACCINE; RESPONSES; ANTIBODY; IMMUNE; CELLS AB Avian influenza highlights the need for novel vaccination techniques that would allow for the rapid design and production of safe and effective vaccines. An ideal platform would be capable of inducing both protective antibodies and potent cellular immune responses. These potential advantages of DNA vaccines remain unrealized due to a lack of efficacy in large animal studies and in human trials. Questions remain regarding the potential utility of cellular immune responses against influenza virus in primates. In this study, by construct optimization and in vivo electroporation of synthetic DNA-encoded antigens, we observed the induction of cross-reactive cellular and humoral immune responses individually capable of providing protection from influenza virus infection in the rhesus macaque. These studies advance the DNA vaccine field and provide a novel, more tolerable vaccine with broad immunogenicity to avian influenza virus. This approach appears important for further investigation, including studies with humans. C1 [Laddy, Dominick J.; Yan, Jian; Weiner, David B.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Andersen, Hanne; Cohn, Amanda; Greenhouse, Jack; Lewis, Mark] Bioqual Inc, Rockville, MD 20850 USA. [Khan, Amir S.; Draghia-Akli, Ruxandra] VGX Pharmaceut Inc, The Woodlands, TX 77381 USA. [Manischewitz, Jody; King, Lisa R.; Golding, Hana] US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod, Bethesda, MD 20892 USA. RP Weiner, DB (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. EM dbweiner@mail.med.upenn.edu RI Weiner, David/H-8579-2014 FU NIH FX This work was supported in part by NIH grants awarded to D. Weiner. NR 30 TC 84 Z9 85 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY 1 PY 2009 VL 83 IS 9 BP 4624 EP 4630 DI 10.1128/JVI.02335-08 PG 7 WC Virology SC Virology GA 431DN UT WOS:000265041600061 PM 19211745 ER PT J AU Fuentes, CMM AF Fuentes, Catherine M. Mitchell TI "Gynecological Risk Outcomes of Interpersonal Violence: Risks and Empowerment in the Lives of Women and Their Children" SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Fuentes, Catherine M. Mitchell] US FDA, Off Womens Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 MAY PY 2009 VL 18 IS 5 MA 20 BP 750 EP 750 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 446DP UT WOS:000266100900039 ER PT J AU Gallauresi, B DiPaola, L Parekh, A Zimmerman, B Uhl, K AF Gallauresi, B. DiPaola, L. Parekh, A. Zimmerman, B. Uhl, K. TI Recently approved medical devices: Are females adequately represented in device clinical trials? SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Gallauresi, B.; DiPaola, L.; Parekh, A.; Uhl, K.] US FDA, Off Womens Hlth, Rockville, MD 20857 USA. [Zimmerman, B.] US FDA, Ctr Devices & Radiol 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 MAY PY 2009 VL 18 IS 5 MA 21 BP 750 EP 750 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 446DP UT WOS:000266100900040 ER PT J AU Thomas, KA AF Thomas, Kimberly A. TI The FDA Office of Women's Health National College Campaign: Increasing college students' access to FDA health information SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Thomas, Kimberly A.] 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 MAY PY 2009 VL 18 IS 5 MA 46 BP 759 EP 759 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 446DP UT WOS:000266100900065 ER PT J AU Gonzalez, JF Reimschuessel, R Shaikh, B Kane, AS AF Fernando Gonzalez, Jaime Reimschuessel, Renate Shaikh, Badar Kane, Andrew S. TI Kinetics of hepatic phase I and II biotransformation reactions in eight finfish species SO MARINE ENVIRONMENTAL RESEARCH LA English DT Article DE Hepatic; Phase I and II biotransformation reactions; Finfish; Kinetics ID GLUTATHIONE S-TRANSFERASES; TROUT ONCORHYNCHUS-MYKISS; DEETHYLASE EROD ACTIVITY; SALMON SALMO-SALAR; RAINBOW-TROUT; CHANNEL CATFISH; OREOCHROMIS-NILOTICUS; ICTALURUS-PUNCTATUS; CYTOCHROMES P450; LARGEMOUTH BASS AB Hepatic microsomes and cytosols of channel catfish (Ictalurus punctatus), rainbow trout (Oncorhynchus mykiss), Atlantic salmon (Salmo salar), red tilapia (Oreochromis sp.), largemouth bass (Micropterus salmoides), striped bass (Morone saxatilis), hybrid striped bass (M. saxatilis x M. crysops), and bluegill (Lepomis macrochuris) (n = 8) were used to study the kinetics of phase I (ECOD, EROD, PROD, BROD) and phase II (UDP-glucuronosyltransferase (UDPGT)-, sulfotransferase (ST)- and glutathione-s-transferase (GST)-mediated) reactions, The best catalytic efficiency for ECOD and GST activities was performed by channel catfish, Atlantic salmon, rainbow trout and tilapia. The highest EROD catalytic efficiency was for Atlantic salmon. None of the species had either PROD or BROD activities. Rainbow trout had very similar UDPGT catalytic efficiency to tilapia. channel catfish, Atlantic salmon, largemouth bass and bluegill. Sulfotransferase conjugation had no significant differences among the species. In summary, tilapia, channel catfish, Atlantic salmon and rainbow trout had the best biotransforming capabilities; striped bass, hybrid striped bass and bluegill were low metabolizers and largemouth bass shared sonic capabilities with both groups. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Fernando Gonzalez, Jaime] Univ Nacl Colombia, Sch Vet Med & Anim Sci, Bogota 146224, Colombia. [Reimschuessel, Renate; Shaikh, Badar] US FDA, Ctr Vet Med, Laurel, MD USA. [Kane, Andrew S.] Univ Florida, Coll Publ Hlth & Hlth Profess, Gainesville, FL USA. RP Gonzalez, JF (reprint author), Calle 23 A 59-72 T4,Ap 704, Bogota, Colombia. EM jfgonzalezma@unal.edu.co FU Institute of Food Safety and Nutrition (JIFSAN) [FDU001418] FX This work was funded by the joint Institute of Food Safety and Nutrition (JIFSAN) - Contract # FDU001418. The authors thank Charlie Gieseker and Stanley Serfling for their help with the acclimation of Atlantic salmon at the Center for Veterinary Medicine (FDA). NR 52 TC 13 Z9 14 U1 2 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0141-1136 J9 MAR ENVIRON RES JI Mar. Environ. Res. PD MAY-JUN PY 2009 VL 67 IS 4-5 BP 183 EP 188 DI 10.1016/j.marenvres.2009.01.002 PG 6 WC Environmental Sciences; Marine & Freshwater Biology; Toxicology SC Environmental Sciences & Ecology; Marine & Freshwater Biology; Toxicology GA 457DA UT WOS:000266904800003 PM 19201019 ER PT J AU Schmerk, CL Duplantis, BN Wang, D Burke, RD Chou, AY Elkins, KL Ludu, JS Nano, FE AF Schmerk, Crystal L. Duplantis, Barry N. Wang, Diana Burke, Robert D. Chou, Alicia Y. Elkins, Karen L. Ludu, Jagjit S. Nano, Francis E. TI Characterization of the pathogenicity island protein PdpA and its role in the virulence of Francisella novicida SO MICROBIOLOGY-SGM LA English DT Article ID VI SECRETION SYSTEM; INTRACELLULAR GROWTH; GENE-EXPRESSION; INTRAMACROPHAGE GROWTH; TULARENSIS; IDENTIFICATION; MACROPHAGES; REGULATOR; CYTOPLASM; ESCAPE AB Francisella tularensis is a highly virulent, intracellular pathogen that causes the disease tularaemia. A research surrogate for F tularensis is Francisella novicida, which causes a tularaemia-like disease in mice, grows similarly in macrophages, and yet is unable to cause disease in humans. Both Francisella species contain a cluster of genes referred to as the Francisella pathogenicity island (FPI). Pathogenicity determinant protein A (PdpA), encoded by the pdpA gene, is located within the FPI and has been associated with the virulence of Francisella species. In this work we examined the properties of PdpA protein expression and localization as well as the phenotype of a F. novicida pdpA deletion mutant. Monoclonal antibody detection of PdpA showed that it is a soluble protein that is upregulated in iron-limiting conditions and undetectable in an mglA or mglB mutant background. Deletion of pdpA resulted in a strain that was highly attenuated for virulence in chicken embryos and mice. C1 [Schmerk, Crystal L.; Duplantis, Barry N.; Wang, Diana; Burke, Robert D.; Ludu, Jagjit S.; Nano, Francis E.] Univ Victoria, Dept Biochem & Microbiol, Victoria, BC, Canada. [Chou, Alicia Y.; Elkins, Karen L.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Nano, FE (reprint author), Univ Victoria, Dept Biochem & Microbiol, Victoria, BC, Canada. EM fnano@uvic.ca OI Burke, Robert/0000-0001-5527-4410 FU National Institute of Allergy and Infectious Diseases [5R01 A1056212-02]; Canadian Institutes of Health Research [MOP 89812]; Biodefense arid Emerging Infections Resources program at the American Type Culture Collection FX This work was supported by grant 5R01 A1056212-02 from the National Institute of Allergy and Infectious Diseases and MOP 89812 from the Canadian Institutes of Health Research to F.L.N. The development of monoclonal antibodies was partially supported by a contract from the Biodefense arid Emerging Infections Resources program at the American Type Culture Collection. NR 35 TC 22 Z9 22 U1 0 U2 1 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 MAY PY 2009 VL 155 BP 1489 EP 1497 DI 10.1099/mic.0.025379-0 PG 9 WC Microbiology SC Microbiology GA 446WJ UT WOS:000266151900011 PM 19372153 ER PT J AU Su, DM Zhang, QY Wang, XX He, P Zhu, YLJ Zhao, JX Rennert, OM Su, YA AF Su, David M. Zhang, Qiuyang Wang, Xuexi He, Ping Zhu, Yuelin Jack Zhao, Jianxiong Rennert, Owen M. Su, Yan A. TI Two types of human malignant melanoma cell lines revealed by expression patterns of mitochondrial and survival-apoptosis genes: implications for malignant melanoma therapy SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID RANDOMIZED PHASE-III; METASTASIS; DACARBAZINE; UACC903(+6); TUMORIGENICITY; MICROARRAY; MICE AB Human malignant melanoma has poor prognosis because of resistance to apoptosis and therapy. We describe identification of the expression profile of 1,037 mitochondria-focused genes and 84 survival-apoptosis genes in 21 malignant melanoma cell lines and 3 normal melanocyte controls using recently developed hMitChip3 cDNA micro-arrays. Unsupervised hierarchical clustering analysis of 1,037 informative genes, and 84 survival-apoptosis genes, classified these malignant melanoma cell lines into type A (n = 12) and type B (n = 9). Three hundred fifty-five of 1,037 (34.2%) genes displayed significant (P:5 0.030; false discovery rate <= 3.68%) differences ( +/->= 2.0-fold) in average expression, with 197 genes higher and 158 genes lower in type A than in type B. Of 84 genes with known survival-apoptosis functions, 38 (45.2%) displayed the significant (P < 0.001; false discovery rate < 0.15%) difference. Antiapoptotic (BCL2, BCL2A1, PPARD, and RAF1), antioxidant (MT3, PRDX5, PRDX3, GPX4, GLRX2, and GSR), and proapoptotic (BAD, BNIP1, APAF1, BNIP3L, CASP7, CYCS, CASP1, and VDAC1) genes expressed at higher levels in type A than in type B, whereas the different set of antiapoptotic (PSEN1, PPP2CA, API5, PPP2R1B, PPP2R1A, and FIS1), antioxidant [HSPD1, GSS, SOD1, ATOX1, and CAT), and proapoptotic (ENDOG, BAK1, CASP2, CASP4, PDCD5, HTRA2 SEPT4, TNFSF10, and PRODH) genes expressed at lower levels in type A than in type B. Microarray data were validated by quantitative reverse transcription-PCR. These results showed the presence of two types of malignant melanoma, each with a specific set of dysregulated survival-apoptosis genes, which may prove useful for development of new molecular targets for therapeutic intervention and novel diagnostic biomarkers for treatment and prognosis of malignant melanoma. [Mol Cancer Ther 2009;8(5):1292-1304] C1 [Su, David M.; Zhang, Qiuyang; Wang, Xuexi; Su, Yan A.] George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Washington, DC 20037 USA. [Su, David M.; Zhang, Qiuyang; Wang, Xuexi; Su, Yan A.] George Washington Univ, Sch Med & Hlth Sci, Catherine Birch McCormick Genom Ctr, Washington, DC 20037 USA. [Wang, Xuexi; Zhao, Jianxiong] Lanzhou Univ, Sch Med Sci, Inst Chinese Western Integrat Med, Lanzhou 730000, Gansu, Peoples R China. [He, Ping] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Cellular Hemostasis, Bethesda, MD 20892 USA. [Rennert, Owen M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Clin Gen, NIH, Bethesda, MD USA. [Zhu, Yuelin Jack] NCI Frederick, Sci Applicat Int Corp Frederick Inc, Adv Biomed Comp Ctr, Frederick, MD USA. RP Su, YA (reprint author), George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Ross Hall,Room 555,2300 1 St NW, Washington, DC 20037 USA. EM bcmyas@gwumc.edu FU Intramural NIH HHS [Z01 HD008868-01]; PHS HHS [NIH-NIDDK-06-925] NR 35 TC 26 Z9 26 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 MAY PY 2009 VL 8 IS 5 BP 1292 EP 1304 DI 10.1158/1535-7163.MCT-08-1030 PG 13 WC Oncology SC Oncology GA 447KL UT WOS:000266189900033 PM 19383853 ER PT J AU Kutner, RH Puthli, S Marino, MP Ramsay, A Reiser, J AF Kutner, Robert H. Puthli, Sharon Marino, Michael P. Ramsay, Alistair Reiser, Jakob TI Simplified Production and Concentration of HIV-1-Based Lentiviral Vectors Using HYPERFlask Vessels and Anion Exchange Membrane Chromatography SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Kutner, Robert H.; Puthli, Sharon; Ramsay, Alistair] Louisiana State Univ, Hlth Sci Ctr, Gene Therapy Program, New Orleans, LA USA. [Marino, Michael P.; Reiser, Jakob] US FDA, Div Cellular & Gene Therapies, Bethesda, MD 20014 USA. NR 0 TC 2 Z9 2 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 BP S274 EP S274 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019801291 ER PT J AU Laddy, D Yan, J Anderson, H Lewis, M Golding, H Khan, A Draghia-Akli, R Sardesai, N Weiner, DB AF Laddy, Dominick Yan, Jian Anderson, Hanne Lewis, Mark Golding, Hana Khan, Amir Draghia-Akli, Ruxandra Sardesai, Niranjan Weiner, David B. TI Improved Challenge Outcome Following Intradermic Vaccination by Electroporation of a Consensus H5N1 Influenza DNA Vaccine in Non-Human Primates SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Laddy, Dominick; Yan, Jian; Weiner, David B.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Anderson, Hanne; Lewis, Mark] Bioqual, Rockville, MD USA. [Khan, Amir; Draghia-Akli, Ruxandra; Sardesai, Niranjan] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Off Vaccines Res & Review, Bethesda, MD 20014 USA. RI Weiner, David/H-8579-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 39 BP S16 EP S16 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800040 ER PT J AU Tian, J Xu, ZL Smith, JS Hofherr, SE Barry, MA Byrnes, AP AF Tian, Jie Xu, Zhili Smith, Jeffrey S. Hofherr, Sean E. Barry, Michael A. Byrnes, Andrew P. TI Adenovirus Activates Complement by Distinctly Different Mechanisms In Vitro and In Vivo: Indirect Complement Activation by Virions In Vivo SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Tian, Jie; Xu, Zhili; Smith, Jeffrey S.; Byrnes, Andrew P.] FDA CBER, Div Cellular & Gene Therapies, Bethesda, MD USA. [Hofherr, Sean E.; Barry, Michael A.] Mayo Clin, Dept Internal Med, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 14 BP S6 EP S6 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800015 ER PT J AU Xu, ZL Smith, JS Tian, J Byrnes, AP AF Xu, Zhili Smith, Jeffrey S. Tian, Jie Byrnes, Andrew P. TI Intravenous Administration of Adenovirus Vectors in Rodents Causes Rapid Shock: An Important Role for the Lipid Mediator PAF in the Early Response to Adenovirus SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Xu, Zhili; Smith, Jeffrey S.; Tian, Jie; Byrnes, Andrew P.] Food & Drug Adm, Div Celluar & Gene Therapies, Bethesda, MD USA. RI Byrnes, Andrew/D-2808-2013 OI Byrnes, Andrew/0000-0003-1135-2629 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 10 BP S4 EP S5 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800011 ER PT J AU Ferguson, SA Delclos, KB Newbold, RR Flynn, KM AF Ferguson, Sherry A. Delclos, K. Barry Newbold, Retha R. Flynn, Katherine M. TI Few effects of multi-generational dietary exposure to genistein or nonylphenol on sodium solution intake in male and female Sprague-Dawley rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Genistein; Nonylphenol; Sodium; Endocrine disrupter; Rat ID ADULT-ONSET DISEASE; ENDOCRINE DISRUPTOR VINCLOZOLIN; SEXUALLY DIMORPHIC BEHAVIORS; INFLUENCING SALT APPETITE; SEX-DIFFERENCES; MULTIGENERATIONAL EXPOSURE; REPRODUCTIVE-SYSTEM; OFFSPRING TOXICITY; NACL INTAKE; PREFERENCE AB Previous work in our laboratory indicated that lifelong dietary exposure to estrogen-like endocrine disrupters; increased sodium solution intake in adult male and female rats. Here, we sought to discern the critical periods necessary for this alteration as well as establish the effects of lower dietary concentrations of genistein and nonylphenol. Male and female Sprague-Dawley rats (F0) consumed phytoestrogen-free chow containing 0, 5, 100, or 500 ppm genistein (approximate to 0.0, 0.4, 8.0, and 40.0 mg/kg/day) or 0, 25, 200, or 750 ppm nonylphenol (approximate to 0.0, 2.0,16.0, and 60.0 mg/kg/day). Rats were mated within treatment groups and offspring (F1) maintained on the same diets. Mating for the F1, F2, and F3 (genistein only) was within treatment groups. At postnatal day (PND) 21, the F3 generation began to consume unadulterated phytoestrogen-free chow such that genistein exposure occurred only in utero and preweaning. The F4 generation was never directly exposed to genistein. On PNDs 65-68, intake of regular water and a 3.0% sodium chloride solution was measured for F1-F4 generations (genistein portion) or F1-F2 (nonylphenol portion). Although body weights were decreased by the highest dietary concentrations of genistein and nonylphenol, there were only minimal effects of exposure on sodium solution intake. As expected, intake was highest in female rats. With previous data, these results indicate that the dietary concentrations necessary to increase adult sodium solution intake in rats are greater than 500 ppm genistein and 750 ppm nonylphenol and such effects do not appear to increase across generations. Published by Elsevier Inc. C1 [Ferguson, Sherry A.; Flynn, Katherine M.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Delclos, K. Barry] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Newbold, Retha R.] NIEHS, Mol Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Ferguson, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT 132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM Sherry.Ferguson@fda.hhs.gov FU U.S. Food and Drug Administration [IAG 224-07-007]; National Institute for Environmental Health Sciences; Oak Ridge Institute for Science Education FX This work was supported by Interagency Agreement IAG 224-07-007 between the U.S. Food and Drug Administration and the National Institute for Environmental Health Sciences. The extensive and expert technical assistance of the NCTR support staff in providing diet preparation, chemical analysis, and computer support services for these studies is gratefully acknowledged. The authors would like to express their appreciation to the animal care technicians of the Bionetics Corporation for their excellent technical expertise and Erika Gray for her skillful data summaries. In particular, grateful appreciation is extended to Connie Weis for her organization in these studies. Katherine Flynn was supported by a post-doctoral fellowship from the Oak Ridge Institute for Science Education. NR 45 TC 8 Z9 8 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 2009 VL 31 IS 3 BP 143 EP 148 DI 10.1016/j.ntt.2009.01.009 PG 6 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 449CZ UT WOS:000266309700001 PM 19452615 ER PT J AU Mudano, AS Bian, J Cope, JU Curtis, JR Gross, TP Allison, JJ Kim, Y Briggs, D Melton, ME Xi, J Saag, KG AF Mudano, A. S. Bian, J. Cope, J. U. Curtis, J. R. Gross, T. P. Allison, J. J. Kim, Y. Briggs, D. Melton, M. E. Xi, J. Saag, K. G. TI Vertebroplasty and kyphoplasty are associated with an increased risk of secondary vertebral compression fractures: a population-based cohort study SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE Bone cement; Kyphoplasty; Osteoporosis; Population-based; Vertebral compression fractures; Vertebroplasty ID COMPARING PERCUTANEOUS VERTEBROPLASTY; CONSERVATIVE THERAPY; PRIMARY OSTEOPOROSIS; FINITE-ELEMENT; CEMENT LEAKAGE; BODY FRACTURE; TRIAL; WOMEN; OUTCOMES; AUGMENTATION AB To better understand the risk of secondary vertebral compression fracture (VCF) following a vertebroplasty or kyphoplasty, we compared patients treated with those procedures to patients with a previous VCF. The risk of subsequent fracture was significantly greater among treatment patients, especially within 90 days of the procedure. Predominantly uncontrolled studies suggest a greater risk of subsequent vertebral compression fractures (VCFs) associated with vertebroplasty/kyphoplasty. To further understand this risk, we conducted a population-based retrospective cohort study using data from a large regional health insurer. Administrative claims procedure codes were used to identify patients receiving either a vertebroplasty or kyphoplasty (treatment group) and a comparison group of patients with a primary diagnosis of VCF who did not receive treatment during the same time period. The main outcomes of interest, validated by two independent medical record reviewers, were any new VCFs within (1) 90 days, (2) 360 days, and (3) at adjacent vertebral levels. Multivariable logistic regression examined the association of vertebroplasty/kyphoplasty with new VCFs. Among 48 treatment (51% vertebroplasty, 49% kyphoplasty) and 164 comparison patients, treated patients had a significantly greater risk of secondary VCFs than comparison patients for fractures within 90 days of the procedure or comparison group time point [adjusted odds ratio (OR) = 6.8; 95% confidence interval (CI) 1.7-26.9] and within 360 days (adjusted OR = 2.9; 95% CI 1.1-7.9). Patients who had undergone vertebroplasty/kyphoplasty had a greater risk of new VCFs compared to patients with prior VCFs who did not undergo either procedure. C1 [Mudano, A. S.; Bian, J.; Curtis, J. R.; Allison, J. J.; Kim, Y.; Melton, M. E.; Xi, J.; Saag, K. G.] Univ Alabama, Ctr Educ & Res Therapeut Musculoskeletal Disorder, Birmingham, AL 35294 USA. [Mudano, A. S.; Briggs, D.] Blue Cross & Blue Shield Alabama, Hlth Management, Birmingham, AL USA. [Bian, J.] Atlanta Vet Affairs Med Ctr, Atlanta, GA USA. [Cope, J. U.; Gross, T. P.] US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Rockville, MD 20857 USA. RP Saag, KG (reprint author), Univ Alabama, Ctr Educ & Res Therapeut Musculoskeletal Disorder, 510 20th St S,820 FOT, Birmingham, AL 35294 USA. EM ksaag@uab.edu OI Allison, Jeroan/0000-0003-4472-2112 FU Agency for Healthcare Research and Quality (AHRQ) [HS10389-07]; National Institute of Arthritis and Musculoskeletal and Skin Disease [AR52361-92]; Social & Scientific Systems [223-02-6003]; Food and Drug Administration (FDA) FX The authors thank Katherine Jackson Donnithorn and Raj Nair, MD for their assistance in medical record review. This study was supported by grants no. HS10389-07 from the Agency for Healthcare Research and Quality (AHRQ); no. AR52361-92 from the National Institute of Arthritis and Musculoskeletal and Skin Disease; and Social & Scientific Systems, Inc. contract no. 223-02-6003 with the Center for Devices and Radiological Health of the Food and Drug Administration (FDA). NR 32 TC 55 Z9 72 U1 0 U2 5 PU SPRINGER LONDON LTD PI ARTINGTON PA ASHBOURNE HOUSE, THE GUILDWAY, OLD PORTSMOUTH ROAD, ARTINGTON GU3 1LP, GUILDFORD, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD MAY PY 2009 VL 20 IS 5 BP 819 EP 826 DI 10.1007/s00198-008-0745-5 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 428LC UT WOS:000264848400018 PM 18797812 ER PT J AU Duchesnes, CE Naggert, JK Tatnell, MA Beckman, N Marnane, RN Rodrigues, JA Halim, A Pontre, B Stewart, AW Wolff, GL Elliott, R Mountjoy, KG AF Duchesnes, Cecile E. Naggert, Juergen K. Tatnell, Michele A. Beckman, Nikki Marnane, Rebecca N. Rodrigues, Jessica A. Halim, Angela Pontre, Beau Stewart, Alistair W. Wolff, George L. Elliott, Robert Mountjoy, Kathleen G. TI New Zealand Ginger mouse: novel model that associates the tyrp1(b) pigmentation gene locus with regulation of lean body mass SO PHYSIOLOGICAL GENOMICS LA English DT Article DE mouse model; pigmentation; body weight; body size; body fat distribution ID RAPID POSTWEANING GROWTH; COAT-COLOR; AGOUTI GENE; MAJOR GENE; HG MICE; PHENOTYPES; MUTATION; RECEPTOR; HORMONE; PROTEIN AB Duchesnes CE, Naggert JK, Tatnell MA, Beckman N, Marnane RN, Rodrigues JA, Halim A, Pontre B, Stewart AW, Wolff GL, Elliott R, Mountjoy KG. New Zealand Ginger mouse: novel model that associates the tyrp1(b) pigmentation gene locus with regulation of lean body mass. Physiol Genomics 37: 164-174, 2009. First published March 17, 2009; doi:10.1152/physiolgenomics.90336.2008. The study of spontaneous mutations in mice over the last century has been fundamental to our understanding of normal physiology and mechanisms of disease. Here we studied the phenotype and genotype of a novel mouse model we have called the New Zealand Ginger (NZG/Kgm) mouse. NZG/Kgm mice are very large, rapidly growing, ginger-colored mice with pink eyes. Breeding NZG/Kgm mice with CAST/Ei or C57BL/6J mice showed that the ginger coat colour is a recessive trait, while the excessive body weight and large body size exhibit a semidominant pattern of inheritance. Backcrossing F1 (NZG/Kgm x CAST/Ei) to NZG/Kgm mice to produce the N2 generation determined that the NZG/Kgm mouse has two recessive pigmentation variant genes (oca2(p) and tyrp-1(b)) and that the tyrp-1(b) gene locus associates with large body size. Three coat colors appeared in the N2 generation; ginger, brown, and dark. Strikingly, N2 male coat colour associated with body weight; the brown-colored mice weighed the most followed by ginger and then dark. The male brown coat-colored offspring reached adult body weights indistinguishable from NZG/Kgm males. The large NZG/Kgm mouse body size is a result of excessive lean body mass since these mice are not obese or diabetic. NZG/Kgm mice exhibit an unusual pattern of fat distribution; compared with other mouse strains they have disproportionately higher amounts of subcutaneous and gonadal fat. These mice are susceptible to high-fat diet-induced obesity but are resistant to high-fat diet-induced diabetes. We propose NZG/Kgm mice as a novel model to delineate gene(s) that regulate 1) growth and metabolism, 2) resistance to Type 2 diabetes, and 3) preferential fat deposition in the subcutaneous and gonadal areas. C1 [Mountjoy, Kathleen G.] Univ Auckland, Dept Physiol, Fac Med & Hlth Sci, Auckland 1023, New Zealand. [Duchesnes, Cecile E.; Mountjoy, Kathleen G.] Univ Auckland, Dept Mol Med & Pathol, Auckland 1023, New Zealand. [Beckman, Nikki; Elliott, Robert] Univ Auckland, Dept Paediat, Auckland 1023, New Zealand. [Pontre, Beau] Univ Auckland, Dept Biomed Imaging, Auckland 1023, New Zealand. [Stewart, Alistair W.] Univ Auckland, Sch Populat Hlth, Fac Med & Hlth Sci, Auckland 1023, New Zealand. [Naggert, Juergen K.] Jackson Lab, Bar Harbor, ME 04609 USA. [Wolff, George L.] US FDA, Div Biomed Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Mountjoy, KG (reprint author), Univ Auckland, Dept Physiol, Fac Med & Hlth Sci, Private Bag 92019, Auckland 1023, New Zealand. EM kmountjoy@auckland.ac.nz FU The Health Research Council of NZ; Auckland Medical Research Foundation; Auckland Uniservices; Lottery Health NZ; Diatranz NZ; Institute of Diabetes and Digestive and Kidney Diseases [DK-46977] FX Funding for this project was provided from The Health Research Council of NZ, Auckland Medical Research Foundation, Auckland Uniservices, Lottery Health NZ, and Diatranz NZ. J.K. Naggert was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-46977. NR 28 TC 3 Z9 3 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD MAY PY 2009 VL 37 IS 3 BP 164 EP 174 DI 10.1152/physiolgenomics.90336.2008 PG 11 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 445CN UT WOS:000266027400002 PM 19293329 ER PT J AU Riner, A Chan-Tack, KM Murray, JS AF Riner, Andrea Chan-Tack, Kirk M. Murray, Jeffrey S. TI Original Research: Intravenous Ribavirin-Review of the FDA's Emergency Investigational New Drug Database (1997-2008) and Literature Review SO POSTGRADUATE MEDICINE LA English DT Review DE Emergency Investigational New Drug application; intravenous; ribavirin; adverse events ID ACUTE-RESPIRATORY-SYNDROME; BONE-MARROW-TRANSPLANTATION; SUBACUTE SCLEROSING-PANENCEPHALITIS; SYNCYTIAL VIRUS PNEUMONIA; ADENOVIRUS INFECTION; HEMORRHAGIC CYSTITIS; INTERFERON-ALPHA; INTRAVENTRICULAR RIBAVIRIN; HUMAN METAPNEUMOVIRUS; CLINICAL-FEATURES AB Intravenous (IV) ribavirin does not have US Food and Drug Administration (FDA) approval, although oral and aerosol formulations have been approved. Intravenous ribavirin can, however, be authorized for use as a result of an Emergency Investigational New Drug (EIND) application as investigational treatment for patients with serious viral infections, including emerging or rare infections for which no alternative treatment is available. This retrospective Study evaluated clinical experience with IV ribavirin based on a review of the FDA's FIND database and a literature review. The main outcome measures were disease condition, clinical outcomes, and adverse events (AEs). First, the FDA's EIND database was evaluated for these variables among patients authorized to receive investigational IV ribavirin. Second, published literature on IV ribavirin was reviewed for diseases treated, reported clinical outcomes, and AEs. Adverse events reported in the literature were compared with AEs listed in approved product labeling (aerosol and oral formulations). From February 1997 to December 2008, 608 IV ribavirin EIND requests were made for 19 disease conditions. Adenovirus, respiratory syncytial virus, and parainfluenza infections comprised 84.7% of IV ribavirin EINDs. Inadequate reporting of clinical outcomes and AEs in the EIND database prevented analysis of either outcome. Data interpretation in the literature was limited by multiple factors, including retrospective design, small sample sizes, differences in reporting outcomes and AEs, lack of generalizability, and potential confounders such as concomitant medications, selection bias, and reporting bias. Reported AEs were consistent with labels of approved aerosol and oral formulations, except for lip and gingival swelling. However. estimates of frequency, severity, and causality of AEs associated with IV ribavirin Could not be determined because of study limitations. Our study findings suggest that the literature is inconclusive on the potential benefit for continued use of IV ribavirin. A review of the literature and the FDA's EIND database suggests that prospective, controlled trials of IV ribavirin in patients with adenovirus, parainfluenza, or serious respiratory syncytial virus infections could be feasible. C1 [Riner, Andrea; Chan-Tack, Kirk M.; Murray, Jeffrey S.] US FDA, Div Antiviral Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Murray, JS (reprint author), FDA CDER OND DAVP, 10903 New Hampshire Ave,Bldg 22,Room 6360, Silver Spring, MD 20993 USA. EM jeffrey.murray@fda.hhs.gov NR 82 TC 13 Z9 13 U1 0 U2 0 PU JTE MULTIMEDIA PI BERWYN PA 1235 WESTLAKES DR, STE 220, BERWYN, PA 19312 USA SN 0032-5481 J9 POSTGRAD MED JI Postgrad. Med. PD MAY PY 2009 VL 121 IS 3 BP 139 EP 146 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 457LV UT WOS:000266931200018 PM 19491552 ER PT J AU Jepsen, C Jepsen, LK AF Jepsen, Christopher Jepsen, Lisa K. TI Does home ownership vary by sexual orientation? SO REGIONAL SCIENCE AND URBAN ECONOMICS LA English DT Article DE Home ownership; Housing demand; Same-sex couples; Marriage ID SAME-SEX; EMPIRICAL-ANALYSIS; OPPOSITE-SEX; INCOME-TAX; GAY MEN; EARNINGS; DISCRIMINATION; LESBIANS; RACE; HOMEOWNERSHIP AB The housing literature considers whether the probability of owning a home is different for ethnic and racial minorities than for native whites. Most studies find that minorities are less likely to own a home than their white counterparts. A logical extension of this line of research is to consider whether home-ownership rates differ based on sexual orientation. We use data on couples from the 2000 Census and find that same-sex couples are less likely to own a home than are married couples. The average value of houses owned by same-sex male couples is statistically similar to the average value of houses owned by married couples, but houses owned by same-sex female and cohabiting couples have lower average values than those owned by married couples. Conditional on owning, same-sex couples are slightly less likely to have a mortgage compared to married couples. (C) 2008 Elsevier B.V. All rights reserved. C1 [Jepsen, Christopher] Univ Kentucky, CBER, Lexington, KY 40506 USA. [Jepsen, Christopher] Univ Kentucky, Dept Econ, Lexington, KY 40506 USA. [Jepsen, Lisa K.] Univ No Iowa, Dept Econ, Cedar Falls, IA 50614 USA. RP Jepsen, C (reprint author), Univ Kentucky, CBER, 335BA Catton B&E Bldg, Lexington, KY 40506 USA. EM jepsen@uky.edu; lisa.jepsen@uni.edu RI Jepsen, Christopher/B-9358-2013 OI Jepsen, Christopher/0000-0002-6419-6650 NR 37 TC 4 Z9 5 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0462 J9 REG SCI URBAN ECON JI Reg. Sci. Urban Econ. PD MAY PY 2009 VL 39 IS 3 BP 307 EP 315 DI 10.1016/j.regsciurbeco.2008.11.002 PG 9 WC Economics; Environmental Studies; Urban Studies SC Business & Economics; Environmental Sciences & Ecology; Urban Studies GA 429AW UT WOS:000264894200006 ER PT J AU Roebuck, BD Johnson, DN Sutter, CH Egner, PA Scholl, PF Friesen, MD Baumgartner, KJ Ware, NM Bodreddigari, S Groopman, JD Kensler, TW Sutter, TR AF Roebuck, Bill D. Johnson, Denise N. Sutter, Carrie Hayes Egner, Patricia A. Scholl, Peter F. Friesen, Marlin D. Baumgartner, Karen J. Ware, Nicholas M. Bodreddigari, Sridevi Groopman, John D. Kensler, Thomas W. Sutter, Thomas R. TI Transgenic Expression of Aflatoxin Aldehyde Reductase (AKR7A1) Modulates Aflatoxin B-1 Metabolism but not Hepatic Carcinogenesis in the Rat SO TOXICOLOGICAL SCIENCES LA English DT Article DE aflatoxin; aldo-keto reductase; chemoprevention; hepatic carcinogenesis; hepatotoxicity; transgenic rat ID ALDO-KETO REDUCTASE; GLUTATHIONE S-TRANSFERASES; TANDEM MASS-SPECTROMETRY; MOLECULAR DOSIMETRY; CATALYTIC-ACTIVITY; ALBUMIN ADDUCTS; HUMAN LIVER; PROTECTION; OLTIPRAZ; CANCER AB In both experimental animals and humans, aflatoxin B-1 (AFB(1)) is a potent hepatic toxin and carcinogen against which a variety of antioxidants and experimental or therapeutic drugs (e.g., oltipraz, related dithiolethiones, and various triterpenoids) protect from both acute toxicity and carcinogenesis. These agents induce several hepatic glutathione S-transferases (GST) as well as aldo-keto reductases (AKR) which are thought to contribute to protection. Studies were undertaken in transgenic rats to examine the role of one inducible enzyme, AKR7A1, for protection against acute and chronic actions of AFB(1) by enhancing detoxication of a reactive metabolite, AFB(1) dialdehyde, by reduction to alcohols. The AFB(1) dialdehyde forms adducts with protein amino groups by a Schiff base mechanism and these adducts have been theorized to be at least one cause of the acute toxicity of AFB(1) and to enhance carcinogenesis. A liver-specific AKR7A1 transgenic rat was constructed in the Sprague-Dawley strain and two lines, AKR7A1(Tg2) and AKR7A1(Tg5), were found to overexpress AKR7A1 by 18- and 8-fold, respectively. Rates of formation of AFB(1) alcohols, both in hepatic cytosols and as urinary excretion products, increased in the transgenic lines with AKR7A1(Tg2) being the highest. Neither line offered protection against acute AFB(1)-induced bile duct proliferation, a functional assessment of acute hepatotoxicity by AFB(1), nor did they protect against the formation of GST-P positive putative preneoplastic foci as a result of chronic exposure to AFB(1). These results imply that the prevention of protein adducts mediated by AKR are not critical to protection against AFB(1) tumorigenicity. C1 [Roebuck, Bill D.; Baumgartner, Karen J.; Ware, Nicholas M.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Pharmacol & Toxicol, Hanover, NH 03755 USA. [Johnson, Denise N.; Egner, Patricia A.; Scholl, Peter F.; Friesen, Marlin D.; Groopman, John D.; Kensler, Thomas W.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. [Scholl, Peter F.] US FDA, Ctr Food Safety & Nutr, College Pk, MD 20740 USA. [Sutter, Carrie Hayes; Bodreddigari, Sridevi; Sutter, Thomas R.] Univ Memphis, W Harry Feinstone Ctr Genom Res, Memphis, TN 38152 USA. RP Roebuck, BD (reprint author), Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Pharmacol & Toxicol, Hanover, NH 03755 USA. EM Bill.D.Roebuck@dartmouth.edu; tsutter@memphis.edu RI Friesen, Marlin/D-7328-2012; Kensler, Thomas/D-8686-2014 OI Kensler, Thomas/0000-0002-6676-261X FU NCI NIH HHS [R01 CA 39416, R01 CA039416]; NIEHS NIH HHS [P30 ES 03819, P30 ES003819] NR 41 TC 13 Z9 15 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 2009 VL 109 IS 1 BP 41 EP 49 DI 10.1093/toxsci/kfp003 PG 9 WC Toxicology SC Toxicology GA 441AQ UT WOS:000265742100006 PM 19168568 ER PT J AU Wang, JY Sawyer, JR Chen, L Chen, T Honma, M Mei, N Moore, MM AF Wang, Jianyong Sawyer, Jeffrey R. Chen, Ling Chen, Tao Honma, Masamitsu Mei, Nan Moore, Martha M. TI The Mouse Lymphoma Assay Detects Recombination, Deletion, and Aneuploidy SO TOXICOLOGICAL SCIENCES LA English DT Article DE mouse lymphoma assay; mutation type; loss of heterozygosity; cytogenetics; copy number; 3'-azido-3'-deoxythymidine; mitomycin C; taxol; thymidine kinase ID THYMIDINE KINASE GENE; TRIFLUOROTHYMIDINE-RESISTANT; CELL COLONIES; CHROMOSOME ANALYSIS; SPINDLE CHECKPOINT; MAMMALIAN-CELLS; MITOMYCIN-C; MUTATIONS; CANCER; TK AB The mouse lymphoma assay (MLA) uses the thymidine kinase (Tk) gene of the L5178Y/Tk(+/-)-3.7.2C mouse lymphoma cell line as a reporter gene to evaluate the mutagenicity of chemical and physical agents. The MLA is recommended by both the United States Food and Drug Administration and the United States Environmental Protection Agency as the preferred in vitro mammalian cell mutation assay for genetic toxicology screening because it detects a wide range of genetic alterations, including both point mutations and chromosomal mutations. However, the specific types of chromosomal mutations that can be detected by the MLA need further clarification. For this purpose, three chemicals, including two clastogens and an aneugen (3'-azido-3'-deoxythymidine, mitomycin C, and taxol), were used to induce Tk mutants. Loss of heterozygosity (LOH) analysis was used to select mutants that could be informative as to whether they resulted from deletion, mitotic recombination, or aneuploidy. A combination of additional methods, G-banding analysis, chromosome painting, and a real-time PCR method to detect the copy number (CN) of the Tk gene was then used to provide a detailed analysis. LOH involving at least 25% of chromosome 11, a normal karyotype, and a Tk CN of 2 would indicate that the mutant resulted from recombination, whereas LOH combined with a karyotypically visible deletion of chromosome 11 and a Tk CN of 1 would indicate a deletion. Aneuploidy was confirmed using G-banding combined with chromosome painting analysis for mutants showing LOH at every microsatellite marker on chromosome 11. From this analysis, it is clear that mouse lymphoma Tk mutants can result from recombination, deletion, and aneuploidy. C1 [Wang, Jianyong; Chen, Ling; Chen, Tao; Mei, Nan; Moore, Martha M.] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Sawyer, Jeffrey R.] Univ Arkansas Med Sci, Dept Pathol, Cytogenet Lab, Little Rock, AR 72205 USA. [Chen, Ling] Shanghai Jiao Tong Univ, Coll Life Sci & Technol, Shanghai 200030, Peoples R China. [Honma, Masamitsu] Natl Inst Hlth Sci, Div Genet & Mutagenesis, Tokyo 1588501, Japan. RP Moore, MM (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM martha.moore@fda.hhs.gov RI mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 FU National Center for Toxicological Research administered by the Oak Ridge Institute of Science and Education (Oak Ridge, TN) FX Supported in part by an appointment (J. W.) to the Research Participation Program at the National Center for Toxicological Research administered by the Oak Ridge Institute of Science and Education (Oak Ridge, TN) through an interagency agreement between the U. S. Department of Energy and the U. S. Food and Drug Administration NR 38 TC 23 Z9 24 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 2009 VL 109 IS 1 BP 96 EP 105 DI 10.1093/toxsci/kfp037 PG 10 WC Toxicology SC Toxicology GA 441AQ UT WOS:000265742100012 PM 19237551 ER PT J AU Choudhuri, S AF Choudhuri, Supratim TI Looking back to the future: From the development of the gene concept to toxicogenomics SO TOXICOLOGY MECHANISMS AND METHODS LA English DT Review DE Gene; gene concept; cistron; genome; toxicogenomics; pharmacogenomics; microarray; sequencing ID HUMAN GENOME; DROSOPHILA-MELANOGASTER; TRYPTOPHAN SYNTHETASE; ESCHERICHIA-COLI; MESSENGER-RNA; CROSSING-OVER; SEQUENCE; HYBRIDIZATION; CHROMOSOMES; COMPONENTS AB Initial progress in the science of genetics' in the first half of the 2011 century was mainly driven by studies utilizing mutations and consequent changes in phenotype. The structural and functional nature of the gene was far from being understood. That state of understanding started changing from the 1940s. In the following decades, with the discovery of the double helix followed by the discoveries on gene structure and expression, there was a period when the structural and functional aspects of the gene could be conceived in terms of one entity, the cistron. However, the discovery of intervening sequences caused this unified concept to fall apart, making the gene concept a subject of philosophical debate again. Meanwhile, over time, technological progress in molecular biology had the field forge ahead rapidly, ultimately leading to the sequencing of the human genome and genomes of other species, and giving birth to the science of genomics. Developments in genomics have given rise to certain applied sub-disciplines like pharmacogenomics and toxicogenomics. While the full potential of pharmaco- and toxicogenomics is yet to be harnessed, they nevertheless have had an impact in drug development and safety assessment, such that the future promise of genomics seems achievable. At present, it is a good opportunity to revisit the path from the development of the initial gene concept and the philosophical debate surrounding the meaning of the term 'gene' to the current state of understanding of genes and genomes and their role in health and disease. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Biotechnol & GRAS Notice Review, OFAS, College Pk, MD 20740 USA. RP Choudhuri, S (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Biotechnol & GRAS Notice Review, OFAS, HFS 255,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM supratim.choudhuri@fda.hhs.gov NR 82 TC 4 Z9 6 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1537-6524 J9 TOXICOL MECH METHOD JI Toxicol. Mech. Methods PD MAY PY 2009 VL 19 IS 4 BP 263 EP 277 DI 10.1080/15376510902855529 PG 15 WC Toxicology SC Toxicology GA 473QW UT WOS:000268224500001 PM 19778216 ER PT J AU Marti, GE AF Marti, Gerald E. TI The changing definition of CLL SO BLOOD LA English DT Editorial Material ID CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELL LYMPHOCYTOSIS C1 US FDA, Rockville, MD 20857 USA. RP Marti, GE (reprint author), US FDA, Rockville, MD 20857 USA. NR 4 TC 1 Z9 2 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 APR 30 PY 2009 VL 113 IS 18 BP 4130 EP 4131 PG 2 WC Hematology SC Hematology GA 442MW UT WOS:000265846300002 PM 19406995 ER PT J AU Epstein-Barash, H Shichor, I Kwon, AH Hall, S Lawlor, MW Langer, R Kohane, DS AF Epstein-Barash, Hila Shichor, Iris Kwon, Albert H. Hall, Sherwood Lawlor, Michael W. Langer, Robert Kohane, Daniel S. TI Prolonged duration local anesthesia with minimal toxicity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE liposomes; myotoxicity; neurotoxicity; pain; saxitoxin ID SCIATIC-NERVE BLOCKADE; LIPOSOMAL BUPIVACAINE; TRICYCLIC ANTIDEPRESSANTS; ANALGESIC DURATION; UP-REGULATION; IN-VIVO; EXPRESSION; LIDOCAINE; RAT; TETRODOTOXIN AB Injectable local anesthetics that would last for many days could have a marked impact on periprocedural care and pain management. Formulations have often been limited in duration of action, or by systemic toxicity, local tissue toxicity from local anesthetics, and inflammation. To address those issues, we developed liposomal formulations of saxitoxin (STX), a compound with ultrapotent local anesthetic properties but little or no cytotoxicity. In vitro, the release of bupivacaine and STX from liposomes depended on the lipid composition and on whether dexamethasone was incorporated. In cell culture, bupivacaine, but not STX, was myotoxic (to C2C12 cells) and neurotoxic (to PC12 cells) in a concentration- and time-dependent manner. Liposomal formulations containing combinations of the above compounds produced sciatic nerve blockade lasting up to 7.5 days (with STX +/- dexamethasone liposomes) in male Sprague-Dawley rats. Systemic toxicity only occurred where high loadings of dexamethasone increased the release of liposomal STX. Mild myotoxicity was only seen in formulations containing bupivacaine. There was no nerve injury on Epon-embedded sections, and these liposomes did not up-regulate the expression of 4 genes associated with nerve injury in the dorsal root ganglia. These results suggest that controlled release of STX and similar compounds can provide very prolonged nerve blocks with minimal systemic and local toxicity. C1 [Epstein-Barash, Hila; Shichor, Iris; Kohane, Daniel S.] Harvard Univ, Sch Med, Childrens Hosp, Dept Anesthesiol,Div Crit Care Med,Lab Biomat & D, Boston, MA 02115 USA. [Epstein-Barash, Hila; Shichor, Iris; Kwon, Albert H.; Langer, Robert] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Hall, Sherwood] US FDA, Chem Contaminants Branch HFS 716, Div Bioanalyt Chem Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Lawlor, Michael W.] Childrens Hosp Boston, Dept Med, Program Genom, Boston, MA 02115 USA. RP Kohane, DS (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Dept Anesthesiol,Div Crit Care Med,Lab Biomat & D, 300 Longwood Ave, Boston, MA 02115 USA. EM daniel.kohane@childrens.harvard.edu FU National Institute of General Medical Sciences [GM073626] FX This work was supported by National Institute of General Medical Sciences Grant GM073626 (to D. S. K.). NR 39 TC 56 Z9 56 U1 2 U2 16 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 28 PY 2009 VL 106 IS 17 BP 7125 EP 7130 DI 10.1073/pnas.0900598106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 438VS UT WOS:000265584500047 PM 19365067 ER PT J AU Zubkova, I Choi, YH Chang, E Priollo, K Uren, T Watanabe, H Wells, F Kachko, A Krawczynski, K Major, ME AF Zubkova, I. Choi, Y. H. Chang, E. Priollo, K. Uren, T. Watanabe, H. Wells, F. Kachko, A. Krawczynski, K. Major, M. E. TI T-cell vaccines that elicit effective immune responses against HCV in chimpanzees may create greater immune pressure for viral mutation SO VACCINE LA English DT Article DE Hepatitis C virus; T-cell; Immune escape; Chimpanzee ID HEPATITIS-C-VIRUS; SINGLE-SOURCE OUTBREAK; NEUTRALIZING ANTIBODIES; RECOVERED CHIMPANZEES; ESCAPE MUTATIONS; PLUS RIBAVIRIN; GENE DELIVERY; PLASMID DNA; INFECTION; PERSISTENCE AB A prime/boost vaccine strategy that transfects antigen-presenting cells using ligand-modified immunoliposomes to efficiently deliver plasmid DNA, followed by boosting with non-replicating recombinant advenovirus was used in chimpanzees to generate HCV-specific memory T-cells. Three chimpanzees (two vaccines, one control) were immunized with immunoliposomes complexed with DNA expressing NS3-NS5B or complexed with empty vector. Animals were boosted with adenovirus expressing NS3-NS5B, or non-recombinant adenovirus (control). Using liposome delivery we were able to obtain specific HCV responses following DNA priming in the chimpanzees. This data and mouse immunization studies confirm this as a more efficient delivery system than direct intramuscular inoculations with naked DNA. Subsequent to the adenovirus boost significant increases in peripheral HCV-specific T-cell responses and intrahepatic IFN-gamma and CD3 epsilon mRNA were also observed in the two vaccinated animals. Following challenge (100 CID(50)) both vaccinated animals showed immediate and significant control of viral replication (peak titers 3.7 x10(4) and 9 x 10(3) IU/mL at weeks 1 and 2), which coincided with increases in HCV-specific T-cell responses. Viral kinetics in the control animals were comparable to historical controls with exponenital increases in titer during the first several weeks. One vaccinated animal developed a low-level persistent infection (2 x 10(3) IU/mL) which correlated with a decrease in HCV-specific T-cell responses. Circulating virus isolated from both vaccinated animals showed similar to 2-fold greater nonsynonymous mutation rates compared to controls and the nonsynonymous/synonymous mutation rate ratio was indicative of positive selection. These data suggest that although T-cell vaccines can include immune responses capable of controlling HCV, they also induce high levels of immune pressure for the potential selection of escape mutants Published by Elsevier Ltd. C1 [Zubkova, I.; Uren, T.; Watanabe, H.; Wells, F.; Kachko, A.; Major, M. E.] US FDA, Lab Hepatitis Virol, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Choi, Y. H.; Krawczynski, K.] Ctr Dis Control & Prevent, Div Viral Hepatitis, NCHHSTP, Atlanta, GA USA. [Chang, E.; Priollo, K.] Georgetown Univ, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC USA. RP Major, ME (reprint author), US FDA, Lab Hepatitis Virol, Div Viral Prod, Ctr Biol Evaluat & Res, Bldg 29A,Rm 1D10,HFM 448,8800 Rockville Pike, Bethesda, MD 20892 USA. EM marian.major@fda.hhs.gov FU CDC; FDA; National Vaccine Program Office FX We Would like to thank Dr. Paul SpLirlock, Animal Resources Branch,SRP,CDCand members of the CDC veterinary staff for excellent veterinary Support and care during the primate experiments at CDC. We also thank Dr. Judy Beeler and Dr. Dino Feigelstock for critical reading of the manuscript. This work was Supported by CDC and FDA intramural research funds. H.W. was Supported by a grant from the National Vaccine Program Office. NR 56 TC 20 Z9 20 U1 0 U2 1 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 28 PY 2009 VL 27 IS 19 BP 2594 EP 2602 DI 10.1016/j.vaccine.2009.02.045 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 440YK UT WOS:000265735400013 PM 19428866 ER PT J AU Wysowski, DK AF Wysowski, Diane K. TI More on Reports of Esophageal Cancer with Oral Bisphosphonate Use Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID FEATURES C1 US FDA, Silver Spring, MD 20993 USA. RP Wysowski, DK (reprint author), US FDA, Silver Spring, MD 20993 USA. EM diane.wysowski@fda.hhs.gov NR 5 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 APR 23 PY 2009 VL 360 IS 17 BP 1791 EP 1792 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 435XY UT WOS:000265377800026 ER PT J AU Soung, NK Park, JE Yu, LR Lee, KH Lee, JM Bang, JK Veenstra, TD Rhee, K Lee, KS AF Soung, Nak-Kyun Park, Jung-Eun Yu, Li-Rong Lee, Kyung H. Lee, Jung-Min Bang, Jeong K. Veenstra, Timothy D. Rhee, Kunsoo Lee, Kyung S. TI PIk1-Dependent and -Independent Roles of an ODF2 Splice Variant, hCenexin1, at the Centrosome of Somatic Cells SO DEVELOPMENTAL CELL LA English DT Article ID POLO-BOX DOMAIN; PRIMARY CILIUM FORMATION; DENSE FIBER PROTEINS; MICROTUBULE NUCLEATION; MOTHER CENTRIOLES; MITOTIC FUNCTIONS; PERICENTRIN; IDENTIFICATION; KINASE; PLK1 AB Outer dense fiber 2 (ODF2) was initially identified as a major component of the sperm tail cytoskeleton, and was later suggested to be localized to somatic centrosomes and required for the formation of primary cilia. Here we show that a splice variant of hODF2 called hCenexin1, but not hODF2 itself, efficiently localizes to somatic centrosomes via a variant-specific C-terminal extension and recruits PIk1 through a Cdc2-dependent phospho-S796 motif within the extension. This interaction and PIk1 activity were important for proper recruitment of pericentrin and gamma-tubulin, and, ultimately, for formation of normal bipolar spindles. Earlier in the cell cycle, hCenexin1, but again not hODF2, also contributed to centrosomal recruitment of ninein and primary cilia formation independent of PIk1 interaction. These findings provide a striking example of how a splice-generated C-terminal extension of a sperm tail-associating protein mediates unanticipated centrosomal events at distinct stages of the somatic cell cycle. C1 [Soung, Nak-Kyun; Park, Jung-Eun; Lee, Kyung H.; Lee, Kyung S.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Yu, Li-Rong] US FDA, Ctr Prote, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Lee, Jung-Min; Rhee, Kunsoo] Seoul Natl Univ, Sch Biol Sci, Seoul 151742, South Korea. [Bang, Jeong K.] Korea Basic Sci Inst, Pusan 609735, South Korea. [Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Ft Detrick, MD 21702 USA. RP Lee, KS (reprint author), NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. EM kyunglee@mail.nih.gov FU NCI intramural grants; Korea Basic Science Institute (KBSI) [N28079] FX We are grateful to Susan Garfield and Rachel H. Lee for critical reading of the manuscript. We also thank Brian Dynlacht, Raymond L. Erikson, Chou-Zen Giam, Sigrid Hoyer-Fender, Seung Ryul Kim, Ryoko Kuriyama, Seongju Lee, Jens Luders, Andreas Merdes, David O. Morgan, Yoshitaka Ono, Myung Hee Park, Laurence Pelletier, Helen Piwnica-Worms, Jerome B. Rattner, Jeffrey L. Salisbury, David J. Sharp, Mikiko Takahashi, and Michael B. Yaffe for reagents, Susan Garfield for technical assistance in microscopy, and Shoshana Segal and David J. Goldstein, Office of Science and Technology Partnerships, NCI for support for antibody production. This work was supported in part by NCI intramural grants (K.S.L. and T.D.V.) and Korea Basic Science Institute (KBSI) project N28079 (J.K.B.). The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration. NR 31 TC 42 Z9 42 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD APR 21 PY 2009 VL 16 IS 4 BP 539 EP 550 DI 10.1016/j.devcel.2009.02.004 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 437EX UT WOS:000265470400010 PM 19386263 ER PT J AU Li, JB Tan, ZW Tang, SX Hewlett, I Pang, RF He, MZ He, SS Tian, BH Chen, K Yang, M AF Li, Jiebo Tan, Zhiwu Tang, Shixing Hewlett, Indira Pang, Ruifang He, Meizi He, Shanshan Tian, Baohe Chen, Kan Yang, Ming TI Discovery of dual inhibitors targeting both HIV-1 capsid and human cyclophilin A to inhibit the assembly and uncoating of the viral capsid SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE HIV-1; Capsid; Cyclophilin A; Assembly; Disassembly; Dual inhibitor ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEIN; THERAPY; COMPLEX; CELLS AB HIV-1 assembly and disassembly (uncoating) processes are critical for the HIV-1 replication. HIV-1 capsid (CA) and human cyclophilin A (CypA) play essential roles in these processes. We designed and synthesized a series of thiourea compounds as HIV-1 assembly and disassembly dual inhibitors targeting both HIV-1 CA protein and human CypA. The SIV-induced syncytium antiviral evaluation indicated that all of the inhibitors displayed antiviral activities in SIV-infected CEM cells at the concentration of 0.6-15.8 mu M for 50% of maximum effective rate. Their abilities to bind CA and CypA were determined by ultraviolet spectroscopic analysis, fluorescence binding affinity and PPIase inhibition assay. Assembly studies in vitro demonstrated that the compounds could potently disrupt CA assembly with a dose-dependent manner. All of these molecules could bind CypA with binding affinities (Kd values) of 51.0-512.8 mu M. Fifteen of the CypA binding compounds showed potent PPIase inhibitory activities (IC(50) values < 1 mu M) while they could not bind either to HIV-1 Protease or to HIV-1 Integrase in the enzyme assays. These results suggested that 15 compounds could block HIV-1 replication by inhibiting the PPIase activity of CypA to interfere with capsid disassembly and disrupting CA assembly. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Li, Jiebo; Tan, Zhiwu; Pang, Ruifang; He, Meizi; He, Shanshan; Tian, Baohe; Chen, Kan; 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 RI Li, Jiebo/D-1516-2015 OI Li, Jiebo/0000-0001-8124-8769 FU National Natural Science Foundation of China [30670415] FX This project was supported by the National Natural Science Foundation of China (No. 30670415). We thank Professor Fangqiu Li for her help in this work. NR 28 TC 26 Z9 30 U1 0 U2 10 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 APR 15 PY 2009 VL 17 IS 8 BP 3177 EP 3188 DI 10.1016/j.bmc.2009.02.051 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 431EQ UT WOS:000265044500027 PM 19328002 ER PT J AU Tian, BH He, MZ Tang, SX Hewlett, I Tan, ZW Li, JB Jin, YX Yang, M AF Tian, Baohe He, Meizi Tang, Shixing Hewlett, Indira Tan, Zhiwu Li, Jiebo Jin, Yinxue Yang, Ming TI Synthesis and antiviral activities of novel acylhydrazone derivatives targeting HIV-1 capsid protein SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Synthesis; Antiviral activity; Acylhydrazones; HIV-1 capsid ID INHIBITION; PEPTIDE; DOMAIN AB HIV-1 capsid protein (CA) plays important roles in the viral replication cycle. A number of acylhydrazone derivatives that act as inhibitors of HIV-1 CA assembly, were designed and synthesized. The synthesized compounds were tested for their antiviral activities and cytotoxicities using CEM cells. Some derivatives also were assayed for their ability to inhibit HIV-1 CA assembly in vitro. Among them, compounds 14f and 14i display the most promising potency with EC(50) values of 0.21 and 0.17 mu M, respectively. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Tian, Baohe; He, Meizi; Tan, Zhiwu; Li, Jiebo; Jin, Yinxue; Yang, Ming] Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China. [Tang, Shixing; Hewlett, Indira] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Yang, M (reprint author), Peking Univ, State Key Lab Nat & Biomimet Drugs, POB 261, Beijing 100191, Peoples R China. EM mingy@bjmu.edu.cn RI Li, Jiebo/D-1516-2015 OI Li, Jiebo/0000-0001-8124-8769 FU National Natural Science Foundation of China [30670415] FX This project was supported by the National Natural Science Foundation of China (No. 30670415). NR 19 TC 27 Z9 30 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD APR 15 PY 2009 VL 19 IS 8 BP 2162 EP 2167 DI 10.1016/j.bmcl.2009.02.116 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 426KI UT WOS:000264706800015 PM 19297155 ER PT J AU Allen, CE Schmitt, MP AF Allen, Courtni E. Schmitt, Michael P. TI HtaA Is an Iron-Regulated Hemin Binding Protein Involved in the Utilization of Heme Iron in Corynebacterium diphtheriae SO JOURNAL OF BACTERIOLOGY LA English DT Article ID CELL-SURFACE PROTEIN; TOXIN REPRESSOR DTXR; STAPHYLOCOCCUS-AUREUS; STREPTOCOCCUS-PYOGENES; TRANSPORT-SYSTEM; ESCHERICHIA-COLI; ACQUISITION; SIDEROPHORE; HEMOGLOBIN; IDENTIFICATION AB Many human pathogens, including Corynebacterium diphtheriae, the causative agent of diphtheria, use host compounds such as heme and hemoglobin as essential iron sources. In this study, we examined the Corynebacterium hmu hemin transport region, a genetic cluster that contains the hmuTUV genes encoding a previously described ABC-type hemin transporter and three additional genes, which we have designated htaA, htaB, and htaC. The hmu gene cluster is composed of three distinct transcriptional units. The htaA gene appears to be part of an iron- and DtxR-regulated operon that includes hmuTUV, while htaB and htaC are transcribed from unique DtxR-regulated promoters. Nonpolar deletion of either htaA or the hmuTUV genes resulted in a reduced ability to use hemin as an iron source, while deletion of htaB had no effect on hemin iron utilization in C. diphtheriae. A comparison of the predicted amino acid sequences of HtaA and HtaB showed that they share some sequence similarity, and both proteins contain leader sequences and putative C-terminal transmembrane regions. Protein localization studies with C. diphtheriae showed that HtaA is associated predominantly with the cell envelope when the organism is grown in minimal medium but is secreted during growth in nutrient-rich broth. HtaB and HmuT were detected primarily in the cytoplasmic membrane fraction regardless of the growth medium. Hemin binding studies demonstrated that HtaA and HtaB are able to bind hemin, suggesting that these proteins may function as cell surface hemin receptors in C. diphtheriae. C1 [Allen, Courtni E.; Schmitt, Michael P.] US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Lab Resp & Special Pathogens, Bethesda, MD 20892 USA. RP Schmitt, MP (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Lab Resp & Special Pathogens, Bldg 29,Room 108,8800 Rockville Pike, Bethesda, MD 20892 USA. EM michael.schmitt@fda.hhs.gov NR 50 TC 39 Z9 39 U1 5 U2 10 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 APR 15 PY 2009 VL 191 IS 8 BP 2638 EP 2648 DI 10.1128/JB.01784-08 PG 11 WC Microbiology SC Microbiology GA 427AS UT WOS:000264752600022 PM 19201805 ER PT J AU Reed, JL Welliver, TP Sims, GP McKinney, L Velozo, L Avendano, L Hintz, K Luma, J Coyle, AJ Welliver, RC AF Reed, Jennifer L. Welliver, Timothy P. Sims, Gary P. McKinney, LuAnn Velozo, Luis Avendano, Luis Hintz, Karen Luma, Jayson Coyle, Anthony J. Welliver, Robert C., Sr. TI Innate Immune Signals Modulate Antiviral and Polyreactive Antibody Responses during Severe Respiratory Syncytial Virus Infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 6th International Respiratory Syncytial Virus Symposium CY OCT 25-28, 2007 CL Marco Isl, FL ID B-CELL ACTIVATION; INFLUENZA-VIRUS; IGA ANTIBODIES; IMMUNOGLOBULIN-A; SECRETORY IGA; T-CELLS; INFANTS; DISEASE; ANTIGEN; LYMPHOCYTE AB Antiviral antibody production during respiratory syncytial virus (RSV) infection in infants is poorly understood. Tocharacterize local B lymphocyte responses, lung tissue and secretions from infants with RSV bronchiolitis were analyzed for innate B cell-stimulating factors and antiviral antibodies. In lung tissues of infants with fatal RSV bronchiolitis, CD20(+) lymphocytes and IgM-positive, IgG-positive, and IgA-positive plasma cells were prominent but CD4(+) T lymphocytes were not. Type I interferon-induced proteins and B cell tropic factors, including B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL), were colocalized in infected epithelium. In nasopharyngeal secretions from infants who survived RSV infection, class-switched antiviral and anti-nucleosomal antibodies were detected at presentation and correlated with BAFF and APRIL levels. Expression of APRIL and antiviral antibodies of IgA and IgM but not IgG isotype predicted better oxygen saturation. We conclude that B lymphocyte-stimulating factors derived from infected epithelium are primary determinants of the mucosal antibody response in infant RSV bronchiolitis. C1 [Reed, Jennifer L.] FDA CBER, Rockville, MD 20852 USA. [Welliver, Timothy P.; Sims, Gary P.; McKinney, LuAnn; Coyle, Anthony J.] Resp Inflammat & Autoimmun Grp, Gaithersburg, MD USA. [Hintz, Karen; Luma, Jayson; Welliver, Robert C., Sr.] SUNY Buffalo, Dept Pediat, Womens & Childrens Hosp, Buffalo, NY 14260 USA. [Velozo, Luis] Hosp Roberto Del Rio, Unidad Anat Patol, Santiago, Chile. [Avendano, Luis] Univ Chile, Programa Virol, Santiago, Chile. RP Reed, JL (reprint author), FDA CBER, 1401 Rockville Pk,HFM-345, Rockville, MD 20852 USA. EM jennifer.reed@fda.hhs.gov NR 50 TC 20 Z9 22 U1 0 U2 2 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 2009 VL 199 IS 8 BP 1128 EP 1138 DI 10.1086/597386 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 422EB UT WOS:000264409000007 PM 19278337 ER PT J AU Jacobs, A AF Jacobs, Abigail TI An FDA perspective on the nonclinical use of the X-Omics technologies and the safety of new drugs SO TOXICOLOGY LETTERS LA English DT Article DE Toxicogenomics; Biomarkers; Drugs ID GENE-EXPRESSION CHANGES; DNA MICROARRAYS; RATS; TOXICITY; TOXICOGENOMICS; EXPOSURE; PROFILES; DIFFERENTIATION; CARCINOGENICITY; NEPHROTOXICITY AB Work in the field "omics" (toxicogenomics, proteomics, and metabolomics) has exploded. It is hoped that 'omics' could be a tool for evaluation of general toxicology, reproductive toxicology, the carcinogenicity potential of pharmaceuticals and several other types of toxicity, eventually replacing the use of animals. Although much progress has been made in the standardization of procedures, challenges remain for evaluation of pharmaceuticals for regulatory Purposes, because Of off-target toxicologic effects, as well as issues of interpretation and the large number of biologic variables that can affect results. Such variables include species/strain, genetic variations, diet. age, dose, duration, and weight of animals. These variables also confound database compilations of expression profiles. The most promising use in the near future Would be to clarify pathways for the various types of toxicity and carcinogenicity and get biomarkers for these pathways, to help assess relevance of nonclinical findings to humans. Published by Elsevier Ireland Ltd. C1 FDA, CDER, Silver Spring, MD 20993 USA. RP Jacobs, A (reprint author), FDA, CDER, 10903 New Hampshire Ave Blg 22,Rm 6484, Silver Spring, MD 20993 USA. EM abigail.jacobs@fda.hhs.gov NR 38 TC 12 Z9 13 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD APR 10 PY 2009 VL 186 IS 1 BP 32 EP 35 DI 10.1016/j.toxlet.2008.08.013 PG 4 WC Toxicology SC Toxicology GA 426TY UT WOS:000264732000007 PM 18809476 ER PT J AU Thompson, KL Pine, PS AF Thompson, Karol L. Pine, P. Scott TI Comparison of the diagnostic performance of human whole genome microarrays using mixed-tissue RNA reference samples SO TOXICOLOGY LETTERS LA English DT Article DE Microarray; Metrics; Standards ID GENE-EXPRESSION MEASUREMENTS; OLIGONUCLEOTIDE MICROARRAYS; QUALITY; AFFYMETRIX; VALIDATION; NOISE AB Universal approaches for assessing the diagnostic performance of microarray assays are essential for the application of microarray technology to clinical and regulatory settings. Reference systems for diagnostic assays in laboratory medicine typically involve the utilization of reference samples, metrics, and reference datasets to ensure that measurements are comparable and true. For microarray performance evaluation and process improvement, reference samples can be composed of mixes of different tissue or cell line RNAs that contain tissue-selective analytes at defined target ratios. The diagnostic accuracy of detected changes in expression, measured as the area under the curve from receiver-operating characteristic plots, can provide a single commutable value for comparing assay specificity and sensitivity. Examples of applying I his method for assessing overall performance are provided using public datasets generated on five commercial human whole genome microarray platforms for the MicroArray Quality Control project, a community-wide effort to address issues Surrounding microarray data reliability. Published by Elsevier Ireland Ltd. C1 [Thompson, Karol L.; Pine, P. Scott] US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, CDER, Silver Spring, MD 20993 USA. RP Thompson, KL (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, CDER, White Oak Life Sci Bldg 64,Room 2036, Silver Spring, MD 20993 USA. EM karol.thompson@fda.hhs.gov NR 20 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD APR 10 PY 2009 VL 186 IS 1 BP 58 EP 61 DI 10.1016/j.toxlet.2008.08.018 PG 4 WC Toxicology SC Toxicology GA 426TY UT WOS:000264732000011 PM 18822358 ER PT J AU Palmer, PT Jacobs, R Baker, PE Ferguson, K Webber, S AF Palmer, Peter T. Jacobs, Richard Baker, Peter E. Ferguson, Kelly Webber, Siri TI Use of Field-Portable XRF Analyzers for Rapid Screening of Toxic Elements in FDA-Regulated Products SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE XRF; EDXRF; toxic elements; elemental analysis; FDA; screening ID X-RAY-FLUORESCENCE; MULTIELEMENT ANALYSIS; FOOD SAMPLES; SPECTROMETRY; IRON; ZINC; QUANTIFICATION; MANGANESE; COPPER AB Analytical instrumentation continues its amazing evolution, especially in regard to generating ever more sensitive, faster, and reliable measurements. Perhaps the most difficult challenges are making these instruments small enough to use in the field, equipping them with well-designed software that facilitates and simplifies their use by nonexperts while preserving enough of their analytical capabilities to render them useful for a wide variety of applications. Perhaps the most impressive and underappreciated example of instruments that meet these criteria are field-portable X-ray fluorescence (XRF) analyzers. In the past, these analyzers have been routinely used for environmental applications (lead in paint and soil, metal particulates in air samples collected onto filters), geology studies (ore and soil analysis, precious metal identification), and recycling industries (alloy identification). However, their use in the analysis of toxic elements in food, food ingredients, dietary supplements, and medicinal and herbal products, especially within the FDA and regulatory environments, has been surprisingly limited to date. Although XRF will not replace atomic spectrometry techniques such as ICP-MS for sub-parts per million level analyses, it offers a number of significant advantages including minimal sample preparation, high sample throughputs, rapid and definitive identification of many toxic elements, and accurate quantitative results. As should be obvious from many recent news reports on elevated levels of toxic elements in children's lunchboxes, toys, and supplements, field-portable XRF analyzers can fill a very important niche and are becoming increasingly popular for a wide variety of elemental analysis applications. This perspective begins with a brief review of the theory of XRF to highlight the underlying principle, instrumentation, and spectra. It includes a discussion of various analytical figures of merit of XRF to illustrate its strengths and limitations compared to existing methods such as ICP-MS. It concludes with a discussion of a number of different FDA applications and case studies in which XRF has been used to screen, identify, and in some cases quantify toxic elements in various products. This work clearly demonstrates that XRF analyzers are an exceedingly valuable tool for routine and nonroutine elemental analysis investigations, both in the laboratory and in the field. In the future, it is hoped that both field-portable and laboratory-grade XRF analyzers will see more widespread use for investigational and forensic-type applications of food and other regulated consumer products. C1 [Palmer, Peter T.; Baker, Peter E.; Ferguson, Kelly; Webber, Siri] San Francisco State Univ, Dept Chem & Biochem, San Francisco, CA 94132 USA. [Palmer, Peter T.; Jacobs, Richard] US FDA, San Francisco Dist Lab, Alameda, CA 94502 USA. RP Palmer, PT (reprint author), San Francisco State Univ, Dept Chem & Biochem, San Francisco, CA 94132 USA. EM palmer@sfsu.edu OI Palmer, Peter/0000-0002-3173-5726 FU FDA Division of Field Science FX We gratefully acknowledge Deblyn Paella (Geotechnical Services/Niton) and Jack Hanson (HMC Analytical Instrumentation/Innov-X) for the loan of XRF analyzers used in some of this work. We also thank David Anderson (CFSAN) and Eileen Maher (FDA Winchester Analytical and Engineering Center) for their comments and input and Rod Asmundson and Barbara Cassens (San Francisco District Laboratory) and the FDA Division of Field Science for their support of this work. NR 23 TC 47 Z9 49 U1 7 U2 57 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 8 PY 2009 VL 57 IS 7 BP 2605 EP 2613 DI 10.1021/jf803285h PG 9 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 427SX UT WOS:000264800500001 PM 19334748 ER PT J AU Bonhoeffer, J Bentsi-Enchill, A Chen, RT Fisher, MC Gold, MS Hartman, K Heininger, U Hoet, B Jefferson, T Khuri-Bulos, N Kohl, KS Marcy, SM Nalin, D Pless, R Sanabria-Rojas, H Sleeman, K Wise, R AF Bonhoeffer, Jan Bentsi-Enchill, Adwoa Chen, Robert T. Fisher, Margaret C. Gold, Michael S. Hartman, Katharina Heininger, Ulrich Hoet, Bernard Jefferson, Thomas Khuri-Bulos, Najwa Kohl, Katrin S. Marcy, S. Michael Nalin, David Pless, Robert Sanabria-Rojas, Hernan Sleeman, Karen Wise, Robert CA The Brighton Collaboration Methods TI Guidelines for collection, analysis and presentation of vaccine safety data in pre- and post-licensure clinical studies SO VACCINE LA English DT Article DE Vaccine; Immunization; Safety; Guidelines ID STATEMENT; QUALITY; TRIALS C1 [Bonhoeffer, Jan; Heininger, Ulrich] Univ Chicago Hosp, Basel, Switzerland. [Bentsi-Enchill, Adwoa] WHO, CH-1211 Geneva, Switzerland. [Chen, Robert T.; Kohl, Katrin S.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Fisher, Margaret C.] Childrens Hosp, Monmouth Med Ctr, Long Branch, NJ USA. [Gold, Michael S.] S Australian Immunisat Coordinat Unit, Adelaide, SA, Australia. [Hartman, Katharina] Berna Biotech AG, Bern, Switzerland. [Hoet, Bernard] GlaxoSmithKline Biol, Rixensart, Belgium. [Jefferson, Thomas] Cochrane Vaccines Field & Hlth Reviews Ltd, Rome, Italy. [Khuri-Bulos, Najwa] Jordan Univ Hosp, Amman, Jordan. [Marcy, S. Michael] Univ So Calif, Los Angeles, CA USA. [Pless, Robert] Ctr Infect Dis Prevent & Control, Ottawa, ON, Canada. [Sanabria-Rojas, Hernan] Inst Nacl Salud, Lima, Peru. [Sleeman, Karen] John Radcliffe Hosp, Oxford OX3 9DU, England. [Wise, Robert] US FDA, Rockville, MD 20857 USA. RP Bonhoeffer, J (reprint author), Univ Chicago Hosp, Basel, Switzerland. EM secretariat@brightoncollaboration.org RI Bonhoeffer, Jan/E-5903-2014; OI SANABRIA ROJAS, HERNAN ARTURO/0000-0003-0838-4064 NR 13 TC 29 Z9 29 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 6 PY 2009 VL 27 IS 16 BP 2282 EP 2288 DI 10.1016/j.vaccine.2008.11.036 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 429XX UT WOS:000264954500012 PM 19056451 ER PT J AU Bonhoeffer, J Bentsi-Enchill, A Chen, RT Fisher, MC Gold, MS Hartman, K Heininger, U Hoet, B Jefferson, T Khuri-Bulos, N Kohl, K Marcy, SM Nalin, D Pless, R Sanabria-Rojas, H Sleeman, K Se, RW AF Bonhoeffer, Jan Bentsi-Enchill, Adwoa Chen, Robert T. Fisher, Margaret C. Gold, Michael S. Hartman, Katharina Heininger, Ulrich Hoet, Bernard Jefferson, Thomas Khuri-Bulos, Najwa Kohl, Katrin Marcy, S. Michael Nalin, David Pless, Robert Sanabria-Rojas, Hernan Sleeman, Karen Se, Robert W. CA The Brighton Collaboration Methods TI Guidelines for collection, analysis and presentation of vaccine safety data in surveillance systems SO VACCINE LA English DT Article DE Vaccine; Immunization; Safety; Guidelines C1 [Bonhoeffer, Jan; Heininger, Ulrich] Univ Childrens Hosp, Basel, Switzerland. [Bentsi-Enchill, Adwoa] WHO, CH-1211 Geneva, Switzerland. [Chen, Robert T.; Kohl, Katrin] Ctr Dis Control & Prevent, Atlanta, GA USA. [Fisher, Margaret C.] Childrens Hosp, Monmouth Med Ctr, Long Branch, NJ USA. [Gold, Michael S.] S Australian Immunisat Coordinat Unit, Adelaide, SA, Australia. [Hartman, Katharina] Berna Biotech AG, Bern, Switzerland. [Hoet, Bernard] GlaxoSmithKline Biol, Rixensart, Belgium. [Jefferson, Thomas] Cochrane Vaccines Field & Hlth Reviews Ltd, Rome, Italy. [Khuri-Bulos, Najwa] Jordan Univ Hosp, Amman, Jordan. [Marcy, S. Michael] Univ So Calif, Los Angeles, CA USA. [Pless, Robert] Ctr Infect Dis Prevent & Control, Ottawa, ON, Canada. [Sanabria-Rojas, Hernan] Inst Nacl Salud, Lima, Peru. [Sleeman, Karen] John Radcliffe Hosp, Oxford OX3 9DU, England. [Se, Robert W.] US FDA, Rockville, MD 20857 USA. RP Bonhoeffer, J (reprint author), Univ Childrens Hosp, Basel, Switzerland. EM secretariat@brightoncollaboration.org RI Bonhoeffer, Jan/E-5903-2014; OI SANABRIA ROJAS, HERNAN ARTURO/0000-0003-0838-4064 NR 8 TC 20 Z9 20 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 6 PY 2009 VL 27 IS 16 BP 2289 EP 2297 DI 10.1016/j.vaccine.2008.11.035 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 429XX UT WOS:000264954500013 PM 19061929 ER PT J AU Gryniewicz, CM Reepmeyer, JC Kauffman, JF Buhse, LF AF Gryniewicz, Connie M. Reepmeyer, John C. Kauffman, John F. Buhse, Lucinda F. TI Detection of undeclared erectile dysfunction drugs and analogues in dietary supplements by ion mobility spectrometry SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Ion mobility spectrometry; Erectile dysfunction drugs; Herbal dietary supplements; Adulterants ID SYNTHETIC PHOSPHODIESTERASE-5 INHIBITORS; PERFORMANCE LIQUID-CHROMATOGRAPHY; STRUCTURE ELUCIDATION; MASS-SPECTROMETRY; HERBAL APHRODISIACS; SILDENAFIL ANALOGS; DESIGNER DRUGS; PRODUCTS; ADULTERANT; VARDENAFIL AB An ion mobility spectrometry (IMS) method was developed to screen for the presence of undeclared synthetic erectile dysfunction (ED) drugs or drug analogues in herbal dietary supplements claiming to enhance male sexual performance. Ion mobility spectra of authenticated reference materials including three FDA approved drugs (sildenafil citrate, tadalafil, vardenafil hydrochloride trihydrate) and five previously identified synthetic analogues (methisosildenafil, homosildenafil, piperidenafil, thiosildenafil, thiomethisosildenafil) were measured to determine their reduced ion mobilities (K-0). All eight compounds exhibited reduced mobilities between 0.8257 and 1.2876 cm(2)/(Vs). Twenty-six herbal products were then screened for the presence of these compounds, and 15 of the 26 products tested positive for the presence of ED drug or drug analogue adulterants based on their reduced ion mobilities. IMS results were compared against the results obtained from an independent LC/MS reference method for the identical samples. Herbal dietary supplements containing adulterants were classified with 100% accuracy and most of the adulterants were correctly identified by a comparison of the K-0 of the adulterant to the K-0 of the authenticated reference material. The results demonstrate that IMS is a viable method for screening herbal dietary supplements for the presence of ED drug or drug analogue adulterants. Published by Elsevier B.V. C1 [Gryniewicz, Connie M.; Reepmeyer, John C.; Kauffman, John F.; Buhse, Lucinda F.] US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Gryniewicz, CM (reprint author), US FDA, Div Pharmaceut Anal, 1114 Market St, St Louis, MO 63101 USA. EM Connie.Gryniewicz@fda.hhs.gov NR 30 TC 34 Z9 35 U1 2 U2 24 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0731-7085 EI 1873-264X J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD APR 5 PY 2009 VL 49 IS 3 BP 601 EP 606 DI 10.1016/j.jpba.2008.12.002 PG 6 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 422EI UT WOS:000264409800004 PM 19150190 ER PT J AU Trehy, ML Reepmeyer, JC Kolinski, RE Westenberger, BJ Buhse, LF AF Trehy, Michael L. Reepmeyer, John C. Kolinski, Richard E. Westenberger, Benjamin J. Buhse, Lucinda F. TI Analysis of heparin sodium by SAX/HPLC for contaminants and impurities SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Heparin; Oversulfated chondroitin sulfate; Dermatan sulfate; Glycosaminoglycan; HPLC ID ADVERSE CLINICAL EVENTS; CHONDROITIN SULFATE; OLIGOSACCHARIDES AB A chromatographic method was developed for the detection and quantification of the contaminant over-sulfated chondroitin sulfate (OSCS) and the impurity dermatan sulfate in heparin active pharmaceutical ingredient (API). The HPLC analysis of heparin is carried out using a polymer-based strong anion exchange (SAX) column with gradient elution from 0.125 M sodium chloride to 2.5 M sodium chloride buffered mobile phase. The limit of detection (LOD) and limit of quantitation (LOQ) for the contaminant OSCS in heparin were determined to be 0.03% and 0.1%, respectively. The LOD and LOQ for dermatan sulfate, an impurity in heparin sulfate, were determined to be 0.1% and 0.8%, respectively. This manuscript is not a policy document and is not intended to replace either of the methods (capillary electrophoresis and NMR) currently required by the FDA. Published by Elsevier B.V. C1 [Trehy, Michael L.; Reepmeyer, John C.; Kolinski, Richard E.; Westenberger, Benjamin J.; Buhse, Lucinda F.] US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Trehy, ML (reprint author), US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. EM michael.trehy@fda.hhs.gov NR 19 TC 57 Z9 61 U1 6 U2 31 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD APR 5 PY 2009 VL 49 IS 3 BP 670 EP 673 DI 10.1016/j.jpba.2008.12.013 PG 4 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 422EI UT WOS:000264409800014 PM 19167854 ER PT J AU Stewart, SFC Walsh, DL Schroeder, RJ AF Stewart, Sandy F. C. Walsh, Donna L. Schroeder, R. Jason TI Not All Mesalamine Enema Bottles Are Created Equal SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter C1 [Stewart, Sandy F. C.] US FDA, Div Solid & Fluid Mech, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Stewart, SFC (reprint author), US FDA, Div Solid & Fluid Mech, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Bldg 62,Room 2210,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM sandy.stewart@fda.hhs.gov NR 1 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD APR PY 2009 VL 104 IS 4 BP 1068 EP 1068 DI 10.1038/ajg.2008.178 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 431AR UT WOS:000265034200052 PM 19277026 ER PT J AU Karbiwnyk, CM Andersen, WC Turnipseed, SB Storey, JM Madson, MR Miller, KE Gieseker, CM Miller, RA Rummel, NG Reimschuessel, R AF Karbiwnyk, Christine M. Andersen, Wendy C. Turnipseed, Sherri B. Storey, Joseph M. Madson, Mark R. Miller, Keith E. Gieseker, Charles M. Miller, Ron A. Rummel, Nathan G. Reimschuessel, Renate TI Determination of cyanuric acid residues in catfish, trout, tilapia, salmon and shrimp by liquid chromatography-tandem mass spectrometry SO ANALYTICA CHIMICA ACTA LA English DT Article; Proceedings Paper CT EuroResidue VI Conference CY MAY 19-21, 2008 CL Egmond aan Zee, NETHERLANDS DE Cyanuric acid; Melamine; Liquid chromatography-tandem mass spectrometry; Fish; Shrimp ID SOLID-PHASE EXTRACTION; POROUS GRAPHITIC CARBON; DEGRADATION-PRODUCTS; ORGANIC POLLUTANTS; AQUEOUS SAMPLES; WATER; MELAMINE; ATRAZINE; URINE; CATS AB In May 2007, investigators discovered that waste material from the pet food manufacturing process contaminated with melamine (MEL) and/or cyanuric acid (CYA) had been added to hog and chicken feeds. At this time, investigators also learned that adulterated wheat gluten had been used in the manufacture of aquaculture feeds. Concern that the contaminated feed had been used in aquaculture and could enter the human food supply prompted the development of a method for the determination of CYA residues in the edible tissues of fish and shrimp. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed as a sensitive technique for the analysis of CYA in catfish, tilapia, salmon, trout and shrimp tissue. CYA was extracted from ground fish or shrimp with an acetic acid solution, defatted with hexane, and isolated with a graphitic carbon black solid-phase extraction column. Residues were separated from matrix components using a porous graphitic carbon LC column, and then analyzed with electrospray ionization in negative ion mode on a triple quadrupole mass spectrometer. Selective reaction monitoring was performed on the [M-H](-) m/z 128 ion resulting in the product ions m/z 85 and 42. Recoveries from catfish, tilapia and trout fortified with 10-100 mu g kg(-1) of CYA averaged 67% with a relative standard deviation (R.S.D.) of 18% (n = 107). The average method detection limit (MDL) for catfish, tilapia and trout is 3.5 mu g kg(-1). An internal standard, (13)C(3)-labeled CYA, was used in the salmon and shrimp extractions. Average recovery of CYA from salmon was 91% (R.S.D. = 15%, n = 18) with an MDL of 7.4 mu g kg(-1). Average recovery of CYA from shrimp was 85% (R.S.D. = 10%, n = 13) with an MDL of 3.5 mu g kg(-1). Published by Elsevier B.V. C1 [Karbiwnyk, Christine M.; Andersen, Wendy C.; Turnipseed, Sherri B.] US FDA, Anim Drugs Res Ctr, Denver, CO 80225 USA. [Storey, Joseph M.; Madson, Mark R.] US FDA, Denver Dist Lab, Denver, CO 80225 USA. [Gieseker, Charles M.; Miller, Ron A.; Rummel, Nathan G.; Reimschuessel, Renate] Univ Denver, Dept Chem & Biochem, Denver, CO 80208 USA. [Miller, Keith E.] 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 29 TC 51 Z9 56 U1 2 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0003-2670 J9 ANAL CHIM ACTA JI Anal. Chim. Acta PD APR 1 PY 2009 VL 637 IS 1-2 BP 101 EP 111 DI 10.1016/j.aca.2008.08.037 PG 11 WC Chemistry, Analytical SC Chemistry GA 429VB UT WOS:000264947100015 PM 19286018 ER PT J AU Andersen, WC Turnipseed, SB Karbiwnyk, CM Lee, RH Clark, SB Rowe, WD Madson, MR Miller, KE AF Andersen, Wendy C. Turnipseed, Sherri B. Karbiwnyk, Christine M. Lee, Rebecca H. Clark, Susan B. Rowe, W. Douglas Madson, Mark R. Miller, Keith E. TI Multiresidue method for the triphenylmethane dyes in fish: Malachite green, crystal (gentian) violet, and brilliant green SO ANALYTICA CHIMICA ACTA LA English DT Article; Proceedings Paper CT EuroResidue VI Conference CY MAY 19-21, 2008 CL Egmond aan Zee, NETHERLANDS DE Crystal violet; Brilliant green; Malachite green; Leuco metabolites; Catfish ID PERFORMANCE LIQUID-CHROMATOGRAPHY; PRESSURE CHEMICAL-IONIZATION; LEUCOMALACHITE GREEN; LEUCOGENTIAN VIOLET; MASS-SPECTROMETRY; LEUCO-METABOLITES; CATFISH TISSUE; CONFIRMATION; RESIDUES; SALMON AB Liquid chromatographic methods are presented for the quantitative and confirmatory determination of crystal violet (CV; also known as gentian violet), leucocrystal violet (LCV), brilliant green (BG), and leucobrilliant green (LBG) in catfish. LCV and LBG were oxidized to the chromic CV and BG by reaction with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, and residues were measured as the combined CV+/-LCV and BG+/-LBG. These methods are extensions of published methods for malachite green (MG) analysis to allow simultaneous determination of MG, CV, and BG. Residues were extracted from muscle with ammonium acetate buffer and acetonitrile, and extracts cleaned up using dichloromethane partitioning and solid-phase extraction. Extracts were analyzed by liquid chromatography with visible detection (LC-VIS). The method was validated for catfish fortified with LCV over the range 0.25-10 ng g(-1) and CV at 2 ng g(-1). Average recoveries were 90.6% (+/-8.1% R.S.D., n=45) for LCV and 84.4% (+/-4.2% R.S.D., n=6) for CV The average recovery for samples fortified with BG or LBG over the range 0.5-10 ng ng(-1) was 67.2% (+/-14.8% R.S.D., n=31). CV and BG were confirmed in fish extracts by ion trap LC-mass spectrometry (LC-MS(n)) with no discharge-atmospheric pressure chemical ionization. Average LC-MS recoveries were 96.5, 96.6, and 70.2% for samples fortified with CV, LCV, and BG or LBG. The limits of detection for CV, BG, and MG were in the range of 0.07-0.24 ng g(-1) (ppb) for the two different instrumental methods. This methodology was applied to the analysis of catfish treated with CV and BG. Published by Elsevier B.V C1 [Andersen, Wendy C.; Turnipseed, Sherri B.; Karbiwnyk, Christine M.] US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Denver, CO 80225 USA. [Lee, Rebecca H.; Clark, Susan B.; Rowe, W. Douglas; Madson, Mark R.] US FDA, Denver Lab, Denver Fed Ctr, Denver, CO 80225 USA. [Miller, Keith E.] Univ Denver, Dept Chem & Biochem, Denver, CO 80208 USA. RP Andersen, WC (reprint author), US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, POB 25087, Denver, CO 80225 USA. EM wendy.andersen@fda.hhs.gov NR 23 TC 59 Z9 62 U1 3 U2 29 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0003-2670 J9 ANAL CHIM ACTA JI Anal. Chim. Acta PD APR 1 PY 2009 VL 637 IS 1-2 BP 279 EP 289 DI 10.1016/j.aca.2008.09.041 PG 11 WC Chemistry, Analytical SC Chemistry GA 429VB UT WOS:000264947100038 PM 19286041 ER PT J AU Ball, R Shadomy, SV Meyer, A Huber, BT Leffell, MS Zachary, A Belotto, M Hilton, E Bryant-Genevier, M Schriefer, ME Miller, FW Braun, MM AF Ball, Robert Shadomy, Sean V. Meyer, Abbie Huber, Brigitte T. Leffell, Mary S. Zachary, Andrea Belotto, Michael Hilton, Eileen Bryant-Genevier, Marthe Schriefer, Martin E. Miller, Frederick W. Braun, M. Miles TI HLA Type and Immune Response to Borrelia burgdorferi Outer Surface Protein A in People in Whom Arthritis Developed After Lyme Disease Vaccination SO ARTHRITIS AND RHEUMATISM LA English DT Article ID T-CELL EPITOPE; ASSOCIATION; THERAPY; MIMICRY; HLA-DR4 AB Objective. To investigate whether persons with treatment-resistant Lyme arthritis-associated HLA alleles might develop arthritis as a result of an autoimmune reaction triggered by Borrelia burgdorferi outer surface protein A (OspA), the Lyme disease vaccine antigen. Methods. Persons in whom inflammatory arthritis had developed after Lyme disease vaccine (cases) were compared with 3 control groups: 1) inflammatory arthritis but not Lyme disease vaccine (arthritis controls), 2) Lyme disease vaccine but not inflammatory arthritis (vaccine controls), and 3) neither Lyme disease vaccine nor inflammatory arthritis (normal controls). HLA-DRB1 allele typing, Western blotting for Lyme antigen, and T cell reactivity testing were performed. Results. Twenty-seven cases were matched with 1.62 controls (54 in each control group). Odds ratios (ORs) for the presence of 1. or 2 treatment-resistant Lyme arthritis alleles were 0.8 (95% confidence interval [95% CI] 10.3-2.1), 1.6 (95% CI 0.5-4.4), and 1.75 (95% CI 0.6-5.3) in cases versus arthritis controls, vaccine controls, and normal controls, respectively. There were no significant differences in the frequency of DRB1 alleles. T cell response to OspA was similar between cases and vaccine controls, as measured using the stimulation index (OR 1.6 [95% CI 0.5-5.1]) or change in uptake of tritiated thymidine (counts per minute) (OR 0.7 [95% CI 0.2-2.3]), but cases were less likely to have IgG antibodies to OspA (OR 0.3 [95% CI 0.1-0.8]). Cases were sampled closer to the time of vaccination (median 3.59 years versus 5.48 years), and fewer cases had received 3 doses of vaccine (37% versus 93%). Conclusion. Treatment-resistant Lyme arthritis alleles were not found more commonly in persons who developed arthritis after Lyme disease vaccination, and immune responses to OspA were not significantly more common in arthritis cases. These results suggest that Lyme disease vaccine is not a major factor in the development of arthritis in these cases. C1 [Ball, Robert; Shadomy, Sean V.; Bryant-Genevier, Marthe; Braun, M. Miles] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Meyer, Abbie; Huber, Brigitte T.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Leffell, Mary S.; Zachary, Andrea] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Belotto, Michael; Hilton, Eileen] Biomed Res Alliance New York, Great Neck, NY USA. [Schriefer, Martin E.] Ctr Dis Control & Prevent, Ft Collins, CO USA. [Miller, Frederick W.] Natl Inst Environm Hlth Sci, NIH, Bethesda, MD USA. RP Ball, R (reprint author), 1401 Rockville Pike,I HFM-222, Rockville, MD 20852 USA. EM Robert.Ball@fda.hhs.gov OI Miller, Frederick/0000-0003-2831-9593 FU US Department of Health; Human Services National Vaccine Program Office; National Institute of Environmental Health Sciences, NIH FX Supported by the US Department of Health and Human Services National Vaccine Program Office, the international program of the National Institute of Environmental Health Sciences, NIH, and the FDA. Dr. Shadomy is recipient of a fellowship from the US Department of Health and Human Services National Vaccine Program Office. NR 29 TC 19 Z9 19 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD APR PY 2009 VL 60 IS 4 BP 1179 EP 1186 DI 10.1002/art.24418 PG 8 WC Rheumatology SC Rheumatology GA 432RW UT WOS:000265152800033 PM 19333928 ER PT J AU Rishikesan, S Gayen, S Thaker, YR Vivekanandan, S Manimekalai, MSS Yau, YH Shochat, SG Gruber, G AF Rishikesan, Sankaranarayanan Gayen, Shovanlal Thaker, Youg R. Vivekanandan, Subramanian Manimekalai, Malathy S. S. Yau, Yin Hoe Shochat, Susana Geifman Grueber, Gerhard TI Assembly of subunit d (Vma6p) and G (Vma10p) and the NMR solution structure of subunit G (G(1-59)) of the Saccharomyces cerevisiae V1VO ATPase SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Article DE Vacuolar-type ATPase; V1VO ATPase; Subunit d; Subunit G; Subunit E; Vma6p; Vma7p; Vma10p ID VACUOLAR H+-ATPASE; YEAST V-ATPASE; ELECTRON-MICROSCOPY; PHYSIOLOGICAL ROLES; PROTON PUMP; PROTEIN; COMPLEX; EXPRESSION; V-1-ATPASE; RESOLUTION AB Understanding the structural traits of subunit G is essential, as it is needed for V1VO assembly and function. Here solution NMR of the recombinant N-(G(1-59)) and C-terminal segment (G(61-114)) of subunit G, has been performed in the absence and presence of subunit d of the yeast V-ATPase. The data show that G does bind to subunit d via its N-terminal part, G(1-59) only. The residues of G(1-59) involved in d binding are Gly7 to Lys34. The structure of G(1-59) has been solved, revealing an alpha-helix between residues 10 and 56, whereby the first nine- and the last three residues of G(1-59) are flexible. The surface charge distribution of G(1-59) reveals an amphiphilic character at the N-terminus due to positive and negative charge distribution at one side and a hydrophobic surface on the opposite side of the structure. The C-terminus exhibits a strip of negative residues. The data imply that G(1-59)-d assembly is accomplished by hydrophobic interactions and salt-bridges of the polar residues. Based on the recently determined NMR structure of segment E18-38 of subunit E of yeast V-ATPase and the presently solved structure of G1-59, both proteins have been docked and binding epitopes have been analyzed. (C) 2009 Elsevier B.V. All rights reserved. C1 [Rishikesan, Sankaranarayanan; Gayen, Shovanlal; Thaker, Youg R.; Vivekanandan, Subramanian; Manimekalai, Malathy S. S.; Yau, Yin Hoe; Shochat, Susana Geifman; Grueber, Gerhard] Nanyang Technol Univ, Sch Biol Sci, Singapore 637551, Singapore. [Vivekanandan, Subramanian] US FDA, Struct Biol NMR Spect, CBER, Bethesda, MD 20892 USA. RP Gruber, G (reprint author), Nanyang Technol Univ, Sch Biol Sci, 60 Nanyang Dr, Singapore 637551, Singapore. EM ggrueber@ntu.edu.sg RI Yau, Yin Hoe/A-2817-2011; S, Vivekanandan/E-5197-2011; Subramanian, Vivekanandan/F-5865-2012; OI Yau, Yin Hoe/0000-0001-8136-2393; thaker, youg/0000-0002-6496-1017 FU School of Biological Sciences; Nanyang Technological University (NTU) FX This research was supported by the School of Biological Sciences, NTU. S. Rishikesan, S. Gayen and Y.R. Thaker are grateful to the authority of Nanyang Technological University (NTU) for awarding research scholarship. NR 43 TC 11 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 EI 0006-3002 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PD APR PY 2009 VL 1787 IS 4 BP 242 EP 251 DI 10.1016/j.bbabio.2009.01.010 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 424OJ UT WOS:000264575700004 PM 19344662 ER PT J AU Tsai, CA Chen, JJ AF Tsai, Chen-An Chen, James J. TI Multivariate analysis of variance test for gene set analysis SO BIOINFORMATICS LA English DT Article ID MICROARRAY DATA; EXPRESSION DATA; GLOBAL TEST; ENRICHMENT; KNOWLEDGE; ONTOLOGY; TOOLS AB Motivation: Gene class testing (GCT) or gene set analysis (GSA) is a statistical approach to determine whether some functionally predefined sets of genes express differently under different experimental conditions. Shortcomings of the Fishers exact test for the overrepresentation analysis are illustrated by an example. Most alternative GSA methods are developed for data collected from two experimental conditions, and most is based on a univariate gene-by-gene test statistic or assume independence among genes in the gene set. A multivariate analysis of variance (MANOVA) approach is proposed for studies with two or more experimental conditions. Results: When the number of genes in the gene set is greater than the number of samples, the sample covariance matrix is singular and ill-condition. The use of standard multivariate methods can result in biases in the analysis. The proposed MANOVA test uses a shrinkage covariance matrix estimator for the sample covariance matrix. The MANOVA test and six other GSA published methods, principal component analysis, SAM-GS, analysis of covariance, Global, GSEA and MaxMean, are evaluated using simulation. The MANOVA test appears to perform the best in terms of control of type I error and power under the models considered in the simulation. Several publicly available microarray datasets under two and three experimental conditions are analyzed for illustrations of GSA. Most methods, except for GSEA and MaxMean, generally are comparable in terms of power of identification of significant gene sets. C1 [Tsai, Chen-An] China Med Univ, Grad Inst Biostat & Biostat Ctr, Taichung, Taiwan. [Chen, James J.] Natl Ctr Toxicol Res, Div Personalized Nutr & Med, FDA, Jefferson, AR 72079 USA. RP Tsai, CA (reprint author), China Med Univ, Grad Inst Biostat & Biostat Ctr, Taichung, Taiwan. EM catsai@mail.cmu.edu.tw; jamesj.chen@fda.hhs.gov OI Tsai, Chen-An/0000-0002-7490-4331 FU National Science Council of Taiwan, R.O.C. [NSC 97-2118-M-039-003, NSC 97-3112-B-001-020]; National Research Program for Genomic Medicine FX National Science Council of Taiwan, R.O.C. (NSC 97-2118-M-039-003 and NSC 97-3112-B-001-020) in the National Research Program for Genomic Medicine (in part). NR 31 TC 55 Z9 55 U1 2 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD APR 1 PY 2009 VL 25 IS 7 BP 897 EP 903 DI 10.1093/bioinformatics/btp098 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 425QI UT WOS:000264651800009 PM 19254923 ER PT J AU Busch, M Walderhaug, M Custer, B Allain, JP Reddy, R McDonough, B AF Busch, Michael Walderhaug, Mark Custer, Brian Allain, Jean-Pierre Reddy, Ravi McDonough, Brian TI Risk assessment and cost-effectiveness/utility analysis SO BIOLOGICALS LA English DT Article; Proceedings Paper CT Annual Meeting of the National-Tax-Association CY OCT 04-05, 2007 CL Washington, DC SP Natl Tax Assoc DE Public health; Policy making; Blood; Transfusions ID WEST-NILE-VIRUS; BLOOD-TRANSFUSION; VIRAL MARKERS; UNITED-STATES; HEPATITIS-B; RAPID TESTS; DONATIONS; AFRICA; DONORS; HEALTH AB Decisions are usually guided by immediately available information and a significant amount of experience and judgment. For decisions concerning familiar situations and common problems, judgment and experience may work quite well, but this type of decision process can lack clarity and accountability. Public health challenges are changing as emerging diseases and expensive technologies complicate the decision-makers' task. confronting the decision-maker with new problems that include multiple potential Solutions. Decisions regarding polices and adoption of technologies are particularly complex in transfusion medicine clue to the scope of the field, implications for public health, and legal, regulatory and public expectations regarding blood safety. To assist clecision-makerS, quantitative risk assessment and cost-effectiveness analysis Lire now being more widely applied. This set of articles will introduce risk assessment and cost-effectiveness methodologies and discuss recent applications of these methods in transfusion medicine. (C) 2009 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved. C1 [Busch, Michael] Univ Calif San Francisco, Blood Syst Res Inst, San Francisco, CA 94143 USA. [Busch, Michael] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. [Walderhaug, Mark] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Custer, Brian] Univ Washington, Pharmaceut Outcomes Res & Policy Program, Seattle, WA 98195 USA. [Allain, Jean-Pierre] Univ Cambridge, Dept Haematol, Cambridge, England. [Reddy, Ravi] S African Natl Blood Serv, Johannesburg, South Africa. [McDonough, Brian] Orthoclin Diagnost, Raritan, NJ USA. RP Busch, M (reprint author), Univ Calif San Francisco, Blood Syst Res Inst, San Francisco, CA 94143 USA. EM mbusch@bloodsystems.org; mark.walderhaug@fda.hhs.gov; bcuster@bloodsystems.org; jpa1000@cam.ac.uk; Ravi.Reddy@sanbs.org.za; BMcDonou@ocdus.jnj.com NR 34 TC 13 Z9 14 U1 2 U2 3 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 APR PY 2009 VL 37 IS 2 BP 78 EP 87 DI 10.1016/j.biologicals.2009.01.007 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 441KQ UT WOS:000265768100004 PM 19243972 ER PT J AU Epstein, J Seitz, R Dhingra, N Ganz, PR Gharehbaghian, A Spindel, R Teo, D Reddy, R AF Epstein, Jay Seitz, Rainer Dhingra, Neelam Ganz, Peter R. Gharehbaghian, Ahmad Spindel, Renato Teo, Diana Reddy, Ravi TI Role of regulatory agencies SO BIOLOGICALS LA English DT Article; Proceedings Paper CT Annual Meeting of the National-Tax-Association CY OCT 04-05, 2007 CL Washington, DC SP Natl Tax Assoc DE Blood regulation; WHO; Reform; Public health AB In this paper the authors discuss the role of regulation in assuring blood safety. After an overview of the subject by a leading expert, examples are provided of regulatory systems for blood transfusion services in several Countries and regions. Additionally, the perspective of WHO is given on the essential role of national regulatory authorities in assuring the quality of national blood programmes. Collectively, the sections of this paper afford an opportunity for readers to make comparisons among different regulatory frameworks and to "benchmark" among the existing systems. Despite many differences in approach, a clear pattern emerges of worldwide efforts to strengthen blood regulatory systems. Published by Elsevier Ltd on behalf of The International Association for Biologicals. C1 [Epstein, Jay] US FDA, Rockville, MD 20857 USA. [Seitz, Rainer] Paul Ehrlich Inst, D-6070 Langen, Germany. [Ganz, Peter R.] Hlth Canada, Ctr Biol Evaluat, Ottawa, ON K1A 0L2, Canada. [Dhingra, Neelam] WHO Headquarters, Geneva, Switzerland. [Gharehbaghian, Ahmad] IBTO, Res Ctr, Tehran, Iran. [Teo, Diana] Hlth Sci Author, Singapore, Singapore. [Reddy, Ravi] S African Natl Blood Transfus Serv, Cape Town, South Africa. RP Epstein, J (reprint author), US FDA, Rockville, MD 20857 USA. EM jay.epstein@fda.hhs.gov; seira@pei.de; dhingran@who.int; peter_ganz@hc-sc.gc.ca; gharehbaghian@ibto.ir; rspindel@uol.com.br; diana_teo@hsa.gov.sg; Ravi.Reddy@sanbs.org.za NR 4 TC 6 Z9 6 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD APR PY 2009 VL 37 IS 2 BP 94 EP 102 DI 10.1016/j.biologicals.2009.01.004 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 441KQ UT WOS:000265768100006 PM 19230707 ER PT J AU Hung, HMJ Wang, SJ O'Neill, R AF Hung, H. M. James Wang, Sue-Jane O'Neill, Robert TI Challenges and regulatory experiences with non-inferiority trial design without placebo arm SO BIOMETRICAL JOURNAL LA English DT Article CT International Conference on Statistics and Life Science CY MAR 10-13, 2008 CL Munich, GERMANY SP Int Biomet Soc, European Network DE Conditional type I error rate; Fixed margin method; Non-inferiority margin; Synthesis method; Unconditional type I error rate ID ACTIVE-CONTROL TRIALS; CLINICAL-TRIALS; STATISTICAL-METHODS; ISSUES; NONINFERIORITY; EQUIVALENCE; CHOICE; EFFICACY; MARGIN; DELTA AB For a non-inferiority trial without a placebo arm, the direct comparison between the test treatment and the selected positive control is in principle the only basis for statistical inference. Therefore, evaluating the test treatment relative to the non-existent placebo presents extreme challenges and requires some kind of bridging from the past to the present with no current placebo data. For such inference based partly on an indirect bridging manipulation, fixed margin method and synthesis method are the two widely discussed methods in the recent literature. There are major differences in statistical inference paradigm between the two methods. The fixed margin method employs the historical data that assess the performances of the active control versus a placebo to guide the selection of the non-inferiority margin. Such guidance is not part of the ultimate statistical inference in the non-inferiority trial. In contrast, the synthesis method connects the historical data to the non-inferiority trial data for making broader inferences relating the test treatment to the non-existent current placebo. On the other hand, the type I error rate associated with the direct comparison between the test treatment and the active control cannot shed any light on the appropriateness of the indirect inference for faring the test treatment against the non-existent placebo. This work explores an approach for assessing the impact of potential bias due to violation of a key statistical assumption to guide determination of the non-inferiority margin. C1 [Hung, H. M. James] US FDA, Div Biometr, OB OTS CDER, Silver Spring, MD 20993 USA. [Wang, Sue-Jane; O'Neill, Robert] US FDA, Off Biostat, OTS CDER, Silver Spring, MD 20993 USA. RP Hung, HMJ (reprint author), US FDA, Div Biometr, OB OTS CDER, 10903 New Hampshire Ave,HFD 710, Silver Spring, MD 20993 USA. EM hsienming.hung@fda.hhs.gov NR 38 TC 22 Z9 23 U1 0 U2 4 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD APR PY 2009 VL 51 IS 2 BP 324 EP 334 DI 10.1002/bimj.200800219 PG 11 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 442UW UT WOS:000265867100007 PM 19358213 ER PT J AU Wang, SJ Hung, HMJ O'Neill, RT AF Wang, Sue-Jane Hung, H. M. James O'Neill, Robert T. TI Adaptive patient enrichment designs in therapeutic trials SO BIOMETRICAL JOURNAL LA English DT Article CT International Conference on Statistics and Life Science CY MAR 10-13, 2008 CL Munich, GERMANY SP Int Biomet Soc, European Network DE Adaptive enrichment algorithm; Futility; Nested patient subset; Strong control of experiment-wise type I error; Weighted Z-statistic ID CLINICAL-TRIALS; BREAST-CANCER; INTERIM; HYPOTHESES AB The utility of clinical trial designs with adaptive patient enrichment is investigated in an adequate and well-controlled trial setting. The overall treatment effect is the weighted average of the treatment effects in the mutually exclusive subsets of the originally intended entire study population. The adaptive enrichment approaches permit assessment of treatment effect that may be applicable to specific nested patient (sub)sets due to heterogeneous patient characteristics and/or differential response to treatment, e.g. a responsive patient subset versus a lack of beneficial patient subset, in all patient (sub)sets studied. The adaptive enrichment approaches considered include three adaptive design scenarios: (i) total sample size fixed and with futility stopping, (ii) sample size adaptation and futility stopping, and (iii) sample size adaptation without futility stopping. We show that regardless of whether the treatment effect eventually assessed is applicable to the originally studied patient population or only to the nested patient subsets; it is possible to devise an adaptive enrichment approach that statistically outperforms one-size-fits-all fixed design approach and the fixed design with a pre-specified multiple test procedure. We emphasize the need of additional studies to replicate the finding of a treatment effect in an enriched patient subset. The replication studies are likely to need fewer number of patients because of an identified treatment effect size that is larger than the diluted overall effect size. The adaptive designs, when applicable, are along the line of efficiency consideration in a drug development program. C1 [Wang, Sue-Jane; O'Neill, Robert T.] US FDA, Off Biostat, Div Biometr I OB, Off Translat Sci,Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Wang, SJ (reprint author), US FDA, Off Biostat, Div Biometr I OB, Off Translat Sci,Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. EM suejane.wang@fda.hhs.gov NR 27 TC 64 Z9 64 U1 1 U2 8 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD APR PY 2009 VL 51 IS 2 BP 358 EP 374 DI 10.1002/bimj.200900003 PG 17 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 442UW UT WOS:000265867100010 PM 19358222 ER PT J AU Swider, MG AF Swider, Marlene Garcia TI FDA Recommendations to Industry Regarding Outsourcing How to ensure compliance in the outsourcing environment SO BIOPHARM INTERNATIONAL LA English DT Article AB Many drug manufacturers may not have the capability to perform all manufacturing operations at their own establishments for economic reasons. Others opt for subcontracting their operations. Outsourcing introduces considerable complexity into ensuring compliance with good manufacturing practices. This article offers FDA guidance for how to ensure compliance in the outsourcing environment. C1 US FDA, CDER, Div Gastroenterol Prod, Silver Spring, MD USA. RP Swider, MG (reprint author), US FDA, CDER, Div Gastroenterol Prod, Silver Spring, MD USA. EM marlene.swider@fda.hhs.gov NR 2 TC 0 Z9 0 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS INC PI WOODLAND HILLS PA 6200 CANOGA AVE, 2ND FLR, WOODLAND HILLS, CA 91367 USA SN 1542-166X J9 BIOPHARM INT JI Biopharm. Int. PD APR PY 2009 BP 6 EP + PG 5 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 435VR UT WOS:000265371900001 ER PT J AU Zhang, M Lute, S Norling, L Hong, C Safta, A O'Connor, D Bernstein, LJ Nvang, H Blank, G Brorson, K Chen, Q AF Zhang, Min Lute, Scott Norling, Lenore Hong, Connie Safta, Aurelia O'Connor, Deborah Bernstein, Lisa J. Nvang, Hua Blank, Greg Brorson, Kurt Chen, Qi TI A Novel, Q-PCR Based Approach to Measuring Endogenous Retroviral Clearance by Capture Protein A Chromatography SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE viral clearance; protein A chromatography; production scale; design space; retrovirus-like particles; CHO cells ID TIME QUANTITATIVE PCR; CELL-CULTURE; MONOCLONAL-ANTIBODIES; RECOMBINANT PROTEINS; VIRUS REMOVAL; INACTIVATION; PARTICLES; SAFETY; CHO AB Quantification of virus removal by the purification process during production is required for clinical use of biopharmaceuticals. The current validation approach for virus removal by chromatography steps typically involves time-consuming spiking experiments with expensive model viruses at bench scale. Here we propose a novel, alternative approach that can be applied in at least one instance: evaluating retroviral clearance by protein A chromatography. Our strategy uses a quantitative PCR (Q-PCR) assay that quantifies the endogenous type C retrovirus-like particle genomes directly in production Chinese Hamster Ovary (CHO) cell culture harvests and protein A pools. This eliminates the need to perform spiking with model viruses, and measures the real virus from the process. Using this new approach, clearance values were obtained that was comparable to those from the old model-virus spike/removal approach. We tested the concept of design space for CHO retrovirus removal using samples front a protein A characterization study, where a wide range of chromatographic operating conditions were challenged, including load density, flow rate, wash, pooling, temperature, and resin life cycles. Little impact of these variables on CHO retrovirus clearance was found, arguing for implementation of the design space approach for viral clearance to Support operational ranges and manufacturing excursions. The viral clearance results from Q-PCR were confirmed by an orthogonal quantitative product-enhanced reverse transcriptase (Q-PERT) assay that quantifies CHO retrovirus by their reverse transcriptase (RT) enzyme activity. Overall, Our results demonstrate that protein A chromatography is a robust retrovirus removal step and CHO retrovirus removal can be directly measured at large scale using Q-PCR assays. C1 [Zhang, Min; Norling, Lenore; Hong, Connie; Safta, Aurelia; O'Connor, Deborah; Bernstein, Lisa J.; Nvang, Hua; Blank, Greg; Chen, Qi] Genentech Inc, Proc Res & Dev, San Francisco, CA 94080 USA. [Lute, Scott; Brorson, Kurt] CDER, FDA, Div Monoclonal Antibodies, Silver Spring, MD 20993 USA. RP Chen, Q (reprint author), Genentech Inc, Proc Res & Dev, MS10,1 DNA Way, San Francisco, CA 94080 USA. EM qi@gene.com NR 34 TC 5 Z9 5 U1 0 U2 4 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 1 PY 2009 VL 102 IS 5 BP 1438 EP 1447 DI 10.1002/bit.22172 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 418DE UT WOS:000264126600017 PM 18988264 ER PT J AU Loud, JT Thiebaut, ACM Abati, AD Filie, AC Nichols, K Danforth, D Giusti, R Prindiville, SA Greene, MH AF Loud, Jennifer T. Thiebaut, Anne C. M. Abati, Andrea D. Filie, Armando C. Nichols, Kathryn Danforth, David Giusti, Ruthann Prindiville, Sheila A. Greene, Mark H. TI Ductal Lavage in Women from BRCA1/2 Families: Is There a Future for Ductal Lavage in Women at Increased Genetic Risk of Breast Cancer? SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FINE-NEEDLE-ASPIRATION; BILATERAL PROPHYLACTIC MASTECTOMY; MUTATION CARRIERS; NIPPLE ASPIRATE; OVARIAN-CANCER; INHERITED MUTATIONS; CYTOLOGIC ATYPIA; FLUID; OOPHORECTOMY; PREVENTION AB Purpose: Ductal lavage has been used for risk stratification and biomarker development and to identify intermediate endpoints for risk-reducing intervention trials. Little is known about patient characteristics associated with obtaining nipple aspirate fluid (NAF) and adequate cell counts (>= 10 cells) in ductal lavage specimens from BRCA mutation carriers. Methods: We evaluated patient characteristics associated with obtaining NAF and adequate cell counts in ductal lavage specimens from the largest cohort of women from BRCA families yet studied (BRCA1/2 = 146, mutation-negative = 23, untested = 2). Fisher's exact test was used to evaluate categorical variables; Wilcoxon nonparametric test was used to evaluate continuous variables associated with NAF or ductal lavage cell count adequacy. Logistic regression was used to identify independent correlates of NAF and ductal lavage cell count adequacy. Results: From 171 women, 45 (26%) women had NAF and 70 (41%) women had ductal lavage samples with >= 10 cells. Postmenopausal women with intact ovaries compared with premenopausal women [odds ratio (OR), 4.8; P = 0.03] and women without a prior breast cancer history (OR, 5.2; P = 0.04) had an increased likelihood of yielding NAF. Having breast-fed (OR, 3.4; P = 0.001), the presence of NAF before ductal lavage (OR, 3.2; P = 0.003), and being premenopausal (OR, 3.0; P = 0.003) increased the likelihood of ductal lavage cell count adequacy. In known BRCA1/2 mutation carriers, only breast-feeding (OR, 2.5; P = 0.01) and the presence of NAF (OR, 3.0; P = 0.01) were independent correlates of ductal lavage cell count adequacy. Conclusions: Ductal lavage is unlikely to be useful in breast cancer screening among BRCA1/2 mutation carriers because the procedure fails to yield adequate specimens sufficient for reliable cytologic diagnosis or to support translational research activities. (Cancer Epidemiol Biomarkers Prev 2009; 18(4):1243-51) C1 [Loud, Jennifer T.; Greene, Mark H.