FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Kweder, SL Dill, S AF Kweder, S. L. Dill, S. TI Drug Shortages:The Cycle of Quantity and Quality SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article AB Shortages of pharmaceutical drugs pose a serious and growing threat to public health. Although the number of drugs in shortage in the United States in any given year is very small, the number of prescription drug shortages in the country nearly tripled between 2005 and 2010. Drug shortages are becoming more severe as well as more frequent. The affected medicines include cancer treatments, anesthesia drugs, and other drugs that are critical to the treatment and prevention of serious diseases and life-threatening conditions. (The White House, Office of the Press Secretary, Executive Order 13588 Reducing Prescription Drug Shortages (http://www.whitehouse.gov/the-press-office/2011/10/31/executive-order-reducing-prescription-drug-shortages)). C1 [Kweder, S. L.; Dill, S.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Kweder, SL (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM sandra.kweder@fda.hhs.gov NR 13 TC 17 Z9 17 U1 0 U2 14 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 2013 VL 93 IS 3 BP 245 EP 251 DI 10.1038/clpt.2012.235 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 095CN UT WOS:000315312400016 PM 23340474 ER PT J AU Foster, L Allan, MC Khan, A Moore, P Williams, DK Hubbard, M Dixon, L Gurley, BJ AF Foster, L. Allan, M. C. Khan, A. Moore, P. Williams, D. K. Hubbard, M. Dixon, L. Gurley, B. J. TI Multiple Dosing of Ephedra-Free Dietary Supplements: Hemodynamic, Electrocardiographic, and Bacterial Contamination Effects SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID WEIGHT-LOSS SUPPLEMENT; BLOOD-PRESSURE; BITTER ORANGE; GREEN TEA; CAFFEINE METABOLISM; FREE XENADRINE; HEART-RATE; EXERCISE; HUMANS; PHARMACOLOGY AB Four popular ephedra-free dietary supplements were evaluated for their effects on heart rate (HR), blood pressure (BP), and electrocardiographic (ECG) parameters. Twelve healthy men participated in a study randomized for product sequence, with a 21-day washout period between supplement-administration phases. Throughout the study, Holter monitors were used to assess ECG and HR activity. BP was assessed automatically on multiple occasions. The supplements were ingested three times daily for 3 days. Caffeine content, microbial load, and serum caffeine concentrations were determined. Mean systolic (SBP) and diastolic BP (DBP) readings showed significant increases relative to baseline (10.8 +/- 2.5 and 5.3 +/- 3.1 mm Hg, respectively; P < 0.05). All supplements significantly increased HR and decreased bradycardia runs; abnormal atrial/ventricular events were frequently noted. Gastrointestinal and sympathomimetic symptoms were also common. Two supplements were heavily contaminated with Bacillus species. In light of these findings, the use of ephedra-free dietary supplements should be discouraged in individuals with hypertension, diabetes, or other cardiovascular diseases. C1 [Foster, L.] Univ Arkansas Med Sci, Coll Hlth Profess, Dept Nutr & Dietet, Little Rock, AR 72205 USA. [Allan, M. C.] Univ Arkansas Med Sci, Coll Med, Dept Cardiol, Little Rock, AR 72205 USA. [Khan, A.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Moore, P.; Williams, D. K.] Univ Arkansas Med Sci, Coll Publ Hlth, Dept Biostat, Little Rock, AR 72205 USA. [Hubbard, M.; Dixon, L.; Gurley, B. J.] Univ Arkansas Med Sci, Coll Pharm, Dept Pharmaceut Sci, Little Rock, AR 72205 USA. RP Gurley, BJ (reprint author), Univ Arkansas Med Sci, Coll Pharm, Dept Pharmaceut Sci, Little Rock, AR 72205 USA. EM gurleybillyj@uams.edu FU Gustavus & Louise Pfeiffer Medical Research Foundation FX Funding was provided by the Gustavus & Louise Pfeiffer Medical Research Foundation. The views presented in this article do not necessarily reflect those of the US Food and Drug Administration. NR 51 TC 2 Z9 2 U1 1 U2 21 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 2013 VL 93 IS 3 BP 267 EP 274 DI 10.1038/clpt.2012.241 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 095CN UT WOS:000315312400020 PM 23361101 ER PT J AU Ilic, K Hawke, RL Thirumaran, RK Schuetz, EG Hull, JH Kashuba, ADM Stewart, PW Lindley, CM Chen, ML AF Ilic, Katarina Hawke, Roy L. Thirumaran, Ranjit K. Schuetz, Erin G. Hull, J. Heyward Kashuba, Angela D. M. Stewart, Paul W. Lindley, Celeste M. Chen, Mei-Ling TI The Influence of Sex, Ethnicity, and CYP2B6 Genotype on Bupropion Metabolism as an Index of Hepatic CYP2B6 Activity in Humans SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID CYTOCHROME P4502B6 CYP2B6; HUMAN LIVER-MICROSOMES; CATALYTIC-ACTIVITY; IN-VIVO; XENOBIOTIC METABOLISM; GENETIC POLYMORPHISMS; ENZYME-ACTIVITY; EXPRESSION; HYDROXYLATION; CYCLOPHOSPHAMIDE AB The effects of sex, ethnicity, and genetic polymorphism on hepatic CYP2B6 (cytochrome P450 2B6) expression and activity were previously demonstrated in vitro. Race/ethnic differences in CYP2B6 genotype and phenotype were observed only in women. To identify important covariates associated with interindividual variation in CYP2B6 activity in vivo, we evaluated these effects in healthy volunteers using bupropion (Wellbutrin SR GlaxoSmithKline, Research Triangle Park, NC) as a CYP2B6 probe substrate. A fixed 150-mg oral sustained-release dose of bupropion was administered to 100 healthy volunteers comprising four sex/ethnicity cohorts (n = 25 each): Caucasian men and Caucasian, African American, and Hispanic women. Blood samples were obtained at 0 and 6 hours postdose for the measurement of serum bupropion (BU) and hydroxybupropion (HB) concentrations. Whole blood was obtained at baseline for CYP2B6 genotyping. To characterize the relationship between CYP2B6 activity and ethnicity, sex, and genotype when accounting for serum BU concentrations (dose-adjusted log(10)-transformed), analysis of covariance model was fitted in which the dependent variable was CYP2B6 activity represented as the log(10)-transformed, metabolic ratio of HB to BU concentrations. Several CYP2B6 polymorphisms were associated with CYP2B6 activity. Evidence of dependence of CYP2B6 activity on ethnicity or genotype-by-ethnicity interactions was not detected in women. These results suggest that CYP2B6 genotype is the most important patient variable for predicting the level of CYP2B6 activity in women, when measured by the metabolism of bupropion. The bupropion metabolic ratio appears to detect known differences in CYP2B6 activity associated with genetic polymorphism, across different ethnic groups. Prospective studies will be needed to validate the use of bupropion as a probe substrate for clinical use. C1 [Ilic, Katarina; Hawke, Roy L.; Hull, J. Heyward; Kashuba, Angela D. M.; Lindley, Celeste M.] Univ N Carolina, Div Pharmacotherapy & Expt Therapeut, UNC Eshelman Sch Pharm, Chapel Hill, NC USA. [Stewart, Paul W.] Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC USA. [Ilic, Katarina] Univ Belgrade, Sch Pharm, Belgrade, Serbia. [Thirumaran, Ranjit K.; Schuetz, Erin G.] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA. [Chen, Mei-Ling] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Hawke, RL (reprint author), UNC Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, CB 7569,Kerr Hall Rm 3310, Chapel Hill, NC 27599 USA. EM rhawke@email.unc.edu FU Office of Women's Health, U.S. Food and Drug Administration [FDA-SOL-05-00050]; GlaxoSmithKline FX This work was supported by the Office of Women's Health, U.S. Food and Drug Administration [Grant FRP#: FDA-SOL-05-00050]. K. I. was a drug research and development fellow (2006-2008) supported by GlaxoSmithKline. NR 30 TC 8 Z9 8 U1 0 U2 13 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 MAR PY 2013 VL 41 IS 3 BP 575 EP 581 DI 10.1124/dmd.112.048108 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 095SH UT WOS:000315354500008 PM 23238783 ER PT J AU Dey, R Dagur, PK Selvapandiyan, A McCoy, JP Salotra, P Duncan, R Nakhasi, HL AF Dey, Ranadhir Dagur, Pradeep K. Selvapandiyan, Angamuthu McCoy, J. Philip Salotra, Poonam Duncan, Robert Nakhasi, Hira L. TI Live Attenuated Leishmania donovani p27 Gene Knockout Parasites Are Nonpathogenic and Elicit Long-Term Protective Immunity in BALB/c Mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN VISCERAL LEISHMANIASIS; AZAR DERMAL LEISHMANIASIS; REGULATORY T-CELLS; CUTANEOUS LEISHMANIASIS; L-MAJOR; MYCOBACTERIUM-TUBERCULOSIS; PERSISTENT PARASITES; MURINE MACROPHAGES; INTERFERON-GAMMA; CROSS-PROTECTION AB Leishmaniasis causes significant morbidity and mortality worldwide, and no vaccines against this disease are available. Previously, we had shown that the amastigote-specific protein p27 (Ldp27) is a component of an active cytochrome c oxidase complex in Leishmania donovani and that upon deletion of its gene the parasite had reduced virulence in vivo. In this study, we have shown that Ldp27(-/-) parasites do not survive beyond 20 wk in BALB/c mice and hence are safe as an immunogen. Upon virulent challenge, mice 12 wk postimmunization showed significantly lower parasite burden in the liver and spleen. When mice were challenged 20 wk postimmunization, a significant reduction in parasite burden was still noted, suggesting long-term protection by Ldp27(-/-) immunization. Immunization with Ldp27(-/-) induced both pro- and anti-inflammatory cytokine responses and activated splenocytes for enhanced leishmanicidal activity in association with NO production. Protection in both short- and long-term immunized mice after challenge with the wild-type parasite correlated with the stimulation of multifunctional Th1-type CD4 and CD8 T cells. Adoptive transfer of T cells from long-term immunized mice conferred protection against virulent challenge in naive recipient mice, suggesting involvement of memory T cell response in protection against Leishmania infection. Immunization of mice with Ldp27(-/-) also demonstrated cross-protection against Leishmania major and Leishmania braziliensis infection. Our data show that genetically modified live attenuated Ldp27(-/-) parasites are safe, induce protective immunity even in the absence of parasites, and can provide protection against homologous and heterologous Leishmania species. The Journal of Immunology, 2013, 190: 2138-2149. C1 [Dey, Ranadhir; Duncan, Robert; Nakhasi, Hira L.] US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20892 USA. [Dagur, Pradeep K.; McCoy, J. Philip] NHLBI, Flow Cytometry Core, NIH, Bethesda, MD 20892 USA. [Selvapandiyan, Angamuthu] Inst Mol Med, New Delhi 110020, India. [Salotra, Poonam] Indian Council Med Res, Inst Pathol, New Delhi 110029, India. RP Nakhasi, HL (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM Ranadhir.Dey@fda.hhs.gov; Hira.Nakhasi@fda.hhs.gov RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 FU Critical Path Initiative of the Center for Biologics Evaluation and Research, Food and Drug Administration FX This work was supported by intramural funds and the Critical Path Initiative of the Center for Biologics Evaluation and Research, Food and Drug Administration. NR 75 TC 28 Z9 29 U1 1 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2013 VL 190 IS 5 BP 2138 EP 2149 DI 10.4049/jimmunol.1202801 PG 12 WC Immunology SC Immunology GA 091ZT UT WOS:000315089100028 PM 23338240 ER PT J AU Kanal, E Barkovich, AJ Bell, C Borgstede, JP Bradley, WG Froelich, JW Gimbel, JR Gosbee, JW Kuhni-Kaminski, E Larson, PA Lester, JW Nyenhuis, J Schaefer, DJ Sebek, EA Weinreb, J Wilkoff, BL Woods, TO Lucey, L Hernandez, D AF Kanal, Emanuel Barkovich, A. James Bell, Charlotte Borgstede, James P. Bradley, William G., Jr. Froelich, Jerry W. Gimbel, J. Rod Gosbee, John W. Kuhni-Kaminski, Ellisa Larson, Paul A. Lester, James W., Jr. Nyenhuis, John Schaefer, Daniel Joe Sebek, Elizabeth A. Weinreb, Jeffrey Wilkoff, Bruce L. Woods, Terry O. Lucey, Leonard Hernandez, Dina CA Expert Panel MR Safety TI ACR guidance document on MR safe practices: 2013 SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE MR safety; MR; MR safe practices ID RADIOLOGY WHITE PAPER; PATIENT-MANAGEMENT; IMAGING SAFETY; CARDIOVERTER-DEFIBRILLATORS; THERAPEUTIC PROCEDURES; PEDIATRIC-PATIENTS; AMERICAN-COLLEGE; GUIDELINES; PACEMAKER; RECOMMENDATIONS AB Because there are many potential risks in the MR environment and reports of adverse incidents involving patients, equipment and personnel, the need for a guidance document on MR safe practices emerged. Initially published in 2002, the ACR MR Safe Practices Guidelines established de facto industry standards for safe and responsible practices in clinical and research MR environments. As the MR industry changes the document is reviewed, modified and updated. The most recent version will reflect these changes. J. Magn. Reson. Imaging 2013;37:501530. (c) 2013 Wiley Periodicals, Inc. C1 [Kanal, Emanuel; Kuhni-Kaminski, Ellisa; Sebek, Elizabeth A.] Univ Pittsburgh, Med Ctr, Dept Radiol, Pittsburgh, PA 15213 USA. [Barkovich, A. James] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA USA. [Bell, Charlotte] Milford Anesthesia Associates, Milford, CT USA. [Borgstede, James P.] Univ Colorado, Denver, CO 80202 USA. [Bradley, William G., Jr.] Univ Calif San Diego Med Ctr, Dept Radiol, San Diego, CA USA. [Froelich, Jerry W.] Univ Minnesota, Dept Radiol, Minneapolis, MN 55455 USA. [Gimbel, J. Rod] Cardiol Associates E Tennessee, Knoxville, TN USA. [Gosbee, John W.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Gosbee, John W.] Red Forest Consulting LLC, Ann Arbor, MI USA. [Larson, Paul A.] Fox Valley, Radiol Associates, Neenah, WI USA. [Lester, James W., Jr.] Durham Radiol Associates, Raleigh, NC USA. [Nyenhuis, John] Purdue Univ, Dept Elect & Comp Engn, W Lafayette, IN 47907 USA. [Schaefer, Daniel Joe] GE Healthcare, MR Syst Engn, Waukesha, WI USA. [Weinreb, Jeffrey] Yale Univ, Sch Med, New Haven, CT USA. [Wilkoff, Bruce L.] Cleveland Clin, Cleveland, OH 44106 USA. [Woods, Terry O.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Lucey, Leonard; Hernandez, Dina] Amer Coll Radiol, Reston, VA USA. RP Kanal, E (reprint author), Univ Pittsburgh, Med Ctr, Presbyterian Univ Hosp, Presbyterian S Tower,Room 4776, Pittsburgh, PA 15213 USA. EM ekanal@pitt.edu OI Wilkoff, Bruce/0000-0001-8905-9233 NR 43 TC 114 Z9 118 U1 4 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD MAR PY 2013 VL 37 IS 3 BP 501 EP 530 DI 10.1002/jmri.24011 PG 30 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 093VE UT WOS:000315220000001 ER PT J AU Hoffman, AC Evans, SE AF Hoffman, Allison C. Evans, Sarah E. TI Abuse Potential of Non-Nicotine Tobacco Smoke Components: Acetaldehyde, Nornicotine, Cotinine, and Anabasine SO NICOTINE & TOBACCO RESEARCH LA English DT Review ID CONDITIONED PLACE PREFERENCE; RAT STRIATAL SLICES; DISCRIMINATIVE STIMULUS PROPERTIES; MAINSTREAM CIGARETTE-SMOKE; CALCIUM-DEPENDENT MANNER; TASTE-AVERSION PROCEDURE; VENTRAL TEGMENTAL AREA; BRAIN REWARD FUNCTION; NUCLEUS-ACCUMBENS; DRUG DISCRIMINATION AB This review identified published animal studies evaluating the possible abuse potential of acetaldehyde, nornicotine, cotinine, and anabasine based on five commonly used paradigms. These include their effects on midbrain dopamine (DA) levels, drug discrimination and substitution for known drugs of abuse, place conditioning, self-administration behavior, and somatic withdrawal symptoms. Acetaldehyde had mixed effects on midbrain DA levels and drug discrimination; however, it consistently produced a conditioned place preference and supported self-administration. The single available study on withdrawal found that cessation of acetaldehyde administration resulted in a somatic withdrawal syndrome. Nornicotine increased DA in the midbrain, especially in the nucleus accumbens. Although there are no data on place conditioning, it substituted for nicotine in drug discrimination testing, partially substituted for cocaine and amphetamine, and, though only a single study, supported self-administration. Anabasine increased midbrain DA levels and that it partially substituted for nicotine in drug discrimination testing. Cotinine increased midbrain DA levels and substituted for nicotine. The existing literature suggests that acetaldehyde and nornicotine likely possess abuse potential, with anabasine having possible abuse potential. Although some cotinine data were available, it was insufficient to draw conclusions about possible abuse potential. Further research is needed to determine the role of minor alkaloids on tobacco dependence. C1 [Hoffman, Allison C.; Evans, Sarah E.] US FDA, Rockville, MD 20850 USA. RP Hoffman, AC (reprint author), US FDA, Rockville, MD 20850 USA. EM allison.hoffman@fda.hhs.gov NR 119 TC 29 Z9 29 U1 5 U2 19 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD MAR PY 2013 VL 15 IS 3 BP 622 EP 632 DI 10.1093/ntr/nts192 PG 11 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 093UY UT WOS:000315219400003 PM 22990226 ER PT J AU Krzyzanski, W Sutjandra, L Perez-Ruixo, JJ Sloey, B Chow, AT Wang, YM AF Krzyzanski, Wojciech Sutjandra, Liviawati Jose Perez-Ruixo, Juan Sloey, Bethlyn Chow, Andrew T. Wang, Yow-Ming TI Pharmacokinetic and Pharmacodynamic Modeling of Romiplostim in Animals SO PHARMACEUTICAL RESEARCH LA English DT Article DE c-Mpl receptor; peptibody; pharmacodynamics-mediated drug disposition (PDMDD); pharmacokinetic and pharmacodynamic modeling ID MEDIATED DRUG DISPOSITION; HEALTHY-HUMAN VOLUNTEERS; PLATELET LIFE-SPAN; MEGAKARYOCYTE GROWTH; MPL LIGAND; IN-VITRO; THROMBOPOIETIN; RECEPTOR; BINDING; THROMBOCYTOPENIA AB Romiplostim is a novel thrombopoiesis-stimulating peptibody that targets the thrombopoietin c-Mpl receptor, resulting in increased platelet production. The pharmacodynamic-mediated disposition (PDMDD) and its stimulatory effect on platelet production in Sprague-Dawley rats, rhesus monkeys, and cynomolgus monkeys following IV bolus and SC administration at various dose levels were determined. The pharmacokinetic (PK) profile was described by a PDMDD model that accounts for romiplostim binding to the c-Mpl receptor. The PD model contained a series of aging compartments for precursor cells in bone marrow and platelets. The stimulatory function was described by an on-and-off function operating on the fractional receptor occupancy (RO). The threshold effect, ROthr, and K-D parameters were determinants of drug potency, whereas S-max reflected drug efficacy. The model implicated that receptor-mediated clearance was negligible. ROthr estimated occupancies were 0.288, 0.385, 0.771 for rats, rhesus, and cynomolgus monkeys, respectively. The analogous estimated values of K-D were 4.05, 2320, and 429 ng/mL, implying that romiplostim was much more potent in rats, which was confirmed by a dose-response (ratio of peak platelet count to baseline) relationship. The model adequately described romiplostim serum concentrations and platelet counts in rats, rhesus monkeys, and cynomolgus monkeys, and quantified linear clearance, PDMDD, and potency of romiplostim. C1 [Krzyzanski, Wojciech] SUNY Buffalo, Dept Pharmaceut Sci, Buffalo, NY 14260 USA. [Sutjandra, Liviawati; Jose Perez-Ruixo, Juan; Sloey, Bethlyn; Chow, Andrew T.] Amgen Inc, Pharmacokinet & Drug Metab, Thousand Oaks, CA 91320 USA. [Wang, Yow-Ming] US FDA, Off Clin Pharmacol, Washington, DC 20204 USA. [Jose Perez-Ruixo, Juan] Amgen Inc, Pharmacokinet & Drug Metab Dept, Quantitat Pharmacol, Valencia 46530, Spain. RP Perez-Ruixo, JJ (reprint author), Amgen Inc, Pharmacokinet & Drug Metab Dept, Quantitat Pharmacol, Picayo 3, Valencia 46530, Spain. EM juanjose@amgen.com FU Amgen Inc. FX This study was supported by an educational donation for the Fellowship in PK/PD Hematology from Amgen Inc. The authors wish to thank Teresa Wong for the bioanalytical support, Michelle Zakson for editing/writing assistance. NR 46 TC 7 Z9 7 U1 0 U2 15 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORDR JI Pharm. Res. PD MAR PY 2013 VL 30 IS 3 BP 655 EP 669 DI 10.1007/s11095-012-0894-2 PG 15 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 094WF UT WOS:000315294800004 PM 23250851 ER PT J AU Agarwal, S Chinn, L Zhang, L AF Agarwal, Sheetal Chinn, Leslie Zhang, Lei TI An Overview of Transporter Information in Package Inserts of Recently Approved New Molecular Entities SO PHARMACEUTICAL RESEARCH LA English DT Editorial Material DE drug-drug interaction; labeling; package insert; regulatory; transporter C1 [Agarwal, Sheetal; Chinn, Leslie; Zhang, Lei] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Zhang, L (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Bldg 51,Room 3106,White Oak 10903 New Hampshire A, Silver Spring, MD 20993 USA. EM leik.zhang@fda.hhs.gov NR 10 TC 9 Z9 9 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-DORDR JI Pharm. Res. PD MAR PY 2013 VL 30 IS 3 BP 899 EP 910 DI 10.1007/s11095-012-0924-0 PG 12 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 094WF UT WOS:000315294800025 PM 23187863 ER PT J AU Lerner, H Whang, J Nipper, R AF Lerner, Herbert Whang, Joyce Nipper, Rebecca TI Benefit-risk paradigm for clinical trial design of obesity devices: FDA proposal SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Review DE Benefit-risk paradigm for obesity reduction; Obesity treatment; Weight reduction devices ID CORONARY-HEART-DISEASE; BODY-MASS INDEX; WEIGHT-LOSS; OVERWEIGHT; ASSOCIATION; ADULTS; METAANALYSIS; HYPERTENSION AB Diet and exercise, except in controlled circumstances, have not been shown to provide effective and prolonged weight loss for the majority of those who are obese. Several older drugs intended to reduce weight have been withdrawn from the market, and the new drugs show only modest weight loss. Surgical intervention, specifically procedures that alter the normal gastrointestinal anatomy, does provide prolonged periods of sustained weight loss, with rebound weight gain over time. A variety of medical devices to assist in weight reduction have been studied, but only two are legally marketed devices for obesity. The authors propose a new paradigm for devices intended to treat obesity, based on a benefit-risk determination, with the hope to provide sponsors an a priori tool for systematic assessment of the risks associated with the devices intended for treatment of obesity and to suggest appropriate levels of benefit for devices with different risk levels. The paradigm is not intended to determine the class of a device from a regulatory perspective. This approach was conceived at a Food and Drug Administration (FDA) co-sponsored workshop in October, 2011 and formally presented to an FDA advisory panel for discussion in May 2012. C1 [Lerner, Herbert; Whang, Joyce; Nipper, Rebecca] US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Silver Spring, MD 20993 USA. [Lerner, Herbert] US FDA, Div Reprod Gastrorenal & Urol Devices, CDRH, ODE, Silver Spring, MD 20993 USA. RP Lerner, H (reprint author), US FDA, Div Reprod Gastrorenal & Urol Devices, CDRH, ODE, WO66 Room G114,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Obesitydevice@fda.hhs.gov NR 14 TC 5 Z9 5 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD MAR PY 2013 VL 27 IS 3 BP 702 EP 707 DI 10.1007/s00464-012-2724-3 PG 6 WC Surgery SC Surgery GA 092TN UT WOS:000315145500002 PM 23247746 ER PT J AU Rao, VA AF Rao, V. Ashutosh TI Iron Chelators with Topoisomerase-Inhibitory Activity and Their Anticancer Applications SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID MEDIATED DNA-DAMAGE; ADVANCED BREAST-CANCER; ANTHRACYCLINE-INDUCED CARDIOTOXICITY; DOXORUBICIN-INDUCED CARDIOTOXICITY; MITOCHONDRIAL NADH DEHYDROGENASE; ISONICOTINOYL HYDRAZONE CLASS; SELECTIVE ANTITUMOR-ACTIVITY; ACUTE LYMPHOBLASTIC-LEUKEMIA; SILIBININ SUPPRESSES GROWTH; CONGESTIVE HEART-FAILURE AB Significance: Iron and topoisomerases are abundant and essential cellular components. Iron is required for several key processes such as DNA synthesis, mitochondrial electron transport, synthesis of heme, and as a co-factor for many redox enzymes. Topoisomerases serve as critical enzymes that resolve topological problems during DNA synthesis, transcription, and repair. Neoplastic cells have higher uptake and utilization of iron, as well as elevated levels of topoisomerase family members. Separately, the chelation of iron and the cytotoxic inhibition of topoisomerase have yielded potent anticancer agents. Recent Advances: The chemotherapeutic drugs doxorubicin and dexrazoxane both chelate iron and target topoisomerase 2 alpha (top2 alpha). Newer chelators such as di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone and thiosemicarbazone -24 have recently been identified as top2 alpha inhibitors. The growing list of agents that appear to chelate iron and inhibit topoisomerases prompts the question of whether and how these two distinct mechanisms might interplay for a cytotoxic chemotherapeutic outcome. Critical Issues: While iron chelation and topoisomerase inhibition each represent mechanistically advantageous anticancer therapeutic strategies, dual targeting agents present an attractive multi-modal opportunity for enhanced anticancer tumor killing and overcoming drug resistance. The commonalities and caveats of dual inhibition are presented in this review. Future Directions: Gaps in knowledge, relevant biomarkers, and strategies for future in vivo studies with dual inhibitors are discussed. Antioxid. Redox Signal. 18, 930-955. C1 US FDA, Div Therapeut Prot, Biochem Lab, Off Biotechnol Prod,Off Pharmaceut Sci,Ctr Drug E, Bethesda, MD 20892 USA. RP Rao, VA (reprint author), US FDA, Div Therapeut Prot, Biochem Lab, Off Biotechnol Prod,Off Pharmaceut Sci,Ctr Drug E, HFD-122,NIH Bldg 29A,Room 2A-11, Bethesda, MD 20892 USA. EM ashutosh.rao@fda.hhs.gov FU Food and Drug Administration Critical Path Initiative; National Cancer Institute FX V.A.R. is thankful to the Food and Drug Administration Critical Path Initiative and the National Cancer Institute for research support. The author wishes to thank Drs. Emily Shacter (FDA), Eugene Herman (FDA), and Yves Pommier (NCI) for insightful discussions and encouragement. Drs. John Nittis (University of Illinois), Neil Osheroff (Vanderbilt University), and Tomas Simunek (Charles University in Prague) are acknowledged for graciously agreeing to allow an adaptation of their published figures. Drs. Jennifer Dickey (FDA) and Melanie Simpson (NCI) are thanked for their critical reading of the article. NR 308 TC 11 Z9 11 U1 2 U2 38 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD MAR PY 2013 VL 18 IS 8 BP 930 EP 955 DI 10.1089/ars.2012.4877 PG 26 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 079OO UT WOS:000314180300005 PM 22900902 ER PT J AU Sun, W Eckels, KH Putnak, JR Lyons, AG Thomas, SJ Vaughn, DW Gibbons, RV Fernandez, S Gunther, VJ Mammen, MP Statler, JD Innis, BL AF Sun, Wellington Eckels, Kenneth H. Putnak, J. Robert Lyons, Arthur G. Thomas, Stephen J. Vaughn, David W. Gibbons, Robert V. Fernandez, Stefan Gunther, Vicky J. Mammen, Mammen P., Jr. Statler, John D. Innis, Bruce L. TI Experimental Dengue Virus Challenge of Human Subjects Previously Vaccinated With Live Attenuated Tetravalent Dengue Vaccines SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE dengue; tetravalent vaccine; live virus challenge ID FLAVIVIRUS-NAIVE ADULTS; PHASE-I TRIAL; HUMAN VOLUNTEERS; CANDIDATE VACCINES; RHESUS-MONKEYS; 4 SEROTYPES; IMMUNOGENICITY; INFECTION; SAFETY; FORMULATIONS AB Background. Protection against dengue requires immunity against all 4 serotypes of dengue virus (DENV). Experimental challenge may be useful in evaluating vaccine-induced immunity. Methods. Ten subjects previously vaccinated with a live attenuated tetravalent dengue vaccine (TDV) and 4 DENV-naive control subjects were challenged by subcutaneous inoculation of either 10(3) plaque-forming units (PFU) of DENV-1 or 10(5) PFU of DENV-3. Two additional subjects who did not develop DENV-3 neutralizing antibody (NAb) from TDV were revaccinated with 104 PFU of live attenuated DENV-3 vaccine to evaluate memory response. Results. All 5 TDV recipients were protected against DENV-1 challenge. Of the 5 TDV recipients challenged with DENV-3, 2 were protected. All DENV-3-challenge subjects who developed viremia also developed elevated liver enzyme levels, and 2 had values that were >10 times greater than normal. Of the 2 subjects revaccinated with DENV-3 vaccine, 1 showed a secondary response to DENV-2, while neither showed such response to DENV-3. All 4 control subjects developed dengue fever from challenge. Protection was associated with presence of NAb, although 1 subject was protected despite a lack of measurable NAb at the time of DENV-1 challenge. Conclusions. Vaccination with TDV induced variable protection against subcutaneous challenge. DENV-3 experimental challenge was associated with transient but marked elevations of transaminases. C1 [Sun, Wellington; Putnak, J. Robert; Lyons, Arthur G.; Thomas, Stephen J.; Vaughn, David W.; Gibbons, Robert V.; Fernandez, Stefan; Gunther, Vicky J.] Walter Reed Army Inst Res, Dept Virus Dis, Silver Spring, MD USA. [Eckels, Kenneth H.] Walter Reed Army Inst Res, Pilot Bioprod Facil, Silver Spring, MD USA. [Statler, John D.] Walter Reed Army Med Ctr, Dept Radiol, Washington, DC 20307 USA. [Innis, Bruce L.] GlaxoSmithKline, Vaccine Discovery & Dev, King Of Prussia, PA USA. [Mammen, Mammen P., Jr.] Armed Forces Res Inst Med Sci, Dept Virol, Bangkok 10400, Thailand. RP Sun, W (reprint author), CBER, Div Vaccines & Related Prod Applicat, Off Vaccine Res & Review, 1451 Rock Ville Pike,Rm 2302, Rockville, MD 20852 USA. EM wellington.sun@fda.hhs.gov RI Lyons, Arthur/B-8923-2011 FU US Army Medical Research and Materiel Command FX This work was supported by the US Army Medical Research and Materiel Command. NR 41 TC 42 Z9 43 U1 0 U2 13 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR 1 PY 2013 VL 207 IS 5 BP 700 EP 708 DI 10.1093/infdis/jis744 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 089FD UT WOS:000314894600002 PM 23225894 ER PT J AU Coleman, AS Akkoyunlu, M AF Coleman, Adam S. Akkoyunlu, Mustafa TI Bacterial Polysaccharide-Mediated Downregulation of TACI and B-Cell Apoptosis Contribute to the Hyporesponsiveness Against Bacterial Polysaccharides Vaccines SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID IMMUNIZATION; EXPRESSION; RESPONSES; MEMORY; BAFF; MICE C1 [Coleman, Adam S.; Akkoyunlu, Mustafa] US FDA, Lab Bacterial Polysaccharides, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Akkoyunlu, M (reprint author), US FDA, 29 Lincoln Dr,Bldg 29,Rm 516-B, Bethesda, MD 20892 USA. EM mustafa.akkoyunlu@fda.hhs.gov NR 10 TC 1 Z9 1 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR 1 PY 2013 VL 207 IS 5 BP 872 EP 873 DI 10.1093/infdis/jis770 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 089FD UT WOS:000314894600023 PM 23242545 ER PT J AU Zhu, PX Degheidy, HA Marti, GE Li, SH Abbasi, F Wiestner, A Amstutz, P Tang, CM AF Zhu, Peixuan Degheidy, Heba A. Marti, Gerald E. Li, Shuhong Abbasi, Fatima Wiestner, Adrian Amstutz, Platte Tang, Cha-Mei TI Quantitative detection of zeta-chain-associated protein 70 expression in chronic lymphocytic leukemia SO LEUKEMIA & LYMPHOMA LA English DT Article DE Chronic lymphocytic leukemia (CLL); ZAP-70; flow cytometry; immunomagnetic fluorescence assay; Signalyte-II spectrofluorometer ID GENE MUTATION STATUS; ZAP70 MESSENGER-RNA; ZAP-70 EXPRESSION; CD38 EXPRESSION; GENOMIC ABERRATIONS; PROGNOSTIC MARKER; B-CELLS; PROGRESSION; MICRORNA; REVEALS AB Overexpression of zeta-chain-associated protein 70 (ZAP-70) was recently recognized as an independent prognostic marker for the aggressive form of chronic lymphocytic leukemia (CLL). The objective of this study was to demonstrate the feasibility and implementation of quantitative detection of ZAP-70 protein in B cells to clearly distinguish patients with CLL with the aggressive form of the disease. B cells were isolated from patient blood and lysed. Released ZAP-70 protein was detected using an immunomagnetic fluorescence assay. The assay protocol was developed using Jurkat cells and recombinant ZAP-70 (rZAP-70). The limit of detection was determined to be lower than 125 Jurkat cells and 39 pg of rZAP-70 protein. The signal response was linear over a wide dynamic range, from 125 to 40 000 Jurkat cells per test (R-2 = 0.9987) and from 0 to 40 000 pg rZAP-70 protein per test (R-2 = 0.9928). The results from 20 patients with CLL correlated strongly with flow cytometry analysis. Concordance between the two methods for positive and negative results was 100% (7/7) and 92% (12/13), respectively, while the overall concordance between the two methods was 95%. The assay reported here is a simple, reliable and reproducible method for quantitative detection of ZAP-70 in patient leukemic cells, without the need for cell fixation or permeabilization. The ZAP-70 signal was linear over a wide dynamic range, which we believe enables quantitative assessment of small changes in ZAP-70 expression over the course of the disease and in response to therapeutic intervention. C1 [Zhu, Peixuan; Li, Shuhong; Amstutz, Platte; Tang, Cha-Mei] Creatv MicroTech Inc, Potomac, MD 20854 USA. [Degheidy, Heba A.; Marti, Gerald E.; Abbasi, Fatima] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Wiestner, Adrian] NHLBI, NIH, Bethesda, MD 20892 USA. RP Zhu, PX (reprint author), Creatv MicroTech Inc, 11609 Lake Potomac Dr, Potomac, MD 20854 USA. EM pzhu@creatvmicrotech.com FU NHLBI, NIH; National Institutes of Health [R44 CA094430-02] FX The authors thank Susan Soto in Dr. Wiestner's laboratory for assistance in the collection of CLL blood samples and Yong-Qiang Wang for assistance in preparation of PBMCs from the samples. This research was supported in part by the intramural research program of NHLBI, NIH.; This work was supported by a grant R44 CA094430-02 from the National Institutes of Health. NR 33 TC 0 Z9 0 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD MAR PY 2013 VL 54 IS 3 BP 579 EP 586 DI 10.3109/10428194.2012.715349 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 084KR UT WOS:000314538600024 PM 22839722 ER PT J AU Kaufman, A Cameron, LD Peters, E Rothman, A Klein, W AF Kaufman, Annette Cameron, Linda D. Peters, Ellen Rothman, Alex Klein, William CA CTP TI SOCIAL POLICY PANEL ON CIGARETTE GRAPHIC WARNING LABELS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Kaufman, Annette; Klein, William] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Cameron, Linda D.] Univ Calif Merced, Psychol, Merced, CA USA. [Peters, Ellen] Ohio State Univ, Psychol, Columbus, OH 43210 USA. [Rothman, Alex] Univ Minnosota, Psychol, Minneapolis, MN USA. [CTP] US FDA, Ctr Tobacco Prod, Rockville, MD 20857 USA. EM kaufmana@mail.nih.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 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA 2054 BP S68 EP S68 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928000267 ER PT J AU Portnoy, DB Choiniere, CJ AF Portnoy, David B. Choiniere, Conrad J. TI TOBACCO-RELATED RISK PERCEPTIONS IN THE REGULATION OF TOBACCO PRODUCTS AT THE FDA CENTER FOR TOBACCO PRODUCTS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Portnoy, David B.; Choiniere, Conrad J.] US FDA, Ctr Tobacco Prod, Rockville, MD 20850 USA. EM david.portnoy@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 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA 3086 BP S172 EP S172 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928001247 ER PT J AU Tanaka, M Kobrin, S Portnoy, D Moser, R AF Tanaka, Miho Kobrin, Sarah Portnoy, David Moser, Richard TI SHARED DECISION MAKING (SDM) PREVALENCE FOR MAMMOGRAPHY SCREENING AMONG WOMEN AGED 40 TO 49 YEARS: THE 2011-12 HEALTH INFORMATION NATIONAL TRENDS SURVEY(HINTS4) SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Tanaka, Miho; Kobrin, Sarah; Moser, Richard] NCI, Rockville, MD 20852 USA. [Portnoy, David] US FDA, Rockville, MD 20857 USA. EM miho.tanaka@nih.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 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD MAR PY 2013 VL 45 SU 2 MA D-026 BP S264 EP S264 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V47BT UT WOS:000209928002011 ER PT J AU Chen, KJ Chen, L Felten, R Vaezy, S Ohara, M Ogden, N AF Chen, Kejing Chen, Long Felten, Richard Vaezy, Shahram Ohara, Michael Ogden, Neil TI INTERSTITIAL LASER DEVICES IN MEDICAL APPLICATIONS: REGULATORY PERSPECTIVE SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 US FDA, Off Device Evaluat, Silver Spring, MD USA. US FDA, Off Vitro Diagnost & Radiol Hlth, 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 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2013 VL 45 SU 25 MA 220 BP 63 EP 63 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA V38YX UT WOS:000209379800182 ER PT J AU Tsai, TT Box, TL Gethoffer, H Noonan, G Varosy, PD Maddox, TM Fihn, SD Gross, TP Jesse, RL Rumsfeld, JS AF Tsai, Thomas T. Box, Tamara L. Gethoffer, Hans Noonan, Gregory Varosy, Paul D. Maddox, Thomas M. Fihn, Stephan D. Gross, Thomas P. Jesse, Robert L. Rumsfeld, John S. TI Feasibility of Proactive Medical Device Surveillance The VA Clinical Assessment Reporting and Tracking (CART) Program SO MEDICAL CARE LA English DT Article DE patient safety; device safety; cardiovascular ID COMPREHENSIVE APPROACH; SAFETY NET; STENTS; HOLES AB Background: Timely identification and reporting of medical device problems is critical to postmarket device surveillance programs to maximize patient safety. Cardiac catheterization laboratories are high-device utilization areas well suited for device surveillance. Objective: To demonstrate the feasibility of the national VA Clinical Assessment, Reporting, and Tracking (CART) system, embedded in the electronic health record of all 76 VA cardiac catheterization laboratories, to document unexpected problems with medical devices at the point of care. Methods: We evaluated 260,258 consecutive cardiac catheterization and/or percutaneous coronary intervention procedures on 175,098 Veterans between August 2006 and February 2012. Unexpected device problems (UDPs) encountered for any equipment used during a procedure were entered by clinicians at the point of care as part of regular care documentation. All UDPs were reviewed in collaboration with the FDA to ascertain the likelihood of a device defect (eg, in manufacture or design) and/or contributing to a procedural complication (level I, unlikely; level II, possibly; level III, likely). Results: Of the 260,258 procedure reports, 974 (0.37%) UDP's were reported by 71 (92.2%) of the 76 VA hospitals. After triage, 739 (75.9%) were deemed level I, 196 (20.1%) level II, and 39 (4.0%) level III. Of the 39 level III reports, 12 (30.7%) are in the submission phase as a FDA MedWatch report. The number of monthly UDP reports increased significantly from 2006 to 2012 (P < 0.001). Conclusions: Leveraging a clinical application embedded in the electronic health record and in collaboration with FDA, a proactive national cardiac device surveillance program has been successfully implemented in the VA. C1 [Tsai, Thomas T.; Box, Tamara L.; Gethoffer, Hans; Noonan, Gregory; Varosy, Paul D.; Maddox, Thomas M.; Rumsfeld, John S.] Univ Colorado, VA Eastern Colorado Hlth Care Syst, Dept Med, CART Coordinating Ctr, Denver, CO 80220 USA. [Fihn, Stephan D.] VA Hlth Serv R&D, Off Analyt & Business Intelligence, Seattle, WA USA. [Fihn, Stephan D.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Gross, Thomas P.