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Abati, Andrea D.; Filie, Armando C.; Danforth, David] NCI, Div Clin Sci, NIH, Rockville, MD 20852 USA. [Prindiville, Sheila A.] NCI, Off Director, NIH, Rockville, MD 20852 USA. [Thiebaut, Anne C. M.] Inst Pasteur, INSERM, U657, F-75724 Paris, France. [Nichols, Kathryn] WESTAT Corp, Rockville, MD USA. [Giusti, Ruthann] Ctr Biol Evaluat & Res, Food & Drug Adm, Dept Hlth & Human Serv, Rockville, MD USA. RP Loud, JT (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Plaza Blvd,EPS 7028, Rockville, MD 20852 USA. EM LondJ@mail.nih.gov FU U.S. National Cancer Institute; Westat support services [NO2-CP-11019-50, N02-CP-65504] FX Intramural Research Program of the U.S. National Cancer Institute and Westat support services contracts NO2-CP-11019-50 and N02-CP-65504. NR 38 TC 13 Z9 13 U1 1 U2 2 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 2009 VL 18 IS 4 BP 1243 EP 1251 DI 10.1158/1055-9965.EPI-08-0795 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 432HV UT WOS:000265125000031 PM 19336560 ER PT J AU Gilbert, KM Przybyla, B Pumford, NR Han, T Fuscoe, J Schnackenberg, LK Holland, RD Doss, JC MacMillan-Crow, LA Blossom, SJ AF Gilbert, Kathleen M. Przybyla, Beata Pumford, Neil R. Han, Tao Fuscoe, James Schnackenberg, Laura K. Holland, Ricky D. Doss, Jason C. MacMillan-Crow, Lee Ann Blossom, Sarah J. TI Delineating Liver Events in Trichloroethylene-Induced Autoimmune Hepatitis SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID T-CELL-ACTIVATION; IMMUNOCHEMICAL DETECTION; ACUTE HEPATOTOXICITY; RETINOIC ACID; RAT-LIVER; MICE; EXPOSURE; METABOLITES; STRESS; CYP2E1 AB Exposure to the environmental pollutant trichloroethylene (TCE) has been linked to autoimmune disease development in humans. Chronic (32-week) low-level exposure to TCE has been shown to promote autoimmune hepatitis in association with CD4(+) T cell activation in autoimmune-prone MRL+/+ mice. MRL+/+ mice are usually thought of as a model of systemic lupus rather than an organ-specific disease such as autoimmune hepatitis. Consequently, the present study examined gene expression and metabolites to delineate the liver events that skewed the autoimmune response toward that organ in TCE-treated mice. Female MRL+/+ mice were treated with 0.5 mg/mL TCE in their drinking water. The results showed that TCE-induced autoimmune hepatitis could be detected in as little as 26 weeks. TCE exposure also generated a time-dependent increase in the number of antibodies specific for liver proteins. The gene expression correlated with the metabolite analysis to show that TCE upregulated the methionine/homocysteine pathway in the liver after 26 weeks of exposure. The results also showed that TCE exposure altered the expression of selective hepatic genes associated with immunity and inflammation. On the basis of these results, future mechanistic studies will focus on how alterations in genes associated with immunity and inflammation, in conjunction with protein alterations in the liver, promote liver immunogenicity in TCE-treated MRL+/+ mice. C1 [Gilbert, Kathleen M.] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Res Inst, Dept Microbiol & Immunol, Little Rock, AR 72202 USA. [Pumford, Neil R.] Univ Arkansas, Fayetteville, AR 72701 USA. [Han, Tao; Fuscoe, James; Schnackenberg, Laura K.; Holland, Ricky D.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Gilbert, KM (reprint author), Univ Arkansas Med Sci, Arkansas Childrens Hosp, Res Inst, Dept Microbiol & Immunol, 1120 Marshall St, Little Rock, AR 72202 USA. EM gilbertkathleenm@uams.edu NR 38 TC 12 Z9 12 U1 0 U2 3 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 APR PY 2009 VL 22 IS 4 BP 626 EP 632 DI 10.1021/tx800409r PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 436KF UT WOS:000265412300005 PM 19254012 ER PT J AU Zhao, BZ He, YY Chignell, CF Yin, JJ Andley, U Roberts, JE AF Zhao, Baozhong He, Yu-Ying Chignell, Colin F. Yin, Jun-Jie Andley, Usha Roberts, Joan E. TI Difference in Phototoxicity of Cyclodextrin Complexed Fullerene [(gamma-CyD)(2)/C-60] and Its Aggregated Derivatives toward Human Lens Epithelial Cells SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID WATER-SOLUBLE FULLERENES; SINGLET OXYGEN; PROTEIN PEROXIDES; STATE PROPERTIES; PLASMA-MEMBRANE; UV-RADIATION; MALONIC-ACID; C-60; CYTOTOXICITY; LIGHT AB The water-soluble fullerene derivative gamma-cyclodextrin bicapped C-60 [(gamma-CyD)(2)/C-60, CDF0] has several clinical applications, including use as a drug carrier to bypass the blood ocular barriers or a photosensitizer to treat tumors in photodynamic therapy. We have assessed the potential ocular toxicity of (gamma-CyD)(2)/C-60 and its aggregated derivatives induced by UVA and visible light in vitro in human lens epithelial cells (HLE B-3). Cell viability using the MTS assay demonstrated that 2 mu M (gamma-CyD)(2)/C-60 was highly phototoxic to HLE B-3 cells with UVA irradiation, while no effect was observed in the presence of visible light or when maintained in the dark. In contrast, the aggregated derivative (CDF150) showed neither cytotoxicity nor any phototoxic effect even at 30 mu M with either UVA or visible light irradiation. In lens cells treated with (gamma-CyD)(2)/C-60, phototoxicity was manifested as apoptosis. Singlet oxygen production measurement using the EPR/TEMP trapping technique determined that (gamma-CyD)(2)/C60 (CDF0) efficiently produced singlet oxygen. The rate of singlet oxygen production decreased with increased aggregation, with no production by the fully aggregated sample formed after 150 min of heating (CDF150). UVA irradiation of HLE B-3 in the presence of (gamma-CyD)(2)/C-60 resulted in a significant rise in intracellular protein-derived peroxides. The singlet oxygen quenchers sodium azide and histidine each significantly protected lens cells against (gamma-CyD)(2)/C-60 photodamage, but lutein and Trolox (vitamin E) did not. Clearly, singlet oxygen is an important intermediate in the phototoxicity of monomeric (gamma-CyD)(2)/fullerene. Our results also demonstrate that UVA-blocking sunglasses can limit the ocular phototoxicity of this nanomaterial, while nontoxic endogenous antioxidants like lutein or Trolox cannot provide adequate protection. C1 [Roberts, Joan E.] Fordham Univ, Dept Nat Sci, New York, NY 10023 USA. [Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Andley, Usha] Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA. [Zhao, Baozhong; He, Yu-Ying; Chignell, Colin F.] Natl Inst Environm Hlth Sci, Pharmacol Lab, Res Triangle Pk, NC 27709 USA. RP Roberts, JE (reprint author), Fordham Univ, Dept Nat Sci, 113 W 60th St, New York, NY 10023 USA. EM jroberts@fordham.edu RI Zhao, Baozhong/B-5865-2011; Yin, Jun Jie /E-5619-2014 FU NIH; National Institute of Environmental Health Sciences FX This paper is dedicated to the memory of Dr. Colin F. Chignell. This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. We thank Dr. Ann Motten, NIEHS, for help in preparation of this manuscript and Dr. Carl Bortner and Maria Sifre for their assistance with flow cytometry measurements. This manuscript has been reviewed by the National Institutes of Environmental Health Sciences and approved for publication. NR 54 TC 38 Z9 41 U1 3 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 APR PY 2009 VL 22 IS 4 BP 660 EP 667 DI 10.1021/tx800478u PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 436KF UT WOS:000265412300009 PM 19281132 ER PT J AU Brass, EP Shay, LE Leonard-Segal, A AF Brass, E. P. Shay, L. E. Leonard-Segal, A. TI Analysis of Multiple End Points in Consumer Research in Support of Switching Drugs From Prescription to Over-the-Counter Status: The Concept of End-Point Hierarchies SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT News Item AB Clinical and regulatory decision making concerning over-the-counter (OTC) drugs requires research designed to understand how consumers will self-manage treatment using the candidate OTC drug. Consumer research for an OTC drug may include studies of label comprehension, self-selection, and actual use. Definition and analysis of end points for these trials have varied in the absence of consensus on optimal approaches. research programs should prospectively prioritize the importance of label messages based on their roles in the safe and effective use of the drug. The assessment of messages for which failure to heed warnings will expose the consumer to increased risk or clinically relevant treatment failure should receive the highest priority as study end points. Based on the consequences of unheeded warnings, message-specific targets for appropriate response rates can be predefined. This prospective, hierarchical approach to end-point definition, combined with prespecification of targeted correct-response rates, has the potential to increase the scientific rigor and regulatory utility of these important research studies. C1 [Brass, E. P.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Brass, E. P.] Harbor Univ Calif, Ctr Clin Pharmacol, Dept Med, Torrance, CA USA. [Shay, L. E.; Leonard-Segal, A.] US FDA, Off Nonprescript Prod, Div Nonprescript Clin Evaluat, Silver Spring, MD USA. RP Brass, EP (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. EM ebrass@ucla.edu NR 9 TC 4 Z9 4 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 APR PY 2009 VL 85 IS 4 BP 369 EP 374 DI 10.1038/clpt.2008.254 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 422VH UT WOS:000264455300012 PM 19145230 ER PT J AU Rosa, C Campbell, A Kleppinger, C Sampson, R Tyson, C Mamay-Gentilin, S AF Rosa, Carmen Campbell, Aimee Kleppinger, Cynthia Sampson, Royce Tyson, Clare Mamay-Gentilin, Stephanie TI Quality assurance of research protocols conducted in the community: The National Institute on Drug Abuse Clinical Trials Network Experience SO CLINICAL TRIALS LA English DT Article AB Background: Quality assurance (QA) of clinical trials is essential to protect the welfare of trial participants and the integrity of the data collected. However, there is little detailed information available on specific procedures and outcomes of QA monitoring for clinical trials. Purpose: This article describes the experience of the National Institute on Drug Abuse's (NIDA) National Drug Abuse Treatment Clinical Trials Network (CTN) in devising and implementing a three-tiered QA model for rigorous multi-site randomized clinical trials implemented in community-based substance abuse treatment programs. The CTN QA model combined local and national resources and was developed to address the unique needs of clinical trial sites with limited research experience. Methods: The authors reviewed internal records maintained by the sponsor, a coordinating site (Lead Nodes), and a local site detailing procedural development, training sessions, protocol violation monitoring, and site visit reporting. Results: Between January 2001 and September 2005, the CTN implemented 21 protocols, of which 18 were randomized clinical trials, one was a quality improvement study and two were surveys. Approximately 160 community-based treatment programs participated in the 19 studies that were monitored, with a total of 6560 participants randomized across the sites. During this time 1937 QA site visits were reported across the three tiers of monitoring and the cost depended on the location of the sites and the salaries of the staff involved. One study reported 109 protocol violations (M=15.6). Examples are presented to highlight training, protocol violation monitoring, site visit frequency and intensity and cost considerations. Limitations: QA data from the entire network were not easily available for review as much of the data were not electronically accessible. The authors reviewed and discussed a representative sample of internal data from the studies and participating sites. Conclusions: The lessons learned from the CTN's experience include the need for balancing thoroughness with efficiency, monitoring early, assessing research staff abilities in order to judge the need for proactive, focused attention, providing targeted training sessions, and developing flexible tools. The CTN model can work for sponsors overseeing studies at sites with limited research experience that require more frequent, in-depth monitoring. We recommend that sponsors not develop a rigid monitoring approach, but work with the study principal investigators to determine the intensity of monitoring needed depending on trial complexity,the risks of the intervention(s), and the experience of the staff with clinical research. After careful evaluation, sponsors should then determine the best approach to site monitoring and what resources will be needed. Clinical Trials 2009; 6: 151-161. http://ctj.sagepub.com C1 [Rosa, Carmen] NIDA, Ctr Clin Trials Network, Bethesda, MD 20892 USA. [Campbell, Aimee] Columbia Univ, Sch Social Work, Social Intervent Grp, New York, NY 10027 USA. [Kleppinger, Cynthia] US FDA, Div Sci Invest, Off Compliance, CDER,Fed Res Ctr, Silver Spring, MD 20993 USA. [Sampson, Royce; Tyson, Clare; Mamay-Gentilin, Stephanie] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. RP Rosa, C (reprint author), 6001 Execut Blvd,MSC 9557, Bethesda, MD 20892 USA. EM crosa@nida.nih.gov FU Intramural NIH HHS [Z99 DA999999] NR 11 TC 9 Z9 10 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD APR PY 2009 VL 6 IS 2 BP 151 EP 161 DI 10.1177/1740774509102560 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 441GB UT WOS:000265756200007 PM 19342468 ER PT J AU Lathers, CM Schraeder, PL AF Lathers, Claire M. Schraeder, Paul L. TI Verbal autopsies and SUDEP SO EPILEPSY & BEHAVIOR LA English DT Review DE Verbal autopsies; Sudden unexpected death in epilepsy; Epilepsy; Sudden death ID SUDDEN-DEATH; EPILEPSY; VALIDITY; AFRICA; NEPAL AB There is a problem in defining the occurrence of sudden unexplained death in persons with epilepsy (SUDEP). The diagnosis of SUDEP in the United States is underused as many do not use the term on the death certificate. SUDEP is found to be more prevalent worldwide than assumed. However, data for developing countries, which are even more limited than those for Europe and North America, and do not depend on the use of autopsies, indicate that SUDEP is an underreported cause of death in persons with epilepsy. To glean information about the circumstances of the "sudden death event" in epilepsy, the verbal autopsy may be used, that is, talking with family members and/or close friends of the patient who has died unexpectedly. In contrast to developing countries, where verbal autopsy may be the only means of establishing a possible or probable cause of death, the technique of verbal autopsy may have a different use in more affluent countries. It is a defined technique to help clarify questions not answered by the standard methods of coroner and postmortem reports and not available in medical records. The purpose of verbal autopsy can be multifaceted. When used in conjunction with postmortem autopsy data on persons who die from SUDEP, it can focus on retrospective data that provide additional help in identifying more accurately the Cause of death and in conducting retrospective analysis of these postmortem examinations. The value of these cumulative data from all sources is that they provide information for future preventative policy. In circumstances where postmortem information is not or cannot be collected, verbal autopsies offer a method to find information regarding the cause of death, whether conducted in developing countries or in developed countries. In either case, the worldwide database on persons with epilepsy who die suddenly and unexpectedly will gain information that will help in determining the prevalence of SUDEP and contribute to the quest for identification of preventive interventions. (C) 2009 Elsevier Inc. All rights reserved. C1 [Lathers, Claire M.] US FDA, Ctr Vet Med, Rockville, MD 20855 USA. [Schraeder, Paul L.] Drexel Univ, Coll Med, Dept Neurol, Philadelphia, PA 19102 USA. RP Lathers, CM (reprint author), 115 S Manning Blvd, Albany, NY 12203 USA. EM lathers@attglobal.net NR 25 TC 6 Z9 6 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 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD APR PY 2009 VL 14 IS 4 BP 573 EP 576 DI 10.1016/j.yebeh.2009.02.001 PG 4 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 435JR UT WOS:000265340700001 PM 19435572 ER PT J AU Ali, SF Boulton, MC Braydish-Stolle, LK Murdock, RC Jiang, H Rongzhu, L Miltatovic, D Aschner, M Schlager, JJ Hussain, SM AF Ali, Syed F. Boulton, M. C. Braydish-Stolle, L. K. Murdock, R. C. Jiang, H. Rongzhu, L. Miltatovic, D. Aschner, M. Schlager, J. J. Hussain, S. M. TI Cytotoxic effects of manganese nanoparticles using different solvent system in astrocytes and neuronal cultured cell SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Ali, Syed F.] NCTR, Div Neurotox, Neurochem Lab, Jefferson, AR USA. [Boulton, M. C.; Braydish-Stolle, L. K.; Murdock, R. C.; Schlager, J. J.; Hussain, S. M.] AFRL HEPB, Wright Patterson AFB, OH USA. [Jiang, H.; Rongzhu, L.; Miltatovic, D.; Aschner, M.] Vanderbilt Uni Med Ctr, Nashville, TN 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 2009 VL 23 MA 759.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621501649 ER PT J AU Guenther, PM Juan, WY Lino, M Hiza, H Fungwe, TV Lucas, R AF Guenther, Patricia M. Juan, WenYen Lino, Mark Hiza, Hazel Fungwe, Thomas V. Lucas, Richard TI Diet Quality of Low-income and Higher-income Americans in 2003-2004 SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Guenther, Patricia M.; Lino, Mark; Hiza, Hazel; Fungwe, Thomas V.; Lucas, Richard] USDA, Ctr Nutr Policy & Promot, Alexandria, VA USA. [Juan, WenYen] US FDA, Div Nutr Programs, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621502599 ER PT J AU Guenther, PM Juan, WY Lino, M Hiza, HA Fungwe, TV Lucas, R AF Guenther, Patricia M. Juan, WenYen Lino, Mark Hiza, Hazel A. Fungwe, Thomas V. Lucas, Richard TI Diet Quality of Low-income and Higher-income Americans in 2003-2004 as Measured by the Healthy Eating Index-2005 SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Guenther, Patricia M.; Lino, Mark; Hiza, Hazel A.; Fungwe, Thomas V.] USDA, Ctr Nutr Policy & Promot, Alexandria, VA USA. [Lucas, Richard] USDA, Off Res & Anal, Alexandria, VA USA. [Juan, WenYen] US FDA, Div Nutr Programs, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 540.5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621502507 ER PT J AU Herman, E Knapton, A Zhang, J Lipshultz, S AF Herman, Eugene Knapton, Alan Zhang, Jun Lipshultz, Steven TI Evaluation of imatinib (Imb)-induced cardiotoxicity in the spontaneously hypertensive rat (SHR) SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Herman, Eugene; Knapton, Alan; Zhang, Jun] US FDA, Silver Spring, MD USA. [Lipshultz, Steven] Univ Miami, Sch Med, Miami, FL 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 2009 VL 23 MA 576.11 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621502307 ER PT J AU Knapton, A Morales, A Robins, T Herman, E AF Knapton, Alan Morales, Azorides Robins, Terry Herman, Eugene TI Studies with Skeletal Muscle Troponin I (sTnI), a New Biomarker of Skeletal Muscle Injury SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Knapton, Alan; Herman, Eugene] US FDA, Silver Spring, MD USA. [Morales, Azorides] Univ Miami, Sch Med, Miami, FL USA. [Robins, Terry] Pathways Diagnost, Malibu, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 760.5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621502395 ER PT J AU Rosas-Hernandez, H Jimenez-Badillo, S Gracia-Espino, E Terrones, H Terrones, M Sadovova, N Zou, X Cheng, W Schlager, JJ Hussain, SM Ali, SF Gonzalez, C AF Rosas-Hernandez, Hector Jimenez-Badillo, S. Gracia-Espino, E. Terrones, H. Terrones, M. Sadovova, N. Zou, X. Cheng, W. Schlager, J. J. Hussain, S. M. Ali, S. F. Gonzalez, C. TI Cytotoxic Effects of Silver Nanoparticles (Ag-45) in Coronary Endothelia Cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Rosas-Hernandez, Hector; Jimenez-Badillo, S.; Gonzalez, C.] Autonomous Univ SLP, San Luis Potosi, Mexico. [Gracia-Espino, E.; Terrones, H.; Terrones, M.] IPICyT, San Luis Potosi, Mexico. [Sadovova, N.; Zou, X.; Cheng, W.; Ali, S. F.] NCTR, Div Neurotoxicol, Jefferson, AR USA. [Schlager, J. J.; Hussain, S. M.] AFRL HEPB, App Biotech Branch, Dayton, OH USA. RI Terrones, Mauricio/B-3829-2014; Hector, Rosas-Hernandez/J-5130-2015 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 2009 VL 23 MA 759.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621505288 ER PT J AU Whittaker, P AF Whittaker, Paul TI Use of a rapid analytical method for identifying closely related Yersinia species to provide a procedure for food safety and security SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Whittaker, Paul] US FDA, Ctr Food Safety & Appied Nutr, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 737.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621500543 ER PT J AU Whittaker, P AF Whittaker, Paul TI Use of a rapid analytical method for identifying closely related Yersinia species to provide a procedure for food safety and security SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Whittaker, Paul] US FDA, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621500539 ER PT J AU Sprando, RL Olejnik, N Cinar, HN Ferguson, M AF Sprando, Robert L. Olejnik, Nicholas Cinar, Hediye Nese Ferguson, Martine TI A method to rank order water soluble compounds according to their toxicity using Caenorhabditis elegans, a Complex Object Parametric Analyzer and Sorter, and axenic liquid media SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Toxicity testing; Alternative animal models; Caenorhabditis elegans; COPAS; Axenic media ID CHEMICALLY-DEFINED MEDIUM; BORIC-ACID; DEVELOPMENTAL TOXICITY; LIFE-SPAN; NEMATODE; BRIGGSAE; CULTURE; RABBITS AB Complex Object Parametric Analyzer and Sorter (COPAS) parameters Time of Flight (TOF) and Extinction (EXT) were utilized to assess growth and development in Caenorhabditis elegans exposed to (in order of decreasing toxicity) sodium arsenite, sodium fluoride, caffeine, valproic acid, sodium borate or DMSO in C. elegans Habitation Medium (CeHM) for 72 h. Using multivariate statistical modeling and unique sub sampling procedures mean p-value ratios were calculated for each compound. Comparison of mean p-value ratios and/or the percent change in mean-p value ratios to controls were utilized to assess test compound toxicity. Using this assay 5 of the 6 compounds tested (83.3%) were correctly ranked according to their toxicity based on oral rat LD(50) data. Test compounds were ranked from most toxic to least toxic as follows: sodium arsenite, sodium fluoride, sodium borate, valproic acid, caffeine and DMSO. Sodium borate was found to be more toxic than caffeine and valproic acid in this bioassay. This study suggests that axenic liquid culture may be used to expose large numbers of nematodes to water soluble toxicants and the COPAS parameters TOF and EXT may be used as functional biomarkers to assess a toxin's effect on growth and development in C. elegans. Published by Elsevier Ltd. C1 [Sprando, Robert L.; Olejnik, Nicholas] US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div Toxicol, Laurel, MD 20708 USA. [Cinar, Hediye Nese] US FDA, Ctr Food Safety & Appl Nutr, Div Virulence Assessment, Laurel, MD 20708 USA. [Ferguson, Martine] US FDA, Ctr Food Safety & Appl Nutr, Off Food Def Commun & Emergency Response, Div Publ Hlth & Biostat, Laurel, MD 20708 USA. RP Sprando, RL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div Toxicol, 8301 Muirkrik Rd, Laurel, MD 20708 USA. EM Robert.sprando@fda.hhs.gov FU United States Food and Drug Administration/Center for Food Safety and Applied Nutrition/Office of Applied Research and Safety Assessment Division of Toxicology FX Funding Source: United States Food and Drug Administration/Center for Food Safety and Applied Nutrition/Office of Applied Research and Safety Assessment Division of Toxicology. The authors would like to thank Mr. Thomas Black and Mr. Michael Scott for skilled technical assistance and also Dr. David Jackson and the United States Army Center for Environmental Health Research (Fort Detrick, Maryland) for allowing us the use of their COPAS (Union Biometrica). NR 37 TC 24 Z9 32 U1 0 U2 6 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 APR PY 2009 VL 47 IS 4 BP 722 EP 728 DI 10.1016/j.fct.2009.01.007 PG 7 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 425FS UT WOS:000264623000009 PM 19162123 ER PT J AU Khan, SA Sung, K Nawaz, MS Cerniglia, CE Tarnplin, ML Phillips, RW Kelley, LC AF Khan, Saeed A. Sung, Kidon Nawaz, Mohamed S. Cerniglia, Carl E. Tarnplin, Mark L. Phillips, Robert W. Kelley, Lynda Collins TI The survivability of Bacillus anthracis (Sterne strain) in processed liquid eggs SO FOOD MICROBIOLOGY LA English DT Article DE Bacillus anthracis; Lysozyme; Spore; Vegetative cells; Liquid eggs; Model ID ANTIMICROBIAL ACTIVITY; BACTERIAL-GROWTH; LYSOZYME; MANAGEMENT; SPORES; MILK; FOOD AB In this study, we investigated the survival and inactivation kinetics of a surrogate strain of Bacillus anthracis (Sterne strain) in whole egg (WE), egg white (EW), sugared egg yolk (YSU), and salted egg yolk (YSA) at low (-20, 0, and 5 degrees C), moderate (15, 20, 25, 30, 35, and 40 degrees C), and high storage temperatures (45, 50, 55, and 60 degrees C). Outgrowth of the spores was measured as lag phase duration (LPD). Replication of vegetative cells was measured in terms of growth rate (GR) and maximum population density (MPD). Spore inactivation was recorded as inactivation rate and percent reduction in viable count. In general, spore viability decreased at low and high temperatures and increased at moderate temperatures. At 0 and 5 degrees C, a 60-100% reduction in spore viability was seen within 2-3 weeks in WE and YSU, 0-30% in YSA, and 50-100% in EW. At -20 degrees C, however, no drop in spore titer was observed in YSU and EW but a 20% drop in titer was seen in YSA and 50% in WE within 2-3 weeks. At high temperatures, WE, EW, and YSA produced a 20-50% drop in the spore titer within 1-4 h whereas YSU showed 100% inactivation within 0.75 h. At moderate storage temperatures, as the temperature increased from 15 to 40 degrees C, LPD decreased from 13.5 to 0.75 h and MPD reached 0.27-2.2 x 10(9) CFU/ml in YSU and WE, respectively. Markedly lower growth was observed in YSA (LPD = 24-270 h, MPD = 9 x 10(5) CFU/ml) and spores were inactivated completely within 1-6 h in EW. The survivability and inactivation data of B. anthracis in liquid egg products reported in this investigation will be helpful in developing risk assessment models on food biosecurity. Published by Elsevier Ltd. C1 [Khan, Saeed A.; Sung, Kidon; Nawaz, Mohamed S.; Cerniglia, Carl E.] Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Tarnplin, Mark L.] Univ Tasmania, Australian Food Safety Ctr Excellence, Hobart, Tas 7001, Australia. [Phillips, Robert W.; Kelley, Lynda Collins] USDA, Russell Res Ctr, Athens, GA USA. RP Khan, SA (reprint author), Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM saeed.khan@fda.hhs.gov FU US Department of Homeland Security (NBACC); US Department of Agriculture; US Food and Drug Administration FX The authors thank Dr Rajesh Nayak and Dr Ashraf Khan of the Division of Microbiology, NCTR, for their help and valuable and insightful discussions during this research. The work was supported in part by the US Department of Homeland Security (NBACC) and the US Department of Agriculture through an interagency agreement between the above entities and US Food and Drug Administration. Views presented in this paper do not necessarily reflect those of the FDA, Department of Homeland Security or the US Department of Agriculture. NR 24 TC 6 Z9 6 U1 0 U2 3 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 APR PY 2009 VL 26 IS 2 BP 123 EP 127 DI 10.1016/j.fm.2008.10.009 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 411FC UT WOS:000263633100001 PM 19171252 ER PT J AU Zimliki, CL Chenault, VM Mears, D AF Zimliki, Charles L. Chenault, V. Michelle Mears, David TI Glucose-dependent and -independent electrical activity in islets of Langerhans of Psammomys obesus, an animal model of nutritionally induced obesity and diabetes SO GENERAL AND COMPARATIVE ENDOCRINOLOGY LA English DT Article DE Pancreatic beta-cell; Insulin; Electrophysiology; Sand rat; Oscillation; Calcium ID PANCREATIC BETA-CELLS; MEMBRANE-POTENTIAL MEASUREMENTS; SINGLE-MOUSE; INTRACELLULAR CALCIUM; CYTOPLASMIC CA2+; OSCILLATIONS; INSULIN; SECRETION; MICE; RELEASE AB Glucose-induced insulin secretion from pancreatic beta-cells involves metabolism-induced membrane depolarization and voltage-dependent Ca(2+) influx. The electrical events in beta-cell glucose sensing have been studied intensely using mouse islets of Langerhans, but data from other species including models, of type 2 diabetes mellitus (T2DM), are lacking. In this work, we made intracellular recordings of electrical activity from cells within islets of the gerbil Psammomys obesus (fat sand rat), a model of dietary-induced T2DM. Most islet cells from lean, non-diabetic sand rats displayed glucose-induced, K(ATP) channel-dependent, oscillatory electrical activity that was similar to the classic "bursting" pattern of mouse beta-cells. However, the oscillations were slower in sand rat islets, and the dose-response curve of electrical activity versus glucose concentration was left-shifted. Of the non-bursting cells, some produced action potentials continuously, while others displayed electrical activity that was largely independent of glucose. The latter activity consisted of continuous or intermittent action potential firing and persisted, for long periods in the absence of glucose. The glucose-insensitive activity was suppressed by diazoxide, indicating that the cells expressed K(ATP) channels. Sand rat islets produced intracellular Ca(2+) oscillations reminiscent of the oscillatory electrical pattern observed in most cells, albeit with a longer period. Finally, we found that the glucose dependence of insulin secretion from sand rat islets closely paralleled that of the bursting electrical activity. We conclude that while subpopulations of K(ATP)-expressing cells in sand rat islets display heterogeneous electrical responses to glucose, insulin secretion most closely follows the oscillatory activity. The ease of recording membrane potential from sand rat islets makes this a useful model for studies of beta-cell electrical signaling during the development of T2DM. Published by Elsevier Inc. C1 [Zimliki, Charles L.; Chenault, V. Michelle; Mears, David] Uniformed Serv Univ Sch Med, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. [Zimliki, Charles L.; Chenault, V. Michelle] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. [Mears, David] Univ Chile, Fac Med, CEMC, Santiago 7, Chile. RP Mears, D (reprint author), Uniformed Serv Univ Sch Med, Dept Anat Physiol & Genet, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM dmears@usuhs.mil FU American Diabetes Association and FONDECYT (Chile) [1050571] FX The authors are indebted to Laiman Tavedi and Carol Schnupp for outstanding technical assistance. This work was supported by grants from the American Diabetes Association and FONDECYT 1050571 (Chile) to D.M. NR 51 TC 3 Z9 3 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 0016-6480 J9 GEN COMP ENDOCR JI Gen. Comp. Endocrinol. PD APR PY 2009 VL 161 IS 2 BP 193 EP 201 DI 10.1016/j.ygcen.2008.12.017 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 426DX UT WOS:000264689300007 PM 19167400 ER PT J AU Kaput, J Cotton, RGH Hardman, L Watson, M Al Aqeel, AI Al-Aama, JY Al-Mulla, F Alonso, S Aretz, S Auerbach, AD Bapat, B Bernstein, IT Bhak, J Bleoo, SL Blocker, H Brenner, SE Burn, J Bustamante, M Calone, R Cambon-Thomsen, A Cargill, M Carrera, P Cavedon, L Cho, YS Chung, YJ Claustres, M Cutting, G Dalgleish, R den Dunnen, JT Diaz, C Dobrowolski, S dos Santos, MRN Ekong, R Flanagan, SB Flicek, P Furukawa, Y Genuardi, M Ghang, H Golubenko, MV Greenblatt, MS Hamosh, A Hancock, JM Hardison, R Harrison, TM Hoffmann, R Horaitis, R Howard, HJ Barash, CI Izagirre, N Jung, J Kojima, T Laradi, S Lee, YS Lee, JY Gil-da-Silva-Lopes, VL Macrae, FA Maglott, D Marafie, MJ Marsh, SGE Matsubara, Y Messiaen, LM Moslein, G Netea, MG Norton, ML Oefner, PJ Oetting, WS O'Leary, JC de Ramirez, AMO Paalman, MH Parboosingh, J Patrinos, GP Perozzi, G Phillips, IR Povey, S Prasad, S Qi, M Quin, DJ Ramesar, RS Richards, CS Savige, J Scheible, DG Scott, RJ Seminara, D Shephard, EA Sijmons, RH Smith, TD Sobrido, MJ Tanaka, T Tavtigian, SV Taylor, GR Teague, J Topel, T Ullman-Cullere, M Utsunomiya, J van Kranen, HJ Vihinen, M Webb, E Weber, TK Yeager, M Yeom, YI Yim, SH Yoo, HS AF Kaput, Jim Cotton, Richard G. H. Hardman, Lauren Watson, Michael Al Aqeel, Aida I. Al-Aama, Jumana Y. Al-Mulla, Fahd Alonso, Santos Aretz, Stefan Auerbach, Arleen D. Bapat, Bharati Bernstein, Inge T. Bhak, Jong Bleoo, Stacey L. Bloecker, Helmut Brenner, Steven E. Burn, John Bustamante, Mariona Calone, Rita Cambon-Thomsen, Anne Cargill, Michele Carrera, Paola Cavedon, Lawrence Cho, Yoon Shin Chung, Yeun-Jun Claustres, Mireille Cutting, Garry Dalgleish, Raymond den Dunnen, Johan T. Diaz, Carlos Dobrowolski, Steven dos Santos, M. Rosario N. Ekong, Rosemary Flanagan, Simon B. Flicek, Paul Furukawa, Yoichi Genuardi, Maurizio Ghang, Ho Golubenko, Maria V. Greenblatt, Marc S. Hamosh, Ada Hancock, John M. Hardison, Ross Harrison, Terence M. Hoffmann, Robert Horaitis, Rania Howard, Heather J. Barash, Carol Isaacson Izagirre, Neskuts Jung, Jongsun Kojima, Toshio Laradi, Sandrine Lee, Yeon-Su Lee, Jong-Young Gil-da-Silva-Lopes, Vera L. Macrae, Finlay A. Maglott, Donna Marafie, Makia J. Marsh, Steven G. E. Matsubara, Yoichi Messiaen, Ludwine M. Moeslein, Gabriela Netea, Mihai G. Norton, Melissa L. Oefner, Peter J. Oetting, William S. O'Leary, James C. Oller de Ramirez, Ana Maria Paalman, Mark H. Parboosingh, Jillian Patrinos, George P. Perozzi, Giuditta Phillips, Ian R. Povey, Sue Prasad, Suyash Qi, Ming Quin, David J. Ramesar, Rajkumar S. Richards, C. Sue Savige, Judith Scheible, Dagmar G. Scott, Rodney J. Seminara, Daniela Shephard, Elizabeth A. Sijmons, Rolf H. Smith, Timothy D. Sobrido, Maria-Jesus Tanaka, Toshihiro Tavtigian, Sean V. Taylor, Graham R. Teague, Jon Toepel, Thoralf Ullman-Cullere, Mollie Utsunomiya, Joji van Kranen, Henk J. Vihinen, Mauno Webb, Elizabeth Weber, Thomas K. Yeager, Meredith Yeom, Young I. Yim, Seon-Hee Yoo, Hyang-Sook CA Human Variome Project Planning TI Planning the Human Variome Project: The Spain Report SO HUMAN MUTATION LA English DT Review DE variome; genome; mutation; database; genetic disease ID INTERNATIONAL HAPMAP PROJECT; LOCUS-SPECIFIC DATABASES; HUMAN GENOME; DEVELOPING-COUNTRIES; GLOBAL HEALTH; GENETIC-VARIATION; MISSENSE VARIANTS; MUTATION DATABASE; GRAND CHALLENGES; HUMAN-DISEASE AB The remarkable progress in characterizing the human genome sequence, exemplified by the Human Genome Project and the HapMap Consortium, has led to the perception that knowledge and the tools (e.g., microarrays) are sufficient for many if not most biomedical research efforts. A large amount of data from diverse studies proves this perception inaccurate at best, and at worst, an impediment for further efforts to characterize the variation in the human genome. Because variation in genotype and environment are the fundamental basis to understand phenotypic variability and heritability at the population level, identifying the range of human genetic variation is crucial to the development of personalized nutrition and medicine. The Human Variome Project (HVP; http://www.humanvariomeproject.org/) was proposed initially to systematically collect mutations that cause human disease and create a cyber infrastructure to link locus specific databases (LSDB). We report here the discussions and recommendations from the 2008 HVP planning meeting held in San Feliu de Guixols Spain, in May 2008. Hum Mutat 30, 496-510, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Kaput, Jim] US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. [Cotton, Richard G. H.; Hardman, Lauren; Horaitis, Rania; Howard, Heather J.; Smith, Timothy D.; Webb, Elizabeth] Genom Disorders Res Ctr, Melbourne, Vic, Australia. [Cotton, Richard G. H.] Univ Melbourne, Fac Med Dent & Hlth Sci, Parkville, Vic 3052, Australia. [Watson, Michael] Amer Coll Med Genet, Bethesda, MD USA. [Al Aqeel, Aida I.] Riyadh Mil Hosp, Dept Paediat, Riyadh, Saudi Arabia. [Al-Aama, Jumana Y.] King Abdulaziz Univ, Princess Al Jawhara Ctr Hereditary Disorders, Jeddah, Saudi Arabia. [Al-Mulla, Fahd] Kuwait Univ, Mol Pathol Unit, Kuwait, Kuwait. [Alonso, Santos] Univ Basque Country, Dept Genet Phys Anthropol & Anim Physiol, Madrid, Spain. [Aretz, Stefan] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany. [Auerbach, Arleen D.] Rockefeller Univ, Lab Human Genet & Hematol, New York, NY 10021 USA. [Bapat, Bharati] Univ Toronto, Mt Sinai Hosp, Lab Med & Pathobiol, Toronto, ON M5S 1A1, Canada. [Bernstein, Inge T.] Hvidovre Univ Hosp, Copenhagen, Denmark. [Bhak, Jong; Ghang, Ho] KRIBB, Korean Bioinformat Ctr, Chungnam, South Korea. [Bleoo, Stacey L.] Univ Alberta, Edmonton, AB, Canada. [Bloecker, Helmut] HZI Helmholtz Ctr Infect Res, Braunschweig, Germany. [Brenner, Steven E.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Bustamante, Mariona] Ctr Genom Regulat, Barcelona, Spain. [Bustamante, Mariona] Ctr Network Biomed Res Epidemiol & Publ Hlth, Barcelona, Spain. [Calone, Rita] Genet Serv ASL, Naples, Italy. [Cargill, Michele] Navigenics, Human Genet, Redwood Shores, CA USA. [Cambon-Thomsen, Anne] Fac Med Toulouse, INSERM, F-31073 Toulouse, France. [Carrera, Paola] Ist Sci San Raffaele, Unit Genom Diagnost Human Dis & Laboraf, I-20132 Milan, Italy. [Cavedon, Lawrence] NICTA, Victorian Res Lab, Parkville, Vic, Australia. [Cho, Yoon Shin; Jung, Jongsun; Lee, Jong-Young] Korean Natl Inst Hlth, Div Struct & Funct Genom, Seoul, South Korea. [Chung, Yeun-Jun] Catholic Univ Korea, Dept Microbiol & Genom, Seoul, South Korea. [Claustres, Mireille] Univ Montpellier 1, Fac Med, Montpellier, France. [Claustres, Mireille] CHU Montpellier, Genet Mol Lab, Montpellier, France. [Cutting, Garry; Hamosh, Ada] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD USA. [Dalgleish, Raymond] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England. [den Dunnen, Johan T.] Leiden Univ, Med Ctr, NL-2300 RA Leiden, Netherlands. [Diaz, Carlos] Fundacio IMIM, European Project Management & Coordinat Off, Barcelona, Spain. [Dobrowolski, Steven] Idaho Technol Inc, Res & Dev, Salt Lake City, UT USA. [Ekong, Rosemary] UCL, Dept Genet Evolut & Environm, London WC1E 6BT, England. [Flanagan, Simon B.; Povey, Sue] Royal Brisbane & Womens Hosp, Herston, Qld, Australia. [Flicek, Paul] EMBL European Bioinformat Inst, Hinxton, England. [Furukawa, Yoichi] Univ Tokyo, Inst Med Sci, Div Clin Genom Res, Tokyo 1138654, Japan. [Genuardi, Maurizio] Univ Florence, I-50121 Florence, Italy. [Golubenko, Maria V.] Inst Med Genet, Tomsk, Russia. [Greenblatt, Marc S.] Univ Vermont, Coll Med, Burlington, VT USA. [Hamosh, Ada] Johns Hopkins Univ, OMIM, Baltimore, MD USA. [Hancock, John M.] MRC Harwell, Bioinformat Grp, Harwell, Berks, England. [Hardison, Ross] Penn State Univ, University Pk, PA 16802 USA. [Harrison, Terence M.] Royal Melbourne Hosp, Hlth Sci Lib, Parkville, Vic 3050, Australia. [Harrison, Terence M.] Royal Melbourne Hosp, Victorian Mental Hlth Lib, Parkville, Vic 3050, Australia. [Hoffmann, Robert] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Barash, Carol Isaacson] Eth & Policy Consulting Inc, Genet, Boston, MA USA. [Kojima, Toshio; Utsunomiya, Joji] RIKEN, Adv Computat Sci Dept, Kanagawa, Japan. [Laradi, Sandrine] Estab Francais Du Sang, Auvergne Loire, France. [Lee, Yeon-Su] Natl Canc Ctr, Funct Genom Branch, Goyang, South Korea. [Gil-da-Silva-Lopes, Vera L.] Univ Estadual Campinas, Dept Med Genet, Campinas, Brazil. [Macrae, Finlay A.] Royal Melbourne Hosp, Dept Colorectal Med & Genet, Melbourne, Vic, Australia. [Maglott, Donna] NCBI, OMIM, Baltimore, MD USA. [Marsh, Steven G. E.] UCL, Inst Canc, Dept Haematol, London, England. [Marsh, Steven G. E.] Anthony Nolan Res Inst, HLA Informat Grp, London, England. [Marafie, Makia J.] Kuwait Med Gent Ctr, Kuwait, Kuwait. [Matsubara, Yoichi] Tohoku Univ, Sch Med, Dept Med Genet, Sendai, Miyagi 980, Japan. [Messiaen, Ludwine M.] Univ Alabama, Dept Genet, Birmingham, AL USA. [Moeslein, Gabriela] St Josefs Hosp Bochum Linden, Bochum, Germany. [Netea, Mihai G.] Radboud Univ Nijmegen, Med Ctr, Dept Med, Nijmegen, Netherlands. [Oefner, Peter J.] Univ Regensburg, Inst Funct Genom, D-8400 Regensburg, Germany. [Oetting, William S.] Univ Minnesota, Inst Human Genet, Dept Med, Minneapolis, MN 55455 USA. [O'Leary, James C.] Genet Alliance, Washington, DC USA. [Oller de Ramirez, Ana Maria] Natl Univ Cordoba, Sch Med, Pediat Clin Dept, Cordoba, Argentina. [Patrinos, George P.] Erasmus Univ, Med Ctr, Fac Med & Hlth Sci, Dept Cell Biol & Genet,MGC, Rotterdam, Netherlands. [Patrinos, George P.] Univ Patras, Dept Pharm, Patras, Greece. [Paalman, Mark H.] Human Mutat, Hoboken, NJ USA. [Parboosingh, Jillian] Univ Calgary, Calgary, AB T2N 1N4, Canada. [Perozzi, Giuditta] Natl Res Inst Food & Nutr, INRAN, Rome, Italy. [Phillips, Ian R.] Univ London, Sch Biol & Chem Sci, London WC1E 7HU, England. [Prasad, Suyash] Genzyme Therapeut Ltd, Oxford, England. [Qi, Ming] Zhejiang Univ, Sch Med, Affiliated Hosp 1, ADINOVO Ctr Genet & Genom Med, Hangzhou 310003, Zhejiang, Peoples R China. [Qi, Ming] Univ Rochester, Med Ctr, New York, NY USA. [Quin, David J.] Funding Hlth Informat Policy, Dept Human Serv, Melbourne, Vic, Australia. [Ramesar, Rajkumar S.] Univ Cape Town, Natl Infect Dis & Mol Med, ZA-7700 Rondebosch, South Africa. [Richards, C. Sue] Oregon Hlth & Sci Univ, DNA Diagnost Lab, Portland, OR 97201 USA. [Savige, Judith] Univ Melbourne, Dept Med, Epping, NSW, Australia. [Scheible, Dagmar G.] Klin Kinder & Jugendmed, Metab Dept, Reutlingen, Germany. [Scott, Rodney J.] Univ Newcastle, Fac Hlth, Discipline Med Genet, Callaghan, NSW 2308, Australia. [Seminara, Daniela] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Shephard, Elizabeth A.] UCL, Dept Biol Mol & Struct, London WC1E 6BT, England. [Sijmons, Rolf H.] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands. [Sobrido, Maria-Jesus] Inst Hlth Carlos III, Comp Network Biomed Res Rare Dis, Madrid, Spain. [Sobrido, Maria-Jesus] Fdn Publ Galega Med Xenom, Santiago De Compostela, Spain. [Tanaka, Toshihiro] RIKEN, Ctr Genom Med, Tokyo, Japan. [Tavtigian, Sean V.] IARC, Lyon, France. [Taylor, Graham R.] UK Mutat Detect Facil, Reg DNA Lab, Leeds, W Yorkshire, England. [Teague, Jon] Wellcome Trust Sanger Inst, Canc Genom Project, Hinxton, England. [Toepel, Thoralf] Univ Bielefeld, Bioinformat Dept, Tech Facil, D-4800 Bielefeld, Germany. [Ullman-Cullere, Mollie] Harvard Univ, Sch Med, Partners HealthCare Ctr Genet & Genom, Cambridge, MA 02138 USA. [van Kranen, Henk J.] Natl Inst Publ Hlth & Environm, Utrecht, Netherlands. [Vihinen, Mauno] Univ Tampere, Inst Med Technol, Bioinformat Grp, FIN-33101 Tampere, Finland. [Vihinen, Mauno] Tampere Univ Hosp, Tampere, Finland. [Weber, Thomas K.] Albert Einstein Coll Med, Dept Surg, New York, NY USA. [Weber, Thomas K.] Albert Einstein Coll Med, Dept Mol Genet, New York, NY USA. [Yeager, Meredith] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Yeom, Young I.] Korea Res Inst Biosci & Biotechnol, Med Genom Res Ctr, Taejon, South Korea. [Yoo, Hyang-Sook] KRIBB, Fred Hutchinson Canc Res Ctr, Ctr Collaborat, Taejon, South Korea. RP Kaput, J (reprint author), US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM James.kaput@fda.hhs.gov RI Bustamante, Mariona/M-7277-2015; Oefner, Peter/K-1116-2016; Brenner, Steven/A-8729-2008; Alonso, Santos/L-8316-2014; Perozzi, Giuditta/A-7460-2016; Ramesar, Raj/I-6941-2015; Netea, Mihai/N-5155-2014; Phillips, Ian/A-7337-2008; Aretz, Stefan/C-1241-2008; Hardison, Ross/G-1142-2010; Dalgleish, Raymond/A-2893-2008; Hancock, John/A-2442-2009; Vihinen, Mauno/A-8452-2012; Sijmons, Rolf/E-5829-2012; LABO, U827/A-8632-2008; Bapat, Bharati/B-5839-2014; Golubenko, Maria/A-8107-2014; Al-Mulla, Fahd/E-2068-2015 OI Flicek, Paul/0000-0002-3897-7955; Burn, John/0000-0002-9823-2322; Savige, Judy/0000-0002-6813-0288; Bustamante, Mariona/0000-0003-0127-2860; Oefner, Peter/0000-0002-1499-3977; Brenner, Steven/0000-0001-7559-6185; Smith, Timothy/0000-0001-9068-4642; Alonso, Santos/0000-0003-0221-4048; Auerbach, Arleen/0000-0002-6911-8379; Perozzi, Giuditta/0000-0003-1755-6104; Ramesar, Raj/0000-0001-5688-1634; Aretz, Stefan/0000-0002-5228-1890; Hardison, Ross/0000-0003-4084-7516; Dalgleish, Raymond/0000-0001-7667-187X; Hancock, John/0000-0003-2991-2217; Vihinen, Mauno/0000-0002-9614-7976; Sijmons, Rolf/0000-0001-8446-2779; Golubenko, Maria/0000-0002-7692-9954; Al-Mulla, Fahd/0000-0001-5409-3829 FU Medical Research Council [MC_U142684171]; NHGRI NIH HHS [RC2 HG005573]; NIDDK NIH HHS [R01 DK065806] NR 105 TC 33 Z9 36 U1 0 U2 21 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD APR PY 2009 VL 30 IS 4 BP 496 EP 510 DI 10.1002/humu.20972 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 430RO UT WOS:000265006400002 PM 19306394 ER PT J AU Osorio, M Wu, YP Singh, S Merkel, TJ Bhattacharyya, S Blake, MS Kopecko, DJ AF Osorio, Manuel Wu, Yanping Singh, Sunil Merkel, Tod J. Bhattacharyya, Siba Blake, Milan S. Kopecko, Dennis J. TI Anthrax Protective Antigen Delivered by Salmonella enterica Serovar Typhi Ty21a Protects Mice from a Lethal Anthrax Spore Challenge SO INFECTION AND IMMUNITY LA English DT Article ID ESCHERICHIA-COLI HEMOLYSIN; BACILLUS-ANTHRACIS; ATTENUATED SALMONELLA; CONFERS PROTECTION; VACCINE VECTOR; EDEMA FACTOR; TOXIN; IMMUNOGENICITY; LIVE; STRAIN AB Bacillus anthracis, the etiological agent of anthrax disease, is a proven weapon of bioterrorism. Currently, the only licensed vaccine against anthrax in the United States is AVA Biothrax, which, although efficacious, suffers from several limitations. This vaccine requires six injectable doses over 18 months to stimulate protective immunity, requires a cold chain for storage, and in many cases has been associated with adverse effects. In this study, we modified the B. anthracis protective antigen (PA) gene for optimal expression and stability, linked it to an inducible promoter for maximal expression in the host, and fused it to the secretion signal of the Escherichia coli alpha-hemolysin protein (HlyA) on a low-copy-number plasmid. This plasmid was introduced into the licensed typhoid vaccine strain, Salmonella enterica serovar Typhi strain Ty21a, and was found to be genetically stable. Immunization of mice with three vaccine doses elicited a strong PA-specific serum immunoglobulin G response with a geometric mean titer of 30,000 (range, 5,800 to 157,000) and lethal-toxin-neutralizing titers greater than 16,000. Vaccinated mice demonstrated 100% protection against a lethal intranasal challenge with aerosolized spores of B. anthracis 7702. The ultimate goal is a temperature-stable, safe, oral human vaccine against anthrax infection that can be self-administered in a few doses over a short period of time. C1 [Osorio, Manuel; Wu, Yanping; Singh, Sunil; Bhattacharyya, Siba; Kopecko, Dennis J.] US FDA, Lab Enter & Sexually Transmitted Dis, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Merkel, Tod J.] US FDA, Lab Resp & Special Pathogens, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Blake, Milan S.] US FDA, Lab Bacterial Polysaccharides, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Osorio, M (reprint author), 29 Lincoln Dr,Bldg 29,Room 431, Bethesda, MD 20892 USA. EM manuel.osorio@fda.hhs.gov FU Trans-NIH/FDA Biodefense Program FX 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 45 TC 21 Z9 25 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2009 VL 77 IS 4 BP 1475 EP 1482 DI 10.1128/IAI.00828-08 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 419AM UT WOS:000264191500023 PM 19179420 ER PT J AU Kopecko, DJ Sieber, H Ures, JA Furer, A Schlup, J Knof, U Collioud, A Xu, DQ Colburn, K Dietrich, G AF Kopecko, Dennis J. Sieber, Heike Ures, Jose A. Fuerer, Andreas Schlup, Jacqueline Knof, Ulrich Collioud, Andre Xu, DeQi Colburn, Kevin Dietrich, Guido TI Genetic stability of vaccine strain Salmonella Typhi Ty21a over 25 years SO INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article DE Typhoid fever vaccine; Vaccine strain Ty21a; Genetic and phenotypic analyses ID ENTERIC-COATED CAPSULES; CONTROLLED FIELD TRIAL; LIVE ORAL VACCINE; VI ANTIGEN; TY 21A; EXPRESSION; MUTANT; TYPHIMURIUM; FORMULATION; PROTECTION AB The attenuated live bacterial vaccine strain Salmonella enterica Serovar Typhi Ty21a is the main constituent of Vivotif, the only licensed oral vaccine against typhoid fever. The strain was developed in the 1970s by chemical mutagenesis. In the course of this mutagenesis, a number of mutations were introduced into the vaccine strain. Characterisation of the vaccine strain during development as well as release of master- and working seed lots (MSL and WSL) and commercial batches is based on phenotypic assays assessing microbiological and biochemical characteristics of Ty21a. In the current study, we have analysed by DNA sequencing the specific mutations originally correlated with the attenuation of strain Ty21a. These data demonstrate the stability of these mutations for MSLs and WSLs of Ty21a produced between 1980 and 2005. Finally, we have confirmed the correlation of these genetic mutations with the expected phenotypic attenuations for the seed lots used in vaccine manufacture over 25 years. (c) 2008 Elsevier GmbH. All rights reserved. C1 [Kopecko, Dennis J.; Xu, DeQi; Colburn, Kevin] US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Sieber, Heike; Ures, Jose A.; Fuerer, Andreas; Schlup, Jacqueline; Knof, Ulrich; Collioud, Andre; Dietrich, Guido] Berna Biotech AG, CH-3018 Bern, Switzerland. RP Dietrich, G (reprint author), GlaxoSmithKline Biol, Parc Noire Epine,Rue Fleming 20, B-1300 Wavre, Belgium. EM guido.h.dietrich@gskbio.com NR 39 TC 17 Z9 19 U1 0 U2 2 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 1438-4221 EI 1618-0607 J9 INT J MED MICROBIOL JI Int. J. Med. Microbiol. PD APR PY 2009 VL 299 IS 4 BP 233 EP 246 DI 10.1016/j.ijmm.2008.09.003 PG 14 WC Microbiology; Virology SC Microbiology; Virology GA 436NN UT WOS:000265420900001 PM 19121604 ER PT J AU Lappalainen, SK Gomatam, SV Hitchins, VM AF Lappalainen, Sharon K. Gomatam, Shanti V. Hitchins, Victoria M. TI Residual Total Protein and Total Organic Carbon Levels on Reprocessed Gastrointestinal (GI) Biopsy Forceps SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE cleaning; single-use devices; residual total proteins; residual total organic carbon; GI biopsy forceps ID LARYNGEAL MASK DEVICES; SURGICAL-INSTRUMENTS; SINGLE-USE; CONTAMINATION; DISINFECTION; ENDOSCOPES; BRONCHOSCOPE; DEPOSITS AB Many single-use (disposable) devices are reprocessed between patient uses. In the past, a visual determination was considered the endpoint of "clean" for cleaned reusable devices. In this report, we measured quantitative endpoints by measuring residual total protein and residual total organic carbon before and after cleaning with commercially available cleaners for medical devices on 15 single-use gastrointestinal biopsy forceps inoculated with a three-protein test soil before and after cleaning. Each device was extracted separately and tested using Bradford's reagent for total protein and a direct digestion method for total organic carbon. Data for pre- and post-cleaned devices were generated for all five cleaning cycles. The highest amounts of residual total protein and total organic carbon found on precleaned devices were 61.8 mu g/cm(2) and 39.1 mu g/cm(2), respectively, on the outer surfaces. The highest amounts of residual total protein and total organic carbon on postcleaned device extracts were 4.0 mu g/cm(2) and 2.2 mu g/cm(2), respectively, on the outer surfaces. All postcleaned devices were visually clean. Our results provide quantitative total protein and total organic carbon levels for cleaned single-use biopsy forceps. (C) 2008 Wiley Periodicals, Inc.* J Biomed Mater Res Part B: Appl Biomater 89B: 172-176, 2009 C1 [Lappalainen, Sharon K.; Gomatam, Shanti V.; Hitchins, Victoria M.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Hitchins, VM (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. EM victoria.hitchins@fda.hhs.gov NR 25 TC 2 Z9 2 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4973 EI 1552-4981 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD APR PY 2009 VL 89B IS 1 BP 172 EP 176 DI 10.1002/jbm.b.31202 PG 5 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 422XE UT WOS:000264460200020 PM 18777580 ER PT J AU Scherr, D Dalal, D Chilukuri, K Dong, J Spragg, D Henrikson, CA Nazarian, S Cheng, A Berger, RD Abraham, TP Calkins, H Marine, JE AF Scherr, Daniel Dalal, Darshan Chilukuri, Karuna Dong, Jun Spragg, David Henrikson, Charles A. Nazarian, Saman Cheng, Alan Berger, Ronald D. Abraham, Theodore P. Calkins, Hugh Marine, Joseph E. TI Incidence and Predictors of Left Atrial Thrombus Prior to Catheter Ablation of Atrial Fibrillation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE ablation; atrial fibrillation; complication; echocardiography; thrombus ID TRANSESOPHAGEAL ECHOCARDIOGRAPHY; APPENDAGE THROMBUS; ANTICOAGULATION; ACCURACY; EFFICACY; STROKE; RECOMMENDATIONS; CARDIOVERSION; TOMOGRAPHY; CONTRAST AB Left Atrial Thrombus Prior to AF Ablation. Background: Transesophageal echocardiography (TEE) is commonly used prior to catheter ablation of atrial fibrillation (AF) in order to exclude left atrial (LA) thrombus. However, the incidence and predictors of LA thrombus detected with TEE have not been systematically examined in this setting. Methods: This study included 732 cases (mean age 57 +/- 11 years; 23% female; 353 persistent AF) in 585 consecutive patients referred for catheter ablation of AF. Patients were anticoagulated for at least 4 weeks prior to the procedure and then bridged with enoxaparin. TEE was performed in all cases within 24 hours prior to ablation. Results: Preprocedural TEE revealed LA thrombus in 12 of 732 cases (1.6%), all located in the LA appendage. Among these 12 patients, 9 had persistent AF and 3 had paroxysmal AF. All patients with thrombus had an LA size >= 4.5 cm. LA thrombus was present in 0.3%, 1.4%, and 5.3% of patients with CHADS(2) scores of 0, 1, and >= 2, respectively. In multivariate analysis, a CHADS(2) score >= 2 and larger LA diameter remained significant predictors of LA thrombus. Conclusions: Despite oral anticoagulation treatment, there is a small but significant incidence of LA thrombus by TEE prior to AF ablation. A CHADS(2) score >= 2 and larger LA diameter are independent predictors of LA thrombus in this patient population, while type of AF or rhythm at the time of TEE is not. The risk of LA thrombus is low in patients with a CHADS(2) score of 0 and in patients with an LA diameter < 4.5 cm. (J Cardiovasc Electrophysiol, Vol. 20, pp. 379-384, April 2009). C1 [Scherr, Daniel; Dalal, Darshan; Chilukuri, Karuna; Dong, Jun; Spragg, David; Henrikson, Charles A.; Nazarian, Saman; Cheng, Alan; Berger, Ronald D.; Abraham, Theodore P.; Calkins, Hugh; Marine, Joseph E.] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Scherr, Daniel] Med Univ Graz, Dept Med, Div Cardiol, Graz, Austria. [Dong, Jun] US FDA, Ctr Devices & Radiol Hlth, Div Cardiovasc Dis, Rockville, MD 20857 USA. RP Marine, JE (reprint author), Johns Hopkins Med Inst, 4940 Eastern Ave,A-1 E, Baltimore, MD 21224 USA. EM jmarine2@jhmi.edu NR 25 TC 56 Z9 58 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD APR PY 2009 VL 20 IS 4 BP 379 EP 384 DI 10.1111/j.1540-8167.2008.01336.x PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 424FB UT WOS:000264549800004 PM 19017348 ER PT J AU Uhlenhaut, C Cohen, JI Fedorko, D Nanda, S Krause, PR AF Uhlenhaut, Christine Cohen, Jeffrey I. Fedorko, Daniel Nanda, Santosh Krause, Philip R. TI Use of a universal virus detection assay to identify human metapneumovirus in a hematopoietic stem cell transplant recipient with pneumonia of unknown origin SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article DE Virus discovery; Virus detection; Immunocompromised host; Virus disease diagnosis; Virus disease etiology ID IDENTIFICATION; CORONAVIRUS; MICROARRAY; PATHOGENS; PCR AB Background: Development of uncommon vital infections in immunocompromised transplant recipients can pose major diagnostic challenges. We present a case report of an immunocompromised patient Suffering from pneumonia, for which the causative agent was not identified by routine methods. Objectives: To identify the potential cause of the pneumonia using a degenerate oligonucleotide primer (DOP)-PCR assay that is designed to detect all viruses. Study design: DOP-PCR was applied to bronchoalveolar lavage fluid from this patient. Generic PCR products were cloned and sequenced. Results: The novel universal virus assay detected human metapneumovirus in the clinical sample. The finding was confirmed by two independent metapneumovirus specific PCRs targeting different regions of the vital genome. Conclusions: The DOP-PCR Was used to detect and identify the sequence of an unidentified virus. This Study provides proof of concept for the use of clinically relevant specimens in this unbiased universal assay, which requires no previous viral sequence information. Published by Elsevier B.V. C1 [Uhlenhaut, Christine; Nanda, Santosh; Krause, Philip R.] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. [Cohen, Jeffrey I.] NIAID, Med Virol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. [Fedorko, Daniel] NIH, Microbiol Lab, Ctr Clin, Bethesda, MD 20892 USA. RP Krause, PR (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bldg 29A,Room 1C16,HFM 457,29 Lincoln Dr, Bethesda, MD 20892 USA. EM philip.krause@fda.hhs.gov OI Krause, Philip/0000-0002-1045-7536 FU National Institute of Allergy and Infectious Diseases; National Institutes of Health Clinical Center FX This study was supported by the intramural research programs of the National Institute of Allergy and Infectious Diseases and the National Institutes of Health Clinical Center. We gratefully acknowledge the FDA/CBER core facility for sequencing. We also thank Dr. Shuang Tang, Dr. Shasta McClenahan and Amita Patel for helpful comments. NR 15 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD APR PY 2009 VL 44 IS 4 BP 337 EP 339 DI 10.1016/j.jcv.2009.01.011 PG 3 WC Virology SC Virology GA 436WL UT WOS:000265446700018 PM 19250860 ER PT J AU Cohen, NJ Deeds, JR Wong, ES Hanner, RH Yancy, HF White, KD Thompson, TM Wahl, M Pham, TD Guichard, FM Huh, I Austin, C Dizikes, G Gerber, SI AF Cohen, Nicole J. Deeds, Jonathan R. Wong, Eugene S. Hanner, Robert H. Yancy, Haile F. White, Kevin D. Thompson, Trevonne M. Wahl, Michael Pham, Tu D. Guichard, Frances M. Huh, In Austin, Connie Dizikes, George Gerber, Susan I. TI Public Health Response to Puffer Fish (Tetrodotoxin) Poisoning from Mislabeled Product SO JOURNAL OF FOOD PROTECTION LA English DT Article ID LAGOCEPHALUS-LUNARIS-LUNARIS; BAYESIAN-INFERENCE; DNA BARCODES; IDENTIFICATION; SAXITOXIN; LIFE AB Tetrodotoxin is a neurotoxin that occurs in select species of the family Tetraodontidae (puffer fish). It causes paralysis and potentially death if ingested in sufficient quantities. In 2007, two individuals developed symptoms consistent with tetrodotoxin poisoning after ingesting home-cooked puffer fish purchased in Chicago. Both the Chicago retailer and the California supplier denied having sold or imported puffer fish but claimed the product was monkfish. However; genetic analysis and visual inspection determined that the ingested fish and others from the implicated lot retrieved from the supplier belonged to the family Tetraodontidae. Tetrodotoxin was detected at high levels in both remnants of the ingested meal and fish retrieved from the implicated lot. The investigation led to a Voluntary recall of monkfish distributed by the supplier in three states and placement of the supplier on the U.S. Food and Drug Administration's Import Alert for species misbranding. This case of tetrodotoxin poisoning highlights the need for continued stringent regulation Of Puffer fish importation by the U.S. Food and Drug Administration, education of the public regarding the dangers of puffer fish consumption. and raising awareness among medical providers of the diagnosis and management of foodborne toxin ingestions and the need for reporting to public health agencies. C1 [Deeds, Jonathan R.; White, Kevin D.] US Food & Drug Adm Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Cohen, Nicole J.; Pham, Tu D.; Guichard, Frances M.; Gerber, Susan I.] Chicago Dept Publ Hlth, Chicago, IL 60612 USA. [Dizikes, George] Illinois Dept Publ Hlth, Chicago, IL 60612 USA. [Austin, Connie] Illinois Dept Publ Hlth, Springfield, IL 62761 USA. [Huh, In] Swedish Covenant Hosp, Chicago, IL 60625 USA. [Wong, Eugene S.; Hanner, Robert H.] Univ Guelph, Biodivers Inst Ontario, Guelph, ON N1G 2W1, Canada. [Yancy, Haile F.] US Food & Drug Adm Ctr Vet Med, Rockville, MD 20855 USA. [Thompson, Trevonne M.; Wahl, Michael] Illinois Poison Ctr, Chicago, IL 60606 USA. RP Cohen, NJ (reprint author), Ctr Dis Control & Prevent, Chicago Quarantine Stn, AMC OHare, POB 66012, Chicago, IL 60666 USA. EM ncohen@cdc.gov; jonathan.deeds@fda.hhs.gov NR 33 TC 56 Z9 58 U1 4 U2 21 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 2009 VL 72 IS 4 BP 810 EP 817 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 432HS UT WOS:000265124700018 PM 19435231 ER PT J AU Cho, CY Keener, WK Garber, EAE AF Cho, Chung Y. Keener, William K. Garber, Eric A. E. TI Application of Deadenylase Electrochemiluminescence Assay for Ricin to Foods in a Plate Format SO JOURNAL OF FOOD PROTECTION LA English DT Article ID N-GLYCOSIDASE ACTIVITY; A-CHAIN; RNA; MECHANISM; ABRIN AB A recently developed bead-based deadenylase electrochemiluminescence assay for ricin is simple and sensitive in its ability to detect ricin, based on the catalytic activity of the toxin subunit, ricin A chain. The assay was modified to work in a 96-well plate format and evaluated by using juice samples. The plate-based assay. unlike the bead-based assay, includes wash steps that enable the removal of food particles. These steps minimize matrix effects and improve the signal-to-noise ratios and limits of detection (LOD). The LOD values for ricin in apple juice, vegetable juice, and citrate buffer by using the bead-based assay were 0.4, 1, and 0.1 mu g/ml, respectively. In contrast, the LOD values for ricin by using the plate-based assay were 0.04, 0.1, and 0.04 mu g/ml in apple juice, vegetable juice, and citrate buffer, respectively. The plate-based assay displayed three- to 10-fold lower LOD values than did the bead-based assay. Signal-to-noise ratios for the plate-based assay were comparable to those for the bead-based assay for ricin in citrate buffer. but 2- to 4.5-fold higher when the plate-based assay was used for analysis of juice samples. C1 [Cho, Chung Y.; Garber, Eric A. E.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Keener, William K.] Idaho Natl Lab, Idaho Falls, ID 83415 USA. RP Cho, CY (reprint author), US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Chung.Cho@fda.hhs.gov NR 17 TC 8 Z9 9 U1 0 U2 2 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD APR PY 2009 VL 72 IS 4 BP 903 EP 906 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 432HS UT WOS:000265124700035 PM 19435248 ER PT J AU Babu, US Gaines, D Raybourne, RB Fonseca, M Williams, K Bigley, E Pereira, M AF Babu, Uma S. Gaines, Dennis Raybourne, Richard B. Fonseca, Maira Williams, Kristina Bigley, Elmer Pereira, Marion TI Effect of caspase inhibitors on Salmonella typhimurium induced apoptosis of chicken macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Babu, Uma S.; Gaines, Dennis; Raybourne, Richard B.; Fonseca, Maira; Williams, Kristina; Bigley, Elmer; Pereira, Marion] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2009 VL 182 SU 1 MA 133.27 PG 1 WC Immunology SC Immunology GA V44QN UT WOS:000209763602265 ER PT J AU Choi, SC Narayanan, S Borrego, F Coligan, JE AF Choi, Seung-Chul Narayanan, Sriram Borrego, Francisco Coligan, John E. TI Toso expression during B cell development SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Choi, Seung-Chul; Narayanan, Sriram; Coligan, John E.] NIAID, RCBS, LIG, NIH, Rockville, MD USA. [Borrego, Francisco] US FDA, LMDB, CDER, 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 2009 VL 182 SU 1 MA 82.3 PG 1 WC Immunology SC Immunology GA V44QN UT WOS:000209763601188 ER PT J AU Narayanan, S Borrego, F Coligan, JE AF Narayanan, Sriram Borrego, Francisco Coligan, John E. TI Role of TOSO in activation induced cell death of human T- and NK cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Narayanan, Sriram; Coligan, John E.] NIAID, RCBS, LIG, NIH, Rockville, MD USA. [Borrego, Francisco] 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 2009 VL 182 SU 1 MA 82.2 PG 1 WC Immunology SC Immunology GA V44QN UT WOS:000209763601182 ER PT J AU Warfel, JM D'Agnillo, F AF Warfel, Jason M. D'Agnillo, Felice TI Anthrax lethal toxin enhances I kappa B kinase (IKK) activation and differentially regulates pro-inflammatory genes in human endothelium SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Warfel, Jason M.; D'Agnillo, Felice] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Warfel, Jason M.] Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20007 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 2009 VL 182 SU 1 MA 135.3 PG 1 WC Immunology SC Immunology GA V44QN UT WOS:000209763602364 ER PT J AU Williams, KM Bigley, EC Babu, US AF Williams, Kristina M. Bigley, Elmer C. Babu, Uma S. TI Identification of a Mamu Class I-restricted listeriolysin T-cell epitope in rhesus macaques infected with Listeria monocytogenes (LM) SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Williams, Kristina M.; Bigley, Elmer C.; Babu, Uma S.] US FDA, CFSAN, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2009 VL 182 SU 1 MA 129.13 PG 1 WC Immunology SC Immunology GA V44QN UT WOS:000209763602174 ER PT J AU Zaitseva, M Meseda, C Kapnick, S Manischewitz, J Nelson, H Merchlinsky, M Weir, J Golding, H AF Zaitseva, Marina Meseda, Clement Kapnick, Senta Manischewitz, Jody Nelson, Henriette Merchlinsky, Michael Weir, Jerry Golding, Hana TI Quantitative bioimaging of the WR and IHDJ vaccinia virus dissemination and the effects of prophylactic immunoglobulin treatments SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Zaitseva, Marina; Meseda, Clement; Kapnick, Senta; Manischewitz, Jody; Merchlinsky, Michael; Weir, Jerry; Golding, Hana] US FDA, Div Viral Prod, CBER, Bethesda, MD 20014 USA. [Nelson, 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 2009 VL 182 SU 1 MA 128.23 PG 1 WC Immunology SC Immunology GA V44QN UT WOS:000209763602129 ER PT J AU Brenner, M Coelho, SG Beer, JZ Miller, SA Wolber, R Smuda, C Hearing, VJ AF Brenner, Michaela Coelho, Sergio G. Beer, Janusz Z. Miller, Sharon A. Wolber, Rainer Smuda, Christoph Hearing, Vincent J. TI Long-Lasting Molecular Changes in Human Skin after Repetitive In Situ UV Irradiation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID MESENCHYMAL-EPITHELIAL INTERACTIONS; CUTANEOUS MALIGNANT-MELANOMA; COLONY-STIMULATING FACTOR; ULTRAVIOLET-B RADIATION; STEM-CELL FACTOR; HUMAN MELANOCYTES; GENE-EXPRESSION; GROWTH-FACTOR; TUMOR PROGRESSION; DOWN-REGULATION AB It is known that UV modulates the expression of paracrine factors that regulate melanocyte function in the skin. We investigated the consequences of repetitive UV exposure of human skin in biopsies of 10 subjects with phototypes 2-3.5 taken 1-4 years later. The expression of melanogenic factors (TYR, MART1, MITF), growth factors/receptors (SCF/KIT, bFGF/FGFR1, ET1/EDNRB, HGF, GM-CSF), adhesion molecules (beta-catenin, E-cadherin, N-cadherin), cell cycle proteins (PCNA, cyclins D1, E2) as well as Bcl-2, DKK1, and DKK3, were analyzed by immunohistochemistry. Most of those markers showed no detectable changes at >= 1 year after the repetitive UV irradiation. Although increased expression of EDNRB protein was detected in 3 of 10 UV-irradiated subjects, there was no detectable change in the expression of ET1 protein or in EDNRB mRNA levels. In summary, only the expression of TYR, MART1, and/or EDNRB, and only in some subjects, was elevated at >= 1 year after UV irradiation. Thus the long-term effects of repetitive UV irradiation on human skin did not lead to significant changes in skin morphology and there is considerable subject-to-subject variation in responses. The possibility that changes in the expression and function of EDNRB triggers downstream activation of abnormal melanocyte proliferation and differentiation deserves further investigation. C1 [Coelho, Sergio G.; Hearing, Vincent J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Brenner, Michaela] Univ Munich, Dept Dermatol, D-8000 Munich, Germany. [Beer, Janusz Z.; Miller, Sharon A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Wolber, Rainer; Smuda, Christoph] Skin Res Beiersdorf AG, R&D, Hamburg, Germany. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 2132,MSC 4256, Bethesda, MD 20892 USA. EM hearingv@nih.gov FU National Cancer Institute; Food and Drug Administration (FDA) FX This research was supported by the Intramural Research Program of the National Cancer Institute at NIH, and by the Office of Science, Office of Women's Health and the Center for Devices and Radiological Health, Food and Drug Administration (FDA). The authors wish to thank Dr Thierry Passeron and Dr Itaru Suzuki for their advice and help on the TISH analysis. NR 70 TC 10 Z9 10 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2009 VL 129 IS 4 BP 1002 EP 1011 DI 10.1038/jid.2008.325 PG 10 WC Dermatology SC Dermatology GA 430MW UT WOS:000264994200025 PM 18946495 ER PT J AU Coelho, SG Miller, SA Zmudzka, BZ Beer, JZ Hearing, VJ AF Coelho, S. G. Miller, S. A. Zmudzka, B. Z. Beer, J. Z. Hearing, V. J. TI Melanin dispersion to basal keratinocytes may play a role in UV-induced long-lasting pigmentation in human skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-of-Investigative-Dermatology CY MAY 06-09, 2009 CL Montreal, CANADA SP Soc Investigat Dematol C1 [Coelho, S. G.; Hearing, V. J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Miller, S. A.; Zmudzka, B. Z.; Beer, J. Z.] US FDA, Ctr Devices & Radiol Hlth, 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2009 VL 129 MA 783 BP S131 EP S131 PG 1 WC Dermatology SC Dermatology GA 430MU UT WOS:000264994000782 ER PT J AU Ha, L Ponnamperuma, R Weinberg, W AF Ha, L. Ponnamperuma, R. Weinberg, W. TI Stable overexpression of Delta Np63 alpha blocks senescence and supports long-term proliferation in keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-of-Investigative-Dermatology CY MAY 06-09, 2009 CL Montreal, CANADA SP Soc Investigat Dematol C1 [Ha, L.; Ponnamperuma, R.; Weinberg, W.] FDA, DMA OBP CDER, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2009 VL 129 MA 165 BP S28 EP S28 PG 1 WC Dermatology SC Dermatology GA 430MU UT WOS:000264994000164 ER PT J AU King, KE Muraleedharan, D Ponnamperuma, RM Gerdes, MJ Weinberg, WC AF King, K. E. Muraleedharan, D. Ponnamperuma, R. M. Gerdes, M. J. Weinberg, W. C. TI Overexpression of Delta Np63 alpha negatively regulates multiple protease inhibitors in keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-of-Investigative-Dermatology CY MAY 06-09, 2009 CL Montreal, CANADA SP Soc Investigat Dematol C1 [King, K. E.; Muraleedharan, D.; Ponnamperuma, R. M.; Weinberg, W. C.] FDA Ctr Drug Evaluat & Res, Off Biotechnol Prod, Bethesda, MD USA. [Gerdes, M. J.] GE Global Res Ctr, Niskayuna, NY 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2009 VL 129 MA 159 BP S27 EP S27 PG 1 WC Dermatology SC Dermatology GA 430MU UT WOS:000264994000158 ER PT J AU Neustadter, J Roberts, S Filler, R Kwong, B Lewis, J Gaian, A Reddy, S Tigelaar, R Fu, P Kaplan, D Hayday, A Girardi, M AF Neustadter, J. Roberts, S. Filler, R. Kwong, B. Lewis, J. Gaian, A. Reddy, S. Tigelaar, R. Fu, P. Kaplan, D. Hayday, A. Girardi, M. TI Langerhans cells are necessary for chemical mutagenesis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-of-Investigative-Dermatology CY MAY 06-09, 2009 CL Montreal, CANADA SP Soc Investigat Dematol C1 [Neustadter, J.; Roberts, S.; Filler, R.; Kwong, B.; Lewis, J.; Gaian, A.; Reddy, S.; Tigelaar, R.; Girardi, M.] Yale Univ, New Haven, CT USA. [Fu, P.] FDA, Jefferson, AR USA. [Kaplan, D.] Univ Minnesota, Minneapolis, MN USA. [Hayday, A.] Kings Coll London, London WC2R 2LS, England. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2009 VL 129 MA 176 BP S30 EP S30 PG 1 WC Dermatology SC Dermatology GA 430MU UT WOS:000264994000178 ER PT J AU Carpenter, JF Randolph, TW Jiskoot, W Crommelin, DJA Middaugh, CR Winter, G Fan, YX Kirshner, S Verthelyi, D Kozlowski, S Clouse, KA Swann, PG Rosenberg, A Cherney, B AF Carpenter, John F. Randolph, Theodore W. Jiskoot, Wim Crommelin, Daan J. A. Middaugh, C. Russell Winter, Gerhard Fan, Ying-Xin Kirshner, Susan Verthelyi, Daniela Kozlowski, Steven Clouse, Kathleen A. Swann, Patrick G. Rosenberg, Amy Cherney, Barry TI Overlooking Subvisible Particles in Therapeutic Protein Products: Gaps That May Compromise Product Quality SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Editorial Material ID IMMUNOGENICITY; AGGREGATION; STABILITY; VACCINES C1 [Carpenter, John F.] Univ Colorado, Hlth Sci Ctr, Dept Pharmaceut Sci, Ctr Pharmaceut Biotechnol, Denver, CO 80262 USA. [Randolph, Theodore W.] Univ Colorado, Dept Biol & Chem Engn, Ctr Pharmaceut Biotechnol, Boulder, CO 80309 USA. [Jiskoot, Wim] Leiden Univ, Div Drug Delivery Technol, LACDR, Leiden, Netherlands. [Crommelin, Daan J. A.] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Dept Pharmaceut, Utrecht, Netherlands. [Middaugh, C. Russell] Univ Kansas, Dept Pharmaceut Chem, Lawrence, KS 66047 USA. [Winter, Gerhard] Univ Munich, Dept Pharm, D-81377 Munich, Germany. [Fan, Ying-Xin; Kirshner, Susan; Verthelyi, Daniela; Rosenberg, Amy; Cherney, Barry] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Kozlowski, Steven] US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Clouse, Kathleen A.; Swann, Patrick G.] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Carpenter, JF (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pharmaceut Sci, Ctr Pharmaceut Biotechnol, Box 238, Denver, CO 80262 USA. EM john.carpenter@uchsc.edu RI randolph, theodore/A-3301-2013; Winter, Gerhard/F-7126-2014; Jiskoot, Wim/A-6877-2016 OI Jiskoot, Wim/0000-0002-1012-3456 FU NIBIB NIH HHS [R01 EB006006, R01 EB006006-03] NR 16 TC 202 Z9 203 U1 5 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 APR PY 2009 VL 98 IS 4 BP 1201 EP 1205 DI 10.1002/jps.21530 PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 428MC UT WOS:000264851400001 PM 18704929 ER PT J AU Tsong, Y Kelly, R Shen, MY Zhong, JL AF Tsong, Yi Kelly, Roswitha Shen, Meiyu Zhong, Jinglin TI Statistics in Pharmaceutical Development and Manufacturing Discussion SO JOURNAL OF QUALITY TECHNOLOGY LA English DT Editorial Material ID QUALITY-ASSURANCE TEST; ALTERNATIVE APPROACH; ASSESSING AGREEMENT; POOLING BATCHES; SHELF-LIFE; STABILITY; EQUIVALENCE; UNIFORMITY; PRODUCTS; TESTS C1 [Tsong, Yi; Kelly, Roswitha; Shen, Meiyu; Zhong, Jinglin] US FDA, Div Biometr 6, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Tsong, Y (reprint author), US FDA, Div Biometr 6, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM yi.tsong@fda.hhs.gov; Roswitha.Kelly@fda.hhs.gov; meiyu.shen@fda.hhs.gov; jinglin.zhong@fda.hhs.gov NR 19 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC QUALITY CONTROL-ASQC PI MILWAUKEE PA 600 N PLANKINTON AVE, MILWAUKEE, WI 53203 USA SN 0022-4065 J9 J QUAL TECHNOL JI J. Qual. Technol. PD APR PY 2009 VL 41 IS 2 BP 142 EP 144 PG 3 WC Engineering, Industrial; Operations Research & Management Science; Statistics & Probability SC Engineering; Operations Research & Management Science; Mathematics GA 424VH UT WOS:000264595900005 ER PT J AU De Jager, LS Perfetti, GA Diachenko, GW AF De Jager, Lowri S. Perfetti, Gracia A. Diachenko, Gregory W. TI Comparison of membrane assisted solvent extraction, stir bar sorptive extraction, and solid phase microextraction in analysis of tetramine in food SO JOURNAL OF SEPARATION SCIENCE LA English DT Article DE Food defense; MASE; SBSE; SPME; Tetramine ID CHROMATOGRAPHY-MASS SPECTROMETRY; TETRAMETHYLENE DISULFOTETRAMINE; ORGANOCHLORINE; COMBINATION; RESIDUES; SAMPLES; WATER AB Three environmentally friendly extraction techniques, membrane assisted solvent extraction (MASE), stir bar sorptive extraction (SBSE), and headspace solid phase microextraction (HS-SPME), were compared for the direct analysis of the highly toxic rodenticide tetramine in food. The optimized MASE method was applied to seven foods fortified with tetramine and compared to previously reported SBSE and HS-SPME results. Parameters such as the standard addition linearity (MASE (0.964-0.999), SBSE (0.966-0.999), HS-SPME (0.955-0.999)), recovery (MASE (12-86%), SBSE (36-130%), HS-SPME (50-200%)), reproducibility (MASE (3.0-30%), SBSE (4.4-9.6%), HS-SPME (1-12%)), and LOD (MASE (1.6-6.4 ng/g), SBSE (0.2-2.1 ng/g), HS-SPME (0.9-4.3 ng/g)) were compared. C1 [De Jager, Lowri S.; Perfetti, Gracia A.; Diachenko, Gregory W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP De Jager, LS (reprint author), 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM lowri.dejager@fda.hhs.gov NR 17 TC 8 Z9 8 U1 1 U2 17 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 APR PY 2009 VL 32 IS 7 BP 1081 EP 1086 DI 10.1002/jssc.200800576 PG 6 WC Chemistry, Analytical SC Chemistry GA 432HC UT WOS:000265123100023 PM 19266557 ER PT J AU Bhasin, S Espeland, MA Evans, WJ Ferrucci, L Fried, LP Gill, TM Pahor, M Studenski, S Guralnik, J Nayfi, S Romashkin, S Perlstein, R Burke, L Parks, M AF Bhasin, Shalender Espeland, Mark A. Evans, William J. Ferrucci, Luigi Fried, Linda P. Gill, Thomas M. Pahor, Marco Studenski, Stephanie Guralnik, Jack Nayfi, Susan Romashkin, Sergei Perlstein, Robert Burke, Laurie Parks, Mary TI Indications, Labeling, and Outcomes Assessment for Drugs Aimed at Improving Functional Status in Older Persons: A Conversation Between Aging Researchers and FDA Regulators SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID MUSCLE MASS SARCOPENIA; SKELETAL-MUSCLE; POSTMENOPAUSAL WOMEN; BODY-COMPOSITION; FRAILTY; STRENGTH; MEN; DISABILITY; CARE; OSTEOPOROSIS C1 [Bhasin, Shalender] Boston Univ, Sch Med, Boston, MA 02215 USA. [Espeland, Mark A.] Wake Forest Univ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA. [Evans, William J.] Univ Arkansas Med Sci, Donald W Reynolds Inst Aging, Little Rock, AR 72205 USA. [Ferrucci, Luigi] NIA, Baltimore Longitudinal Study Aging, Bethesda, MD 20892 USA. [Fried, Linda P.] Cornell Univ, Ithaca, NY 14853 USA. [Gill, Thomas M.] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Pahor, Marco] Univ Florida, Sch Med, Gainesville, FL 32611 USA. [Studenski, Stephanie] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Guralnik, Jack] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Nayfi, Susan; Romashkin, Sergei] NIA, Geriatr & Clin Gerontol Program, Bethesda, MD 20892 USA. [Perlstein, Robert; Burke, Laurie; Parks, Mary] US FDA, Rockville, MD 20857 USA. RP Evans, WJ (reprint author), Univ Arkansas Med Sci, Donald W Reynolds Inst Aging, Slot 806,4301 W Markham, Little Rock, AR 72205 USA. EM evanswilliamj@uams.edu NR 31 TC 15 Z9 15 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD APR PY 2009 VL 64 IS 4 BP 487 EP 491 DI 10.1093/gerona/gln042 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 421XD UT WOS:000264390700010 ER PT J AU Hakim, BM Beard, BB Davis, CC AF Hakim, B. M. Beard, B. B. Davis, C. C. TI Precise dielectric property measurements and E-field probe calibration for specific absorption rate measurements using a rectangular waveguide SO MEASUREMENT SCIENCE AND TECHNOLOGY LA English DT Article DE dielectric property measurement; SAR; dosimetry; E-field probe; E-field probe calibration; waveguide; uncertainty analysis ID TISSUE-EQUIVALENT LIQUIDS; GHZ; SAR; MHZ; PERMITTIVITY; FREQUENCIES AB Specific absorption rate (SAR) measurements require accurate calculations of the dielectric properties of tissue-equivalent liquids and associated calibration of E-field probes. We developed a precise tissue-equivalent dielectric measurement and E-field probe calibration system. The system consists of a rectangular waveguide, electric field probe, and data control and acquisition system. Dielectric properties are calculated using the field attenuation factor inside the tissue-equivalent liquid and power reflectance inside the waveguide at the air/dielectric-slab interface. Calibration factors were calculated using isotropicity measurements of the E-field probe. The frequencies used are 900 MHz and 1800 MHz. The uncertainties of the measured values are within +/- 3%, at the 95% confidence level. Using the same waveguide for dielectric measurements as well as calibrating E-field probes used in SAR assessments eliminates a source of uncertainty. Moreover, we clearly identified the system parameters that affect the overall uncertainty of the measurement system. C1 [Hakim, B. M.; Beard, B. B.] US FDA, Ctr Devices & Radiol Hlth CDRH, Silver Spring, MD 20993 USA. [Davis, C. C.] Univ Maryland, Dept Elect & Comp Engn, College Pk, MD 20742 USA. RP Hakim, BM (reprint author), US FDA, Ctr Devices & Radiol Hlth CDRH, Silver Spring, MD 20993 USA. EM hakim@umd.edu OI Beard, Brian/0000-0001-6480-0857 NR 26 TC 2 Z9 2 U1 0 U2 5 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0957-0233 EI 1361-6501 J9 MEAS SCI TECHNOL JI Meas. Sci. Technol. PD APR PY 2009 VL 20 IS 4 AR 045702 DI 10.1088/0957-0233/20/4/045702 PG 9 WC Engineering, Multidisciplinary; Instruments & Instrumentation SC Engineering; Instruments & Instrumentation GA 421VQ UT WOS:000264386800032 ER PT J AU Godar, DE Landry, RJ Lucas, AD AF Godar, Dianne E. Landry, Robert J. Lucas, Anne D. TI Increased UVA exposures and decreased cutaneous Vitamin D-3 levels may be responsible for the increasing incidence of melanoma SO MEDICAL HYPOTHESES LA English DT Review ID MALIGNANT-MELANOMA; SUN EXPOSURE; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; ULTRAVIOLET-RADIATION; SKIN-CANCER; HAIRLESS MICE; 1,25-DIHYDROXYVITAMIN D-3; MONODELPHIS-DOMESTICA; XERODERMA-PIGMENTOSUM; SEASONAL-VARIATION AB Cutaneous malignant melanoma (CMM) has been increasing at a steady exponential rate in fair-skinned, indoor workers since before 1940. A paradox exists between indoor and outdoor workers because indoor workers get three to nine times less solar UV (290-400 nm) exposure than outdoor workers get, yet only indoor workers have an increasing incidence of CMM. Thus, another "factor(s)" is/are involved that increases the CMM risk for indoor workers. We hypothesize that one factor involves indoor exposures to UVA (321-400 nm) passing through windows, which can cause mutations and can break down vitamin D-3 formed after outdoor UVB (290-320 nm) exposure, and the other factor involves low levels of cutaneous vitamin D-3. After vitamin D-3 forms, melanoma cells can convert it to the hormone, 1,25-dihydroxyvitamin D-3, or calcitriol, which causes growth inhibition and apoptotic cell death in vitro and in vivo. We measured the outdoor and indoor solar irradiances and found indoor solar UVA irradiances represent about 25% (or 5-10 W/m(2)) of the outdoor irradiances and are about 60 times greater than fluorescent light irradiances. We calculated the outdoor and indoor UV contributions toward different biological end-points by weighting the emission spectra by the action spectra: erythema, squamous cell carcinoma, melanoma (fish), and previtamin D-3. Furthermore, we found production of previtamin D-3 only occurs outside where there is enough UVB. We agree that intense, intermittent outdoor UV overexposures and sunburns initiate CMM; we now propose that increased UVA exposures and inadequately maintained cutaneous levels of vitamin D-3 promotes CMM. Published by Elsevier Ltd. C1 [Godar, Dianne E.; Landry, Robert J.; Lucas, Anne D.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Godar, DE (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,HFZ-120, Silver Spring, MD 20993 USA. EM DEG@CDRH.FDA.GOV OI GODAR, DIANNE/0000-0002-7690-5223 NR 104 TC 43 Z9 43 U1 0 U2 8 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD APR PY 2009 VL 72 IS 4 BP 434 EP 443 DI 10.1016/j.mehy.2008.09.056 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 425EM UT WOS:000264619800019 PM 19155143 ER PT J AU Johnson, CN Flowers, AR Young, VC Gonzalez-Escalona, N DePaola, A Noriea, NF Grimes, DJ AF Johnson, C. N. Flowers, A. R. Young, V. C. Gonzalez-Escalona, N. DePaola, A. Noriea, N. F., III Grimes, D. J. TI Genetic Relatedness Among tdh (+) and trh (+) Vibrio parahaemolyticus Cultured from Gulf of Mexico Oysters (Crassostrea virginica) and Surrounding Water and Sediment SO MICROBIAL ECOLOGY LA English DT Article ID MOLECULAR CHARACTERIZATION; SEQUENCE; PCR; SHELLFISH; STRAINS; AMPLIFICATION; ENVIRONMENT; VULNIFICUS; WASHINGTON; ABUNDANCE AB Pathogenic Vibrio parahaemolyticus (Vp) (tdh (+)/trh (+)) represent a small percentage of environmental Vp populations, and very little is known about this subpopulation. Repetitive extragenic palindromic PCR and multilocus sequence analysis revealed heterogeneity among 41 Vp containing thermostable direct hemolysin (tdh) and tdh-related hemolysin (trh) that were isolated from Mississippi coastal environments from October 2006 to April 2007. There was no source-specific sequestering in oysters, water, or sediment. C1 [Johnson, C. N.; Flowers, A. R.; Young, V. C.; Noriea, N. F., III; Grimes, D. J.] Univ So Mississippi, Gulf Coast Res Lab, Ocean Springs, MS 39564 USA. [DePaola, A.] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL USA. [Gonzalez-Escalona, N.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Grimes, DJ (reprint author), Univ So Mississippi, Gulf Coast Res Lab, 703 E Beach Dr, Ocean Springs, MS 39564 USA. EM jay.grimes@usm.edu RI Gonzalez-Escalona, Narjol/A-7598-2009; OI Gonzalez-Escalona, Narjol/0000-0003-4568-0022 FU NOAA Oceans and Human Health Initiative [NA-04-OAR4600214]; U. S. Department of Agriculture; Cooperative State Research; Education and Extension Service; National Research Initiative; Competitive Grants Program; Epidemiological Approaches to Food Safety [2004-35212-14882] FX Special thanks go to Jessica Jones and Read Hendon for manuscript review and graphics support, respectively. This study was funded by a NOAA Oceans and Human Health Initiative grant (NA-04-OAR4600214). Narjol Gonzalez-Escalona was supported by a grant from the U. S. Department of Agriculture, Cooperative State Research, Education and Extension Service, National Research Initiative, Competitive Grants Program, Epidemiological Approaches to Food Safety, Project #2004-35212-14882. NR 35 TC 24 Z9 24 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0095-3628 J9 MICROB ECOL JI Microb. Ecol. PD APR PY 2009 VL 57 IS 3 BP 437 EP 443 DI 10.1007/s00248-008-9418-3 PG 7 WC Ecology; Marine & Freshwater Biology; Microbiology SC Environmental Sciences & Ecology; Marine & Freshwater Biology; Microbiology GA 418VM UT WOS:000264177500005 PM 18607657 ER PT J AU Joseph, A Lee, T Moland, CL Branham, WS Fuscoe, JC Leakey, JEA Allaben, WT Lewis, SM Ali, AA Desai, VG AF Joseph, Ajay Lee, Taewon Moland, Carrie L. Branham, William S. Fuscoe, James C. Leakey, Julian E. A. Allaben, William T. Lewis, Sherry M. Ali, Akhtar A. Desai, Varsha G. TI Effect of (+)-usnic acid on mitochondrial functions as measured by mitochondria-specific oligonucleotide microarray in liver of B6C3F(1) mice SO MITOCHONDRION LA English DT Article DE Usnic acid; Liver; Female B6C3F(1) mice; Gene expression; Mitochondrial functions ID USNIC ACID; GENE-EXPRESSION; OXIDATIVE STRESS; DIETARY-SUPPLEMENT; (-)-USNIC ACID; BIOGENESIS; MODEL; HEPATOCYTES; INHIBITION; DAMAGE AB Usnic acid is a lichen metabolite used as a weight-loss dietary supplement due to its uncoupling action on mitochondria. However, its use has been associated with severe liver disorders in some individuals. Animal studies conducted thus far evaluated the effects of usnic acid on mitochondria primarily by measuring the rate of oxygen consumption and/or ATP generation. To obtain further insight into usnic acid-mediated effects on mitochondria, we examined the expression levels of 542 genes associated with mitochondrial structure and functions in liver of B6C3F(1) female mice using a mitochondria-specific microarray. Beginning at 8 weeks of age, mice received usnic acid at 0, 60, 180, and 600 ppm in ground, irradiated 5LG6 diet for 14 days. Microarray analysis showed a significant effect of usnic acid on the expression of several genes only at the highest dose of 600 ppm. A prominent finding of the study was a significant induction of genes associated with complexes I through IV of the electron transport chain. Moreover, several genes involved in fatty acid oxidation, the Krebs cycle, apoptosis, and membrane transporters were over-expressed. Usnic acid is a lipophilic weak acid that can diffuse through mitochondrial membranes and cause a proton leak (uncoupling). The up-regulation of complexes I-IV may be a compensatory mechanism to maintain the proton gradient across the mitochondrial inner membrane. in addition, induction of fatty acid oxidation and the Krebs cycle may be an adaptive response to uncoupling of mitochondria. Published by Elsevier B.V. on behalf of Mitochondria Research Society. C1 [Moland, Carrie L.; Branham, William S.; Fuscoe, James C.; Desai, Varsha G.] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Ctr Funct Genom, Jefferson, AR 72079 USA. [Joseph, Ajay] Univ Abertay Dundee, Dundee DD1 1HG, Scotland. [Lee, Taewon] Korea Univ, Dept Math & Informat, Jochiwon 339700, Chungnam, South Korea. [Leakey, Julian E. A.; Allaben, William T.; Lewis, Sherry M.; Ali, Akhtar A.] US FDA, Natl Ctr Toxicol Res, Off Sci Coordinat, Jefferson, AR 72079 USA. RP Desai, VG (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Ctr Funct Genom, Jefferson, AR 72079 USA. EM varsha.desai@fda.hhs.gov FU National Center for Toxicological Research/US Food and Drug Administration; National Toxicology Program/the National Institute for Environmental Health Sciences/National Institutes of Health; Oak Ridge Institute of Science and Education through an Interagency agreement between the US Food and Drug Administration and US Department of Energy FX This research was supported in part by Interagency Agreement (IAG 224-07-007) between the National Center for Toxicological Research/US Food and Drug Administration and National Toxicology Program/the National Institute for Environmental Health Sciences/National Institutes of Health. Also, research was supported in part by an international student training program administered by the Oak Ridge Institute of Science and Education through an Interagency agreement between the US Food and Drug Administration and US Department of Energy. The authors wish to thank Drs. Ritchie J. Feuers and William H. Tolleson for their critical review of the manuscript. NR 40 TC 16 Z9 16 U1 2 U2 6 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 APR PY 2009 VL 9 IS 2 BP 149 EP 158 DI 10.1016/j.mito.2009.02.002 PG 10 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 428PO UT WOS:000264861400010 PM 19460291 ER PT J AU Bradley, JS Wassel, RT Lee, L Nambiar, S AF Bradley, John S. Wassel, Ronald T. Lee, Lucia Nambiar, Sumathi TI Intravenous Ceftriaxone and Calcium in the Neonate: Assessing the Risk for Cardiopulmonary Adverse Events SO PEDIATRICS LA English DT Article DE ceftriaxone; calcium; newborn; drug therapy/adverse event; cardiopulmonary arrest AB OBJECTIVES. Unsolicited reports regarding potentially serious adverse drug reactions in neonates and young infants were reported to the Food and Drug Administration, leading to changes in the package label for ceftriaxone. This report describes and summarizes the reported cases that led to safety concerns regarding the concurrent administration of intravenous ceftriaxone and calcium in this age group. METHODS. Nine reported cases were assessed. The Food and Drug Administration Adverse Event Reporting System database was searched for potential drug interactions in patients who were receiving concomitant ceftriaxone and calcium therapy. RESULTS. Eight of the reported 9 cases (7 were <= 2 months of age) represented possible or probable adverse drug events. There were 7 deaths. None of the cases were reported from the United States. The dosage of ceftriaxone that was administered to 4 of 6 infants for whom this information was available was between 150 and 200 mg/kg per day. The rate of occurrence of these serious adverse drug reactions cannot be accurately determined from available data. CONCLUSIONS. The concurrent use of intravenous ceftriaxone and calcium-containing solutions in the newborn and young infant may result in a life-threatening adverse drug reaction. Contributing factors for infants in this report may include the use of ceftriaxone at dosages higher than those approved by the Food and Drug Administration, intravenous "push" administration, and administration of the total daily dosage as a single infusion. Pediatrics 2009; 123: e609-e613 C1 [Bradley, John S.] Rady Childresn Hosp San Diego, San Diego, CA USA. [Wassel, Ronald T.] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. [Nambiar, Sumathi] US FDA, Ctr Drug Evaluat & Res, Off Antimicrobiol Prod, Off New Drugs, Silver Spring, MD USA. [Lee, Lucia] US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Rockville, MD 20857 USA. RP Bradley, JS (reprint author), 3020 Childrens Way,Mail Code 5041, San Diego, CA 92123 USA. EM jbradley@rchsd.org NR 9 TC 31 Z9 31 U1 0 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2009 VL 123 IS 4 BP E609 EP E613 DI 10.1542/peds.2008-3080 PG 5 WC Pediatrics SC Pediatrics GA 425UO UT WOS:000264663100037 PM 19289450 ER PT J AU Pham, AN Wang, J Fang, JL Gao, X Zhang, YL Blower, PE Sadee, WG Huang, Y AF Pham, Anh-Nhan Wang, Jeffrey Fang, Jialong Gao, Xin Zhang, Yilong Blower, Paul E. Sadee, Wolfgang Huang, Ying TI Pharmacogenomics Approach Reveals MRP1 (ABCC1)-Mediated Resistance to Geldanamycins SO PHARMACEUTICAL RESEARCH LA English DT Article DE geldanamycin; membrane transporter and chemoresistance; MRP1; pharmacogenomics ID GLUTAMATE TRANSPORTER SLC7A11; MULTIDRUG-RESISTANCE; MEMBRANE TRANSPORTERS; GENE-EXPRESSION; CANCER CHEMOSENSITIVITY; MEDIATES RESISTANCE; DRUG EFFLUX; CELL-LINE; GLUTATHIONE; HSP90 AB Geldanamycin and its analogues belong to a new class of anticancer agents that inhibit the molecular chaperone heat shock protein 90. We hypothesized that membrane transporters expressed on tumor cells may contribute at least in part to cellular sensitivity to these agents. The purpose of this study is to identify novel transporters as determinant for sensitivity and resistance to geldanamycins. To facilitate a systematic study of chemosensitivity across multiple geldanamycin analogues, we correlated mRNA expression profiles of majority of transporters with anticancer drug activities in 60 human tumor cell lines (NCI-60). We subsequently validated the gene-drug correlations using cytotoxicity and transport assays. The GA analogues displayed negative correlations with mRNA expression levels of the multidrug resistance protein 1 (MRP1, ABCC1). Suppressing MRP1 efflux using the inhibitor MK-571 and small interfering RNA in cell lines with intrinsic and acquired MRP1 overexpression (A549 and HL-60/ADR) and in cell lines stably transduced with MRP1 (MCF7/MRP1) increased intracellular drug accumulation and increased tumor cell sensitivity to geldanamycin analogues. These results suggest that elevated expression of MRP1, like the alternative efflux transporter MDR1 (ABCB1, P-glycoprotein), can significantly influence tumor cell sensitivity to geldanamycins as a potential chemoresistance factor. C1 [Pham, Anh-Nhan; Wang, Jeffrey; Huang, Ying] Western Univ Hlth Sci, Coll Pharm, Dept Pharmaceut Sci, Pomona, CA 91766 USA. [Fang, Jialong] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Gao, Xin] York Univ, Dept Math & Stat, Toronto, ON L4E OA1, Canada. [Zhang, Yilong] Allergan Pharmaceut Inc, Clin Pharmacokinet Dept, Irvine, CA 92612 USA. [Blower, Paul E.; Sadee, Wolfgang] Ohio State Univ, Coll Med & Publ Hlth, Ctr Comprehens Canc, Dept Pharmacol,Program Pharmacogenom, Columbus, OH 43210 USA. RP Huang, Y (reprint author), Western Univ Hlth Sci, Coll Pharm, Dept Pharmaceut Sci, Pomona, CA 91766 USA. EM yhuang@westernu.edu FU NIH [GM61390]; Food and Drug Administration; Western University of Health Sciences FX This work was supported by NIH grant GM61390, the Food and Drug Administration and Western University of Health Sciences. We thank the staff of NCI DTP for generation of the pharmacological database used in this study. NR 37 TC 8 Z9 9 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORD JI Pharm. Res. PD APR PY 2009 VL 26 IS 4 BP 936 EP 945 DI 10.1007/s11095-008-9796-8 PG 10 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 413NE UT WOS:000263799000019 PM 19067123 ER PT J AU Rowan, C Brinker, AD Noutjah, P Chang, J Mosholder, A Barrett, JS Avigan, M AF Rowan, Christopher Brinker, Allen D. Noutjah, Parivash Chang, Jennie Mosholder, Andrew Barrett, Jeffrey S. Avigan, Mark TI Rhabdomyolysis reports show interaction between simvastatin and CYP3A4 inhibitors SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE rhabdomyolysis; statins; CYP3A4 inhibitors; HMG-CoA reductase inhibitors; adverse reactions; interaction; spontaneous reports ID HMG-COA REDUCTASE; DRUG-DRUG INTERACTION; HEPATIC-UPTAKE; COMPARATIVE PHARMACOKINETICS; GLUCURONIDE INHIBIT; PRAVASTATIN; GEMFIBROZIL; LOVASTATIN; LIVER; CERIVASTATIN AB Purpose To assess spontaneous reports of rhabdomyolysis associated with simvastatin (SV) and pravastatin (PV) for evidence of CYP3A4 interaction. Clinical trial results advocate cholesterol lowering in high-risk patients including diabetics and the elderly. Given the association between advancing age, metabolic, and cardiovascular disease, many patients are treated with concomitant medications upon statin initiation. Although statins are generally safe, minor and severe adverse reactions arise, especially when given to patients taking concomitant medications that inhibit the statin clearance and lead to increased statin plasma concentration. Methods We conducted a comparative case series of rhabdomyolysis reports associated with SV and PV. Domestic spontaneous reports were obtained from the FDA's Adverse Event Reporting System (AERS). Drug utilization data were obtained from IMS HEALTH and the National Ambulatory Medical Care Survey (NAMCS). Adverse event reporting rates (AER) and ratios (AERR) of rhabdomyolysis associated with SV and PV-with and without stratification by CYP3A4 inhibitor concomitancy were determined. Results Stratification by CYP3A4 inhibitor concomitancy did not change the rhabdomyolysis AER for PV with or without a CYP3A4 inhibitor (2.4 cases and 3.1 cases per 10 million Rx, respectively). However, stratification of SV reports with or without a concomitant CYP3A4 inhibitor resulted in a rhabdomyolysis AER (38.4 and 6.0 cases per 10 million Rx, respectively). The corresponding AERR with or without a CYP3A4 inhibitor were 0.77 for PV and 6.43 for SV. Conclusions Spontaneous adverse event reports provide evidence of increased risk for rhabdomyolysis based on interaction between SV and selected CYP3A4 inhibitors. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Rowan, Christopher] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Brinker, Allen D.; Noutjah, Parivash; Chang, Jennie; Mosholder, Andrew; Avigan, Mark] US FDA, Div Drug Risk Evaluat, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Barrett, Jeffrey S.] Childrens Hosp Philadelphia, Clin Pharmacol & Therapeut Div, Lab Appl PK PD, Philadelphia, PA USA. RP Rowan, C (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Room 108,Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM crowan@mail.med.upenn.edu RI Barrett, Jeffrey/B-4010-2010 FU NIA NIH HHS [R01 AG025152] NR 34 TC 27 Z9 28 U1 0 U2 6 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 APR PY 2009 VL 18 IS 4 BP 301 EP 309 DI 10.1002/pds.1711 PG 9 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 434CJ UT WOS:000265252500006 PM 19206087 ER PT J AU Coelho, SG Zhou, Y Bushar, HF Miller, SA Zmudzka, BZ Hearing, VJ Beer, JZ AF Coelho, Sergio G. Zhou, Yanchun Bushar, Harry F. Miller, Sharon A. Zmudzka, Barbara Z. Hearing, Vincent J. Beer, Janusz Z. TI Long-lasting pigmentation of human skin, a new look at an overlooked response to UV SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Letter DE long-lasting pigmentation; melanogenesis; ultraviolet radiation ID MECHANISMS; EXPOSURE C1 [Coelho, Sergio G.; Hearing, Vincent J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Zhou, Yanchun; Bushar, Harry F.; Miller, Sharon A.; Zmudzka, Barbara Z.; Beer, Janusz Z.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Coelho, SG (reprint author), NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM coelhos@mail.nih.gov FU Intramural NIH HHS [Z01 BC010784-01, Z99 CA999999] NR 14 TC 9 Z9 9 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD APR PY 2009 VL 22 IS 2 BP 238 EP 241 DI 10.1111/j.1755-148X.2009.00550.x PG 4 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 417NY UT WOS:000264084200016 PM 19226313 ER PT J AU Khurana, S Suguitan, AL Rivera, Y Simmons, CP Lanzavecchia, A Sallusto, F Manischewitz, J King, LR Subbarao, K Golding, H AF Khurana, Surender Suguitan, Amorsolo L., Jr. Rivera, Yonaira Simmons, Cameron P. Lanzavecchia, Antonio Sallusto, Federica Manischewitz, Jody King, Lisa R. Subbarao, Kanta Golding, Hana TI Antigenic Fingerprinting of H5N1 Avian Influenza Using Convalescent Sera and Monoclonal Antibodies Reveals Potential Vaccine and Diagnostic Targets SO PLOS MEDICINE LA English DT Article ID A-VIRUS; NEUTRALIZING ANTIBODY; DIFFERENTIAL-DIAGNOSIS; HEMAGGLUTININ MOLECULE; GENERATED ANTIBODIES; HIV-INFECTIONS; M2 PROTEIN; MICE; SITES; IDENTIFICATION AB Background: Transmission of highly pathogenic avian H5N1 viruses from poultry to humans have raised fears of an impending influenza pandemic. Concerted efforts are underway to prepare effective vaccines and therapies including polyclonal or monoclonal antibodies against H5N1. Current efforts are hampered by the paucity of information on protective immune responses against avian influenza. Characterizing the B cell responses in convalescent individuals could help in the design of future vaccines and therapeutics. Methods and Findings: To address this need, we generated whole-genome-fragment phage display libraries (GFPDL) expressing fragments of 15-350 amino acids covering all the proteins of A/Vietnam/1203/2004 (H5N1). These GFPDL were used to analyze neutralizing human monoclonal antibodies and sera of five individuals who had recovered from H5N1 infection. This approach led to the mapping of two broadly neutralizing human monoclonal antibodies with conformation-dependent epitopes. In H5N1 convalescent sera, we have identified several potentially protective H5N1-specific human antibody epitopes in H5 HA[(-10)-223], neuraminidase catalytic site, and M2 ectodomain. In addition, for the first time to our knowledge in humans, we identified strong reactivity against PB1-F2, a putative virulence factor, following H5N1 infection. Importantly, novel epitopes were identified, which were recognized by H5N1-convalescent sera but did not react with sera from control individuals (H5N1 naive, H1N1 or H3N2 seropositive). Conclusion: This is the first study, to our knowledge, describing the complete antibody repertoire following H5N1 infection. Collectively, these data will contribute to rational vaccine design and new H5N1-specific serodiagnostic surveillance tools. C1 [Khurana, Surender; Rivera, Yonaira; Manischewitz, Jody; King, Lisa R.; Golding, Hana] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD USA. [Suguitan, Amorsolo L., Jr.; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Simmons, Cameron P.] Univ Oxford, Clin Res Unit, Hosp Trop Dis, Ho Chi Minh City, Vietnam. [Lanzavecchia, Antonio; Sallusto, Federica] Biomed Res Inst, Bellinzona, Switzerland. RP Khurana, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD USA. EM hana.golding@fda.hhs.gov OI Simmons, Cameron P./0000-0002-9039-7392 FU OPHEMC/HHS (2007); BARDA/HHS (2008); CBER (FDA); NIAID (NIH) FX This study was partly supported by funds from OPHEMC/HHS (2007) and BARDA/HHS (2008). This research was supported by the Intramural Research Program of CBER (FDA) and NIAID (NIH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 95 Z9 96 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD APR PY 2009 VL 6 IS 4 AR e1000049 DI 10.1371/journal.pmed.1000049 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 447TN UT WOS:000266214800004 PM 19381279 ER PT J AU Gavrielides, MA Kinnard, LM Myers, KJ Petrick, N AF Gavrielides, Marios A. Kinnard, Lisa M. Myers, Kyle J. Petrick, Nicholas TI Noncalcified Lung Nodules: Volumetric Assessment with Thoracic CT SO RADIOLOGY LA English DT Article ID SMALL PULMONARY NODULES; IMAGE DATABASE CONSORTIUM; COMPUTED-TOMOGRAPHY IMAGES; MULTIDETECTOR ROW CT; MULTISLICE CT; INTRAOBSERVER VARIABILITY; AUTOMATIC SEGMENTATION; PRELIMINARY EXPERIENCE; TREATMENT RESPONSE; AIDED DETECTION AB Lung nodule volumetry is used for nodule diagnosis, as well as for monitoring tumor response to therapy. Volume measurement precision and accuracy depend on a number of factors, including image-acquisition and reconstruction parameters, nodule characteristics, and the performance of algorithms for nodule segmentation and volume estimation. The purpose of this article is to provide a review of published studies relevant to the computed tomographic (CT) volumetric analysis of lung nodules. A number of underexamined areas of research regarding volumetric accuracy are identified, including the measurement of non-solid nodules, the effects of pitch and section overlap, and the effect of respiratory motion. The need for public databases of phantom scans, as well as of clinical data, is discussed. The review points to the need for continued research to examine volumetric accuracy as a function of a multitude of interrelated variables involved in the assessment of lung nodules. Understanding and quantifying the sources of volumetric measurement error in the assessment of lung nodules with CT would be a first step toward the development of methods to minimize that error through system improvements and to correctly account for any remaining error. (c) RSNA, 2009 C1 [Gavrielides, Marios A.; Kinnard, Lisa M.; Myers, Kyle J.; Petrick, Nicholas] US FDA, Natl Inst Biomed Imaging & Bioengn,Ctr Devices &, Ctr Devices & Radiol Hlth,Off Sci & Engn Labs, Joint Lab Assessment Med Imaging Syst,Div Imaging, Silver Spring, MD 20993 USA. RP Gavrielides, MA (reprint author), US FDA, Natl Inst Biomed Imaging & Bioengn,Ctr Devices &, Ctr Devices & Radiol Hlth,Off Sci & Engn Labs, Joint Lab Assessment Med Imaging Syst,Div Imaging, 10903 New Hampshire Ave,Bldg 62,Room 3139, Silver Spring, MD 20993 USA. EM marios.gavrielides@fda.hhs.gov FU Cancer Imaging Program of the National Cancer Institute; Intramural Program of the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health FX This research was supported by the Cancer Imaging Program of the National Cancer Institute and the Intramural Program of the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health. NR 62 TC 103 Z9 104 U1 1 U2 6 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 APR PY 2009 VL 251 IS 1 BP 26 EP 37 DI 10.1148/radiol.2511071897 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 439QV UT WOS:000265643000005 PM 19332844 ER PT J AU Delclos, KB Weis, CC Bucci, TJ Olson, G Mellick, P Sadovova, N Latendresse, JR Thorn, B Newbold, RR AF Delclos, K. Barry Weis, Constance C. Bucci, Thomas J. Olson, Greg Mellick, Paul Sadovova, Natalya Latendresse, John R. Thorn, Brett Newbold, Retha R. TI Overlapping but distinct effects of genistein and ethinyl estradiol (EE2) in female Sprague-Dawley rats in multigenerational reproductive and chronic toxicity studies SO REPRODUCTIVE TOXICOLOGY LA English DT Review DE Genistein; Ethinyl estradiol; Rat; Multigenerational; Reproductive toxicity; Estrous cycle; Puberty acceleration; Reproductive senescence; Soy-free diet ID ESTROGEN-RECEPTOR-BETA; SUPPRESSES MAMMARY-CANCER; PHYTOESTROGEN GENISTEIN; NEONATAL EXPOSURE; SOY ISOFLAVONE; BREAST-CANCER; GENE-EXPRESSION; IN-UTERO; DIETARY GENISTEIN; PRENATAL EXPOSURE AB Genistein and ethinyl estradiol (EE2) were examined in multigenerational reproductive and chronic toxicity studies that had different treatment intervals among generations. Sprague-Dawley rats received genistein (0, 5, 100, or 500 ppm) or EE2 (0, 2, 10, or 50 ppb) in a low phytoestrogen diet. Nonneoplastic effects in females are summarized here. Genistein at 500 ppm and EE2 at 50 ppb produced similar effects in continuously exposed rats, including decreased body weights, accelerated vaginal opening, and altered estrous cycles in young animals. At the high dose, anogenital distance was subtly affected by both compounds, and a reduction in litter size was evident in genistein-treated animals. Genistein at 500 ppm induced an early onset of aberrant cycles relative to controls in the chronic studies. EE2 significantly increased the incidence of uterine lesions (atypical focal hyperplasia and squamous metaplasia). These compound-specific effects appeared to be enhanced in the offspring of prior exposed generations. Published by Elsevier Inc. C1 [Delclos, K. Barry] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Bucci, Thomas J.; Olson, Greg; Mellick, Paul; Sadovova, Natalya; Latendresse, John R.] Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Newbold, Retha R.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Delclos, KB (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT 110,3900 NCTR Rd, Jefferson, AR 72079 USA. EM barry.delclos@fda.hhs.gov FU U.S. Food and Drug Administration [IAG 224-07-007]; National Institute for Environmental Health Sciences FX This work was supported by Interagency Agreement IAG 224-07-007 between the U.S. Food and Drug Administration and the National Institute for Environmental Health Sciences. The extensive and expert technical assistance of the NCTR support staff in providing diet preparation, chemical analysis, animal care, computer support, necropsy, and tissue processing services for these studies is gratefully acknowledged. The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration. NR 133 TC 36 Z9 39 U1 0 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD APR PY 2009 VL 27 IS 2 BP 117 EP 132 DI 10.1016/j.reprotox.2008.12.005 PG 16 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 429BA UT WOS:000264894600004 PM 19159674 ER PT J AU Kannan, M Saxena, R Adiguzel, C Fareed, J AF Kannan, Meganathan Saxena, Renu Adiguzel, Cafer Fareed, Jawed TI An Update on the Prevalence and Characterization of H-PF4 Antibodies in Asian-Indian Patients SO SEMINARS IN THROMBOSIS AND HEMOSTASIS LA English DT Article DE Heparin-PF4 antibody; diagnosis; Indian; heparin contaminant ID HEPARIN-INDUCED THROMBOCYTOPENIA; ADVERSE CLINICAL EVENTS; LABORATORY DIAGNOSIS; RISK-FACTORS; PREVENTION; INHIBITORS; THERAPY AB Heparin is the second most widely used anticoagulant/antithrombotic agent besides warfarin and is commonly used for various purposes such as treatment and surgical indications. A significant adverse effect of heparin treatment can occur when heparin binds platelet factor 4 (H-PF4) to form a complex that results in formation of H-PF4 antibodies, which in turn leads to platelet/endothelial cell activation followed by heparin-induced thrombocytopenia (HIT). Based on the heparin-induced platelet aggregation and enzyme-linked immunosorbent assay tests, the H-PF4 antibody (HIT antibody) was diagnosed in 6% of Indian patients undergoing cardiovascular surgery who received unfractionated heparin, but the frequency of occurrence rose to 15% when the patients were tested with the (14)C-serotonin release assay. This highlights some methodological variations in the diagnosis of HIT antibodies. It was also found that all the HIT-positive patients were either homozygous or heterozygous for the Fc gamma RIIa polymorphism, which also highlights the role of this polymorphism in the occurrence of HIT. Very recent studies show that increases in HIT antibody production may also be due to heparin contaminants. Although these antibodies do not result in thrombocytopenia, contaminants in heparin may be capable of triggering a differential immunogenic response in comparison with contaminant-free heparin. Here we discuss the methodological differences in diagnosing HIT, the potential impact of contaminants in heparin, as well as future considerations. C1 [Kannan, Meganathan] US FDA, Div Hematol, NIH, Bethesda, MD 20014 USA. [Adiguzel, Cafer] Marmara Univ, Sch Med, Dept Hematol, Istanbul, Turkey. [Fareed, Jawed] Loyola Univ, Med Ctr, Dept Pharmacol, Chicago, IL 60611 USA. RP Fareed, J (reprint author), Loyola Univ, Med Ctr, Dept Pathol, Hemostasis & Thrombosis Res Program, 2160 S 1st Ave, Maywood, IL 60153 USA. EM jfareed@lumc.edu NR 34 TC 4 Z9 4 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0094-6176 J9 SEMIN THROMB HEMOST JI Semin. Thromb. Hemost. PD APR PY 2009 VL 35 IS 3 BP 337 EP 343 DI 10.1055/s-0029-1222612 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 450DZ UT WOS:000266382500011 PM 19452409 ER PT J AU Gillum, N Karabekian, Z Swift, LM Brown, RP Kay, MW Sarvazyan, N AF Gillum, Nikki Karabekian, Zaruhi Swift, Luther M. Brown, Ronald P. Kay, Matthew W. Sarvazyan, Narine TI Clinically relevant concentrations of di (2-ethylhexyl) phthalate (DEHP) uncouple cardiac syncytium SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Phthalate; Connexin; Gap junction; Cardiomyocytes ID JUNCTIONAL INTERCELLULAR COMMUNICATION; EXTRACORPOREAL MEMBRANE-OXYGENATION; ACTIVATED-RECEPTOR-ALPHA; PROTEIN-KINASE-C; DI(2-ETHYLHEXYL) PHTHALATE; PPAR-ALPHA; DI-(2-ETHYLHEXYL) PHTHALATE; DI-2-ETHYLHEXYL PHTHALATE; SERTOLI-CELLS; GAP-JUNCTIONS AB Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer found in a variety of polyvinyl chloride (PVC) medical products. The results of studies in experimental animals suggest that DEHP leached from flexible PVC tubing may cause health problems in some patient populations. While the cancerogenic and reproductive effects of DEHP are well recognized, little is known about the potential adverse impact of phthalates on the heart. This Study examined the effects of clinically relevant concentrations of DEHP on neonatal rat cardiomyocytes. It was found that application of DEHP to a confluent, synchronously beating cardiac cell network, leads to a marked, concentration-dependent decrease in conduction velocity and asynchronous cell beating. The mechanism behind these changes was a loss of gap junctional connexin-43, documented using Western blot analysis, dye-transfer assay and immunofluorescence. In addition to its DEHP treatment also affected the mechanical movement of myocyte layers. The effect on electrical coupling, latter was linked to the decreased stiffness of the underlying fibroblasts, as the amount of triton-insoluble vimentin was significantly decreased in DEHP-treated samples. The data indicate that DEHP, in clinically relevant concentrations, can impair the electrical and mechanical behavior of a cardiac cell network. Applicability of these findings to human patients remains to be established. (C) 2009 Elsevier Inc. All rights reserved. C1 [Gillum, Nikki; Karabekian, Zaruhi; Swift, Luther M.; Kay, Matthew W.; Sarvazyan, Narine] George Washington Univ, Dept Physiol & Pharmacol, Washington, DC 20037 USA. [Brown, Ronald P.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Kay, Matthew W.] George Washington Univ, Dept Elect & Comp Engn, Washington, DC 20037 USA. RP Sarvazyan, N (reprint author), George Washington Univ, Dept Physiol & Pharmacol, 2300 Eye St, Washington, DC 20037 USA. EM phynas@gwumc.edu RI Posnack, Nikki/F-1170-2013; OI Posnack, Nikki/0000-0002-3880-7200; Swift, Luther/0000-0002-0050-1329 FU National Institutes of Health [HL076722, HL087529]; Mid-Atlantic American Heart Association [0715335U, 0665377U] FX We thank Drs. Ara Arutunyan, Felipe Aguel, and Joe Nielsen for helpful discussions and Dr. Paul Lampe for his advice on site-specific connexin antibodies. Financial support by the National Institutes of Health (HL076722 NS and HL087529 ZK and Mid-Atlantic American Heart Association (0715335U NDG and 0665377U MWK) is gratefully acknowledged. NR 58 TC 24 Z9 25 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 APR 1 PY 2009 VL 236 IS 1 BP 25 EP 38 DI 10.1016/j.taap.2008.12.027 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 424ZO UT WOS:000264607000004 PM 19344669 ER PT J AU Burns, JM Hall, S Ferry, JL AF Burns, Justina M. Hall, Sherwood Ferry, John L. TI The adsorption of saxitoxin to clays and sediments in fresh and saline waters SO WATER RESEARCH LA English DT Article DE STX; Harmful algal bloom; Paralytic shellfish poison; Cyanobacteria; Karenia brevis ID PARALYTIC SHELLFISH POISONS; GULF-OF-MEXICO; KARENIA-BREVIS; CATION EXCHANGE; ORGANIC CATIONS; DRINKING-WATER; PSP TOXINS; BLOOMS; DINOFLAGELLATE; REMOVAL AB The adsorption of saxitoxin to Na- and Ca-montmorillonite, kaolin (crystalline and amorphous), kaolinite, Bread and Butter Creek sediment (an estuarine tidal creek), Gulf of Mexico sediment, and Santa Barbara Basin sediment in deionized water and 32 parts per thousand salinity simulated seawater (Instant Ocean (TM)) is reported. Adsorption was partially reversible for all cases and best described using a Freundlich isotherm. The corresponding Freundlich constants (K(F)) ranged from 8.83 X 10(3) mu mol/kg to 6.76 x 10(4) mu mol/kg for freshwater and 4.73 x 10(3) mu mol/kg-1.11 x 10(4) mu mol/kg for seawater. There is a positive linear correlation seen between the K(F) values and the cation-exchange capacity of the adsorbents. The release of saxitoxin from previously equilibrated adsorbents was determined in freshwater (0-18%) and seawater (4-53%). (C) 2009 Elsevier Ltd. All rights reserved. C1 [Burns, Justina M.; Ferry, John L.] Univ S Carolina, Dept Chem & Biochem, Columbia, SC 29208 USA. [Hall, Sherwood] US FDA, CHCB DBC ORS CFSAN, College Pk, MD 20740 USA. RP Ferry, JL (reprint author), Univ S Carolina, Dept Chem & Biochem, GSRC 631 Sumter St, Columbia, SC 29208 USA. EM fishe@mail.chem.sc.edu; sherwood.hall@fda.hhs.gov; ferry@mail.chem.sc.edu RI Ferry, John/G-8646-2013; OI Ferry, John/0000-0002-1420-8406 NR 37 TC 14 Z9 14 U1 2 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0043-1354 J9 WATER RES JI Water Res. PD APR PY 2009 VL 43 IS 7 BP 1899 EP 1904 DI 10.1016/j.watres.2009.02.004 PG 6 WC Engineering, Environmental; Environmental Sciences; Water Resources SC Engineering; Environmental Sciences & Ecology; Water Resources GA 437SR UT WOS:000265507700012 PM 19249070 ER PT J AU Vellozzi, C Burwen, DR Dobardzic, A Ball, R Walton, K Haber, P AF Vellozzi, Claudia Burwen, Dale R. Dobardzic, Azra Ball, Robert Walton, Kimp Haber, Penina TI Safety of trivalent inactivated influenza vaccines in adults: Background for pandemic influenza vaccine safety monitoring SO VACCINE LA English DT Article DE Influenza vaccines; Vaccine safety; Post-marketing surveillance ID GUILLAIN-BARRE-SYNDROME; EVENT-REPORTING-SYSTEM; OCULO-RESPIRATORY SYNDROME; TRANSVERSE MYELITIS; UNITED-STATES; VAERS; IMMUNIZATION; US; ASSOCIATION; VASCULITIS AB In preparation for pandemic vaccine safety monitoring, we assessed adverse events reported to the Vaccine Adverse Event Reporting System following receipt of trivalent inactivated influenza vaccines among adults from 1990 through 2005. We calculated reporting rates for nonserious, serious, and neurological adverse events. We reviewed reports of recurrent events and deaths, as well as reports identified through advanced signal detection. The most frequently reported events were local reactions and systemic symptoms. Guillain-Barre syndrome was the most frequently reported serious event (0.70 reports per million vaccinations). Adverse event reporting rates have been reasonably constant over time. No new safety concerns emerged after our review of 15 years of post-licensure surveillance data. These findings provide useful information if pandemic vaccine is rapidly distributed and pre-licensure data are limited. Published by Elsevier Ltd. C1 [Vellozzi, Claudia; Walton, Kimp; Haber, Penina] Ctr Dis Control & Prevent, ISO, OCSO, Atlanta, GA USA. [Vellozzi, Claudia] Ctr Dis Control & Prevent, Natl Ctr HIV Hepatitis STD & TB Prevent, Atlanta, GA USA. [Burwen, Dale R.; Dobardzic, Azra; Ball, Robert] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Vellozzi, C (reprint author), 1600 Clifton Rd,MS E-45, Atlanta, GA 30333 USA. EM bno1@cdc.gov; PHaber@cdc.gov NR 61 TC 73 Z9 82 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAR 26 PY 2009 VL 27 IS 15 BP 2114 EP 2120 DI 10.1016/j.vaccine.2009.01.125 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 426AW UT WOS:000264680800006 PM 19356614 ER PT J AU Perera, PY Derrick, SC Kolibab, K Momoi, F Yamamoto, M Morris, SL Waldmann, TA Perera, LR AF Perera, Pin-Yu Derrick, Steven C. Kolibab, Kristopher Momoi, Fumiki Yamamoto, Masafumi Morris, Sheldon L. Waldmann, Thomas A. Perera, Liyanage R. TI A multi-valent vaccinia virus-based tuberculosis vaccine molecularly adjuvanted with interleukin-15 induces robust immune responses in mice SO VACCINE LA English DT Article DE Tuberculosis; Vaccines; IL-15 ID CD8(+) T-CELLS; MYCOBACTERIUM-TUBERCULOSIS; INTERFERON-GAMMA; ANTIGEN 85A; IL-15; INFECTION; BCG; DIFFERENTIATION; IMMUNIZATION; PROTECTION AB Tuberculosis caused by Mycobacterium tuberculosis is responsible for nearly two million deaths every year globally. A single licensed vaccine derived from Mycobacterium bovis, bacille Calmette-Guerin (BCG) administered perinatally as a prophylactic vaccine has been in use for over 80 years and confers substantial protection against childhood tuberculous meningitis and miliary tuberculosis. However, the BCG Vaccine is Virtually ineffective against the adult pulmonary form of tuberculosis that is pivotal in the transmission Of tuberculosis that has infected almost 33% of the global population. Thus, an effective vaccine to both prevent tuberculosis and reduce its transmission is urgently needed. We have generated a multi-valent, vectored vaccine candidate utilizing the modified virus Ankara (MVA) strain of vaccinia virus to tandemly express five antigens, ESAT6, Ag85A, Ag85B, HSP65 and Mtb39A of M. tuberculosis that have been reported to be protective individually in certain animal models together with an immunostimulatory cytokine interleukin-15 (MVA/IL-15/5Mtb). Although, immunological correlates of protection against tuberculosis in humans remain to be established, we demonstrate that our vaccine induced comparable CD4(+) T cell and greater CD8(+) T cell and antibody responses against M. tuberculosis in vaccinated mice in a direct comparison with the BCG vaccine and conferred protection against an aerogenic challenge of M. tuberculosis, thus warranting its further preclinical development. Published by Elsevier Ltd. C1 [Waldmann, Thomas A.; Perera, Liyanage R.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Perera, Pin-Yu] Vet Affairs Med Ctr, Washington, DC 20422 USA. [Derrick, Steven C.; Kolibab, Kristopher; Morris, Sheldon L.] US FDA, Lab Mycobacterial Dis & Cellular Immunol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Momoi, Fumiki; Yamamoto, Masafumi] Nihon Univ, Sch Dent Matsudo, Dept Microbiol & Immunol, Chiba 2718587, Japan. RP Perera, LR (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bldg 10,Room 4B40, Bethesda, MD 20892 USA. EM pereral@mail.nih.gov FU National Cancer Institute; NIH; Trans-NIH/FDA Intramural Biodefense Program FX This work was in part supported by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research, NIH and by a 3-year competitive research funding award to L.P.P. from the Trans-NIH/FDA Intramural Biodefense Program. NR 28 TC 16 Z9 19 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 MAR 26 PY 2009 VL 27 IS 15 BP 2121 EP 2127 DI 10.1016/j.vaccine.2009.01.132 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 426AW UT WOS:000264680800007 PM 19356615 ER PT J AU Zhang, K AF Zhang, Kai TI Multiresidue pesticide analysis of wines by dispersive solid-phase extraction and ultrahigh performance liquid chromatography-tandem mass spectrometry SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Zhang, Kai] FDA Ctr Food Safety & Appl Nutr, ORS DAC Methods Dev Branch, College Pk, MD 20740 USA. EM kai.zhang@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 22 PY 2009 VL 237 MA 140-AGFD BP 92 EP 92 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16GJ UT WOS:000207857800091 ER PT J AU Turujman, S AF Turujman, Saleh TI CHAL 24 - Chemistry review of a new dietary ingredient notification at FDA SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Turujman, Saleh] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM saleh.turujman@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 22 PY 2009 VL 237 MA 24-CHAL BP 932 EP 932 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16GJ UT WOS:000207857800813 ER PT J AU Williams, B AF Williams, Brad TI CHAL 25 - Dietary supplement cGMPs SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Williams, Brad] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM brad.williams@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 22 PY 2009 VL 237 MA 25-CHAL BP 933 EP 933 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16GJ UT WOS:000207857800814 ER PT J AU Furukawa, ES AF Furukawa, Elizabeth S. TI Perspectives on how the US Food and Drug Administration regulates nanotechnology in food contact articles, including food packaging materials and components of food processing equipment SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Furukawa, Elizabeth S.] US FDA, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, Div Food Contact Notificat, College Pk, MD 20740 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 22 PY 2009 VL 237 MA 2-CHAS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16GJ UT WOS:000207857801937 ER PT J AU Cole, LE Yang, Y Elkins, KL Fernandez, ET Qureshi, N Shlomchik, MJ Herzenberg, LA Herzenberg, LA Vogel, SN AF Cole, Leah E. Yang, Yang Elkins, Karen L. Fernandez, Ellen T. Qureshi, Nilofer Shlomchik, Mark J. Herzenberg, Leonard A. Herzenberg, Leonore A. Vogel, Stefanie N. TI Antigen- specific B-1a antibodies induced by Francisella tularensis LPS provide long-term protection against F. tularensis LVS challenge SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LIVE VACCINE STRAIN; BRUTONS TYROSINE KINASE; TOLL-LIKE RECEPTORS; ADAPTIVE IMMUNITY; DEFICIENT MICE; LIPID-A; B-CELLS; LIPOPOLYSACCHARIDE; RESPONSES; INNATE AB Francisella tularensis (Ft), a Gram-negative intracellular bacterium, is the etiologic agent of tularemia. Infection of mice with < 10 Ft Live Vaccine Strain (Ft LVS) organisms i.p. causes a lethal infection that resembles human tularemia. Here, we show that immunization with as little as 0.1 ng Ft LVS lipopolysaccharide (Ft-LPS), but not Ft lipid A, generates a rapid antibody response that protects wild-type (WT) mice against lethal Ft LVS challenge. Protection is not induced in Ft-LPS-immunized B cell-deficient mice (mu MT or JhD), male xid mice, or Ig transgenic mice that produce a single IgH (not reactive with Ft-LPS). Focusing on the cellular mechanisms that underlie this protective response, we show that Ft-LPS specifically stimulates proliferation of B-1a lymphocytes that bind fluoro-chrome-labeled Ft-LPS and the differentiation of these cells to plasma cells that secrete antibodies specific for Ft-LPS. This exclusively B-1a antibody response is equivalent in WT, T-deficient (TCR alpha beta(-/-), TCR gamma delta(-/-)), and Toll-like receptor 4 (TLR4)-deficient (TLR4(-/-)) mice and thus is not dependent on T cells or typical inflammatory processes. Serum antibody levels peak approximate to 5 days after Ft-LPS immunization and persist at low levels for months. Thus, immunization with Ft-LPS activates a rare population of antigen-specific B-1a cells to produce a persistent T- independent antibody response that provides long-term protection against lethal Ft LVS infection. These data support the possibility of creating effective, minimally invasive vaccines that can provide effective protection against pathogen invasion. C1 [Yang, Yang; Herzenberg, Leonard A.; Herzenberg, Leonore A.] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA. [Cole, Leah E.; Vogel, Stefanie N.] Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. [Elkins, Karen L.; Fernandez, Ellen T.] US FDA, Lab Mycobacteriol Dis & Cellular Immunol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Qureshi, Nilofer] Univ Missouri, Dept Basic Med Sci, Kansas City, MO 64108 USA. [Shlomchik, Mark J.] Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06520 USA. [Shlomchik, Mark J.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA. RP Herzenberg, LA (reprint author), Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA. EM lenherz@standford.edu; svogel@som.umaryland.edu FU National Institutes of Health [AI18797, U54 AI157168, AI076434, AI57168, GM50870, AI43603]; Center for Biologics Evaluation and Research/Food and Drug Administration-National Institute of Allergy and Infectious Diseases/National Institutes of Health [Y1-AI-6153-01/224-06-1322] FX The authors thank Suzanne M. Michalek, Jan Cerny, Martin Flajnik and John Mantovani for their thoughtful comments, suggestions, and help. This work was supported in part by National Institutes of Health Grant AI18797 and Subaward U54 AI157168 (to S. N. V.), National Institutes of Health Grant AI076434 (to L. A. H.), Center for Biologics Evaluation and Research/Food and Drug Administration-National Institute of Allergy and Infectious Diseases/National Institutes of Health Interagency Agreement Y1-AI-6153-01/224-06-1322 (to K. L. E.), and National Institutes of Health Grants AI57168 and GM50870 (to N. Q.) and AI43603 (to M. J. S.). NR 33 TC 67 Z9 69 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 17 PY 2009 VL 106 IS 11 BP 4343 EP 4348 DI 10.1073/pnas.0813411106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 420HD UT WOS:000264278800053 PM 19251656 ER PT J AU Rich, RL Papalia, GA Flynn, PJ Furneisen, J Quinn, J Klein, JS Katsamba, PS Waddell, MB Scott, M Thompson, J Berlier, J Corry, S Baltzinger, M Zeder-Lutzi, G Schoenemann, A Clabbers, A Wieckowski, S Murphy, MM Page, P Ryan, TE Duffner, J Ganguly, T Corbin, J Gautam, S Anderluh, G Bavdek, A Reichmann, D Yadav, SP Hommema, E Pol, E Drake, A Klakamp, S Chapman, T Kernaghan, D Miller, K Schuman, J Lindquist, K Herlihy, K Murphy, MB Bohnsack, R Andrien, B Brandani, P Terwey, D Millican, R Darling, RJ Wang, L Carter, Q Dotzlaf, J Lopez-Sagaseta, J Campbell, I Torreri, P Hoos, S England, P Liu, Y Abdiche, Y Malashock, D Pinkerton, A Wong, M Lafer, E Hinck, C Thompson, K Di Primo, C Joyce, A Brooks, J Torta, F Hagel, ABB Krarup, J Pass, J Ferreira, M Shikov, S Mikolajczyk, M Abe, Y Barbato, G Giannetti, AM Krishnamoorthy, G Beusink, B Satpaev, D Tsang, T Fang, E Partridge, J Brohawn, S Horn, J Pritsch, O Obal, G Nilapwar, S Busby, B Gutierrez-Sanchez, G Das Gupta, R Canepa, S Witte, K Nikolovska-Coleska, Z Cho, YH D'Agata, R Schlick, K Calvert, R Munoz, EM Hernaiz, MJ Bravman, T Dines, M Yang, MH Puskas, A Boni, E Li, JJ Wear, M Grinberg, A Baardsnes, J Dolezal, O Gainey, M Anderson, H Peng, JL Lewis, M Spies, P Trinh, Q Bibikov, S Raymond, J Yousef, M Chandrasekaran, V Feng, YG Emerick, A Mundodo, S Guimaraes, R McGirr, K Li, YJ Hughes, H Mantz, H Skrabana, R Witmer, M Ballard, J Martin, L Skladal, P Korza, G Laird-Offringa, I Lee, CS Khadir, A Podlaski, F Neuner, P Rothacker, J Rafique, A Dankbar, N Kainz, P Gedig, E Vuyisich, M Boozer, C Ly, N Toews, M Uren, A Kalyuzhniy, O Lewis, K Chomey, E Pak, BJ Myszka, DG AF Rich, Rebecca L. Papalia, Giuseppe A. Flynn, Peter J. Furneisen, Jamie Quinn, John Klein, Joshua S. Katsamba, Phini S. Waddell, M. Brent Scott, Michael Thompson, Joshua Berlier, Judie Corry, Schuyler Baltzinger, Mireille Zeder-Lutzi, Gabrielle Schoenemann, Andreas Clabbers, Anca Wieckowski, Sebastien Murphy, Mary M. Page, Phillip Ryan, Thomas E. Duffner, Jay Ganguly, Tanmoy Corbin, John Gautam, Satyen Anderluh, Gregor Bavdek, Andrej Reichmann, Dana Yadav, Satya P. Hommema, Eric Pol, Ewa Drake, Andrew Klakamp, Scott Chapman, Trevor Kernaghan, Dawn Miller, Ken Schuman, Jason Lindquist, Kevin Herlihy, Kara Murphy, Michael B. Bohnsack, Richard Andrien, Bruce Brandani, Pietro Terwey, Danny Millican, Rohn Darling, Ryan J. Wang, Liann Carter, Quincy Dotzlaf, Joe Lopez-Sagaseta, Jacinto Campbell, Islay Torreri, Paola Hoos, Sylviane England, Patrick Liu, Yang Abdiche, Yasmina Malashock, Daniel Pinkerton, Alanna Wong, Melanie Lafer, Eileen Hinck, Cynthia Thompson, Kevin Di Primo, Carmelo Joyce, Alison Brooks, Jonathan Torta, Federico Hagel, Anne Birgitte Bagge Krarup, Janus Pass, Jesper Ferreira, Monica Shikov, Sergei Mikolajczyk, Malgorzata Abe, Yuki Barbato, Gaetano Giannetti, Anthony M. Krishnamoorthy, Ganeshram Beusink, Bianca Satpaev, Daulet Tsang, Tiffany Fang, Eric Partridge, James Brohawn, Stephen Horn, James Pritsch, Otto Obal, Gonzalo Nilapwar, Sanjay Busby, Ben Gutierrez-Sanchez, Gerardo Das Gupta, Ruchira Canepa, Sylvie Witte, Krista Nikolovska-Coleska, Zaneta Cho, Yun Hee D'Agata, Roberta Schlick, Kristian Calvert, Rosy Munoz, Eva M. Hernaiz, Maria Jose Bravman, Tsafir Dines, Monica Yang, Min-Hsiang Puskas, Agnes Boni, Erica Li, Jiejin Wear, Martin Grinberg, Asya Baardsnes, Jason Dolezal, Olan Gainey, Melicia Anderson, Henrik Peng, Jinlin Lewis, Mark Spies, Peter Trinh, Quyhn Bibikov, Sergei Raymond, Jill Yousef, Mohammed Chandrasekaran, Vidya Feng, Yuguo Emerick, Anne Mundodo, Suparna Guimaraes, Rejane McGirr, Katy Li, Yue-Ji Hughes, Heather Mantz, Hubert Skrabana, Rostislav Witmer, Mark Ballard, Joshua Martin, Loic Skladal, Petr Korza, George Laird-Offringa, Ite Lee, Charlene S. Khadir, Abdelkrim Podlaski, Frank Neuner, Phillippe Rothacker, Julie Rafique, Ashique Dankbar, Nico Kainz, Peter Gedig, Erk Vuyisich, Momchilo Boozer, Christina Ly, Nguyen Toews, Mark Uren, Aykut Kalyuzhniy, Oleksandr Lewis, Kenneth Chomey, Eugene Pak, Brian J. Myszka, David G. TI A global benchmark study using affinity-based biosensors SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE Biacore; Kinetics; Optical biosensor; Surface plasmon resonance ID BIACORE TECHNOLOGY; RATE CONSTANTS; KINETICS; BINDING; USERS AB To explore the variability in biosensor studies, 150 participants from 20 countries were given the same protein samples and asked to determine kinetic rate constants for the interaction. We chose a protein system that was amenable to analysis using different biosensor platforms as well as by users of different expertise levels. The two proteins (a 50-kDa Fab and a 60-kDa glutathione S-transferase [GST] antigen) form a relatively high-affinity complex, so participants needed to optimize several experimental parameters, including ligand immobilization and regeneration conditions as well as analyte concentrations and injection/dissociation times. Although most participants collected binding responses that could be fit to yield kinetic parameters, the quality of a few data sets could have been improved by optimizing the assay design. Once these outliers were removed, the average reported affinity across the remaining panel of participants was 620 pM with a standard deviation of 980 pM. These results demonstrate that when this biosensor assay was designed and executed appropriately, the reported rate constants were consistent, and independent of which protein was immobilized and which biosensor was used. (C) 2008 Elsevier Inc. All rights reserved. C1 [Rich, Rebecca L.; Papalia, Giuseppe A.; Myszka, David G.] Univ Utah, Sch Med, Ctr Biomol Interact Anal, Salt Lake City, UT 84132 USA. [Flynn, Peter J.] KaloBios Pharmaceut, San Francisco, CA 94080 USA. [Furneisen, Jamie] Schering Plough Biopharma, Palo Alto, CA 94304 USA. [Quinn, John] Nomadics, Oklahoma City, OK 73104 USA. [Klein, Joshua S.] CALTECH, Pasadena, CA 91125 USA. [Katsamba, Phini S.] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. [Waddell, M. Brent] St Jude Childrens Hosp, Hartwell Ctr Bioinformat & Biotechnol, Memphis, TN 38105 USA. [Scott, Michael] Univ Zurich, CH-8057 Zurich, Switzerland. [Thompson, Joshua; Berlier, Judie; Corry, Schuyler] Mol Probes Invitrogen, Eugene, OR 97402 USA. [Baltzinger, Mireille; Zeder-Lutzi, Gabrielle] Univ Strasbourg, F-67412 Illkirch Graffenstaden, France. [Schoenemann, Andreas] Merck KGaA, D-64293 Darmstadt, Germany. [Clabbers, Anca] Abbott Biores Ctr, Worcester, MA 01605 USA. [Wieckowski, Sebastien] Univ Strasbourg, Inst Mol & Cellular Biol, F-67084 Strasbourg, France. [Murphy, Mary M.; Page, Phillip; Ryan, Thomas E.] Reichert, Depew, NY 14043 USA. [Duffner, Jay; Ganguly, Tanmoy] Momenta Pharmaceut, Cambridge, MA 02142 USA. [Corbin, John] XOMA US, Emeryville, CA 94608 USA. [Gautam, Satyen] Natl Univ Singapore, Dept Chem & Biomol Engn, Singapore 119260, Singapore. [Anderluh, Gregor; Bavdek, Andrej] Univ Ljubljana, Dept Biol, Ljubljana 1000, Slovenia. [Reichmann, Dana] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. [Yadav, Satya P.] Cleveland Clin Fdn, Mol Biotechnol Core Lab, Cleveland, OH 44195 USA. [Hommema, Eric] ThermoFisher Sci, Rockford, IL 61101 USA. [Pol, Ewa] Biacore GE Healthcare, SE-75450 Uppsala, Sweden. [Drake, Andrew; Klakamp, Scott] AstraZeneca, Hayward, CA 94545 USA. [Chapman, Trevor] GlaxoSmithKline Inc, Neurodegenerat Res Dept, Harlow CM19 5AW, Essex, England. [Kernaghan, Dawn; Miller, Ken] Medimmune Inc, Gaithersburg, MD 20878 USA. [Schuman, Jason; Lindquist, Kevin; Herlihy, Kara; Murphy, Michael B.] Biacore GE Healthcare, Piscataway, NJ 08854 USA. [Bohnsack, Richard] Med Coll Wisconsin, Dept Biochem, Milwaukee, WI 53226 USA. [Andrien, Bruce] Alex Pharmaceut, Cheshire, CT 06410 USA. [Brandani, Pietro] Appl Biosyst Inc, Foster City, CA 94404 USA. [Terwey, Danny] DiaDexus, San Francisco, CA 94080 USA. [Millican, Rohn; Darling, Ryan J.; Wang, Liann; Carter, Quincy; Dotzlaf, Joe] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Lopez-Sagaseta, Jacinto] Univ Navarra, Ctr Appl Med Res, Lab Thrombosis & Haemostasis, E-31080 Pamplona, Spain. [Campbell, Islay] EMD Lexigen Res Ctr, Billerica, MA 01821 USA. [Torreri, Paola] Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy. [Hoos, Sylviane; England, Patrick] Inst Pasteur, Dept Struct Biol & Chem, F-75724 Paris, France. [Liu, Yang] Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA. [Abdiche, Yasmina; Malashock, Daniel; Pinkerton, Alanna] Pfizer Rinat Labs, San Francisco, CA 94080 USA. [Wong, Melanie] PDL BioPharma, Fremont, CA 94555 USA. [Lafer, Eileen; Hinck, Cynthia] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Thompson, Kevin] Akubio, Cambridge CB4 0GJ, England. [Di Primo, Carmelo] Univ Bordeaux, Inst Europeen Chim & Biol, INSERM, U869, F-33607 Pessac, France. [Joyce, Alison; Brooks, Jonathan] Wyeth Res, Cambridge, MA 02140 USA. [Torta, Federico] Univ So Denmark, Dept Biochem & Mol Biol, DK-5230 Odense M, Denmark. [Hagel, Anne Birgitte Bagge; Krarup, Janus; Pass, Jesper] Novo Nordisk AS, DK-2820 Gentofte, Denmark. [Ferreira, Monica] Sodertorns Univ Coll, S-14152 Huddinge, Sweden. [Shikov, Sergei] Temple Univ, Dept Biochem, Philadelphia, PA 19140 USA. [Mikolajczyk, Malgorzata] US FDA, Bethesda, MD 20892 USA. [Abe, Yuki] UCL, Dept Biochem Engn, London WC1E 7JE, England. [Barbato, Gaetano] Merck, I-00040 Rome, Italy. [Giannetti, Anthony M.] Roche, Palo Alto, CA 94304 USA. [Krishnamoorthy, Ganeshram; Beusink, Bianca] Univ Twente, NL-7500 AE Enschede, Netherlands. [Satpaev, Daulet] Agensys, Santa Monica, CA 90404 USA. [Tsang, Tiffany; Fang, Eric] Novartis, Emeryville, CA 94608 USA. [Partridge, James; Brohawn, Stephen] MIT, Cambridge, MA 02139 USA. [Horn, James] No Illinois Univ, De Kalb, IL 60115 USA. [Pritsch, Otto; Obal, Gonzalo] Pasteur Inst Montevideo, Montevideo, Uruguay. [Nilapwar, Sanjay] Univ Manchester, Manchester M1 7ND, Lancs, England. [Busby, Ben] Univ Maryland, Dept Physiol, Baltimore, MD 21201 USA. [Gutierrez-Sanchez, Gerardo] Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA. [Das Gupta, Ruchira] Adnexus Therapeut, Waltham, MA 02453 USA. [Canepa, Sylvie] Univ Tours, F-37380 Nouzilly, France. [Witte, Krista] ForteBio, Menlo Pk, CA 94025 USA. [Nikolovska-Coleska, Zaneta] Univ Michigan, Ann Arbor, MI 48109 USA. [Cho, Yun Hee] Human Genome Sci, Rockville, MD 20850 USA. [D'Agata, Roberta] Univ Catania, Dept Chem Sci, I-95125 Catania, Italy. [Schlick, Kristian] Montana State Univ, Bozeman, MT 59717 USA. [Calvert, Rosy] GKT Sch Biomed Sci, London SE1 1UL, England. [Munoz, Eva M.; Hernaiz, Maria Jose] Univ Complutense, Organ & Pharmaceut Chem Dept, E-28040 Madrid, Spain. [Bravman, Tsafir; Dines, Monica] Biorad Haifa, IL-32000 Haifa, Israel. [Yang, Min-Hsiang] Acad Sinica, Inst Chem, Taipei 115, Taiwan. [Puskas, Agnes] Univ Texas Houston, Sch Med, Houston, TX 77030 USA. [Boni, Erica] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Li, Jiejin] Natl Inst Med Res UK, Div Mol Struct, London NW7 1AA, England. [Wear, Martin] Univ Edinburgh, Inst Struct & Mol Biol, Ctr Translat & Chem Biol, Edinburgh EH9 3JR, Midlothian, Scotland. [Grinberg, Asya] Acceleron Pharma, Cambridge, MA 02139 USA. [Baardsnes, Jason] Natl Res Council Canada, Biotechnol Res Inst, Montreal, PQ H4P 2R2, Canada. [Dolezal, Olan] CSIRO, Hlth Sci & Nutr, Parkville, Vic 3052, Australia. [Gainey, Melicia] Battelle Biomed Res Ctr, Columbus, OH 43201 USA. [Anderson, Henrik] Attana AB, SE-11347 Stockholm, Sweden. [Peng, Jinlin; Lewis, Mark] Corning Inc, Corning, NY 14831 USA. [Spies, Peter] Univ Appl Sci NW Switzerland, Sch Life Sci, Inst Chem & Bioanalyt, CH-4132 Muttenz, Switzerland. [Trinh, Quyhn; Bibikov, Sergei; Raymond, Jill; Yousef, Mohammed; Chandrasekaran, Vidya; Feng, Yuguo; Emerick, Anne; Mundodo, Suparna; Guimaraes, Rejane; McGirr, Katy] Biorad, Hercules, CA 94547 USA. [Li, Yue-Ji] Monsanto Co, St Louis, MO 63198 USA. [Hughes, Heather] Genzyme, Cambridge, MA 02142 USA. [Mantz, Hubert] Univ Saarland, D-66041 Saarbrucken, Germany. [Skrabana, Rostislav] SAS, Inst Neuroimmunol, Bratislava 84510, Slovakia. [Witmer, Mark] Bristol Myers Squibb Co, Princeton, NJ 08543 USA. [Ballard, Joshua] Array Biopharma, Boulder, CO 80301 USA. [Martin, Loic] CEA, IBiTecs, Serv Ingn Mol Prot, F-91191 Gif Sur Yvette, France. [Skladal, Petr] Masaryk Univ, Dept Biochem, CS-61137 Brno, Czech Republic. [Korza, George] Univ Connecticut, Ctr Hlth, Farmington, CT 06030 USA. [Laird-Offringa, Ite; Lee, Charlene S.] Univ So Calif, Los Angeles, CA 90033 USA. [Khadir, Abdelkrim] GeminX Biotechnol, Montreal, PQ H2X 2H7, Canada. [Podlaski, Frank] Hoffmann La Roche Inc, Nutley, NJ 07110 USA. [Neuner, Phillippe] IRBM, I-00040 Rome, Italy. [Rothacker, Julie] Royal Melbourne Hosp, Ludwig Inst Canc Res, Parkville, Vic 3050, Australia. [Rafique, Ashique] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. [Dankbar, Nico] Univ Munster, D-48149 Munster, Germany. [Kainz, Peter] Salzburg Univ, Dept Mol Biol, A-5020 Salzburg, Austria. [Gedig, Erk] XanTec Bioanalyt, D-48149 Munster, Germany. [Vuyisich, Momchilo] Los Alamos Natl Lab, Biosci Div, Los Alamos, NM 87545 USA. [Boozer, Christina] Lumera, Bothell, WA 98011 USA. [Ly, Nguyen] Arizona State Univ, Tempe, AZ 85287 USA. [Toews, Mark] Dyax, Cambridge, MA 02139 USA. [Uren, Aykut] Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20057 USA. [Kalyuzhniy, Oleksandr] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. [Lewis, Kenneth] Zymogenet Inc, Seattle, WA 98102 USA. [Chomey, Eugene] Biorad Canada, Edmonton, AB T6R 2W6, Canada. [Pak, Brian J.] Biorad Canada, Toronto, ON, Canada. RP Myszka, DG (reprint author), Univ Utah, Sch Med, Ctr Biomol Interact Anal, Salt Lake City, UT 84132 USA. EM dmyszka@cores.utah.edu RI TORRERI, PAOLA/A-6656-2015; Dolezal, Olan/E-1691-2015; Horn, James/B-4011-2009; Li, Jiejin/G-4980-2010; Barbato, Gaetano/G-4904-2011; Anderluh, Gregor/C-6905-2014; Klakamp, Scott/D-7738-2014; Skladal, Petr/E-4308-2012 OI TORRERI, PAOLA/0000-0002-0488-956X; Katsamba, Phinikoula/0000-0003-3981-1604; Anderluh, Gregor/0000-0002-9916-8465; Klakamp, Scott/0000-0002-1231-9655; Skladal, Petr/0000-0002-3868-5725 FU NCI NIH HHS [P30 CA051008, P30 CA054174]; NCRR NIH HHS [S10 RR027551] NR 14 TC 46 Z9 46 U1 4 U2 51 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 MAR 15 PY 2009 VL 386 IS 2 BP 194 EP 216 DI 10.1016/j.ab.2008.11.021 PG 23 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 413JN UT WOS:000263789500009 PM 19133223 ER PT J AU Shabalina, SA Zaykin, DV Gris, P Ogurtsov, AY Gauthier, J Shibata, K Tchivileva, IE Belfer, I Mishra, B Kiselycznyk, C Wallace, MR Staud, R Spiridonov, NA Max, MB Goldman, D Fillingim, RB Maixner, W Diatchenko, L AF Shabalina, Svetlana A. Zaykin, Dmitri V. Gris, Pavel Ogurtsov, Aleksey Y. Gauthier, Josee Shibata, Kyoko Tchivileva, Inna E. Belfer, Inna Mishra, Bikashkumar Kiselycznyk, Carly Wallace, Margaret R. Staud, Roland Spiridonov, Nikolay A. Max, Mitchell B. Goldman, David Fillingim, Roger B. Maixner, William Diatchenko, Luda TI Expansion of the human mu-opioid receptor gene architecture: novel functional variants SO HUMAN MOLECULAR GENETICS LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISM; MORPHINE-INDUCED ANALGESIA; EXPERIMENTAL PAIN; INTERGENIC REGIONS; OPIATE RECEPTOR; MESSENGER-RNAS; MOUSE GENOMES; MICE LACKING; OPRM GENE; ASSOCIATION AB The mu-opioid receptor (OPRM1) is the principal receptor target for both endogenous and exogenous opioid analgesics. There are substantial individual differences in human responses to painful stimuli and to opiate drugs that are attributed to genetic variations in OPRM1. In searching for new functional variants, we employed comparative genome analysis and obtained evidence for the existence of an expanded human OPRM1 gene locus with new promoters, alternative exons and regulatory elements. Examination of polymorphisms within the human OPRM1 gene locus identified strong association between single nucleotide polymorphism (SNP) rs563649 and individual variations in pain perception. SNP rs563649 is located within a structurally conserved internal ribosome entry site (IRES) in the 5'-UTR of a novel exon 13-containing OPRM1 isoforms (MOR-1K) and affects both mRNA levels and translation efficiency of these variants. Furthermore, rs563649 exhibits very strong linkage disequilibrium throughout the entire OPRM1 gene locus and thus affects the functional contribution of the corresponding haplotype that includes other functional OPRM1 SNPs. Our results provide evidence for an essential role for MOR-1K isoforms in nociceptive signaling and suggest that genetic variations in alternative OPRM1 isoforms may contribute to individual differences in opiate responses. C1 [Shabalina, Svetlana A.; Ogurtsov, Aleksey Y.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Zaykin, Dmitri V.; Shibata, Kyoko] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Gris, Pavel; Gauthier, Josee; Tchivileva, Inna E.; Maixner, William; Diatchenko, Luda] Univ N Carolina, Ctr Neurosensory Disorders, Sch Dent, Chapel Hill, NC 27599 USA. [Belfer, Inna; Mishra, Bikashkumar; Kiselycznyk, Carly; Max, Mitchell B.] NIH, Dept Hlth & Human Serv, Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. [Belfer, Inna; Mishra, Bikashkumar; Kiselycznyk, Carly; Goldman, David] NIAAA, Neurogenet Lab, Dept Hlth & Human Serv, NIH, Rockville, MD 20852 USA. [Belfer, Inna; Max, Mitchell B.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA 15261 USA. [Wallace, Margaret R.] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32608 USA. [Staud, Roland; Fillingim, Roger B.] Univ Florida, Coll Dent Community Dent & Behav Sci, Gainesville, FL 32608 USA. [Spiridonov, Nikolay A.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Shabalina, SA (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM shabalin@ncbi.nlm.nih.gov; lbdiatch@email.unc.edu RI Goldman, David/F-9772-2010; Shabalina, Svetlana/N-8939-2013; Spiridonov, Nikolay/B-6287-2014 OI Goldman, David/0000-0002-1724-5405; Shabalina, Svetlana/0000-0003-2272-7473; FU NIDCR; NINDS [RO1-DE16558, UO1-DE017018, NS41670, PO1 NS045685]; RO1-DE16558, UO1-DE017018, NS41670 and PO1 NS045685, and the Intramural Research Programs of NIEHS; NCBI/NLM; NIDRC; National Institutes of Health; National Library of Medicine FX This work was supported in part by NIDCR and NINDS grants RO1-DE16558, UO1-DE017018, NS41670 and PO1 NS045685, and the Intramural Research Programs of NIEHS, NCBI/NLM and NIDRC. Funding to pay the Open Access Charge was provided by Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 77 TC 89 Z9 94 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAR 15 PY 2009 VL 18 IS 6 BP 1037 EP 1051 DI 10.1093/hmg/ddn439 PG 15 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 413XT UT WOS:000263828100005 PM 19103668 ER PT J AU Kioi, M Shimamura, T Nakashima, H Hirota, M Tohnai, I Husain, SR Puri, RK AF Kioi, Mitomu Shimamura, Takeshi Nakashima, Hideyuki Hirota, Makoto Tohnai, Iwai Husain, Syed R. Puri, Raj K. TI IL-13 cytotoxin has potent antitumor activity and synergizes with paclitaxel in a mouse model of oral squamous cell carcinoma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE interleukin-13 receptor; squamous cell carcinoma; oral cancer; synergistic effect; gene transfer; retrovirus; paclitaxel; orthotopic animal model ID RECEPTOR ALPHA-2 CHAIN; INTERLEUKIN-13 RECEPTOR; PSEUDOMONAS EXOTOXIN; NECK-CANCER; INDUCTION CHEMOTHERAPY; OVARIAN-CANCER; BREAST-CANCER; HEAD; CISPLATIN; SUBUNIT AB Interleukin-13 receptor-targeted cytotoxin (IL13-PE38) is highly cytotoxic to certain types of human cancers expressing abundant levels of IL-13R alpha 2 chain. Although IL13-PE38 is being tested in a Phase III clinical trial in brain tumors, the activity of IL13-PE38 alone or when combined with taxane, a chemotherapeutic drug for oral squamous cell carcinoma (OSCC), has not been investigated. Here, we show that approximately 40% of OSCCs (n = 150) in a tissue array are strongly positive for IL-13R alpha 2, whereas normal oral mucosa (n = 10) expresses very low or undetectable levels evaluated by immunohistochemistry. IL13-PE38 was highly cytotoxic to OSCC cell lines, but not cytotoxic to normal oral fibroblasts. IL13-PE38 mediated a synergistic antitumor effect with paclitaxel in OSC-19 in vitro and in vivo in the orthotopic OSCC tongue tumor model. Real-time tumor growth was monitored by optical imaging using a Xenogen-IVIS imaging system. Treated animals showed significant (p < 0.05) improvement in survival, which correlated with in vivo imaging of tumor response without evidence of visible toxicity. Gene transfer of IL-13Ra2 in oral cancer cells increased sensitivity of OSCC cell line to IL13-PE38 in vitro. Retro-virus-mediated gene-transfer of IL-13R alpha 2 in HSC-3 into tongue tumors in vivo dramatically enhanced the antitumor activity of IL13-PE38, providing complete elimination of established tumors and prolonging survival of these animals. These results indicate that IL13-PE38 in combination with paclitaxel acting via different mechanisms may be a potential treatment option for IL-13R alpha 2 expressing OSCC or for the treatment of nom-IL-13R alpha 2 expressing OSCC combined with gene transfer of IL-13R alpha 2. Published 2008 Wiley-Liss, Inc. C1 [Kioi, Mitomu; Shimamura, Takeshi; Nakashima, Hideyuki; Husain, Syed R.; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Hirota, Makoto; Tohnai, Iwai] Yokohama City Univ, Sch Med, Dept Oral & Maxillofacial Surg, Kanazawa Ku, Yokohama, Kanagawa 232, Japan. RP Puri, RK (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN20,29 Lincoln Dr, Bethesda, MD 20892 USA. EM raj.puri@fda.hhs.gov OI Kioi, Mitomu/0000-0002-7981-3340 NR 34 TC 13 Z9 13 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 15 PY 2009 VL 124 IS 6 BP 1440 EP 1448 DI 10.1002/ijc.24067 PG 9 WC Oncology SC Oncology GA 409XR UT WOS:000263539600027 PM 19065664 ER PT J AU Parveen, S Hettiarachchi, KA Bowers, JC Jones, JL Tamplin, ML Mckay, R Beatty, W Brohawn, K DaSilva, LV DePaola, A AF Parveen, Salina Hettiarachchi, Kumidini A. Bowers, John C. Jones, Jessica L. Tamplin, Mark L. McKay, Rusty Beatty, William Brohawn, Kathy DaSilva, Ligia V. DePaola, Angelo TI Seasonal distribution of total and pathogenic Vibrio parahaemolyticus in Chesapeake Bay oysters and waters (vol 128, pg 354, 2008) SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Correction C1 [Parveen, Salina; Hettiarachchi, Kumidini A.; DaSilva, Ligia V.] Univ Maryland Eastern Shore, Dept Agr Food & Resource Sci, Food Sci & Technol PhD Program, Princess Anne, MD 21853 USA. [Bowers, John C.] US FDA, Div Publ Hlth & Biostat, College Pk, MD 20740 USA. [Jones, Jessica L.] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. [Tamplin, Mark L.] Univ Tasmania, Food Safety Ctr, Hobart, Tas 7001, Australia. [McKay, Rusty; Beatty, William; Brohawn, Kathy; DePaola, Angelo] Maryland Dept Environm, Baltimore, MD 21230 USA. RP Parveen, S (reprint author), Univ Maryland Eastern Shore, Dept Agr Food & Resource Sci, Food Sci & Technol PhD Program, Princess Anne, MD 21853 USA. EM sparveen@umes.edu NR 1 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD MAR 15 PY 2009 VL 130 IS 1 BP 75 EP 75 DI 10.1016/j.ijfoodmicro.2008.11.018 PG 1 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 417AX UT WOS:000264048000014 ER PT J AU Pogribny, IR Muskhelishvili, L Tryndyak, VP Beland, FA AF Pogribny, Igor R. Muskhelishvili, Levan Tryndyak, Volodymyr P. Beland, Frederick A. TI The tumor-promoting activity of 2-acetylaminofluorene is associated with disruption of the p53 signaling pathway and the balance between apoptosis and cell proliferation SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE 2-Acetylaminofluore; Hepatocarcinogenesis; Cell proliferation; Apoptosis; p53; MicroRNA ID PRENEOPLASTIC RAT HEPATOCYTES; HEPATOCELLULAR-CARCINOMA; GENE-EXPRESSION; LIVER-CANCER; DNA-DAMAGE; IN-VITRO; PROTEIN EXPRESSION; DOSE-RESPONSE; E-CADHERIN; C-MYC AB The aromatic amine 2-acetylaminifluore (2-AAF) is a powerful complete genotoxic rat liver carcinogen that induces tumors without any additional interventions. While the tumor-initiating genotoxic activity of 2-AAF is well established, its tumor-promotion activity is far less understood. It is believed that the tumor-promoting Property of 2-AAF is associated with selective enhancement of cell replication and sustained suppression of apoptosis in initiated cells. In the present study, we investigated the underlying mechanisms of tumor promoting events induced by 2-AAF-exposure. Male Sprague-Dawley rats were fed NIH-31 diet containing 0.02% of 2-AAF for 12 and 24 weeks, and the expression pattern of genes associated with the p53-signaling pathway and microRNA genes was determined in the livers of control and 2-AAF-fed rats. The results indicate that the tumor-promoting property of 2-AAF during hepatocarcinogenesis is associated predominantly with the up-regulation of anti-apoptotic growth-related genes and clown-regulation of expression of pro-apoptotic genes. This disrupts the balance between cell proliferation and apoptosis, which leads to consequential unrestricted cell proliferation, especially of initiated cells. Also, the long-term-ad ministration of 2-AAF resulted in disruption of regulatory miR-34a-p53 feed-back loop that mediates apoptosis. This was evidenced by an increased expression of miR-34a in response to genotoxic effects of 2-AAF in the absence of p53 up-regulation, and loss of regulatory control of mir-34a on SIRT1 function. Additionally, the livers of 2-AAF-exposed rats were characterized by the substantial deregulation of expression of miR-18, miR-21, miR-182, and miR-200 family, microRNAs involved in control of apoptosis/cell proliferation and cell-cell contact pathways, two major pathways disrupted during the promotion stage of hepatocarcinogenesis. Published by Elsevier Inc. C1 [Pogribny, Igor R.; Tryndyak, Volodymyr P.; Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Pogribny, IR (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM igor.pogrjbny@fda.hhs.gov NR 61 TC 49 Z9 50 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 15 PY 2009 VL 235 IS 3 BP 305 EP 311 DI 10.1016/j.taap.2008.12.021 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 419GQ UT WOS:000264207900005 PM 19167416 ER PT J AU Buehler, PW Abraham, B Vallelian, F Linnemayr, C Pereira, CP Cipollo, JF Jia, YP Mikolajczyk, M Boretti, FS Schoedon, G Alayash, AI Schaer, DJ AF Buehler, Paul W. Abraham, Bindu Vallelian, Florence Linnemayr, Charlotte Pereira, Claudia P. Cipollo, John F. Jia, Yiping Mikolajczyk, Malgorzata Boretti, Felicitas S. Schoedon, Gabriele Alayash, Abdu I. Schaer, Dominik J. TI Haptoglobin preserves the CD163 hemoglobin scavenger pathway by shielding hemoglobin from peroxidative modification SO BLOOD LA English DT Article ID CROSS-LINKED HEMOGLOBIN; SPERM-WHALE MYOGLOBIN; HYDROGEN-PEROXIDE; BINDING-SITE; ENDOTHELIAL-CELLS; HEME DEGRADATION; OXIDATIVE STRESS; REDOX PROPERTIES; ACUTE HEMOLYSIS; OXYGEN-BINDING AB Detoxification and clearance of extracellular hemoglobin (Hb) have been attributed to its removal by the CD163 scavenger receptor pathway. However, even low-level hydrogen peroxide (H(2)O(2)) exposure irreversibly modifies Hb and severely impairs Hb endocytosis by CD163. We show here that when Hb is bound to the high-affinity Hb scavenger protein haptoglobin (Hp), the complex protects Hb from structural modification by preventing alpha-globin cross-links and oxidations of amino acids in critical regions of the beta-globin chain (eg, Trp15, Cys93, and Cys112). As a result of this structural stabilization, H(2)O(2)-exposed Hb-Hp binds to CD163 with the same affinity as nonoxidized complex. Endocytosis and lysosomal translocation of oxidized Hb-Hp by CD163-expressing cells were found to be as efficient as with nonoxidized complex. Hp complex formation did not alter Hb's ability to consume added H(2)O(2) by redox cycling, suggesting that within the complex the oxidative radical burden is shifted to Hp. We provide structural and functional evidence that Hp protects Hb when oxidatively challenged with H(2)O(2) preserving CD163-mediated Hb clearance under oxidative stress conditions. In addition, our data provide in vivo evidence that unbound Hb is oxidatively modified within extravascular compartments consistent with our in vitro findings. (Blood. 2009;113:2578-2586) C1 [Buehler, Paul W.; Abraham, Bindu; Cipollo, John F.; Jia, Yiping; Mikolajczyk, Malgorzata; Alayash, Abdu I.] US FDA, CBER, Washington, DC 20204 USA. [Vallelian, Florence; Linnemayr, Charlotte; Pereira, Claudia P.; Schoedon, Gabriele; Schaer, Dominik J.] Univ Zurich, Div Internal Med, Zurich, Switzerland. [Boretti, Felicitas S.] Univ Zurich, Clin Small Anim Internal Med, Vetsuisse Fac, Zurich, Switzerland. RP Schaer, DJ (reprint author), Univ Zurich Hosp, Med Clin Res Unit, CH-8091 Zurich, Switzerland. EM abdu.alayash@fda.hhs.gov; dominik.schaer@usz.ch FU Swiss National Science Foundation (Bern, Switzerland) [31-120658]; Helmut Horten Foundation (Lugano, Switzerland) FX This study was supported by the Swiss National Science Foundation (Bern, Switzerland, grant 31-120658) and the Helmut Horten Foundation (Lugano, Switzerland; both to D.J.S.). NR 58 TC 98 Z9 99 U1 1 U2 5 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 MAR 12 PY 2009 VL 113 IS 11 BP 2578 EP 2586 DI 10.1182/blood-2008-08-174466 PG 9 WC Hematology SC Hematology GA 417XA UT WOS:000264110600026 PM 19131549 ER PT J AU De Jager, LS Perfetti, GA Diachenko, GW AF De Jager, Lowri S. Perfetti, Gracia A. Diachenko, Gregory W. TI Stir bar sorptive extraction-gas chromatography-mass spectrometry analysis of tetramethylene disulfotetramine in food: Method development and comparison to solid-phase microextraction SO ANALYTICA CHIMICA ACTA LA English DT Article DE Tetramine; Stir bar sorptive extraction; Solid-phase microextraction; Food analysis; Food defense; Tetramethylene disulfotetramine ID TETRAMINE; SAMPLES AB A stir bar sorptive extraction-gas chromatography-mass spectrometry (SBSE-GC-MS) method for the determination of tetramethylene disulfotetramine is presented. The limits of detection (LOD) of the optimized method was 0.2 ng g(-1) for extractions from water and 0.3-2.1 ng g(-1) for extractions from foods. Recovery was highly matrix dependent (36-130%) and quantification required standard addition calibrations. Standard addition calibration lines had high linearity (R(2) > 0.97) and replicate extractions had good reproducibility (R.S.D. = 4.4-9.8%). A comparison of the SBSE method and a previously developed headspace (HS)-solid-phase microextraction (SPME) method was performed. Generally, SBSE provided higher sensitivity with decreased analysis time. Published by Elsevier B.V. C1 [De Jager, Lowri S.; Perfetti, Gracia A.; Diachenko, Gregory W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP De Jager, LS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM lowri.dejager@fda.hhs.gov NR 12 TC 7 Z9 7 U1 0 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0003-2670 J9 ANAL CHIM ACTA JI Anal. Chim. Acta PD MAR 9 PY 2009 VL 635 IS 2 BP 162 EP 166 DI 10.1016/j.aca.2008.12.048 PG 5 WC Chemistry, Analytical SC Chemistry GA 413AE UT WOS:000263764500005 PM 19216873 ER PT J AU Klontz, KC Abraham, A Plakas, SM Dickey, RW AF Klontz, Karl C. Abraham, Ann Plakas, Steven M. Dickey, Robert W. TI Mussel-Associated Azaspiracid Intoxication in the United States SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 [Klontz, Karl C.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Abraham, Ann; Plakas, Steven M.; Dickey, Robert W.] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Klontz, KC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 5 TC 18 Z9 18 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 3 PY 2009 VL 150 IS 5 BP 361 EP 361 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 417CC UT WOS:000264051700016 PM 19258569 ER PT J AU Yetley, EA Brule, D Cheney, MC Davis, CD Esslinger, KA Fischer, PWF Friedl, KE Greene-Finestone, LS Guenther, PM Klurfeld, DM L'Abbe, MR McMurry, KY Starke-Reed, PE Trumbo, PR AF Yetley, Elizabeth A. Brule, Danielle Cheney, Margaret C. Davis, Cindy D. Esslinger, Krista A. Fischer, Peter W. F. Friedl, Karl E. Greene-Finestone, Linda S. Guenther, Patricia M. Klurfeld, David M. L'Abbe, Mary R. McMurry, Kathryn Y. Starke-Reed, Pamela E. Trumbo, Paula R. TI Dietary Reference Intakes for vitamin D: justification for a review of the 1997 values SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID CURRENT DILEMMAS; RESEARCH NEEDS; HEALTH; CANCER AB Recent Institute of Medicine (IOM) reviews of the process for deriving Dietary Reference Intakes (DRIs) suggest that determining the need for a new nutrient review should be evaluated against criteria set a priori. After selecting the criterion of significant new and relevant research, a working group of US and Canadian government scientists used results from a systematic review and 2 conferences on vitamin D and health to evaluate whether significant new and relevant scientific evidence had become available since the 1997 IOM publication of the DRIs for vitamin D. This working group concluded that there appears to be new research meeting the criteria for 4 key DRI questions. The new research is of larger quantity and quality for the elderly than for other groups, but overall 1) adds to the bone-related and status evidence available to the 1997 DRI Committee for several of the life-stage groups, 2) identifies new outcomes with respect to risk of falls and performance measures in the elderly and potential adverse effects, and 3) provides additional information on dose-response relations between intakes and circulating 25-hydroxyvitamin D concentrations and between 25-hydroxyvitamin D concentrations and several health outcomes (ie, bone-related outcomes for all ages and risk of falls and performance measures in older adults). Members of the working group concluded that significant new and relevant research was available for reviewing the existing DRIs for vitamin D while leaving the decision of whether the new research will result in changes to the current DRIs to a future IOM-convened DRI committee. Am J Clin Nutr 2009; 89: 719-27. C1 [Yetley, Elizabeth A.] Off Dietary Supplements, NIH, Bethesda, MD 20892 USA. [Klurfeld, David M.] Agr Res Serv, USDA, Washington, DC USA. [Guenther, Patricia M.] USDA, Ctr Nutr Policy & Promot, Washington, DC 20250 USA. [Friedl, Karl E.] USA, Med Res & Mat Command, Ft Detrick, MD USA. [Fischer, Peter W. F.; L'Abbe, Mary R.] Hlth Canada, Bur Nutr Sci, Food Directorate, Ottawa, ON K1A 0L2, Canada. [Brule, Danielle; Cheney, Margaret C.; Esslinger, Krista A.] Hlth Canada, Off Nutr Policy & Promot, Ottawa, ON K1A 0L2, Canada. [Trumbo, Paula R.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Starke-Reed, Pamela E.] NIH, Div Nutr Res Coordinat, Bethesda, MD 20892 USA. [Davis, Cindy D.] NCI, NIH, Bethesda, MD 20892 USA. [McMurry, Kathryn Y.] US Dept Hlth & Human Serv, Off Dis Prevent & Hlth Promot, Washington, DC USA. [Greene-Finestone, Linda S.] Publ Hlth Agcy Canada, Ottawa, ON, Canada. RP Yetley, EA (reprint author), Off Dietary Supplements, NIH, 6100 Executive Blvd,Room 3B01, Bethesda, MD 20892 USA. EM beth@yetley.com OI Friedl, Karl/0000-0002-3134-8427 NR 20 TC 36 Z9 39 U1 0 U2 1 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAR 1 PY 2009 VL 89 IS 3 BP 719 EP 727 DI 10.3945/ajcn.2008.26903 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 410IS UT WOS:000263571300001 PM 19176741 ER PT J AU Mukhtyar, C Guillevin, L Cid, MC Dasgupta, B de Groot, K Gross, W Hauser, T Hellmich, B Jayne, D Kallenberg, CGM Merkel, PA Raspe, H Salvarani, C Scott, DGI Stegeman, C Watts, R Westman, K Witter, J Yazici, H Luqmani, R AF Mukhtyar, C. Guillevin, L. Cid, M. C. Dasgupta, B. de Groot, K. Gross, W. Hauser, T. Hellmich, B. Jayne, D. Kallenberg, C. G. M. Merkel, P. A. Raspe, H. Salvarani, C. Scott, D. G. I. Stegeman, C. Watts, R. Westman, K. Witter, J. Yazici, H. Luqmani, R. CA European Vasculitis Study Grp TI EULAR recommendations for the management of primary small and medium vessel vasculitis SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Review ID ANTIBODY-ASSOCIATED VASCULITIS; CHURG-STRAUSS-SYNDROME; ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; PNEUMOCYSTIS-CARINII-PNEUMONIA; ANCA-ASSOCIATED VASCULITIS; HEPATITIS-C VIRUS; REFRACTORY WEGENERS-GRANULOMATOSIS; INTERNATIONAL CONSENSUS STATEMENT; MIXED CRYOGLOBULINEMIA RESISTANT; URINARY-BLADDER CANCER AB Objectives: To develop European League Against Rheumatism (EULAR) recommendations for the management of small and medium vessel vasculitis. Methods: An expert group ( consisting of 10 rheumatologists, 3 nephrologists, 2 immunologists, 2 internists representing 8 European countries and the USA, a clinical epidemiologist and a representative from a drug regulatory agency) identified 10 topics for a systematic literature search using a modified Delphi technique. In accordance with standardised EULAR operating procedures, recommendations were derived for the management of small and medium vessel vasculitis. In the absence of evidence, recommendations were formulated on the basis of a consensus opinion. Results: In all, 15 recommendations were made for the management of small and medium vessel vasculitis. The strength of recommendations was restricted by low quality of evidence and by EULAR standardised operating procedures. Conclusions: On the basis of evidence and expert consensus, recommendations have been made for the evaluation, investigation, treatment and monitoring of patients with small and medium vessel vasculitis for use in everyday clinical practice. C1 [Luqmani, R.] Univ Oxford, Nuffield Orthopaed Ctr, Oxford OX3 7LD, England. [Guillevin, L.] Univ Paris 05, Paris, France. [Cid, M. C.] Hosp Clin Barcelona, Barcelona, Spain. [Dasgupta, B.] Southend Univ Hosp NHS Fdn Trust, Westcliff On Sea, England. [de Groot, K.] Klinikum Offenbach, Offenbach, Germany. [Gross, W.; Raspe, H.] Univ Hosp Schleswig Holstein, Lubeck, Germany. [Hauser, T.] Univ Zurich Hosp, CH-8091 Zurich, Switzerland. [Hellmich, B.] Kreiskrankenhaus Plochingen, Plochingen, Germany. [Jayne, D.] Addenbrookes Hosp, Cambridge, England. [Kallenberg, C. G. M.; Stegeman, C.