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Jesse, Robert L.; Rumsfeld, John S.] VA Cent Off, Washington, DC USA. [Jesse, Robert L.] Richmond VA Med Ctr, Richmond, VA USA. RP Tsai, TT (reprint author), Univ Colorado, VA Eastern Colorado Hlth Care Syst, Dept Med, CART Coordinating Ctr,Cardiol Sect 111B, 1055 Clermont St, Denver, CO 80220 USA. EM thomas.tsai@va.gov NR 18 TC 11 Z9 11 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD MAR PY 2013 VL 51 IS 3 SU 1 BP S57 EP S61 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AJ7YH UT WOS:000337917300010 PM 23407013 ER PT J AU Chang, SJ O'Connor, PM Slade, BA Woo, EJ AF Chang, Soju O'Connor, Patrick M. Slade, Barbara A. Woo, Emily Jane TI U.S. Postlicensure safety surveillance for adolescent and adult tetanus, diphtheria and acellular pertussis vaccines: 2005-2007 SO VACCINE LA English DT Article DE Tetanus toxoid; Reduced diphtheria toxoid and acellular pertussis (Tdap) vaccines; VAERS; Postlicensure safety ID REPORTING-SYSTEM VAERS; UNITED-STATES; BELLS-PALSY; VACCINATION; IMMUNIZATION; RISK; MYOPERICARDITIS; MYOCARDITIS; CHILDREN; SYNCOPE AB Background: Pre-licensure clinical trials for two U.S. licensed tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccines did not reveal any major safety concerns. However, routine use in large adolescent and adult populations could reveal rare and potentially serious adverse events (AEs). Methods: To characterize reported AEs following Tdap vaccination and identify potential safety concerns warranting further evaluation, we analyzed data from the Vaccine Adverse Event Reporting System (VAERS) and assessed the frequency and proportions of AEs and reporting rates (reports per 100,000 vaccine doses distributed). Results: A total of 2090 reports (7% were serious; 55% listed Tdap alone) involving Tdap vaccines were submitted to VAERS May 2005-June 2007. The crude reporting rate was 10.2 per 100,000 vaccine doses distributed. The median age of vaccinees was 22 years, and the female to male ratio was about 2 to 1. The majority of reports described common local and systemic signs and symptoms, such as injection site reactions, fever, and headache. Rarely reported AEs included myopericarditis, demyelinating diseases of the central nervous system, Guillain-Barre Syndrome, syncope, encephalopathy/encephalitis, seizure, Bell's palsy, anaphylaxis, and thrombocytopenia. Conclusions: Because adolescents and adults were not routinely vaccinated against pertussis in the past, this surveillance summary provides important - and reassuring - information about the use of Tdap in these age groups. Although subject to the limitations of passive surveillance, the findings of this VAERS review support the pre-licensure clinical trial data with regard to the safety of the U.S. licensed Tdap vaccines. Continued monitoring of clinically significant AEs that are temporally associated with Tdap vaccination and further assessment of such events using controlled observational studies may provide additional information about the safety of these vaccines. Published by Elsevier Ltd. C1 [Chang, Soju; Woo, Emily Jane] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [O'Connor, Patrick M.] Gen Prevent Med Residency Program, Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Slade, Barbara A.] US Ctr Dis Control & Prevent CDC, Immunizat Safety Off, Div Healthcare Qual Promot, Atlanta, GA USA. RP Chang, SJ (reprint author), US FDA, Div Epidemiol, Off Biostat & Epidemiol, Ctr Biol Res & Evaluat, 1401 Rockville Pike,HFM-222, Rockville, MD 20852 USA. EM soju.chang@nih.hhs.gov NR 29 TC 12 Z9 12 U1 0 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD FEB 27 PY 2013 VL 31 IS 10 BP 1447 EP 1452 DI 10.1016/j.vaccine.2012.10.097 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 098HM UT WOS:000315540000016 PM 23142308 ER PT J AU Salazar, JK Deng, KP Tortorello, ML Brandl, MT Wang, H Zhang, W AF Salazar, Joelle K. Deng, Kaiping Tortorello, Mary Lou Brandl, Maria T. Wang, Hui Zhang, Wei TI Genes ycfR, sirA and yigG Contribute to the Surface Attachment of Salmonella enterica Typhimurium and Saintpaul to Fresh Produce SO PLOS ONE LA English DT Article ID COLI BIOFILM FORMATION; PHYLOGENETIC ANALYSIS; OXIDATIVE STRESS; RAW PRODUCE; FOOD SAFETY; PATHOGENS; RESPONSES; OUTBREAKS; PROTEIN; LIKELIHOOD AB Salmonella enterica is a frequent contaminant of minimally-processed fresh produce linked to major foodborne disease outbreaks. The molecular mechanisms underlying the association of this enteric pathogen with fresh produce remain largely unexplored. In our recent study, we showed that the expression of a putative stress regulatory gene, ycfR, was significantly induced in S. enterica upon exposure to chlorine treatment, a common industrial practice for washing and decontaminating fresh produce during minimal processing. Two additional genes, sirA involved in S. enterica biofilm formation and yigG of unknown function, were also found to be differentially regulated under chlorine stress. To further characterize the roles of ycfR, sirA, and yigG in S. enterica attachment and survival on fresh produce, we constructed in-frame deletions of all three genes in two different S. enterica serovars, Typhimurium and Saintpaul, which have been implicated in previous disease outbreaks linked to fresh produce. Bacterial attachment to glass and polystyrene microtiter plates, cell aggregation and hydrophobicity, chlorine resistance, and surface attachment to intact spinach leaf and grape tomato were compared among wild-type strains, single-gene deletion mutants, and their respective complementation mutants. The results showed that deletions of ycfR, sirA, and yigG reduced bacterial attachment to glass and polystyrene as well as fresh produce surface with or without chlorine treatment in both Typhimurium and Saintpaul. Deletion of ycfR in Typhimurium significantly reduced bacterial chlorine resistance and the attachment to the plant surfaces after chlorinated water washes. Deletions of ycfR in Typhimurium and yigG in Saintpaul resulted in significant increase in cell aggregation. Our findings suggest that ycfR, sirA, and yigG collectively contribute to S. enterica surface attachment and survival during post-harvest minimal processing of fresh produce. C1 [Salazar, Joelle K.; Zhang, Wei] IIT, Inst Food Safety & Hlth, Bedford Pk, IL USA. [Deng, Kaiping; Tortorello, Mary Lou] US FDA, Bedford Pk, IL USA. [Brandl, Maria T.] ARS, Produce Safety & Microbiol Res Unit, Western Reg Res Ctr, USDA, Albany, CA USA. [Wang, Hui] Chinese Acad Sci, Food Safety Res Ctr, Shanghai Inst Biol Sci, Shanghai, Peoples R China. RP Zhang, W (reprint author), IIT, Inst Food Safety & Hlth, Bedford Pk, IL USA. EM zhangw@iit.edu FU United States Department of Agriculture National Institute of Food and Agriculture Grant under the Agriculture and Food Research Initiative Foundational Program Priority Area of Foodborne Pathogen-Plant Interactions [2011-67017-30016, A1301] FX This work was supported by the United States Department of Agriculture National Institute of Food and Agriculture Grant no. 2011-67017-30016 under the Agriculture and Food Research Initiative Foundational Program Priority Area of Foodborne Pathogen-Plant Interactions (Program Area Code - A1301). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 10 Z9 10 U1 3 U2 30 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 22 PY 2013 VL 8 IS 2 AR e57272 DI 10.1371/journal.pone.0057272 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 113IC UT WOS:000316658800096 PM 23451197 ER PT J AU Biju, KC Santacruz, RA Chen, C Zhou, Q Yao, JM Rohrabaugh, SL Clark, RA Roberts, JL Phillips, KA Imam, SZ Li, SL AF Biju, K. C. Santacruz, Rene A. Chen, Cang Zhou, Qing Yao, Jiemin Rohrabaugh, Sara L. Clark, Robert A. Roberts, James L. Phillips, Kimberley A. Imam, Syed Z. Li, Senlin TI Bone marrow-derived microglia-based neurturin delivery protects against dopaminergic neurodegeneration in a mouse model of Parkinson's disease SO NEUROSCIENCE LETTERS LA English DT Article DE Parkinson's disease; Gene therapy; Neurodegenerative disease; Neurotrophic factors; Dopamine ID GENE-THERAPY; NEUROTROPHIC FACTOR; TRANSPLANTATION; GDNF; CNS AB Although neurotrophic factors have long been recognized as potent agents for protecting against neuronal degeneration, clinical success in treating Parkinson's disease and other neurodegenerative disorders has been hindered by difficulties in delivery of trophic factors across the blood brain barrier (BBB). Bone marrow hematopoietic stem cell-based gene therapy is emerging as a promising tool for overcoming drug delivery problems, as myeloid cells can cross the BBB and are recruited in large numbers to sites of neurodegeneration, where they become activated microglia that can secrete trophic factors. We tested the efficacy of bone marrow-derived microglial delivery of neurturin (NTN) in protecting dopaminergic neurons against neurotoxin-induced death in mice. Bone marrow cells were transduced ex vivo with lentivirus expressing the NTN gene driven by a synthetic macrophage-specific promoter. Infected bone marrow cells were then collected and transplanted into recipient animals. Eight weeks after transplantation, the mice were injected with the neurotoxin1-methyl-4-phenyl-1,2,3,6-tetrahydropuridine (MPTP) for seven days to induce dopaminergic neurodegeneration. Microglia-mediated NTN delivery dramatically ameliorated MPTP-induced degeneration of tyrosine hydroxylase (TH)-positive neurons of the substantia nigra and their terminals in the striatum. Microglia-mediated NTN delivery also induced significant recovery of synaptic marker staining in the striatum of MPTP-treated animals. Functionally, NTN treatment restored MPTP-induced decline in general activity, rearing behavior, and food intake. Thus, bone marrow-derived microglia can serve as cellular vehicles for sustained delivery of neurotrophic factors capable of mitigating dopaminergic injury. Published by Elsevier Ireland Ltd. C1 [Biju, K. C.; Santacruz, Rene A.; Chen, Cang; Zhou, Qing; Yao, Jiemin; Rohrabaugh, Sara L.; Clark, Robert A.; Li, Senlin] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Santacruz, Rene A.; Li, Senlin] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Roberts, James L.; Li, Senlin] Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Clark, Robert A.; Roberts, James L.; Li, Senlin] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Roberts, James L.] Trinity Univ, Dept Biol, San Antonio, TX 78212 USA. [Phillips, Kimberley A.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA. [Imam, Syed Z.] US FDA, Div Neurotoxicol, NCTR, Jefferson, AR USA. RP Li, SL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM lis1@uthscsa.edu OI Phillips, Kimberley/0000-0002-5517-3596 FU NIH [NS046004, AG024579]; Veterans Health Administration; NIH Clinical and Translational Science Award [UL1 TR0000149] FX This work was supported by NIH grants (NS046004 and AG024579), a Merit Review Grant from the Veterans Health Administration, and a NIH Clinical and Translational Science Award (UL1 TR0000149) Pilot Project grant awarded to S.L. NR 23 TC 11 Z9 11 U1 0 U2 13 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 FEB 22 PY 2013 VL 535 BP 24 EP 29 DI 10.1016/j.neulet.2012.12.034 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 095XK UT WOS:000315368100005 PM 23295906 ER PT J AU Schaer, DJ Buehler, PW Alayash, AI Belcher, JD Vercellotti, GM AF Schaer, Dominik J. Buehler, Paul W. Alayash, Abdu I. Belcher, John D. Vercellotti, Gregory M. TI Hemolysis and free hemoglobin revisited: exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins SO BLOOD LA English DT Article ID SICKLE-CELL-DISEASE; LOW-DENSITY-LIPOPROTEIN; NITRIC-OXIDE BIOAVAILABILITY; RED-BLOOD-CELLS; PULMONARY-HYPERTENSION; HAPTOGLOBIN THERAPY; STORAGE LESION; STORED-BLOOD; GUINEA-PIGS; HEMOPEXIN AB Hemolysis occurs in many hematologic and nonhematologic diseases. Extracellular hemoglobin (Hb) has been found to trigger specific pathophysiologies that are associated with adverse clinical outcomes in patients with hemolysis, such as acute and chronic vascular disease, inflammation, thrombosis, and renal impairment. Among the molecular characteristics of extracellular Hb, translocation of the molecule into the extravascular space, oxidative and nitric oxide reactions, hemin release, and molecular signaling effects of hemin appear to be the most critical. Limited clinical experience with a plasma-derived haptoglobin (Hp) product in Japan and more recent preclinical animal studies suggest that the natural Hb and the hemin-scavenger proteins Hp and hemopexin have a strong potential to neutralize the adverse physiologic effects of Hb and hemin. This includes conditions that are as diverse as RBC transfusion, sickle cell disease, sepsis, and extracorporeal circulation. This perspective reviews the principal mechanisms of Hb and hemin toxicity in different disease states, updates how the natural scavengers efficiently control these toxic moieties, and explores critical issues in the development of human plasma-derived Hp and hemopexin as therapeutics for patients with excessive intravascular hemolysis. C1 [Schaer, Dominik J.] Univ Zurich Hosp, Div Internal Med, CH-8091 Zurich, Switzerland. [Buehler, Paul W.; Alayash, Abdu I.] US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Belcher, John D.; Vercellotti, Gregory M.] Univ Minnesota, Sch Med, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA. RP Schaer, DJ (reprint author), Univ Zurich Hosp, Div Internal Med, CH-8091 Zurich, Switzerland. EM dominik.schaer@usz.ch; verce001@umn.edu FU Swiss National Science Foundation [310030/120658, 31003A/138500]; University of Zurich Research Priority Program Integrative Human Physiology; Swiss Federal Commission for Technology and Innovation; National Heart, Lung and Blood Institute, National Institutes of Health [P01 HL55552, R01 HL115467-01]; National Institutes of Health [HL110900]; US Food and Drug Administration FX This work was supported by the Swiss National Science Foundation (grants 310030/120658 and 31003A/138500), the University of Zurich Research Priority Program Integrative Human Physiology, and the Swiss Federal Commission for Technology and Innovation. Additional funding was received from the National Heart, Lung and Blood Institute, National Institutes of Health (P01 HL55552 and R01 HL115467-01 to J.D.B. and G. M. V.), the National Institutes of Health (HL110900 to A. I. A.), and the US Food and Drug Administration (to P.W.B. and A.I.A.). NR 99 TC 141 Z9 145 U1 4 U2 35 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 21 PY 2013 VL 121 IS 8 BP 1276 EP 1284 DI 10.1182/blood-2012-11-451229 PG 9 WC Hematology SC Hematology GA 182NK UT WOS:000321750000012 PM 23264591 ER PT J AU Markoff, L AF Markoff, Lewis TI Yellow Fever Outbreak in Sudan SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 US FDA, Ctr Biol Evaluat & Res, Lab Vector Borne Virus Dis, Bethesda, MD USA. RP Markoff, L (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Vector Borne Virus Dis, Bethesda, MD USA. NR 5 TC 10 Z9 11 U1 0 U2 7 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 21 PY 2013 VL 368 IS 8 BP 689 EP 691 DI 10.1056/NEJMp1300772 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 092CG UT WOS:000315095800001 PM 23387798 ER PT J AU Cokic, VP Smith, RD Biancotto, A Noguchi, CT Puri, RK Schechter, AN AF Cokic, Vladan P. Smith, Reginald D. Biancotto, Angelique Noguchi, Constance T. Puri, Raj K. Schechter, Alan N. TI Globin gene expression in correlation with G protein-related genes during erythroid differentiation SO BMC GENOMICS LA English DT Article DE G protein; G protein-coupled receptors; Erythroid progenitors; Ontogeny; Globins ID SOLUBLE GUANYLYL CYCLASE; NITRIC-OXIDE-SYNTHASE; COUPLED RECEPTOR; FETAL-HEMOGLOBIN; K562 CELLS; BETA(2)-ADRENERGIC RECEPTOR; DEPENDENT ACTIVATION; HEMATOPOIETIC-CELLS; BINDING PROTEIN; CD34(+) CELLS AB Background: The guanine nucleotide binding protein (G protein)-coupled receptors (GPCRs) regulate cell growth, proliferation and differentiation. G proteins are also implicated in erythroid differentiation, and some of them are expressed principally in hematopoietic cells. GPCRs-linked NO/cGMP and p38 MAPK signaling pathways already demonstrated potency for globin gene stimulation. By analyzing erythroid progenitors, derived from hematopoietic cells through in vitro ontogeny, our study intends to determine early markers and signaling pathways of globin gene regulation and their relation to GPCR expression. Results: Human hematopoietic CD34(+) progenitors are isolated from fetal liver (FL), cord blood (CB), adult bone marrow (BM), peripheral blood (PB) and G-CSF stimulated mobilized PB (mPB), and then differentiated in vitro into erythroid progenitors. We find that growth capacity is most abundant in FL- and CB-derived erythroid cells. The erythroid progenitor cells are sorted as 100% CD71(+), but we did not find statistical significance in the variations of CD34, CD36 and GlyA antigens and that confirms similarity in maturation of studied ontogenic periods. During ontogeny, beta-globin gene expression reaches maximum levels in cells of adult blood origin (176 fmol/mu g), while gamma-globin gene expression is consistently up-regulated in CB-derived cells (60 fmol/mu g). During gamma-globin induction by hydroxycarbamide, we identify stimulated GPCRs (PTGDR, PTGER1) and GPCRs-coupled genes known to be activated via the cAMP/PKA (ADIPOQ), MAPK pathway (JUN) and NO/cGMP (PRPF18) signaling pathways. During ontogeny, GPR45 and ARRDC1 genes have the most prominent expression in FL-derived erythroid progenitor cells, GNL3 and GRP65 genes in CB-derived cells (high gamma-globin gene expression), GPR110 and GNG10 in BM-derived cells, GPR89C and GPR172A in PB-derived cells, and GPR44 and GNAQ genes in mPB-derived cells (high beta-globin gene expression). Conclusions: These results demonstrate the concomitant activity of GPCR-coupled genes and related signaling pathways during erythropoietic stimulation of globin genes. In accordance with previous reports, the stimulation of GPCRs supports the postulated connection between cAMP/PKA and NO/cGMP pathways in activation of.-globin expression, via JUN and p38 MAPK signaling. C1 [Cokic, Vladan P.] Univ Belgrade, Inst Med Res, Lab Expt Hematol, Belgrade 11129, Serbia. [Smith, Reginald D.] GE Global Res Ctr, Niskayuna, NY USA. [Biancotto, Angelique] NHLBI, Ctr Human Immunol, NIH, Bethesda, MD 20892 USA. [Noguchi, Constance T.; Schechter, Alan N.] NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA. [Puri, Raj K.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Cokic, VP (reprint author), Univ Belgrade, Inst Med Res, Lab Expt Hematol, Dr Subotica 4, Belgrade 11129, Serbia. EM vl@imi.bg.ac.rs OI Schechter, Alan N/0000-0002-5235-9408 FU Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases; Serbian Ministry of Education and Science [175053] FX This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases and by grant from the Serbian Ministry of Education and Science [175053]. NR 46 TC 6 Z9 6 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD FEB 20 PY 2013 VL 14 AR 116 DI 10.1186/1471-2164-14-116 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 109WV UT WOS:000316401900001 PM 23425329 ER PT J AU Hardy, GAD Sieg, S Rodriguez, B Anthony, D Asaad, R Jiang, W Mudd, J Schacker, T Funderburg, NT Pilch-Cooper, HA Debernardo, R Rabin, RL Lederman, MM Harding, CV AF Hardy, Gareth A. D. Sieg, Scott Rodriguez, Benigno Anthony, Donald Asaad, Robert Jiang, Wei Mudd, Joseph Schacker, Timothy Funderburg, Nicholas T. Pilch-Cooper, Heather A. Debernardo, Robert Rabin, Ronald L. Lederman, Michael M. Harding, Clifford V. TI Interferon-alpha Is the Primary Plasma Type-I IFN in HIV-1 Infection and Correlates with Immune Activation and Disease Markers SO PLOS ONE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; MYELOID DENDRITIC CELLS; ADAPTIVE IMMUNITY; T-CELLS; HIV-1-INFECTED PATIENTS; SIV INFECTION; EXPRESSION; INNATE; BLOOD; MATURATION AB Type-I interferon (IFN-I) has been increasingly implicated in HIV-1 pathogenesis. Various studies have shown elevated IFN-I and an IFN-I-induced gene and protein expression signature in HIV-1 infection, yet the elevated IFN-I species has not been conclusively identified, its source remains obscure and its role in driving HIV-1 pathogenesis is controversial. We assessed IFN-I species in plasma by ELISAs and bioassay, and we investigated potential sources of IFN-I in blood and lymph node tissue by qRT-PCR. Furthermore, we measured the effect of therapeutic administration of IFN alpha in HCV-infected subjects to model the effect of IFN alpha on chronic immune activation. IFN-I bioactivity was significantly increased in plasma of untreated HIV-1-infected subjects relative to uninfected subjects (p = 0.012), and IFN alpha was the predominant IFN-I subtype correlating with IFN-I bioactivity (r = 0.658, p<0.001). IFN alpha was not detectable in plasma of subjects receiving anti-retroviral therapy. Elevated expression of IFN alpha mRNA was limited to lymph node tissue cells, suggesting that peripheral blood leukocytes are not a major source of IFN alpha in untreated chronic HIV-1 infection. Plasma IFN-I levels correlated inversely with CD4 T cell count (p = 0.003) and positively with levels of plasma HIV-1 RNA and CD38 expression on CD8 T cells (p = 0.009). In hepatitis C virus-infected subjects, treatment with IFN-I and ribavirin increased expression of CD38 on CD8 T cells (p = 0.003). These studies identify IFN alpha derived from lymph nodes, rather than blood leukocytes, as a possible source of the IFN-I signature that contributes to immune activation in HIV-1 infection. C1 [Hardy, Gareth A. D.; Mudd, Joseph; Lederman, Michael M.; Harding, Clifford V.] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. [Hardy, Gareth A. D.; Sieg, Scott; Rodriguez, Benigno; Anthony, Donald; Asaad, Robert; Jiang, Wei; Mudd, Joseph; Funderburg, Nicholas T.; Pilch-Cooper, Heather A.; Debernardo, Robert; Lederman, Michael M.; Harding, Clifford V.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Sieg, Scott; Rodriguez, Benigno; Anthony, Donald; Asaad, Robert; Jiang, Wei; Mudd, Joseph; Funderburg, Nicholas T.; Pilch-Cooper, Heather A.; Lederman, Michael M.; Harding, Clifford V.] Case Western Reserve Univ, Dept Med, Div Infect Dis, Cleveland, OH 44106 USA. [Hardy, Gareth A. D.; Sieg, Scott; Rodriguez, Benigno; Anthony, Donald; Asaad, Robert; Jiang, Wei; Lederman, Michael M.; Harding, Clifford V.] Case Western Reserve Univ, Ctr AIDS Res, Cleveland, OH 44106 USA. [Anthony, Donald] Cleveland Vet Adm Med Ctr, Cleveland, OH USA. [Schacker, Timothy] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Debernardo, Robert] Case Western Reserve Univ, Dept Obstet & Gynecol, Cleveland, OH 44106 USA. [Rabin, Ronald L.] US FDA, Ctr Biol Evaluat & Res, Lab Immunobiochem, Bethesda, MD 20014 USA. RP Harding, CV (reprint author), Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. EM cvh3@cwru.edu RI Funderburg, Nicholas/L-8022-2013; Rodriguez, Benigno/C-3365-2009 OI Rodriguez, Benigno/0000-0001-9736-7957 FU National Institutes of Health (NIH) [AI034343, AI069085]; Case Western Reserve University Center for AIDS Research (NIH) [AI036219] FX This work was supported by National Institutes of Health (NIH) grants AI034343 and AI069085 to CVH and by core facilities of the Case Western Reserve University Center for AIDS Research (NIH grant AI036219). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 38 Z9 38 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 20 PY 2013 VL 8 IS 2 AR e56527 DI 10.1371/journal.pone.0056527 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 093IE UT WOS:000315184200093 PM 23437155 ER PT J AU Teferedegne, B Lewis, AM Peden, K Murata, H AF Teferedegne, Belete Lewis, Andrew M., Jr. Peden, Keith Murata, Haruhiko TI Development of a Neutralization Assay for Influenza Virus Using an Endpoint Assessment Based on Quantitative Reverse-Transcription PCR SO PLOS ONE LA English DT Article ID HEMAGGLUTINATION-INHIBITING ANTIBODY; SEROLOGIC ASSAYS; MEDIATED NEUTRALIZATION; PARVOVIRUS B19; INFECTION; SERUM; VACCINATION; PROTECTION; CHALLENGE; DIAGNOSIS AB A microneutralization assay using an ELISA-based endpoint assessment (ELISA-MN) is widely used to measure the serological response to influenza virus infection and vaccination. We have developed an alternative microneutralization assay for influenza virus using a quantitative reverse transcription PCR-based endpoint assessment (qPCR-MN) in order to improve upon technical limitations associated with ELISA-MN. For qPCR-MN, infected MDCK-London cells in 96-well cell-culture plates are processed with minimal steps such that resulting samples are amenable to high-throughput analysis by downstream one-step quantitative reverse transcription PCR (qRT-PCR; SYBR Green chemistry with primers targeting a conserved region of the M1 gene of influenza A viruses). The growth curves of three recent vaccine strains demonstrated that the qRT-PCR signal detected at 6 hours post-infection reflected an amplification of at least 100-fold over input. Using ferret antisera, we have established the feasibility of measuring virus neutralization at 6 hours post-infection, a duration likely confined to a single virus-replication cycle. The neutralization titer for qPCR-MN was defined as the highest reciprocal serum dilution necessary to achieve a 90% inhibition of the qRT-PCR signal; this endpoint was found to be in agreement with ELISA-MN using the same critical reagents in each assay. qPCR-MN was robust with respect to assay duration (6 hours vs. 12 hours). In addition, qPCR-MN appeared to be compliant with the Percentage Law (i.e., virus neutralization results appear to be consistent over an input virus dose ranging from 500 to 12,000 TCID50). Compared with ELISA-MN, qPCR-MN might have inherent properties conducive to reducing intra-and inter-laboratory variability while affording suitability for automation and high-throughput uses. Finally, our qRT-PCR-based approach may be broadly applicable to the development of neutralization assays for a wide variety of viruses. C1 [Teferedegne, Belete; Lewis, Andrew M., Jr.; Peden, Keith; Murata, Haruhiko] US FDA, Lab DNA Viruses, Div Viral Prod, Off Vaccines Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Murata, H (reprint author), US FDA, Lab DNA Viruses, Div Viral Prod, Off Vaccines Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM haruhiko.murata@fda.hhs.gov FU Division of Microbiology and Infectious Diseases, NIAID, NIH [YI-AI-4893-02NIAID] FX This study was funded by a contract from the Division of Microbiology and Infectious Diseases, NIAID, NIH (YI-AI-4893-02NIAID; http://www.niaid.nih.gov/about/organization/dmid/Pages/default.aspx). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 35 TC 6 Z9 6 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 20 PY 2013 VL 8 IS 2 AR e56023 DI 10.1371/journal.pone.0056023 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 093IE UT WOS:000315184200038 PM 23437084 ER PT J AU Chen, HC Chen, JJ AF Chen, Hung-Chia Chen, James J. TI Assessment of reproducibility of cancer survival risk predictions across medical centers SO BMC MEDICAL RESEARCH METHODOLOGY LA English DT Article ID CELL-LUNG-CANCER; GENE-EXPRESSION PROFILES; AMERICAN JOINT COMMITTEE; STAGING SYSTEM; MULTIPLE-MYELOMA; MICROARRAY DATA; COX REGRESSION; SIGNATURES; MELANOMA; ADENOCARCINOMA AB Background: Two most important considerations in evaluation of survival prediction models are 1) predictability ability to predict survival risks accurately and 2) reproducibility - ability to generalize to predict samples generated from different studies. We present approaches for assessment of reproducibility of survival risk score predictions across medical centers. Methods: Reproducibility was evaluated in terms of consistency and transferability. Consistency is the agreement of risk scores predicted between two centers. Transferability from one center to another center is the agreement of the risk scores of the second center predicted by each of the two centers. The transferability can be: 1) model transferability - whether a predictive model developed from one center can be applied to predict the samples generated from other centers and 2) signature transferability - whether signature markers of a predictive model developed from one center can be applied to predict the samples from other centers. We considered eight prediction models, including two clinical models, two gene expression models, and their combinations. Predictive performance of the eight models was evaluated by several common measures. Correlation coefficients between predicted risk scores of different centers were computed to assess reproducibility - consistency and transferability. Results: Two public datasets, the lung cancer data generated from four medical centers and colon cancer data generated from two medical centers, were analyzed. The risk score estimates for lung cancer patients predicted by three of four centers agree reasonably well. In general, a good prediction model showed better cross-center consistency and transferability. The risk scores for the colon cancer patients from one (Moffitt) medical center that were predicted by the clinical models developed from the another (Vanderbilt) medical center were shown to have excellent model transferability and signature transferability. Conclusions: This study illustrates an analytical approach to assessing reproducibility of predictive models and signatures. Based on the analyses of the two cancer datasets, we conclude that the models with clinical variables appear to perform reasonable well with high degree of consistency and transferability. There should have more investigations on the reproducibility of prediction models including gene expression data across studies. C1 [Chen, Hung-Chia; Chen, James J.] US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. [Chen, Hung-Chia] China Med Univ, Grad Inst Biostat, Taichung, Taiwan. [Chen, Hung-Chia] China Med Univ, Biostat Ctr, Taichung, Taiwan. RP Chen, JJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. EM jamesj.chen@fda.hhs.gov FU Taiwan National Science Council [NSC-101-2118-M-039-002] FX The authors are very grateful to reviewers for much helpful comments and suggestions for revising and improving this paper. This work was supported in part by the Taiwan National Science Council grant NSC-101-2118-M-039-002 to HCC. The views presented in this paper are those of the authors and do not necessarily represent those of the U.S. Food and Drug Administration. NR 58 TC 3 Z9 3 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2288 J9 BMC MED RES METHODOL JI BMC Med. Res. Methodol. PD FEB 20 PY 2013 VL 13 AR 25 DI 10.1186/1471-2288-13-25 PG 11 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 101MM UT WOS:000315779100001 PM 23425000 ER PT J AU Wang, Y Fu, TJ Howard, A Kothary, MH McHugh, TH Zhang, YZ AF Wang, Yang Fu, Tong-Jen Howard, Andrew Kothary, Mahendra H. McHugh, Tara H. Zhang, Yuzhu TI Crystal Structure of Peanut (Arachis hypogaea) Allergen Ara h 5 SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Peanut allergy; allergen stability; X-ray crystallography; Ara h 5; profilin ID IGE-BINDING EPITOPES; FOOD ALLERGY; CROSS-REACTIVITY; ALIGNMENT ALGORITHM; MUTATIONAL ANALYSIS; MOLECULAR GRAPHICS; TRYPSIN-INHIBITOR; MAJOR ALLERGEN; PROFILIN; PROTEIN AB Profilins from numerous species are known to be allergens, including food allergens, such as peanut (Arachis hypogaea) allergen Ara h 5, and pollen allergens, such as birch allergen Bet v 2. Patients with pollen allergy can also cross-react to peanut. Structural characterization of allergens will allow a better understanding of the allergenicity of food allergens and their cross-reactivities. The three-dimensional structures of most known food allergens remain to be elucidated. Here, we report the first crystallographic study of a food allergen in the profilin family. The structure of peanut allergen Ara h 5 was determined, and the resolution of the final refined structure was 1.1 angstrom. Structure alignment revealed that Ara h 5 is more similar to Bet v 2 than to Hey b 8, although sequence alignment suggested that Ara h 5 is more closely related to Hev b 8 than to Bet v 2, indicating that homology-model-based prediction of immunoglobulin E epitopes needs to be interpreted with caution. C1 [Wang, Yang; Howard, Andrew; Zhang, Yuzhu] IIT, Dept Biol & Chem Sci, Chicago, IL 60616 USA. [Fu, Tong-Jen] US FDA, Ctr Food Safety & Appl Nutr, Bedford Pk, IL 60501 USA. [Kothary, Mahendra H.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [McHugh, Tara H.; Zhang, Yuzhu] ARS, Western Reg Res Ctr, USDA, Albany, CA 94710 USA. RP Zhang, YZ (reprint author), IIT, Dept Biol & Chem Sci, 3101 South Dearborn St, Chicago, IL 60616 USA. EM yuzhu.zhang@ars.usda.gov RI Zhang, Yuzhu/A-7109-2009 OI Zhang, Yuzhu/0000-0001-7882-5692 FU Office of Basic Energy Sciences, Office of Science, U.S. Department of Energy [W-31-109-Eng-38]; U.S. Food and Drug Administration [5U01FD003801]; Institute for Food Safety and Health, Illinois Institute of Technology [5U01FD003801] FX X-ray diffraction data were collected at Southeast Regional Collaborative Access Team (SER-CAT) 22-ID beamline at the APS, Argonne National Laboratory. Use of the APS was supported by the Office of Basic Energy Sciences, Office of Science, U.S. Department of Energy, under Contract W-31-109-Eng-38. This work was partially supported by Cooperative Agreement 5U01FD003801 between the U.S. Food and Drug Administration and Institute for Food Safety and Health, Illinois Institute of Technology. NR 44 TC 10 Z9 10 U1 0 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD FEB 20 PY 2013 VL 61 IS 7 BP 1573 EP 1578 DI 10.1021/jf303861p PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 095HV UT WOS:000315326200020 PM 23350842 ER PT J AU Karzai, FH Adesunloye, B Ning, YMM Madan, RA Gulley, JL Apolo, AB Beatson, MA Couvillon, A Harold, N Parnes, HL Arlen, PM Wright, JJ Chen, C Dawson, NA Figg, WD Dahut, WL AF Karzai, Fatima H. Adesunloye, Bamidele Ning, Yangmin M. Madan, Ravi Amrit Gulley, James L. Apolo, Andrea Borghese Beatson, Melony A. Couvillon, Anna Harold, Nancy Parnes, Howard L. Arlen, Philip M. Wright, John Joseph Chen, Clara Dawson, Nancy Ann Figg, William Douglas Dahut, William L. TI Use of supportive measures to improve outcome and decrease toxicity in docetaxel-based antiangiogenesis combinations SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Genitourinary Cancers Symposium of the Conquer-Cancer-Foundation of American-Society-of-Clinical-Oncology (ASCO) CY FEB 14-16, 2013 CL Orlando, FL SP Amer Soc Clin Oncol, Conquer Canc Fdn C1 NCI, Med Oncol Branch, Bethesda, MD 20892 USA. NCI, US FDA, Silver Spring, MD USA. NCI, Lab Tumor Immunol & Biol, Med Oncol Branch, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NCI, Canc Prevent Div, Bethesda, MD 20892 USA. Neogenix Oncol, Rockville, MD USA. NCI, Rockville, MD USA. NCI, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2013 VL 31 IS 6 SU S MA 128 PG 1 WC Oncology SC Oncology GA AE0TR UT WOS:000333679600129 ER PT J AU Hall, B Nakashima, H Sun, ZJ Sato, Y Bian, YS Husain, SR Puri, RK Kulkarni, AB AF Hall, Bradford Nakashima, Hideyuki Sun, Zhi-Jun Sato, Yuki Bian, Yansong Husain, Syed R. Puri, Raj K. Kulkarni, Ashok B. TI Targeting of interleukin-13 receptor alpha 2 for treatment of head and neck squamous cell carcinoma induced by conditional deletion of TGF-beta and PTEN signaling SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article DE IL-13 receptor; Immunotoxin; TGF-beta; PTEN; HNSCC ID POTENT ANTITUMOR-ACTIVITY; CHIMERIC FUSION PROTEINS; MURINE TUMOR-MODELS; PSEUDOMONAS EXOTOXIN; IL-13 CYTOTOXIN; MOUSE MODEL; EXPRESSION; CANCER; THERAPY; CHAIN AB Background: The sixth leading class of cancer worldwide is head and neck cancer, which typically arise within the squamous epithelium of the oral mucosa. Human head and neck squamous cell carcinoma (HNSCC) is known to be difficult to treat and has only a 50% five-year survival rate. With HNSCC, novel therapeutics are needed along with a means of rapidly screening anti-cancer agents in vivo, such as mouse models. Methods: In order to develop new animal models of cancer to test safety and efficacy of novel therapeutic agents for human HNSCC, tumors resembling clinical cases of human HNSCC were induced in the head and neck epithelium of a genetically engineered mouse model. This mouse model was generated by conditional deletion of two tumor suppressors, Transforming Growth Factor-beta Receptor 1 (TGF beta RI) and Phosphatase and Tensin homolog (PTEN), in the oral epithelium. We discovered that the tumors derived from these Tgfbr1/Pten double conditional knockout (2cKO) mice over-expressed IL-13R alpha 2, a high affinity receptor for IL-13 that can function as a tumor antigen. To demonstrate a proof-of-concept that targeted therapy against IL-13R alpha 2 expression would have any antitumor efficacy in this spontaneous tumor model, these mice were treated systemically with IL-13-PE, a recombinant immunotoxin consisting of IL-13 fused to the Pseudomonas exotoxin A. Results: Tgfbr1/Pten 2cKO mice when treated with IL-13-PE displayed significantly increased survival when compared to the untreated control mice. The untreated mice exhibited weight loss, particularly with the rapid onset of tongue tumors, but the treated mice gained weight while on IL-13-PE therapy and showed no clinical signs of toxicity due to the immunotoxin. Expression of IL-13Ra2 in tumors was significantly decreased with IL-13-PE treatment as compared to the controls and the number of myeloid-derived suppressor cells (MDSC) was also significantly reduced in the spleens of the IL-13-PE treated mice. Conclusions: Our study demonstrates that the Tgfbr1/Pten 2cKO mouse model of human HNSCC is a useful model for assessing antitumor activity of new cancer therapeutic agents, and that IL-13-PE has therapeutic potential to treat human head and neck cancer. C1 [Hall, Bradford; Sun, Zhi-Jun; Bian, Yansong; Kulkarni, Ashok B.] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. [Nakashima, Hideyuki; Sato, Yuki; Husain, Syed R.; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Bian, Yansong] Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD USA. RP Kulkarni, AB (reprint author), Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, 30 Convent Dr,Bldg 30,Room 130, Bethesda, MD USA. EM ak40m@nih.gov FU Division of Intramural Research of the National Institute of Dental and Craniofacial Research, NIH [ZIA-DE-000698]; Center for Biologics Evaluation and Research, U.S. Food and Drug Administration; National Institute of Dental and Craniofacial Research; National Institute on Deafness and Other Communication Disorders, NIH FX We thank Riddhi Patel for help with the biochemical analysis of tumors, Alfredo Molinolo for the analysis of the tumor sections, and Shelagh Johnson for expert editorial assistance. We are grateful to Drs. Jing Han and Shyh-Ching Lo, CBER, FDA for internal review of the manuscript. These studies were supported by the Division of Intramural Research of the National Institute of Dental and Craniofacial Research, NIH to ABK (ZIA-DE-000698), and the Center for Biologics Evaluation and Research, U.S. Food and Drug Administration.; Intramural Research Programs of the National Institute of Dental and Craniofacial Research and National Institute on Deafness and Other Communication Disorders, NIH, and the Center for Biologics Evaluation and Research, U.S. Food and Drug Administration. NR 31 TC 5 Z9 8 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD FEB 19 PY 2013 VL 11 AR 45 DI 10.1186/1479-5876-11-45 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 099PL UT WOS:000315633600002 PM 23421960 ER PT J AU MacDonald, JK Julian, E Chu, A Dion, J Boden, W Viazis, S Beal, J Lanier, W Nguyen, TA Burnworth, L Williams, I Gieraltowski, L Hancock, WT AF MacDonald, J. Kathryn Julian, Ernest Chu, Alvina Dion, Jamie Boden, William Viazis, Stelios Beal, Jennifer Lanier, William Thai-An Nguyen Burnworth, Laura Williams, Ian Gieraltowski, Laura Hancock, W. Thane TI Salmonella Bredeney Infections Linked to a Brand of Peanut Butter - United States, 2012 SO MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT LA English DT Article C1 [MacDonald, J. Kathryn] Washington State Dept Hlth, Washington, DC USA. [Julian, Ernest] Rhode Isl Dept Hlth, Providence, RI 02908 USA. [Chu, Alvina] Maryland Dept Hlth & Mental Hyg, Baltimore, MD 21201 USA. [Viazis, Stelios; Beal, Jennifer; Lanier, William] US FDA, Coordinated Outbreak Response & Evaluat Network, Rockville, MD 20857 USA. [Hancock, W. Thane] CDC, Atlanta, GA 30333 USA. RP Hancock, WT (reprint author), CDC, Atlanta, GA 30333 USA. EM vie1@cdc.gov NR 3 TC 3 Z9 3 U1 0 U2 4 PU CENTER DISEASE CONTROL & PREVENTION PI ATLANTA PA MAILSTOP E-90, ATLANTA, GA 30333 USA SN 0149-2195 J9 MMWR-MORBID MORTAL W JI MMWR-Morb. Mortal. Wkly. Rep. PD FEB 15 PY 2013 VL 62 IS 6 BP 107 EP 107 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 188EP UT WOS:000322175300004 ER PT J AU Biezonski, DK Piper, BJ Shinday, NM Kim, PJ Ali, SF Meyer, JS AF Biezonski, Dominik K. Piper, Brian J. Shinday, Nina M. Kim, Peter J. Ali, Syed F. Meyer, Jerrold S. TI Effects of a short-course MDMA binge on dopamine transporter binding and on levels of dopamine and its metabolites in adult male rats SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE 3,4-methylenedioxymethamphetamine; Neurotoxicity; Dopamine transporter; Dihydroxyphenylacetic acid; Homovanillic acid; Serotonin ID (ECSTASY)-INDUCED SEROTONIN NEUROTOXICITY; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; INCREASED ANXIETY; PARTIAL RECOVERY; 52-WEEK PERIOD; ECSTASY; BRAIN; TERMINALS; DEFICITS; PHARMACOLOGY AB Although the recreational drug 3,4-methylenedioxymethamphetamine (MDMA) is often described as a selective serotonergic neurotoxin, some research has challenged this view. The objective of this study was to determine the influence of MDMA on subsequent levels of two different markers of dopaminergic function, the dopamine transporter (DAT) as well as dopamine and its major metabolites. In experiment I, adult male Sprague-Dawley rats were administered either a low or moderate dose MDMA binge (2.5 or 5.0 mg/kg x 4 with an inter-dose interval of 1 h) or saline, and were killed 1 week later. The moderate dose dramatically reduced [H-3]WIN 35,428 binding to striatal DAT by 73.7% (P <= 0.001). In experiment II, animals were binged with a higher dose of MDMA (10 mg/kg x 4) to determine the drug's effects on concentrations of serotonin (5-HT), dopamine, and their respective major metabolites 5-hydroxyindoleacetic acid (5-HIAA), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the striatum and frontal cortex 1 week later. As expected, MDMA significantly reduced 5-HT and 5-HIAA (>= 50%) in these structures, while only a marginal decrease in dopamine was noted in the striatum. In contrast, levels of DOPAC (34.3%, P < 0.01) and HVA (33.5%, P < 0.001) were reduced by MDMA treatment, suggesting a decrease in dopamine turnover. Overall, these findings indicate that while serotonergic markers are particularly vulnerable to MDMA-induced depletion, significant dopaminergic deficits may also occur under some conditions. Importantly, DAT expression may be more vulnerable to perturbation by MDMA than dopamine itself. (C) 2012 Elsevier B.V. All rights reserved. C1 [Biezonski, Dominik K.; Piper, Brian J.; Shinday, Nina M.; Meyer, Jerrold S.] Univ Massachusetts, Neurosci & Behav Program, Amherst, MA 01003 USA. [Kim, Peter J.; Meyer, Jerrold S.] Univ Massachusetts, Dept Biochem, Amherst, MA 01003 USA. [Ali, Syed F.] Natl Ctr Toxicol Res, Neurochem Lab, Jefferson, AR 72079 USA. RP Piper, BJ (reprint author), Husson Univ, Dept Basic Pharmaceut Sci, Bangor, ME 04401 USA. EM piperbj@husson.edu OI Meyer, Jerrold/0000-0002-8382-7075 FU National Institute of Drug Abuse [L30DA027582] FX MDMA was provided by Research Triangle Institute and Lauren Daniels and Charles Betts provided technical assistance. BJP was supported by the National Institute of Drug Abuse (Grant no. L30DA027582) during the latter stages of manuscript preparation. NR 42 TC 3 Z9 3 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD FEB 15 PY 2013 VL 701 IS 1-3 BP 176 EP 180 DI 10.1016/j.ejphar.2012.12.024 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 100NY UT WOS:000315709100023 PM 23276666 ER PT J AU Melching, CS Ao, Y Alp, E AF Melching, Charles S. Ao, Yaping Alp, Emre TI Modeling evaluation of integrated strategies to meet proposed dissolved oxygen standards for the Chicago waterway system SO JOURNAL OF ENVIRONMENTAL MANAGEMENT LA English DT Article DE Water-quality management; Water-quality modeling; Dissolved oxygen; Use attainability analysis; In-stream aeration ID RIVER; AERATION AB The Chicago Waterway System (CWS) is a 113.8 km branching network of navigable waterways controlled by hydraulic structures in which the majority of flow is treated sewage effluent and there are periods of substantial combined sewer overflow. The Illinois Pollution Control Board (IPCB) designated the majority of the CWS as Secondary Contact and Indigenous Aquatic Life Use waters in the 1970s and made small alterations to these designations in 1988. Between 1988 and 2002 substantial improvements in the pollution control and water-quality management facilities were made in the Chicago area. The results of a Use Attainability Analysis led the Illinois Environmental Protection Agency (IEPA) to propose the division of the CWS into two new aquatic life use classes with appropriate dissolved oxygen (DO) standards. To aid the IPCB in their deliberations regarding the appropriate water use classifications and DO standards for the CWS, the DUFLOW model that is capable of simulating hydraulics and water-quality processes under unsteady-flow conditions was used to evaluate integrated strategies of water-quality improvement facilities that could meet the proposed DO standards during representative wet (2001) and dry (2003) years. A total of 28 new supplementary aeration stations with a maximum DO load of 80 or 100 g/s and aerated flow transfers at three locations in the CWS would be needed to achieve the IEPA proposed DO standards 100% of the time for both years. A much simpler and less costly (approximate to one tenth of the cost) system of facilities would be needed to meet the IEPA proposed DO standards 90% of the time. In theory, the combinations of flow augmentation and new supplemental aeration stations can achieve 100% compliance with the IEPA proposed DO standards, however, 100% compliance will be hard to achieve in practice because of (1) difficulties in determining when to turn on the aeration stations and (2) localized heavy loads of pollutants during storms that may yield violations of the DO standards even with an extensive network of supplemental aeration stations. Thus, because absolute DO standards that must be met 100% of the time will be difficult, if not impossible to comply with, DO standards that include a Wet Weather Limited Use (WWLU) designation based on rainfall amount triggering CSO events and a maximum duration that the WWLU could be applied should be considered to obtain a healthy ecosystem by applying water-quality improvement features that can be practically operated and maintained. Such a WWLU approach also was evaluated in this paper. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Ao, Yaping] US FDA, CFSAN, College Pk, MD 20740 USA. [Alp, Emre] Middle E Tech Univ, Dept Environm Engn, TR-06531 Ankara, Turkey. RP Melching, CS (reprint author), 4030 W Edgerton Ave, Greenfield, WI 53221 USA. EM steve.melching17@gmail.com; yaping.ao@fda.hhs.gov; emrealp@metu.edu.tr RI Alp, Emre/B-3026-2013 FU Metropolitan Water Reclamation District of Greater Chicago [3048074] FX The work reported here was supported by grant number 3048074 from the Metropolitan Water Reclamation District of Greater Chicago to Marquette University. This support is gratefully acknowledged. NR 43 TC 5 Z9 5 U1 3 U2 38 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0301-4797 EI 1095-8630 J9 J ENVIRON MANAGE JI J. Environ. Manage. PD FEB 15 PY 2013 VL 116 BP 145 EP 155 DI 10.1016/j.jenvman.2012.11.040 PG 11 WC Environmental Sciences SC Environmental Sciences & Ecology GA 101DC UT WOS:000315754400016 PM 23298716 ER PT J AU Hida, K Kulka, M Papafragkou, E AF Hida, Kaoru Kulka, Michael Papafragkou, Efstathia TI Development of a rapid total nucleic acid extraction method for the isolation of hepatitis A virus from fresh produce SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE Foodborne virus; Extraction methods; Produce; Spinach; Tomatoes; RT-qPCR ID POLYMERASE CHAIN-REACTION; ENTERIC VIRUSES; UNITED-STATES; RT-PCR; OUTBREAK; FOOD; VEGETABLES; PATHOGENS; SHELLFISH; NOROVIRUS AB Recently, there have been increasing reports of foodborne illnesses associated with the consumption of fresh produce. Among these, hepatitis A virus (HAV) remains epidemiologically important and has been continually implicated in several outbreaks. We describe a rapid method (<8 h)for the isolation and subsequent detection with real-time quantitative PCR (RT-qPCR) of the HAV HM-175 cytopathic strain seeded onto baby spinach and sliced tomatoes using a total RNA extraction method, utilizing a high concentration (4 M) guanidine thiocyanate buffer. Consistent detection of HAV genome from both produce items was achieved at an inoculation level of 3 x 10(3) PFU/25 g of food, with less consistent detection achieved at 3 x 10(2) PFU/25 g. Initial studies revealed that a final precipitation of recovered RNA with potassium acetate to reduce carryover of polysaccharides and the addition of polyvinylpyrrolidone to remove polyphenolics in spinach were essential. For tomatoes, virus isolation was achieved with the incorporation of either an elution step with a high pH Tris-glycine-beef extract (TGBE) buffer or with an enzymatic digestion with pectinase. We also describe the development of a protocol for the detection of HAV from tomatoes utilizing a Luminex (R) microbead-based suspension array. The results correlated well with the RT-qPCR assay suggesting the feasibility of the Bioplex (R) as a detection platform for viruses isolated from foods. Published by Elsevier B.V. C1 [Hida, Kaoru; Kulka, Michael; Papafragkou, Efstathia] US FDA, Div Mol Biol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Papafragkou, E (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 Efstathia.Papafragkou@fda.hhs.gov FU Commissioner's Fellowship Program (FDA) FX This research was funded in part by the Commissioner's Fellowship Program (FDA) and appointment with the Oak Ridge Institute for Science and Education (ORISE) for K. Hida. We would like to thank Dr. Chris Elkins for critically reviewing this manuscript and Dr. Biswendu Goswami for helpful initial discussions. NR 57 TC 9 Z9 10 U1 1 U2 27 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 FEB 15 PY 2013 VL 161 IS 3 BP 143 EP 150 DI 10.1016/j.ijfoodmicro.2012.12.007 PG 8 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 095VJ UT WOS:000315362800001 PM 23334093 ER PT J AU Clotilde, LM Bernard, C Salvador, A Lin, A Lauzon, CR Muldoon, M Xu, YC Lindpaintner, K Carter, JM AF Clotilde, Laurie M. Bernard, Clay Salvador, Alexandra Lin, Andrew Lauzon, Carol R. Muldoon, Mark Xu, Yichun Lindpaintner, Klaus Carter, J. Mark TI A 7-plex microbead-based immunoassay for serotyping Shiga toxin-producing Escherichia coli SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE Escherichia coli; Serotyping; Multiplex; Immunoassay; Antisera; Luminex ID HEMOLYTIC-UREMIC SYNDROME; UNITED-STATES; NON-O157; INFECTIONS; O157; O111; IDENTIFICATION; PATHOGENS; OUTBREAK; SAMPLES AB Serotyping of Shiga toxin-producing Escherichia coli (STEC) has been contingent upon the availability of antisera. Here we describe a 7-plex microbead-based immunoassay to simultaneously serotype seven STECs (i.e., belonging to serogroups O26, O45,O103, O111, O121, O145, and O157) by the Luminex xMAP (R) technology. This technology presents many advantages: Its multiplexed format (up to 100 analytes) saves time, reagents, and test sample, and many regulatory agencies currently utilize this platform for other assays. In this study, a total of seventy-nine STEC strains belonging to the 7 different serogroups of interest were tested. These strains had been previously serotyped and their serogroup was confirmed by PCR. Except for one strain belonging to the O111 serogroup, nearly all strains (i.e., 98.7%; 78/79) were correctly identified on the Bio-Plex 100 instrument in less than 4 h. This newly developed microbead-based immunoassay could be extended to include other STEC serogroups, virulence factors, and/or bacterial species. Published by Elsevier B.V. C1 [Clotilde, Laurie M.; Lin, Andrew] US FDA, San Francisco Dist Lab, Alameda, CA 94502 USA. [Bernard, Clay; Salvador, Alexandra; Carter, J. Mark] ARS, USDA, Albany, CA 94710 USA. [Lauzon, Carol R.] Calif State Univ Hayward, Dept Biol Sci, Hayward, CA 94542 USA. [Muldoon, Mark] Romer Labs Technol Inc, Newark, DE 19713 USA. [Xu, Yichun; Lindpaintner, Klaus] Strateg Diagnost Inc SDIX, Newark, DE 19702 USA. RP Carter, JM (reprint author), 800 Buchanan St, Albany, CA 94710 USA. EM j.mark.carter@ars.usda.gov RI Carter, John Mark/K-2485-2015 OI Carter, John Mark/0000-0001-8251-4168 NR 29 TC 6 Z9 6 U1 0 U2 15 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 FEB 15 PY 2013 VL 92 IS 2 BP 226 EP 230 DI 10.1016/j.mimet.2012.11.023 PG 5 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 095YM UT WOS:000315370900024 PM 23228591 ER PT J AU Patterson, TA Twaddle, NC Roegge, CS Callicott, RJ Fisher, JW Doerge, DR AF Patterson, Tucker A. Twaddle, Nathan C. Roegge, Cindy S. Callicott, Ralph J. Fisher, Jeffrey W. Doerge, Daniel R. TI Concurrent determination of bisphenol A pharmacokinetics in maternal and fetal rhesus monkeys SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Bisphenol A; Placental transfer; Rhesus monkey; Mass spectrometry; Pharmacokinetics ID TANDEM MASS-SPECTROMETRY; SPRAGUE-DAWLEY RATS; LIQUID-CHROMATOGRAPHY; HUMAN URINE; CD-1 MICE; EXPOSURE; SERUM; ADULT; TISSUES; DERIVATIVES AB Bisphenol A (BPA) is an important industrial chemical used as the monomer for polycarbonate plastic and in epoxy resins for food can liners. Worldwide biomonitoring studies consistently find a high prevalence of BPA conjugates in urine (>90%) in amounts consistent with aggregate exposure at levels below 1 mu g/kg bw/d. The current study used LC/MS/MS to measure concurrently the pharmacokinetics of aglycone (active) and conjugated (inactive) deuterated BPA (d6) in maternal and fetal rhesus monkey serum, amniotic fluid, and placenta following intravenous injection in the dam (100 mu g/kg bw). Internal exposures of the fetus to aglycone d6-BPA (serum AUC) were attenuated by maternal, placental, and fetal Phase II metabolism to less than half that in the dam. Levels of aglycone and conjugated d6-BPA measured in whole placenta were consistent with a role in metabolic detoxification. The monotonic elimination of aglycone d6-BPA from the fetal compartment accompanied by persistent conjugate levels provides further evidence arguing against the hypothesis that BPA conjugates are selectively deconjugated by either the placenta or fetus. These results also provide benchmarks to guide the interpretation of human cord blood, amniotic fluid, and placenta sampling and measurement strategies as a basis for estimating fetal exposures to BPA. This study in a non-human primate model provides additional pharmacokinetic data for use in PBPK modeling of perinatal exposures to BPA from food contact, medical devices, and other environmental sources. Published by Elsevier Inc. C1 [Patterson, Tucker A.; Roegge, Cindy S.] Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Twaddle, Nathan C.; Fisher, Jeffrey W.; Doerge, Daniel R.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Callicott, Ralph J.] US FDA, Jefferson, AR 72079 USA. [Callicott, Ralph J.] Prior One Serv Corp, Jefferson, AR 72079 USA. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM daniel.doerge@fda.hhs.gov FU NCTR/FDA [FDA 224-07-0007, NIH Y1ES1027]; National Institute of Environmental Health Sciences/National Toxicology Program [FDA 224-07-0007, NIH Y1ES1027] FX This research was supported in part by an Interagency Agreement (FDA 224-07-0007; NIH Y1ES1027) between NCTR/FDA and the National Institute of Environmental Health Sciences/National Toxicology Program. The authors are grateful to Drs. K. Barry Delclos and Luisa Camacho, NCTR, for helpful discussions. The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration. NR 47 TC 32 Z9 32 U1 1 U2 56 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 2013 VL 267 IS 1 BP 41 EP 48 DI 10.1016/j.taap.2012.12.006 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 085PI UT WOS:000314626300005 PM 23261975 ER PT J AU Shrivas, K Mindaye, ST Getie-Kebtie, M Alterman, MA AF Shrivas, Kamlesh Mindaye, Samuel T. Getie-Kebtie, Melkamu Alterman, Michail A. TI Mass spectrometry-based proteomic analysis of human liver cytochrome(s) P450 SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Cytochrome P450 expression; Human liver microsomes; Drug metabolizing enzymes; Proteomics; MALDI mass spectrometry; Pharmacoproteomics ID MESSENGER-RNA; GENETIC POLYMORPHISMS; ABSOLUTE QUANTIFICATION; TRYPTIC PEPTIDES; PROTEIN; EXPRESSION; MALDI; IDENTIFICATION; MICROSOMES; ACTIVATION AB The major objective of personalized medicine is to select optimized drug therapies and to a large degree such mission is determined by the expression profiles of cytochrome(s) P450 (CYP). Accordingly, a proteomic case study in personalized medicine is provided by the superfamily of cytochromes P450. Our knowledge about CYP isozyme expression on a protein level is very limited and based exclusively on DNA/mRNA derived data. Such information is not sufficient because transcription and translation events do not lead to correlated levels of expressed proteins. Here we report expression profiles of CYPs in human liver obtained by mass spectrometry (MS)-based proteomic approach. We analyzed 32 samples of human liver microsomes (HLM) of different sexes, ages and ethnicity along with samples of recombinant human CYPs. We have experimentally confirmed that each CYP isozyme can be effectively differentiated by their unique isozyme-specific tryptic peptide(s). Trypsin digestion patterns for almost 30 human CYP isozymes were established. Those findings should assist in selecting tryptic peptides suitable for MS-based quantitation. The data obtained demonstrate remarkable differences in CYP expression profiles. CYP2E1, CYP2C8 and CYP4A11 were the only isozymes found in all HLM samples. Female and pediatric HLM samples revealed much more diverse spectrum of expressed CYPs isozymes compared to male HLM. We have confirmed expression of a number of "rare" CYP (CYP2J2, CYP4B1, CYP4V2, CYP4F3, CYP4F11, CYP8B1, CYP19A1, CYP24A1 and CYP27A1) and obtained first direct experimental data showing expression of such CYPs as CYP2F1, CYP2S1, CYP2W1, CYP4A22, CYP4X1, and CYP26A1 on a protein level. Published by Elsevier Inc. C1 [Shrivas, Kamlesh; Mindaye, Samuel T.; Getie-Kebtie, Melkamu; Alterman, Michail A.] US FDA, Tumor Vaccines & Biotechnol Branch, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Alterman, MA (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM Michail.Alterman@fda.hhs.gov NR 44 TC 7 Z9 7 U1 2 U2 31 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 2013 VL 267 IS 1 BP 125 EP 136 DI 10.1016/j.taap.2012.12.008 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 085PI UT WOS:000314626300013 PM 23274569 ER PT J AU Gans, HA Yasukawa, LL Sung, P Sullivan, B DeHovitz, R Audet, S Beeler, J Arvin, AM AF Gans, Hayley A. Yasukawa, Linda L. Sung, Phillip Sullivan, Barbara DeHovitz, Ross Audet, Susette Beeler, Judy Arvin, Ann M. TI Innate Immune Dysfunction is Associated with Enhanced Disease Severity In Infants with Severe Respiratory Syncytial Virus Bronchiolitis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE RSV; bronchiolitis; immunoparalysis; innate immunity; disease severity ID T-CELL RESPONSES; UNITED-STATES; MEASLES-VACCINE; 6-MONTH-OLD INFANTS; RHESUS-MONKEYS; ANTIBODY; AGE; MORTALITY; MOTHERS; CHILDREN AB Background. Most patients with respiratory syncytial virus (RSV) bronchiolitis requiring admission to the pediatric intensive care unit (PICU) have no risk factors for severe disease. We sought to investigate the relationship between serum cytokine concentrations, innate immune responsiveness, and RSV disease severity. Methods. Previously healthy infants (median age, 2.6 months) with RSV bronchiolitis (PICU, n = 20; floor, n = 46) and healthy matched controls (n = 14) were enrolled, and blood samples were obtained within 24 hours of admission to measure plasma tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), interleukin 8 (IL-8), and interleukin 10 (IL-10) concentrations and, whole blood lipopolysaccharide-stimulated cytokine production capacity. Results. Plasma IL-6, IL-8, and IL-10 concentrations were comparable between PICU and floor patients, but higher than in healthy controls (P < .05). In contrast, TNF-alpha, IL-6, and IL-8 production capacity was significantly decreased in PICU compared with both floor patients and healthy controls. In adjusted analyses, only impaired TNF-alpha and IL-8 production capacity were associated with longer length of stay (P = .035) and greater disease severity scores (P = .001). Conclusions. Infants with severe RSV bronchiolitis had increased plasma cytokine concentrations and yet impaired innate immunity cytokine production capacity, which predicted worse disease outcomes. Immune monitoring of otherwise healthy infants with RSV lower respiratory tract infection could help identify patients at risk for severe disease at the time of hospitalization. C1 [Gans, Hayley A.; Yasukawa, Linda L.; Sung, Phillip; Sullivan, Barbara; Arvin, Ann M.] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. [DeHovitz, Ross] Palo Alto Med Fdn, Dept Pediat, Palo Alto, CA USA. [Audet, Susette; Beeler, Judy] US FDA, Div Viral Prod, Bethesda, MD 20014 USA. RP Gans, HA (reprint author), Stanford Univ, Sch Med, Dept Pediat, 300 Pasteur Dr,Rm G 312, Stanford, CA 94305 USA. EM hagans@stanford.edu FU National Institute of Allergy and Infectious Diseases [AI37127] FX This work was supported by a grant from the National Institute of Allergy and Infectious Diseases (AI37127). NR 50 TC 9 Z9 11 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB 15 PY 2013 VL 207 IS 4 BP 574 EP 582 DI 10.1093/infdis/jis719 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 078TG UT WOS:000314121800005 PM 23300162 ER PT J AU Gross, TP Crowley, J AF Gross, Thomas P. Crowley, Jay TI Unique Device Identification and Public Health Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Gross, Thomas P.; Crowley, Jay] US FDA, Silver Spring, MD USA. RP Gross, TP (reprint author), US FDA, Silver Spring, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 14 PY 2013 VL 368 IS 7 BP 683 EP 684 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 194VA UT WOS:000322659600026 PM 23406044 ER PT J AU Yu, LX Geba, GP AF Yu, Lawrence X. Geba, Gregory P. TI Generic Pills From the Patient Perspective Dressed for Success? SO JAMA INTERNAL MEDICINE LA English DT Editorial Material C1 [Yu, Lawrence X.; Geba, Gregory P.] 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 2 TC 3 Z9 3 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD FEB 11 PY 2013 VL 173 IS 3 BP 208 EP 209 DI 10.1001/jamainternmed.2013.2283 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 121JV UT WOS:000317240400013 PM 23277345 ER PT J AU Cao, GJ Meng, JH Strain, E Stones, R Pettengill, J Zhao, SH McDermott, P Brown, E Allard, M AF Cao, Guojie Meng, Jianghong Strain, Errol Stones, Robert Pettengill, James Zhao, Shaohua McDermott, Patrick Brown, Eric Allard, Marc TI Phylogenetics and Differentiation of Salmonella Newport Lineages by Whole Genome Sequencing SO PLOS ONE LA English DT Article ID PROVIDES ACQUIRED-RESISTANCE; FIELD GEL-ELECTROPHORESIS; ESCHERICHIA-COLI K-12; UNITED-STATES; POSITIVE SELECTION; ENTERICA; EVOLUTION; RECOMBINATION; CRISPR; TYPHIMURIUM AB Salmonella Newport has ranked in the top three Salmonella serotypes associated with foodborne outbreaks from 1995 to 2011 in the United States. In the current study, we selected 26 S. Newport strains isolated from diverse sources and geographic locations and then conducted 454 shotgun pyrosequencing procedures to obtain 16-24 x coverage of high quality draft genomes for each strain. Comparative genomic analysis of 28 S. Newport strains (including 2 reference genomes) and 15 outgroup genomes identified more than 140,000 informative SNPs. A resulting phylogenetic tree consisted of four sublineages and indicated that S. Newport had a clear geographic structure. Strains from Asia were divergent from those from the Americas. Our findings demonstrated that analysis using whole genome sequencing data resulted in a more accurate picture of phylogeny compared to that using single genes or small sets of genes. We selected loci around the mutS gene of S. Newport to differentiate distinct lineages, including those between invH and mutS genes at the 39 end of Salmonella Pathogenicity Island 1 (SPI-1), ste fimbrial operon, and Clustered, Regularly Interspaced, Short Palindromic Repeats (CRISPR) associated-proteins (cas). These genes in the outgroup genomes held high similarity with either S. Newport Lineage II or III at the same loci. S. Newport Lineages II and III have different evolutionary histories in this region and our data demonstrated genetic flow and homologous recombination events around mutS. The findings suggested that S. Newport Lineages II and III diverged early in the serotype evolution and have evolved largely independently. Moreover, we identified genes that could delineate sublineages within the phylogenetic tree and that could be used as potential biomarkers for trace-back investigations during outbreaks. Thus, whole genome sequencing data enabled us to better understand the genetic background of pathogenicity and evolutionary history of S. Newport and also provided additional markers for epidemiological response. C1 [Cao, Guojie; Meng, Jianghong] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Strain, Errol] US FDA, Biostat Branch, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Stones, Robert] Food & Environm Res Agcy, York, N Yorkshire, England. [Pettengill, James; Brown, Eric; Allard, Marc] US FDA, Div Microbiol, Off Regular Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Zhao, Shaohua; McDermott, Patrick] US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD USA. RP Allard, M (reprint author), US FDA, Div Microbiol, Off Regular Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM marc.allard@fda.hhs.gov FU U.S. Food and Drug Administration FX Research funds were provided by the U.S. Food and Drug Administration. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 62 TC 19 Z9 19 U1 3 U2 35 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 11 PY 2013 VL 8 IS 2 AR e55687 DI 10.1371/journal.pone.0055687 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 092DU UT WOS:000315100000020 PM 23409020 ER PT J AU Rao, SS Mohan, KVK Atreya, CD AF Rao, Shilpakala Sainath Mohan, Ketha V. K. Atreya, Chintamani D. TI A Peptide Derived from Phage Display Library Exhibits Antibacterial Activity against E. coli and Pseudomonas aeruginosa SO PLOS ONE LA English DT Article ID CATIONIC ANTIMICROBIAL PEPTIDES; POSITIVELY CHARGED RESIDUES; ESCHERICHIA-COLI; BIOLOGICAL-ACTIVITY; PROTEIN DOCKING; NET CHARGE; HYDROPHOBICITY; ANTIBIOTICS; DISCOVERY; MEMBRANE AB Emergence of drug resistant strains to currently available antibiotics has resulted in the quest for novel antimicrobial agents. Antimicrobial peptides (AMPs) are receiving attention as alternatives to antibiotics. In this study, we used phage-display random peptide library to identify peptides binding to the cell surface of E. coli. The peptide with sequence RLLFRKIRRLKR (EC5) bound to the cell surface of E. coli and exhibited certain features common to AMPs and was rich in Arginine and Lysine residues. Antimicrobial activity of the peptide was tested in vitro by growth inhibition assays and the bacterial membrane permeabilization assay. The peptide was highly active against Gram-negative organisms and showed significant bactericidal activity against E. coli and P. aeruginosa resulting in a reduction of 5 log(10) CFU/ml. In homologous plasma and platelets, incubation of EC5 with the bacteria resulted in significant reduction of E. coli and P. aeruginosa, compared to the peptide-free controls. The peptide was non-hemolytic and non-cytotoxic when tested on eukaryotic cells in culture. EC5 was able to permeabilize the outer membrane of E. coli and P. aeruginosa causing rapid depolarization of cytoplasmic membrane resulting in killing of the cells at 5 minutes of exposure. The secondary structure of the peptide showed a a-helical conformation in the presence of aqueous environment. The bacterial lipid interaction with the peptide was also investigated using Molecular Dynamic Simulations. Thus this study demonstrates that peptides identified to bind to bacterial cell surface through phage-display screening may additionally aid in identifying and developing novel antimicrobial peptides. C1 [Rao, Shilpakala Sainath; Mohan, Ketha V. K.; Atreya, Chintamani D.] US FDA, Sect Cell Biol, Lab Cellular Hematol, Div Hematol,Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Mohan, KVK (reprint author), US FDA, Sect Cell Biol, Lab Cellular Hematol, Div Hematol,Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM krishna.ketha@fda.hhs.gov; chintamani.atreya@fda.hhs.gov FU Center for Biologics Evaluation and Research (CBER) FX SSR is a recipient of a postdoctoral fellowship at the Center for Biologics Evaluation and Research (CBER) administered by the Oak Ridge Institute for Science and Education (ORISE) through an intra -agency agreement between the U. S. Department of Energy and the U. S. Food and Drug Administration. Review of the manuscript by Drs. Salim Haddad and Xuan Chi, CBER is highly appreciated. 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 57 TC 11 Z9 15 U1 3 U2 34 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 11 PY 2013 VL 8 IS 2 AR e56081 DI 10.1371/journal.pone.0056081 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 092DU UT WOS:000315100000043 ER PT J AU McCabe, MS Bhatia, S Oeffinger, KC Reaman, GH Tyne, C Wollins, DS Hudson, MM AF McCabe, Mary S. Bhatia, Smita Oeffinger, Kevin C. Reaman, Gregory H. Tyne, Courtney Wollins, Dana S. Hudson, Melissa M. TI American Society of Clinical Oncology Statement: Achieving High-Quality Cancer Survivorship Care SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID YOUNG-ADULT SURVIVORS; ROUTINE FOLLOW-UP; BREAST-CANCER; CHILDHOOD-CANCER; PREVENTIVE CARE; POLICY STATEMENT; RANDOMIZED-TRIAL; PHYSICIANS; SURVEILLANCE; ADOLESCENT C1 [McCabe, Mary S.; Oeffinger, Kevin C.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Bhatia, Smita] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Reaman, Gregory H.] US FDA, Silver Spring, MD USA. [Tyne, Courtney; Wollins, Dana S.] Amer Soc Clin Oncol, Alexandria, VA USA. [Hudson, Melissa M.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. RP Hudson, MM (reprint author), St Jude Childrens Res Hosp, 262 Danny Thomas Pl,Mailstop 735, Memphis, TN 38105 USA. EM melissa.hudson@stjude.org FU NCI NIH HHS [K05 CA160724] NR 44 TC 107 Z9 109 U1 0 U2 11 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 FEB 10 PY 2013 VL 31 IS 5 BP 631 EP 640 DI 10.1200/JCO.2012.46.6854 PG 10 WC Oncology SC Oncology GA 088FY UT WOS:000314820400022 PM 23295805 ER PT J AU Kordzakhia, G Dmitrienko, A AF Kordzakhia, George Dmitrienko, Alex TI Superchain procedures in clinical trials with multiple objectives SO STATISTICS IN MEDICINE LA English DT Article DE multiple comparisons; familywise error rate; gatekeeping procedures; mixture procedures ID CLOSED TESTING PROCEDURES; GATEKEEPING PROCEDURES; CONFIDENCE-REGIONS; STRATEGIES; MULTISTAGE AB This paper introduces a new class of multiple testing procedures for addressing multiplicity problems arising in clinical trials with multiple objectives grouped into families. The families may correspond to equally important sets of objectives (co-primary endpoints) or ordered sets of objectives (primary and secondary endpoints). The procedures, termed superchain procedures, serve as an extension of several classes of other multiple testing procedures, including chain procedures and parallel gatekeeping procedures. Superchain procedures exhibit several desirable features, including flexible decision rules that can be tailored to a broad class of win criteria in confirmatory clinical trials. Additionally, superchain procedures enable the trial's sponsor to efficiently incorporate available distributional information to improve overall power. Finally, superchain procedures rely on straightforward testing algorithms, which facilitates their development. We illustrate the new methodology by using clinical trial examples with two and three families of objectives. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 [Kordzakhia, George] US FDA, Silver Spring, MD 20993 USA. [Dmitrienko, Alex] Quintiles Innovat, Overland Pk, KS USA. RP Kordzakhia, G (reprint author), US FDA, 10903 New Hampshire Ave,Bldg 21,Room 4603, Silver Spring, MD 20993 USA. EM george.kordzakhia@fda.hhs.gov NR 19 TC 5 Z9 5 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD FEB 10 PY 2013 VL 32 IS 3 SI SI BP 486 EP 508 DI 10.1002/sim.5537 PG 23 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 070QD UT WOS:000313524200014 PM 22903837 ER PT J AU Liu, Y Shen, JX Kainz, W Qian, SS Wu, W Chen, J AF Liu, Yan Shen, Jianxiang Kainz, Wolfgang Qian, Songsong Wu, Wen Chen, Ji TI Numerical investigations of MRI RF field induced heating for external fixation devices SO BIOMEDICAL ENGINEERING ONLINE LA English DT Article DE RF heating; External fixation device; MRI compatible devices AB Background: The magnetic resonance imaging (MRI) radio frequency (RF) field induced heating on external fixation devices can be very high in the vicinity of device screws. Such induced RF heating is related to device constructs, device placements, as well as the device insertion depth into human subjects. In this study, computational modeling is performed to determine factors associated with such induced heating. Methods: Numerical modeling, based on the finite-difference time-domain (FDTD) method, is used to evaluate the temperature rises near external device screw tips inside the ASTM phantom for both 1.5-T and 3-T MRI systems. The modeling approach consists of 1) the development of RF coils for 1.5-T and 3-T, 2) the electromagnetic simulations of energy deposition near the screw tips of external fixation devices, and 3) the thermal simulations of temperature rises near the tips of these devices. Results: It is found that changing insertion depth and screw spacing could largely affect the heating of these devices. In 1.5-T MRI system, smaller insertion depth and larger pin spacing will lead to higher temperature rise. However, for 3-T MRI system, the relation is not very clear when insertion depth is larger than 5 cm or when pin spacing became larger than 20 cm. The effect of connection bar material on device heating is also studied and the heating mechanism of the device is analysed. Conclusions: Numerical simulation is used to study RF heating for external fixation devices in both 1.5-T and 3-T MRI coils. Typically, shallower insertion depth and larger pin spacing with conductive bar lead to higher RF heating. The heating mechanism is explained using induced current along the device and power decay inside ASTM phantom. C1 [Liu, Yan; Shen, Jianxiang; Chen, Ji] Univ Houston, Houston, TX 77204 USA. [Kainz, Wolfgang] US FDA, Silver Spring, MD 20993 USA. [Qian, Songsong; Wu, Wen] Nanjing Univ Sci & Technol, Nanjing 210094, Jiangsu, Peoples R China. RP Chen, J (reprint author), Univ Houston, Houston, TX 77204 USA. EM jchen18@uh.edu NR 15 TC 4 Z9 4 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-925X J9 BIOMED ENG ONLINE JI Biomed. Eng. Online PD FEB 9 PY 2013 VL 12 AR 12 DI 10.1186/1475-925X-12-12 PG 14 WC Engineering, Biomedical SC Engineering GA 113KK UT WOS:000316665800001 PM 23394173 ER PT J AU Tobon-Velasco, JC Limon-Pacheco, JH Orozco-Ibarra, M Macias-Silva, M Vazquez-Victorio, G Cuevas, E Ali, SF Cuadrado, A Pedraza-Chaverri, J Santamaria, A AF Tobon-Velasco, Julio C. Limon-Pacheco, Jorge H. Orozco-Ibarra, Marisol Macias-Silva, Marina Vazquez-Victorio, Genaro Cuevas, Elvis Ali, Syed F. Cuadrado, Antonio Pedraza-Chaverri, Jose Santamaria, Abel TI 6-OHDA-induced apoptosis and mitochondrial dysfunction are mediated by early modulation of intracellular signals and interaction of Nrf2 and NF-kappa B factors SO TOXICOLOGY LA English DT Article DE 6-Hydroxydopamine; Nrf2/NF-kappa B pathways; Mitochondrial dysfunction; Apoptosis; Kinases signaling ID RESPIRATORY COMPLEX-I; CYTOCHROME-C RELEASE; NEURONAL CELL-DEATH; PARKINSONS-DISEASE; OXIDATIVE STRESS; PC12 CELLS; DOPAMINERGIC-NEURONS; NEUROBLASTOMA-CELLS; DISTINCT MECHANISMS; HYDROGEN-PEROXIDE AB 6-Hydroxydopainine (6-OHDA) is a neurotoxin that generates an experimental model of Parkinson's disease in rodents and is commonly employed to induce a lesion in dopaminergic pathways. The characterization of those molecular mechanisms linked to 6-OHDA-induced early toxicity is needed to better understand the cellular events further leading to neurodegeneration. The present work explored how 6-OHDA triggers early downstream signaling pathways that activate neurotoxicity in the rat striatum. Mitochondrial function, caspases-dependent apoptosis, kinases signaling (Akt, ERK 1/2, SAP/JNK and p38) and crosstalk between nuclear factor kappa B (NF-kappa B) and nuclear factor-erythroid-2-related factor 2 (Nrf2) were evaluated at early times post-lesion. We found that 6-OHDA initiates cell damage via mitochondrial complex I inhibition, cytochrome c and apoptosis-inducing factor (AIF) release, as well as activation of caspases 9 and 3 to induce apoptosis, kinase signaling modulation and NF-kappa B-mediated inflammatory responses, accompanied by inhibition of antioxidant systems regulated by the Nrf2 pathway. Our results suggest that kinases SAP/JNK and p38 up-regulation may play a role in the early stages of 6-OHDA toxicity to trigger intrinsic pathways for apoptosis and enhanced NF-kappa B activation. In turn, these cellular events inhibit the activation of cytoprotective mechanisms, thereby leading to a condition of general damage. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Tobon-Velasco, Julio C.; Santamaria, Abel] SSA, Inst Nacl Neurol & Neurocirugia, Lab Aminoacidos Excitadores, Mexico City 14269, DF, Mexico. [Tobon-Velasco, Julio C.; Limon-Pacheco, Jorge H.; Pedraza-Chaverri, Jose] Univ Nacl Autonoma Mexico, Fac Quim, Dept Biol, Mexico City 04510, DF, Mexico. [Limon-Pacheco, Jorge H.; Orozco-Ibarra, Marisol] SSA, Inst Nacl Neurol & Neurocirugia, Lab Neurobiol Mol & Celular INNN UNAM, Mexico City 14269, DF, Mexico. [Macias-Silva, Marina; Vazquez-Victorio, Genaro] Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Biol Celular & Desarrollo, Mexico City 04510, DF, Mexico. [Cuevas, Elvis; Ali, Syed F.; Santamaria, Abel] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Cuadrado, Antonio] Ctr Invest Red Sobre Enfermedades Neurodegenerat, Inst Invest Biomed Alberto Sols UAM CSIC, Madrid, Spain. RP Santamaria, A (reprint author), SSA, Inst Nacl Neurol & Neurocirugia, Lab Aminoacidos Excitadores, Mexico City 14269, DF, Mexico. EM pedraza@unam.mx; absada@yahoo.com OI Cuadrado, Antonio/0000-0002-3444-9012 FU PAPIIT/UNAM [IN201910]; CONACyT [129838, 168356]; CONACyT-Mexico [239757, 46497]; Santander Bank FX This work was supported in part by PAPIIT/UNAM (IN201910) and CONACyT (129838 J.P.-C.) and (168356 MO-I). J.C. Tobon-Velasco is scholarship holder from CONACyT-Mexico (239757, 46497), and gratefully acknowledges Santander Bank for the fellowship and scholarship student exchange. J.H. Limon-Pacheco is grant-fellowship from CONACYT 129838- J.P.-C. Authors would like to thank Dr. Isabel Lastres-Becker (IIB-UAM and CIBERNED) and Dr. Monica Torres-Ramos (INNN-MVS/SSA) for critical reading of the manuscript and stimulating discussions. We also thank Drs. Ismael Torres and Enrique Pinzon for their support in supplying experimental animals, and M.Sc. Omar N. Medina-Campos (FQ-UNAM) for technical support. NR 48 TC 28 Z9 31 U1 0 U2 20 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD FEB 8 PY 2013 VL 304 BP 109 EP 119 DI 10.1016/j.tox.2012.12.011 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 111LH UT WOS:000316522300013 PM 23274087 ER PT J AU Mollan, TL Banerjee, S Wu, G Siburt, CJP Tsai, AL Olson, JS Weiss, MJ Crumbliss, AL Alayash, AI AF Mollan, Todd L. Banerjee, Sambuddha Wu, Gang Siburt, Claire J. Parker Tsai, Ah-Lim Olson, John S. Weiss, Mitchell J. Crumbliss, Alvin L. Alayash, Abdu I. TI alpha-Hemoglobin Stabilizing Protein (AHSP) Markedly Decreases the Redox Potential and Reactivity of alpha-Subunits of Human HbA with Hydrogen Peroxide SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-THALASSEMIA; IN-VIVO; MOLECULAR-MECHANISM; HUMAN OXYHEMOGLOBIN; GLOBIN BINDING; GUINEA-PIGS; CHAINS; OXIDATION; HEME; MYOGLOBIN AB alpha-Hemoglobin stabilizing protein (AHSP) is a molecular chaperone that binds monomeric alpha-subunits of human hemoglobin A (HbA) and modulates heme iron oxidation and subunit folding states. Although AHSP center dot alpha Hb complexes autoxidize more rapidly than HbA, the redox mechanisms appear to be similar. Both metHbA and isolated met-beta-subunits undergo further oxidation in the presence of hydrogen peroxide (H2O2) to form ferryl heme species. Surprisingly, much lower levels of H2O2-induced ferryl heme are produced by free met-alpha-subunits as compared with met-beta-subunits, and no ferryl heme is detected in H2O2-treated AHSP center dot met-alpha-complex at pH values from 5.0 to 9.0 at 23 degrees C. Ferryl heme species were similarly not detected in AHSP center dot met-alpha Pro-30 mutants known to exhibit different rates of autoxidation and hemin loss. EPR data suggest that protein-based radicals associated with the ferryl oxidation state exist within HbA alpha- and beta-subunits. In contrast, treatment of free alpha-subunits with H2O2 yields much smaller radical signals, and no radicals are detected when H2O2 is added to AHSP center dot alpha-complexes. AHSP binding also dramatically reduces the redox potential of alpha-subunits, from +40 to -78 mV in 1 M glycine buffer, pH 6.0, at 8 degrees C, demonstrating independently that AHSP has a much higher affinity for Fe(III) versus Fe(II) alpha-subunits. Hexacoordination in the AHSP center dot met-alpha complex markedly decreases the rate of the initial H2O2 reaction with iron and thus provides alpha-subunits protection against damaging oxidative reactions. C1 [Mollan, Todd L.; Alayash, Abdu I.] US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20852 USA. [Banerjee, Sambuddha; Siburt, Claire J. Parker; Crumbliss, Alvin L.] Duke Univ, Dept Chem, Durham, NC 27708 USA. [Wu, Gang; Tsai, Ah-Lim] Univ Texas Houston, Sch Med, Dept Internal Med, Div Hematol, Houston, TX 77030 USA. [Olson, John S.] Rice Univ, Dept Biochem & Cell Biol, Houston, TX 77251 USA. [Weiss, Mitchell J.] Univ Penn, Cell & Mol Biol Grp, Philadelphia, PA 19104 USA. RP Alayash, AI (reprint author), US FDA, CBER, NIH, 8800 Rockville Pike,Bldg 29,Rm 112, Bethesda, MD 20852 USA. EM abdu.alayash@fda.hhs.gov FU National Institutes of Health [HL110900, HL095821, HL47020, GM35649, DK61692, HL087427, GM008362]; Welch Grant [C-0612]; National Science Foundation [CHE 0809466]; United States Food and Drug Administration [MODSCI 2011]; Duke University FX This work was supported, in whole or in part, by National Institutes of Health Grants HL110900 (to A. I. A.), HL095821 (to A.-L. T.), HL47020 (to J. S. O.), HL110900 (to J. S. O.), GM35649 (to J. S. O.), DK61692 (to M. J. W.), HL087427 (to M. J. W.), and GM008362 (to T. L. M.), Welch Grant C-0612 (to J. S. O.), National Science Foundation Grant CHE 0809466 (to A. L. C.), and the United States Food and Drug Administration (MODSCI 2011) (to A. I. A.).; Supported by a grant from Duke University. NR 58 TC 11 Z9 11 U1 0 U2 9 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 8 PY 2013 VL 288 IS 6 BP 4288 EP 4298 DI 10.1074/jbc.M112.412064 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 088OP UT WOS:000314845000057 PM 23264625 ER PT J AU Turner, JW Paranjpye, RN Landis, ED Biryukov, SV Gonzalez-Escalona, N Nilsson, WB Strom, MS AF Turner, Jeffrey W. Paranjpye, Rohinee N. Landis, Eric D. Biryukov, Stanley V. Gonzalez-Escalona, Narjol Nilsson, William B. Strom, Mark S. TI Population Structure of Clinical and Environmental Vibrio parahaemolyticus from the Pacific Northwest Coast of the United States SO PLOS ONE LA English DT Article ID PANDEMIC SPREAD; CHESAPEAKE BAY; SEROVARS O3-K6; SEQUENCE; STRAINS; DIVERSITY; OYSTERS; GASTROENTERITIS; INFECTIONS; SHELLFISH AB Vibrio parahaemolyticus is a common marine bacterium and a leading cause of seafood-borne bacterial gastroenteritis worldwide. Although this bacterium has been the subject of much research, the population structure of cold-water populations remains largely undescribed. We present a broad phylogenetic analysis of clinical and environmental V. parahaemolyticus originating largely from the Pacific Northwest coast of the United States. Repetitive extragenic palindromic PCR (REP-PCR) separated 167 isolates into 39 groups and subsequent multilocus sequence typing (MLST) separated a subset of 77 isolates into 24 sequence types. The Pacific Northwest population exhibited a semi-clonal structure attributed to an environmental clade (ST3, N = 17 isolates) clonally related to the pandemic O3:K6 complex and a clinical clade (ST36, N = 20 isolates) genetically related to a regionally endemic O4:K12 complex. Further, the identification of at least five additional clinical sequence types (i.e., ST43, 50, 65, 135 and 417) demonstrates that V. parahaemolyticus gastroenteritis in the Pacific Northwest is polyphyletic in nature. Recombination was evident as a significant source of genetic diversity and in particular, the recA and dtdS alleles showed strong support for frequent recombination. Although pandemic-related illnesses were not documented during the study, the environmental occurrence of the pandemic clone may present a significant threat to human health and warrants continued monitoring. It is evident that V. parahaemolyticus population structure in the Pacific Northwest is semi-clonal and it would appear that multiple sequence types are contributing to the burden of disease in this region. C1 [Turner, Jeffrey W.; Paranjpye, Rohinee N.; Biryukov, Stanley V.; Nilsson, William B.; Strom, Mark S.] NOAA, NW Fisheries Sci Ctr, Natl Marine Fisheries Serv, Seattle, WA 98115 USA. [Turner, Jeffrey W.] Univ Washington, Sch Oceanog, Ctr Environm Genom, Seattle, WA 98195 USA. [Landis, Eric D.] US FDA, Ctr Vet Med, Rockville, MD 20857 USA. [Gonzalez-Escalona, Narjol] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Turner, JW (reprint author), NOAA, NW Fisheries Sci Ctr, Natl Marine Fisheries Serv, Seattle, WA 98115 USA. EM jeff.turner@noaa.gov OI Gonzalez-Escalona, Narjol/0000-0003-4568-0022 FU National Oceanic and Atmospheric Administration's (NOAA) Oceans and Human Health Initiative (OHHI); NOAA's National Marine Fisheries Service (NMFS); National Research Council's Research Associateship Program (NRC-RAP) FX Funding sources for this study include National Oceanic and Atmospheric Administration's (NOAA) Oceans and Human Health Initiative (OHHI) (http://oceansandhumanhealth.noaa.gov), NOAA's National Marine Fisheries Service (NMFS) (http://www.nmfs.noaa.gov) and the National Research Council's Research Associateship Program (NRC-RAP) (http://sites.nationalacademies.org/pga/rap/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 34 Z9 38 U1 2 U2 26 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 7 PY 2013 VL 8 IS 2 AR e55726 DI 10.1371/journal.pone.0055726 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 092XV UT WOS:000315157200053 PM 23409028 ER PT J AU Lawrence, B Gantt, G Samuels-Reid, J Wagman, V Cummins, S Wanna-Nakamura, S Gilchrist, J AF Lawrence, Brenda Gantt, Gail Samuels-Reid, Joy Wagman, Victoria Cummins, Susan Wanna-Nakamura, Suad Gilchrist, Julie TI Suffocation Deaths Associated With Use of Infant Sleep Positioners-United States, 1997-2011 (Reprinted from MMWR, vol 46, pg 933-937, 2012) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 [Lawrence, Brenda; Gantt, Gail; Samuels-Reid, Joy; Wagman, Victoria] CDC, Ctr Devices & Radiol Hlth, Atlanta, GA 30333 USA. [Cummins, Susan] CDC, Ctr Drug Evaluat & Res, US FDA, Atlanta, GA 30333 USA. [Wanna-Nakamura, Suad] CDC, Div Hlth Sci, Consumer Prod Safety Commiss, Atlanta, GA 30333 USA. [Gilchrist, Julie] CDC, Div Unintent Injury Prevent, Natl Ctr Injury Prevent & Control, Atlanta, GA 30333 USA. RP Samuels-Reid, J (reprint author), CDC, Ctr Devices & Radiol Hlth, Atlanta, GA 30333 USA. EM joy.samuels-reid@fda.hhs.gov NR 1 TC 0 Z9 0 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 6 PY 2013 VL 309 IS 5 BP 432 EP 434 DI 10.1001/jama.2012.157080 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 083LY UT WOS:000314466900008 ER PT J AU Handy, SM Timme, RE Jacob, SM Deeds, JR AF Handy, Sara M. Timme, Ruth E. Jacob, Salena M. Deeds, Jonathan R. TI Development of a Locked Nucleic Acid Real-Time Polymerase Chain Reaction Assay for the Detection of Pinus armandii in Mixed Species Pine Nut Samples Associated with Dysgeusia SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Locked nucleic acid; RT-PCR; pine nut; pine mouth; Pinus armandii; dysgeusia ID PCR; FOOD; IDENTIFICATION; DNA AB Recent work has shown that the presence of the species Pinus armandii, even when occurring as species mixtures of pine nuts, is correlated with taste disturbance (dysgeusia), also referred to as "pine mouth". Because of this known possibility of pine nut mixtures, a need was identified for a rapid streamlined assay to detect the presence of this species in the presence of other types of pine nuts. A locked nucleic acid probe was employed in a real-time polymerase chain reaction (RT-PCR) forrnat to detect a single nucleotide polymorphism (SNP) unique to this species. This assay was able to detect P. armandii in homogenates down to similar to 1% concentration (the lowest level tested) in the presence of several commonly co-occurring and closely related species of pine and should prove to be a useful tool for the detection of this species in food products. C1 [Handy, Sara M.; Timme, Ruth E.; Jacob, Salena M.; Deeds, Jonathan R.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. RP Handy, SM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. EM sara.handy@fda.hhs.gov RI Handy, Sara/C-6195-2008 NR 24 TC 6 Z9 6 U1 3 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD FEB 6 PY 2013 VL 61 IS 5 BP 1060 EP 1066 DI 10.1021/jf304223a PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 087WL UT WOS:000314795000007 PM 23311709 ER PT J AU Bird, ST Hartzema, AG Brophy, JM Etminan, M Delaney, JAC AF Bird, Steven T. Hartzema, Abraham G. Brophy, James M. Etminan, Mahyar Delaney, Joseph A. C. TI Risk of venous thromboembolism in women with polycystic ovary syndrome: a population-based matched cohort analysis SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; ORAL-CONTRACEPTIVES; METABOLIC SYNDROME; DISEASE; METAANALYSIS; PREVALENCE AB Background: There is an increased risk of venous thromboembolism among women taking oral contraceptives. However, whether there is an additional risk among women with polycystic ovary syndrome (PCOS) is unknown. Methods: We developed a population-based cohort from the IMS LifeLink Health Plan Claims Database, which includes managed care organizations in the United States. Women aged 1846 years taking combined oral contraceptives and who had a claim for PCOS (n = 43 506) were matched, based on a propensity score, to control women (n = 43 506) taking oral contraceptives. Venous thromboembolism was defined using administrative coding and use of anticoagulation. We used Cox proportional hazards models to assess the relative risk (RR) of venous thromboembolism among users of combined oral contraceptives with and without PCOS. Results: The incidence of venous thromboembolism among women with PCOS was 23.7/10 000 person-years, while that for matched controls was 10.9/10 000 person-years. Women with PCOS taking combined oral contraceptives had an RR for venous thromboembolism of 2.14 (95% confidence interval [CI] 1.41-3.24) compared with other contraceptive users. The incidence of venous thromboembolism was 6.3/10 000 person-years among women with PCOS not taking oral contraceptives; the incidence was 4.1/10 000 person-years among matched controls. The RR of venous thromboembolism among women with PCOS not taking oral contraceptives was 1.55 (95% CI 1.10-2.19). Interpretation: We found a 2-fold increased risk of venous thromboembolism among women with PCOS who were taking combined oral contraceptives and a 1.5-fold increased risk among women with PCOS not taking oral contraceptives. Physicians should consider the increased risk of venous thromboembolism when prescribing contraceptive therapy to women with PCOS. C1 [Bird, Steven T.] US FDA, Dept Hlth & Human Serv, Ctr Drug Evaluat & Res, Off Management & Acad Collaborat Program, Gainesville, FL USA. [Bird, Steven T.; Hartzema, Abraham G.; Delaney, Joseph A. C.] Univ Florida, Coll Pharm, Dept Pharmaceut Outcome & Policy, Gainesville, FL USA. [Brophy, James M.] McGill Univ, Dept Med & Epidemiol, Montreal, PQ, Canada. [Etminan, Mahyar] Univ British Columbia, Sch Med, Pharmaceut Outcomes Programme, Vancouver, BC V5Z 1M9, Canada. RP Bird, ST (reprint author), US FDA, Dept Hlth & Human Serv, Ctr Drug Evaluat & Res, Off Management & Acad Collaborat Program, Gainesville, FL USA. EM bird.steven@gmail.com FU McGill University Health Centre; Fonds de la Recherche en Sante du Quebec; Ministere de la Sante et des Services Sociaux; le Fonds de la Recherche en Sante du Quebec; Agency for Healthcare Research and Quality [R21 HS019516-01]; National Institutes of Health FX This work was supported by an unrestricted operating grant funded in part by the McGill University Health Centre, Fonds de la Recherche en Sante du Quebec, and the Ministere de la Sante et des Services Sociaux. James Brophy is a physician scientist who receives financial support from le Fonds de la Recherche en Sante du Quebec. Joseph Delaney receives financial support from Agency for Healthcare Research and Quality (grant no. R21 HS019516-01). Abraham Hartzema holds a grant from the National Institutes of Health and is the principal investigator for the Observational Medical Outcomes Partnership, a private-public partnership designed to help improve drug safety monitoring. NR 20 TC 38 Z9 38 U1 0 U2 1 PU CMA-CANADIAN MEDICAL ASSOC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 5W8, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD FEB 5 PY 2013 VL 185 IS 2 BP E115 EP E120 DI 10.1503/cmaj.120677 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 132AV UT WOS:000318041000021 PM 23209115 ER PT J AU Benskin, JP Ikonomou, MG Gobas, FAPC Begley, TH Woudneh, MB Cosgrove, JR AF Benskin, Jonathan P. Ikonomou, Michael G. Gobas, Frank A. P. C. Begley, Timothy H. Woudneh, Million B. Cosgrove, John R. TI Biodegradation of N-Ethyl Perfluorooctane Sulfonamido Ethanol (EtFOSE) and EtFOSE-Based Phosphate Diester (SAmPAP Diester) in Marine Sediments SO ENVIRONMENTAL SCIENCE & TECHNOLOGY LA English DT Article ID FOOD-WEB; LAKE-ONTARIO; PERFLUOROALKYL CONTAMINANTS; PERFLUORINATED COMPOUNDS; TROPHIC MAGNIFICATION; LIVER-MICROSOMES; CARBOXYLIC-ACIDS; PFOS EXPOSURE; PRECURSORS; PERFLUOROCHEMICALS AB Investigations into the biodegradation potential of perfluorooctane sulfonate (PFOS)-precursor candidates have focused on low molecular weight substances (e.g., N-ethyl perfluorooctane sulfonamido ethanol (EtFOSE)) in wastewater treatment plant sludge. Few data are available on PFOS-precursor biodegradation in other environmental compartments, and nothing is known about the stability of high-molecular-weight perfluorooctane sulfonamide-based substances such as the EtFOSE-based phosphate diester (SAmPAP diester) in any environmental compartment. In the present work, the biodegradation potential of SAmPAP diester and EtFOSE by bacteria in marine sediments was evaluated over 120 days at 4 and 25 degrees C. At both temperatures, EtFOSE was transformed to a suite of products, including N-ethyl perfluorooctane sulfonamidoacetate, perfluorooctane sulfonamidoacetate, N-ethyl perfluorooctane sulfonamide, perfluorooctane sulfonamide, and perfluorooctane sulfonate. Transformation was significantly more rapid at 25 degrees C (t(1/2) = 44 +/- 3.4 days; error represents standard error of the mean (SEM)) compared to 4 degrees C (t(1/2) = 160 +/- 17 days), but much longer than previous biodegradation studies involving EtFOSE in sludge (t(1/2) similar to 0.7-4.2 days). In contrast, SAmPAP diester was highly recalcitrant to microbial degradation, with negligible loss and/or associated product formation observed after 120 days at both temperatures, and an estimated half-life of >380 days at 25 degrees C (estimated using the lower bounds 95% confidence interval of the slope). We hypothesize that the hydrophobicity of SAmPAP diester reduces its bioavailability, thus limiting biotransformation by bacteria in sediments. The lengthy biodegradation half-life of EtFOSE and recalcitrant nature of SAmPAP diester in part explains the elevated concentrations of PFOS-precursors observed in urban marine sediments from Canada, Japan, and the U.S, over a decade after phase-out of their production and commercial application in these countries. C1 [Benskin, Jonathan P.; Woudneh, Million B.; Cosgrove, John R.] AXYS Analyt Serv Ltd, Sidney, BC V8L 5X2, Canada. [Benskin, Jonathan P.; Ikonomou, Michael G.] Fisheries & Oceans Canada DFO, Inst Ocean Sci, Sidney, BC V8L 4B2, Canada. [Gobas, Frank A. P. C.] Simon Fraser Univ, Sch Resource & Environm Management, Fac Environm, Burnaby, BC V5A 1S6, Canada. [Begley, Timothy H.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Benskin, JP (reprint author), AXYS Analyt Serv Ltd, 2045 Mills Rd W, Sidney, BC V8L 5X2, Canada. EM jbenskin@axys.com OI Benskin, Jonathan/0000-0001-5940-637X FU Natural Sciences and Engineering Research Council (NSERC) FX The Natural Sciences and Engineering Research Council (NSERC) is acknowledged for support in the form of an Industrial Research and Development Fellowship (J.P.B.). Scott McCaughran and Erik Klaasen (DFO) are thanked for their assistance with setup of biodegradation experiments. NR 42 TC 24 Z9 26 U1 7 U2 110 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0013-936X J9 ENVIRON SCI TECHNOL JI Environ. Sci. Technol. PD FEB 5 PY 2013 VL 47 IS 3 BP 1381 EP 1389 DI 10.1021/es304336r PG 9 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA 086HU UT WOS:000314675500028 PM 23305554 ER PT J AU Delmonte, P Fardin-Kia, AR Rader, JI AF Delmonte, Pierluigi Fardin-Kia, Ali Reza Rader, Jeanne I. TI Separation of Fatty Acid Methyl Esters by GC-Online Hydrogenation x GC SO ANALYTICAL CHEMISTRY LA English DT Article ID 2-DIMENSIONAL GAS-CHROMATOGRAPHY; LIQUID STATIONARY-PHASE; QUADRUPOLE MASS-SPECTROMETER; IONIC LIQUIDS; SAMPLE DIMENSIONALITY; COLUMN; MARINE; BLENDS; SYSTEM; OIL AB The separation of fatty acid methyl esters (FAME) provided by a 200 m x 0.25 mm SLB-IL111 capillary column is enhanced by adding a second dimension of separation (D-2) in a GC x GC design. Rather than employing two GC columns of different polarities or using different elution temperatures, the separation in the two-dimensional space is achieved by altering the chemical structure of selected analytes between the two dimensions of separation. A capillary tube coated with palladium is added between the first dimension of separation (D-1) column and the cryogenic modulator, providing the reduction of unsaturated FAMEs to their fully saturated forms. The D-2 separation is achieved using a 2.5 m x 0.10 mm SLB-IL111 capillary column and separates FAMEs based solely on their carbon skeleton. The two-dimensional separation can be easily interpreted based on the principle that all the saturated FAMEs lie on a straight diagonal line bisecting the separation plane, while the FAMEs with the same carbon skeleton but differing in the number, geometric configuration or position of double bonds lie on lines parallel to the D-1 time axis. This technique allows the separation of trans fatty acids (FM) and polyunsaturated FM (PUFAs) in a single experiment and eliminates the overlap between PUFAs with different chain lengths. To our knowledge, this the first example of GC X GC in which a chemical change is instituted between the two dimensions to alter the relative retentions of components and identify unsaturated FAMEs. C1 [Delmonte, Pierluigi; Fardin-Kia, Ali Reza; Rader, Jeanne I.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Delmonte, P (reprint author), US FDA, HFS-717,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Pierluigi.delmonte@fda.hhs.gov NR 44 TC 12 Z9 13 U1 0 U2 57 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD FEB 5 PY 2013 VL 85 IS 3 BP 1517 EP 1524 DI 10.1021/ac302707z PG 8 WC Chemistry, Analytical SC Chemistry GA 086IA UT WOS:000314676100041 PM 23256663 ER PT J AU Ye, HP Boyne, MT Buhse, LF Hill, J AF Ye, Hongping Boyne, Michael T., II Buhse, Lucinda F. Hill, John TI Direct Approach for Qualitative and Quantitative Characterization of Glycoproteins Using Tandem Mass Tags and an LTQ Orbitrap XL Electron Transfer Dissociation Hybrid Mass Spectrometer SO ANALYTICAL CHEMISTRY LA English DT Article ID POSTTRANSLATIONAL MODIFICATIONS; CULTURE-CONDITIONS; PROTEOMIC ANALYSIS; LINKED GLYCANS; CELL-CULTURE; GLYCOSYLATION; PROTEIN; QUANTIFICATION; IDENTIFICATION; ITRAQ AB The application of multiplexed isobaric tandem mass tag (TMT) labeling and an LTQ Orbitrap XL ETD (electron transfer dissociation) hybrid mass spectrometer as a direct approach for qualitative and quantitative characterization of glycoproteins is reported. Bovine fetuin was used as a model glycoprotein in this study. For online liquid chromatography-mass spectrometry (LC-MS) analysis, high-resolution, mass accurate full scan MS spectra were acquired in the Orbitrap mass analyzer followed by data-dependent tandem mass spectrometry (MS/MS) with alternating collision-induced dissociation (CID), ETD, and higher-energy collisional dissociation (H CD) scans. An additional in-source dissociation scan was used as a highly sensitive and selective detection method for eluting glycosylated peptides. By alternatively using three different dissociation methods, 23 glycoforms from all 5 corresponding glycopeptides were identified from a trypsin digest of bovine fetuin. With ETD, labile glycans were retained without any signs of carbohydrate cleavage with concurrent fragmentation of the peptide backbone. Glycosylation sites were clearly localized from the ETD fragmentation data. Glycan structure elucidation was accomplished using CID. The CID experiments generated fragment ions predominantly from cleavage of glycosidic bonds without breaking the peptide bond. Novel to this method, the TMT labeling protocol was modified and adapted for higher labeling efficiency, and a TriVersa NanoMate was used to reinfuse samples to improve ETD and HCD spectra of glycopeptides. Quantification with TMT was verified based on the HCD spectra from multiple nonglycopeptides and glycopeptides. This method can be used as a qualitative and quantitative technique for direct characterization of glycoproteins and has applicability for detection of counterfeit glycoprotein drug products. C1 [Ye, Hongping; Boyne, Michael T., II; Buhse, Lucinda F.] US FDA, CDER, DPA, St Louis, MO 63101 USA. [Hill, John] US FDA, CDER, ONDQA DPAII, Silver Spring, MD 20993 USA. RP Ye, HP (reprint author), US FDA, Div Pharmaceut Anal, 1114 Market St,Room 1002, St Louis, MO 63101 USA. EM hongping.ye@fda.hhs.gov NR 42 TC 23 Z9 23 U1 8 U2 93 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD FEB 5 PY 2013 VL 85 IS 3 BP 1531 EP 1539 DI 10.1021/ac3026465 PG 9 WC Chemistry, Analytical SC Chemistry GA 086IA UT WOS:000314676100043 PM 23249142 ER PT J AU Slayton, RB Turabelidze, G Bennett, SD Schwensohn, CA Yaffee, AQ Khan, F Butler, C Trees, E Ayers, TL Davis, ML Laufer, AS Gladbach, S Williams, I Gieraltowski, LB AF Slayton, Rachel B. Turabelidze, George Bennett, Sarah D. Schwensohn, Colin A. Yaffee, Anna Q. Khan, Faisal Butler, Cindy Trees, Eija Ayers, Tracy L. Davis, Marjorie L. Laufer, Alison S. Gladbach, Stephen Williams, Ian Gieraltowski, Laura B. TI Outbreak of Shiga Toxin-Producing Escherichia coli (STEC) O157:H7 Associated with Romaine Lettuce Consumption, 2011 SO PLOS ONE LA English DT Article ID FOODBORNE ILLNESS; UNITED-STATES; CALIFORNIA; O157-H7 AB Background: Shiga toxin-producing Escherichia coli (STEC) O157:H7 is the causal agent for more than 96,000 cases of diarrheal illness and 3,200 infection-attributable hospitalizations annually in the United States. Materials and Methods: We defined a confirmed case as a compatible illness in a person with the outbreak strain during 10/07/2011-11/30/2011. Investigation included hypothesis generation, a case-control study utilizing geographically-matched controls, and a case series investigation. Environmental inspections and tracebacks were conducted. Results: We identified 58 cases in 10 states; 67% were hospitalized and 6.4% developed hemolytic uremic syndrome. Any romaine consumption was significantly associated with illness (matched Odds Ratio (mOR) = 10.0, 95% Confidence Interval (CI) = 2.1-97.0). Grocery Store Chain A salad bar was significantly associated with illness (mOR = 18.9, 95% CI = 4.5-176.8). Two separate traceback investigations for romaine lettuce converged on Farm A. Case series results indicate that cases (64.9%) were more likely than the FoodNet population (47%) to eat romaine lettuce (p-value = 0.013); 61.3% of cases reported consuming romaine lettuce from the Grocery Store Chain A salad bar. Conclusions: This multistate outbreak of STEC O157:H7 infections was associated with consumption of romaine lettuce. Traceback analysis determined that a single common lot of romaine lettuce harvested from Farm A was used to supply Grocery Store Chain A and a university campus linked to a case with the outbreak strain. An investigation at Farm A did not identify the source of contamination. Improved ability to trace produce from the growing fields to the point of consumption will allow more timely prevention and control measures to be implemented. C1 [Slayton, Rachel B.; Bennett, Sarah D.; Laufer, Alison S.] Ctr Dis Control & Prevent, Epidem Intelligence Serv, Atlanta, GA 30333 USA. [Slayton, Rachel B.; Bennett, Sarah D.; Schwensohn, Colin A.; Yaffee, Anna Q.; Trees, Eija; Ayers, Tracy L.; Laufer, Alison S.; Williams, Ian; Gieraltowski, Laura B.] Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, Atlanta, GA USA. [Turabelidze, George; Butler, Cindy; Gladbach, Stephen] Missouri Dept Hlth & Senior Serv, Eastern Dist Off, St Louis, MO USA. [Khan, Faisal] St Louis Cty Dept Hlth, Communicable Dis Control Serv, St Louis, MO USA. [Davis, Marjorie L.] US FDA, Coordinated Outbreak Response & Evaluat Team, College Pk, MD USA. RP Slayton, RB (reprint author), Ctr Dis Control & Prevent, Epidem Intelligence Serv, Atlanta, GA 30333 USA. EM RSlayton@cdc.gov OI Slayton, Rachel/0000-0003-4699-8040; Ayers, Tracy/0000-0003-4140-3263 NR 12 TC 13 Z9 13 U1 1 U2 27 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 4 PY 2013 VL 8 IS 2 AR e55300 DI 10.1371/journal.pone.0055300 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 086NH UT WOS:000314691100041 PM 23390525 ER PT J AU Gendel, SM Khan, N Yajnik, M AF Gendel, Steven M. Khan, Nazleen Yajnik, Monali TI A Survey of Food Allergen Control Practices in the U.S. Food Industry SO JOURNAL OF FOOD PROTECTION LA English DT Article AB Despite awareness of the importance of food allergy as a public health issue, recalls and adverse reactions linked to undeclared allergens in foods continue to occur with high frequency. To reduce the overall incidence of such problems and to ensure that food-allergic consumers have the information they need to prevent adverse reactions, it is important to understand which allergen control practices are currently used by the food industry. Therefore, the U. S. Food and Drug Administration carried out directed inspections of registered food facilities in 2010 to obtain a broader understanding of industry allergen control practices in the United States. The results of these inspections show that allergen awareness and the use of allergen controls have increased greatly in the last decade, but that small facilities lag in implementing allergen controls. C1 [Gendel, Steven M.; Khan, Nazleen; Yajnik, Monali] 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 15 TC 4 Z9 4 U1 3 U2 13 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X EI 1944-9097 J9 J FOOD PROTECT JI J. Food Prot. PD FEB PY 2013 VL 76 IS 2 BP 302 EP 306 DI 10.4315/0362-028X.JFP-12-373 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 240EP UT WOS:000326078000015 PM 23433378 ER PT J AU Maks, N Fu, TJ AF Maks, Nicole Fu, Tong-Jen TI Evaluation of PCR Detection of Salmonella in Alfalfa Sprouts and Spent Irrigation Water Collected during Sprouting of Naturally Contaminated Seed SO JOURNAL OF FOOD PROTECTION LA English DT Article ID POLYMERASE-CHAIN-REACTION; ESCHERICHIA-COLI O157-H7; REACTION-BASED SYSTEM; LISTERIA; GROWTH; SPP.; FOOD; BAX AB This study evaluated the efficacy of a PCR-based system (DuPont Qualicon BAX) for detection of Salmonella in sprouts and spent irrigation water collected during sprouting of seeds naturally contaminated with Salmonella. Alfalfa seeds were grown in Mason jars at 20 and 30 degrees C for 3 days. Levels of Salmonella present in the water and sprouts were determined by most-probable-number (MPN) analysis. Background microflora levels were also determined. Samples of spent irrigation water and sprouts were enriched overnight individually in tetrathionate broth and in buffered peptone water with novobiocin at 42 degrees C and then run in the BAX system. Samples were also enriched according to the U.S. Food and Drug Administration's Bacteriological Analytical Manual (FDA BAM) method for Salmonella as a comparison. Salmonella levels were lower at 20 degrees C compared with 30 degrees C for some trials, and background microflora levels ranged from 10(7) to 10(8) CFU/g or ml at 20 degrees C and 10(8) to 10(9) CFU/g or ml at 30 degrees C. In trials with a Salmonella level >1.1 MPN/g or ml, both the BAX and FDA BAM methods were able to detect Salmonella in all samples. In trials with lower levels (0.21 MPN/g or ml or lower) of Salmonella, BAX was able to detect more positive samples than FDA BAM. For one trial with <0.003 MPN/g or ml of Salmonella, the presence of the pathogen was not indicated by either the BAX or the FDA BAM method. The results suggest that PCR detected low levels of Salmonella in sprouts or spent irrigation water collected from sprouting of naturally contaminated seeds. C1 [Maks, Nicole] IIT, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. [Fu, Tong-Jen] US FDA, Ctr Food Safety & Appl Nutr, Div Food Proc Sci & Technol, Bedford Pk, IL 60501 USA. RP Maks, N (reprint author), IIT, Inst Food Safety & Hlth, 6502 South Archer Rd, Bedford Pk, IL 60501 USA. EM maks@iit.edu FU FDA [5U01FD003801]; Institute for Food Safety and Health [5U01FD003801] FX This work was supported by Cooperative Agreement 5U01FD003801 between the FDA and Institute for Food Safety and Health. The authors thank Dr. Hongliu Ding for his assistance with the statistical analysis. NR 22 TC 4 Z9 4 U1 2 U2 17 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X EI 1944-9097 J9 J FOOD PROTECT JI J. Food Prot. PD FEB PY 2013 VL 76 IS 2 BP 314 EP 317 DI 10.4315/0362-028X.JFP-12-155 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 240EP UT WOS:000326078000017 PM 23433380 ER PT J AU Wiley, KL Treadwell, E Manigaba, K Word, B Lyn-Cook, BD AF Wiley, Kenneth L. Treadwell, Edward Manigaba, Kayihura Word, Beverly Lyn-Cook, Beverly D. TI Ethnic Differences in DNA Methyltransferases Expression in Patients with Systemic Lupus Erythematosus SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE Lupus; DNA methyltransferases; DHEA; DNMT3A; DNMT3B; DNMT1 ID T-CELLS; HISTONE DEACETYLASES; AUTOIMMUNE-DISEASES; B-CELLS; METHYLATION; DNMT1; DEMETHYLATION; ACTIVATION; PATTERNS; SEQUENCE AB Purpose Systemic lupus erythematous (SLE) is a systemic autoimmune inflammatory disease with both genetic and epigenetic etiologies. Evidence suggests that deregulation of specific genes through epigenetic mechanisms may be a contributing factor to SLE pathology. There is increasing evidence that DNA methyltransferase activity may be involved. This study demonstrated modulation in expression of DNA methyltransferases (DNMTs) according to ethnicity in patients diagnosed with SLE. Furthermore, differential expression in one of the DNMTs was found in a subset of lupus patients on dehydroepiandrosterone (DHEA) therapy. Methods Real-time PCR analyses of DNMT1, DNMT3A and DNMT3B in peripheral blood mononuclear cells from a cohort of African American and European American lupus and non-lupus women were conducted. Also, global DNA methylation was assessed using the MethylFlash (TM) methylated quantification colorimetric assay. Results Significant increase in DNMT3A (p<0.001) was shown in lupus patients when compared to age-matched healthy controls. This increase was associated with a higher SLEDI index. More striking was that expression levels for African American (AA) women were higher than European American women in the lupus populations. A subset of AA women on DHEA therapy showed a significant decrease (p<0.05) in DNMT3A expression in comparison to lupus patients not on the therapy. DHEA is an androgenic steroid found in low levels in the serum of lupus patients. Supplementation of this hormone has been shown to be beneficial to some lupus patients. DHEA was not shown to effect DNMT1 or DNMT3B expression. Increased expression was also noted in DNMT3B (p<0.05) in lupus patients compared to age-matched healthy controls. However, no significant difference was noted in DNMT1 (p=0.2148) expression between lupus patients and healthy controls. Although increases were detected in de novo methyltransferases, a global decrease (p<0.001) in 5-methycytosine was observed in lupus patients when compared to age-matched healthy controls. Conclusion These findings suggest that epigenetic changes may play a critical role in the manifestations of the disease observed among ethnic groups, particularly African American women who often have a higher incidence of lupus. DHEA therapy effects on DNMT3A expression in AA women warrant further investigation in a larger population. C1 [Wiley, Kenneth L.; Manigaba, Kayihura; Word, Beverly; Lyn-Cook, Beverly D.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Treadwell, Edward] East Carolina Brody Sch Med, Greenville, NC USA. RP Lyn-Cook, BD (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM beverly.lyn-cook@fda.hhs.gov FU FDA Office of Women's Health FX This research was funded in part by a grant from the FDA Office of Women's Health. We acknowledge Dr. George Hammons for critical reading of the manuscript and the members of our research group for valuable discussions. NR 46 TC 13 Z9 13 U1 0 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD FEB PY 2013 VL 33 IS 2 BP 342 EP 348 DI 10.1007/s10875-012-9803-z PG 7 WC Immunology SC Immunology GA 201DX UT WOS:000323122000010 PM 23054340 ER PT J AU William-Faltaos, D Chen, Y Wang, YN Gobburu, J Zhu, H AF William-Faltaos, Demiana Chen, Ying Wang, Yaning Gobburu, Jogarao Zhu, Hao TI Quantification of disease progression and dropout for Alzheimer's disease SO INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE Alzheimer's disease model; dropout model; disease model ID CLINICAL-TRIALS; COGNITIVE DETERIORATION; MODEL; PREDICTORS; PATTERNS; OUTCOMES; TACRINE AB This research aimed to quantitatively describe the natural progression of Alzheimer's disease (AD) based on ADAS-cog scores in patients with mild-to-moderate AD. ADAS-cog data from 10 placebo-controlled clinical trials including more than 2,400 patients with up to 72 weeks of treatment were used. Different models describing the time course of ADAS-cog were evaluated. Patient characteristics potentially affect score changes were assessed. Furthermore, patient dropout patterns were characterized using parametric survival models. Covariate selection was performed to identify the risk factors associated with a higher dropout rate. ADAS-cog time course in mild-to-moderate AD patients receiving placebo was best described by a log-linear model, where the intercept represents the log-transformed ADAS-cog score at Week 10, the slope is the disease progression (i.e., natural increase of ADAS-cog score) on the log scale. Covariates influencing the intercept were baseline ADAS-cog score and baseline Mini Mental State Exam score. No covariates influenced the disease progression slope. A parametric log-normal model fit the dropout data best. Baseline ADAS-cog score and age were found to be significant predictors for dropout. AD disease and dropout models were both established. These models set up a quantitative basis for future clinical trial design and endpoint selection. C1 [William-Faltaos, Demiana; Chen, Ying; Wang, Yaning; Gobburu, Jogarao; Zhu, Hao] US FDA, Off Clin Pharmacol, Div Pharmacometr, Silver Spring, MD 20993 USA. RP Zhu, H (reprint author), US FDA, Off Clin Pharmacol, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Hao.Zhu@fda.hhs.gov FU American Association of Pharmaceutical Scientists (AAPS) FX The authors declare that they have no competing interests and financial disclosure. Dr. Demiana Faltaos was supported by American Association of Pharmaceutical Scientists (AAPS) grant under the Cooperative Research And Development Agreement (CRADA) between AAPS and FDA. Dr. Kevin Krudys from Pharmacometrics division at FDA generously assisted in the preparation of the manuscript. NR 18 TC 3 Z9 3 U1 0 U2 5 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0946-1965 J9 INT J CLIN PHARM TH JI Int. J. Clin. Pharmacol. Ther. PD FEB PY 2013 VL 51 IS 2 BP 120 EP 131 DI 10.5414/CP201787 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 170GV UT WOS:000320839300005 PM 23211395 ER PT J AU Chen, JJ Mikelis, CM Zhang, YQ Gutkind, JS Zhang, BL AF Chen, Jun-Jie Mikelis, Constantinos M. Zhang, Yaqin Gutkind, J. Silvio Zhang, Baolin TI TRAIL induces apoptosis in oral squamous carcinoma cells - a crosstalk with oncogenic Ras regulated cell surface expression of death receptor 5 SO ONCOTARGET LA English DT Article DE oral cancer; TRAIL; death receptors; apoptosis; Ras; oncotarget ID CANCER-CELLS; MEDIATED APOPTOSIS; TUMOR-GROWTH; NECK-CANCER; LIGAND; ACTIVATION; INHIBITION; PATHWAY; HEAD; TRANSFORMATION AB TNF-related apoptosis inducing ligand (TRAIL) induces apoptosis through its death receptors (DRs) 4 and/or 5 expressed on the surface of target cells. The selectivity of TRAIL towards cancer cells has promoted clinical evaluation of recombinant human TRAIL (rhTRAIL) and its agonistic antibodies in treating several major human cancers including colon and non-Hodgkin's lymphoma. However, little is known about their ability in killing oral squamous cell carcinoma (OSCC) cells. In this study, we tested the apoptotic responses of a panel of seven human OSCC cell lines (HN31, HN30, HN12, HN6, HN4, Cal27, and OSCC3) to rhTRAIL and monoclonal antibodies against DR4 or DR5. We found that rhTRAIL is a potent inducer of apoptosis in most of the oral cancer cell lines tested both in vitro and in vivo. We also showed that DR5 was expressed on the surface of the tested cell lines which correlated with the cellular susceptibility to apoptosis induced by rhTRAIL and anti-DR5 antibody. By contrast, little or no DR4 was detected on the surface of OSCC3 and HN6 cells rendering cellular resistance to DR4 antibody and a reduced sensitivity to rhTRAIL. Notably, the overall TRAIL sensitivity correlated well with the levels of endogenous active Ras in the cell lines tested. Expression of a constitutively active Ras mutant (RasV12) in OSCC3 cells selectively upregulated surface expression of DR5, but not DR4, and restored TRAIL sensitivity. Our findings could have implications for the use of TRAIL receptor targeted therapies in the treatment of human OSCC tumors particularly the ones harboring constitutively active Ras mutant. C1 [Chen, Jun-Jie; Zhang, Yaqin; Zhang, Baolin] US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Off Biotechnol Prod, Bethesda, MD 20014 USA. [Mikelis, Constantinos M.; Gutkind, J. Silvio] NIH, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. RP Zhang, BL (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Off Biotechnol Prod, Bethesda, MD 20014 USA. EM Baolin.Zhang@fda.hhs.gov FU U.S. FDA Critical Path Research FX This project is supported by funding from the U.S. FDA Critical Path Research. NR 42 TC 15 Z9 16 U1 0 U2 2 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD FEB PY 2013 VL 4 IS 2 BP 206 EP 217 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 142FO UT WOS:000318782500008 PM 23470485 ER PT J AU Shabalina, SA Spiridonov, NA Kashina, A AF Shabalina, Svetlana A. Spiridonov, Nikolay A. Kashina, Anna TI Sounds of silence: synonymous nucleotides as a key to biological regulation and complexity SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RNA SECONDARY STRUCTURE; EUKARYOTIC MESSENGER-RNAS; ZIPCODE-BINDING-PROTEIN; CODON USAGE BIAS; RETICULOCYTE TRANSFER-RNA; GENOME-WIDE MEASUREMENT; BETA-ACTIN SYNTHESIS; ESCHERICHIA-COLI; GENE-EXPRESSION; CODING REGIONS AB Messenger RNA is a key component of an intricate regulatory network of its own. It accommodates numerous nucleotide signals that overlap protein coding sequences and are responsible for multiple levels of regulation and generation of biological complexity. A wealth of structural and regulatory information, which mRNA carries in addition to the encoded amino acid sequence, raises the question of how these signals and overlapping codes are delineated along non-synonymous and synonymous positions in protein coding regions, especially in eukaryotes. Silent or synonymous codon positions, which do not determine amino acid sequences of the encoded proteins, define mRNA secondary structure and stability and affect the rate of translation, folding and post-translational modifications of nascent polypeptides. The RNA level selection is acting on synonymous sites in both prokaryotes and eukaryotes and is more common than previously thought. Selection pressure on the coding gene regions follows three-nucleotide periodic pattern of nucleotide base-pairing in mRNA, which is imposed by the genetic code. Synonymous positions of the coding regions have a higher level of hybridization potential relative to non-synonymous positions, and are multifunctional in their regulatory and structural roles. Recent experimental evidence and analysis of mRNA structure and interspecies conservation suggest that there is an evolutionary tradeoff between selective pressure acting at the RNA and protein levels. Here we provide a comprehensive overview of the studies that define the role of silent positions in regulating RNA structure and processing that exert downstream effects on proteins and their functions. C1 [Shabalina, Svetlana A.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20984 USA. [Spiridonov, Nikolay A.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Kashina, Anna] Univ Penn, Sch Vet Med, Dept Anim Biol, Philadelphia, PA 19104 USA. RP Shabalina, SA (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20984 USA. EM shabalin@ncbi.nlm.nih.gov RI Shabalina, Svetlana/N-8939-2013; Spiridonov, Nikolay/B-6287-2014 OI Shabalina, Svetlana/0000-0003-2272-7473; FU DHHS (NIH, National Library of Medicine); NIH [R01HL084419] FX DHHS (NIH, National Library of Medicine) intramural funds; NIH [R01HL084419 to A.K.]. Funding for open access charge: DHHS (NIH, National Library of Medicine) intramural funds. NR 221 TC 65 Z9 67 U1 0 U2 39 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB PY 2013 VL 41 IS 4 BP 2073 EP 2094 DI 10.1093/nar/gks1205 PG 22 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 132IV UT WOS:000318062000009 PM 23293005 ER PT J AU Ishimaru, D Plant, EP Sims, AC Yount, BL Roth, BM Eldho, NV Perez-Alvarado, GC Armbruster, DW Baric, RS Dinman, JD Taylor, DR Hennig, M AF Ishimaru, Daniella Plant, Ewan P. Sims, Amy C. Yount, Boyd L., Jr. Roth, Braden M. Eldho, Nadukkudy V. Perez-Alvarado, Gabriela C. Armbruster, David W. Baric, Ralph S. Dinman, Jonathan D. Taylor, Deborah R. Hennig, Mirko TI RNA dimerization plays a role in ribosomal frameshifting of the SARS coronavirus SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RESPIRATORY SYNDROME CORONAVIRUS; IMMUNODEFICIENCY-VIRUS RNA; STEM-LOOP B; GENOMIC RNA; MESSENGER-RNA; VIRAL INFECTIVITY; CROSS-LINKING; PSEUDOKNOT; SEQUENCE; SIGNAL AB Messenger RNA encoded signals that are involved in programmed -1 ribosomal frameshifting (-1 PRF) are typically two-stemmed hairpin (H)-type pseudoknots (pks). We previously described an unusual three-stemmed pseudoknot from the severe acute respiratory syndrome (SARS) coronavirus (CoV) that stimulated -1 PRF. The conserved existence of a third stem-loop suggested an important hitherto unknown function. Here we present new information describing structure and function of the third stem of the SARS pseudoknot. We uncovered RNA dimerization through a palindromic sequence embedded in the SARS-CoV Stem 3. Further in vitro analysis revealed that SARS-CoV RNA dimers assemble through 'kissing' loop-loop interactions. We also show that loop-loop kissing complex formation becomes more efficient at physiological temperature and in the presence of magnesium. When the palindromic sequence was mutated, in vitro RNA dimerization was abolished, and frameshifting was reduced from 15 to 5.7%. Furthermore, the inability to dimerize caused by the silent codon change in Stem 3 of SARS-CoV changed the viral growth kinetics and affected the levels of genomic and subgenomic RNA in infected cells. These results suggest that the homodimeric RNA complex formed by the SARS pseudoknot occurs in the cellular environment and that loop-loop kissing interactions involving Stem 3 modulate -1 PRF and play a role in subgenomic and full-length RNA synthesis. C1 [Ishimaru, Daniella; Roth, Braden M.; Eldho, Nadukkudy V.; Armbruster, David W.; Hennig, Mirko] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Plant, Ewan P.; Taylor, Deborah R.] US FDA, Lab Hepatitis & Related Emerging Agents, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20892 USA. [Sims, Amy C.; Yount, Boyd L., Jr.; Baric, Ralph S.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Sims, Amy C.; Yount, Boyd L., Jr.; Baric, Ralph S.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. [Perez-Alvarado, Gabriela C.] So Illinois Univ, Dept Chem & Biochem, Carbondale, IL 62901 USA. [Dinman, Jonathan D.] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. RP Hennig, M (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. EM hennig@musc.edu RI Roth, Braden/L-9386-2015; OI Roth, Braden/0000-0001-7559-7671; Plant, Ewan/0000-0003-0166-5939; Dinman, Jonathan/0000-0002-2402-9698 FU Hollings Marine Laboratory NMR Facility; National Institutes of Health [AI064307, AI075297]; National Science Foundation [MCB 0845512]; National Institutes of Health; National Science Foundation FX We acknowledge the support of the Hollings Marine Laboratory NMR Facility for this work.; National Institutes of Health (www.nih.gov) to JDD [AI064307] and to RSB [AI075297]; National Science Foundation (www.nsf.gov) to MH (MCB 0845512). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding for open access charge: National Institutes of Health and National Science Foundation. NR 59 TC 6 Z9 6 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB PY 2013 VL 41 IS 4 BP 2594 EP 2608 DI 10.1093/nar/gks1361 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 132IV UT WOS:000318062000048 PM 23275571 ER PT J AU Etminan, M Bird, ST Delaney, JA Bressler, B Brophy, JM AF Etminan, Mahyar Bird, Steven T. Delaney, Joseph A. Bressler, Brian Brophy, James M. TI Isotretinoin and Risk for Inflammatory Bowel Disease A Nested Case-Control Study and Meta-analysis of Published and Unpublished Data SO JAMA DERMATOLOGY LA English DT Article ID CROHNS-DISEASE; ACNE AB Objective: To examine the association between isotretinoin and the risk for inflammatory bowel disease (IBD) among women of reproductive age. Design: Nested case-control study and meta-analysis. Setting: A US health claims database. Participants: We formed a cohort of women aged 18 to 46 years who had received at least 1 oral contraceptive prescription from May 1, 2001, through December 31, 2009. The IBD cases were required to have 3 health care contacts with documentation of IBD or a single health care contact followed by use of a drug to treat IBD. Twenty controls were selected for each case using incidence-density sampling, matched on age and date of diagnosis. Main Outcome Measures: Risk ratios (RRs) were formed for incident cases of IBD associated with the use of isotretinoin. A subgroup analysis examined the risk for IBD among those diagnosed as having Crohn disease (CD) and ulcerative colitis (UC). A meta-analysis of published and unpublished studies assessing isotretinoin and IBD used a random-effects model to estimate a pooled RR. Results: In the case-control study, we identified 2159 IBD cases (1056 with UC and 1103 with CD) and matched them with 43 180 controls. Only 10 cases (0.46%) and 191 controls (0.44%) were exposed to isotretinoin. The adjusted RR for IBD was 0.99 (95% CI, 0.52-1.90). The RRs for UC and CD were 1.10 (95% CI, 0.44-2.70) and 0.91 (0.37-2.25), respectively. For the meta-analysis, the pooled RR for IBD for the 5 studies was 0.94 (95% CI, 0.65-1.36). Conclusions: The results of this study do not suggest an increase in the risk for IBD, including UC or CD, with use of isotretinoin. Because inflammatory acne in children and adolescents carries a high psychological burden, clinicians should not be discouraged from prescribing this drug owing to a putative association with IBD. JAMA Dermatol. 2013;149(2):216-220 C1 [Etminan, Mahyar] Univ British Columbia, Therapeut Evaluat Unit, Child & Family Res Inst British Columbia, Vancouver, BC V5Z 4H4, Canada. [Bressler, Brian] Univ British Columbia, Div Gastroenterol, Vancouver, BC V5Z 4H4, Canada. [Etminan, Mahyar] Univ British Columbia, Fac Med, Dept Med, Vancouver, BC V5Z 4H4, Canada. [Bird, Steven T.] USDA, Off Management, Ctr Drug Evaluat & Res, Acad Collaborat Program, Silver Spring, MD USA. [Delaney, Joseph A.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Brophy, James M.] McGill Univ, Dept Epidemiol Biostat & Med, Montreal, PQ, Canada. RP Etminan, M (reprint author), Univ British Columbia, Therapeut Evaluat Unit, Child & Family Res Inst British Columbia, 950 W 28th Ave,Room A4-195, Vancouver, BC V5Z 4H4, Canada. EM metminan@popi.ubc.ca NR 14 TC 27 Z9 29 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6068 J9 JAMA DERMATOL JI JAMA Dermatol. PD FEB PY 2013 VL 149 IS 2 BP 216 EP 220 DI 10.1001/jamadermatol.2013.1344 PG 5 WC Dermatology SC Dermatology GA 127CH UT WOS:000317672300018 PM 23426479 ER PT J AU Kurtz, SL Foreman, O Bosio, CM Anver, MR Elkins, KL AF Kurtz, Sherry L. Foreman, Oded Bosio, Catharine M. Anver, Miriam R. Elkins, Karen L. TI Interleukin-6 Is Essential for Primary Resistance to Francisella tularensis Live Vaccine Strain Infection SO INFECTION AND IMMUNITY LA English DT Article ID CELL-MEDIATED-IMMUNITY; ACUTE-PHASE RESPONSE; T-CELLS; IN-VIVO; CHLAMYDIA-TRACHOMATIS; RESPIRATORY TULAREMIA; PULMONARY INFECTION; GAMMA-INTERFERON; DENDRITIC CELLS; KNOCKOUT MICE AB We employed Francisella tularensis live vaccine strain (LVS) to study mechanisms of protective immunity against intracellular pathogens and, specifically, to understand protective correlates. One potential molecular correlate identified previously was interleukin-6 (IL-6), a cytokine with pleotropic roles in immunity, including influences on T and B cell functions. Given its role as an immune modulator and the correlation with successful anti-LVS vaccination, we examined the role IL-6 plays in the host response to LVS. IL-6-deficient (IL-6 knockout [KO]) mice infected with LVS intradermally or intranasally or anti-IL-6-treated mice, showed greatly reduced 50% lethal doses compared to wild-type (WT) mice. Increased susceptibility was not due to altered splenic immune cell populations during infection or decreased serum antibody production, as IL-6 KO mice had similar compositions of each compared to WT mice. Although LVS-infected IL-6 KO mice produced much less serum amyloid A and haptoglobin (two acute-phase proteins) than WT mice, there were no other obvious pathophysiological differences between LVS-infected WT and IL-6 KO mice. IL-6 KO or WT mice that survived primary LVS infection also survived a high-dose LVS secondary challenge. Using an in vitro overlay assay that measured T cell activation, cytokine production, and abilities of primed splenocytes to control intracellular LVS growth, we found that IL-6 KO total splenocytes or purified T cells were slightly defective in controlling intracellular LVS growth but were equivalent in cytokine production. Taken together, IL-6 is an integral part of a successful immune response to primary LVS infection, but its exact role in precipitating adaptive immunity remains elusive. C1 [Kurtz, Sherry L.; Elkins, Karen L.] US FDA, Lab Mycobacterial Dis & Cellular Immunol, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Foreman, Oded] Jackson Lab, Sacramento, CA USA. [Bosio, Catharine M.] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. [Anver, Miriam R.] SAIC Frederick Inc, Pathol Histotechnol Lab, Frederick Natl Lab Canc Res, Frederick, MD USA. RP Elkins, KL (reprint author), US FDA, Lab Mycobacterial Dis & Cellular Immunol, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM karen.elkins@fda.hhs.gov RI Bosio, Catharine/D-7456-2015 FU National Institute of Allergy and Infectious Diseases [Y1-AI-6153-01/224-06-1322]; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This project has been funded in part by an interagency agreement with the National Institute of Allergy and Infectious Diseases (Y1-AI-6153-01/224-06-1322) and by federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. NR 54 TC 20 Z9 20 U1 0 U2 12 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 FEB PY 2013 VL 81 IS 2 BP 585 EP 597 DI 10.1128/IAI.01249-12 PG 13 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 108RD UT WOS:000316312800022 PM 23230288 ER PT J AU Khurana, T Collison, M Chew, FT Slater, JE AF Khurana, Taruna Collison, Maggie Chew, Fook Tim Slater, Jay E. TI Per a 3 Homologue of German Cockroach; A Novel Allergen Identified Using Avian Scfv Antibodies SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI) CY FEB 22-26, 2013 CL San Antonio, TX SP Amer Acad Allergy, Asthma & Immunol (AAAAI) C1 [Collison, Maggie] FDA Ctr Biol Evaluat & Resea, Rockville, MD USA. [Chew, Fook Tim] Natl Univ Singapore, Singapore 117548, Singapore. [Slater, Jay E.] FDA CBER OVRR DBPAP, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2013 VL 131 IS 2 SU S BP AB26 EP AB26 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 111WC UT WOS:000316550800094 ER PT J AU Kim, E Chin, S Steele, PH Kamilaris, JS Kamilaris, N Burk, C Vickery, BP Kulis, MD Burks, AW AF Kim, Edwin Chin, Stacy Steele, Pamela H. Kamilaris, Janet S. Kamilaris, Nikolas Burk, Caitlin Vickery, Brian P. Kulis, Michael D., Jr. Burks, A. Wesley TI Tolerance Induction in an Interim Analysis of Peanut Sublingual Immunotherapy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI) CY FEB 22-26, 2013 CL San Antonio, TX SP Amer Acad Allergy, Asthma & Immunol (AAAAI) C1 [Kim, Edwin; Steele, Pamela H.; Kamilaris, Janet S.; Kamilaris, Nikolas; Burk, Caitlin; Vickery, Brian P.; Kulis, Michael D., Jr.; Burks, A. Wesley] Univ N Carolina, Chapel Hill, NC USA. [Chin, Stacy] FDA CDER, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2013 VL 131 IS 2 SU S BP AB130 EP AB130 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 111WC UT WOS:000316550800466 ER PT J AU Virkud, Y Chin, S Kamilaris, N Kulis, MD Kamilaris, JS Steele, PH Smith, PB Vickery, BP Burks, AW AF Virkud, Yamini Chin, Stacy Kamilaris, Nik Kulis, Michael D., Jr. Kamilaris, Janet S. Steele, Pamela H. Smith, P. Brian Vickery, Brian P. Burks, A. Wesley TI Predictors of Clinical Tolerance After Peanut Oral Immunotherapy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI) CY FEB 22-26, 2013 CL San Antonio, TX SP Amer Acad Allergy, Asthma & Immunol (AAAAI) C1 [Virkud, Yamini] Duke Univ, Durham, NC USA. [Chin, Stacy] US FDA, Ctr Drug Evaluat & Res, Washington, DC 20204 USA. [Kamilaris, Nik; Kulis, Michael D., Jr.; Kamilaris, Janet S.; Steele, Pamela H.; Vickery, Brian P.; Burks, A. Wesley] Univ N Carolina, Chapel Hill, NC USA. [Smith, P. Brian] Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2013 VL 131 IS 2 SU S BP AB91 EP AB91 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 111WC UT WOS:000316550800329 ER PT J AU Seeff, LB AF Seeff, Leonard B. TI Sustained Virologic Response: Is This Equivalent to Cure of Chronic Hepatitis C? SO HEPATOLOGY LA English DT Editorial Material ID BLOOD MONONUCLEAR-CELLS; VIRUS HCV RNA; ANTIVIRAL THERAPY; DRUG-USERS; IN-VITRO; OCCULT; INFECTION; LIVER; REINFECTION; REEMERGENCE C1 [Seeff, Leonard B.] Hill Grp, Bethesda, MD USA. RP Seeff, LB (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20903 USA. EM Leonard.Seeff@fda.hhs.gov NR 31 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 2013 VL 57 IS 2 BP 438 EP 440 DI 10.1002/hep.25964 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 099TA UT WOS:000315643400004 PM 22815252 ER PT J AU Harrington, PR Naeger, LK Zeng, W AF Harrington, Patrick R. Naeger, Lisa K. Zeng, Wen TI Clinical Relevance of Detectable Hepatitis C Virus RNA in the Context of Direct-Acting Antivirals Reply SO HEPATOLOGY LA English DT Letter C1 [Harrington, Patrick R.; Naeger, Lisa K.] US FDA, Div Antiviral Prod, Off Antimicrobial Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Zeng, Wen] US FDA, Div Biometr 4, Off Biometr, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Harrington, PR (reprint author), US FDA, Div Antiviral Prod, Off Antimicrobial Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 2013 VL 57 IS 2 BP 856 EP 856 DI 10.1002/hep.25948 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 099TA UT WOS:000315643400050 PM 22806687 ER PT J AU James, SJ Shpyleva, S Melnyk, S Pavliv, O Pogribny, IP AF James, S. J. Shpyleva, Svitlana Melnyk, Stepan Pavliv, Oleksandra Pogribny, I. P. TI Complex epigenetic regulation of Engrailed-2 (EN-2) homeobox gene in the autism cerebellum SO TRANSLATIONAL PSYCHIATRY LA English DT Article DE Autism; cerebellum; DNA; EN-2; Epigenetics; histone methylation ID REAL-TIME PCR; SPECTRUM DISORDER; DNA METHYLATION; PURKINJE-CELLS; BDNF GENE; PROMOTER METHYLATION; MEMORY FORMATION; HUMAN BRAIN; EXPRESSION; CANCER AB The elucidation of epigenetic alterations in the autism brain has potential to provide new insights into the molecular mechanisms underlying abnormal gene expression in this disorder. Given strong evidence that engrailed-2 (EN-2) is a developmentally expressed gene relevant to cerebellar abnormalities and autism, the epigenetic evaluation of this candidate gene was undertaken in 26 case and control post-mortem cerebellar samples. Assessments included global DNA methylation, EN-2 promoter methylation, EN-2 gene expression and EN-2 protein levels. Chromatin immunoprecipitation was used to evaluate trimethylation status of histone H3 lysine 27 (H3K27) associated with gene downregulation and histone H3 lysine 4 (H3K4) associated with gene activation. The results revealed an unusual pattern of global and EN-2 promoter region DNA hypermethylation accompanied by significant increases in EN-2 gene expression and protein levels. Consistent with EN-2 overexpression, histone H3K27 trimethylation mark in the EN-2 promoter was significantly decreased in the autism samples relative to matched controls. Supporting a link between reduced histone H3K27 trimethylation and increased EN-2 gene expression, the mean level of histone H3K4 trimethylation was elevated in the autism cerebellar samples. Together, these results suggest that the normal EN-2 downregulation that signals Purkinje cell maturation during late prenatal and early-postnatal development may not have occurred in some individuals with autism and that the postnatal persistence of EN-2 overexpression may contribute to autism cerebellar abnormalities. Translational Psychiatry (2013) 3, e232; doi:10.1038/tp.2013.8; published online 19 February 2013 C1 [James, S. J.; Shpyleva, Svitlana; Melnyk, Stepan; Pavliv, Oleksandra] Univ Arkansas Med Sci, Dept Pediat, Arkansas Childrens Hosp Res Inst, Little Rock, AR 72202 USA. [Pogribny, I. P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP James, SJ (reprint author), Univ Arkansas Med Sci, Dept Pediat, Arkansas Childrens Hosp Res Inst, 13 Childrens Way Slot 512-41B, Little Rock, AR 72202 USA. EM jamesjill@uams.edu FU National Institute of Child Health and Development [1RO1HD051873]; Arkansas Biosciences Institute; Jane Botsford Johnson Foundation FX We would like to thank the families of individuals with autism for the thoughtful donation of post-mortem tissues to the Autism Tissue Program at the Harvard Brain Tissue Resource Center and the NICHD Brain and Tissue Bank for Developmental Disorders at the University of Maryland. This study was sponsored by National Institute of Child Health and Development; grant number: 1RO1HD051873, Arkansas Biosciences Institute and Jane Botsford Johnson Foundation. NR 65 TC 37 Z9 37 U1 2 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2158-3188 J9 TRANSL PSYCHIAT JI Transl. Psychiatr. PD FEB PY 2013 VL 3 AR e232 DI 10.1038/tp.2013.8 PG 8 WC Psychiatry SC Psychiatry GA 104LE UT WOS:000315993600007 PM 23423141 ER PT J AU Mirshekar-Syahkal, B Haak, E Kimber, GM van Leusden, K Harvey, K O'Rourke, J Laborda, J Bauer, SR de Bruijn, MFTR Ferguson-Smith, AC Dzierzak, E Ottersbach, K AF Mirshekar-Syahkal, Bahar Haak, Esther Kimber, Gillian M. van Leusden, Kevin Harvey, Kirsty O'Rourke, John Laborda, Jorge Bauer, Steven R. de Bruijn, Marella F. T. R. Ferguson-Smith, Anne C. Dzierzak, Elaine Ottersbach, Katrin TI Dlk1 is a negative regulator of emerging hematopoietic stem and progenitor cells SO HAEMATOLOGICA LA English DT Article ID PREADIPOCYTE FACTOR-1 PREF-1; ADIPOCYTE DIFFERENTIATION; REPEAT MOTIFS; GENE-PRODUCT; PROTEIN DLK; AGM REGION; DELTA-LIKE; NICHE; EXPRESSION; TISSUES AB The first mouse adult-repopulating hematopoietic stem cells emerge in the aorta-gonad-mesonephros region at embryonic day (E) 10.5. Their numbers in this region increase thereafter and begin to decline at E12.5, thus pointing to the possible existence of both positive and negative regulators of emerging hematopoietic stem cells. Our recent expression analysis of the aorta-gonad-mesonephros region showed that the Delta-like homologue 1 (Dlk1) gene is up-regulated in the region of the aorta-gonad-mesonephros where hematopoietic stem cells are preferentially located. To analyze its function, we studied Dlk1 expression in wild-type and hematopoietic stem cell-deficient embryos and determined hematopoietic stem and progenitor cell activity in Dlk1 knockout and overexpressing mice. Its role in hematopoietic support was studied in co-culture experiments using stromal cell lines that express varying levels of Dlk1. We show here that Dlk1 is expressed in the smooth muscle layer of the dorsal aorta and the ventral sub-aortic mesenchyme, where its expression is dependent on the hematopoietic transcription factor Runx1. We further demonstrate that Dlk1 has a negative impact on hematopoietic stem and progenitor cell activity in the aorta-gonad-mesonephros region in vivo, which is recapitulated in co-cultures of hematopoietic stem cells on stromal cells that express varying levels of Dlk1. This negative effect of Dlk1 on hematopoietic stem and progenitor cell activity requires the membrane-bound form of the protein and cannot be recapitulated by soluble Dlk1. Together, these data suggest that Dlk1 expression by cells of the aorta-gonad-mesonephros hematopoietic microenvironment limits hematopoietic stem cell expansion and is, to our knowledge, the first description of such a negative regulator in this tissue. C1 [Mirshekar-Syahkal, Bahar; Kimber, Gillian M.; Ottersbach, Katrin] Univ Cambridge, Wellcome Trust & MRC Stem Cell Inst, Cambridge Inst Med Res, Dept Haematol, Cambridge, England. [Haak, Esther; van Leusden, Kevin; Harvey, Kirsty; Dzierzak, Elaine] Erasmus MC, Erasmus Stem Cell Inst, Dept Cell Biol, Rotterdam, Netherlands. [O'Rourke, John; de Bruijn, Marella F. T. R.] Univ Oxford, MRC Mol Haematol Unit, Weatherall Inst Mol Med, Oxford, England. [Laborda, Jorge] Univ Castilla La Mancha, Sch Med, Reg Ctr Biomed Res, Dept Inorgan & Organ Chem & Biochem, Albacete, Spain. [Bauer, Steven R.] US FDA, Cellular & Tissue Therapies Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Ferguson-Smith, Anne C.] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge, England. RP Ottersbach, K (reprint author), Univ Cambridge, Wellcome Trust & MRC Stem Cell Inst, Cambridge Inst Med Res, Dept Haematol, Cambridge, England. EM ko268@cam.ac.uk RI Laborda, Jorge/L-5726-2014; OI Laborda, Jorge/0000-0002-9210-838X; Bauer, Steven/0000-0003-2831-846X; Ottersbach, Katrin/0000-0002-6880-4895 FU Kay Kendall Leukaemia Fund [KKL276]; British Society for Haematology Early Stage Researcher Fellowship; Leukaemia & Lymphoma Research [10015]; Frank Edward Elmore Fund; James Baird Fund; Dutch Organization for Scientific Research [916.36.601]; National Institutes of Health [R37DK054077] FX This work was funded by the Kay Kendall Leukaemia Fund (KKL276 to KO), a British Society for Haematology Early Stage Researcher Fellowship (KO), Leukaemia & Lymphoma Research (10015 to KO), the Frank Edward Elmore Fund and James Baird Fund (BM-S), the Dutch Organization for Scientific Research (916.36.601, ED), and the National Institutes of Health (R37DK054077, ED). NR 45 TC 17 Z9 18 U1 0 U2 5 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD FEB PY 2013 VL 98 IS 2 BP 163 EP 171 DI 10.3324/haematol.2012.070789 PG 9 WC Hematology SC Hematology GA 096PD UT WOS:000315415800007 PM 22801971 ER PT J AU Calvert, RJ Vohra, S AF Calvert, Richard J. Vohra, Sanah TI Doxorubicin-treated H9c2 cells: caution with luminescent ATP and Hoechst 33258 assays SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Letter C1 [Calvert, Richard J.; Vohra, Sanah] US FDA, Div Toxicol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20740 USA. RP Calvert, RJ (reprint author), US FDA, Div Toxicol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20740 USA. EM richard.calvert@fda.hhs.gov NR 1 TC 6 Z9 6 U1 0 U2 5 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 FEB PY 2013 VL 49 IS 2 BP 95 EP 96 DI 10.1007/s11626-012-9573-1 PG 2 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 096VX UT WOS:000315433900001 PM 23288412 ER PT J AU Azevedo, MP Vlasova, AN Saif, LJ AF Azevedo, Marli P. Vlasova, Anastasia N. Saif, Linda J. TI Human rotavirus virus-like particle vaccines evaluated in a neonatal gnotobiotic pig model of human rotavirus disease SO EXPERT REVIEW OF VACCINES LA English DT Review DE diarrhea; human rotavirus; gnotobiotic pigs; rotavirus-like particles; vaccine ID HEAT-LABILE TOXIN; SECRETING CELL RESPONSES; ATTENUATED HUMAN ROTAVIRUS; GROUP-A ROTAVIRUSES; WA HUMAN ROTAVIRUS; INDUCE PROTECTIVE IMMUNITY; CORE-LIKE PARTICLES; ANTIBODY-RESPONSES; ESCHERICHIA-COLI; NASAL IMMUNIZATION AB The authors discuss here rotavirus-like particle vaccines as an alternative approach to oral live-attenuated rotavirus vaccine and their efficacy in a gnotobiotic pig model. Rotavirus virus-like particles (VLPs) were evaluated in different doses, and routes of administration, and combined with live-attenuated virus and adjuvants. A VLP vaccine composed of rotavirus VP2 and VP6 was immunogenic in gnotobiotic pigs when inoculated intranasally; however, this vaccine failed to confer protection. A combination of oral attenuated human rotavirus and intranasal 2/6VLP vaccines conferred immunogenicity, partial protection against a human rotavirus challenge and induced IFN-gamma-producing T cells in the ileum of pigs with similar frequencies to human rotavirus infection. Vaccination through a combination of mucosal inductive sites and live-attenuated vaccine combined with VLP vaccines was the most effective regimen, compared with the use of a single route or a single vaccine alone. However, if formulated with neutralizing antigens, VLP vaccines may constitute a better approach in a high maternal antibody scenario. C1 [Azevedo, Marli P.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Vlasova, Anastasia N.; Saif, Linda J.] Ohio State Univ, Ohio Agr Res & Dev Ctr, Food Anim Hlth Res Program, Dept Vet Prevent Med, Wooster, OH 44691 USA. RP Saif, LJ (reprint author), Ohio State Univ, Ohio Agr Res & Dev Ctr, Food Anim Hlth Res Program, Dept Vet Prevent Med, Wooster, OH 44691 USA. EM saif.2@osu.edu RI Vlasova, Anastasia/C-2062-2016 FU NIH (NIH, NIAID) [R01A1033561] FX This work was supported by a grant from the NIH (NIH, NIAID, R01A1033561) to LJ Saif. 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 125 TC 12 Z9 13 U1 2 U2 9 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 FEB PY 2013 VL 12 IS 2 BP 169 EP 181 DI 10.1586/ERV.13.3 PG 13 WC Immunology SC Immunology GA 093BS UT WOS:000315167300014 PM 23414408 ER PT J AU Yang, J Zhao, H Garnett, C Rahman, A Gobburu, JV Pierce, W Schechter, G Summers, J Keegan, P Booth, B Wang, Y AF Yang, Jun Zhao, Hong Garnett, Christine Rahman, Atiqur Gobburu, Jogarao V. Pierce, William Schechter, Genevieve Summers, Jeffery Keegan, Patricia Booth, Brian Wang, Yaning TI The Combination of Exposure-Response and Case-Control Analyses in Regulatory Decision Making SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE case-control; confounding; exposure-response; oncology; regulatory; scientific affairs ID SIMULATION AB To reduce the bias introduced by confounding risk factors, a case-control comparison was incorporated in the exposure-response (ER) analysis to evaluate the recommended dosing regimen for trastuzumab in a pivotal trial. Results of Kaplan-Meier survival analysis suggest that patients with metastatic gastric cancer (mGC) in the lowest quartile trough concentrations of trastuzumab in cycle 1 (Cmin 1) had shorter overall survival (OS) than did those in other quartiles. The result of the case-matched control comparison suggests that adjusting for these risk factors, patients with the lowest quartile of trastuzumab exposure did not benefit from addition of trastuzumab treatment to chemotherapy. The identified subgroup without survival benefit and the ER relationship support the recommendation on conducting clinical trials to identify a treatment regimen with greater exposure and acceptable safety profiles and to prospectively evaluate whether this treatment regimen will result in survival benefit for the identified subgroup. C1 [Yang, Jun; Zhao, Hong; Garnett, Christine; Rahman, Atiqur; Gobburu, Jogarao V.; Booth, Brian; Wang, Yaning] US FDA, Off Clin Pharmacol, Off Translat Sci, Silver Spring, MD 20903 USA. [Pierce, William; Schechter, Genevieve; Summers, Jeffery; Keegan, Patricia] US FDA, Off Oncol Drug Prod, Off New Drugs, Silver Spring, MD 20903 USA. RP Wang, YN (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, 10903 New Hampshire Ave,Bldg 51,Rm 1252, Silver Spring, MD 20903 USA. EM Yaning.Wang@fda.hhs.gov NR 12 TC 17 Z9 18 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 FEB PY 2013 VL 53 IS 2 BP 160 EP 166 DI 10.1177/0091270012445206 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 096XS UT WOS:000315438800004 PM 23436261 ER PT J AU Agarwal, S Arya, V Zhang, L AF Agarwal, Sheetal Arya, Vikram Zhang, Lei TI Review of P-gp Inhibition Data in Recently Approved New Drug Applications: Utility of the Proposed [I1]/IC50 and [I2]/IC50 Criteria in the P-gp Decision Tree SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE [I1]; IC50 and [I2]; IC50 criteria; P-gp decision tree; digoxin ID IN-VITRO; TRANSPORTERS; GLYCOPROTEIN; DIGOXIN C1 [Agarwal, Sheetal; Arya, Vikram; Zhang, Lei] US FDA, Silver Spring, MD 20993 USA. RP Zhang, L (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Bldg 51,Room 3106,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM leik.zhang@fda.hhs.gov NR 20 TC 22 Z9 22 U1 0 U2 9 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 FEB PY 2013 VL 53 IS 2 BP 228 EP 233 DI 10.1177/0091270011436344 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 096XS UT WOS:000315438800011 PM 23436268 ER PT J AU Henrichs, DW Scott, PS Steidinger, KA Errera, RM Abraham, A Campbell, L AF Henrichs, Darren W. Scott, Paula S. Steidinger, Karen A. Errera, Reagan M. Abraham, Ann Campbell, Lisa TI Morphology and Phylogeny of Prorocentrum texanum sp nov (Dinophyceae): A New Toxic Dinoflagellate From the Gulf of Mexico Coastal Waters Exhibiting Two Distinct Morphologies SO JOURNAL OF PHYCOLOGY LA English DT Article DE dinoflagellate; Gulf of Mexico; internal transcribed spacer; large subunit; Prorocentrum texanum sp; nov; small subunit ID BRITTANY NORTHWESTERN FRANCE; MITOCHONDRIAL CYTOCHROME-B; BENTHIC DINOFLAGELLATE; MOLECULAR PHYLOGENY; SEQUENCES; TAXONOMY; POSITION; COMPLEX; DIATOM; MICANS AB A new planktonic species of Prorocentrum is described from the Gulf of Mexico. First observed with the Imaging FlowCytobot, Prorocentrum texanum sp. nov. was characterized using LM, SEM, and TEM along with sequencing of the SSU, LSU, and ITS ribosomal regions and the mitochondrial cob and cox1 regions. P. texanum sp. nov. is a round to oval bivalvate dinoflagellate, with a prominent anterior, serrated solid flange on periflagellar a platelet and an opposing short, flat flange on the h platelet. The periflagellar area consists of 10 platelets. Both left and right valves have shallow round depressions and two-sized valve pores. The anterior ejectosome pore pattern differs between the left and right valve in relation to the periflagellar area and margins. Ten to eleven rows of tangential ejectosome pores are present on each valve. P. texanum sp. nov. has two varieties which exhibit distinct morphotypes, one round to oval (var. texanum) and the other pointed (var. cuspidatum). P. texanum var. cuspidatum is morphologically similar to P. micans in surface markings, but is smaller, and has a serrated periflagellar flange, and is genetically distinct from P. micans. Cytologically, P. texanum has two parietal chlo-roplasts, each with a compound, interlamellar pyrenoid, trichocysts, fibrous vesicles that resemble mucocysts, pusules, V- to U-shaped posterior nucleus, golgi, and tubular mitochondria. No genetic difference was found between the two varieties in the five genes examined. Phylogenetic analysis of the SSU, LSU, and ITS ribosomal regions place P. texanum sp. nov. as a sister group to P. micans. One isolate of P. texanum var. texanum produces okadaic acid. C1 [Henrichs, Darren W.; Campbell, Lisa] Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. [Scott, Paula S.; Steidinger, Karen A.] Fish & Wildlife Res Inst, Florida Fish & Wildlife Conservat Commiss, St Petersburg, FL 33701 USA. [Errera, Reagan M.; Campbell, Lisa] Texas A&M Univ, Dept Oceanog, College Stn, TX 77843 USA. [Abraham, Ann] US FDA, Div Seafood Sci & Technol, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Campbell, L (reprint author), Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. EM lisacampbell@tamu.edu RI Campbell, Lisa/E-6587-2011 OI Campbell, Lisa/0000-0003-2756-2743 NR 47 TC 6 Z9 6 U1 1 U2 32 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3646 J9 J PHYCOL JI J. Phycol. PD FEB PY 2013 VL 49 IS 1 BP 143 EP 155 DI 10.1111/jpy.12030 PG 13 WC Plant Sciences; Marine & Freshwater Biology SC Plant Sciences; Marine & Freshwater Biology GA 089QM UT WOS:000314925100014 PM 27008396 ER PT J AU Gavrielides, MA Zeng, RP Myers, KJ Sahiner, B Petrick, N AF Gavrielides, Marios A. Zeng, Rongping Myers, Kyle J. Sahiner, Berkman Petrick, Nicholas TI Benefit of Overlapping Reconstruction for Improving the Quantitative Assessment of CT Lung Nodule Volume SO ACADEMIC RADIOLOGY LA English DT Article DE Quantitative imaging; lung nodules; volumetric assessment; reconstruction; overlapping; size change; phantom study; computed tomography ID MULTIDETECTOR ROW CT; PULMONARY NODULES; SPIRAL CT; IMAGE-RECONSTRUCTION; HELICAL CT; SIZE ESTIMATION; SOLID TUMORS; THORACIC CT; TRUTH DATA; PARAMETERS AB Rationale and Objectives: The aim of this study was to quantify the effect of overlapping reconstruction on the precision and accuracy of lung nodule volume estimates in a phantom computed tomographic (CT) study. Materials and Methods: An anthropomorphic phantom was used with a vasculature insert on which synthetic lung nodules were attached. Repeated scans of the phantom were acquired using a 64-slice CT scanner. Overlapping and Contiguous reconstructions were performed for a range of CT imaging parameters (exposure, slice thickness, pitch, reconstruction kernel) and a range of nodule characteristics (size, density). Nodule volume was estimated with a previously developed matched-filter algorithm. Results: Absolute percentage bias across all nodule sizes (n = 2880) was significantly lower when overlapping reconstruction was used, with an absolute percentage bias of 6.6% (95% confidence interval [CI], 6.4-6.9), compared to 13.2% (95% CI, 12.7-13.8) for contiguous reconstruction. Overlapping reconstruction also showed a precision benefit, with a lower standard percentage error of 7.1% (95% CI, 6.9-7.2) compared with 15.3% (95% CI, 14.9-15.7) for contiguous reconstructions across all nodules. Both effects were more pronounced for the smaller, subcentimeter nodules. Conclusions: These results support the use of overlapping reconstruction to improve the quantitative assessment of nodule size with CT imaging. C1 [Gavrielides, Marios A.; Zeng, Rongping; Myers, Kyle J.; Sahiner, Berkman; Petrick, Nicholas] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Gavrielides, MA (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62,Room 4114, Silver Spring, MD 20993 USA. EM marios.gavrielides@fda.hhs.gov FU Food and Drug Administration Critical Path Initiative FX This work is supported in part by funding from the Food and Drug Administration Critical Path Initiative. The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the US Department Of Health and Human Services. Address correspondence to: M.A.G. e-mail: marios.gavrielides@fda.hhs.gov NR 22 TC 13 Z9 13 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD FEB PY 2013 VL 20 IS 2 BP 173 EP 180 DI 10.1016/j.acra.2012.08.014 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 091RW UT WOS:000315068500006 PM 23085408 ER PT J AU Mun, KS Kumar, G Co, CC Ho, CC AF Mun, Kyu-Shik Kumar, Girish Co, Carlos C. Ho, Chia-Chi TI Micropatterning Different Cell Types with Microarray Amplification of Natural Directional Persistence SO ADVANCED HEALTHCARE MATERIALS LA English DT Article ID SELF-ASSEMBLED MONOLAYERS; MIGRATION; GROWTH; FILMS; GASTRULATION; RECOGNITION; ATTACHMENT; MOTILITY; ADHESION; SIGNALS AB In vivo, different cell types assemble in specific patterns to form functional tissues. Reproducing this process in vitro by designing scaffold materials to direct cells precisely to the right locations at the right time is important for the next generation of biomaterials. Here, using microarray amplification of natural directional persistence (MANDIP), simultaneous assembly of fibroblasts and endothelial cells is demonstrated by directing their long-range migration. Amplification of the directional persistence occurs through morphology-induced polarity and the asymmetric positioning of individual microsized adhesive islands that restrict lamellipodia attachment, and thus migration, to one preset direction. Quantitative analysis of cell migration on different MANDIP designs yields insight to the relative importance of the asymmetric island shapes and their arrangement. The approach enables spatial patterning of different cell types with micrometer-scale precision over large areas for investigation of cell-cell interactions within complex tissue architectures. C1 [Mun, Kyu-Shik; Kumar, Girish; Co, Carlos C.; Ho, Chia-Chi] Univ Cincinnati, Chem & Mat Engn Program, Cincinnati, OH 45221 USA. [Kumar, Girish] US FDA, Div Biol, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Ho, CC (reprint author), Univ Cincinnati, Chem & Mat Engn Program, Cincinnati, OH 45221 USA. EM hocc@ucmail.uc.edu FU National Institutes of Health [R01EB010043]; National Science Foundation [CBET0928219] FX This work was supported by the National Institutes of Health (R01EB010043) and the National Science Foundation (CBET0928219). We thank Ross Andrews for synthesizing the OEGMA/MA and fluorescein OEGMA/MA and Dr. Young-Gwang Ko for helpful discussions and experimental assistance. NR 31 TC 7 Z9 7 U1 1 U2 33 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2192-2640 J9 ADV HEALTHC MATER JI Adv. Healthc. Mater. PD FEB PY 2013 VL 2 IS 2 BP 334 EP 342 DI 10.1002/adhm.201200141 PG 9 WC Engineering, Biomedical; Nanoscience & Nanotechnology; Materials Science, Biomaterials SC Engineering; Science & Technology - Other Topics; Materials Science GA 092LJ UT WOS:000315122900015 PM 23184681 ER PT J AU Singh, AK Stanker, LH Sharma, SK AF Singh, Ajay K. Stanker, Larry H. Sharma, Shashi K. TI Botulinum neurotoxin: Where are we with detection technologies? SO CRITICAL REVIEWS IN MICROBIOLOGY LA English DT Review DE Botulism; botulinum neurotoxin; BoNT; detection; mouse bioassay; immunoassay; ELISA; FRET assay; mass spectrometry; PCR; DNA microarray; endopeptidase; flow cytometry; cell based assay ID PHRENIC NERVE-HEMIDIAPHRAGM; SINGLE-DOMAIN ANTIBODIES; LINKED-IMMUNOSORBENT-ASSAY; TOXIN TYPE-A; CLOSTRIDIUM-BOTULINUM; IN-VITRO; MOUSE BIOASSAY; SEROTYPE-A; SMALL NUMBERS; PCR ASSAY AB Because of its high toxicity, botulinum neurotoxin (BoNT) poses a significant risk to humans and it represents a possible biological warfare agent. Nevertheless, BoNT serotypes A and B are considered an effective treatment for a variety of neurological disorders. The growing applicability of BoNT as a drug, and its potential use as a biological threat agent, highlight the urgent need to develop sensitive detection assays and therapeutic counter measures. In the last decade, significant progress has been made in BoNT detection technologies but none have fully replaced the mouse lethality assay, the current "gold standard". Recently, new advances in robotics and the availability of new reagents have allowed development of methods for rapid toxin analysis. These technologies while promising need further refinement. C1 [Singh, Ajay K.; Sharma, Shashi K.