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Merkel, P. A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Salvarani, C.] Arcispedale S Maria Nuova, Reggio Emilia, Italy. [Scott, D. G. I.] Norfolk & Norwich Univ Hosp Trust, Norwich, Norfolk, England. [Watts, R.] Ipswich Hosp NHS Trust, Ipswich, Suffolk, England. [Westman, K.] Malmo Univ Hosp, Malmo, Sweden. [Witter, J.] US FDA, Rockville, MD 20857 USA. [Yazici, H.] Istanbul Univ, Istanbul, Turkey. RP Luqmani, R (reprint author), Univ Oxford, Nuffield Orthopaed Ctr, Windmill Rd, Oxford OX3 7LD, England. EM raashid.luqmani@noc.anglox.nhs.uk RI Raspe, Heiner /E-3612-2010; OI Luqmani, Raashid/0000-0002-4446-5841; Cid Xutgla, Maria Cinta/0000-0002-4730-0938; Salvarani, Carlo/0000-0001-5426-5133 NR 95 TC 398 Z9 427 U1 2 U2 20 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD MAR PY 2009 VL 68 IS 3 BP 310 EP 317 DI 10.1136/ard.2008.088096 PG 8 WC Rheumatology SC Rheumatology GA 406TQ UT WOS:000263318200004 PM 18413444 ER PT J AU Mukhtyar, C Guillevin, L Cid, MC Dasgupta, B de Groot, K Gross, W Hauser, T Hellmich, B Jayne, D Kallenberg, CGM Merkel, PA Raspe, H Salvarani, C Scott, DGI Stegeman, C Watts, R Westman, K Witter, J Yazici, H Luqmani, R AF Mukhtyar, C. Guillevin, L. Cid, M. C. Dasgupta, B. de Groot, K. Gross, W. Hauser, T. Hellmich, B. Jayne, D. Kallenberg, C. G. M. Merkel, P. A. Raspe, H. Salvarani, C. Scott, D. G. I. Stegeman, C. Watts, R. Westman, K. Witter, J. Yazici, H. Luqmani, R. CA European Vasculitis Study Grp TI EULAR recommendations for the management of large vessel vasculitis SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Review ID GIANT-CELL ARTERITIS; PLACEBO-CONTROLLED TRIAL; PRIMARY SYSTEMIC VASCULITIDES; TAKAYASUS-ARTERITIS; TEMPORAL ARTERITIS; POLYMYALGIA-RHEUMATICA; SURGICAL-TREATMENT; DOUBLE-BLIND; DISEASE-ACTIVITY; AORTIC-ANEURYSM AB Objectives: To develop European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis. Methods: An expert group (10 rheumatologists, 3 nephrologists, 2 immunolgists, 2 internists representing 8 European countries and the USA, a clinical epidemiologist and a representative from a drug regulatory agency) identified 10 topics for a systematic literature search through a modified Delphi technique. In accordance with standardised EULAR operating procedures, recommendations were derived for the management of large vessel vasculitis. In the absence of evidence, recommendations were formulated on the basis of a consensus opinion. Results: Seven recommendations were made relating to the assessment, investigation and treatment of patients with large vessel vasculitis. The strength of recommendations was restricted by the low level of evidence and EULAR standardised operating procedures. Conclusions: On the basis of evidence and expert consensus, management recommendations for large vessel vasculitis have been formulated and are commended for use in everyday clinical practice. C1 [Luqmani, R.] Univ Oxford, Nuffield Orthopaed Ctr, Oxford OX3 7LD, England. [Guillevin, L.] Univ Paris 05, Paris, France. [Cid, M. C.] Hosp Clin Barcelona, Barcelona, Spain. [Dasgupta, B.] Southend Univ Hosp NHS Fdn Trust, Westcliff On Sea, England. [de Groot, K.] Klinikum Offenbach, Offenbach, Germany. [Gross, W.; Raspe, H.] Univ Hosp Schleswig Holstein, Lubeck, Germany. [Hauser, T.] Univ Zurich Hosp, CH-8091 Zurich, Switzerland. [Hellmich, B.] Kreiskrankenhaus Plochingen, Plochingen, Germany. [Jayne, D.] Addenbrookes Hosp, Cambridge, England. [Kallenberg, C. G. M.; Stegeman, C.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Merkel, P. A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Salvarani, C.] Arcispedale S Maria Nuova, Reggio Emilia, Italy. [Scott, D. G. I.] Norfolk & Norwich Univ Hosp Trust, Norwich, Norfolk, England. [Watts, R.] Ipswich Hosp NHS Trust, Ipswich, Suffolk, England. [Westman, K.] Malmo Univ Hosp, Malmo, Sweden. [Witter, J.] US FDA, Rockville, MD 20857 USA. [Yazici, H.] Istanbul Univ, Istanbul, Turkey. RP Luqmani, R (reprint author), Univ Oxford, Nuffield Orthopaed Ctr, Windmill Rd, Oxford OX3 7LD, England. EM raashid.luqmani@noc.anglox.nhs.uk RI Raspe, Heiner /E-3612-2010; OI Luqmani, Raashid/0000-0002-4446-5841; Cid Xutgla, Maria Cinta/0000-0002-4730-0938; Salvarani, Carlo/0000-0001-5426-5133 NR 88 TC 180 Z9 195 U1 0 U2 9 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD MAR PY 2009 VL 68 IS 3 BP 318 EP 323 DI 10.1136/ard.2008.088351 PG 6 WC Rheumatology SC Rheumatology GA 406TQ UT WOS:000263318200005 PM 18413441 ER PT J AU Adiguzel, C Bansal, V Litinas, E Cunanan, J Iqbal, O Nelson, K Kannan, M Hoppensteadt, D Fareed, J AF Adiguzel, Cafer Bansal, Vinod Litinas, Evangelos Cunanan, Josephine Iqbal, Omer Nelson, Kelly Kannan, Meganathan Hoppensteadt, Debra Fareed, Jawed TI Increased Prevalence of Antiheparin Platelet Factor 4 Antibodies in Patients May Be Due to Contaminated Heparin SO CLINICAL AND APPLIED THROMBOSIS-HEMOSTASIS LA English DT Article DE contaminated heparin; oversulfated chondroitin sulfate; heparin-induced thrombocytopenia; end-stage renal disease; antiheparin platelet factor 4 antibodies ID INDUCED THROMBOCYTOPENIA; HEMODIALYSIS-PATIENTS; ACCESS THROMBOSIS; ASSOCIATION; FREQUENCY; RISK AB During the period of November 2007 to January 2008, an increased prevalence of adverse reactions to heparin was noted. These adverse events have been attributed to the presence of purposeful contaminant, oversulfated chondroitin sulfate (OSCS) from April 2007 to May 2008. An analysis of dialysis patients' plasma obtained in 2006 and 2007 consistently had a low (5%) prevalence of AHPF4 antibodies. Blood samples from 78 patients on maintenance hemodialysis, who were potentially exposed. to OSCS-contaminated heparin, were analyzed for the presence of all AHPF4 antibodies using a commercially available ELISA kit from GTI. Although there was no change in the platelet Count of these patients, 15 of 78 patients (19.2%) studied had an increased prevalence of AHPF4 antibodies. Subtyping of the all platelet factor 4 (PF4) antibodies documented showed a higher prevalence of immunoglobulin G antibodies as compared to their previously determined antibodies. These observations Suggest that the OSCS contaminant in the recalled heparin triggers in immunogenic response not seen with OSCS-contaminated free heparin. C1 [Adiguzel, Cafer; Litinas, Evangelos; Cunanan, Josephine; Iqbal, Omer; Nelson, Kelly; Hoppensteadt, Debra; Fareed, Jawed] Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. [Bansal, Vinod] Loyola Univ, Med Ctr, Dept Med, Div Nephrol, Maywood, IL 60153 USA. [Hoppensteadt, Debra; Fareed, Jawed] Loyola Univ, Med Ctr, Dept Pharmacol, Maywood, IL 60153 USA. [Kannan, Meganathan] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. RP Fareed, J (reprint author), Loyola Univ, Med Ctr, Dept Pathol, 2160 S 1st Ave, Maywood, IL 60153 USA. EM jfareed@lumc.edu NR 20 TC 11 Z9 12 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1076-0296 J9 CLIN APPL THROMB-HEM JI Clin. Appl. Thromb.-Hemost. PD MAR-APR PY 2009 VL 15 IS 2 BP 145 EP 151 DI 10.1177/1076029609332802 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 429GW UT WOS:000264909900002 PM 19357103 ER PT J AU Xing, D von Konig, CHW Newland, P Riffelmann, M Meade, BD Corbel, M Gaines-Das, R AF Xing, Dorothy von Koenig, Carl Heinz Wirsing Newland, Penny Riffelmann, Marion Meade, Bruce D. Corbel, Michael Gaines-Das, Rose TI Characterization of Reference Materials for Human Antiserum to Pertussis Antigens by an International Collaborative Study SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID BORDETELLA-PERTUSSIS; HOUSEHOLD EXPOSURE; ANTIBODIES; ASSAY; DIAGNOSIS; PROGRAM; SERUM; IMMUNOASSAYS; ADOLESCENTS; INFECTIONS AB Enzyme-linked immunosorbent assay (ELISA) has been widely used to evaluate antibody responses to pertussis vaccination and infection. A common reference serum is essential for the standardization of these assays. However, no internationally recognized reference serum is available. At the request of the Expert Committee on Biological Standardization (ECBS) of the World Health Organization (WHO), a set of four candidate international standards has been prepared. These candidate materials have been assessed for suitability and compared to the widely used U. S. reference pertussis antiserum (human) lot 3, lot 4, and lot 5 by 22 laboratories from 15 countries in an international collaborative study. Laboratories measured immunoglobulin G (IgG) and IgA antibodies to pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae (Fim2&3) using their established immunoassays. The results of this study showed each of the four candidates to be suitable as an international standard. With the agreement of the participants, a recommendation has been made to the ECBS that the candidate material coded 06/140 be established as the First International Standard for pertussis antiserum (human), with the following assigned international units (IU): IgG anti-PT, 335 IU/ampoule; IgA anti-PT, 65 IU/ampoule; IgG anti-FHA, 130 IU/ampoule; IgA anti-FHA, 65 IU/ampoule; IgG anti-PRN, 65 IU/ampoule; and IgA anti-PRN, 42 IU/ampoule. No formal units have been proposed for anti-Fim2& 3 because most assays used a mixture of fimbrial antigens. In addition, the candidate material coded 06/142 has been proposed as a WHO working preparation for characterization of assay systems. C1 [Xing, Dorothy; Newland, Penny; Corbel, Michael; Gaines-Das, Rose] Natl Inst Biol Stand & Controls, Potters Bar EN6 3QG, Herts, England. [von Koenig, Carl Heinz Wirsing; Riffelmann, Marion] Inst Infektiol Krefeld GmbH, D-47805 Krefeld, Germany. [von Koenig, Carl Heinz Wirsing; Riffelmann, Marion] HELIOS Klinikum Krefeld, Inst Hyg & Labormed, D-47805 Krefeld, Germany. [Meade, Bruce D.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Xing, D (reprint author), Natl Inst Biol Stand & Controls, Blanche Lane S Mimms, Potters Bar EN6 3QG, Herts, England. EM dxing@nibsc.ac.uk NR 26 TC 39 Z9 41 U1 0 U2 1 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 MAR PY 2009 VL 16 IS 3 BP 303 EP 311 DI 10.1128/CVI.00372-08 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 414HJ UT WOS:000263854200002 PM 19109448 ER PT J AU Tang, SX Moayeri, M Chen, ZC Harma, H Zhao, JQ Hu, HJ Purcell, RH Leppla, SH Hewlett, IK AF Tang, Shixing Moayeri, Mahtab Chen, Zhaochun Harma, Harri Zhao, Jiangqin Hu, Haijing Purcell, Robert H. Leppla, Stephen H. Hewlett, Indira K. TI Detection of Anthrax Toxin by an Ultrasensitive Immunoassay Using Europium Nanoparticles SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID PROSTATE-SPECIFIC ANTIGEN; IMMUNOGLOBULIN-G ANTIBODIES; LINKED-IMMUNOSORBENT-ASSAY; TIME-RESOLVED FLUORESCENCE; PROTECTIVE ANTIGEN; BACILLUS-ANTHRACIS; MONOCLONAL-ANTIBODIES; LABEL TECHNOLOGY; LETHAL FACTOR; RECEPTOR AB We developed a europium nanoparticle-based immunoassay (ENIA) for the sensitive detection of anthrax protective antigen (PA). The ENIA exhibited a linear dose-dependent pattern within the detection range of 0.01 to 100 ng/ml and was approximately 100-fold more sensitive than enzyme-linked immunosorbent assay (ELISA). False-positive results were not observed with serum samples from healthy adults, mouse plasma without PA, or plasma samples collected from mice injected with anthrax lethal factor or edema factor alone. For the detection of plasma samples spiked with PA, the detection sensitivities for ENIA and ELISA were 100% (11/11 samples) and 36.4% (4/11 samples), respectively. The assay exhibited a linear but qualitative correlation between the PA injected and the PA detected in murine blood (r = 0.97731; P < 0.0001). Anthrax PA was also detected in the circulation of mice infected with spores from a toxigenic Sterne-like strain of Bacillus anthracis, but only in the later stages of infection. These results indicate that the universal labeling technology based on europium nanoparticles and its application may provide a rapid and sensitive testing platform for clinical diagnosis and laboratory research. C1 [Tang, Shixing; Zhao, Jiangqin; Hewlett, Indira K.] US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Moayeri, Mahtab; Hu, Haijing; Leppla, Stephen H.] NIAID, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA. [Chen, Zhaochun; Purcell, Robert H.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Harma, Harri] Univ Turku, Biophys Lab, FIN-20520 Turku, Finland. RP Tang, SX (reprint author), US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bldg 29B,Room 4NN16,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Shixing.tang@fda.hhs.gov; Indira.hewlett@fda.hhs.gov FU Biodefense Advanced Research and Development Agency, DHHS; DIR, NIAID, NIH FX The findings and conclusions in this article have not been formally disseminated by the FDA and should not be construed to represent any agency determination or policy. NR 32 TC 62 Z9 68 U1 1 U2 7 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 MAR PY 2009 VL 16 IS 3 BP 408 EP 413 DI 10.1128/CVI.00412-08 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 414HJ UT WOS:000263854200017 PM 19129473 ER PT J AU Zhang, Y Zhang, L Abraham, S Apparaju, S Wu, TC Strong, JM Xiao, S Atkinson, AJ Thummel, KE Leeder, JS Lee, C Burckart, GJ Lesko, LJ Huang, SM AF Zhang, Y. Zhang, L. Abraham, S. Apparaju, S. Wu, T-C Strong, J. M. Xiao, S. Atkinson, A. J., Jr. Thummel, K. E. Leeder, J. S. Lee, C. Burckart, G. J. Lesko, L. J. Huang, S-M TI Assessment of the Impact of Renal Impairment on Systemic Exposure of New Molecular Entities: Evaluation of Recent New Drug Applications SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article; Proceedings Paper CT 109th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2008 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut ID HEPATIC CYTOCHROME-P450; KIDNEY-DISEASE; FAILURE; METABOLISM; PHARMACOKINETICS; HEMODIALYSIS; DISPOSITION; TRANSPORT AB The US Food and Drug Administration (FDA) is currently developing a guidance for industry to replace a previous guidance, "Pharmacokinetics in Patients With Impaired Renal Function-Study Design, Data Analysis, and Impact on Dosing and Labeling" (renal guidance) issued in may 1998. The impact of the 1998 renal guidance was assessed following a survey of 94 new drug applications (NDAs) for small-molecule new molecular entities (NMEs) approved over the past 5 years (2003-2007). The survey results indicate that 57% of these NDAs included renal impairment study data, that 44% of those with renal data included evaluation in patients on hemodialysis, and that 41% of those with renal data resulted in recommendation of dose adjustment in renal impairment. in addition, the survey results provided evidence that renal impairment can affect the pharmacokinetics of drugs that are predominantly eliminated by nonrenal processes such as metabolism and/or active transport. The latter finding supports our updated recommendation to evaluate pharmacokinetic/pharmacodynamic alterations in renal impairment for those drugs that are mainly eliminated by nonrenal processes, in addition to those that are mainly excreted unchanged by the kidney. C1 [Zhang, Y.; Zhang, L.; Abraham, S.; Apparaju, S.; Wu, T-C; Burckart, G. J.; Lesko, L. J.; Huang, S-M] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Strong, J. M.] US FDA, Lab Clin Pharmacol, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Xiao, S.] US FDA, Div Cardiovasc & Renal Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Atkinson, A. J., Jr.; Thummel, K. E.; Leeder, J. S.; Lee, C.] US FDA, Sabbat 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 25 TC 68 Z9 69 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2009 VL 85 IS 3 BP 305 EP 311 DI 10.1038/clpt.2008.208 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 410VN UT WOS:000263606500019 PM 19020495 ER PT J AU Senior, JR AF Senior, J. R. TI Monitoring for Hepatotoxicity: What Is the Predictive Value of Liver "Function" Tests? SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID DISEASE; SURVEILLANCE; TUBERCULOSIS; TROGLITAZONE; INJURY; SERUM AB Drug-induced liver injury (DILI) is a major reason drugs fail during development or are withdrawn from the market.(1) The ability to predict, detect, and avoid DILI through appropriate patient selection and effective monitoring has proved to be an elusive goal. Many approved drugs have labeling recommendations for serum enzyme monitoring intended to detect and prevent hepatotoxicity, but such monitoring is often seen as inconvenient, uncomfortable, costly, and inefficient by both patients and doctors, and thus monitoring recommendations are poorly followed, if at all. This review considers whether monitoring works to prevent DILI, whether monitoring recommendations are derived from data or opinions, and whether any better alternatives exist. C1 US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Senior, JR (reprint author), US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM john.senior@fda.hhs.gov NR 30 TC 51 Z9 57 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 MAR PY 2009 VL 85 IS 3 BP 331 EP 334 DI 10.1038/clpt.2008.262 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 410VN UT WOS:000263606500023 PM 19129750 ER PT J AU Seligman, PJ Osborne, SF AF Seligman, P. J. Osborne, S. F. TI Perspectives on Early Communication of Drug Risks to the Public SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID SAFETY INFORMATION; CHALLENGE AB The way in which important, emerging information about the safety of marketed drugs is communicated to the public and health-care professionals has changed remarkably over the past 5 years. In an environment of instant and global electronic communication, and in response to the challenge of meeting the public's expectations of transparency and accountability, the US Food and Drug Administration (FDA) has implemented new communication tools, including early communications about ongoing safety reviews, and new policies that describe what and when we communicate. In 2009, the FDA will complete a major overhaul of its website, one of its principal vehicles for communication. C1 [Seligman, P. J.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Osborne, S. F.] US FDA, Drug Safety Oversight Board, Silver Spring, MD USA. RP Seligman, PJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM paul.seligman@fda.hhs.gov NR 8 TC 3 Z9 3 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 MAR PY 2009 VL 85 IS 3 BP 335 EP 339 DI 10.1038/clpt.2008.272 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 410VN UT WOS:000263606500024 PM 19158665 ER PT J AU Gomez, MC Pope, CE Kutner, RH Ricks, DM Lyons, LA Ruhe, MT Dumas, C Lyons, J Dresser, BL Reiser, J AF Gomez, Martha C. Pope, Charles Earle Kutner, Robert H. Ricks, David M. Lyons, Leslie A. Ruhe, Mark T. Dumas, Cherie Lyons, Justine Dresser, Betsy L. Reiser, Jakob TI Generation of Domestic Transgenic Cloned Kittens Using Lentivirus Vectors SO CLONING AND STEM CELLS LA English DT Article ID MESENCHYMAL STEM-CELLS; IN-VITRO DEVELOPMENT; NUCLEAR TRANSFER; GENE-TRANSFER; CAT OOCYTES; MOUSE EMBRYOS; PREIMPLANTATION EMBRYOS; NONDIVIDING CELLS; BOVINE EMBRYOS; SOMATIC-CELLS AB The efficient use of somatic cell nuclear transfer ( SCNT), in conjunction with genetic modification of donor cells provides a general means to add or inactivate genes in mammals. This strategy has substantially improved the efficacy of producing genetically identical animals carrying mutant genes corresponding to specific human disorders. Lentiviral (LV) vectors have been shown to be well suited for introducing transgenes into cells to be used as donor nuclei for SCNT. In the present study, we established an LV vector-based transgene delivery approach for producing live transgenic domestic cats by SCNT. We have demonstrated that cat fetal fibroblasts can be transduced with EGFP-encoding LV vectors bearing various promoters including the human cytomegalovirus immediate early (hCMV-IE) promoter, the human translation elongation factor 1 alpha (hEF-1 alpha) promoter and the human ubiquitin C (hUbC) promoter. Among the promoters tested, embryos reconstructed with donor cells transduced with a LV-vector bearing the hUbC promoter displayed sustained transgene expression at the blastocyst stage while embryos reconstructed with LV vector-transduced cells containing hCMV-IE-EGFP or hEF-1 alpha-EGFP cassettes did not. After transfer of 291 transgenic cloned embryos into the oviducts of eight recipient domestic cats (mean = 36.5 +/- 10.1), three (37.5%) were diagnosed to be pregnant, and a total of six embryos (2.1%) implanted. One live male offspring was delivered by Cesarean section on day 64 of gestation, and two kittens were born dead after premature delivery on day 55. In summary, we report the birth of transgenic cloned kittens produced by LV vector-mediated transduction of donor cells and confirm that cloned kittens express the EGFP reporter transgene in all body tissues. C1 [Gomez, Martha C.; Pope, Charles Earle; Ricks, David M.; Dumas, Cherie; Lyons, Justine; Dresser, Betsy L.] Audubon Ctr Res Endangered Species, New Orleans, LA 70131 USA. [Kutner, Robert H.; Ricks, David M.; Reiser, Jakob] Louisiana State Univ, Hlth Sci Ctr, Gene Therapy Program, Dept Med, New Orleans, LA USA. [Lyons, Leslie A.; Ruhe, Mark T.] Univ Calif Davis, Sch Vet Med, Davis, CA 95616 USA. [Dresser, Betsy L.] Univ New Orleans, Dept Biol Sci, New Orleans, LA 70148 USA. [Reiser, Jakob] US FDA, CBER, Div Cellular & Gene Therapies, Bethesda, MD 20014 USA. RP Gomez, MC (reprint author), Audubon Ctr Res Endangered Species, 14001 River Rd, New Orleans, LA 70131 USA. EM mgomez@auduboninstitute.org RI Ricks, David/A-8139-2010 FU NCRR NIH HHS [R24 RR016094] NR 67 TC 12 Z9 12 U1 2 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1536-2302 J9 CLONING STEM CELLS JI Cloning Stem Cells PD MAR PY 2009 VL 11 IS 1 BP 167 EP 175 DI 10.1089/clo.2008.0054 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Genetics & Heredity SC Cell Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 419CP UT WOS:000264197000016 PM 19203232 ER PT J AU Hinton, DE Hardman, RC Kullman, SW Law, JM Schmale, MC Walter, RB Winn, RN Yoder, JA AF Hinton, David E. Hardman, Ron C. Kullman, Seth W. Law, Jerry M. (Mac) Schmale, Michael C. Walter, Ronald B. Winn, Richard N. Yoder, Jeffrey A. TI Aquatic animal models of human disease: Selected papers and recommendations from the 4th Conference SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY LA English DT Editorial Material ID MEDAKA ORYZIAS-LATIPES; ZEBRAFISH DANIO-RERIO; BASS MORONE-SAXATILIS; RESEARCH FACILITIES; FISH MODELS; FUNDULUS-HETEROCLITUS; CONTAMINANT-EXPOSURE; VERTEBRATE ORIGINS; HEPATIC NEOPLASMS; TRANSGENIC MEDAKA C1 [Hinton, David E.] Duke Univ, Div Environm Sci & Policy, Nicholas Sch Environm, Durham, NC 27708 USA. [Hardman, Ron C.] US FDA, College Pk, MD 20740 USA. [Kullman, Seth W.] N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. [Yoder, Jeffrey A.] N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, Raleigh, NC 27606 USA. [Schmale, Michael C.] Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Div Marine Biol & Fisheries, Miami, FL 33149 USA. [Walter, Ronald B.] Texas State Univ, Mol Biosci Res Grp, Dept Chem & Biochem, San Marcos, TX 78666 USA. [Winn, Richard N.] Univ Georgia, ABEL, Warnell Sch Forestry & Nat Resources, Athens, GA 30602 USA. RP Hinton, DE (reprint author), Duke Univ, Div Environm Sci & Policy, Nicholas Sch Environm, Box 90328,A333B LSRC, Durham, NC 27708 USA. EM dhinton@duke.edu; ron.hardman@duke.edu; sethwkullma@ncsu.edu; mac_law@ncsu.edu; mschmale@rsmas.miami.edu; rwalter@txstate.edu; rwinn@uga.edu; jef_yoder@ncsu.edu OI Yoder, Jeffrey/0000-0002-6083-1311 FU NCRR NIH HHS [R13 RR024332, R13 RR024332-01] NR 91 TC 6 Z9 6 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1532-0456 J9 COMP BIOCHEM PHYS C JI Comp. Biochem. Physiol. C-Toxicol. Pharmacol. PD MAR PY 2009 VL 149 IS 2 SI SI BP 121 EP 128 DI 10.1016/j.cbpc.2008.12.006 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Toxicology; Zoology SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Toxicology; Zoology GA 419NG UT WOS:000264225700001 PM 19150511 ER PT J AU Kisby, GE Olivas, A Park, T Churchwell, M Doerge, D Samson, LD Gerson, SL Turker, MS AF Kisby, G. E. Olivas, A. Park, T. Churchwell, M. Doerge, D. Samson, L. D. Gerson, S. L. Turker, M. S. TI DNA repair modulates the vulnerability of the developing brain to alkylating agents SO DNA REPAIR LA English DT Article DE Methylazoxymethanol (MAM); Nitrogen mustard (HN2); Granule cell; Cerebellum; O(6)-Methylguanine methyltransferase (Mgmt); Alkyladenine DNA glycosylase (Aag) ID BASE-EXCISION-REPAIR; ENVIRONMENTAL TOBACCO-SMOKE; HAMSTER OVARY CELLS; CROSS-LINK REPAIR; NUCLEOTIDE-EXCISION; NITROGEN MUSTARDS; OXIDATIVE DAMAGE; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; CHEMOTHERAPEUTIC-AGENTS AB Neurons of the developing brain are especially vulnerable to environmental agents that damage DNA (i.e., genotoxicants), but the mechanism is poorly understood. The focus of the present study is to demonstrate that DNA damage plays a key role in disrupting neurodevelopment. To examine this hypothesis, we compared the cytotoxic and DNA damaging properties of the methylating agents methylazoxymethanol (MAM) and dimethyl sulfate (DMS) and the mono- and bifunctional alkylating agents chloroethylamine (CEA) and nitrogen mustard (HN2), in granule cell neurons derived from the cerebellum of neonatal wild type mice and three transgenic DNA repair strains. Wild type cerebellar neurons were significantly more sensitive to the alkylating agents DMS and HN2 than neuronal cultures treated with MAM or the half-mustard CEA. Parallel studies with neuronal cultures from mice deficient in alkylguanine DNA glycosylase (Aag(-/-)) or O(6)-methylguanine methyltransferase (Mgmt(-/-)), revealed significant differences in the sensitivity of neurons to all four genotoxicants. Mgmt(-/-) neurons were more sensitive to MAM and HN2 than the other genotoxicants and wild type neurons treated with either alkylating agent. In contrast, Aag(-/-) neurons were for the most part significantly less sensitive than wild type or Mgmt(-/-) neurons to MAM and HN2.Aag(-/-) neurons were also significantly less sensitive than wild type neurons treated with either DMS or CEA. Granule cell development and motor function were also more severely disturbed by MAM and HN2 in Mgmt(-/-) mice than in comparably treated wild type mice. In contrast, cerebellar development and motor function were well preserved in MAM-treated Aag(-/-) or MGMT-overexpressing (Mgmt(Tg+)) mice, even as compared with wild type mice suggesting that AAG protein increases MAM toxicity, whereas MGMT protein decreases toxicity. Surprisingly, neuronal development and motor function were severely disturbed in Mgmt(Tg+) mice treated with HN2. Collectively, these in vitro and in vivo studies demonstrate that the type of DNA lesion and the efficiency of DNA repair are two important factors that determine the vulnerability of the developing brain to long-term injury by a genotoxicant. (C) 2008 Elsevier B.V. All rights reserved. C1 [Kisby, G. E.; Olivas, A.; Park, T.; Turker, M. S.] Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97239 USA. [Churchwell, M.; Doerge, D.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Samson, L. D.] MIT, Ctr Environm Hlth Sci, Biol Engn Div, Cambridge, MA 02139 USA. [Gerson, S. L.] Case Western Reserve Univ, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. RP Kisby, GE (reprint author), Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97239 USA. EM kisby@ohsu.edu FU U.S. Army [DAMD 17-98-1-8625]; NIH [CA075576RO1, C63193, P30 CA043703] FX We thank Mr. Dan Austin for technical assistance. This work was supported by a grant from the U.S. Army Medical Research Materiel Command under Contract/Grant/Intergovernmental Project Order DAMD 17-98-1-8625 (GEK) and by NIH grants CA075576 (LDS), RO1 C63193 and P30 CA043703 (SLG). NR 63 TC 27 Z9 29 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD MAR 1 PY 2009 VL 8 IS 3 BP 400 EP 412 DI 10.1016/j.dnarep.2008.12.002 PG 13 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 415LC UT WOS:000263934300013 PM 19162564 ER PT J AU Lawrence, J Li, XB AF Lawrence, John Li, Xiaobai TI A Multiple Comparisons Procedure for Comparing All Arms in Three-Arm Clinical Trials SO DRUG INFORMATION JOURNAL LA English DT Article DE Multiple comparisons; Strong familywise error rate; Combination drugs; Active control; Noninferiority ID PLACEBO-CONTROLLED TRIALS; ACTIVE-CONTROL TRIALS; BONFERRONI PROCEDURE; ISSUES; TESTS AB In three-arm studies, there are often multiple hypotheses to be tested among the arms. In this article, we describe a multiple comparisons procedure that controls the familywise error rate in the strong sense. The procedure is appropriate when one of the arms is a control, and both treatment arms will be compared to the control as well as to each other. The procedure is shown to be consistent and the asymptotic relative efficiency (compared to the uniformly most powerful test for the individual comparisons) is close to 1 in many scenarios. Furthermore, the special case where the arms are placebo, active control, and test drug with one goal of showing noninferiority is examined. C1 [Lawrence, John] US FDA, Silver Spring, MD 20993 USA. [Li, Xiaobai] Ohio State Univ, Ctr Biostat, Columbus, OH 43210 USA. RP Lawrence, J (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD MAR PY 2009 VL 43 IS 2 BP 177 EP 184 PG 8 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 413UX UT WOS:000263819100009 ER PT J AU Samuels-Reid, J Cope, JU Morrison, AE AF Samuels-Reid, Joy Cope, Judith U. Morrison, Audrey E. TI Device safety and effectiveness in the pediatric population: a US FDA perspective SO EXPERT REVIEW OF MEDICAL DEVICES LA English DT Article DE children; device classification; diagnostic test; human factor; implanted device; medical device; pediatric; safety; US FDA AB The US FDA recognizes that there are many challenges to ensuring that medical devices are used responsibly and safely in the pediatric population. Education plays a key role, and manufacturers and healthcare providers must be informed of medical device issues unique to the pediatric population. Healthcare workers and device manufacturers must recognize that adverse events may differ between the adult and pediatric population and among pediatric subpopulations. Risk mitigation may also differ, and heightened awareness will reduce the potential for adverse events and promote the safe use of medical devices in children. C1 [Samuels-Reid, Joy] US FDA, CDER, Div Anesthesiol, Gen Hosp,ODE, Rockville, MD 20857 USA. [Cope, Judith U.] US FDA, Off Commissioner, Rockville, MD 20857 USA. [Cope, Judith U.] US FDA, Off Pediat Therapeut, Rockville, MD 20857 USA. [Morrison, Audrey E.] US FDA, Div Postmarket Surveillance, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Samuels-Reid, J (reprint author), US FDA, CDER, Div Anesthesiol, Gen Hosp,ODE, 9200 Corp Blvd, Rockville, MD 20857 USA. EM joy.samuels-reid@fda.hhs.gov; judith.cope@fda.hhs.gov; audrey.morrison@fda.hhs.gov NR 4 TC 3 Z9 3 U1 0 U2 3 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1743-4440 J9 EXPERT REV MED DEVIC JI Expert Rev. Med. Devices PD MAR PY 2009 VL 6 IS 2 BP 131 EP 135 DI 10.1586/17434440.6.2.131 PG 5 WC Engineering, Biomedical SC Engineering GA 429RM UT WOS:000264937800011 PM 19298160 ER PT J AU Lynne, AM Kaldhone, P David, D White, DG Foley, SL AF Lynne, Aaron M. Kaldhone, Pravin David, Donna White, David G. Foley, Steven L. TI Characterization of Antimicrobial Resistance in Salmonella enterica Serotype Heidelberg Isolated from Food Animals SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID ANTIBIOTIC-RESISTANCE; MULTIDRUG-RESISTANT; SEROVAR TYPHIMURIUM; BETA-LACTAMASES; GENES; INFECTIONS AB Fifty-eight Salmonella enterica serovar Heidelberg isolates isolated from food animals were tested for antimicrobial susceptibilities and further characterized for select antimicrobial resistance genes, plasmid carriage, class 1 integrons, and genetic relatedness using pulsed-field gel electrophoresis (PFGE). Seventy-two percent of isolates displayed resistance to at least one of the antimicrobial agents tested, while 24% exhibited resistance to eight or more antimicrobial agents. Resistance was most commonly observed to tetracycline (71%), streptomycin (62%), and kanamycin (52%). Isolates obtained from cattle and swine displayed the highest rates of resistance while isolates from chickens more often displayed susceptibility to the tested antimicrobials. When resistance was detected, a corresponding resistance gene was detected in 97.3% of the isolates. Thirteen percent of the isolates contained class I integrons containing at least one resistance gene, most often either the aadA or dhfrA genes, which are often associated with resistance to streptomycin and trimethoprim, respectively. Twenty isolates contained plasmids estimated to be at least 75 kb in size, 17 of which exhibited resistance to five or more antimicrobial agents. Thirty PFGE patterns were generated among the 58 isolates tested using XbaI, indicating extensive heterogeneity among this serotype across different animal origins. Results confirm the presence of multidrug-resistance (MDR) phenotypes among food animal isolates of serovar Heidelberg, especially those obtained from mammalian species. The observed MDR was typically associated with the presence of large plasmids. C1 [Lynne, Aaron M.; Kaldhone, Pravin; David, Donna; Foley, Steven L.] Marshfield Clin Res Fdn, Natl Farm Med Ctr, Marshfield, WI 54449 USA. [Kaldhone, Pravin] Univ Cent Arkansas, Dept Biol, Conway, AR USA. [White, David G.] US FDA, Div Anim & Food Microbiol, Ctr Vet Med, Laurel, MD USA. RP Foley, SL (reprint author), Marshfield Clin Res Fdn, Natl Farm Med Ctr, 1000 N Oak Ave, Marshfield, WI 54449 USA. EM foley.steven@mcrf.mfldclin.edu FU Marshfield Clinic Research Foundation FX We appreciate the financial support for this project provided by the Marshfield Clinic Research Foundation. The use of trade names is for identification purposes only, and does not imply endorsement by the U.S. Food and Drug Administration or the U.S. Department of Health and Human Services. Views presented in this manuscript do not necessarily reflect those of the U.S. Food and Drug Administration. NR 34 TC 26 Z9 26 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1535-3141 J9 FOODBORNE PATHOG DIS JI Foodborne Pathog. Dis. PD MAR PY 2009 VL 6 IS 2 BP 207 EP 215 DI 10.1089/fpd.2008.0172 PG 9 WC Food Science & Technology SC Food Science & Technology GA 413UO UT WOS:000263818200008 PM 19099358 ER PT J AU Park, S Badano, A Gallas, BD Myers, KJ AF Park, Subok Badano, Aldo Gallas, Brandon D. Myers, Kyle J. TI Incorporating Human Contrast Sensitivity in Model Observers for Detection Tasks SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Anthropomorphic observer; channelized-Hotelling observer; human contrast sensitivity; lumpy backgrounds; signal detection ID HOTELLING OBSERVER; VISUAL-SYSTEM; PERFORMANCE; NOISE; SIGNAL; DISPLAYS; DISCRIMINATION; DETECTABILITY; BACKGROUNDS; COMPUTATION AB Contrast sensitivity of the human visual system is a characteristic that can adversely affect human performance in detection tasks. In this paper, we propose a method for incorporating human contrast sensitivity in anthropomorphic model observers. In our method, we model human contrast sensitivity using the Barten model with the mean luminance of a region of interest centered at the signal location. In addition, one free parameter is varied to control the effect of the contrast sensitivity on the model observer's performance. We investigate our model of human contrast sensitivity in a channelized-Hotelling observer (CHO) with difference-of-Gaussian channels. We call the CHO incorporating the contrast sensitivity a contrast-sensitive CHO (CS-CHO). The human data from a psychophysical study by Park et al. [1] are used for comparing the performance of the CS-CHO to human performance. That study used Gaussian signals with six different signal intensities in non-Gaussian lumpy backgrounds. A value of the free parameter is chosen to match the performance of the CS-CHO to the mean human performance only at the strongest signal. Results show that the CS-CHO with the chosen value of the free parameter predicts the mean human performance at the five lower signal intensities. Our results show that the CS-CHO predicts human performance well as a function of signal intensity. C1 [Park, Subok; Badano, Aldo; Gallas, Brandon D.; Myers, Kyle J.] US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Div Imaging & Appl Math, Ctr Devices & Radiol Hlth, White Oak, MD 20993 USA. RP Park, S (reprint author), US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Div Imaging & Appl Math, Ctr Devices & Radiol Hlth, White Oak, MD 20993 USA. EM subok.park@fda.hhs.gov RI Bouwman, Ramona/B-7215-2013; OI Gallas, Brandon/0000-0001-7332-1620; badano, aldo/0000-0003-3712-6670 FU National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health FX This work was supported in part by the National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health. NR 30 TC 19 Z9 19 U1 1 U2 7 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD MAR PY 2009 VL 28 IS 3 BP 339 EP 347 DI 10.1109/TMI.2008.929096 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 415FU UT WOS:000263920500003 PM 19244006 ER PT J AU Flynn, TJ Garcia, MC AF Flynn, T. J. Garcia, M. C. TI Limited Success in the Long-term Culture and Maintenance of Function of Non-plateable Lots of Cryopreserved Primary Human Hepatocytes on a 2-dimensional Surface. SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Meeting Abstract C1 [Flynn, T. J.; Garcia, M. C.] US FDA, Div Toxicol, Labs MOD 1, Laurel, MD 20708 USA. EM thomas.flynn@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD SPR PY 2009 VL 45 BP S51 EP S51 PG 1 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 481ZS UT WOS:000268853400132 ER PT J AU Jones, J AF Jones, J. TI Animal Clones and their Progeny, FDA's GE Animal Guidance, and Other Recent Actions SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Meeting Abstract C1 [Jones, J.] US FDA, Off New Anim Drug Evaluat, Ctr Vet Med, Rockville, MD 20857 USA. EM jeffery.jones@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD SPR PY 2009 VL 45 BP S5 EP S5 PG 1 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 481ZS UT WOS:000268853400014 ER PT J AU Anderson, DL AF Anderson, David L. TI Determination of Bromine in Regulated Foods with a Field-Portable X-Ray Fluorescence Analyzer SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PRODUCTS AB A field-portable X-ray fluorescence analyzer, factory-calibrated for soil analysis, was used to measure bromine (Br) mass fractions in reference materials, flour, bakery products, malted barley, selected U.S. Food and Drug Administration Total Diet Study foods, and other food products. By using a calibration based on instrumental neutron activation analysis results for Br in reference materials, accurate quantitative results, confirmed by z-scores, could be obtained for mass fractions of about 2-55 mg/kg. These results confirmed accuracy of results (with larger uncertainties) obtained by applying a simple correction factor to the analyzer's output value. Results showed that very short analysis times (<2 min) would be needed to screen foods for Br content at regulatory levels for brominated and enriched brominated flour (24 mg/kg Br) and whole wheat flour and bakery products (36 mg/kg Br). Feasibility for determination of Br in malted barley at the regulatory level (75 mg/kg Br) was demonstrated, but quantitative results at that level could not be assured because no reference material with a suitable mass fraction was available. Br mass fractions for all foods tested were well below regulatory levels. 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 6 Z9 6 U1 0 U2 5 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2009 VL 92 IS 2 BP 502 EP 510 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 434YB UT WOS:000265309100019 PM 19485210 ER PT J AU Schenck, F Wong, J Lu, CS Li, J Holcomb, JR Mitchell, LM AF Schenck, Frank Wong, Jon Lu, Chenseng Li, Jing Holcomb, Jim R. Mitchell, Latonya M. TI Multiresidue Analysis of 102 Organophosphorus Pesticides in Produce at Parts-per-Billion Levels Using a Modified QuEChERS Method and Gas Chromatography with Pulsed Flame Photometric Detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID SOLID-PHASE EXTRACTION; RESIDUE ANALYSIS; EXPOSURE; CHILDREN; SPECTROMETRY; VEGETABLES; CLEANUP; FRUITS; FOODS AB A multiresidue method for the analysis of organophosphorus pesticides in fresh produce at levels down to 1.0 mu g/kg (ppb) has been developed using a modification of the QuEChERS (quick, easy, cheap, effective, rugged, and safe) procedure. The procedure entails extraction of pesticides from the sample with acetonitrile, salting-out with magnesium sulfate (MgSO4) and sodium chloride, and cleanup of the resulting extracts with dispersive solid-phase extraction using primary-secondary amine, graphitized carbon black, and MgSO4. Fortification studies were performed for 102 organophosphorus pesticides at 1.0, 10, and 100 ppb in 4 different pesticide-free commodities (grape, orange, spinach, and tomato). Recoveries ranged from 63-125%, with >80% being achieved for most of the pesticides tested in each commodity. The procedure was applied to the analysis of 400 produce samples collected from a cohort of children that participated in the Children's Pesticide Exposure Study and the Longitudinal Dietary Pesticide Exposure Study in which selected 24 h duplicate food items were collected throughout a 12-month period. Residues of 15 of the 102 pesticides were detected at levels ranging from <1 to 526 ppb. C1 [Schenck, Frank; Holcomb, Jim R.; Mitchell, Latonya M.] US FDA, Off Regulatory Affairs, Atlanta, GA 30309 USA. [Wong, Jon] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Lu, Chenseng; Li, Jing] Harvard Univ, Harvard Sch Publ Hlth, Landmark Ctr W, Boston, MA 02215 USA. RP Schenck, F (reprint author), US FDA, Off Regulatory Affairs, 60 8th St NE, Atlanta, GA 30309 USA. EM fschenck@live.com NR 23 TC 17 Z9 17 U1 0 U2 4 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2009 VL 92 IS 2 BP 561 EP 573 PG 13 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 434YB UT WOS:000265309100026 PM 19485217 ER PT J AU Smith, KF Bibb, LA Schmitt, MP Oram, DM AF Smith, Kelsy F. Bibb, Lori A. Schmitt, Michael P. Oram, Diana M. TI Regulation and Activity of a Zinc Uptake Regulator, Zur, in Corynebacterium diphtheriae SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; MYCOBACTERIUM-TUBERCULOSIS; BACILLUS-SUBTILIS; TRANSCRIPTIONAL REGULATORS; METALLOREGULATORY PROTEIN; TOXIN PRODUCTION; UPTAKE SYSTEM; BACTERIAL; IRON; REPRESSOR AB Regulation of metal ion homeostasis is essential to bacterial cell survival, and in most species it is controlled by metal-dependent transcriptional regulators. In this study, we describe a Corynebacterium diphtheriae ferric uptake regulator-family protein, Zur, that controls expression of genes involved in zinc uptake. By measuring promoter activities and mRNA levels, we demonstrate that Zur represses transcription of three genes (zrg, cmrA, and troA) in zinc-replete conditions. All three of these genes have similarity to genes involved in zinc uptake. Transcription of zrg and cmrA was also shown to be regulated in response to iron and manganese, respectively, by mechanisms that are independent of Zur. We demonstrate that the activity of the zur promoter is slightly decreased under low zinc conditions in a process that is dependent on Zur itself. This regulation of zur transcription is distinctive and has not yet been described for any other zur. An adjacent gene, predicted to encode a metal-dependent transcriptional regulator in the ArsR/SmtB family, is transcribed from a separate promoter whose activity is unaffected by Zur. A C. diphtheriae zur mutant was more sensitive to peroxide stress, which suggests that zur has a role in protecting the bacterium from oxidative damage. Our studies provide the first evidence of a zinc specific transcriptional regulator in C. diphtheriae and give new insights into the intricate regulatory network responsible for regulating metal ion concentrations in this toxigenic human pathogen. C1 [Oram, Diana M.] Univ Maryland, Sch Dent, Dept Microbial Pathogenesis, Baltimore, MD 21201 USA. [Bibb, Lori A.; Schmitt, Michael P.] FDA CBER, Bethesda, MD 20892 USA. RP Oram, DM (reprint author), Univ Maryland, Sch Dent, Dept Microbial Pathogenesis, 650 W Baltimore St 7 S, Baltimore, MD 21201 USA. EM doram@umaryland.edu FU NIH/NIAID [K22 AI60882] FX We thank Mark Strauch, Mark Oram, and Kelley Hovis for their careful reading and helpful comments of the manuscript and Dean Dessem for assistance with statistical analysis.; This study was supported by research grant NIH/NIAID K22 AI60882 to D.M.O. NR 44 TC 18 Z9 18 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAR PY 2009 VL 191 IS 5 BP 1595 EP 1603 DI 10.1128/JB.01392-08 PG 9 WC Microbiology SC Microbiology GA 409KC UT WOS:000263503600026 PM 19074382 ER PT J AU Zhao, P Ragueneau-Majlessi, I Zhang, L Strong, JM Reynolds, KS Levy, RH Thummel, KE Huang, SM AF Zhao, Ping Ragueneau-Majlessi, Isabelle Zhang, Lei Strong, John M. Reynolds, Kellie S. Levy, Rene H. Thummel, Kenneth E. Huang, Shiew-Mei TI Quantitative Evaluation of Pharmacokinetic Inhibition of CYP3A Substrates by Ketoconazole: A Simulation Study SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE Ketoconazole; pharmacokinetics; CYP3A; inhibition; drug interaction; dosing regimen; bioavailability; half-life; FDA guidance ID IN-VIVO; HEPATIC-INJURY; ALPRAZOLAM; CLEARANCE; MIDAZOLAM; TRIAZOLAM; CACO-2 AB The US Food and Drug Administration draft drug interaction guidance recommends that 400 mg ketoconazole (KTZ) be administered once daily for several days (QD400) for maximal CYP3A inhibition. Some investigators suggest that a single dose of 400 mg (SD400) KTZ is sufficient given its short half-life (t(1/2) similar to 3-5 hr). To determine the impact of KTZ regimens on CYP3A inhibition, we simulated AUC fold-change (AUCR) in the presence of SD400, QD400, or 200 mg twice-daily (BID200) KTZ for theoretical CYP3A substrates. Ratios of AUCR (AUCR(QD400)/AUCR(SD400) and AUCR(BID200) AUCR(QD400)) increase with increasing bioavailability and increasing substrate t(1/2). The SD400 KTZ regimen may provide maximal inhibition only for a subset of substrates (ie, low bioavailability and short t(1/2)). For substrates with t(1/2) longer than that of KTZ, multiple KTZ dosing is critical and BID200 appears to provide greater inhibition than QD400. Also, timing of KTZ administration should be optimized to allow maximal presystemic enzyme inhibition prior to substrate administration. C1 [Zhao, Ping; Zhang, Lei; Reynolds, Kellie S.; Huang, Shiew-Mei] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Ragueneau-Majlessi, Isabelle; Levy, Rene H.; Thummel, Kenneth E.] Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA. [Strong, John M.] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Huang, SM (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Room 3188,Bldg 51,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM shiewmei.huang@fda.hhs.gov NR 19 TC 53 Z9 53 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD MAR PY 2009 VL 49 IS 3 BP 351 EP 359 DI 10.1177/0091270008331196 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 412AM UT WOS:000263695600009 PM 19246732 ER PT J AU Huang, SM Lesko, LJ AF Huang, Shiew-Mei Lesko, Lawrence J. TI The Need for Multiple Doses of 400 mg Ketoconazole as a Precipitant Inhibitor of a CYP3A Substrate in an In Vivo Drug-Drug Interaction Study Response SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Letter C1 [Huang, Shiew-Mei; Lesko, Lawrence J.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Huang, SM (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 6 TC 6 Z9 6 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD MAR PY 2009 VL 49 IS 3 BP 370 EP 370 DI 10.1177/0091270008330989 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 412AM UT WOS:000263695600012 ER PT J AU McEgan, R Fu, TJ Warriner, K AF McEgan, R. Fu, T. J. Warriner, K. TI Concentration and Detection of Salmonella in Mung Bean Sprout Spent Irrigation Water by Use of Tangential Flow Filtration Coupled with an Amperometric Flowthrough Enzyme-Linked Immunosorbent Assay SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ESCHERICHIA-COLI O157-H7; ALFALFA SPROUTS; GROWTH; IMMUNOSENSORS; MEMBRANES; ENTERICA; SEEDS; INTERNALIZATION; PURIFICATION; POLYSULFONE AB The development of a culture-free method for Salmonella screening of spent irrigation water derived from sprouting mung bean beds is described. The system used tangential flow filtration (TFF) to nonspecifically concentrate cells from large (2- to 10-liter) sample volumes. The retentate (100 ml) from the TFF was then flowed over an anti-Salmonella antibody-modified cellulose acetate membrane. The captured Salmonella was detected by reacting with a secondary anti-Salmonella and goat anti-rabbit biotin labeled antibody, followed by avidin-tagged glucose oxidase. The hydrogen peroxide generated from the enzymic oxidation of glucose was amperometrically detected at an underlying platinum electrode. It was found that 10 liters of Salmonella suspensions of 2 log CFU/ml could be concentrated to 4 log CFU/ml with 60% recovery regardless of the flow rate ( 112 to 511 ml/min) or transmembrane pressure (0 to 20 lb/in(2)) applied. The solids content of spent irrigation water negatively affected the filtration rate of TFF. This was most evident in spent irrigation water collected in the initial 24 h of the Sprouting period, where the Solids content was high (4,170 mg/liter) compared with samples collected at 96 h (560 mg/liter). Trials were performed using mung bean beds inoculated with different Salmonella levels (1.3 to 3.3 log CFU/g). By using the optimized TFF and flowthrough immunoassay it was possible to detect Salmonella in spent irrigation water at levels of 2.43 log CFU/ml within 4 h. The integrated concentration and detection system will provide a useful tool for sprout producers to perform in-house pathogen screening of spent irrigation water. C1 [McEgan, R.; Warriner, K.] Univ Guelph, Dept Food Sci, Guelph, ON N1G 2W1, Canada. [Fu, T. J.] US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Warriner, K (reprint author), Univ Guelph, Dept Food Sci, Guelph, ON N1G 2W1, Canada. EM kwarrine@uoguelph.ca FU Ontario Ministry of Agriculture and Food (OMAFRA) Food Safety Research and Innovation Program [FS050633] FX The authors thank the commercial sprout grower for donating mung beans used in the study and Ontario Ministry of Agriculture and Food (OMAFRA) Food Safety Research and Innovation Program (project FS050633) for their financial support. NR 46 TC 13 Z9 13 U1 0 U2 12 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD MAR PY 2009 VL 72 IS 3 BP 591 EP 600 PG 10 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 418HT UT WOS:000264140000020 PM 19343949 ER PT J AU Newsome, R Tran, N Paoli, GM Jaykus, LA Tompkin, B Miliotis, M Ruthman, T Hartnett, E Busta, FF Petersen, B Shank, F McEntire, J Hotchkiss, J Wagner, M Schaffner, DW AF Newsome, R. Tran, N. Paoli, G. M. Jaykus, L. A. Tompkin, B. Miliotis, M. Ruthman, T. Hartnett, E. Busta, F. F. Petersen, B. Shank, F. McEntire, J. Hotchkiss, J. Wagner, M. Schaffner, D. W. TI Development of a Risk-Ranking Framework to Evaluate Potential High-Threat Microorganisms, Toxins, and Chemicals in Food SO JOURNAL OF FOOD SCIENCE LA English DT Article DE food safety; risk; risk ranking AB Through a cooperative agreement with the U. S. Food and Drug Administration, the Institute of Food Technologists developed a risk-ranking framework prototype to enable comparison of microbiological and chemical hazards in foods and to assist policy makers, risk managers, risk analysts, and others in determining the relative public health impact of specific hazard-food combinations. The prototype is a bottom-up system based on assumptions that incorporate expert opinion/insight with a number of exposure and hazard-related risk criteria variables, which are propagated forward with food intake data to produce risk-ranking determinations. The prototype produces a semi-quantitative comparative assessment of food safety hazards and the impacts of hazard control measures. For a specific hazard-food combination the prototype can produce a single metric: a final risk value expressed as annual pseudo-disability adjusted life years (pDALY). The pDALY is a harmonization of the very different dose- response relationships observed for chemicals and microbes. The prototype was developed on 2 platforms, a web-based user interface and an Analytica (R) model ( LuminaDecision Systems, LosGatos, Calif., U. S. A.). Comprising visual basic language, the web-based platform facilitates data input and allows use concurrently from multiple locations. The Analytica model facilitates visualization of the logic flow, interrelationship of input and output variables, and calculations/algorithms comprising the prototype. A variety of sortable risk-ranking reports and summary information can be generated for hazard-food pairs, showing hazard and dose- response assumptions and data, per capita consumption by population group, and annual p-DALY. C1 [Newsome, R.; McEntire, J.] Inst Food Technologists, Chicago, IL 60607 USA. [Tran, N.; Petersen, B.] Exponent Inc, Washington, DC 20036 USA. [Paoli, G. M.; Ruthman, T.; Hartnett, E.] Decisionalysis Risk Consultants Inc, Ottawa, ON K1H 653, Canada. [Jaykus, L. A.] N Carolina State Univ, Raleigh, NC 27695 USA. [Tompkin, B.] ConAgra, La Grange, IL 60532 USA. [Miliotis, M.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Busta, F. F.] Natl Ctr Food Protect & Def, Minneapolis, MN 55455 USA. [Busta, F. F.] Univ Minnesota, Minneapolis, MN 55455 USA. [Shank, F.] Inst Food Technologists, Washington, DC 20036 USA. [Hotchkiss, J.] Cornell Univ, Ithaca, NY 14853 USA. [Wagner, M.] Mars Symbiosci, Rockville, MD 20850 USA. [Schaffner, D. W.] Rutgers State Univ, New Brunswick, NJ 08901 USA. RP Newsome, R (reprint author), Inst Food Technologists, Chicago, IL 60607 USA. EM rlnewsome@ift.org FU FDA [FD-U-002255-01]; Food Risk Analysis Initiative of Rutgers Univ FX This study was supported under FDA cooperative agreement grant number FD-U-002255-01 and by additional funding from the Food Risk Analysis Initiative of Rutgers Univ. NR 9 TC 12 Z9 12 U1 0 U2 28 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 MAR PY 2009 VL 74 IS 2 BP R39 EP R45 DI 10.1111/j.1750-3841.2008.01042.x PG 7 WC Food Science & Technology SC Food Science & Technology GA 420EU UT WOS:000264272500046 PM 19323766 ER PT J AU Webb, KM Allard, MW AF Webb, Kristen M. Allard, Marc W. TI Mitochondrial Genome DNA Analysis of the Domestic Dog: Identifying Informative SNPs Outside of the Control Region SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; canine; mitochondrial genome; control region; SNP; haplotype; haplogroup ID CANIS-FAMILIARIS; SUBSTITUTION RATE; HAIRS; PSEUDOGENES; SEQUENCE; DATABASE; BREEDS; NUMBER; MTDNA AB While the mitochondrial control region has proven successful for human forensic evaluations by indicating ethnic origin, domestic dogs (Canis lupus familiaris) of seemingly unrelated breeds often form large groups based on identical control region sequences. In an attempt to break up these large haplotype groups, we have analyzed the remaining c. 15,484 base pairs of the canine mitochondrial genome for 79 dogs and used phylogenetic and population genetic methods to search for additional variability in the form of single nucleotide polymorphisms (SNPs). We have identified 356 SNPs and 65 haplotypes in the remainder of the mitochondrial genome excluding the control region. The exclusion capacity was found to be 0.018. The mitochondrial control region was also evaluated for the same 79 dogs. The signals from the different fragments do not conflict, but instead support one another and provide a larger fragment of DNA that can be analyzed as forensic evidence. C1 [Webb, Kristen M.] ARS, Anim Parasit Dis Lab, USDA, Beltsville, MD 20705 USA. [Allard, Marc W.] US FDA, Mol Methods & Subtyping Branch, Div Microbiol, Off Regulatory Sci,Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Webb, KM (reprint author), ARS, Anim Parasit Dis Lab, USDA, Bldg 1180, Beltsville, MD 20705 USA. NR 28 TC 25 Z9 25 U1 1 U2 23 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD MAR PY 2009 VL 54 IS 2 BP 275 EP 288 DI 10.1111/j.1556-4029.2008.00952.x PG 14 WC Medicine, Legal SC Legal Medicine GA 412AI UT WOS:000263695200006 PM 19261050 ER PT J AU Webb, KM Allard, MW AF Webb, Kristen M. Allard, Marc W. TI Identification of Forensically Informative SNPs in the Domestic Dog Mitochondrial Control Region SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; mitochondrial genome; domestic dog; control region; single nucleotide polymorphism; haplotype ID CANIS-FAMILIARIS; SEQUENCE-ANALYSIS; D-LOOP; DNA; MTDNA; GENOMES; BREEDS; HAIRS AB Dog hair is often found at crime scenes either due to the dog's involvement in the crime or secondary transfer. As little nuclear DNA is present in shed hair, a 1000 base pair fragment of the mitochondrial control region (mtCR) from 552 dogs was assessed for forensically useful sequence variation. Through pairwise alignment to a standard reference sequence, existing haplotypes were further described and 36 new haplotypes and 24 new single nucleotide polymorphisms were identified. The probability of exclusion was found to be 0.957. Breeds were found to have similar sequences, although not identical. No genetic basis was found for grouping dogs by either purebred or mixed or geographic location within the continental United States. Our research demonstrates that the domestic dog mtCR has not been thoroughly surveyed for sequence variation and that a single database comprised of purebred and mixed breed dogs is sufficient for the continental United States. C1 [Webb, Kristen M.] ARS, Anim Parasit Dis Lab, USDA, Beltsville, MD 20705 USA. [Allard, Marc W.] US FDA, Mol Methods & Subtyping Branch, Div Microbiol, Off Regulatory Sci,Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Webb, KM (reprint author), ARS, Anim Parasit Dis Lab, USDA, Bldg 1180, Beltsville, MD 20705 USA. NR 28 TC 19 Z9 20 U1 0 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD MAR PY 2009 VL 54 IS 2 BP 289 EP 304 DI 10.1111/j.1556-4029.2008.00953.x PG 16 WC Medicine, Legal SC Legal Medicine GA 412AI UT WOS:000263695200007 PM 19261051 ER PT J AU Baek, S Kweon, O Kim, SJ Baek, DH Chen, JJ Cerniglia, CE AF Baek, Songjoon Kweon, Ohgew Kim, Seong-Jae Baek, Dong-Heon Chen, James J. Cerniglia, Carl E. TI ClassRHO: A platform for classification of bacterial rieske non-heme iron ring-hydroxylating oxygenases SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE RHO; Classification; PD matrix; Sequence alignment ID DIOXYGENASES AB We have developed an easy-to-use multiplatform classification tool, ClassRHO, which facilitates classification and comparison of bacterial Rieske non-heme iron aromatic ring-hydroxylating oxygenases (RHOs). Visualization and analysis can be generated on-the-fly by entering or uploading RHO query sequences. Pre-computed classifications were implemented for 42 standard RHO sequences. These 42 RHO sequences can be flexibly selected based on user requests. ClassRHO provides users with many options to view and analyze RHO sequences. Published by Elsevier B.V. C1 [Baek, Songjoon; Chen, James J.] US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. [Kweon, Ohgew; Kim, Seong-Jae; Cerniglia, Carl E.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Baek, Dong-Heon] Dankook Univ, Sch Dent, Dept Oral Microbiol & Immunol, Cheonan 330714, South Korea. RP Chen, JJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM jamesj.chen@fda.hhs.gov; carl.cerniglia@fda.hhs.gov FU U. S. Department of Energy; U. S. Food and Drug Administration FX We thank J. B. Sutherland, H. Chen and CH, Chen for critical review of the manuscript. 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. The views presented in this article do not necessarily reflect those of the Food and Drug Administration. NR 7 TC 6 Z9 6 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD MAR PY 2009 VL 76 IS 3 BP 307 EP 309 DI 10.1016/j.mimet.2008.11.003 PG 3 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 421VJ UT WOS:000264386100015 PM 19095015 ER PT J AU Wight, PA Dobretsova, A Johnson, JW Jones, RC Edmondson, RD AF Wight, P. A. Dobretsova, A. Johnson, J. W. Jones, R. C. Edmondson, R. D. TI PROTEOMIC ANALYSIS OF NUCLEAR FACTORS BINDING TO AN INTRONIC ENHANCER IN THE MYELIN PROTEOLIPID PROTEIN GENE SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 07-11, 2009 CL Charleston, SC SP Amer Soc Neurochem C1 [Wight, P. A.; Dobretsova, A.; Johnson, J. W.] Univ Arkansas Med Sci, Dept Physiol & Biophys, Little Rock, AR 72205 USA. [Jones, R. C.; Edmondson, R. D.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2009 VL 108 BP 111 EP 111 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 407AU UT WOS:000263336800250 ER PT J AU Mackey, AC Green, L Leptak, C Avigan, M AF Mackey, Ann Corken Green, Lanh Leptak, Christopher Avigan, Mark TI Hepatosplenic T Cell Lymphoma Associated with Infliximab Use in Young Patients Treated for Inflammatory Bowel Disease: Update SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Letter ID CROHNS-DISEASE; THERAPY C1 [Mackey, Ann Corken; Green, Lanh; Leptak, Christopher; Avigan, Mark] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Mackey, AC (reprint author), Bldg 22,Room 3472,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM ann.mackey@fda.hhs.gov NR 11 TC 73 Z9 77 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD MAR PY 2009 VL 48 IS 3 BP 386 EP 388 PG 3 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 414SP UT WOS:000263885800027 PM 19274799 ER PT J AU Martinez, MN Papich, MG AF Martinez, Marilyn N. Papich, Mark G. TI Factors Influencing the Gastric Residence of Dosage Forms in Dogs SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Review DE preclinical pharmacology; gastrointestinal transit; bioavailability; food effects; oral absorption ID IMPREGNATED POLYETHYLENE SPHERES; MECHANICAL DESTRUCTIVE FORCE; BEAGLE DOGS; ELECTRICAL-STIMULATION; GASTROINTESTINAL-TRACT; NONDIGESTIBLE SOLIDS; NUCLEAR-MEDICINE; DISSOLUTION RATE; EMPTYING RATE; HUMANS AB An appreciation of the variables influencing canine gastric transit time is of interest both because of the push to develop pharmaceutical products that meet the therapeutic needs of the veterinary patient and because of efforts to improve our understanding of the strengths and weaknesses associated with the use of the dog as a preclinical model to support human product development. The gastric transit time of monogastric species is influenced by many factors. Physiological variables include the time of dosing relative to the phase of the interdigestive migrating myoelectric current (IMMC), the sieving properties of the pylorus, the presence or absence of food, and the inherent crushing force of the stomach. Pharmacological factors include particle size, shape and density, drug solubility, and the hardness of the tablet. Despite the importance of understanding the factors influencing gastric residence time in dogs, an in-depth examination of currently available information on this topic has not as yet been published. Therefore, this review provides an examination of each of these factors and their potential impact on canine oral drug absorption characteristics. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:844-860, 2009 C1 [Martinez, Marilyn N.] US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. [Papich, Mark G.] N Carolina State Univ, Coll Vet Med, Dept Anat, Raleigh, NC 27606 USA. RP Martinez, MN (reprint author), US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, 7500 Standish Pl, Rockville, MD 20855 USA. EM marilyn.martinez@fda.hhs.gov NR 63 TC 20 Z9 20 U1 2 U2 9 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD MAR PY 2009 VL 98 IS 3 BP 844 EP 860 DI 10.1002/jps.21499 PG 17 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 413PD UT WOS:000263804100004 PM 18661535 ER PT J AU Xiang, D Berry, J Buntz, S Gargiulo, P Cheney, J Joshi, Y Wabuyele, B Wu, HQ Hamed, M Hussain, AS Khan, MA AF Xiang, Dong Berry, Joseph Buntz, Susan Gargiulo, Paul Cheney, James Joshi, Yatindra Wabuyele, Busolo Wu, Huiquan Hamed, Mazen Hussain, Ajaz S. Khan, Mansoor A. TI Robust Calibration Design in the Pharmaceutical Quantitative Measurements with Near-Infrared (NIR) Spectroscopy: Avoiding the Chemometric Pitfalls SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE near-infrared (NIR); pharmaceutical tablets; content uniformity; multivariate calibration design; partial least-squares regression (PLS) ID CONTENT UNIFORMITY; DOSAGE FORMS; MODELS; SPECTRA; ASSAY; PRODUCTS; TABLETS AB Quantification analysis with near-infrared (NIR) spectroscopy typically requires utilizing chemometric techniques, such as partial least squares (PLS) method, to achieve the desired selectivity. This article points out a major limitation of these statistical-based calibration methods. The limitation is that the techniques suffer from the potential for chance correlation. In this article, the impact of chance correlation oil the robustness of PLS model was illustrated via a pharmaceutical application with NIR to the content uniformity determination of tablets. The procedure involves evaluating the PLS models generated with two sets of calibration tablets incorporated with distinct degree of concentration correlation between the active pharmaceutical ingredient (API) and excipients. The selectivity and robustness of the two models were examined by using a series of data sets associated with placebo tablets and tablets incorporated with variations from excipient content, hardness and particle size. The result clearly revealed that the strong correlation observed in the PLS model created by the correlated design was not solely based on the API information, and there was an intrinsic difference in the variances described by the two calibration models. Diagnostic tools that enable the characterization of the chemical selectivity of the calibration model were also proposed for pharmaceutical quantitative analysis. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:1155-1166, 2009 C1 [Xiang, Dong; Berry, Joseph; Buntz, Susan; Gargiulo, Paul; Cheney, James; Joshi, Yatindra; Wabuyele, Busolo] Novartis Pharmaceut, Pharmaceut & Analyt Dev, E Hanover, NJ 07936 USA. [Wu, Huiquan; Hamed, Mazen; Khan, Mansoor A.] FDA CDER OPS OTR, Div Prod Qual Res, Silver Spring, MD 20993 USA. [Hussain, Ajaz S.] Philip Morris Prod SA, Biol Syst R&D, Philip Morris Int Res & Dev, CH-2000 Neuchatel, Switzerland. RP Xiang, D (reprint author), Novartis Pharmaceut, Pharmaceut & Analyt Dev, E Hanover, NJ 07936 USA. EM dongx_s@yahoo.com NR 19 TC 33 Z9 37 U1 2 U2 14 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 2009 VL 98 IS 3 BP 1155 EP 1166 DI 10.1002/jps.21482 PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 413PD UT WOS:000263804100028 PM 18702120 ER PT J AU Zhang, ZW AF Zhang, Zhiwei TI Likelihood-based confidence sets for partially identified parameters SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE Censoring; Confidence set; Likelihood; Missing data; Partial identification; Verification bias ID EMPIRICAL LIKELIHOOD; INTERVALS AB There has been growing interest in partial identification of probability distributions and parameters. This paper considers statistical inference on parameters that are partially identified because data are incompletely observed, due to nonresponse or censoring, for instance. A method based on likelihood ratios is proposed for constructing confidence sets for partially identified parameters. The method can be used to estimate a proportion or a mean in the presence of missing data, without assuming missing-at-random or modeling the missing-data mechanism. It can also be used to estimate a survival probability with censored data without assuming independent censoring or modeling the censoring mechanism. A version of the verification bias problem is studied as well. Published by Elsevier B.V C1 US FDA, Ctr Devices & Radiol Hlth, Div Biostat, Rockville, MD 20850 USA. RP Zhang, ZW (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Biostat, HFZ 550, Rockville, MD 20850 USA. EM zhiwei.zhang@fda.hhs.gov NR 19 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD MAR 1 PY 2009 VL 139 IS 3 BP 696 EP 710 DI 10.1016/j.jspi.2007.08.009 PG 15 WC Statistics & Probability SC Mathematics GA 389AE UT WOS:000262061300002 ER PT J AU Zhang, X Helms, S Azhar, G Burton, B Huang, C Zhong, Y Gu, X Fang, H Tong, W Wei, JY AF Zhang, X. Helms, S. Azhar, G. Burton, B. Huang, C. Zhong, Y. Gu, X. Fang, H. Tong, W. Wei, J. Y. TI Identification of novel SRF target genes in response to mild overexpression of serum response factor in adult mouse hearts SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Zhang, X.; Helms, S.; Azhar, G.; Burton, B.; Huang, C.; Zhong, Y.; Gu, X.; Wei, J. Y.] Univ Arkansas Med Sci, GRECC, GRE, CAVHS, Little Rock, AR 72205 USA. [Fang, H.; Tong, W.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S79 EP S80 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900226 ER PT J AU Kloke, JD Mckean, JW Rashid, MM AF Kloke, John D. Mckean, Joseph W. Rashid, M. Mushfiqur TI Rank-Based Estimation and Associated Inferences for Linear Models With Cluster Correlated Errors SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Compound symmetry; Joint rankings; Mixed models; Nonparametric; Rank regression scores; Robust; Wilcoxon procedures ID REGRESSION COEFFICIENTS; ROBUST ESTIMATORS; FACTORIAL-DESIGNS; BEHAVIOR; SAMPLES AB R estimators based on the joint ranks (JR) of all the residuals have been developed over the last 20 years for fitting linear models with independently distributed errors. In this article, we extend these estimators to estimating the fixed effects in a linear model with cluster correlated continuous error distributions for general score functions. We discuss the asymptotic theory of the estimators and standard errors of the estimators. For the related mixed model with a single random effect, we discuss robust estimators of the variance components. These are used to obtain Studentized residuals for the JR fit. A real example is discussed, which illustrates the efficiency of the JR analysis over the traditional analysis and the efficiency of a prudent choice of a score function. Simulation studies over situations similar to the example confirm the validity and efficiency of the analysis. C1 [Kloke, John D.] Bucknell Univ, Dept Math, Lewisburg, PA 17837 USA. [Mckean, Joseph W.] Western Michigan Univ, Dept Stat, Kalamazoo, MI 49008 USA. [Rashid, M. Mushfiqur] Ctr Drug Evaluat & Res FDA, Div Biometr 4, Silver Spring, MD 20993 USA. RP Kloke, JD (reprint author), Bucknell Univ, Dept Math, Lewisburg, PA 17837 USA. EM john.kloke@bucknell.edu; joseph.mckean@wmich.edu; mushfiqur.rashid@fda.hhs.gov NR 24 TC 15 Z9 15 U1 1 U2 1 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 2009 VL 104 IS 485 BP 384 EP 390 DI 10.1198/jasa.2009.0116 PG 7 WC Statistics & Probability SC Mathematics GA 425PI UT WOS:000264649200036 ER PT J AU Yang, YS Carlin, AS Faustino, PJ Motta, MIP Hamad, ML He, RY Watanuki, Y Pinnow, EE Khan, MA AF Yang, Yongsheng Carlin, Alan S. Faustino, Patrick J. Motta, Monica I. Pagan Hamad, Mazen L. He, Ruyi Watanuki, Y. Pinnow, E. E. Khan, Mansoor A. TI Participation of Women in Clinical Trials for New Drugs Approved by the Food and Drug Administration in 2000-2002 SO JOURNAL OF WOMENS HEALTH LA English DT Article AB Objective: This study aimed to track the inclusion of women in clinical trials for new drugs approved by the Food and Drug Administration (FDA) between 2000 and 2002 and to evaluate the extent of analyses by sex. Methods: Data were extracted from FDA reviewers' reports, summaries of clinical trials in New Drug Applications (NDAs), and product labeling and organized into a Microsoft Access database. The information collected includes subject enrollment by sex per clinical phase and sex differences in pharmacokinetics, safety, and efficacy as determined by either sponsors or reviewers. Results: There were 67 New Molecular Entities (NMEs) approved by the FDA between 2000 and 2002. A total of 397,825 subjects were enrolled in 2,323 clinical trials. If 9 sex-specific NMEs are excluded, 297,697 subjects were enrolled in 1,974 clinical trials. Forty-seven percent of participants were male, 49% were female, and 4% of subjects were not specified. Of the 58 sex-nonspecific products in the study, 71% (41 of 58) of sex analyses were performed either by the sponsor or FDA reviewers. Twenty-five NMEs were found to have sex differences in pharmacokinetics, efficacy or adverse events. However, no recommendation was made to adjust dosage based on sex differences. Conclusions: The percentages of women and men participating in clinical trials varied by year, phase, and product type. However, the overall participation by women and men was comparable, suggesting an improvement in including more women in clinical trials when compared with the previous FDA study evaluating women's participation from 1995 through 1999. As with the previous study, however, a significant underrepresentation of women in early phase trials and in certain areas, such as cardiovascular products, was observed and continues to be an issue of concern. Lack of appropriate analyses by sex should also be noted as an issue of concern. C1 [Yang, Yongsheng; Carlin, Alan S.; Faustino, Patrick J.; Hamad, Mazen L.; He, Ruyi; Watanuki, Y.; Khan, Mansoor A.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Motta, Monica I. Pagan] Natl Alliance Hispan Hlth, Washington, DC USA. [Pinnow, E. E.] US FDA, Off Womens Hlth, Rockville, MD 20857 USA. RP Yang, YS (reprint author), US FDA, Ctr Drug Evaluat & Res, White Oak Life Sci Bldg 64,Room 1024,10903 New Ha, Silver Spring, MD 20993 USA. EM yongsheng.yang@fda.hhs.gov FU Office of Women's Health at the Food and Drug Administration FX The study was supported by a grant from the Office of Women's Health at the Food and Drug Administration. NR 15 TC 21 Z9 21 U1 0 U2 2 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 2009 VL 18 IS 3 BP 303 EP 310 DI 10.1089/jwh.2008.0971 PG 8 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 417ZF UT WOS:000264116300005 PM 19243271 ER PT J AU Wagner, RD Johnson, SJ Rubin, DK AF Wagner, Robert Doug Johnson, Shemedia J. Rubin, Dedeh Kurniasih TI Probiotic bacteria are antagonistic to Salmonella enterica and Campylobacter jejuni and influence host lymphocyte responses in human microbiota-associated immunodeficient and immunocompetent mice SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Article DE Food safety; Germfree animals; Intestinal bacteria; Immunodeficiency; Probiotics ID COMPETITIVE-EXCLUSION PRODUCTS; GERM-FREE MICE; SEROVAR TYPHIMURIUM; LACTIC-ACID; HUMAN COLON; LACTOBACILLUS-ACIDOPHILUS; GASTROINTESTINAL-TRACT; FECAL MICROBIOTA; T-LYMPHOCYTE; IN-VITRO AB A defined human microbiota-associated (HMA) mouse model in BALB/c and immunodeficient Tg epsilon 26 mice was used to assess the ability of probiotic lactobacilli and bifidobacteria to enhance colonization resistance to gastrointestinal (GI) tract pathogens. Probiotic bacteria (1 x 10(8) colony forming unit (CFU)/mL) successfully excluded Campylobacter jejuni from both strains of mice 7 days after challenge. The probiotic bacteria also reduced the number of Salmonella in the large intestines of both mouse strains. The nylon wool fractionated spleen lymphocyte Populations were incubated with Salmonella or C jejuni antigens. The probiotic treatments did not affect lymphocyte proliferation to C jejuni antigens, but significantly increased proliferation of lymphocytes to Salmonella antigens by 68 and 55%, respectively, over untreated mice. Caspase 3/7 activation was significantly reduced 33 and 38% in the T and B lymphocyte fractions, respectively, of probiotic-treated, Salmonella-challenged HMA BALB/c mice, suggesting that lymphocyte rescue from apoptosis was Occurring as a result of probiotic bacteria activity. These results revealed an immunosuppressive activity by Salmonella that was inhibited by the presence of probiotic bacteria. In summary, lactobacilli and bifidobacteria competitively excluded C. jejuni from immunocompetent and immunodeficient mice and antagonized an observable Salmonella-induced immunosuppression in immunocompetent mice. C1 [Wagner, Robert Doug; Johnson, Shemedia J.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Rubin, Dedeh Kurniasih] Univ Syiah Kuala, Banda Aceh, Indonesia. RP Wagner, RD (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, HFT-250,3900 NCTR Rd, Jefferson, AR 72079 USA. EM doug.wagner@fda.hhs.gov FU Oak Ridge Institute for Science and Education FX The authors have declared no conflict of interest. NR 48 TC 18 Z9 19 U1 0 U2 10 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1613-4125 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD MAR PY 2009 VL 53 IS 3 BP 377 EP 388 DI 10.1002/mnfr.200800101 PG 12 WC Food Science & Technology SC Food Science & Technology GA 427NZ UT WOS:000264787300008 PM 19065588 ER PT J AU Fang, JL McGarrity, LJ Beland, FA AF Fang, Jia-Long McGarrity, Lynda J. Beland, Frederick A. TI Interference of cell cycle progression by zidovudine and lamivudine in NIH 3T3 cells SO MUTAGENESIS LA English DT Article ID VIRUS REVERSE-TRANSCRIPTASE; PLACEBO-CONTROLLED TRIAL; AIDS-RELATED-COMPLEX; IN-VITRO; AZIDOTHYMIDINE AZT; MITOCHONDRIAL TOXICITY; DNA-POLYMERASES; DOUBLE-BLIND; 3'-AZIDO-3'-DEOXYTHYMIDINE; MICE AB Zidovudine (3'-azido-3'-deoxythymidine; AZT) and lamivudine [(-)2',3'-dideoxy-3'-thiacytidine; 3TC] are nucleoside reverse transcriptase inhibitors used to treat and prevent human immunodeficiency virus-1 infections. In short-term incubations (< 48 h), AZT, but not 3TC, has been shown to interfere with cell cycle progression. In the present study, we examined if these alterations persist during long-term incubations in which cells were exposed to AZT (0-1000 mu M) or 3TC (0-500 mu M) in continuous culture for up to 5 weeks. In addition, we investigated the reversibility of these effects upon removal of the drugs. Both drugs caused concentration- and time-dependent decreases in the number of viable cells, with the effect being more pronounced with AZT. There was only a slight increase in the number of viable cells treated with AZT for 5 weeks and then allowed a 1-week recovery period; cell viability in cells treated with 3TC returned to control levels during the recovery period. The decrease in viable cells was not due to apoptotic or necrotic cell death, but rather was associated with S and G2/M phase cell cycle arrest. Western blot analysis indicated that AZT treatment caused a decrease in checkpoint kinase 1 (Chk1) and checkpoint kinase 2 (Chk2) at all time points. Cyclin-dependent kinase 1 was decreased at later time points, while cyclin A was increased at early times. These data indicate that AZT and, to a lesser extent, 3TC interfere with cell growth by slowing cell cycle progression and that checkpoint proteins Chk1 and Chk2 may play an important role in this delay. C1 [Fang, Jia-Long; Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [McGarrity, Lynda J.] Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Fang, JL (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM jia-long.fang@fda.hhs.gov NR 37 TC 12 Z9 12 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD MAR PY 2009 VL 24 IS 2 BP 133 EP 141 DI 10.1093/mutage/gen059 PG 9 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 413YO UT WOS:000263831300003 PM 18936108 ER PT J AU Willy, M Kelly, JP Nourjah, P Kaufman, DW Budnitz, DS Staffa, J AF Willy, Mary Kelly, Judith P. Nourjah, Parivash Kaufman, David W. Budnitz, Daniel S. Staffa, Judy TI Emergency department visits attributed to selected analgesics, United States, 2004-2005 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE analgesics; emergency department; adverse events ID ADVERSE DRUG EVENTS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; US ADULT-POPULATION; NATIONAL SURVEILLANCE; ACETAMINOPHEN TOXICITY; NONPRESCRIPTION; PRESCRIPTION; CHILDREN AB Purpose To estimate the rate of emergency department (ED) visits attributed to selected analgesic-containing medications. Methods We used a nationally representative public health surveillance system to provide estimates of adverse events identified in EDs, and a national telephone survey to provide estimates of selected analgesic-containing medication usage in the US population, 2004-2005. Analysis was restricted to products containing acetaminophen, aspirin, ibuprofen, or naproxen. Types of adverse events and outcomes were compared. Estimated numbers and rates of ED visits were calculated by analgesic groupings and patient age groups. Results The estimated overall rate of ED visits attributed to analgesic-containing medications was 1.6 visits/100 000 users per week. The very old and very young had the highest rates; there were minimal differences in rates by patient gender. Acetaminophen was the attributed drug with the most estimated ED visits and generally had the highest rates of ED visits. The highest estimated rate for a specific product group was among subjects 18-64 years of age taking narcotic-acetaminophen products (8.9 ED visits /100 000 users per week). Overall, 12% of patients presenting to EDs with analgesic-attributed events were hospitalized. Conclusions Rates of ED visits due to analgesics vary depending on the age of the patient and the product; most do not result in hospitalization. Although the rate of emergency visits is relatively low, because of the wide use of the analgesics, public health impact is considerable. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [Willy, Mary; Staffa, Judy] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Kelly, Judith P.; Kaufman, David W.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. [Nourjah, Parivash] Agcy Healthcare Res & Qual, Ctr Outcomes & Evidence, Rockville, MD USA. [Budnitz, Daniel S.] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Atlanta, GA USA. RP Willy, M (reprint author), 10903 New Hampshire Ave,Room 2488, Silver Spring, MD 20993 USA. EM mary.willy@fda.hhs.gov FU Slone Epidemiology Center funds; FDA FX The authors greatly appreciate the contributions to the Slone Survey of Theresa Anderson, study coordinator; Marie Berarducci and Marilyn Wasti, study supervisors; Gene Sun, information systems; and the interviewing staff. Slone Survey data collection was supported by internal Slone Epidemiology Center funds; the present analysis was supported by the FDA. The authors thank Kelly Weidenbach, M.P.H., and Victor Johnson of CDC and Cathy Irish, B.S., and Joel Friedman, B.A. of the U.S. Consumer Product Safety Commission for assistance with data collection and database management in NEISS-CADES. NR 23 TC 6 Z9 6 U1 3 U2 6 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 MAR PY 2009 VL 18 IS 3 BP 188 EP 195 DI 10.1002/pds.1691 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 421PR UT WOS:000264371300002 PM 19116955 ER PT J AU Brown, JS Kulldorff, M Petronis, KR Reynolds, R Chan, KA Davis, RL Graham, D Andrade, SE Raebel, MA Herrinton, L Roblin, D Boudreau, D Smith, D Gurwitz, JH Gunter, MJ Platt, R AF Brown, Jeffrey S. Kulldorff, Martin Petronis, Kenneth R. Reynolds, Robert Chan, K. Arnold Davis, Robert L. Graham, David Andrade, Susan E. Raebel, Marsha A. Herrinton, Lisa Roblin, Douglas Boudreau, Denise Smith, David Gurwitz, Jerry H. Gunter, Margaret J. Platt, Richard TI Early adverse drug event signal detection within population-based health networks using sequential methods: key methodologic considerations SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE adverse drug event; methodology; sequential analysis; safety surveillance; maxSPRT ID VACCINE SAFETY; SURVEILLANCE; RECOMMENDATIONS; RESPONDS; FDA AB Purpose Active surveillance of population-based health networks may improve the timeliness of detection of adverse events (AEs). Our objective was to expand our previous signal detection work by investigating the effect on signal detection of alternative study specifications. Methods We compared the signal detection performance under various study specifications using historical data from nine health plans involved in the HMO Research Network's Center for Education and Research on Therapeutics (CERT). Five drug-event pairs representing generally accepted associations with an AE and two pairs representing "negative controls" were analyzed. Alternative study specifications related to the definition of incident users and incident AEs were assessed and compared to our previous findings. Results Relaxing the incident AE exclusion criteria by (1) including members with prior outpatient diagnoses of interest and (2) halving (to 90 days) the time window specified to define incident exposure and diagnoses increased the number of members under surveillance and as a consequence increased the number of exposed days and diagnoses by about 10-20%. The alternative specifications tend to result in earlier signal detection by 10-16 months, a likely consequence of more exposures and events entering the analysis. Conclusions This paper provides additional preliminary information related to conducting prospective safety monitoring using health plan data and sequential analytic methods. Our findings support continued investigation of using health plan data and sequential analytic methods as a potentially important contribution to active drug safety surveillance. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Brown, Jeffrey S.; Kulldorff, Martin; Platt, Richard] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. [Petronis, Kenneth R.; Reynolds, Robert] Pfizer Inc, New York, NY USA. [Chan, K. Arnold] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Chan, K. Arnold] i3 Drug Safety, Waltham, MA USA. [Davis, Robert L.; Roblin, Douglas] Kaiser Permanente Georgia, Atlanta, GA USA. [Graham, David] US FDA, Off Drug Safety, Rockville, MD 20857 USA. [Andrade, Susan E.; Gurwitz, Jerry H.] Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Fallon Fdn, Worcester, MA USA. [Andrade, Susan E.; Gurwitz, Jerry H.] Fallon Community Hlth Plan, Worcester, MA USA. [Raebel, Marsha A.] Kaiser Permanente Colorado, Denver, CO USA. [Herrinton, Lisa] Kaiser Permanente No Calif, Oakland, CA USA. [Boudreau, Denise] Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. [Smith, David] Kaiser Permanente NW, Portland, OR USA. [Gunter, Margaret J.] Lovelace Clin Fdn, Albuquerque, NM USA. RP Brown, JS (reprint author), Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA. EM jeff_brown@harvardpilgrim.org RI Kulldorff, Martin/H-4282-2011; OI Chan, Kinwei/0000-0001-8161-1986; Kulldorff, Martin/0000-0002-5284-2993 FU AHRQ [2UI8HS010391] FX The authors are indebted to the statistical programmers at each of the sites for their work in extracting the study data and testing the programming algorithms, to Kimberly Lane and the HMORN CERT Data Coordinating Center for their help in overseeing the study. Study has been funded by a grant from AHRQ (2UI8HS010391) supporting the HMO Research Network Centers for Education and Research on Therapeutics (CERT) and Pfizer Inc. NR 30 TC 18 Z9 19 U1 0 U2 2 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 MAR PY 2009 VL 18 IS 3 BP 226 EP 234 DI 10.1002/pds.1706 PG 9 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 421PR UT WOS:000264371300006 PM 19148879 ER PT J AU Andrade, SE McPhillips, H Loren, D Raebel, MA Lane, K Livingston, J Boudreau, DM Smith, DH Davis, RL Willy, ME Platt, R AF Andrade, Susan E. McPhillips, Heather Loren, David Raebel, Marsha A. Lane, Kimberly Livingston, James Boudreau, Denise M. Smith, David H. Davis, Robert L. Willy, Mary E. Platt, Richard TI Antidepressant medication use and risk of persistent pulmonary hypertension of the newborn SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE pregnancy; antidepressant medications; persistent pulmonary hypertension ID SEROTONIN-REUPTAKE INHIBITORS; CONGENITAL-MALFORMATIONS; BIRTH-DEFECTS; PREGNANCY AB Purpose To determine the prevalence of persistent pulmonary hypertension of the newborn (PPHN) among infants whose mothers were exposed to antidepressants in the third trimester of pregnancy compared to the prevalence among infants whose mothers were not exposed to antidepressants in the third trimester. Methods A retrospective study was conducted using the automated databases of four health plans participating in the HMO Research Network Center for Education and Research on Therapeutics. Women who delivered an infant in a hospital from I January 1996 through 31 December 2000 were identified. The administrative databases were used to identify full-term infants whose mothers received an antidepressant during the third trimester of pregnancy and unexposed infants whose mothers did not receive an antidepressant during the third trimester. Hospitalization data were used to identify diagnoses or procedure codes potentially indicative of PPHN. Results Among 1104 infants exposed to antidepressants in the third trimester and a matched sample of 1104 unexposed infants, five infants were classified by the expert reviewers as having PPHN. Among those infants whose mothers were exposed to selective serotonin reuptake inhibitors (SSRIs) in the third trimester, the prevalence of PPHN was 2.14 per 1000 (95% confidence interval (CI) 0.26, 7.74), while the prevalence among infants whose mothers were not exposed was 2.72 per 1000 (95%CI 0.56, 7.93). Conclusions We did not find an association between SSRI use in late pregnancy and PPHN. Limitations of the present study, including the small number of confirmed cases, suggest further research in this area may be warranted. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Andrade, Susan E.] Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Fallon Fdn, Worcester, MA 01605 USA. [Andrade, Susan E.] Fallon Community Hlth Plan, Worcester, MA USA. [Andrade, Susan E.; McPhillips, Heather; Raebel, Marsha A.; Lane, Kimberly; Livingston, James; Boudreau, Denise M.; Smith, David H.; Davis, Robert L.; Platt, Richard] Ctr Educ & Res Therapeut, HMO Res Network, Boston, MA USA. [McPhillips, Heather; Loren, David] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Raebel, Marsha A.] Kaiser Permanente Colorado, Denver, CO USA. [Lane, Kimberly; Livingston, James; Platt, Richard] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Boudreau, Denise M.] Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. [Smith, David H.] Kaiser Permanente NW, Portland, OR USA. [Davis, Robert L.] Kaiser Permanente SE, Ctr Hlth Res, Atlanta, GA USA. [Willy, Mary E.] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Andrade, SE (reprint author), Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Fallon Fdn, 630 Plantat St, Worcester, MA 01605 USA. EM sandrade@meyersprimary.org FU U.S. Food and Drug Administration (Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research) [HHSF223200510012C]; Agency for Healthcare Research and Quality FX This study was supported by a contract HHSF223200510012C from the U.S. Food and Drug Administration (Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research). Drs Andrade, Boudreau, Davis, Raebel, Smith, and Platt are investigators in the HMO Research Network Center for Education and Research in Therapeutics (CERT), supported by the Agency for Healthcare Research and Quality. We acknowledge the thoughtful input of Susan K. McCune, MD and Sascha Dublin, MD, PhD. We are grateful to April Duddy for her technical support. NR 15 TC 84 Z9 85 U1 0 U2 6 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 MAR PY 2009 VL 18 IS 3 BP 246 EP 252 DI 10.1002/pds.1710 PG 7 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 421PR UT WOS:000264371300009 PM 19148882 ER PT J AU Dou, J Chen, S AF Dou, J. Chen, S. TI improving the Odds of Developing New Drugs from Botanicals: Botanical Review Team's Perspectives SO PLANTA MEDICA LA English DT Meeting Abstract CT 8th Annual Oxford International Conference on Science of Botanicals CY APR 06, 2009 CL Oxford, ENGLAND SP NCNPR, Ctr Food Safety & Appl Nutr, Food & Drug Adm, CFSAN/FDA, Shanghai Inst Mat Plant Res, Inst Indigenous Med, Sri Lanka, Amer Soc Pharmocognosy C1 [Dou, J.; Chen, S.] Food & Drug Adm, Bot Review Team, Off Drug Evaluat 1, HFD 101,CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD MAR PY 2009 VL 75 IS 4 BP 411 EP 411 PG 1 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 429BF UT WOS:000264895100064 ER PT J AU Frankos, VH AF Frankos, V. H. TI FDA's Dietary Supplement Good Manufacturing Practice Regulatory Requirements for Globally Marketed Botanicals SO PLANTA MEDICA LA English DT Meeting Abstract CT 8th Annual Oxford International Conference on Science of Botanicals CY APR 06, 2009 CL Oxford, ENGLAND SP NCNPR, Ctr Food Safety & Appl Nutr, Food & Drug Adm, CFSAN/FDA, Shanghai Inst Mat Plant Res, Inst Indigenous Med, Sri Lanka, Amer Soc Pharmocognosy C1 [Frankos, V. H.] US FDA, Div Dietary Supplement Programs, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD MAR PY 2009 VL 75 IS 4 BP 411 EP 411 PG 1 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 429BF UT WOS:000264895100062 ER PT J AU Pawar, RS Grundel, E Mazzola, E White, KD Krynitsky, A Rader, JI AF Pawar, R. S. Grundel, E. Mazzola, E. White, K. D. Krynitsky, A. Rader, J., I TI Isolation of Pyrrolizidine Alkaloid Isomers from Symphytum Species by Semi-Preparative Chiral Chromatography SO PLANTA MEDICA LA English DT Meeting Abstract CT 8th Annual Oxford International Conference on Science of Botanicals CY APR 06, 2009 CL Oxford, ENGLAND SP NCNPR, Ctr Food Safety & Appl Nutr, Food & Drug Adm, CFSAN/FDA, Shanghai Inst Mat Plant Res, Inst Indigenous Med, Sri Lanka, Amer Soc Pharmocognosy ID NMR-SPECTROSCOPY; OFFICINALE C1 [Pawar, R. S.; Grundel, E.; Mazzola, E.; White, K. D.; Krynitsky, A.; Rader, J., I] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 5 TC 0 Z9 0 U1 1 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD MAR PY 2009 VL 75 IS 4 BP 433 EP 434 PG 2 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 429BF UT WOS:000264895100130 ER PT J AU Betz, JM Saldanha, LG Fisher, KD Coates, PM Klein, M Engel, J Pho, AN Sharpless, KE Sander, LC Wise, SA Rimmer, CA Phinney, KW AF Betz, J. M. Saldanha, L. G. Fisher, K. D. Coates, P. M. Klein, M. Engel, J. Pho, Nguyen A. Sharpless, K. E. Sander, L. C. Wise, S. A. Rimmer, C. A. Phinney, K. W. TI The NIH/ODS Analytical Methods and Reference Materials Program for Dietary Supplements: Five-Year Accomplishments and Future Directions SO PLANTA MEDICA LA English DT Meeting Abstract CT 8th Annual Oxford International Conference on Science of Botanicals CY APR 06, 2009 CL Oxford, ENGLAND SP NCNPR, Ctr Food Safety & Appl Nutr, Food & Drug Adm, CFSAN/FDA, Shanghai Inst Mat Plant Res, Inst Indigenous Med, Sri Lanka, Amer Soc Pharmocognosy C1 [Betz, J. M.; Saldanha, L. G.; Fisher, K. D.; Coates, P. M.; Klein, M.; Engel, J.] US Natl Inst Hlth, Off Dietary Supplements, Bethesda, MD 20892 USA. [Pho, Nguyen A.] US FDA, Silver Spring, MD 20993 USA. [Sharpless, K. E.; Sander, L. C.; Wise, S. A.; Rimmer, C. A.; Phinney, K. W.] NIST, Gaithersburg, MD 20899 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD MAR PY 2009 VL 75 IS 4 BP 435 EP 435 PG 1 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 429BF UT WOS:000264895100135 ER PT J AU Sajadi, MM Roddy, KM Chan-Tack, KM Forrest, GN AF Sajadi, Mohammad M. Roddy, Kristina M. Chan-Tack, Kirk M. Forrest, Graeme N. TI Original Research: Risk Factors for Mortality from Primary Cryptococcosis in Patients with HIV SO POSTGRADUATE MEDICINE LA English DT Article DE HIV; cryptococcosis; AIDS; outcomes; mortality; pneumonia; inpatient; infectious disease ID RECONSTITUTION INFLAMMATORY SYNDROME; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; ACTIVE ANTIRETROVIRAL THERAPY; NEUROGENIC PULMONARY-EDEMA; IMMUNE RECONSTITUTION; AMPHOTERICIN-B; PRACTICE GUIDELINES; INFECTED PATIENTS; RANDOMIZED-TRIAL; MENINGITIS AB Cryptococcosis continues to have a high mortality rate in human immunodeficiency virus (HIV)-positive patients despite advances made in antifungal treatment, intracranial pressure management, and antiretroviral therapy. This retrospective chart review was conducted at the University of Maryland Medical Center and Baltimore VA Medical Center from 1993 to 2004. We reviewed all inpatient cases of cryptococcal infections to assess predictors of inpatient mortality among HIV-positive patients. Data collected included patient demographics, presenting symptoms and CD4 counts, lumbar puncture (LP) results including opening pressure (OP), cryptococcal antigen (CAg) levels, sites of infection, and drug therapy. Multivariate and survival analyses were performed. We identified 202 patients with primary cryptococcosis. The main sites of infection included blood (72%), central nervous system (85%), and lower respiratory tract (34%). Overall 30-day mortality was 14%. Predictors of mortality included syncope (P = 0.039; OR, 4.5), concomitant pneumonia (P = 0.001; OR, 3.5), respiratory failure (P < 0.001; OR, 10.5), and admission into the intensive care unit (P < 0.001; OR, 8). Amphotericin dose, OP >= 250 mm H(2)O, and number of LPs were not found to be predictive of mortality. Mortality attributable to cryptococcosis remains high. Our study findings suggest that syncope, respiratory failure, pneumonia, and admission to the intensive care unit are independently associated with an increased risk of death within 30 days after cryptococcosis diagnosis. C1 [Sajadi, Mohammad M.] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. [Roddy, Kristina M.; Forrest, Graeme N.] Univ Maryland, Sch Med, Div Infect Dis, Baltimore, MD 21201 USA. [Chan-Tack, Kirk M.] US FDA, Div Antiviral Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Sajadi, MM (reprint author), Univ Maryland, Sch Med, Inst Human Virol, 725 W Lombard St,N54B, Baltimore, MD 21201 USA. EM msajadi@ihv.umaryland.edu RI Andrade, Hugo/M-6631-2013 OI Andrade, Hugo/0000-0001-6781-6125 NR 36 TC 5 Z9 6 U1 0 U2 0 PU JTE MULTIMEDIA PI BERWYN PA 1235 WESTLAKES DR, STE 220, BERWYN, PA 19312 USA SN 0032-5481 J9 POSTGRAD MED JI Postgrad. Med. PD MAR PY 2009 VL 121 IS 2 BP 107 EP 113 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 430FV UT WOS:000264975100011 PM 19332968 ER PT J AU Reepmeyer, JC AF Reepmeyer, John C. TI Direct intramolecular gas-phase transfer reactions during fragmentation of sildenafil and thiosildenafil analogs in electrospray ionization mass spectrometry SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID ION-NEUTRAL COMPLEXES; HERBAL DIETARY-SUPPLEMENT; STRUCTURE ELUCIDATION; IDENTIFICATION; ADULTERANT AB A study is made of the mass spectral fragmentation pathways of sildenafil, thiosildenafil, and analogous compounds. A prominent gas-phase reaction that occurs during collision-induced dissociation (CID) of thiosildenafil compounds is the transfer of an alkyl group from the piperazine nitrogen atom to the sulfur atom of the thiocarbonyl group. This phenomenon is clearly demonstrated through a comparison of electrospray ionization mass spectral fragmentation patterns of four sildenafil-type compounds and three related thiosildenafil derivatives. Molecular modeling and fragmentation patterns support a direct intramolecular alkyl transfer mechanism rather than an ion-neutral complex mechanism. CID of thiohydroxyhomosildenafil results in a facile hydroxyethyl migration to the sulfur atom followed by a second intramolecular reaction to form a spiro-1,3-oxathiolane ring, which fragments in two directions to generate both carbonyl and thiocarbonyl product ions from this thiocarbonyl compound. While methyl migration to the thiocarbonyl sulfur atom of thiosildenafil is dominant, methyl migration to the carbonyl oxygen atom of sildenafil may occur to a small extent. Published in 2009 by John Wiley & Sons, Ltd. C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Div Pharmaceut Anal,FDA, St Louis, MO 63101 USA. RP Reepmeyer, JC (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Div Pharmaceut Anal,FDA, 1114 Market St,Room 1002, St Louis, MO 63101 USA. EM reepmeyer@gmail.com NR 16 TC 13 Z9 13 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PD MAR PY 2009 VL 23 IS 6 BP 927 EP 936 DI 10.1002/rcm.3948 PG 10 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 416NX UT WOS:000264013900021 PM 19222058 ER PT J AU McCright, B Dang, JM Hursh, DA Kaplan, DS Ballica, R Benton, KA Plant, AL AF McCright, Brent Dang, Jiyoung M. Hursh, Deborah A. Kaplan, David S. Ballica, Rabia Benton, Kimberly A. Plant, Anne L. TI Synopsis of the Food and Drug Administration-National Institute of Standards and Technology Co-Sponsored "In Vitro Analyses of Cell/Scaffold Products" Workshop SO TISSUE ENGINEERING PART A LA English DT Article ID EMBRYONIC STEM-CELLS; BIOARTIFICIAL LIVER; TISSUE; BIOMATERIALS; BIOREACTOR; RESPONSES; SYSTEMS; GROWTH; MODEL; VIVO C1 [McCright, Brent; Hursh, Deborah A.; Ballica, Rabia; Benton, Kimberly A.] US FDA, Off Cellular Tissue & Gene Therapy, Ctr Biol Evaluat & Res, Rockville, MD USA. [Dang, Jiyoung M.] US FDA, Off Device Evaluat, Rockville, MD USA. [Kaplan, David S.] US FDA, Ctr Devices & Radiol Hlth, Sci & Engn Labs, Rockville, MD USA. [Plant, Anne L.] NIST, Div Biochem Sci, Gaithersburg, MD USA. RP McCright, B (reprint author), US FDA, Off Cellular Tissue & Gene Therapy, Ctr Biol Evaluat & Res, Rockville, MD USA. EM brenton.mccright@fda.hhs.gov NR 28 TC 3 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 J9 TISSUE ENG PT A JI Tissue Eng. Part A PD MAR PY 2009 VL 15 IS 3 BP 455 EP 460 PG 6 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 415DG UT WOS:000263913900194 PM 19215220 ER PT J AU Keil, DE McGuinn, WD Dudley, AC EuDaly, JG Gilkeson, GS Peden-Adams, MM AF Keil, Deborah E. McGuinn, W. David Dudley, Andrew C. EuDaly, Jackie G. Gilkeson, Gary S. Peden-Adams, Margie M. TI N,N,-Diethyl-m-Toluamide (DEET) Suppresses Humoral Immunological Function in B6C3F1 Mice SO TOXICOLOGICAL SCIENCES LA English DT Article DE DEET; immune function; Gulf War Illness; PFC response; T-cell subpopulations ID LISTERIA-MONOCYTOGENES INFECTION; REPELLENT N,N-DIETHYL-M-TOLUAMIDE DEET; NATURAL-KILLER-CELLS; GULF-WAR SYNDROME; PYRIDOSTIGMINE BROMIDE; INSECT REPELLENT; HOST-RESISTANCE; TOXIC ENCEPHALOPATHY; MOSQUITO REPELLENTS; RISK-ASSESSMENT AB N,N-diethyl-meta-toluamide (DEET) is a particularly effective broad-spectrum insect repellent used commonly in recreational, occupational and military environments. Due to its widespread use and suggested link to Gulf War Illness, this study examined the immunotoxicity of DEET. Adult female B6C3F1 mice were injected sc for 14 days with DEET at 0, 7.7, 15.5, 31, or 62 mg/kg/day. Due to differences in the dermal absorption of DEET between mice and humans, this study eliminated this confounding factor by utilizing sc injection and measured circulating blood levels of DEET to assess bioavailability from sc administration. Effects on lymphocyte proliferation, natural killer cell activity, thymus and spleen weight and cellularity, the antibody plaque-forming cell (PFC) response, and thymic and splenic CD4/CD8 lymphocyte subpopulations were assessed 24 h after the last dose. No effect was observed in lymphocyte proliferation, natural killer cell activity, thymic weight, splenic weight, thymic cellularity, or splenic cellularity. Significant decreases were observed in the percentage of splenic CD4-/CD8- and CD4+/CD8- lymphocytes but only at the 62 mg DEET/kg/day treatment level and not in absolute numbers of these cells types. Additionally, significant decreases in the antibody PFC response were observed following treatment with 15.5, 31, or 62 mg DEET/kg/day. Pharmacokinetic (PK) data from the current study indicate 95% bioavailability of the administered dose. Therefore, it is likely that DEET exposure ranges applied in this study are comparable to currently reported occupational usage. Together, the evidence for immunosuppression and available PK data suggest a potential human health risk associated with DEET in the occupational or military environments assuming similar sensitivity between human and rodent responses. C1 [Keil, Deborah E.] Univ Nevada, Clin Sci Lab, Las Vegas, NV 89154 USA. US FDA, Silver Spring, MD 20993 USA. [EuDaly, Jackie G.; Peden-Adams, Margie M.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29412 USA. [McGuinn, W. David; EuDaly, Jackie G.; Gilkeson, Gary S.; Peden-Adams, Margie M.] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29412 USA. [Dudley, Andrew C.; EuDaly, Jackie G.; Peden-Adams, Margie M.] Med Univ S Carolina, Marine Biomed & Environm Sci Ctr, Charleston, SC 29412 USA. [Gilkeson, Gary S.] Ralph Johnson VAMC, Med Res Serv, Charleston, SC 29425 USA. RP Keil, DE (reprint author), Univ Nevada, Clin Sci Lab, 4505 Maryland Pkwy,Box 453021, Las Vegas, NV 89154 USA. EM deborah.keil@unlv.edu OI Keil, Deborah/0000-0002-5787-8514 FU U. S. Department of Defense [DAMD17-99-1-9013] FX U. S. Department of Defense (grant # DAMD17-99-1-9013) to D. E. K.; the Veterans Administration Medical Research Service to G. S. G.; and internal support from UNLV. NR 74 TC 7 Z9 8 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2009 VL 108 IS 1 BP 110 EP 123 DI 10.1093/toxsci/kfp001 PG 14 WC Toxicology SC Toxicology GA 410VO UT WOS:000263606600012 PM 19141786 ER PT J AU Zou, XJ Patterson, TA Sadovova, N Twaddle, NC Doerge, DR Zhang, X Fu, X Hanig, JP Paule, MG Slikker, W Wang, C AF Zou, Xiaoju Patterson, Tucker A. Sadovova, Natalya Twaddle, Nathan C. Doerge, Daniel R. Zhang, Xuan Fu, Xin Hanig, Joseph P. Paule, Merle G. Slikker, William Wang, Cheng TI Potential Neurotoxicity of Ketamine in the Developing Rat Brain SO TOXICOLOGICAL SCIENCES LA English DT Article DE N-methyl-D-aspartate (NMDA) receptor; neuronal cell death; apoptosis ID APOPTOTIC NEURODEGENERATION; CARDIOPULMONARY BYPASS; ASPARTATE RECEPTORS; ANESTHETIC AGENTS; CORTICAL-NEURONS; NMDA RECEPTORS; CELL-DEATH; EXPOSURE; MECHANISMS; BLOCKADE AB Ketamine, an N-methyl-D-aspartate (NMDA) receptor ion channel blocker, is a widely used anesthetic recently reported to enhance neuronal death in developing rodents and nonhuman primates. This study evaluated dose-response and time-course effects of ketamine, levels of ketamine in plasma and brain, and the relationship between altered NMDA receptor expression and ketamine-induced neuronal cell death during development. Postnatal day 7 rats were administered 5, 10, or 20 mg/kg ketamine using single or multiple injections (subcutaneously) at 2-h intervals, and the potential neurotoxic effects were examined 6 h after the last injection. No significant neurotoxic effects were detected in layers II or III of the frontal cortex of rats administered one, three, or six injections of 5 or 10 mg/kg ketamine. However, in rats administered six injections of 20 mg/kg ketamine, a significant increase in the number of caspase-3- and Fluoro-Jade C-positive neuronal cells was observed in the frontal cortex. Electron microscopic observations showed typical nuclear condensation and fragmentation indicating enhanced apoptotic characteristics. Increased cell death was also apparent in other brain regions. In addition, apoptosis occurred after plasma and brain levels of ketamine had returned to baseline levels. In situ hybridization also showed a remarkable increase in mRNA signals for the NMDA NR1 subunit in the frontal cortex. These data demonstrate that ketamine administration results in a dose-related and exposure-time dependent increase in neuronal cell death during development. Ketamine-induced cell death appears to be apoptotic in nature and closely associated with enhanced NMDA receptor subunit mRNA expression. C1 [Zou, Xiaoju; Patterson, Tucker A.; Zhang, Xuan; Paule, Merle G.; Slikker, William; Wang, Cheng] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Sadovova, Natalya] Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Twaddle, Nathan C.; Doerge, Daniel R.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Fu, Xin] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. [Hanig, Joseph P.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Wang, C (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, HFT 132, Jefferson, AR 72079 USA. EM Cheng.wang@fda.hhs.gov FU National Center for Toxicological Research/U.S. Food and Drug Administration [IAG 224-07-007]; National Institute for Environmental Health Sciences/National Toxicology Program; Center for Drug Evaluation and Research/U.S. Food and Drug Administration; National Institute of Child Health and Human Development FX Interagency Agreement (IAG 224-07-007) between the National Center for Toxicological Research/U.S. Food and Drug Administration and the National Institute for Environmental Health Sciences/National Toxicology Program; Center for Drug Evaluation and Research/U.S. Food and Drug Administration; and National Institute of Child Health and Human Development. NR 31 TC 86 Z9 91 U1 1 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 MAR PY 2009 VL 108 IS 1 BP 149 EP 158 DI 10.1093/toxsci/kfn270 PG 10 WC Toxicology SC Toxicology GA 410VO UT WOS:000263606600015 PM 19126600 ER PT J AU Le Nouen, C Munir, S Losq, S Winter, CC McCarty, T Stephany, DA Holmes, KL Bukreyev, A Rabin, RL Collins, PL Buchholz, UJ AF Le Nouen, Cyril Munir, Shirin Losq, Stephanie Winter, Christine C. McCarty, Thomas Stephany, David A. Holmes, Kevin L. Bukreyev, Alexander Rabin, Ronald L. Collins, Peter L. Buchholz, Ursula J. TI Infection and maturation of monocyte-derived human dendritic cells by human respiratory syncytial virus, human metapneumovirus, and human parainfluenza virus type 3 SO VIROLOGY LA English DT Article DE Metapneumovirus; Pneumovirus; Paramyxovirus; Monocyte derived dendritic cells; Cytokine; Maturation marker ID CD4 T-CELLS; IN-VITRO; INFLUENZA-VIRUS; YOUNG-CHILDREN; TRACT DISEASE; RIG-I; EXPRESSION; CD38; CD83; DIFFERENTIATION AB Human respiratory syncytial virus (HRSV), human metapneumovirus (HMPV), and human parainfluenza virus type 3 (HPIV3) are common, important respiratory pathogens, but HRSV has a substantially greater impact with regard to acute disease, long-term effects oil airway function, and frequency of re-infection. It has been reported to strongly interfere with the functioning of dendritic cells (DC). We compared HRSV to HMPV and HPIV3 with regard to their effects on human monocyte-derived immature DC (IDC). Side-by-side analysis distinguished between common effects versus those specific to individual viruses. The use of GFP-expressing viruses yielded clear identification of robustly infected cells and provided the means to distinguish between direct effects of robust viral gene expression versus bystander effects. All three viruses infected inefficiently based oil GFP expression, with considerable donor-to donor-variability. The GFP-negative cells exhibited low, abortive levels of viral RNA synthesis. The three viruses induced low-to-moderate levels of DC maturation and cytokine/chemokine responses, increasing slightly in the order HRSV, HMPV, and HPIV3. Infection at the individual cell level was relatively benign, such that in general GFP-positive cells were neither more nor less able to mature compared to GFP-negative bystanders, and cells were responsive to a secondary treatment with lipopolysaccharide, indicating that the ability to mature was not impaired. However, there was a single exception, namely that HPIV3 Clown-regulated CD38 expression at the RNA level. Maturation by these viruses was anti-apoptotic. Inefficient infection of IDC and sub-optimal maturation might result in reduced immune responses, but these effects would be common to all three viruses rather than specific to HRSV. Published by Elsevier Inc. C1 [Le Nouen, Cyril; Munir, Shirin; Losq, Stephanie; Winter, Christine C.; McCarty, Thomas; Bukreyev, Alexander; Collins, Peter L.; Buchholz, Ursula J.