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Stanker, Larry H.] ARS, Western Reg Res Ctr, USDA, Albany, CA USA. RP Sharma, SK (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM shashi.sharma@fda.hhs.gov FU US Department of Homeland Security FX This work was supported by funding from the US Department of Homeland Security to SKS and LHS. The views or opinions presented in this review are those of the authors and should not be construed as an official views of the US Food and Drug Administration or of the USDA. The FDA and USDA are an equal opportunity provider and employer. NR 92 TC 24 Z9 25 U1 3 U2 92 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1040-841X J9 CRIT REV MICROBIOL JI Crit. Rev. Microbiol. PD FEB PY 2013 VL 39 IS 1 BP 43 EP 56 DI 10.3109/1040841X.2012.691457 PG 14 WC Microbiology SC Microbiology GA 075CT UT WOS:000313862100004 PM 22676403 ER PT J AU Liu, ZC Fang, H Reagan, K Xu, XW Mendrick, DL Slikker, W Tong, WD AF Liu, Zhichao Fang, Hong Reagan, Kelly Xu, Xiaowei Mendrick, Donna L. Slikker, William, Jr. Tong, Weida TI In silico drug repositioning - what we need to know SO DRUG DISCOVERY TODAY LA English DT Review ID DISCOVERY; DISEASE; THALIDOMIDE; TARGETS; THERAPY; NETWORK AB Drug repositioning, exemplified by sildenafil and thalidomide, is a promising way to explore alternative indications for existing drugs. Recent research has shown that bioinformatics-based approaches have the potential to offer systematic insights into the complex relationships among drugs, targets and diseases necessary for successful repositioning. In this article, we propose the key bioinformatics steps essential for discovering valuable repositioning methods. The proposed steps (repurposing with a purpose, repurposing with a strategy and repurposing with confidence) are aimed at providing a repurposing pipeline, with particular focus on the proposed Drugs of New Indications (DNI) database, which can be used alongside currently available resources to improve in silico drug repositioning. C1 [Liu, Zhichao; Fang, Hong] US FDA, Natl Ctr Toxicol Res, ICF Int, Jefferson, AR 72079 USA. [Reagan, Kelly; Xu, Xiaowei; Mendrick, Donna L.; Tong, Weida] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Xu, Xiaowei] Univ Arkansas, Dept Informat Sci, Little Rock, AR 72204 USA. RP Liu, ZC (reprint author), US FDA, Natl Ctr Toxicol Res, ICF Int, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM weida.tong@fda.hhs.gov RI Liu, Zhichao/C-4035-2011 FU FDA National Center for Toxicological Research (NCTR) through the Oak Ridge Institute for Science and Education (ORISE) FX ZL and XX are grateful to the FDA National Center for Toxicological Research (NCTR) for postdoctoral support through the Oak Ridge Institute for Science and Education (ORISE). NR 39 TC 38 Z9 38 U1 2 U2 24 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD FEB PY 2013 VL 18 IS 3-4 BP 110 EP 115 DI 10.1016/j.drudis.2012.08.005 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 090YX UT WOS:000315017000002 PM 22935104 ER PT J AU Pagan, AJ Peters, NC Debrabant, A Ribeiro-Gomes, F Pepper, M Karp, CL Jenkins, MK Sacks, DL AF Pagan, Antonio J. Peters, Nathan C. Debrabant, Alain Ribeiro-Gomes, Flavia Pepper, Marion Karp, Christopher L. Jenkins, Marc K. Sacks, David L. TI Tracking antigen-specific CD4+T cells throughout the course of chronic Leishmania major infection in resistant mice SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CD4+T cells; IFN-; IL-10; Leishmania major; Tetramer ID REGULATORY T-CELLS; TRANSCRIPTION FACTOR; IN-VIVO; C-MAF; MEMORY; NAIVE; EXPANSION; CD8(+); PERSISTENCE; PROTECTION AB Primary Leishmania major infection typically produces cutaneous lesions that not only heal but also harbor persistent parasites. While the opposing roles of CD4+ T-cell-derived IFN- and IL-10 in promoting parasite killing and persistence have been well established, how these responses develop from naive precursors has not been directly monitored throughout the course of infection. We used peptide:Major Histocompatibility Complex class II (pMHCII) tetramers to investigate the endogenous, parasite-specific primary CD4+ T-cell response to L. major in mice resistant to infection. Maximal frequencies of IFN-+ CD4+ T cells were observed in the spleen and infected ears within a month after infection and were maintained into the chronic phase. In contrast, peak frequencies of IL-10+ CD4+ T cells emerged within 2 weeks of infection, persisted into the chronic phase, and accumulated in the infected ears but not the spleen, via a process that depended on local antigen presentation. T helper type-1 (Th1) cells, not Foxp3+ regulatory T cells, were the chief producers of IL-10 and were not exhausted. Therefore, tracking antigen-specific CD4+ T cells revealed that IL-10 production by Th1 cells is not due to persistent T-cell antigen receptor stimulation, but rather driven by early antigen encounter at the site of infection. C1 [Pagan, Antonio J.; Pepper, Marion; Jenkins, Marc K.] Univ Minnesota, Sch Med, Dept Microbiol, Ctr Immunol, Minneapolis, MN 55455 USA. [Peters, Nathan C.; Ribeiro-Gomes, Flavia; Sacks, David L.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Debrabant, Alain] US FDA, Div Emerging & Transfus Transmitted Dis, OBRR, CBER, Bethesda, MD 20014 USA. [Karp, Christopher L.] Cincinnati Childrens Hosp Res Fdn, Div Mol Immunol, Div Infect Dis, Cincinnati, OH USA. [Karp, Christopher L.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. RP Sacks, DL (reprint author), NIAID, Parasit Dis Lab, Bldg 4,Room B1-12,4 Ctr Dr,MSC 0425, Bethesda, MD 20892 USA. EM dsacks@nih.gov RI Jenkins, Marc/G-1063-2012; Ribeiro-Gomes, Flavia/F-7609-2015; OI Jenkins, Marc/0000-0001-8009-7655; Karp, Christopher/0000-0002-0832-2659 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health; US National Institutes of Health [R37 AI027998, R01 AI039614, R01 AI066016, T32 AI07313, T32 CA9138]; Minnesota Medical Foundation FX We thank Kim Beacht, J. Walter, and R. Speier for expert technical assistance. This work was supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by grants from the US National Institutes of Health, R37 AI027998, R01 AI039614, and R01 AI066016 (M. K. J.), T32 AI07313 (A. J. P.), and T32 CA9138 (M. P.), and a Frieda M. Kunze Fellowship from the Minnesota Medical Foundation (A.J.P.). NR 56 TC 15 Z9 15 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD FEB PY 2013 VL 43 IS 2 BP 427 EP 438 DI 10.1002/eji.201242715 PG 12 WC Immunology SC Immunology GA 091LN UT WOS:000315051100016 PM 23109292 ER PT J AU Banugaria, SG Prater, SN McGann, JK Feldman, JD Tannenbaum, JA Bailey, C Gera, R Conway, RL Viskochil, D Kobori, JA Rosenberg, AS Kishnani, PS AF Banugaria, Suhrad G. Prater, Sean N. McGann, Judeth K. Feldman, Jonathan D. Tannenbaum, Jesse A. Bailey, Carrie Gera, Renuka Conway, Robert L. Viskochil, David Kobori, Joyce A. Rosenberg, Amy S. Kishnani, Priya S. TI Bortezomib in the rapid reduction of high sustained antibody titers in disorders treated with therapeutic protein: lessons learned from Pompe disease SO GENETICS IN MEDICINE LA English DT Article DE antibodies; bortezomib; enzyme replacement therapy; glycogen storage disease type II; immune modulation ID ACID ALPHA-GLUCOSIDASE; ENZYME REPLACEMENT THERAPY; SEVERE HEMOPHILIA-A; IMMUNE TOLERANCE; PROTEASOME INHIBITOR; ALGLUCOSIDASE ALPHA; CLINICAL-OUTCOMES; PLASMA-CELLS; FACTOR-VIII; INFANTS AB Purpose: High sustained antibody titers complicate many disorders treated with a therapeutic protein, including those treated with enzyine replacement therapy, such as Pompe disease. Although enzyme replacement therapy with alglucosidase alfa (Myozyme) in Pompe disease has improved the prognosis of this otherwise lethal disorder, patients who develop high sustained antibody titers to alglucosidase alfa enter a prolonged phase of clinical decline resulting in death despite continued enzyme replacement therapy. Clinically effective immune-tolerance induction strategies have yet to be described in the setting of an entrenched immune response characterized by high sustained antibody titers, wherein antibody-producing plasma cells play an especially prominent role. Methods: We treated three patients with infantile Pompe disease experiencing marked clinical decline due to high Sustained antibody titers. To target the plasma cell source of high sustained antibody titers, a regimen based on bortezomib (Velcade) was used in combination with rituximab, methotrexate, and intravenous immunoglobulin. Results; The treatment regimen was well tolerated, with no obvious side effects. Patient 1 had a 2,048-fold, and patients 2 and 3 each had a 64-fold, reduction in anti-alglucosidase alfa antibody titer, with concomitant sustained clinical improvement. Conclusion: The addition of bortezomib to immunomodulatory regimens is an effective and safe treatment strategy in infantile Pompe disease, with potentially broader clinical implications. Genet Med 2013:15(2):123-131 C1 [Banugaria, Suhrad G.; Prater, Sean N.; Kishnani, Priya S.] Duke Univ, Med Ctr, Dept Pediat, Div Med Genet, Durham, NC 27710 USA. [McGann, Judeth K.; Feldman, Jonathan D.; Tannenbaum, Jesse A.] Kaiser Permanente, Dept Pediat, Santa Clara, CA USA. [Bailey, Carrie; Viskochil, David] Univ Utah, Dept Pediat, Div Med Genet, Salt Lake City, UT USA. [Gera, Renuka; Conway, Robert L.] Michigan State Univ, Dept Pediat Human Dev, E Lansing, MI 48824 USA. [Kobori, Joyce A.] Kaiser Permanente, Dept Pediat, San Jose, CA USA. [Rosenberg, Amy S.] US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Kishnani, PS (reprint author), Duke Univ, Med Ctr, Dept Pediat, Div Med Genet, Durham, NC 27710 USA. EM kishn001@dm.duke.edu FU Genzyme; Gaucher Disease Registry Advisory Boards FX P.S.K. reports receiving research and grant support from Genzyme. P.S.K. also receives honoraria and consulting fees from Genzyme and is a member of the Pompe disease and the Gaucher Disease Registry Advisory Boards. Duke University and the inventors of the method of treatment and precursors of the cell lines used to generate the enzyme (rhGAA) used commercially have received royalties pursuant to the University's policy on inventions, patents, and technology transfer. This potential conflict for Duke University has been resolved through monetization. S.G.B., S.N.P., and P.S.K. are listed as inventors on a Duke University pending patent application for the work described in this article. To date, neither Duke University nor the inventors have received any money from rights associated with this pending patent. D.V. receives clinical research support from Genzyme and serves as a board member for the MPS I Registry in which honoraria are provided for attendees at meetings by the host company, Genzyme. The other authors declare no conflict of interest. NR 39 TC 29 Z9 29 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD FEB PY 2013 VL 15 IS 2 BP 123 EP 131 DI 10.1038/gim.2012.110 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 087WK UT WOS:000314794900005 PM 23060045 ER PT J AU Orue, N Garcia, S Feng, P Heredia, N AF Orue, Nydia Garcia, Santos Feng, Peter Heredia, Norma TI Decontamination of Salmonella, Shigella, and Escherichia coli O157:H7 from Leafy Green Vegetables Using Edible Plant Extracts SO JOURNAL OF FOOD SCIENCE LA English DT Article DE cilantro; E. coli O157:H7; fresh greens; parsley; Salmonella; Shigella; spinach ID ANTIMICROBIAL ACTIVITY; ANTIBACTERIAL ACTIVITY; CAMPYLOBACTER-JEJUNI; ESSENTIAL OILS; CILANTRO; O157-H7; REDUCTION; PATHOGENS; CARVACROL; TOMATOES AB Fresh cilantro, parsley, and spinach are products that are regularly consumed fresh, but are difficult to decontaminate, as a result, they are common vehicles of transmission of enteropathogenic bacteria. In this study, the efficacy of plant extracts as alternatives for disinfection of cilantro, parsley, and spinach that were artificially contaminated with Salmonella, Escherichia coli O157:H7, and Shigella sonnei was determined. Edible plant extracts obtained using ethanol as the extraction solvent were tested to determine the minimum bactericidal concentration (MBC) and those that exhibited the lowest MBC were selected for further studies. Leaves of fresh greens were washed with sterile water and dried. For seeding, leaves were submerged in suspensions of 2 different concentrations of bacteria (1.5 x 108 and 1 x 105), dried, and then stored at 4 degrees C until use. To determine the effects of the extracts, inoculated leafy greens were submerged in a container and subjected to treatments with chlorine, Citrol (R), or selected plant extracts. Each treatment type was stored at 4 degrees C for 0, 1, 5, and 7 d, and the bacterial counts were determined. From the 41 plant extracts tested, the extracts from oregano leaves and from the peel and pulp of limes were found to be as effective as chlorine or Citrol (R) in reducing by > 2 logs, the population of pathogenic bacteria on leafy greens and therefore, may be a natural and edible alternative to chemicals to reduce the risk of Salmonella, E. coli O157:H7 and S. sonnei contamination on leafy vegetables. Practical Application: The antimicrobial efficacy of the extracts of Mexican lime and oregano was clearly demonstrated on cilantro, parsley, and spinach. The extracts of Mexican lime and oregano provide alternatives to chlorine to significantly reduce bacterial pathogens that have been associated with outbreaks from contaminated leafy green vegetables. A simple, low cost, and labor-saving extraction system for production of the extracts was used. C1 [Orue, Nydia; Garcia, Santos; Heredia, Norma] Univ Autonoma Nuevo Leon, Fac Ciencias Biol, Dept Microbiol & Inmunol, San Nicolas 66451, Nuevo Leon, Mexico. [Feng, Peter] US FDA, CFSAN, College Pk, MD 20740 USA. RP Heredia, N (reprint author), Univ Autonoma Nuevo Leon, Fac Ciencias Biol, Dept Microbiol & Inmunol, Apdo Postal 124-F, San Nicolas 66451, Nuevo Leon, Mexico. EM norma@microbiosymas.com RI Garcia, Santos/F-5193-2010 FU Consejo Nacional de Ciencia y Tecnologia de Mexico (CONACYT) [105389]; CONACYT FX This research was supported by the Consejo Nacional de Ciencia y Tecnologia de Mexico (CONACYT) grant nr 105389. The authors thank CONACYT for the scholarship granted to Nydia Orue. NR 34 TC 6 Z9 6 U1 7 U2 46 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD FEB PY 2013 VL 78 IS 2 BP M290 EP M296 DI 10.1111/1750-3841.12016 PG 7 WC Food Science & Technology SC Food Science & Technology GA 090PE UT WOS:000314990500023 PM 23324049 ER PT J AU Lando, AM Lo, SC AF Lando, Amy M. Lo, Serena C. TI Single-Larger-Portion-Size and Dual-Column Nutrition Labeling May Help Consumers Make More Healthful Food Choices SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS LA English DT Article DE Nutrition Fads label; Serving size; Experiment ID BODY-MASS INDEX; US ADULTS; INFORMATION; CONSUMPTION; PREVALENCE; OBESITY; FORMATS; TRENDS AB Background The Food and Drug Administration is considering changes to the Nutrition Facts label to help consumers make more healthful choices. Objective To examine the effects of modifications to the Nutrition Facts label on foods that can be listed as having 1 or 2 servings per container, but are reasonably consumed at a single eating occasion. Design Participants were randomly assigned to study conditions that varied on label format, product, and nutrition profile. Data were collected via an online consumer panel. Participants/setting Adults aged 18 years and older were recruited from Synovate's online household panel. Data were collected during August 2011. A total of 32,897 invitations were sent for a final sample of 9,493 interviews. Intervention Participants were randomly assigned to one of 10 label formats classified into three groups: listing 2 servings per container with a single column, listing 2 servings per container with a dual column, and listing a single serving per container. Within these groups there were versions that enlarged the font size for "calories," removed "calories from fat," and changed the wording for serving size declaration. Main outcome measures The single product task measured product healthfulness, the amount of calories and various nutrients per serving and per container, and label perceptions. The product comparison task measured ability to identify the healthier product and the product with fewer calories per container and per serving. Statistical analyses performed Analysis of covariance models with Tukey-Kramer tests were used. Covariates included general label use, age, sex, level of education, and race/ethnicity. Results Single-serving and dual-column formats performed better and scored higher on most outcome measures. Conclusions For products that contain 2 servings but are customarily consumed at a single eating occasion, using a single-serving or dual-column labeling approach may help consumers make healthier food choices. J Acad Nutr Diet. 2013;113:241-250. C1 [Lando, Amy M.; Lo, Serena C.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Lando, AM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Amy.Lando@fda.hhs.gov FU US Food and Drug Administration FX All funding for this study was provided by the US Food and Drug Administration. NR 19 TC 7 Z9 8 U1 4 U2 24 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-2672 J9 J ACAD NUTR DIET JI J. Acad. Nutr. Diet. PD FEB PY 2013 VL 113 IS 2 BP 241 EP 250 DI 10.1016/j.jand.2012.11.006 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 086HP UT WOS:000314675000009 PM 23351627 ER PT J AU Roman, D Mahoney, K Mohamadi, A AF Roman, Dragos Mahoney, Karen Mohamadi, Ali TI Sarcopenia: What's in a Name? SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Editorial Material ID MORTALITY; CONSENSUS; DIAGNOSIS; MOBILITY; DISEASE; MUSCLE C1 [Roman, Dragos; Mahoney, Karen; Mohamadi, Ali] US FDA, Div Metab & Endocrinol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Roman, D (reprint author), US FDA, Div Metab & Endocrinol Prod, 10903 New Hampshire Ave,Bldg 22,Room 3116, Silver Spring, MD 20993 USA. EM dragos.roman@fda.hhs.gov NR 13 TC 23 Z9 23 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD FEB PY 2013 VL 14 IS 2 BP 80 EP 82 DI 10.1016/j.jamda.2012.09.021 PG 3 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 088EV UT WOS:000314817500002 PM 23131548 ER PT J AU Beeler, JA Eichelberger, MC AF Beeler, Judy A. Eichelberger, Maryna C. TI Influenza and respiratory syncytial virus (RSV) vaccines for infants: Safety, immunogenicity, and efficacy SO MICROBIAL PATHOGENESIS LA English DT Review DE Influenza virus; Respiratory syncytial virus; RSV; Vaccine; Infant; Immunity ID ALASKA NATIVE CHILDREN; T-CELL RESPONSES; YOUNG-CHILDREN; MATERNAL ANTIBODIES; UNITED-STATES; MF59-ADJUVANTED VACCINE; REVERSE GENETICS; IMMUNE-RESPONSES; INFECTION; LIVE AB Respiratory viral infections in infants and young children frequently cause illness that can easily progress to hospitalization and death. There are currently no licensed vaccines to prevent respiratory viral disease in children younger than 6 months, reflecting safety concerns and the difficulty in inducing effective immune responses in infants. This review discusses vaccines that have been developed, or are currently being developed, against influenza and respiratory syncytial virus, with a focus on studies performed to demonstrate their safety and efficacy, and the impact of immunologic immaturity and maternal antibodies on the infant response to vaccines. Published by Elsevier Ltd. C1 [Beeler, Judy A.; Eichelberger, Maryna C.] US FDA, Div Viral Prod, CBER, OVRR, Bethesda, MD 20892 USA. RP Beeler, JA (reprint author), US FDA, Lab Pediat & Resp Virus Dis, Div Viral Prod, Off Vaccine Res & Review,Ctr Biol Evaluat & Res, Bldg 29A,Room 3B05,HFM 463,29 Lincoln Dr, Bethesda, MD 20892 USA. EM judy.beeler@fda.hhs.gov NR 82 TC 11 Z9 13 U1 0 U2 17 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 FEB PY 2013 VL 55 BP 9 EP 15 DI 10.1016/j.micpath.2012.11.013 PG 7 WC Immunology; Microbiology SC Immunology; Microbiology GA 083ED UT WOS:000314444600002 PM 23247146 ER PT J AU Sha, J Rosenzweig, JA Kirtley, ML van Lier, CJ Fitts, EC Kozlova, EV Erova, TE Tiner, BL Chopra, AK AF Sha, Jian Rosenzweig, Jason A. Kirtley, Michelle L. van Lier, Christina J. Fitts, Eric C. Kozlova, Elena V. Erova, Tatiana E. Tiner, Bethany L. Chopra, Ashok K. TI A non-invasive in vivo imaging system to study dissemination of bioluminescent Yersinia pestis CO92 in a mouse model of pneumonic plague SO MICROBIAL PATHOGENESIS LA English DT Article DE Bioluminescent Yersinia pestis; Pneumonic plague; In vivo imaging; Levofloxacin; Immunofluorescence microscopy; Flow cytometry; Bacterial dissemination ID TRANSFERABLE PLASMID; BACTERIAL PATHOGENS; MURINE TOXIN; AEROSOLIZATION; LEVOFLOXACIN; RESISTANCE; INFECTION; VIRULENCE; GENES AB The gold standard in microbiology for monitoring bacterial dissemination in infected animals has always been viable plate counts. This method, despite being quantitative, requires sacrificing the infected animals. Recently, however, an alternative method of in vivo imaging of bioluminescent bacteria (IVIBB) for monitoring microbial dissemination within the host has been employed. Yersinia pestis is a Gram-negative bacterium capable of causing bubonic, septicemic, and pneumonic plague. In this study, we compared the conventional counting of bacterial colony forming units (cfu) in the various infected tissues to IVIBB in monitoring Y. pearls dissemination in a mouse model of pneumonic plague. By using a transposon mutagenesis system harboring the luciferase (luc) gene, we screened approximately 4000 clones and obtained a fully virulent, luc-positive Y. pestis CO92 (Y pestis-luc2) reporter strain in which transposition occurred within the largest pMT1 plasmid which possesses murine toxin and capsular antigen encoding genes. The aforementioned reporter strain and the wild-type CO92 exhibited similar growth curves, formed capsule based on immunofluorescence microscopy and flow cytometry, and had a similar LD50. Intranasal infection of mice with 15 LD50 of CO92-luc2 resulted in animal mortality by 72 h, and an increasing number of bioluminescent bacteria were observed in various mouse organs over a 24-72 h period when whole animals were imaged. However, following levofloxacin treatment (10 mg/kg/day) for 6 days 24 h post infection, no luminescence was observed after 72 h of infection, indicating that the tested antimicrobial killed bacteria preventing their detection in host peripheral tissues. Overall, we demonstrated that IVIBB is an effective and non-invasive way of monitoring bacterial dissemination in animals following pneumonic plague having strong correlation with cfu, and our reporter CO92-luc2 strain can be employed as a useful tool to monitor the efficacy of antimicrobial countermeasures in real time. (c) 2012 Elsevier Ltd. All rights reserved. C1 [Sha, Jian; Kirtley, Michelle L.; van Lier, Christina J.; Fitts, Eric C.; Kozlova, Elena V.; Erova, Tatiana E.; Tiner, Bethany L.; Chopra, Ashok K.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. [Rosenzweig, Jason A.] Texas So Univ, CBER, Dept Biol, Houston, TX 77004 USA. [Chopra, Ashok K.] Univ Texas Med Branch, Sealy Ctr Vaccine Dev, Galveston, TX 77555 USA. [Chopra, Ashok K.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA. [Chopra, Ashok K.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. RP Chopra, AK (reprint author), UTMB, Dept Microbiol & Immunol, 301 Univ Blvd, Galveston, TX 77555 USA. EM achopra@utmb.edu FU NIH/NIAID [AI064389, N01 AI30065]; National Aeronautics and Space Administration (NASA) [NNX08B4A47A, AI64389]; UC7 grant; T32 predoctoral training grant on Biodefense [AI060549] FX Studies conducted for this manuscript were supported by the NIH/NIAID AI064389 and N01 AI30065 grants (AKC). JAR was supported by the National Aeronautics and Space Administration (NASA) cooperative agreement NNX08B4A47A as well as AI64389. We thank Dr. A.G. Torres, UTMB, for providing pUTmini-Tn5::luxKm2 plasmid and Ms. K. Johnston for her initial help in imaging. We also thank Dr. S. Massey for his initial help with the software to determine total flux. We would also like to acknowledge UC7 grant which facilitated our research in the Galveston National Laboratory and the Biomedical Imaging Network Core for providing imaging facilities. Christina van Lier was supported by the T32 predoctoral training grant on Biodefense (AI060549). NR 31 TC 11 Z9 11 U1 0 U2 16 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 FEB PY 2013 VL 55 BP 39 EP 50 DI 10.1016/j.micpath.2012.09.011 PG 12 WC Immunology; Microbiology SC Immunology; Microbiology GA 083ED UT WOS:000314444600007 PM 23063826 ER PT J AU Yang, YS Shah, RB Yu, LX Khan, MA AF Yang, Yongsheng Shah, Rakhi B. Yu, Lawrence X. Khan, Mansoor A. TI In Vitro Bioequivalence Approach for a Locally Acting Gastrointestinal Drug: Lanthanum Carbonate SO MOLECULAR PHARMACEUTICS LA English DT Review DE bioavailability; bioequivalence; locally acting GI drugs; dissolution; lanthanum carbonate; phosphate binding ID PHOSPHATE BINDER; BIOAVAILABILITY; MODELS; VIVO AB A conventional human pharmacokinetic (PK) in vivo study is often considered as the "gold standard" to determine bioequivalence (BE) of drug products. However, this BE approach is not always applicable to the products not intended to be delivered into the systemic circulation. For locally acting gastrointestinal (GI) products, well designed in vitro approaches might be more practical in that they are able not only to qualitatively predict the presence of the active substance at the site of action but also to specifically assess the performance of the active substance. For example, lanthanum carbonate chewable tablet, a locally acting GI phosphate binder when orally administrated, can release free lanthanum ions in the acid environment of the upper GI tract. The lanthanum ions directly reach the site of action to bind with dietary phosphate released from food to form highly insoluble lanthanum-phosphate complexes. This prevents the absorption of phosphate consequently reducing the serum phosphate. Thus, using a conventional PK approach to demonstrate BE is meaningless since plasma levels are not relevant for local efficacy in the GI tract. Additionally the bioavailability of lanthanum carbonate is less than 0.002%, and therefore, the PK approach is not feasible. Therefore, an alternative assessment method is required. This paper presents an in vitro approach that can be used in lieu of PK or clinical studies to determine the BE of lanthanum carbonate chewable tablets. It is hoped that this information can be used to finalize an in vitro guidance for BE studies of lanthanum carbonate chewable tablets as well as to assist with "in vivo" biowaiver decision malcing. The scientific information might be useful to the pharmaceutical industry for the purpose of planning and designing future BE studies. C1 [Yang, Yongsheng; Shah, Rakhi B.; Khan, Mansoor A.] US FDA, Div Prod Qual Res, Off Pharmaceut Sci, Silver Spring, MD 20993 USA. [Yu, Lawrence X.] US FDA, Off Gener Drugs, Rockville, MD 20855 USA. RP Yang, YS (reprint author), 10903 New Hampshire Ave,LS Bldg 64, Silver Spring, MD 20993 USA. EM Yongsheng.Yang@fda.hhs.gov NR 15 TC 2 Z9 2 U1 3 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD FEB PY 2013 VL 10 IS 2 BP 544 EP 550 DI 10.1021/mp300517p PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 085PT UT WOS:000314627400013 PM 23249191 ER PT J AU Castiello, L Sabatino, M Zhao, YD Tumaini, B Ren, JQ Ping, J Wang, EN Wood, LV Marincola, FM Puri, RK Stroncek, DF AF Castiello, Luciano Sabatino, Marianna Zhao, Yingdong Tumaini, Barbara Ren, Jiaqiang Ping, Jin Wang, Ena Wood, Lauren V. Marincola, Francesco M. Puri, Raj K. Stroncek, David F. TI Quality Controls in Cellular Immunotherapies: Rapid Assessment of Clinical Grade Dendritic Cells by Gene Expression Profiling SO MOLECULAR THERAPY LA English DT Article ID T-CELLS; VACCINES; INFLAMMATION; ACTIVATION; GENERATION; CANCER; SITES AB Cell-based immunotherapies are among the most promising approaches for developing effective and targeted immune response. However, their clinical usefulness and the evaluation of their efficacy rely heavily on complex quality control assessment. Therefore, rapid systematic methods are urgently needed for the in-depth characterization of relevant factors affecting newly developed cell product consistency and the identification of reliable markers for quality control. Using dendritic cells (DCs) as a model, we present a strategy to comprehensively characterize manufactured cellular products in order to define factors affecting their variability, quality and function. After generating clinical grade human monocyte-derived mature DCs (mDCs), we tested by gene expression profiling the degrees of product consistency related to the manufacturing process and variability due to intra- and interdonor factors, and how each factor affects single gene variation. Then, by calculating for each gene an index of variation we selected candidate markers for identity testing, and defined a set of genes that may be useful comparability and potency markers. Subsequently, we confirmed the observed gene index of variation in a larger clinical data set. In conclusion, using high-throughput technology we developed a method for the characterization of cellular therapies and the discovery of novel candidate quality assurance markers. C1 [Castiello, Luciano; Sabatino, Marianna; Tumaini, Barbara; Ren, Jiaqiang; Ping, Jin; Stroncek, David F.] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Zhao, Yingdong] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Wang, Ena; Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Wang, Ena; Marincola, Francesco M.] NIH, CHI, Bethesda, MD 20892 USA. [Wood, Lauren V.] NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Stroncek, DF (reprint author), NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, 10 Ctr Dr,Room 3C731, Bethesda, MD 20892 USA. EM DStroncek@mail.nih.gov RI Castiello, Luciano/K-8616-2016 OI Castiello, Luciano/0000-0001-7146-3158 FU Department of Transfusion Medicine, Clinical Center, NIH FX We thank Thomas B. Buttolph (CBER, FDA) and Brenton K. McCright (CBER, FDA) for their critical reading of the manuscript. We also thank Anthony Suffredini (Clinical Center, NIH) for its kind gift of clinical grade LPS. This research was supported by the Department of Transfusion Medicine, Clinical Center, NIH. The authors declared no conflict of interest. NR 28 TC 1 Z9 1 U1 0 U2 5 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 FEB PY 2013 VL 21 IS 2 BP 476 EP 484 DI 10.1038/mt.2012.89 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 083AH UT WOS:000314434600024 PM 23147403 ER PT J AU Boggon, R van Staa, TP Chapman, M Gallagher, AM Hammad, TA Richards, MA AF Boggon, Rachael van Staa, Tjeerd P. Chapman, Michael Gallagher, Arlene M. Hammad, Tarek A. Richards, Mike A. TI Cancer recording and mortality in the General Practice Research Database and linked cancer registries SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE data quality; cancer; electronic health records; cancer registry; hospital data; pharmacoepidemiology ID COMPLETENESS; SURVIVAL; UK; REGISTRATION AB Purpose Large electronic datasets are increasingly being used to evaluate healthcare delivery. The aim of this study was to compare information held by cancer registries with that of the General Practice Research Database (GPRD). Methods A convenience sample of 101020 patients aged 40+ years drawn from GPRD formed the primary data source. This cohort was derived from a larger sample originally established for a cohort study of diabetes. GPRD records were linked with those from cancer registries in the National Cancer Data Repository (NCDR). Concordance between the two datasets was then evaluated. For cases recorded only on one dataset, validation was sought from other datasets (Hospital Episode Statistics and death registration) and by detailed analysis of a subset of GPRD records. Results A total of 5797 cancers (excluding non-melanomatous skin cancer) were recorded on GPRD. Of these cases, 4830 were also recorded on NCDR (concordance rate of 83.3%). Of the 976 cases recorded on GPRD but not on NCDR, 528 were present also in the hospital records or death certificates. Of the 341 cases recorded on NCDR but not on GPRD, 307 were recorded in these other two datasets. Rates of concordance varied by cancer type. Cancer registries recorded larger numbers of patients with lung, colorectal, and pancreatic cancers, whereas GPRD recorded more haematological cancers and melanomas. As expected, GPRD recorded significantly more non-melanomatous skin cancer. Concordance decreased with increasing age. Conclusion Although concordance levels were reasonably high, the findings from this study can be used to direct efforts for better recording in both datasets. Copyright (c) 2012 Crown copyright. C1 [Boggon, Rachael; van Staa, Tjeerd P.; Gallagher, Arlene M.] Med & Healthcare Prod Regulatory Agcy, Clin Practice Res Datalink, London SW1W 9SZ, England. [Boggon, Rachael; van Staa, Tjeerd P.; Gallagher, Arlene M.] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Utrecht, Netherlands. [van Staa, Tjeerd P.] London Sch Hyg & Trop Med, London WC1, England. [Chapman, Michael] Natl Canc Intelligence Network, London, England. [Hammad, Tarek A.] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. [Richards, Mike A.] Natl Canc Act Team, London, England. RP van Staa, TP (reprint author), Med & Healthcare Prod Regulatory Agcy, Gen Practice Res Database, 151 Buckingham Palace Rd, London SW1W 9SZ, England. EM Tjeerd.vanstaa@CPRD.com RI Research Datalink, Clinical Practice/H-2477-2013; Research Datalink RT, Clinical Practice/I-7852-2013; CPRD, CPRD/B-9594-2017; OI van Staa, Tjeerd/0000-0001-9363-742X FU MHRA; Wellcome Trust; Medical Research Council; NIHR Health Technology Assessment programme; Innovative Medicine Initiative; UK Department of Health; Technology Strategy Board; Seventh Framework Programme EU; GlaxoSmithKline; Dutch Medicines Evaluation Board; Dutch Ministry of Health; Novo Nordisk FX This study did not receive external funding. CPRD is owned by the UK Department of Health and operates within the Medicines and Healthcare products Regulatory Agency (MHRA). CPRD has received funding from the MHRA, Wellcome Trust, Medical Research Council, NIHR Health Technology Assessment programme, Innovative Medicine Initiative, UK Department of Health, Technology Strategy Board, Seventh Framework Programme EU, various universities, contract research organisations, and pharmaceutical companies. The Department of Pharmacoepidemiology & Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, has received unrestricted funding for pharmacoepidemiological research from GlaxoSmithKline, Novo Nordisk, the private-public-funded Top Institute Pharma (www.tipharma.nl, includes c-funding from universities, government, and industry), the Dutch Medicines Evaluation Board, and the Dutch Ministry of Health. NR 11 TC 35 Z9 35 U1 0 U2 12 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD FEB PY 2013 VL 22 IS 2 BP 168 EP 175 DI 10.1002/pds.3374 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 088FM UT WOS:000314819200008 PM 23239282 ER PT J AU Weng, LM Zhang, L Peng, Y Huang, RS AF Weng, Liming Zhang, Li Peng, Yan Huang, R. Stephanie TI Pharmacogenetics and pharmacogenomics: a bridge to individualized cancer therapy SO PHARMACOGENOMICS LA English DT Review DE anticancer agents; drug label; pharmacogenetics; pharmacogenomics ID DIHYDROPYRIMIDINE DEHYDROGENASE GENE; ACUTE LYMPHOBLASTIC-LEUKEMIA; SINGLE NUCLEOTIDE POLYMORPHISMS; SEVERE 5-FLUOROURACIL TOXICITY; COLORECTAL-CANCER; COST-EFFECTIVENESS; HERITABILITY; DISCOVERY; MUTATION; KRAS AB In the past decade, advances in pharmacogenetics and pharmacogenomics (PGx) have gradually unveiled the genetic basis of interindividual differences in drug responses. A large portion of these advances have been made in the field of anticancer therapy. Currently, the US FDA has updated the package inserts of approximately 30 anticancer agents to include PGx information. Given the complexity of this genetic information (e.g., tumor mutation and gene overexpression, chromosomal translocation and germline variations), as well as the variable level of scientific evidence, the FDA recommendation and potential action needed varies among drugs. In this review, we have highlighted some of these PGx discoveries for their scientific values and utility in improving therapeutic efficacy and reducing side effects. Furthermore, examples are also provided for the role of PGx in new anticancer drug development by revealing novel druggable targets. C1 [Weng, Liming; Huang, R. Stephanie] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Zhang, Li] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Peng, Yan] Wuhan Univ, Renmin Hosp, Dept Pharm, Wuhan, Peoples R China. RP Huang, RS (reprint author), Univ Chicago, Dept Med, 900 E 57th St,KCBD Room 7148, Chicago, IL 60637 USA. EM rhuang@medicine.bsd.uchicago.edu RI Weng, Liming/E-7791-2015 FU NIH/NIGMS [K08GM089941]; NIH/NCI [R21 CA139278]; NIH/NIGMS Pharmacogenomics of Anticancer Agents grant [U01GM61393]; University of Chicago Breast Cancer SPORE Career Development Award; University of Chicago Cancer Center [P30 CA14599]; National Center for Advancing Translational Sciences of the NIH [UL1RR024999] FX RS Huang received support from NIH/NIGMS grant K08GM089941, NIH/NCI Grant R21 CA139278, NIH/NIGMS Pharmacogenomics of Anticancer Agents grant U01GM61393, the University of Chicago Breast Cancer SPORE Career Development Award, the University of Chicago Cancer Center Support Grant (#P30 CA14599) and the National Center for Advancing Translational Sciences of the NIH (UL1RR024999). 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 23 Z9 24 U1 0 U2 32 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 EI 1744-8042 J9 PHARMACOGENOMICS JI Pharmacogenomics PD FEB PY 2013 VL 14 IS 3 BP 315 EP 324 DI 10.2217/PG3.12.213 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 087WG UT WOS:000314794500017 PM 23394393 ER PT J AU Liu, Y Chen, J Shellock, FG Kainz, W AF Liu, Yan Chen, Ji Shellock, Frank G. Kainz, Wolfgang TI Computational and experimental studies of an orthopedic implant: MRI-related heating at 1.5-T/64-MHz and 3-T/128-MHz SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE MRI safety; heating; electromagnetic modeling; medical implants ID SIMULATION; SAR AB Purpose: To use numerical modeling to predict the worst-case of magnetic resonance imaging (MRI)-induced heating of an orthopedic implant of different sizes under 1.5-T/64-MHz and 3-T/128-MHz conditions and to apply the experimental test to validate the numerical results for worst-case heating. Materials and Methods: Investigations of specific absorption rate (SAR) and the temperature rise of an orthopedic implant of different sizes within a standard phantom were accomplished by numerical finite-difference time-domain modeling and experimental measurements. MRI-related heating experiments were performed using standardized techniques at 1.5-T/64-MHz and 3-T/128-MHz. Results: The numerical modeling results indicated that the induced energy deposition is almost linearly related to the dimension of the orthopedic implant when it is less than 100 mm for 1.5-T/64-MHz and 3-T/128-MHz conditions. At 3-T/128-MHz, when the dimension is greater than 100 mm, the linear relation does not exist, which suggests a wavelength effect at higher frequency. Higher temperature rises occurred at 1.5-T/64-MHz MRI than at 3-T/128-MHz for both numerical modeling and experimental studies. Conclusion: The numerical technique predicted which device size had maximum heating and its location. Temperature rise data agreed well with thermal simulation results. The presented method proved to be suitable to assess MRI-induced heating of complex medical implants. J. Magn. Reson. Imaging 2013;37:491497. (C) 2012 Wiley Periodicals, Inc. C1 [Liu, Yan; Chen, Ji] Univ Houston, Dept Elect & Comp Engn, Houston, TX 77204 USA. [Shellock, Frank G.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Shellock, Frank G.] Inst Magnet Resonance Safety Educ & Res, Los Angeles, CA USA. [Kainz, Wolfgang] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Chen, J (reprint author), Univ Houston, Dept Elect & Comp Engn, Houston, TX 77204 USA. EM jchen18@uh.edu NR 10 TC 14 Z9 14 U1 2 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD FEB PY 2013 VL 37 IS 2 BP 491 EP 497 DI 10.1002/jmri.23764 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 079OP UT WOS:000314180400025 PM 22851423 ER PT J AU Lacana, E AF Lacana, Emanuela TI Regulatory science and product quality perspectives for lysosomal storage diseases SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 9th Annual World Symposium of the Lysosomal-Disease-Network (LDN) CY FEB 12-15, 2013 CL Orlando, FL SP Lysosomal Dis Network (LDN) C1 [Lacana, Emanuela] US FDA, Off Biotechnol Prod, Ctr Drugs Evaluat & Res, Bethesda, MD 20014 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2013 VL 108 IS 2 MA 126 BP S57 EP S57 DI 10.1016/j.ymgme.2012.11.140 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 086FW UT WOS:000314670500128 ER PT J AU Maliepaard, M Nofziger, C Papaluca, M Zineh, I Uyama, Y Prasad, K Grimstein, C Pacanowski, M Ehmann, F Dossena, S Paulmichl, M AF Maliepaard, Marc Nofziger, Charity Papaluca, Marisa Zineh, Issam Uyama, Yoshiaki Prasad, Krishna Grimstein, Christian Pacanowski, Michael Ehmann, Falk Dossena, Silvia Paulmichl, Markus TI Pharmacogenetics in the evaluation of new drugs: a multiregional regulatory perspective SO NATURE REVIEWS DRUG DISCOVERY LA English DT Article ID PROTEIN INTERACTION NETWORK; GENOMIC MEDICINE; INTERACTOME; INCIDENTALOME; CLOPIDOGREL; TRANSPORTERS; ASSOCIATION; EXPRESSION; VARIANTS; GENOTYPE AB Pharmacogenetics, one of the cornerstones of personalized medicine, has the potential to change the way in which health care is offered by stratifying patients into various pretreatment categories, such as likely responders, likely non-responders or likely to experience adverse drug reactions. In order to advance drug development and regulatory science, regulatory agencies globally have promulgated guidelines on pharmacogenetics for nearly a decade. The aim of this article is to provide an overview of new guidelines for the implementation of pharmacogenetics in drug development from a multiregional regulatory perspective - encompassing Europe, the United States and Japan - with an emphasis on clinical pharmacokinetics. C1 [Maliepaard, Marc] Med Evaluat Board, Utrecht, Netherlands. [Maliepaard, Marc] Radboud Univ Nijmegen, Med Ctr, NL-3503 RC Utrecht, Netherlands. [Nofziger, Charity; Dossena, Silvia; Paulmichl, Markus] Paracelsus Med Univ, A-5020 Salzburg, Austria. [Papaluca, Marisa; Ehmann, Falk] European Med Agcy, London E14 4HB, England. [Zineh, Issam; Grimstein, Christian; Pacanowski, Michael] US FDA, Silver Spring, MD 20993 USA. [Prasad, Krishna] Med & Healthcare Prod Regulatory Agcy, London SW8 5NQ, England. [Uyama, Yoshiaki] Pharmaceut & Med Devices Agcy, Chiyoda Ku, Tokyo 1000013, Japan. RP Paulmichl, M (reprint author), Paracelsus Med Univ, Strubergasse 21, A-5020 Salzburg, Austria. EM markus.paulmichl@pmu.ac.at FU Fonds cur Forderung der Wissenschaftlichen Forschung (FWF) [M11108-B11]; FP-7 [P18608, PIRSES-GA-2008-230661] FX The authors greatly appreciated helpful discussions with I. Kohane (Harvard, USA), R. Diasio (Mayo Clinic, USA) and F. Innocenti (University of North Carolina, Chapel Hill, USA). C.N. is supported by the Line Meitner stipend of the Fonds cur Forderung der Wissenschaftlichen Forschung (FWF) (M11108-B11). Further support was given by the FWF and the FP-7 to M. Paulmichl (P18608; PIRSES-GA-2008-230661). The authors acknowledge the expert secretarial assistance of E. Mooslechner. NR 50 TC 30 Z9 31 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD FEB PY 2013 VL 12 IS 2 BP 103 EP 115 DI 10.1038/nrd3931 PG 13 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 087CS UT WOS:000314739500017 PM 23370249 ER PT J AU Hong, HX Zhang, WQ Shen, J Su, ZQ Ning, BT Han, T Perkins, R Shi, LM Tong, WD AF Hong HuiXiao Zhang WenQian Shen Jie Su ZhenQiang Ning BaiTang Han Tao Perkins, Roger Shi LeMing Tong WeiDa TI Critical role of bioinformatics in translating huge amounts of next-generation sequencing data into personalized medicine SO SCIENCE CHINA-LIFE SCIENCES LA English DT Review DE personalized medicine; next-generation sequencing; bioinformatics; short reads; alignment; assemble; data analysis ID ALIGNMENT PROGRAM; SHORT READS; DNA; GENOME; OLIGONUCLEOTIDES; ALGORITHMS; QUALITY; SEARCH; RNA AB Realizing personalized medicine requires integrating diverse data types with bioinformatics. The most vital data are genomic information for individuals that are from advanced next-generation sequencing (NGS) technologies at present. The technologies continue to advance in terms of both decreasing cost and sequencing speed with concomitant increase in the amount and complexity of the data. The prodigious data together with the requisite computational pipelines for data analysis and interpretation are stressors to IT infrastructure and the scientists conducting the work alike. Bioinformatics is increasingly becoming the rate-limiting step with numerous challenges to be overcome for translating NGS data for personalized medicine. We review some key bioinformatics tasks, issues, and challenges in contexts of IT requirements, data quality, analysis tools and pipelines, and validation of biomarkers. C1 [Hong HuiXiao; Shen Jie; Su ZhenQiang; Perkins, Roger; Shi LeMing; Tong WeiDa] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Zhang WenQian] Beijing Genom Inst, Shenzhen 518083, Peoples R China. [Ning BaiTang; Han Tao] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Hong, HX (reprint author), US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM huixiao.hong@fda.hhs.gov NR 55 TC 15 Z9 19 U1 1 U2 42 PU SCIENCE PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1674-7305 EI 1869-1889 J9 SCI CHINA LIFE SCI JI Sci. China-Life Sci. PD FEB PY 2013 VL 56 IS 2 BP 110 EP 118 DI 10.1007/s11427-013-4439-7 PG 9 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 086PF UT WOS:000314697200003 PM 23393026 ER PT J AU Guo, YL Shi, LM Hong, HX Su, ZQ Fuscoe, J Ning, BT AF Guo YongLi Shi LeMing Hong HuiXiao Su ZhenQiang Fuscoe, James Ning BaiTang TI Studies on abacavir-induced hypersensitivity reaction: a successful example of translation of pharmacogenetics to personalized medicine SO SCIENCE CHINA-LIFE SCIENCES LA English DT Review DE personalized medicine; pharmacogenetics; drug safety; abacavir; hypersensitivity reaction (HSR); HLA-B*57:01; HLA-B*57:01 screening ID HUMAN-LEUKOCYTE ANTIGEN-B-ASTERISK-5701; COST-EFFECTIVENESS ANALYSIS; HIV-INFECTED PATIENTS; RISK-FACTOR-ANALYSIS; HLA-B REGION; CLASS-I; DRUG HYPERSENSITIVITY; GENETIC-VARIATIONS; HLA-B-ASTERISK-5701; POPULATION AB Abacavir is an effective nucleoside analog reverse transcriptase inhibitor used to treat human immunodeficiency virus (HIV) infected patients. Its main side effect is hypersensitivity reaction (HSR). The incidence of the HSR is associated with ethnicity among patients exposed to abacavir, and retrospective and prospective studies show a significantly increased risk of abacavir-induced HSR in human leukocyte antigen (HLA)-B*57:01-carrying patients. Immunological studies indicated that abacavir interacts specifically with HLA-B*57:01 and changed the binding specificity between the HLA molecule and the HLA-presented endogenous peptide repertoire, leading to a systemic autoimmune reaction. HLA-B*57:01 screening, combined with patch testing, had clinically predictive value and cost-effective impact in reducing the incidence of abacavir-induced HSR regardless of the HLA-B*57:01 prevalence in the population. Therefore, the US Food and Drug Administration (FDA) and international HIV treatment guidelines recommend a routine HLA-B*57:01 screening prior to abacavir treatment to decrease false positive diagnosis and prevent abacavir-induced HSR. The studies of abacavir-induced HSR and the implementation of the HLA-B*57:01 screening in the clinic represent a successful example of the use of pharmacogenetics for personalized diagnosis and therapy. C1 [Guo YongLi; Fuscoe, James; Ning BaiTang] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Shi LeMing; Hong HuiXiao; Su ZhenQiang] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Ning, BT (reprint author), US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM Baitang.Ning@fda.hhs.gov NR 55 TC 15 Z9 15 U1 0 U2 14 PU SCIENCE PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1674-7305 J9 SCI CHINA LIFE SCI JI Sci. China-Life Sci. PD FEB PY 2013 VL 56 IS 2 BP 119 EP 124 DI 10.1007/s11427-013-4438-8 PG 6 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 086PF UT WOS:000314697200004 PM 23393027 ER PT J AU Gallagher, LM Ganz, PR Yang, H Kessler, DA O'Brien, SF Custer, BS Busch, MP Dodd, RY Stramer, SL Walderhaug, MO Forshee, RA Williams, AE Epstein, JS Anderson, SA AF Gallagher, Lou M. Ganz, Peter R. Yang, Hong Kessler, Debra A. O'Brien, Sheila F. Custer, Brian S. Busch, Michael P. Dodd, Roger Y. Stramer, Susan L. Walderhaug, Mark O. Forshee, Richard A. Williams, Alan E. Epstein, Jay S. Anderson, Steven A. TI Advancing risk assessment for emerging infectious diseases for blood and blood products: proceedings of a public workshop SO TRANSFUSION LA English DT Article ID WEST-NILE-VIRUS; TRYPANOSOMA-CRUZI INFECTION; UNITED-STATES; TRANSFUSION TRANSMISSION; BABESIA-MICROTI; DENGUE VIREMIA; CHAGAS-DISEASE; RESIDUAL RISK; PUERTO-RICO; DONORS C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Hlth Canada, Ottawa, ON K1A 0L2, Canada. New York Blood Ctr, New York, NY 10021 USA. Canadian Blood Serv, Ottawa, ON, Canada. Univ Calif San Francisco, Blood Syst Res Inst, San Francisco, CA 94143 USA. Amer Red Cross, Washington, DC 20006 USA. RP Gallagher, LM (reprint author), 1401 Rockville Pike,HFM 210,WOC1, Rockville, MD 20852 USA. EM lou.gallagher@fda.hhs.gov NR 47 TC 3 Z9 3 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD FEB PY 2013 VL 53 IS 2 BP 455 EP 463 DI 10.1111/j.1537-2995.2012.03808.x PG 9 WC Hematology SC Hematology GA 087ST UT WOS:000314783700029 PM 22845334 ER PT J AU Grider, A Wickwire, K Ho, E Chung, CS King, J AF Grider, Arthur Wickwire, Kathie Ho, Emily Chung, Carolyn S. King, Janet TI Dietary zinc depletion and repletion affects plasma proteins: an analysis of the plasma proteome SO BIOMETALS LA English DT Article DE Fibrin beta; Zn biomarker; Marginal Zn deficiency; Dietary Zn depletion and repletion; Two-dimensional gel electrophoresis; Hemostasis ID DEFICIENT RATS; FACTOR-XII; ACTIVATION; IONS; ZN2+; ACCELERATION; FIBRINOLYSIS; PLASMINOGEN; THROMBIN; ENZYMES AB Zinc (Zn) deficiency is a problem world-wide. Current methods for assessing Zn status are limited to measuring plasma or serum Zn within populations suspected of deficiency. Despite the high prevalence of Zn deficiency in the human population there are no methods currently available for sensitively assessing Zn status among individuals. The purpose of this research was to utilize a proteomic approach using two-dimensional gel electrophoresis (2DE) and mass spectrometry to identify protein biomarkers that were sensitive to changes in dietary Zn levels in humans. Proteomic analysis was performed in human plasma samples (n = 6) obtained from healthy adult male subjects that completed a dietary Zn depletion/repletion protocol, current dietary zinc intake has a greater effect on fractional zinc absorption than does longer term zinc consumption in healthy adult men. Chung et al. (Am J Clin Nutr 87 (5):1224-1229, 2008). After a 13 day Zn acclimatization period where subjects consumed a Zn-adequate diet, the male subjects consumed a marginal Zn-depleted diet for 42 days followed by consumption of a Zn-repleted diet for 28 days. The samples at baseline, end of depletion and end of repletion were pre-fractionated through immuno-affinity columns to remove 14 highly abundant proteins, and each fraction separated by 2DE. Following staining by colloidal Coomassie blue and densitometric analysis, three proteins were identified by mass spectrometry as affected by changes in dietary Zn. Fibrin beta and chain E, fragment double D were observed in the plasma protein fraction that remained bound to the immunoaffinity column. An unnamed protein that was related to immunoglobulins was observed in the immunodepleted plasma fraction. Fibrin beta increased two-fold following the Zn depletion period and decreased to baseline values following the Zn repletion period; this protein may serve as a viable biomarker for Zn status in the future. C1 [Grider, Arthur; Wickwire, Kathie] Univ Georgia, Dept Foods & Nutr, Coll Family & Consumer Sci, Athens, GA 30602 USA. [Ho, Emily] Oregon State Univ, Sch Biol & Populat Hlth Sci, Coll Publ Hlth & Human Sci, Corvallis, OR 97331 USA. [Chung, Carolyn S.] US FDA, Off Nutr Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [King, Janet] Childrens Hosp Oakland, Res Inst, Ctr Nutr & Metab, Oakland, CA 94609 USA. RP Grider, A (reprint author), Univ Georgia, Dept Foods & Nutr, Coll Family & Consumer Sci, Athens, GA 30602 USA. EM agrider@fcs.uga.edu; kwickwir@fcs.uga.edu; emily.ho@oregonstate.edu; carolyn.chung@fda.hhs.gov; jking@chori.org FU General Clinical Research Center, University of California, San Francisco at the San Francisco General Hospital; National Center for Research Resources, National Institutes of Health [MO1-RR00083-43]; Oregon Agriculture Experiment Station [OR00735]; Environmental Health Science Center at Oregon State University [NIEHS P30 ES00210]; USANA Health Sciences, Inc., Salt Lake City, UT; Georgia Agriculture Experiment Station [GEO00513] FX Supported, in part, by beef and veal producers and importers through their $1-per-head checkoff and was produced for the Cattlemen's Beef Board and State Beef Councils by the National Cattlemen's Beef Association; by the General Clinical Research Center, University of California, San Francisco at the San Francisco General Hospital; the National Center for Research Resources, National Institutes of Health (Grant MO1-RR00083-43); Oregon Agriculture Experiment Station (OR00735); the Environmental Health Science Center at Oregon State University (NIEHS P30 ES00210); USANA Health Sciences, Inc., Salt Lake City, UT and Georgia Agriculture Experiment Station (GEO00513). NR 37 TC 2 Z9 2 U1 0 U2 19 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0966-0844 J9 BIOMETALS JI Biometals PD FEB PY 2013 VL 26 IS 1 BP 133 EP 140 DI 10.1007/s10534-012-9600-4 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 080VC UT WOS:000314271200012 PM 23255060 ER PT J AU Hoffmann, M Monday, SR McCarthy, PJ Lopez, JV Fischer, M Brown, EW AF Hoffmann, Maria Monday, Steven R. McCarthy, Peter J. Lopez, Jose V. Fischer, Markus Brown, Eric W. TI Genetic and phylogenetic evidence for horizontal gene transfer among ecologically disparate groups of marine Vibrio SO CLADISTICS LA English DT Article ID MULTILOCUS SEQUENCE-ANALYSIS; LENGTH DIFFERENCE TEST; ATHEROSCLEROSIS OBSERVATIONS; ESCHERICHIA-COLI; CHESAPEAKE BAY; HEMOLYSIN TLH; RIBOSOMAL-RNA; BACTERIA; SPONGE; EVOLUTIONARY AB Vibrio represents a diverse bacterial genus found in different niches of the marine environment, including numerous genera of marine sponges (phylum Porifera), inhabiting different depths and regions of benthic seas, that are potentially important in driving adaptive change among Vibrio spp. Using 16S rRNA gene sequencing, a previous study showed that sponge-derived (SD) vibrios clustered with their mainstream counterparts present in shallow, coastal ecosystems, suggesting a genetic relatedness between these populations. Sequences from the topA, ftsZ, mreB, rpoD, rctB and toxR genes were used to investigate the degree of relatedness existing between these two separate populations by examining their phylogenetic and genetic disparity. Phylogenies were constructed from the concatenated sequences of the six housekeeping genes using maximum-parsimony, maximum-likelihood and neighbour-joining algorithms. Genetic recombination was evaluated using the incongruence length difference test, Split decomposition and measuring overall compatibility of sites. This combined technical approach provided evidence that SD Vibrio strains are largely genetically homologous to their shallow-water counterparts. Moreover, the analyses conducted support the existence of extensive horizontal gene transfer between these two groups, supporting the idea of a single panmictic population structure among vibrios from two seemingly distinct, marine environments. (C) The Willi Hennig Society 2013 C1 [Hoffmann, Maria; Monday, Steven R.; Brown, Eric W.] US FDA, Div Microbiol, Off Regulatory Sci, College Pk, MD 20740 USA. [Hoffmann, Maria; Fischer, Markus] Univ Hamburg, Inst Food Chem, Dept Chem, D-20146 Hamburg, Germany. [McCarthy, Peter J.] Florida Atlantic Univ, Ctr Marine Biomed & Biotechnol Res, Harbor Branch Oceanog Inst, Ft Pierce, FL 34946 USA. [Lopez, Jose V.] Nova SE Univ, Oceanog Ctr, Dania, FL 33004 USA. RP Hoffmann, M (reprint author), US FDA, Div Microbiol, Off Regulatory Sci, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM maria.hoffman@fda.hhs.gov OI McCarthy, Peter/0000-0002-2396-7463 NR 67 TC 2 Z9 2 U1 0 U2 25 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0748-3007 J9 CLADISTICS JI Cladistics PD FEB PY 2013 VL 29 IS 1 BP 46 EP 64 DI 10.1111/j.1096-0031.2012.00416.x PG 19 WC Evolutionary Biology SC Evolutionary Biology GA 074LW UT WOS:000313815000006 ER PT J AU Gupta, DK Huang, SM AF Gupta, D. K. Huang, S-M TI Drug Shortages in the United States: A Critical Evaluation of Root Causes and the Need for Action SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID CHEMOTHERAPY; PHARMACOLOGY AB Every day it is easy to find news articles detailing the impact of drug shortages on patients. Where this was once only a concern of patients with rare, orphan diseases, it is now the concern of patients receiving even the most common chemotherapeutic regimens, the most efficacious antimicrobial therapy, or even the most rapid-acting analgesics, largely as a result of manufacturing quality problems. Unfortunately for many of these patients, there are no efficacious alternatives. C1 [Gupta, D. K.] Northwestern Univ, Feinberg Sch Med, Dept Anesthesiol, Chicago, IL 60611 USA. [Gupta, D. K.] Northwestern Univ, Feinberg Sch Med, Dept Neurol Surg, Chicago, IL 60611 USA. [Huang, S-M] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Gupta, DK (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Anesthesiol, Chicago, IL 60611 USA. EM dhanesh-gupta@northwestern.edu NR 11 TC 6 Z9 6 U1 0 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2013 VL 93 IS 2 BP 133 EP 135 DI 10.1038/clpt.2012.229 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 078ZH UT WOS:000314139100001 PM 23337520 ER PT J AU Huang, SM Bhattaram, A Mehrotra, N Wang, Y AF Huang, S-M Bhattaram, A. Mehrotra, N. Wang, Y. TI Is This the Dose for You?: The Role of Modeling SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID DRUG DEVELOPMENT; IMPACT AB To make an informed benefit-risk evaluation of a drug, a range of doses needs to be evaluated and its dose-response and exposure-response relationships for safety and effectiveness assessed during drug development (International Conference on Harmonisation E4). Once a safe and effective population dose (or doses) has been determined for indicated use(s), the individual patient dose can then be adjusted based on patient-specific factors (e.g., age, race, genetics, organ functions, concomitant medications).(1) C1 [Huang, S-M; Bhattaram, A.; Mehrotra, N.; Wang, Y.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Huang, SM (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM shiewmei.huang@fda.hhs.gov NR 5 TC 4 Z9 4 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2013 VL 93 IS 2 BP 159 EP 162 DI 10.1038/clpt.2012.228 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 078ZH UT WOS:000314139100017 PM 23281423 ER PT J AU Woodcock, J Wosinska, M AF Woodcock, J. Wosinska, M. TI Economic and Technological Drivers of Generic Sterile Injectable Drug Shortages SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article AB Over the past few years, an increasing number of critically needed medicines have been in short supply. Using economic theory to frame the drug-shortage problem, this paper explores why and how manufacturing-quality problems could combine with other economic and technological factors to result in shortages of generic sterile injectable drugs. The fundamental problem we identify is the inability of the market to observe and reward quality. This lack of reward for quality can reinforce price competition and encourage manufacturers to keep costs down by minimizing quality investments. The US Food and Drug Administration's (FDA's) need to use its regulatory flexibility, on behalf of patients, to avoid shortages of medically necessary drugs may further strengthen the incentive to "push the envelope" on quality. These dynamics may have produced a market situation in which quality problems have become sufficiently common and severe to result in drug shortages. C1 [Woodcock, J.; Wosinska, M.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Wosinska, M (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM marta.wosinska@fda.hhs.gov NR 16 TC 49 Z9 49 U1 0 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2013 VL 93 IS 2 BP 170 EP 176 DI 10.1038/clpt.2012.220 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 078ZH UT WOS:000314139100019 PM 23337525 ER PT J AU Anathula, H Agarwal, S Zhang, L AF Anathula, H. Agarwal, S. Zhang, L. TI REVIEW OF IN VITRO TRANSPORTER DATA IN RECENTLY APPROVED NEW DRUG APPLICATIONS SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) / Quantitative Systems Pharmacology - An Integrating Framework for Translational Medicine Pre-Conference CY MAR 05-09, 2013 CL Indianapolis, IN SP Amer Soc Clin Pharmacol & Therapeut (ASCPT) C1 [Anathula, H.] Univ Cincinnati, James L Winkle Coll Pharm, Cincinnati, OH USA. [Agarwal, S.; Zhang, L.] US FDA, Off Clin Pharmacol, Off Translat Sci, CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2013 VL 93 SU 1 BP S91 EP S92 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 078ZD UT WOS:000314138700249 ER PT J AU Bai, PJ Abernethy, DR Guo, L Liu, Z Tong, W AF Bai, P. J. Abernethy, D. R. Guo, L. Liu, Z. Tong, W. TI ROLE OF CARNITINE PALMITOYLTRANSFERASE II IN DRUG-INDUCED RHABDOMYOLYSIS SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) / Quantitative Systems Pharmacology - An Integrating Framework for Translational Medicine Pre-Conference CY MAR 05-09, 2013 CL Indianapolis, IN SP Amer Soc Clin Pharmacol & Therapeut (ASCPT) C1 [Bai, P. J.; Abernethy, D. R.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Guo, L.; Liu, Z.; Tong, W.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2013 VL 93 SU 1 BP S13 EP S13 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 078ZD UT WOS:000314138700033 ER PT J AU Jiang, X Zhao, P Lesko, LJ Schmidt, S AF Jiang, X. Zhao, P. Lesko, L. J. Schmidt, S. TI APPLICATION OF PHYSIOLOGICALLY-BASED PHARMACOKINETIC (PBPK) MODEL IN PREDICTING DRUG METABOLISM AND PHARMACOKINETICS IN PEDIATRIC POPULATIONS - A CASE STUDY OF ACETAMINOPHEN. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) / Quantitative Systems Pharmacology - An Integrating Framework for Translational Medicine Pre-Conference CY MAR 05-09, 2013 CL Indianapolis, IN SP Amer Soc Clin Pharmacol & Therapeut (ASCPT) C1 [Jiang, X.; Lesko, L. J.; Schmidt, S.] Univ Florida, Orlando, FL USA. [Zhao, P.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 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 FEB PY 2013 VL 93 SU 1 BP S50 EP S50 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 078ZD UT WOS:000314138700133 ER PT J AU Jiang, X Zhao, P Lesko, LJ Schmidt, S AF Jiang, X. Zhao, P. Lesko, L. J. Schmidt, S. TI APPLICATION OF PHYSIOLOGICALLY-BASED PHARMACO-KINETIC (PBPK) MODEL IN PREDICTING DRUG METABOLISM AND PHARMACOKINETICS IN PEDIATRIC POPULATIONS-A CASE STUDY OF ACETAMINOPHEN SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) / Quantitative Systems Pharmacology - An Integrating Framework for Translational Medicine Pre-Conference CY MAR 05-09, 2013 CL Indianapolis, IN SP Amer Soc Clin Pharmacol & Therapeut (ASCPT) C1 [Jiang, X.; Lesko, L. J.; Schmidt, S.] Univ Florida, Orlando, FL USA. [Zhao, P.] US FDA, Silver Spring, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2013 VL 93 SU 1 BP S8 EP S8 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 078ZD UT WOS:000314138700019 ER PT J AU Kim, H Moon, Y Jain, R Khurana, M Lee, J Vaidyanathan, J Sahajwalla, C Chung, S AF Kim, H. Moon, Y. Jain, R. Khurana, M. Lee, J. Vaidyanathan, J. Sahajwalla, C. Chung, S. TI INSULIN PHARMACOKINETICS (PK) AND PHARMACODYNAMICS (PD) IN GESTATIONAL DIABETES (GD) COMPARED TO THOSE OF HEALTHY SUBJECTS (HS). SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) / Quantitative Systems Pharmacology - An Integrating Framework for Translational Medicine Pre-Conference CY MAR 05-09, 2013 CL Indianapolis, IN SP Amer Soc Clin Pharmacol & Therapeut (ASCPT) C1 [Kim, H.; Moon, Y.] ORISE, Silver Spring, MD USA. [Jain, R.; Khurana, M.; Lee, J.; Vaidyanathan, J.; Sahajwalla, C.; Chung, S.] US FDA, CDER, OTS, OCP, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2013 VL 93 SU 1 BP S71 EP S71 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 078ZD UT WOS:000314138700191 ER PT J AU Lee, S Chung, S Volpe, DA Jappar, D Fan, Y Zhang, L AF Lee, S. Chung, S. Volpe, D. A. Jappar, D. Fan, Y. Zhang, L. TI POTENTIAL IMPACT OF RENAL OR HEPATIC IMPAIRMENT ON DRUG TRANSPORTERS SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) / Quantitative Systems Pharmacology - An Integrating Framework for Translational Medicine Pre-Conference CY MAR 05-09, 2013 CL Indianapolis, IN SP Amer Soc Clin Pharmacol & Therapeut (ASCPT) C1 [Lee, S.; Chung, S.; Volpe, D. A.; Jappar, D.; Fan, Y.; Zhang, L.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2013 VL 93 SU 1 BP S85 EP S86 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 078ZD UT WOS:000314138700232 ER PT J AU Liu, D Jain, R Chung, SM Khurana, M Vaidyanathan, J Zadezensky, I Sahajwalla, CG AF Liu, D. Jain, R. Chung, S. M. Khurana, M. Vaidyanathan, J. Zadezensky, I. Sahajwalla, C. G. TI CHANGES OF CLEARANCE IN OBESE SUBJECTS: IS BODY SIZE THE ONLY REASON? SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) / Quantitative Systems Pharmacology - An Integrating Framework for Translational Medicine Pre-Conference CY MAR 05-09, 2013 CL Indianapolis, IN SP Amer Soc Clin Pharmacol & Therapeut (ASCPT) C1 [Liu, D.; Jain, R.; Chung, S. M.; Khurana, M.; Vaidyanathan, J.; Zadezensky, I.; Sahajwalla, C. G.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2013 VL 93 SU 1 BP S77 EP S77 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 078ZD UT WOS:000314138700208 ER PT J AU Sarntivijai, S Hwang, S Shon, J Zhichkin, P He, Y Athey, BD Abernethy, DR AF Sarntivijai, S. Hwang, S. Shon, J. Zhichkin, P. He, Y. Athey, B. D. Abernethy, D. R. TI AN INTEGRATIVE TRANSLATIONAL BIOINFORMATICS APPROACH TO STUDY TYROSINE KINASE INHIBITOR INDUCED NON-QT CARDIOTOXICITY SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) / Quantitative Systems Pharmacology - An Integrating Framework for Translational Medicine Pre-Conference CY MAR 05-09, 2013 CL Indianapolis, IN SP Amer Soc Clin Pharmacol & Therapeut (ASCPT) C1 [Sarntivijai, S.; Hwang, S.; Shon, J.; Zhichkin, P.; Abernethy, D. R.] US FDA, Silver Spring, MD USA. [He, Y.; Athey, B. D.] Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2013 VL 93 SU 1 BP S13 EP S13 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 078ZD UT WOS:000314138700032 ER PT J AU Sarntivijai, S Hwang, S Shon, J Zhichkin, P He, Y Athey, BD Abernethy, DR AF Sarntivijai, S. Hwang, S. Shon, J. Zhichkin, P. He, Y. Athey, B. D. Abernethy, D. R. TI AN INTEGRATIVE TRANSLATIONAL BIOINFORMATICS APPROACH TO STUDY TYROSINE KINASE INHIBITOR INDUCED NON-QT CARDIOTOXICITY SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) / Quantitative Systems Pharmacology - An Integrating Framework for Translational Medicine Pre-Conference CY MAR 05-09, 2013 CL Indianapolis, IN SP Amer Soc Clin Pharmacol & Therapeut (ASCPT) C1 [Sarntivijai, S.; Hwang, S.; Shon, J.; Zhichkin, P.; Abernethy, D. R.] US FDA, Silver Spring, MD USA. [He, Y.; Athey, B. D.] Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2013 VL 93 SU 1 BP S5 EP S5 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 078ZD UT WOS:000314138700011 ER PT J AU Shon, J Fujita, K Ghosh, S Matsuoka, Y Hwang, S Yang, Y Sarntivijai, S Bai, J Kitano, H Abernethy, DR AF Shon, J. Fujita, K. Ghosh, S. Matsuoka, Y. Hwang, S. Yang, Y. Sarntivijai, S. Bai, J. Kitano, H. Abernethy, D. R. TI A MECHANISTIC PATHWAYS MAP FOR DRUG INDUCED LIVER INJURY: MOLECULAR NETWORK FOR MITOCHONDRIAL DYSFUNCTION SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) / Quantitative Systems Pharmacology - An Integrating Framework for Translational Medicine Pre-Conference CY MAR 05-09, 2013 CL Indianapolis, IN SP Amer Soc Clin Pharmacol & Therapeut (ASCPT) C1 [Shon, J.; Hwang, S.; Yang, Y.; Sarntivijai, S.; Bai, J.; Abernethy, D. R.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Fujita, K.; Ghosh, S.; Matsuoka, Y.; Kitano, H.] Syst Biol Inst, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2013 VL 93 SU 1 BP S3 EP S4 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 078ZD UT WOS:000314138700007 ER PT J AU Sun, W Hochhaus, G Wang, Y AF Sun, W. Hochhaus, G. Wang, Y. TI PRELIMINARY DEVELOPMENT OF DISEASE PROGRESSION MODEL FOR HUNTINGTON'S DISEASE SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) / Quantitative Systems Pharmacology - An Integrating Framework for Translational Medicine Pre-Conference CY MAR 05-09, 2013 CL Indianapolis, IN SP Amer Soc Clin Pharmacol & Therapeut (ASCPT) C1 [Sun, W.; Hochhaus, G.] Univ Florida, Dept Pharmaceut, Gainesville, FL USA. [Wang, Y.] US FDA, Off Clin Pharmacol, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2013 VL 93 SU 1 BP S110 EP S110 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 078ZD UT WOS:000314138700303 ER PT J AU Wu, F Zhao, P Lee, SH AF Wu, F. Zhao, P. Lee, S. H. TI PREDICTING NONLINEAR PHARMACOKINETICS OF OMEPRAZOLE ENANTIOMERS AND RACEMIC DRUG USING PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELING AND SIMULATION SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) / Quantitative Systems Pharmacology - An Integrating Framework for Translational Medicine Pre-Conference CY MAR 05-09, 2013 CL Indianapolis, IN SP Amer Soc Clin Pharmacol & Therapeut (ASCPT) C1 [Wu, F.; Zhao, P.; Lee, S. H.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2013 VL 93 SU 1 BP S85 EP S85 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 078ZD UT WOS:000314138700231 ER PT J AU Younis, IR Uppoor, RS Mehta, MU AF Younis, I. R. Uppoor, R. S. Mehta, M. U. TI IS THERE A NEED FOR PHARMACOKINETIC STUDIES IN CHILD-PUGH CLASS A PATIENTS? SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) / Quantitative Systems Pharmacology - An Integrating Framework for Translational Medicine Pre-Conference CY MAR 05-09, 2013 CL Indianapolis, IN SP Amer Soc Clin Pharmacol & Therapeut (ASCPT) C1 [Younis, I. R.; Uppoor, R. S.; Mehta, M. U.