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Stephany, David A.; Holmes, Kevin L.] NIAID, Flow Cytometry Sect, NIH, Bethesda, MD 20892 USA. [Rabin, Ronald L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Buchholz, UJ (reprint author), Bldg 50,Room 6505,50 S Dr MSC 8007, Bethesda, MD 20892 USA. EM ubuchholz@niaid.nih.gov FU Intramural NIH HHS [Z99 AI999999] NR 62 TC 35 Z9 35 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 0042-6822 J9 VIROLOGY JI Virology PD MAR 1 PY 2009 VL 385 IS 1 BP 169 EP 182 DI 10.1016/j.virol.2008.11.043 PG 14 WC Virology SC Virology GA 416EW UT WOS:000263989400021 PM 19128816 ER PT J AU Pinnow, E Sharma, P Parekh, A Gevorkian, N Uhl, K AF Pinnow, Ellen Sharma, Pellavi Parekh, Ameeta Gevorkian, Natalie Uhl, Kathleen TI INCREASING PARTICIPATION OF WOMEN IN EARLY PHASE CLINICAL TRIALS APPROVED BY THE FDA SO WOMENS HEALTH ISSUES LA English DT Article ID GENDER; PHARMACOKINETICS; PHARMACODYNAMICS; PERSPECTIVE AB Background. Historically women were excluded from participation in phase 1 clinical trials. The goal of this study was to determine the participation of women and evaluate if participation has increased over time. Methods. Clinical trial data submitted to the FDA for New Molecular Entities (NMEs) for adult, non-sex specific indications between January 2006 and December 2007 were reviewed. Electronic data available on phase 1 trial were evaluated for proposed indications, sex of participants, and doses tested. Therapeutic doses were obtained from the approved labeling. Results. FDA approved 34 NMEs in 2006-2007. Data for 352 phase 1 trial of 30 NMEs were obtained. Data for 1 NME was not available electronically, 2 did not include new phase 1 data, and 1 provided only summary demographic data. All NMEs reviewed were for drugs used to treat conditions occurring in both men and women. Overall 1.20 (34.1%) trials had only male participants while 232 (65.9%) trials also enrolled female participants. 30.6% (3106/10,134) of participants were women. 149/352 (42.3%) of trials included safety and tolerability testing above the highest approved dose. In those trials, 32.5% (1628/5011) of the participants were women. An evaluation of trial start date illustrated the number of trials that enrolled women (P = 0.01) and the number of female participants (p < 0.001) has increased over time. Conclusion. Females subjects have traditionally been underrepresented in phase 1 trials. The number trials enrolling women and the number of women participating in phase 1 trials has increased since 2001, however, women are still underrepresented. C1 [Pinnow, Ellen; Sharma, Pellavi; Parekh, Ameeta; Gevorkian, Natalie; Uhl, Kathleen] US FDA, Rockville, MD 20850 USA. RP Pinnow, E (reprint author), US FDA, 1350 Piccard, Rockville, MD 20850 USA. EM ellen.pinnow@fda.hhs.gov NR 18 TC 26 Z9 26 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD MAR-APR PY 2009 VL 19 IS 2 BP 89 EP 93 DI 10.1016/j.whi.2008.09.009 PG 5 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 423CA UT WOS:000264472800001 PM 19272558 ER PT J AU Yamada, A Suzuki, D Miyazono, A Oshima, K Kamiya, A Zhao, BH Takami, M Donnelly, RP Itabe, H Yamamoto, M Kimura, S Kamijo, R AF Yamada, Atsushi Suzuki, Dai Miyazono, Agasa Oshima, Kumiko Kamiya, Akihide Zhao, Baohong Takami, Masamichi Donnelly, Raymond P. Itabe, Hiroyuki Yamamoto, Matsuo Kimura, Shioko Kamijo, Ryutaro TI IFN-gamma down-regulates Secretoglobin 3A1 gene expression SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE SCGB3A1; Uteroglobin-related protein 2; IFN-gamma ID JAK-STAT PATHWAY; INTERFERON-GAMMA; EPITHELIAL-CELLS; INDUCTION; RECEPTOR; UGRP2; MOUSE; RESPONSES; PROTEINS; SCGB3A1 AB STAT1 mediates Interferon (IFN)-dependent positive and negative regulation of inflammatory gene expression in lung. In this Study, we examined the effect of IFN-gamma on the expression of SCGB3A1 which is thought to play crucial roles in inflammation and epithelial cell differentiation in lung. We found that expression of SCGB3A1 was down-regulated by IFN-gamma in a time- and dose-dependent manner in the murine transformed Clara Cells (mtCC) line. IFN-gamma induced the phosphorylation of STAT1, which binds to a STAT-binding element (SBE) in the SCGB3A1 gene promoter, leading to decreased transcriptional activation of this gene. (C) 2009 Elsevier Inc. All rights reserved, C1 [Yamada, Atsushi; Suzuki, Dai; Miyazono, Agasa; Zhao, Baohong; Takami, Masamichi; Kamijo, Ryutaro] Showa Univ, Sch Dent, Dept Biochem, Shinagawa Ku, Tokyo 1428555, Japan. [Yamada, Atsushi; Kimura, Shioko] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Miyazono, Agasa; Yamamoto, Matsuo] Showa Univ, Sch Dent, Dept Periodontol, Tokyo 1458515, Japan. [Oshima, Kumiko; Itabe, Hiroyuki] Showa Univ, Sch Pharm, Dept Biol & Chem, Shinagawa Ku, Tokyo 1428555, Japan. [Kamiya, Akihide] Univ Tokyo, Inst Med Sci, Ctr Stem Cell & Regenerat Med, Div Stem Cell Therapy,Minato Ku, Tokyo 1088639, Japan. [Donnelly, Raymond P.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Yamada, A (reprint author), Showa Univ, Sch Dent, Dept Biochem, Shinagawa Ku, 1-5-8 Hatanodai, Tokyo 1428555, Japan. EM yamadaa@dent.showa-u.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology of Japan; Japan Society for the Promotion of Science FX We would like to thank Dr. J. Francesco DeMayo for providing mtCC cells. This work was supported in part by the 'High-Tech Research Center' Project for Private Universities matching fund subsidy from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and Grants-in-Aid for Scientific research from the Japan Society for the Promotion of Science. NR 23 TC 4 Z9 4 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 20 PY 2009 VL 379 IS 4 BP 964 EP 968 DI 10.1016/j.bbrc.2008.12.187 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 407AT UT WOS:000263336700032 PM 19135978 ER PT J AU Dobrovolsky, VN Shaddock, JG Mittelstaedt, RA Manjanatha, MG Miura, D Uchikawa, M Mattison, DR Morris, SM AF Dobrovolsky, Vasily N. Shaddock, Joseph G. Mittelstaedt, Roberta A. Manjanatha, Mugimane G. Miura, Daishiro Uchikawa, Makoto Mattison, Donald R. Morris, Suzanne M. TI Evaluation of Macaca mulatta as a model for genotoxicity studies SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Rhesus monkey; Mutation; ENU; HPRT; PIG-A; Cloning; Flow cytometry; Lymphocytes; Erythrocytes ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; ETHYL-N-NITROSOUREA; DNA-SEQUENCE ANALYSIS; MONKEY T-LYMPHOCYTES; IN-VIVO; PERIPHERAL-BLOOD; CYNOMOLGUS MONKEY; MONOCLONAL-ANTIBODIES; MOLECULAR ANALYSIS; ANCHORED PROTEINS AB We have investigated the use of peripheral blood from the nonhuman primate (NHP) rhesus monkey (Macaca mulatta) as a model system for mutation detection. The rhesus monkey is metabolically closer to humans than most common laboratory animals, and therefore may be a relevant model for hazard identification and human risk assessment. To validate the model, conditions were determined for in vitro selection and expansion of 6-thioguanine-resistant (6-TGr) HPRT mutant and proaerolysin-resistant (ProAERr) PIG-A mutant lymphocytes from peripheral blood obtained by routine venipuncture. Also, flow cytometric methods were developed for the rapid detection of PIG-A mutant erythrocytes. The flow cytometric analysis of PIG-A mutant erythrocytes was based on enumerating cells deficient in surface markers attached to the cellular membrane via glycosylphosphatidyl inositol (GPI) anchors. Mutant cells were enumerated over an extended period of time in peripheral blood of male monkeys receiving daily doses of the electrolyte replenisher Prang (TM) (a common carrier for oral delivery of drugs in NHPs), and in the blood of one male monkey treated with a single i.p. dose of 50 mg/kg of N-ethyl-N-nitrosourea at similar to 2 years of age and another similar injection at approximately 3.5 years of age. The spontaneous PIG-A and HPRT T-cell mutant frequency (MF) was low in animals receiving Prang (0-8 x 10(-6)), and treatment with ENU resulted in a clearly detectable increase in the frequency of ProAERr and 6-TGr lymphocytes (up to similar to 28 x 10(-6) and similar to 30 x 10(-6), respectively). Also, the ENU-treated animal had higher frequency of GPI-deficient erythrocytes (46.5 x 10(-6) in the treated animal vs. 7.8 +/- 4.2 x 10(-6) in control animals). our results indicate that the rhesus monkey can be a valuable model for the identification of agents that may impact upon human health as mutagens and that the PIG-A gene can be a useful target for detection of mutation in both white and red blood cells. Published by Elsevier B.V. C1 [Dobrovolsky, Vasily N.; Shaddock, Joseph G.; Mittelstaedt, Roberta A.; Manjanatha, Mugimane G.; Miura, Daishiro; Morris, Suzanne M.] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Miura, Daishiro] Teijin Pharma Ltd, Tokyo, Japan. [Uchikawa, Makoto] Tokyo Blood Ctr, Tokyo, Japan. [Mattison, Donald R.] NICHD, US NIH, Bethesda, MD 20852 USA. RP Dobrovolsky, VN (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd,HFT-120, Jefferson, AR 72079 USA. EM vasily.dobrovolsky@fda.hhs.gov RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 FU NICHD FX We would like to thank the following people for their important contributions to the study. We thank Dr. R. Albertini for providing human T-cell growth factor supplement, Dr. Patrick O'Neill for providing HPRT-deficient human lymphoblastoid TK6 cell line. Special thanks to employees of animal care facility for multiple blood samplings of experimental animals. Also we thank Drs. Charlotte Hotchkiss and Jeff Carraway for administering ENU and monitoring health of monkey colony at NCTR. This work was partially supported by the NICHD through the U.S. Congressional Best Pharmaceuticals for Children Act of 2002. The views presented in this article do not necessary reflect those of the U.S. Food and Drug Administration. NR 37 TC 19 Z9 21 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD FEB 19 PY 2009 VL 673 IS 1 BP 21 EP 28 DI 10.1016/j.mrgentox.2008.11.006 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 412TZ UT WOS:000263748400005 PM 19073277 ER PT J AU Morris, SA Dobrovolsky, VN Shaddock, JG Mittelstaedt, RA Bishop, ME Manjanatha, MG Shelton, SD Doerge, DR Twaddle, NC Chen, JJ Lin, CJ Paule, MG Slikker, W Hotchkiss, CE Petibone, D Tucker, JD Mattison, DR AF Morris, Suzanne A. Dobrovolsky, Vasily N. Shaddock, Joseph G. Mittelstaedt, Roberta A. Bishop, Michelle E. Manjanatha, Mugimane G. Shelton, Sharon D. Doerge, Daniel R. Twaddle, Nathan C. Chen, James J. Lin, Chien-Ju Paule, Merle G. Slikker, William, Jr. Hotchkiss, Charlotte E. Petibone, Dayton Tucker, James D. Mattison, Donald R. TI The genetic toxicology of methylphenidate hydrochloride in non-human primates SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Methylphenidate; Non-human primates; Chromosome aberrations; Micronuclei; HPRT mutations ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; FLOW-CYTOMETRIC ANALYSIS; DNA-SEQUENCE ANALYSIS; PERIPHERAL-BLOOD; IN-VIVO; CALORIE RESTRICTION; CHROMOSOMAL DAMAGE; MACACA-MULATTA; LYMPHOCYTES; CHILDREN AB The studies presented in this work were designed to evaluate the genetic toxicity of methylphenidate hydrochloride (MPH) in non-human primates (NHP) using a long-term, chronic dosing regimen. Thus, approximately two-year old, male rhesus monkeys of Indian origin were orally exposed to MPH diluted in the electrolyte replenisher, Prang (R), five days per week over a 20-month period. There were 10 animals per dose group and the doses were (1) control, Prang only, (2) low, 0.15 mg/kg of MPH twice per day increased to 2.5 mg/kg twice per day and (3) high, 1.5 mg/kg of MPH twice per day increased to 12.5 mg/kg twice per day. Blood samples were obtained from each animal to determine the base-line serum levels of MPH and the major metabolite of MPH in NHP, ritalinic acid (RA). In addition, the base-line frequency of micronucleated erythrocytes (MN-RETs) by flow cytometry, HPRT mutants by a lymphocyte cloning assay, and chromosome aberrations by FISH painting were determined from peripheral blood samples. Once dosing began, the serum levels of MPH and its major metabolite, RA, were determined monthly. The MN-RET frequency and health parameters (CBC, serum chemistries) were also determined monthly. HPRT mutant and chromosome aberration frequencies were measured every three months. CBC values and serum chemistries. with the exception of alanine amino transferase, were within normal limits over the course of drug exposure. The final plasma levels of MPH were similar to those produced by the pediatric dose of 0.3 mu g/ml. No significant increases in the frequencies of MN-RETs, HPRT mutants, or chromosome aberrations were detected in the treated animals compared to the control animals over the 20-month exposure period. Published by Elsevier B.V. C1 [Morris, Suzanne A.; Dobrovolsky, Vasily N.; Shaddock, Joseph G.; Mittelstaedt, Roberta A.; Bishop, Michelle E.; Manjanatha, Mugimane G.; Shelton, Sharon D.] US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Doerge, Daniel R.; Twaddle, Nathan C.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Chen, James J.; Lin, Chien-Ju] US FDA, Div Personalized Med & Nutr, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Paule, Merle G.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Slikker, William, Jr.] US FDA, Off Director, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Hotchkiss, Charlotte E.] Washington Natl Primate Res Ctr, Seattle, WA USA. [Petibone, Dayton; Tucker, James D.] Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA. [Mattison, Donald R.] Eunice Kennedy Shriver Natl Ctr Child Hlth & Dev, Bethesda, MD USA. RP Morris, SA (reprint author), US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM suzanne.morris@fda.hhs.gov RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 FU National Center for Toxicological Research/FDA; Best Pharmaceuticals for Children Act/Eunice M. Kennedy Shriver National Institute for Child Health and Development/NIH; NCTR/FDA; Wayne State University FX Funding: These studies were supported by an Inter-Agency Agreement between the National Center for Toxicological Research/FDA and the Best Pharmaceuticals for Children Act/Eunice M. Kennedy Shriver National Institute for Child Health and Development/NIH. The studies were also supported by a contract between the NCTR/FDA and Wayne State University. NR 34 TC 18 Z9 18 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD FEB 19 PY 2009 VL 673 IS 1 BP 59 EP 66 DI 10.1016/j.mrgentox.2008.12.001 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 412TZ UT WOS:000263748400010 PM 19135169 ER PT J AU Yan, H Parsons, DW Jin, GL McLendon, R Rasheed, BA Yuan, WS Kos, I Batinic-Haberle, I Jones, S Riggins, GJ Friedman, H Friedman, A Reardon, D Herndon, J Kinzler, KW Velculescu, VE Vogelstein, B Bigner, DD AF Yan, Hai Parsons, D. Williams Jin, Genglin McLendon, Roger Rasheed, B. Ahmed Yuan, Weishi Kos, Ivan Batinic-Haberle, Ines Jones, Sian Riggins, Gregory J. Friedman, Henry Friedman, Allan Reardon, David Herndon, James Kinzler, Kenneth W. Velculescu, Victor E. Vogelstein, Bert Bigner, Darell D. TI IDH1 and IDH2 Mutations in Gliomas SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DEPENDENT ISOCITRATE DEHYDROGENASE; COMPARATIVE GENOMIC HYBRIDIZATION; FACTOR RECEPTOR GENE; MALIGNANT GLIOMAS; GLIOBLASTOMA; PATHWAYS; AMPLIFICATION; EXPRESSION; MECHANISM; MAJORITY AB Background A recent genomewide mutational analysis of glioblastomas ( World Health Organization [ WHO] grade IV glioma) revealed somatic mutations of the isocitrate dehydrogenase 1 gene ( IDH1) in a fraction of such tumors, most frequently in tumors that were known to have evolved from lower- grade gliomas ( secondary glioblastomas). Methods We determined the sequence of the IDH1 gene and the related IDH2 gene in 445 central nervous system ( CNS) tumors and 494 non- CNS tumors. The enzymatic activity of the proteins that were produced from normal and mutant IDH1 and IDH2 genes was determined in cultured glioma cells that were transfected with these genes. Results We identified mutations that affected amino acid 132 of IDH1 in more than 70% of WHO grade II and III astrocytomas and oligodendrogliomas and in glioblastomas that developed from these lower- grade lesions. Tumors without mutations in IDH1 often had mutations affecting the analogous amino acid ( R172) of the IDH2 gene. Tumors with IDH1 or IDH2 mutations had distinctive genetic and clinical characteristics, and patients with such tumors had a better outcome than those with wild- type IDH genes. Each of four tested IDH1 and IDH2 mutations reduced the enzymatic activity of the encoded protein. Conclusions Mutations of NADP(+)-dependent isocitrate dehydrogenases encoded by IDH1 and IDH2 occur in a majority of several types of malignant gliomas. C1 [Yan, Hai; Jin, Genglin; McLendon, Roger; Rasheed, B. Ahmed; Bigner, Darell D.] Duke Univ, Med Ctr, Dept Pathol, Pediat Brain Tumor Fdn Inst, Durham, NC 27710 USA. [Kos, Ivan; Batinic-Haberle, Ines] Duke Univ, Med Ctr, Dept Radiat Oncol, Pediat Brain Tumor Fdn Inst, Durham, NC 27710 USA. [Friedman, Henry] Duke Univ, Med Ctr, Dept Neurooncol, Pediat Brain Tumor Fdn Inst, Durham, NC 27710 USA. [Friedman, Allan; Reardon, David] Duke Univ, Med Ctr, Dept Surg, Pediat Brain Tumor Fdn Inst, Durham, NC 27710 USA. [Yan, Hai; Jin, Genglin; McLendon, Roger; Rasheed, B. Ahmed; Kos, Ivan; Batinic-Haberle, Ines; Friedman, Henry; Friedman, Allan; Reardon, David; Bigner, Darell D.] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA. [Herndon, James] Duke Univ, Med Ctr, Canc Stat Ctr, Durham, NC 27710 USA. [Parsons, D. Williams; Jones, Sian; Kinzler, Kenneth W.; Velculescu, Victor E.; Vogelstein, Bert] Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD USA. [Parsons, D. Williams; Jones, Sian; Kinzler, Kenneth W.; Velculescu, Victor E.; Vogelstein, Bert] Johns Hopkins Kimmel Canc Ctr, Howard Hughes Med Inst, Baltimore, MD USA. [Riggins, Gregory J.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Parsons, D. Williams] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Yuan, Weishi] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Yan, H (reprint author), Duke Univ, Med Ctr, Dept Pathol, Pediat Brain Tumor Fdn Inst, Durham, NC 27710 USA. EM yan00002@mc.duke.edu; dwparson@txccc.org RI Jin, Genglin/F-6868-2011; leng, xianwei/F-9073-2011; Jones, Sian/A-5050-2012 FU Pediatric Brain Tumor Foundation Institute; Damon Runyon Foundation Scholar Award; Southeastern Brain Tumor Foundation; Alex's Lemonade Stand Foundation; V Foundation for Cancer Research; Virginia and D. K. Ludwig Fund for Cancer Research; Pew Charitable Trusts; American Brain Tumor Association; Brain Tumor Research Fund at Johns Hopkins [R01CA118822, NS20023-21, R37CA11898-34, CA121113, CA43460, CA57345, 5P50-CA-108786, 5P50-NS-20023, 5R37CA-11898, 2P30-CA-14236]; Beckman Coulter; Accelerate Brain Cancer Cure Foundation; Johns Hopkins University FX We thank Melissa J. Ehinger, Diane L. Satterfield, Eric Lipp, Michael Leonard, Jennifer D. Funkhouser, and Patrick Killela for their assistance with the clinical information; P. Buckhaults, S. Powell, S. Kern, J. Eshleman, C. Civin, I.- M. Shih, and A. Gazdar for providing DNA from non-central nervous system cancers; and Dr. A. T. Campagnoni at the University of California, Los Angeles, for donating the human oligodendroglioma cell line. NR 24 TC 1809 Z9 1869 U1 14 U2 118 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 19 PY 2009 VL 360 IS 8 BP 765 EP 773 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 408CN UT WOS:000263411300006 PM 19228619 ER PT J AU Woodcock, J Lesko, LJ AF Woodcock, Janet Lesko, Lawrence J. TI Pharmacogenetics-Tailoring Treatment for the Outliers SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Woodcock, Janet; Lesko, Lawrence J.] US FDA, Ctr Drug Evaluat & Res, White Oak, MD USA. RP Woodcock, J (reprint author), US FDA, Ctr Drug Evaluat & Res, White Oak, MD USA. NR 5 TC 57 Z9 58 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 19 PY 2009 VL 360 IS 8 BP 811 EP 813 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 408CN UT WOS:000263411300013 PM 19228625 ER PT J AU Kutner, RH Puthli, S Marino, MP Reiser, J AF Kutner, Robert H. Puthli, Sharon Marino, Michael P. Reiser, Jakob TI Simplified production and concentration of HIV-1-based lentiviral vectors using HYPERFlask vessels and anion exchange membrane chromatography SO BMC BIOTECHNOLOGY LA English DT Article ID LARGE-SCALE PRODUCTION; MESENCHYMAL STEM-CELLS; GENE-TRANSFER; IN-VIVO; TRANSIENT TRANSFECTION; PURIFICATION; TRANSDUCTION; THERAPY; TROPISM; HIV AB Background: During the past twelve years, lentiviral (LV) vectors have emerged as valuable tools for transgene delivery because of their ability to transduce nondividing cells and their capacity to sustain long-term transgene expression in target cells in vitro and in vivo. However, despite significant progress, the production and concentration of high-titer, high-quality LV vector stocks is still cumbersome and costly. Methods: Here we present a simplified protocol for LV vector production on a laboratory scale using HYPERFlask vessels. HYPERFlask vessels are high-yield, high-performance flasks that utilize a multilayered gas permeable growth surface for efficient gas exchange, allowing convenient production of high-titer LV vectors. For subsequent concentration of LV vector stocks produced in this way, we describe a facile protocol involving Mustang Q anion exchange membrane chromatography. Results: Our results show that unconcentrated LV vector stocks with titers in excess of 108 transduction units (TU) per ml were obtained using HYPERFlasks and that these titers were higher than those produced in parallel using regular 150-cm(2) tissue culture dishes. We also show that up to 500 ml of an unconcentrated LV vector stock prepared using a HYPERFlask vessel could be concentrated using a single Mustang Q Acrodisc with a membrane volume of 0.18 ml. Up to 5.3 x 1010 TU were recovered from a single HYPERFlask vessel. Conclusion: The protocol described here is easy to implement and should facilitate high-titer LV vector production for preclinical studies in animal models without the need for multiple tissue culture dishes and ultracentrifugation-based concentration protocols. C1 [Kutner, Robert H.; Puthli, Sharon; Marino, Michael P.; Reiser, Jakob] Louisiana State Univ, Hlth Sci Ctr, Gene Therapy Program, New Orleans, LA USA. [Marino, Michael P.; Reiser, Jakob] US FDA, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Kutner, RH (reprint author), Louisiana State Univ, Hlth Sci Ctr, Gene Therapy Program, New Orleans, LA USA. EM rkutne@lsuhsc.edu; sputhli@yahoo.com; Michael.Marino@fda.hhs.gov; Jakob.Reiser@fda.hhs.gov FU NIH grants [R01 NS044832, P01 HL076100] FX Support for this work was provided by NIH grants R01 NS044832 and P01 HL076100. NR 28 TC 28 Z9 29 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1472-6750 J9 BMC BIOTECHNOL JI BMC Biotechnol. PD FEB 16 PY 2009 VL 9 AR 10 DI 10.1186/1472-6750-9-10 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 416TS UT WOS:000264029000001 PM 19220915 ER PT J AU Fan, XH Fang, H Hong, HX Perkins, R Shi, LM Tong, WD AF Fan, Xiaohui Fang, Hong Hong, Huixiao Perkins, Roger Shi, Leming Tong, Weida TI Correlation analysis of external RNA controls reveals its utility for assessment of microarray assay SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE Gene expression; DNA microarray; Quality control; External RNA controls; MAQC; Outlier identification ID GENE-EXPRESSION MEASUREMENTS; QUALITY-CONTROL; CONSISTENCY AB Quality control of a microarray experiment has become an important issue for both research and regulation. External RNA controls (ERCs), which call be either added to the total RNA level (tERCs) or introduced right before hybridization (cERCs), are designed and recommended by commercial microarray platforms for assessment of performance of a microarray experiment. However, the utility of ERCs has not been fully realized mainly due to the lack of sufficient data resources. The US Food and Drug Administration (FDA)-led community-wide Microarray Quality Control (MAQC) study generates a large amount of microarray data with implementation of ERCs across several commercial microarray platforms. The utility of ERCs in quality control by assessing the ERCs' concentration-response behavior was investigated in the MAQC study. In this work, an ERC-based correlation analysis was conducted to assess the quality of a microarray experiment. We found that the pairwise correlations of tERCs are sample independent, indicating that the array data obtained from different biological samples can be treated as technical replicates in analysis of tERCs. Consequently, the commonly used quality control method of applying correlation analysis on technical replicates can be adopted for assessing array performance based on different biological samples using tERCs. The proposed approach is sensitive to identifying Outlying assays and is not dependent on the choice of normalization method. (C) Published by Elsevier Inc. C1 [Fan, Xiaohui; Fang, Hong; Hong, Huixiao; Perkins, Roger] US FDA, Natl Ctr Toxicol Res, ICF Int, Jefferson, AR 72079 USA. [Fan, Xiaohui] Zhejiang Univ, Coll Pharmaceut Sci, Pharmaceut Informat Inst, Hangzhou 310027, Peoples R China. RP Tong, WD (reprint author), US FDA, Natl Ctr Toxicol Res, ICF Int, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM weida.tong@fda.hhs.gov FU Oak Ridge Institute for Science and Education (ORISE) FX Xiaohui Fan thanks the Oak Ridge Institute for Science and Education (ORISE) for its support with a research fellowship. The views presented in this article do not necessarily reflect those of the US Food and Drug Administration. NR 16 TC 2 Z9 2 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD FEB 15 PY 2009 VL 385 IS 2 BP 203 EP 207 DI 10.1016/j.ab.2008.11.019 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 400OI UT WOS:000262877400003 PM 19059192 ER PT J AU Khan, AA Ponce, E Nawaz, MS Cheng, CM Khan, JA West, CS AF Khan, Ashraf A. Ponce, Elizabeth Nawaz, M. S. Cheng, Chorng-Ming Khan, Junaid A. West, Christine S. TI Identification and Characterization of Class 1 Integron Resistance Gene Cassettes among Salmonella Strains Isolated from Imported Seafood SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID SEROVAR TYPHIMURIUM DT104; MULTIDRUG-RESISTANCE; UNITED-STATES; ENTERICA SEROVARS; AGONA; INFECTIONS; PREVALENCE; REGION; FOODS AB A total of 210 Salmonella isolates, representing 64 different serovars, were isolated from imported seafood samples, and 55/210 isolates were found to be resistant to at least one antibiotic. Class 1 integrons from three multidrug-resistant Salmonella enterica strains ( Salmonella enterica serovars Newport [ strain 62], Typhimurium var. Copenhagen [ strain 629], and Lansing [ strain 803], originating from Hong Kong, the Philippines, and Taiwan, respectively) were characterized. Southern hybridization of plasmids isolated from these strains, using a class 1 integron probe, showed that trimethoprim-sulfamethoxazole and streptomycin resistance genes were located on a megaplasmid in strain 629. Our study indicates that imported seafood could be a reservoir for Salmonella isolates resistant to multiple antibiotics. C1 [Khan, Ashraf A.; Nawaz, M. S.; West, Christine S.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Ponce, Elizabeth] CICESE, Dept Biotecnol Marina, Ensenada 22860, Baja California, Mexico. [Cheng, Chorng-Ming] US FDA, Pacific Reg Lab SW, Jefferson, AR 72079 USA. [Khan, Junaid A.] Univ Arkansas Med Sci, Dept Cardiol, Little Rock, AR 72205 USA. RP Khan, AA (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM Ashraf.khan@fda.hhs.gov RI Khan, Ashraf/E-8133-2013; Ponce-Rivas, Elizabeth/K-3278-2016 OI Ponce-Rivas, Elizabeth/0000-0002-2842-7300 NR 27 TC 27 Z9 29 U1 0 U2 6 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 15 PY 2009 VL 75 IS 4 BP 1192 EP 1196 DI 10.1128/AEM.02054-08 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 403YY UT WOS:000263119100037 PM 19074612 ER PT J AU Chill, L Trinh, L Azadi, P Ishihara, M Sonon, R Karnaukhova, E Ophir, Y Golding, B Shiloach, J AF Chill, Liat Trinh, Loc Azadi, Parastoo Ishihara, Mayumi Sonon, Roberto Karnaukhova, Elena Ophir, Yakir Golding, Basil Shiloach, Joseph TI Production, Purification, and Characterization of Human alpha 1 Proteinase Inhibitor From Aspergillus niger SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE Aspergillus niger; glycosylation; alpha 1-PI ID OXIDIZED ALPHA-1-PROTEINASE INHIBITOR; ACTIVE HUMAN ALPHA-1-ANTITRYPSIN; HIGH-LEVEL EXPRESSION; FUSION PROTEIN; FILAMENTOUS FUNGI; YEAST; ALPHA(1)-ANTITRYPSIN; GLYCOSYLATION; GLYCOPROTEINS; CONCENTRATE AB Human alpha one proteinase inhibitor (alpha 1-PI) was cloned and expressed in Aspergillus niger, filamentious fungus that can grow in defined media and can perform glycosylation. Submerged culture conditions were established using starch as carbon source, 30% dissolved oxygen concentration, pH 7.0 and 28 degrees C. Eight milligrams per liter of active alpha 1-PI were secreted to the growth media in about 40 h. Controlling the protein proteolysis was found to be an important factor in the production. The effects of various carbon sources, pH and temperature on the production and stability of the protein were tested and the product was purified and characterized. Two molecular weights variants of the recombinant alpha 1-PI were produced by the fungus; the difference is attributed to the glycosylated part of the molecule. The two glycoproteins were treated with PNGAse F and the released glycans were analyzed by HPAEC, MALDI/TOF-MS, NSI-MS(n) and GC-MS. The MALDI and NSI- full MS spectra of permethylated N-glycans revealed that the N-glycans of both variants contain a series of high-mannose type glycans with 5-20 hexose units. Monosaccharide analysis showed that these were composed of N-acetylglucosamine, mannose, and galactose. Linkage analysis revealed that the galactosyl component was in the furanoic conformation, which was attaching in a terminal non-reducing position. The Galactofuranose-containing high-mannnose type N-glycans are typical structures, which recently have been found as part of several glycoproteins produced by Aspergillus niger. C1 [Chill, Liat; Trinh, Loc; Shiloach, Joseph] NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA. [Trinh, Loc; Azadi, Parastoo; Ishihara, Mayumi] Univ Georgia, Complex Carbohydrate Res Ctr, Analyt Serv, Athens, GA 30602 USA. [Karnaukhova, Elena; Ophir, Yakir; Golding, Basil] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Shiloach, J (reprint author), NIDDK, Biotechnol Core Lab, NIH, Bldg 14A,Room 170,9000 Rockville Rike, Bethesda, MD 20892 USA. EM yossi@nih.gov FU National institute of Diabetes & Digestive & Kidney diseases; National Institutes of Health FX Funding was provided by the intramural program at the National institute of Diabetes & Digestive & Kidney diseases, National Institutes of Health. The authors thank Dr. John Cipollo, CBER, FDA, for reviewing the manuscript and for his valuable remarks and Suggestions, and for Mrs D Livilat for assisting with editing the manuscript. NR 43 TC 12 Z9 12 U1 2 U2 8 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 15 PY 2009 VL 102 IS 3 BP 828 EP 844 DI 10.1002/bit.22099 PG 17 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 396NK UT WOS:000262598200019 PM 18828177 ER PT J AU Schnackenberg, LK Chen, MJ Sun, JC Holland, RD Dragan, Y Tong, WD Welsh, W Beger, RD AF Schnackenberg, Laura K. Chen, Minjun Sun, Jinchun Holland, Ricky D. Dragan, Yvonne Tong, Weida Welsh, William Beger, Richard D. TI Evaluations of the trans-sulfuration pathway in multiple liver toxicity studies SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Metabolomics; Hepatotoxicity; S-Adenosylmethionine; Creatine; Guanidinoacetate N-methyltransferase ID S-ADENOSYLMETHIONINE; INDUCED HEPATOTOXICITY; RAT; EXPOSURE; STRESS; DAMAGE; HYPERCREATINURIA; ISOTHIOCYANATE; THIOACETAMIDE; SENSITIZATION AB Drug-induced liver injury has been associated with the generation of reactive metabolites, which are primarily detoxified via glutathione conjugation. In this study, it was hypothesized that molecules involved in the synthesis of glutathione would be diminished to replenish the glutathione depleted through conjugation reactions. Since S-adenosylmethionine (SAMe) is the primary source of the sulfur atom in glutathione, UPLC/MS and NMR were used to evaluate metabolites involved with the transulfuration pathway in urine samples collected during studies of eight liver toxic compounds in Sprague-Dawley rats. Urinary levels of creatine were increased on day 1 or day 2 in 8 high dose liver toxicity studies. Taurine concentration in urine was increased in only 3 of 8 liver toxicity Studies while SAMe was found to be reduced in 4 of 5 liver toxicity studies. To further validate the results from the metabonomic studies, microarray data from rat liver samples following treatment with acetaminophen was obtained from the Gene Expression Omnibus (GEO) database. Some genes involved in the trans-sulfuration pathway, including guanidinoacetate N-methyltransferase, glycine N-methyltransferase, betaine-homocysteine methyltransferase and cysteine dioxygenase were found to be significantly decreased while methionine adenosyl transferase II, alpha increased at 24 h post-dosing, which is consistent with the SAMe and creatine findings. The metabolic and transcriptomic results show that the trans-sulfuration pathway from SAMe to glutathione was disturbed due to the administration of heptatotoxicants. Published by Elsevier Inc. C1 [Schnackenberg, Laura K.; Sun, Jinchun; Holland, Ricky D.; Dragan, Yvonne; Tong, Weida; Beger, Richard D.] US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Chen, Minjun; Welsh, William] Univ Med & Dent New Jersey, Environm Bioinformat Computat Toxicol Ctr, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 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 FU USEPA-funded Environmental Bioinformatics and Computational Toxicology Center (ebCTC) [GAD R 832721-010] FX We thank Don Robertson and Mike Reily who provided the urine sample sets through material transfer agreements between Pfizer and NCTR. We thank John Wijsrnan, Glenn Cantor, Daniel Branstetter, and Gary Cockerell of Pharmacia Corp. for carrying out the in-life portion of the study. We thank Mary Bollard, Olaf Beckonert, Hector Ketm, Henrik Antti, Timothy Ebbels, Elaine Holmes, John Lindon, and Jeremy Nicholson (Imperial College, London, UK) for their key role in organizing the COMET effort. We would also like to thank Imperial College and the other four companies involved in COMET for allowing Pfizer to provide the NCCR Center for Metabolornics with the urine samples through a material transfer agreement. ACD/Labs 1 D NMR manager is part of "beta test" collaboration between the NCFR and ACD/Labs. Support for this work has been provided by the USEPA-funded Environmental Bioinformatics and Computational Toxicology Center (ebCTC), under STAR Grant number GAD R 832721-010. This work has not been reviewed by and does not represent the opinions of the USEPA. Furthermore, the views presented in this article do not necessarily reflect those of the U. S. Food and Drug Administration. NR 43 TC 18 Z9 20 U1 2 U2 17 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD FEB 15 PY 2009 VL 235 IS 1 BP 25 EP 32 DI 10.1016/j.taap.2008.11.015 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 409YL UT WOS:000263541600004 PM 19103213 ER PT J AU Tsai, CM Jankowska-Stephens, E Mizanur, RM Cipollo, JF AF Tsai, Chao-Ming Jankowska-Stephens, Ewa Mizanur, Rahman M. Cipollo, John F. TI The Fine Structure of Neisseria meningitidis Lipooligosaccharide from the M986 Strain and Three of Its Variants SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INNER-CORE LIPOPOLYSACCHARIDE; OUTER-MEMBRANE PROTEINS; GROUP-B; IMMUNOTYPE EPITOPES; SECONDARY RESPONSE; GROUP-A; OLIGOSACCHARIDE; PHOSPHOETHANOLAMINE; IMMUNORESPONSES; IDENTIFICATION AB Neisseria meningitidis is a cause of fatal sepsis and epidemic meningitis. A major virulence factor is cell wall lipooligosaccharide (LOS). The M986 strain has been used extensively in immunological and vaccine research. Yet, the LOS repertoire of this strain is not known. Here we have investigated the LOS structures of M986 and three of its variants OP1, OP2-, and OP2+. This strain and its variants present a series of related LOS families that are increasingly truncated in their listed order. The major structural differences are seen in the lacto-N-neotetraose alpha-chain. The gamma-chain Hep II contains two phosphoethanolamine (PEA) substitutions at C3 and C6/7. These substitutions were seen in all strains except OP2+ where the canonical core Hep II is missing. The PEA disubstitution was present in nearly stoichiometric amounts with only minor amounts of monosubstitution observed, and no glycomers devoid of PEA were seen. This was also the case in LOS with a complete lacto-N-neotetraosyl alpha-chain even though previous reports suggested that the presence of an extended alpha-chain hinders C3 PEA substitution of Hep II. Approximately 50% of gamma-chain GlcNAc was present in its 3-OAc-substituted form. Because Hep II C3 PEA substitution and gamma-chain GlcNAc OAc addition have been reported to negatively interact, the co-existence of these two modifications in these strains is unique. The LOS structures of M986 and three of its variants have been determined, which better defines these strains as tools for immunological and vaccine research. C1 [Cipollo, John F.] NIH, Ctr Biol Evaluat & Res, US FDA, Bethesda, MD 20892 USA. RP Cipollo, JF (reprint author), NIH, Ctr Biol Evaluat & Res, US FDA, Bldg 29,Rm 126,8800 Rockville Pike, Bethesda, MD 20892 USA. EM john.cipollo@fda.hhs.gov FU Department of Energy [DE-FG09-93ER-20097] FX This work was supported by the Department of Energy-funded (Grant DE-FG09-93ER-20097) Center for Plant and Microbial Complex Carbohydrates. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 44 TC 14 Z9 14 U1 0 U2 2 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 FEB 13 PY 2009 VL 284 IS 7 BP 4616 EP 4625 DI 10.1074/jbc.M808209200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 404ET UT WOS:000263134400061 PM 19095648 ER PT J AU Landgren, O Albitar, M Ma, WL Abbasi, F Hayes, RB Ghia, P Marti, GE Caporaso, NE AF Landgren, Ola Albitar, Maher Ma, Wanlong Abbasi, Fatima Hayes, Richard B. Ghia, Paolo Marti, Gerald E. Caporaso, Neil E. TI B-Cell Clones as Early Markers for Chronic Lymphocytic Leukemia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HODGKINS-DISEASE; MUTATIONAL STATUS; NATURAL-HISTORY; IMMUNOGLOBULIN; BLOOD; MBL; CLL; CLASSIFICATION; EXPRESSION; RECEPTOR AB Background Otherwise healthy persons with a small number of B- cell clones circulating in the peripheral blood have been designated as having monoclonal B- cell lymphocytosis ( MBL). Hospital- based series indicate an excess risk of progression from MBL to chronic lymphocytic leukemia ( CLL). In this prospective cohort study, we tested the hypothesis that CLL is always preceded by MBL. Methods Among 77,469 healthy adults who were enrolled in the nationwide, population- based Prostate, Lung, Colorectal, and Ovarian ( PLCO) Cancer Screening Trial, we identified 45 subjects in whom CLL was subsequently diagnosed ( up to 6.4 years later) through the collection of a peripheral- blood sample. Using six- color flow cytometry ( with antibodies CD45, CD19, CD5, CD10, kappa, and lambda) and immunoglobulin heavy-chain gene rearrangement by reverse- transcriptase - polymerase- chain- reaction assay, we determined the association between MBL and subsequent CLL and characterized the immunoglobulin gene repertoire of the prediagnostic B- cell clones. Results On the basis of either flow- cytometric or molecular analysis, 44 of 45 patients with CLL ( 98%; 95% confidence interval [ CI], 88 to 100) had a prediagnostic B- cell clone; in 41 patients ( 91%; 95% CI, 79 to 98), the presence of the B- cell clone was confirmed by both methods. The presence of immunoglobulin heavy- chain variable ( IGHV) genes was determined in 35 of 45 prediagnostic clones ( 78%). Of these clones, 16 ( 46%) were IGHV3 subgroup genes ( including 6 [ 17%] IGHV3- 23 genes) and 9 ( 26%) were IGHV4 subgroup genes ( including 4 [ 11%] IGHV4- 34 genes). Furthermore, 27 of 35 of the IGHV sequences ( 77%) had mutations, with similar distributions after stratification either below or above the median time between the collection of the prediagnostic blood sample and the subsequent CLL diagnosis. Conclusions In peripheral blood obtained up to 77 months before a CLL diagnosis, prediagnostic B- cell clones were present in 44 of 45 patients with CLL. C1 [Landgren, Ola; Hayes, Richard B.; Caporaso, Neil E.] NCI, Canc Res Ctr, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Marti, Gerald E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Albitar, Maher; Ma, Wanlong] Nichols Inst, Quest Diagnost, San Juan Capistrano, CA USA. [Ghia, Paolo] Univ Vita Salute San raffaele, Unit & Lab Lymphoid Malignancies, Dept Oncol, Milan, Italy. [Ghia, Paolo] Ist Sci San Raffaele, Milan, Italy. RP Landgren, O (reprint author), NCI, Canc Res Ctr, Div Canc Epidemiol & Genet, NIH, Bldg 10,Rm 13N240,10 Center Dr, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov RI Ghia, Paolo/K-7138-2016 OI Ghia, Paolo/0000-0003-3750-7342 FU Intramural Research Program of the National Cancer Institute; Italian Association for Cancer Research; CLL Global Research Foundation FX We thank Christine Berg and Philip Prorok of the Division of Cancer Prevention, National Cancer Institute; the Screening Center investigators and staff of the PLCO Cancer Screening Trial; Tom Riley and the staff of Information Management Services; Barbara O'Brien and the staff of Westat; Ruth Pfeiffer of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, for statistical help; Kostas Stamatopoulos of Thessaloniki, Greece, for his most helpful advice and suggestions; and the patients who made this study possible. NR 36 TC 155 Z9 161 U1 1 U2 10 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 12 PY 2009 VL 360 IS 7 BP 659 EP 667 DI 10.1056/NEJMoa0806122 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 405YQ UT WOS:000263260500003 PM 19213679 ER PT J AU Hao, JJ Liu, Y Kruhlak, M Debell, KE Rellahan, BL Shaw, S AF Hao, Jian-Jiang Liu, Yin Kruhlak, Michael Debell, Karen E. Rellahan, Barbara L. Shaw, Stephen TI Phospholipase C-mediated hydrolysis of PIP2 releases ERM proteins from lymphocyte membrane SO JOURNAL OF CELL BIOLOGY LA English DT Article ID T-CELL CHEMOTAXIS; F-ACTIN BINDING; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; EZRIN/RADIXIN/MOESIN PROTEINS; ACTIVATION MECHANISMS; SIGNALING PATHWAY; PLASMA-MEMBRANE; THREONINE 558; FERM DOMAIN; IN-VIVO AB Mechanisms controlling the disassembly of ezrin/radixin/moesin (ERM) proteins, which link the cytoskeleton to the plasma membrane, are incompletely understood. In lymphocytes, chemokine (e. g., SDF-1) stimulation inactivates ERM proteins, causing their release from the plasma membrane and dephosphorylation. SDF-1-mediated inactivation of ERM proteins is blocked by phospholipase C (PLC) inhibitors. Conversely, reduction of phosphatidylinositol 4,5-bisphosphate (PIP2) levels by activation of PLC, expression of active PLC mutants, or acute targeting of phosphoinositide 5-phosphatase to the plasma membrane promotes release and dephosphorylation of moesin and ezrin. Although expression of phosphomimetic moesin (T558D) or ezrin (T567D) mutants enhances membrane association, activation of PLC still relocalizes them to the cytosol. Similarly, in vitro binding of ERM proteins to the cytoplasmic tail of CD44 is also dependent on PIP2. These results demonstrate a new role of PLCs in rapid cytoskeletal remodeling and an additional key role of PIP2 in ERM protein biology, namely hydrolysis-mediated ERM inactivation. C1 [Hao, Jian-Jiang; Liu, Yin; Kruhlak, Michael; Shaw, Stephen] NIH, Natl Canc Inst, Expt Immunol Branch, Bethesda, MD 20892 USA. [Debell, Karen E.; Rellahan, Barbara L.] US FDA, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Shaw, S (reprint author), NIH, Natl Canc Inst, Expt Immunol Branch, Bldg 10, Bethesda, MD 20892 USA. EM shaws@mail.nih.gov FU National Cancer Institute Intramural Research Programs of the National Institutes of Health FX This research was supported by the National Cancer Institute Intramural Research Programs of the National Institutes of Health. NR 50 TC 66 Z9 67 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD FEB 9 PY 2009 VL 184 IS 3 BP 451 EP 462 PG 12 WC Cell Biology SC Cell Biology GA 409PK UT WOS:000263518100013 PM 19204146 ER PT J AU Tondella, ML Carlone, GM Messonnier, N Quinn, CR Meade, BD Burns, DL Cherry, JD Guiso, N Hewlett, EL Edwards, KM Xing, D Giammanco, A von Konig, CHW Han, L Hueston, L Robbins, JB Powell, M Mink, CM Poolman, JT Hildreth, SW Lynn, F Morris, A AF Tondella, M. L. Carlone, G. M. Messonnier, N. Quinn, C. R. Meade, B. D. Burns, D. L. Cherry, J. D. Guiso, N. Hewlett, E. L. Edwards, K. M. Xing, D. Giammanco, A. von Koenig, C. H. Wirsing Han, L. Hueston, L. Robbins, J. B. Powell, M. Mink, C. M. Poolman, J. T. Hildreth, S. W. Lynn, F. Morris, A. TI International Bordetella pertussis assay standardization and harmonization meeting report. Centers for Disease Control and Prevention, Atlanta, Georgia, United States, 19-20 July 2007 SO VACCINE LA English DT Article DE Bordetella pertussis; Whooping cough; Standardization of serologic assays; ELISA; Pertussis vaccines ID ADENYLATE-CYCLASE TOXIN; LINKED IMMUNOSORBENT ASSAYS; TRACHEAL EPITHELIAL-CELLS; HOUSEHOLD EXPOSURE; FILAMENTOUS HEMAGGLUTININ; UNVACCINATED CHILDREN; LABORATORY DIAGNOSIS; MEDIATED-IMMUNITY; VACCINE EFFICACY; MURINE MODEL AB An international meeting on Bordetella pertussis assay standardization and harmonization was held at the Centers for Disease Control and Prevention (CDC), Atlanta, GA, 19-20 July 2007. The goal of the meeting was to harmonize the immunoassays used for pertussis diagnostics and vaccine evaluation, as agreed upon by academic and government researchers, regulatory authorities, vaccine manufacturers, and the World Health Organization (WHO). The primary objectives were (1) to provide epidemiologic, laboratory, and statistical background for support of global harmonization; (2) to overview the current status of global epidemiology, pathogenesis and immunology of pertussis; (3) to develop a consensus opinion on existing gaps in understanding standardization of pertussis assays used for serodiagnosis and vaccine evaluation; and (4) to search for a multicenter process for addressing these priority gaps. Presentations and discussions by content experts addressed these objectives. A prioritized list of action items to improve standardization and harmonization of pertussis assays was identified during a group discussion at the end of the meeting. The major items included: (I) to identify a group that will organize, prepare, maintain, and distribute proficiency panels and key reagents such as reference and control sera; (2) to encourage the development and identification of one or more reference laboratories that can serve as an anchor and resource for other laboratories; (3) to define a performance-based assay method that can serve as a reference point for evaluating laboratory differences; (4) to develop guidance on quality of other reagents, e.g., pertussis toxin and other antigens, and methods to demonstrate their Suitability; (5) to establish an international working group to harmonize the criteria to evaluate the results obtained on reference and proficiency panel sera; (6) to create an inventory to determine the amount of appropriate and well-characterized sera that are available globally to be used as bridging reagents for vaccine licensure: and (7) to seek specific guidance from regulatory authorities regarding the expectations and requirements for the licensure of new multicomponent pertussis vaccines. C1 [Tondella, M. L.; Carlone, G. M.; Messonnier, N.; Quinn, C. R.] Ctr Dis Control & Prevent, CDC, Atlanta, GA 30333 USA. [Burns, D. L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Cherry, J. D.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Guiso, N.] Inst Pasteur, F-75724 Paris, France. [Hewlett, E. L.] Univ Virginia, Sch Med, Charlottesville, VA 22902 USA. [Edwards, K. M.] Vanderbilt Univ Sch Med, Nashville, TN 37232 USA. [Xing, D.] Natl Inst Biol Stand & Controls, Blanche Lane, Potters Bar EN6 3QG, Herts, England. [Giammanco, A.] Univ Palermo, Dept Hyg & Microbiol, I-90127 Palermo, Italy. [von Koenig, C. H. Wirsing] Stadt Krankenanstalten, Inst Hyg & Lab Med, D-47805 Krefeld, Germany. [Han, L.] Dept Publ Hlth, Bur Lab Sci, Boston, MA 02130 USA. [Hueston, L.] Univ Sydney, Westmead Hosp, Ctr Infect Dis & Microbiol, ICPMR, Westmead, NSW 2145, Australia. [Robbins, J. B.] NICHHD, NIH, Bethesda, MD 20892 USA. [Powell, M.] UK Med & Healthcare Prod Regulatory Agcy MHRA, London SW8 5NQ, England. [Mink, C. M.] Harbor UCLA Med Ctr, David Geffen Sch Med, Torrance, CA 90509 USA. [Poolman, J. T.] GlaxoSmithKline Biol, Bacterial Vaccine R&D, B-1330 Rixensart, Belgium. [Hildreth, S. W.] Sanofi Pasteur, Swiftwater, PA 18370 USA. [Lynn, F.] NIAID, NIH, Bethesda, MD 20892 USA. [Morris, A.] Dalhousie Univ, Canadian Ctr Vaccinol, IWK Hlth Ctr, Halifax, NS B3K 6R8, Canada. RP Tondella, ML (reprint author), Ctr Dis Control & Prevent, CDC, 1600 Clifton Rd NE,MS-D11, Atlanta, GA 30333 USA. EM mtondella@cdc.gov NR 93 TC 25 Z9 26 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD FEB 5 PY 2009 VL 27 IS 6 BP 803 EP 814 DI 10.1016/j.vaccine.2008.11.072 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 408FV UT WOS:000263421800001 PM 19071179 ER PT J AU Welch, TJ Evenhuis, J White, DG McDermott, PF Harbottle, H Miller, RA Griffin, M Wise, D AF Welch, Timothy J. Evenhuis, Jason White, David G. McDermott, Patrick F. Harbottle, Heather Miller, Ron A. Griffin, Matt Wise, David TI IncA/C Plasmid-Mediated Florfenicol Resistance in the Catfish Pathogen Edwardsiella ictaluri SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Letter ID SALMONICIDA SUBSP-SALMONICIDA; SALMONELLA-ENTERICA; ESCHERICHIA-COLI; SUSCEPTIBILITY; ANIMALS C1 [Welch, Timothy J.; Evenhuis, Jason] USDA ARS, Natl Ctr Cool & Cold Water Aquaculture, Kearneysville, WV 25430 USA. [White, David G.; McDermott, Patrick F.; Harbottle, Heather; Miller, Ron A.] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [Griffin, Matt; Wise, David] Mississippi State Univ, Thad Cochran Natl Warmwater Aquaculture Ctr, Stoneville, MS 38776 USA. RP Welch, TJ (reprint author), USDA ARS, Natl Ctr Cool & Cold Water Aquaculture, 11861 Leetown Rd, Kearneysville, WV 25430 USA. EM tim.welch@ars.usda.gov NR 16 TC 24 Z9 27 U1 2 U2 5 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 FEB PY 2009 VL 53 IS 2 BP 845 EP 846 DI 10.1128/AAC.01312-08 PG 2 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 397EY UT WOS:000262646500076 PM 19029319 ER PT J AU Yin, JJ Lao, F Fu, PP Wamer, WG Zhao, YL Wang, PC Qiu, Y Sun, BY Xing, GM Dong, JQ Liang, XJ Chen, CY AF Yin, Jun-Jie Lao, Fang Fu, Peter P. Wamer, Wayne G. Zhao, Yuliang Wang, Paul C. Qiu, Yang Sun, Baoyun Xing, Gengmei Dong, Jinquan Liang, Xing-Jie Chen, Chunying TI The scavenging of reactive oxygen species and the potential for cell protection by functionalized fullerene materials SO BIOMATERIALS LA English DT Article DE Gadolinium endohedral metallofullerenol; Fullerenol; Carboxyfullerene; Scavenging activity; Cytoprotection; Reactive oxygen species ID FREE-RADICALS; NANOPARTICLES; C-60; CYTOTOXICITY; GENERATION; CANCER; DAMAGE; C60; METALLOFULLERENES; RELAXIVITY AB We demonstrated that three different types of water-soluble fullerenes materials can intercept all of the major physiologically relevant ROS. C(60)(C(COOH)(2))(2), C(60)(OH)(22), and Gd@C(82)(OH)(22) can protect cells against H(2)O(2)-induced oxidative damage, stabilize the mitochondrial membrane potential and reduce intracellular ROS production with the following relative potencies: Gd@C(82)(OH)(22)>= C(60)(OH)(22)> C(60)(C(COOH)(2))(2). Consistent with their cytoprotective abilities, these derivatives can scavenge the stable 2,2-diplienyl-1-picryhydrazl radical (DPPH), and the reactive oxygen species (ROS) superoxide radical anion (O(2)(center dot-)). singlet oxygen, and hydroxyl radical (HO(center dot)), and can also efficiently inhibit lipid peroxidation in vitro. The observed differences in free radical-scavenging capabilities Support the hypothesis that both chemical Properties, such as Surface chemistry induced differences in electron affinity, and physical properties, such as degree of aggregation, influence the biological and biomedical activities of functionalized fullerenes. This represents the first report that different types of fullerene derivatives can scavenge all physiologically relevant ROS. The role of oxidative stress and damage in the etiology and Progression of many diseases suggests that these fullerene derivatives may be valuable in vivo cytoprotective and therapeutic agents. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Lao, Fang; Zhao, Yuliang; Qiu, Yang; Liang, Xing-Jie; Chen, Chunying] Natl Ctr Nanosci & Technol China, Div Nanomed & Nanobiol, Beijing 100190, Peoples R China. [Yin, Jun-Jie; Wamer, Wayne G.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Zhao, Yuliang; Sun, Baoyun; Xing, Gengmei; Dong, Jinquan; Chen, Chunying] Chinese Acad Sci, Inst High Energy Phys, Lab Bioenvironm Effects Nanomat & Nanosafety, Beijing 100049, Peoples R China. [Fu, Peter P.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Wang, Paul C.] Howard Univ, Dept Radiol, Lab Mol Imaging, Washington, DC 20060 USA. RP Zhao, YL (reprint author), Natl Ctr Nanosci & Technol China, Div Nanomed & Nanobiol, 11 Beiyitiao Zhongguancun, Beijing 100190, Peoples R China. EM zhaoyuliang@ihep.ac.cn; liangxj@nanoctr.cn; chenchy@nanactr.cn RI Yin, Jun Jie /E-5619-2014 FU NCI NIH HHS [5U 54CA091431]; NCRR NIH HHS [2G12RR003048] NR 48 TC 190 Z9 192 U1 12 U2 121 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 2009 VL 30 IS 4 BP 611 EP 621 DI 10.1016/j.biomaterials.2008.09.061 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 389BR UT WOS:000262065500023 PM 18986699 ER PT J AU Li, QH AF Li, Qian H. TI Evaluating Co-primary Endpoints Collectively in Clinical Trials SO BIOMETRICAL JOURNAL LA English DT Article DE Co-primary endpoints; Decision rules; Error rates for individual endpoints; Family wise error rates; Overall hypothesis ID BONFERRONI PROCEDURE; MULTIPLE TESTS AB Often a treatment is assessed by co-primary endpoints so that a comprehensive picture of the treatment effect can be obtained. Co-primary endpoints can be different medical assessments angled at different aspects of a disease, therefore, are used collectively to strengthen evidence for the treatment effect. It is common sense that if a treatment is ineffective, the chance to show that the treatment is effective in all co-primary endpoints should be small. Therefore, it may not be necessary to require all the co-primary endpoints to be statistically significant at the I-sided 0.025 level to control the error rate of wrongly approving an ineffective treatment. Rather it is reasonable to allow certain variation for the p-values within a range close to 0.025. In this paper, statistical methods are developed to derive decision rules to evaluate co-primary endpoints collectively. The decision rules control the error rate of wrongly accepting an ineffective treatment at the level of 0.025 for a study and the error rate at a slightly higher level for a treatment that works for all the co-primary endpoints except perhaps one. The decision rules also control the error rates for individual endpoints. Potential applications in clinical trials are presented. C1 US FDA, Ctr Drug Evaluat & Res, Silve Spring, MD 20993 USA. RP Li, QH (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silve Spring, MD 20993 USA. EM qian.li@fda.hhs.gov NR 13 TC 3 Z9 3 U1 1 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD FEB PY 2009 VL 51 IS 1 BP 137 EP 145 DI 10.1002/bimj.200710497 PG 9 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 417NE UT WOS:000264082000011 PM 19219905 ER EF