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2013 VL 93 SU 1 BP S91 EP S91 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 078ZD UT WOS:000314138700247 ER PT J AU Yu, C Kim, S Kim, M AF Yu, C. Kim, S. Kim, M. TI UNINTENDED INTERPERSONAL TRANSFERABILITY OF TOPICAL ESTRADIOL AND TESTOSTERONE PRODUCTS: A SAFETY CONCERN FOR CHILDREN SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) / Quantitative Systems Pharmacology - An Integrating Framework for Translational Medicine Pre-Conference CY MAR 05-09, 2013 CL Indianapolis, IN SP Amer Soc Clin Pharmacol & Therapeut (ASCPT) C1 [Yu, C.; Kim, M.] US FDA, Silver Spring, MD USA. [Kim, S.] Shenandoah Univ, Bernard J Dunn Sch Pharm, Winchester, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2013 VL 93 SU 1 BP S91 EP S91 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 078ZD UT WOS:000314138700248 ER PT J AU Huwe, JK Archer, JC AF Huwe, J. K. Archer, J. C. TI Dioxin congener patterns in commercial catfish from the United States and the indication of mineral clays as the potential source SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT LA English DT Article DE dioxins; catfish; feeds; kaolin clay; congener pattern ID DIBENZO-P-DIOXINS; FARM-RAISED CATFISH; CONTAMINATION; HEALTH; BIPHENYLS; PCBS; PCDD; USA AB Since 1991 the US Department of Agriculture (USDA) has conducted annual surveys of pesticide residues in foods under the Agricultural Marketing Service's Pesticide Data Program (PDP). To assess chemical residues in domestically marketed catfish products, 1479 catfish samples were collected during the 20082010 PDPs. A subset of 202 samples was analysed for 17 toxic polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs). The average pattern of the individual PCDD/F congener concentrations in the catfish was rather unique in that it had almost no measurable amounts of polychlorinated dibenzofurans (PCDFs), but all PCDDs were present. This pattern was more dominant in the domestically produced catfish products than in the imported products (China/Taiwan). Comparison of the pattern to known sources of PCDD/Fs showed strong similarities to the pattern of PCDD/Fs found in kaolin clays which have often been used as anti-caking agents in animal feeds. To investigate whether catfish feeds may be the source of the PCDD/Fs found in the catfish, archived catfish feed data from a US Food and Drug Administration (USFDA) database were examined. In 61 out of 112 feed samples, the PCDD concentrations were 50 times higher than the PCDF concentrations and resembled the pattern found in the catfish products and in clays mined in the south-eastern United States. Although the source of PCDD/Fs in domestically marketed catfish products cannot be definitively established, mined clay products used in feeds should be considered a likely source and, given the wide concentration range of PCDD/Fs that has been found in clays, a critical control point for PCDD/Fs entrance to the food supply. C1 [Huwe, J. K.] ARS, USDA, Biosci Res Lab, Fargo, ND 58102 USA. [Archer, J. C.] US FDA, Arkansas Reg Lab, Jefferson, AR 72079 USA. RP Huwe, JK (reprint author), ARS, USDA, Biosci Res Lab, 1605 Albrecht Blvd, Fargo, ND 58102 USA. EM Janice.Huwe@ars.usda.gov FU FSIS-ARS [60-5442-9-0476] FX The authors would like to acknowledge Kristin McDonald and Jean Picard for technical assistance with sample purification, and Margaret Lorentzsen and Grant Harrington for HRGC-HRMS analysis. Mention of trade names or commercial products in this paper is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the US Department of Agriculture (USDA) and the US Food and Drug Administration (USFDA). The USDA and USFDA are equal opportunity providers and employers. Funding for this exploratory assessment study was provided through FSIS-ARS Interagency Agreement #60-5442-9-0476. NR 26 TC 1 Z9 1 U1 0 U2 26 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1944-0049 J9 FOOD ADDIT CONTAM A JI Food Addit. Contam. Part A-Chem. PD FEB 1 PY 2013 VL 30 IS 2 BP 331 EP 338 DI 10.1080/19440049.2012.745199 PG 8 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 072KW UT WOS:000313670900014 PM 23234292 ER PT J AU Choi, SC Wang, HS Tian, LJ Murakami, Y Shin, DM Borrego, F Morse, HC Coligan, JE AF Choi, Seung-Chul Wang, Hongsheng Tian, Linjie Murakami, Yousuke Shin, Dong-Mi Borrego, Francisco Morse, Herbert C., III Coligan, John E. TI Mouse IgM Fc Receptor, FCMR, Promotes B Cell Development and Modulates Antigen-Driven Immune Responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID B-1 CELLS; SECRETED IGM; BONE-MARROW; NATURAL IGM; T-CELLS; AUTOIMMUNE-DISEASE; INDUCED APOPTOSIS; GERMINAL-CENTERS; DEFICIENT MICE; CUTTING EDGE AB FcR specific for pentameric IgM (FCMR) is expressed at high levels by B cells. Although circulating IgM has profound effects on responses to pathogens, autoimmunity, and B cell homeostasis, the biologic consequences of its binding to FCMR are poorly understood. We interrogated FCMR contributions to B cell function by studying mice that lack FCMR. FCMR transcripts are expressed at different levels by various B cell subsets. FCMR-deficient mice have reduced numbers of developing B cells, splenic follicular and peritoneal B-2 cells, but increased levels of peritoneal B-1a cells and autoantibodies. After immunization, germinal center B cell and plasma cell numbers are increased. FCMR-deficient B cells are sensitive to apoptosis induced by BCR ligation. Our studies demonstrate that FCMR is required for B cell differentiation and homeostasis, the prevention of autoreactive B cells, and responsiveness to antigenic challenge. The Journal of Immunology, 2013, 190: 987-996. C1 [Choi, Seung-Chul; Tian, Linjie; Murakami, Yousuke; Coligan, John E.] NIAID, Receptor Cell Biol Sect, Lab Immunogenet, NIH, Rockville, MD 20852 USA. [Wang, Hongsheng; Shin, Dong-Mi; Morse, Herbert C., III] NIAID, Virol & Cellular Immunol Sect, Lab Immunogenet, NIH, Rockville, MD 20852 USA. [Borrego, Francisco] US FDA, Lab Mol & Dev Biol, Div Monoclonal Antibodies, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Morse, HC (reprint author), NIAID, Virol & Cellular Immunol Sect, Lab Immunogenet, NIH, 5640 Fishers Lane, Rockville, MD 20852 USA. EM hmorse@niaid.nih.gov; jcoligan@niaid.nih.gov RI Tian, Linjie/E-6878-2014; OI Morse, Herbert/0000-0002-9331-3705 FU National Institutes of Health, National Institute of Allergy and Infectious Diseases FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 48 TC 29 Z9 31 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2013 VL 190 IS 3 BP 987 EP 996 DI 10.4049/jimmunol.1202227 PG 10 WC Immunology SC Immunology GA 074AM UT WOS:000313784200017 PM 23267023 ER PT J AU Karesh, A Mulberg, AE AF Karesh, Alyson Mulberg, Andrew E. TI US Perspective on Off-label Use in Pediatrics SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Editorial Material ID DRUG-USE; CHILDREN C1 [Mulberg, Andrew E.] US FDA, Div Gastroenterol & Inborn Errors Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Mulberg, AE (reprint author), 10903 New Hampshire Ave,Bldg 22,Room 5114, Silver Spring, MD 20993 USA. EM andrew.mulberg@fda.hhs.gov NR 11 TC 1 Z9 1 U1 1 U2 5 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 FEB PY 2013 VL 56 IS 2 BP 113 EP 114 DI 10.1097/MPG.0b013e3182824ccb PG 2 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 078LE UT WOS:000314099600007 PM 23254442 ER PT J AU Prokunina-Olsson, L Muchmore, B Tang, W Pfeiffer, RM Park, H Dickensheets, H Hergott, D Porter-Gill, P Mumy, A Kohaar, I Chen, S Brand, N Tarway, M Liu, LY Sheikh, F Astemborski, J Bonkovsky, HL Edlin, BR Howell, CD Morgan, TR Thomas, DL Rehermann, B Donnelly, RP O'Brien, TR AF Prokunina-Olsson, Ludmila Muchmore, Brian Tang, Wei Pfeiffer, Ruth M. Park, Heiyoung Dickensheets, Harold Hergott, Dianna Porter-Gill, Patricia Mumy, Adam Kohaar, Indu Chen, Sabrina Brand, Nathan Tarway, McAnthony Liu, Luyang Sheikh, Faruk Astemborski, Jacquie Bonkovsky, Herbert L. Edlin, Brian R. Howell, Charles D. Morgan, Timothy R. Thomas, David L. Rehermann, Barbara Donnelly, Raymond P. O'Brien, Thomas R. TI A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; EARLY VIRAL KINETICS; INTERLEUKIN 28B; MULTIETHNIC COHORT; STIMULATED GENES; GENOTYPE 1; LAMBDA; EXPRESSION; THERAPY; PEGINTERFERON AB Chronic infection with hepatitis C virus (HCV) is a common cause of liver cirrhosis and cancer. We performed RNA sequencing in primary human hepatocytes activated with synthetic double-stranded RNA to mimic HCV infection. Upstream of IFNL3 (IL28B) on chromosome 19q13.13, we discovered a new transiently induced region that harbors a dinucleotide variant ss469415590 (TT or Delta G), which is in high linkage disequilibrium with rs12979860, a genetic marker strongly associated with HCV clearance. ss469415590[Delta G] is a frameshift variant that creates a novel gene, designated IFNL4, encoding the interferon-lambda 4 protein (IFNL4), which is moderately similar to IFNL3. Compared to rs12979860, ss469415590 is more strongly associated with HCV clearance in individuals of African ancestry, although it provides comparable information in Europeans and Asians. Transient overexpression of IFNL4 in a hepatoma cell line induced STAT1 and STAT2 phosphorylation and the expression of interferon-stimulated genes. Our findings provide new insights into the genetic regulation of HCV clearance and its clinical management. C1 [Prokunina-Olsson, Ludmila; Muchmore, Brian; Tang, Wei; Hergott, Dianna; Porter-Gill, Patricia; Mumy, Adam; Kohaar, Indu; Brand, Nathan; Tarway, McAnthony; Liu, Luyang] NCI, Lab Translat Gen, Div Canc Epidemiol & Genet, US NIH, Bethesda, MD 20892 USA. [Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, US NIH, Bethesda, MD 20892 USA. [Park, Heiyoung; Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, US NIH, Bethesda, MD 20892 USA. [Dickensheets, Harold; Sheikh, Faruk; Donnelly, Raymond P.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. [Hergott, Dianna; O'Brien, Thomas R.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, US NIH, Bethesda, MD 20892 USA. [Chen, Sabrina] Informat Management Serv Inc, Silver Spring, MD USA. [Astemborski, Jacquie; Thomas, David L.] Johns Hopkins Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Bonkovsky, Herbert L.] Carolinas Med Ctr, Dept Med, Charlotte, NC 28203 USA. [Edlin, Brian R.] Natl Dev & Res Inst Inc, New York, NY USA. [Edlin, Brian R.] Cornell Univ, Ctr Study Hepatitis C, Weill Med Coll, New York, NY 10021 USA. [Howell, Charles D.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Morgan, Timothy R.] Vet Affairs VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. [Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Thomas, David L.] Johns Hopkins Univ, Div Infect Dis, Baltimore, MD USA. RP Prokunina-Olsson, L (reprint author), NCI, Lab Translat Gen, Div Canc Epidemiol & Genet, US NIH, Bethesda, MD 20892 USA. EM prokuninal@mail.nih.gov; obrient@mail.nih.gov RI Tang, Wei/H-7103-2013; OI Tang, Wei/0000-0002-7089-4391; Prokunina-Olsson, Ludmila/0000-0002-9622-2091; Edlin, Brian/0000-0001-8172-8797 FU Intramural Research Program of the US National Institutes of Health (National Cancer Institute, Division of Cancer Epidemiology and Genetics); Intramural Research Program of the US National Institutes of Health (National Institute for Diabetes, Digestive and Kidney Diseases); ALIVE cohort [R01-DA-04334, R01-DA-12568]; US National Institutes of Health [R01-DA09532, R01-DA12109, R01-DA13245, R01-DA16159]; National Cancer Institute [N02-CP-91027, N01-CO-12400]; Substance Abuse and Mental Health Services Administration [H79-TI12103]; National Cancer Institute Director's Innovation Award; National Institute of Diabetes and Digestive and Kidney Diseases; [DA R01 013324] FX We thank the National Cancer Institute Sequencing Core Facility for help with RNA-seq. This research was supported by the Intramural Research Program of the US National Institutes of Health (National Cancer Institute, Division of Cancer Epidemiology and Genetics; National Institute for Diabetes, Digestive and Kidney Diseases), as well as the following grants: DA R01 013324 (J.A. and D.L.T.); ALIVE cohort, R01-DA-04334 and R01-DA-12568, and US National Institutes of Health grants R01-DA09532, R01-DA12109, R01-DA13245 and R01-DA16159 (B.R.E.); National Cancer Institute contracts N02-CP-91027 and N01-CO-12400 (B.R.E.); Substance Abuse and Mental Health Services Administration grant H79-TI12103 (B.R.E.); and the National Cancer Institute Director's Innovation Award (L.P.-O.). The Virahep-C and HALT-C studies were conducted, respectively, by the Virahep-C and HALT-C Investigators and supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The data and samples from the Virahep-C and HALT-C studies reported here were supplied by the National Institute of Diabetes and Digestive and Kidney Diseases Central Repositories. This manuscript was not prepared in collaboration with the Virahep-C study group or the HALT-C study group and does not necessarily reflect the opinions or views of the Virahep-C Trial and HALT-C Trial, the National Institute of Diabetes and Digestive and Kidney Diseases Central Repositories or the National Institute of Diabetes and Digestive and Kidney Diseases. The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services nor does mention of trade names, commercial products or organizations imply endorsement by the US government. NR 54 TC 350 Z9 364 U1 2 U2 45 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 2013 VL 45 IS 2 BP 164 EP 171 DI 10.1038/ng.2521 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 081PB UT WOS:000314333000011 PM 23291588 ER PT J AU Moon, H Kim, SB Chen, JJ George, NI Kodell, RL AF Moon, Hojin Kim, Steven B. Chen, James J. George, Nysia I. Kodell, Ralph L. TI Model Uncertainty and Model Averaging in the Estimation of Infectious Doses for Microbial Pathogens SO RISK ANALYSIS LA English DT Article DE Bias-skewness correction; confidence limit; data uncertainty; food safety; Kullback information criterion ID RISK-ASSESSMENT; FRACTIONAL POLYNOMIALS; HEALTH-RISK; CRITERION; SELECTION; EXPOSURE AB Food-borne infection is caused by intake of foods or beverages contaminated with microbial pathogens. Dose-response modeling is used to estimate exposure levels of pathogens associated with specific risks of infection or illness. When a single dose-response model is used and confidence limits on infectious doses are calculated, only data uncertainty is captured. We propose a method to estimate the lower confidence limit on an infectious dose by including model uncertainty and separating it from data uncertainty. The infectious dose is estimated by a weighted average of effective dose estimates from a set of dose-response models via a Kullback information criterion. The confidence interval for the infectious dose is constructed by the delta method, where data uncertainty is addressed by a bootstrap method. To evaluate the actual coverage probabilities of the lower confidence limit, a Monte Carlo simulation study is conducted under sublinear, linear, and superlinear dose-response shapes that can be commonly found in real data sets. Our model-averaging method achieves coverage close to nominal in almost all cases, thus providing a useful and efficient tool for accurate calculation of lower confidence limits on infectious doses. C1 [Moon, Hojin] Calif State Univ Long Beach, Dept Math & Stat, Long Beach, CA 90840 USA. [Kim, Steven B.] Univ Calif Irvine, Dept Stat, Irvine, CA USA. [Chen, James J.; George, Nysia I.] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR USA. [Chen, James J.] China Med Univ, Ctr Biostat, Sch Publ Hlth, Taichung, Taiwan. [Kodell, Ralph L.] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. RP Moon, H (reprint author), Calif State Univ Long Beach, Dept Math & Stat, 1250 Bellflower Blvd, Long Beach, CA 90840 USA. EM hojin.moon@csulb.edu FU CSULB; Faculty Research Participation Program at the NCTR FX Hojin Moon's research was partially supported by the Research, Scholarship, and Creative Activity (RSCA) Award from CSULB and was partially supported by the Faculty Research Participation Program at the NCTR administered by the Oak Ridge Institute for Science and Education through an interagency agreement between USDOE and USFDA. The views presented in this paper are those of the authors and do not necessarily represent those of the U. S. Food and Drug Administration. Steven Kim's research was originated at CSULB while he was doing his Master's thesis work. NR 33 TC 6 Z9 6 U1 0 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD FEB PY 2013 VL 33 IS 2 BP 220 EP 231 DI 10.1111/j.1539-6924.2012.01853.x PG 12 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 075OC UT WOS:000313895400006 PM 22681783 ER PT J AU Momper, JD Zhao, Y Shapiro, R Schonder, KS Gao, Y Randhawa, PS Venkataramanan, R AF Momper, J. D. Zhao, Y. Shapiro, R. Schonder, K. S. Gao, Y. Randhawa, P. S. Venkataramanan, R. TI Pharmacokinetics of low-dose cidofovir in kidney transplant recipients with BK virus infection SO TRANSPLANT INFECTIOUS DISEASE LA English DT Article DE cidofovir; BK virus; pharmacokinetics; kidney transplantation ID POLYOMAVIRUS-ASSOCIATED NEPHROPATHY; NUCLEOTIDE ANALOGS CIDOFOVIR; IN-VITRO; CLINICAL PHARMACOKINETICS; TRANSPORTERS; REPLICATION; EXPRESSION; EXCRETION; ADEFOVIR; THERAPY AB Background. BK virus (BKV) infection in kidney transplant recipients is associated with progressive graft dysfunction and graft loss. Cidofovir, an antiviral agent with known nephrotoxicity, has been used in low doses to treat BKV infections. However, the systemic exposure and disposition of the low-dose cidofovir regimen are not known in kidney transplant recipients. Methods. We investigated the pharmacokinetics (PK) of low-dose cidofovir (0.24 - 0.62 mg/kg) both without and with oral probenecid in 9 transplant patients with persistent BK viremia without nephropathy in a crossover design. Results. The mean estimated glomerular filtration rate (eGFR) of the study participants was 46.2 mL/min/1.73 m(2) (range: 17-75 mL/min/1.73 m(2)). The contribution of active renal secretion to cidofovir total body clearance was assessed by evaluating the effect of probenecid on cidofovir PK. Maximum cidofovir plasma concentrations, which averaged approximately 1 mu g/mL, were significantly below the 36 mu g/mL 50% effective concentration in vitro for cidofovir against BKV. The plasma concentration of cidofovir declined with an overall disposition half-life of 5.1 +/- 3.5 and 5.3 +/- 2.9 h in the absence and in the presence of probenecid, respectively (P > 0.05). Conclusions. Cidofovir clearance and eGFR were linearly related irrespective of probenecid administration (r(2) = 0.8 without probenecid; r(2) = 0.7 with probenecid). This relationship allows for the prediction of systemic cidofovir exposure in individual patients and may be utilized to evaluate exposure-response relationships to optimize the cidofovir dosing regimen for BKV infection. C1 [Momper, J. D.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Zhao, Y.; Gao, Y.; Venkataramanan, R.] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. [Shapiro, R.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15261 USA. [Schonder, K. S.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Randhawa, P. S.; Venkataramanan, R.] Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Sch Med, Dept Pathol, Pittsburgh, PA 15261 USA. RP Venkataramanan, R (reprint author), Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, 718 Salk Hall,3501 Terrace St, Pittsburgh, PA 15261 USA. EM rv@pitt.edu FU NIH [R01-AI063360-05]; NIH/NCRR/CTSA [UL1 RR024153] FX This work was supported in part by the NIH grant R01-AI063360-05 and NIH/NCRR/CTSA Grant UL1 RR024153. NR 32 TC 4 Z9 4 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-2273 J9 TRANSPL INFECT DIS JI Transpl. Infect. Dis. PD FEB PY 2013 VL 15 IS 1 BP 34 EP 41 DI 10.1111/tid.12014 PG 8 WC Immunology; Infectious Diseases; Transplantation SC Immunology; Infectious Diseases; Transplantation GA 085ZA UT WOS:000314651600015 PM 23025519 ER PT J AU Khurana, T Collison, M Le Haynes, B Cambareri, E Slater, JE AF Khurana, Taruna Collison, Maggie Le Haynes, Binh Cambareri, Edward Slater, Jay E. TI Glucoamylase is a potential allergen in products expressed in Neurospora crassa SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Letter ID EXPOSURE; ASTHMA C1 [Khurana, Taruna; Collison, Maggie; Slater, Jay E.] US FDA, Lab Immunobiochem, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20014 USA. [Le Haynes, Binh; Cambareri, Edward] Neugenesis Corp, Burlingame, CA USA. RP Khurana, T (reprint author), US FDA, Lab Immunobiochem, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20014 USA. EM jay.slater@fda.hhs.gov NR 8 TC 0 Z9 0 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD FEB PY 2013 VL 110 IS 2 BP 124 EP 126 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 078PK UT WOS:000314111400017 PM 23352537 ER PT J AU Williams, DK Galvin, TA Gao, YM O'Neill, C Glasner, D Khan, AS AF Williams, Dhanya K. Galvin, Teresa A. Gao, Yamei O'Neill, Christina Glasner, Dustin Khan, Arifa S. TI No Evidence of Xenotropic Murine Leukemia Virus-Related Virus Transmission by Blood Transfusion from Infected Rhesus Macaques SO JOURNAL OF VIROLOGY LA English DT Article ID PROSTATE CARCINOMA-CELLS; CD4(+) T-CELLS; MONONUCLEAR-CELLS; RETROVIRUS XMRV; MOUSE DNA; IN-VIVO; HYPERMUTATION; DONORS; CONTAMINATION; SEQUENCES AB The discovery of xenotropic murine leukemia virus-related virus (XMRV) in human tissue samples has been shown to be due to virus contamination with a recombinant murine retrovirus. However, due to the unknown pathogenicity of this novel retrovirus and its broad host range, including human cell lines, it is important to understand the modes of virus transmission and develop mitigation and management strategies to reduce the risk of human exposure and infection. XMRV transmission was evaluated by whole-blood transfusion in rhesus macaques. Monkeys were infected with XMRV to serve as donor monkeys for blood transfers at weeks 1, 2, and 3 into naive animals. The donor and recipient monkeys were evaluated for XMRV infection by nested PCR assays with nucleotide sequence confirmation, Western blot assays for development of virus-specific antibodies, and coculture of monkey peripheral blood mononuclear cells (PBMCs) with a sensitive target cell line for virus isolation. XMRV infection was demonstrated in the virus-injected donor monkeys, but there was no evidence of virus transmission by whole-blood transfusion to naive monkeys based upon PCR analysis of PBMCs using XMRV-specific gag and env primers, Western blot analysis of monkey plasma up to 31 to 32 weeks after transfusion, and coculture studies using monkey PBMCs from various times after transfusion. The study demonstrates the lack of XMRV transmission by whole-blood transfusion during the acute phase of infection. Furthermore, analysis of PBMC viral DNA showed extensive APOBEC-mediated G-to-A hypermutation in a donor animal at week 9, corroborating previous results using macaques and supporting the possible restriction of XMRV replication in humans by a similar mechanism. C1 [Williams, Dhanya K.; Galvin, Teresa A.; O'Neill, Christina; Glasner, Dustin; Khan, Arifa S.] US FDA, Lab Retroviruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Gao, Yamei] US FDA, Lab Resp Viral Dis, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Khan, AS (reprint author), US FDA, Lab Retroviruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM arifa.khan@fda.hhs.gov NR 52 TC 4 Z9 4 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2013 VL 87 IS 4 BP 2278 EP 2286 DI 10.1128/JVI.02326-12 PG 9 WC Virology SC Virology GA 078BB UT WOS:000314072000033 PM 23236064 ER PT J AU Chen, IL AF Chen, Ii-Lun TI FDA Summary of Adverse Events on Electronic Cigarettes SO NICOTINE & TOBACCO RESEARCH LA English DT Letter C1 US FDA, Off Sci, Ctr Tobacco Prod, Rockville, MD 20850 USA. RP Chen, IL (reprint author), US FDA, Off Sci, Ctr Tobacco Prod, 9200 Corp Blvd, Rockville, MD 20850 USA. EM ii-lun.chen@fda.hhs.gov NR 4 TC 56 Z9 56 U1 0 U2 64 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD FEB PY 2013 VL 15 IS 2 BP 615 EP 616 DI 10.1093/ntr/nts145 PG 2 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 074QD UT WOS:000313826600042 PM 22855883 ER PT J AU Rostron, B AF Rostron, Brian TI Methodology, Menthol, and Mortality SO NICOTINE & TOBACCO RESEARCH LA English DT Letter ID LUNG-CANCER RISK C1 US FDA, Ctr Tobacco Prod, Rockville, MD 20580 USA. RP Rostron, B (reprint author), US FDA, Ctr Tobacco Prod, 9200 Corp Blvd, Rockville, MD 20580 USA. EM brian.rostron@fda.hhs.gov NR 2 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD FEB PY 2013 VL 15 IS 2 BP 619 EP 619 DI 10.1093/ntr/nts179 PG 1 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 074QD UT WOS:000313826600044 PM 23291639 ER PT J AU Liu, F Patterson, TA Sadovova, N Zhang, X Liu, SL Zou, XJ Hanig, JP Paule, MG Slikker, W Wang, C AF Liu, Fang Patterson, Tucker A. Sadovova, Natalya Zhang, Xuan Liu, Shuliang Zou, Xiaoju Hanig, Joseph P. Paule, Merle G. Slikker, William, Jr. Wang, Cheng TI Ketamine-Induced Neuronal Damage and Altered N-Methyl-d-Aspartate Receptor Function in Rat Primary Forebrain Culture SO TOXICOLOGICAL SCIENCES LA English DT Article DE ketamine; NMDA receptor; reactive oxygen species; calcium influx; l-carnitine ID NICOTINIC ACETYLCHOLINE-RECEPTORS; INDUCED CORTICAL APOPTOSIS; CYTOCHROME-C-OXIDASE; NMDA RECEPTOR; CELL-DEATH; EARLY EXPOSURE; GLUTAMATE RECEPTORS; HIPPOCAMPAL-NEURONS; NITRIC-OXIDE; BRAIN AB Ketamine, a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, is frequently used in pediatric general anesthesia. Accumulating evidence from animal experiments has demonstrated that ketamine causes neuronal cell death during the brain growth spurt. To elucidate the underlying mechanisms associated with ketamine-induced neuronal toxicity and search for approaches or agents to prevent ketamine's adverse effects on the developing brain, a primary nerve cell culture system was utilized. Neurons harvested from the forebrain of newborn rats were maintained under normal control conditions or exposed to either ketamine (10M) or ketamine plus l-carnitine (an antioxidant; 1100M) for 24h, followed by a 24-h withdrawal period. Ketamine exposure resulted in elevated NMDA receptor (NR1) expression, increased generation of reactive oxygen species (ROS) as indicated by higher levels of 8-oxoguanine production, and enhanced neuronal damage. Coadministration of l-carnitine significantly diminished ROS generation and provided near complete protection of neurons from ketamine-induced cell death. NMDA receptors regulate channels that are highly permeable to calcium, and calcium imaging data demonstrated that neurons exposed to ketamine had a significantly elevated amplitude of calcium influx and higher intracellular free calcium concentrations ([Ca-2]i) evoked by NMDA (50M), compared with control neurons. These findings suggest that prolonged ketamine exposure produces an increase in NMDA receptor expression (compensatory upregulation), which allows for a higher/toxic influx of calcium into neurons once ketamine is removed from the system, leading to elevated ROS generation and neuronal cell death. l-Carnitine appears to be a promising agent in preventing or reversing ketamine's toxic effects on neurons at an early developmental stage. C1 [Liu, Fang; Patterson, Tucker A.; Zhang, Xuan; Liu, Shuliang; Zou, Xiaoju; Paule, Merle G.; Wang, Cheng] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Sadovova, Natalya] Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Hanig, Joseph P.] US FDA, Off Testing & Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20908 USA. [Slikker, William, Jr.] US FDA, Off Director, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Wang, C (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, HFT 132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM Cheng.Wang@fda.hhs.gov RI Liu, Shuliang/J-4696-2014 FU National Center for Toxicological Research (NCTR)/US Food and Drug Administration (FDA) [E-7405]; Center for Drug Evaluation and Research (CDER)/FDA; National Toxicology Program (NTP) [E-7255/NIEHS]; National Institute of Child Health and Human Development (NICHD) FX The National Center for Toxicological Research (NCTR)/US Food and Drug Administration (FDA) Protocol E-7405; the Center for Drug Evaluation and Research (CDER)/FDA; the National Toxicology Program (NTP) Protocol E-7255/NIEHS; the National Institute of Child Health and Human Development (NICHD). NR 69 TC 34 Z9 40 U1 0 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD FEB PY 2013 VL 131 IS 2 BP 548 EP 557 DI 10.1093/toxsci/kfs296 PG 10 WC Toxicology SC Toxicology GA 079EL UT WOS:000314153100020 PM 23065140 ER PT J AU Flamm, EG AF Flamm, Edwin G. TI Neonatal animal testing paradigms and their suitability for testing infant formula SO TOXICOLOGY MECHANISMS AND METHODS LA English DT Review DE Autosow; colostrum; gavage; "pup-in-a-cup" ID AUTOMATIC FEEDING DEVICE; MONOSODIUM GLUTAMATE METABOLISM; INDUCED DIARRHEAL DISEASE; ARTIFICIALLY REARED RATS; SOY TRYPSIN-INHIBITOR; ESCHERICHIA-COLI; 2,2',4,4',5-PENTABROMODIPHENYL ETHER; SPONTANEOUS BEHAVIOR; BRAIN-DEVELOPMENT; HIGH-CARBOHYDRATE AB Due to the ever increasing number of substances added to infant formula, and the fact that the majority of data determining the safety of these substances has been derived from adult animals, a search of the available data was performed to determine if an appropriate neonatal model could be found that could be used for performing toxicological safety studies. This exercise utilized three different forms of media. The first informational source is from a publication from the Institute of Medicine (IOM) of the National Academies. The second form of informational data utilized was from simple YAHOO and Google Scholar searches on the internet. The third source of information was from the U. S. Food and Drug Administration (FDA), more specifically, the Center for Drug Evaluation and Review (CDER) preclinical guidance document. Following the examination of the above informational sources, it became apparent that neonatal rats and pigs have been the most utilized of the neonatal models. Following the evaluation of the papers, the experimental paradigm which appears to be the most appropriate for testing substances new to infant formula, and could be used as a pivotal study was the neonatal pig utilizing the automated feeding device called the Autosow. C1 US FDA, Div Biotechnol & GRAS Notice Review, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Flamm, EG (reprint author), US FDA, Div Biotechnol & GRAS Notice Review, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Edwin.Flamm@fda.hhs.gov NR 69 TC 9 Z9 9 U1 0 U2 18 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1537-6516 J9 TOXICOL MECH METHOD JI Toxicol. Mech. Methods PD FEB PY 2013 VL 23 IS 2 BP 57 EP 67 DI 10.3109/15376516.2012.725108 PG 11 WC Toxicology SC Toxicology GA 079DC UT WOS:000314149400001 PM 22924893 ER PT J AU Cabot, E Lloyd, T Christ, A Kainz, W Douglas, M Stenzel, G Wedan, S Kuster, N AF Cabot, Eugenia Lloyd, Tom Christ, Andreas Kainz, Wolfgang Douglas, Mark Stenzel, Gregg Wedan, Steve Kuster, Niels TI Evaluation of the RF heating of a generic deep brain stimulator exposed in 1.5 T magnetic resonance scanners SO BIOELECTROMAGNETICS LA English DT Article DE MRI; RF safety; active implantable medical devices ID NEUROSTIMULATION SYSTEMS; INTERVENTIONAL MRI; MEDICAL DEVICES; PACEMAKER LEADS; SAFETY; WIRES; 1.5-TESLA; MODELS; FIELD AB The radio frequency (RF) electromagnetic field of magnetic resonance (MR) scanners can result in significant tissue heating due to the RF coupling with the conducting parts of medical implants. The objective of this article is to evaluate the advantages and shortcomings of a new four-tier approach based on a combined numerical and experimental procedure, designed to demonstrate safety of implants during MR scans. To the authors' best knowledge, this is the first study analyzing this technique. The evaluation is performed for 1.5?T MR scanners using a generic model of a deep brain stimulator (DBS) with a straight lead and a helical lead. The results show that the approach is technically feasible and provides sound and conservative information about the potential heating of implants. We demonstrate that (1) applying optimized tools results in reasonable uncertainties for the overall evaluation; (2) each tier reduces the overestimation by several dB at the cost of more demanding evaluation steps; (3) the implant with the straight lead would cause local temperature increases larger than 18 degrees C at the RF exposure limit for the normal operating mode; (4) Tier 3 is not sufficient for the helical implant; and (5) Tier 4 might be too demanding to be performed for complex implants. We conclude with a suggestion for a procedure that follows the same concept but is between Tier 3 and 4. In addition, the evaluation of Tier 3 has shown consistency with current scan practice, namely, the resulting heat at the lead tip is less than 3.5 degrees C for the straight lead and 0.7 degrees C for the helix lead for scans at the current applied MR scan restrictions for deep brain stimulation at a head average SAR of 0.1?W/kg. Bioelectromagnetics 34:104113, 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Cabot, Eugenia; Christ, Andreas; Douglas, Mark; Kuster, Niels] Fdn Res Informat Technol Soc ITIS, CH-8004 Zurich, Switzerland. [Lloyd, Tom; Stenzel, Gregg; Wedan, Steve] Imricor Med Syst, Burnsville, MN USA. [Kainz, Wolfgang] US FDA, Silver Spring, MD USA. [Kuster, Niels] Swiss Fed Inst Technol ETHZ, Zurich, Switzerland. RP Cabot, E (reprint author), Fdn Res Informat Technol Soc ITIS, Zeughausstr 43, CH-8004 Zurich, Switzerland. EM cabot@itis.ethz.ch FU Medical Devices Research Forum (MDRF), Burnsville, MN, USA FX Grant sponsor: Medical Devices Research Forum (MDRF), Burnsville, MN, USA. NR 27 TC 17 Z9 17 U1 1 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0197-8462 J9 BIOELECTROMAGNETICS JI Bioelectromagnetics PD FEB PY 2013 VL 34 IS 2 BP 104 EP 113 DI 10.1002/bem.21745 PG 10 WC Biology; Biophysics SC Life Sciences & Biomedicine - Other Topics; Biophysics GA 071MD UT WOS:000313596000003 PM 23060256 ER PT J AU Juliao, PC Maslanka, S Dykes, J Gaul, L Bagdure, S Granzow-Kibiger, L Salehi, E Zink, D Neligan, RP Barton-Behravesh, C Luquez, C Biggerstaff, M Lynch, M Olson, C Williams, I Barzilay, EJ AF Juliao, Patricia C. Maslanka, Susan Dykes, Janet Gaul, Linda Bagdure, Satish Granzow-Kibiger, Lynae Salehi, Ellen Zink, Donald Neligan, Robert P. Barton-Behravesh, Casey Luquez, Carolina Biggerstaff, Matthew Lynch, Michael Olson, Christine Williams, Ian Barzilay, Ezra J. TI National Outbreak of Type A Foodborne Botulism Associated With a Widely Distributed Commercially Canned Hot Dog Chili Sauce SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE botulism; commercial canning; outbreak; foodborne botulism ID CLOSTRIDIUM-BOTULINUM; UNITED-STATES; FOOD AB Background. On 7 and 11 July 2007, health officials in Texas and Indiana, respectively, reported 4 possible cases of type A foodborne botulism to the US Centers for Disease Control and Prevention. Foodborne botulism is a rare and sometimes fatal illness caused by consuming foods containing botulinum neurotoxin. Methods. Investigators reviewed patients' medical charts and food histories. Clinical specimens and food samples were tested for botulinum toxin and neurotoxin-producing Clostridium species. Investigators conducted inspections of the cannery that produced the implicated product. Results. Eight confirmed outbreak associated cases were identified from Indiana (n = 2), Texas (n = 3), and Ohio (n = 3). Botulinum toxin type A was identified in leftover chili sauce consumed by the Indiana patients and 1 of the Ohio patients. Cannery inspectors found violations of federal canned-food regulations that could have led to survival of Clostridium botulinum spores during sterilization. The company recalled 39 million cans of chili. Following the outbreak, the US Food and Drug Administration inspected other canneries with similar canning systems and issued warnings to the industry about the danger of C. botulinum and the importance of compliance with canned food manufacturing regulations. Conclusions. Commercially produced hot dog chili sauce caused these cases of type A botulism. This is the first US foodborne botulism outbreak involving a commercial cannery in >30 years. Sharing of epidemiologic and laboratory findings allowed for the rapid identification of implicated food items and swift removal of potentially deadly products from the market by US food regulatory authorities. C1 [Juliao, Patricia C.; Barton-Behravesh, Casey; Biggerstaff, Matthew; Lynch, Michael; Olson, Christine; Williams, Ian; Barzilay, Ezra J.] Ctr Dis Control & Prevent, Enter Dis Epidemiol Branch, Atlanta, GA USA. [Juliao, Patricia C.; Barton-Behravesh, Casey; Williams, Ian] Ctr Dis Control & Prevent, Epidem Intelligence Serv, Atlanta, GA USA. [Maslanka, Susan; Dykes, Janet; Luquez, Carolina] Ctr Dis Control & Prevent, Enter Dis Lab Branch, Atlanta, GA USA. [Gaul, Linda; Bagdure, Satish] Texas Dept State Hlth Serv, Austin, TX USA. [Granzow-Kibiger, Lynae] Indiana State Dept Hlth, Indianapolis, IN 46202 USA. [Salehi, Ellen] Ohio Dept Hlth, Columbus, OH 43266 USA. [Zink, Donald; Neligan, Robert P.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Juliao, PC (reprint author), 179 Pine Bluffs, Roscommon, MI 48653 USA. EM pcjuliao@gmail.com RI bagdure, satish/L-5622-2013 FU CDC; US Food and Drug Administration; USDA; state health department of Texas, Indiana; state health department of Texas, Ohio FX This work was supported by the CDC; the US Food and Drug Administration; the USDA; and the state health departments of Texas, Indiana, and Ohio. NR 26 TC 8 Z9 8 U1 1 U2 37 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 1 PY 2013 VL 56 IS 3 BP 376 EP 382 DI 10.1093/cid/cis901 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 071TM UT WOS:000313617400016 PM 23097586 ER PT J AU Jarow, JP Troiani, J McNellis, D Wiederhorn, R Fang, GD Handelsman, H AF Jarow, Jonathan P. Troiani, John McNellis, Donald Wiederhorn, Roger Fang, Guodong Handelsman, Harry TI Use of Biomarkers to Assess Tissue Specific Androgen Adequacy: Defining Male Hypogonadism SO JOURNAL OF UROLOGY LA English DT Article DE testis; hypogonadism; testosterone; reference values; biological markers ID LATE-ONSET HYPOGONADISM; REPLACEMENT THERAPY; MEN; TESTOSTERONE AB Purpose: The criteria for normal testosterone have been established by expert consensus rather than by evidence. We determined whether a cutoff point for normal could be established using biomarkers. Materials and Methods: We performed an exploratory investigation of 1,492 hypogonadal men pooled from 7 registration trials. Serum testosterone, prostate specific antigen and hematocrit were measured at baseline and after 90 days of continuous testosterone replacement therapy. Results: Baseline prostate specific antigen, percent change in prostate specific antigen and hematocrit appeared to be most strongly related to baseline serum testosterone. Subgroup analysis and visual inspection of linear spline fit of these data suggested an approximate serum testosterone cutoff for normal of 300 ng/dl for percent change in hematocrit, and 200 ng/dl for baseline prostate specific antigen and percent change in prostate specific antigen. Conclusions: This exploratory study revealed considerable variation among individuals and target tissues in individuals. Further study should be performed using standardized assays in a broader population. C1 [Jarow, Jonathan P.; Troiani, John; McNellis, Donald; Wiederhorn, Roger; Fang, Guodong; Handelsman, Harry] US FDA, Div Reprod & Urol Prod, Off New Drugs, Silver Spring, MD USA. RP Jarow, JP (reprint author), W022 Room 5387,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM jonathan.jarow@fda.hhs.gov NR 9 TC 7 Z9 7 U1 0 U2 1 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 FEB PY 2013 VL 189 IS 2 BP 633 EP 637 DI 10.1016/j.juro.2012.09.025 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 069VI UT WOS:000313464800080 PM 23260553 ER PT J AU Mahmood, M Xu, Y Dantuluri, V Mustafa, T Zhang, Y Karmakar, A Casciano, D Ali, S Biris, A AF Mahmood, M. Xu, Y. Dantuluri, V. Mustafa, T. Zhang, Y. Karmakar, A. Casciano, D. Ali, S. Biris, A. TI Carbon nanotubes enhance the internalization of drugs by cancer cells and decrease their chemoresistance to cytostatics SO NANOTECHNOLOGY LA English DT Article ID IN-VITRO; LIQUID-CHROMATOGRAPHY; TOPOISOMERASE-II; ANTITUMOR DRUG; HUMAN SERUM; STEM-CELLS; ETOPOSIDE; INHIBITION; DELIVERY; PROLIFERATION AB Etoposide is a semisynthetic, chemotherapeutic drug widely recommended to treat an extensive range of human cancers. Our studies indicate that, while etoposide is capable of killing human cancer cells, exposure to single-walled carbon nanotubes (SWCNTs) and etoposide results in enhanced cell death that appears to be synergistic and not merely additive. In this study, we used high pressure liquid chromatography and mass spectrometry to quantify the internal effective dose of etoposide when the human pancreatic cancer cell (PANC-1) was exposed to the combination of these agents. Our results unequivocally indicate that SWCNTs improve etoposide uptake and increase its capacity to kill cancer cells. We suggest that a combination of SWCNTs and etoposide may prove to be a more efficient chemotherapeutic protocol, especially because of the potential to lower toxic drug doses to levels that may be useful in decreasing adverse side effects, as well as in lowering the probability of inducing chemoresistance in exposed cancer cells. C1 [Mahmood, M.; Xu, Y.; Dantuluri, V.; Mustafa, T.; Karmakar, A.; Casciano, D.; Biris, A.] Univ Arkansas, Nanotechnol Ctr, Little Rock, AR 72204 USA. [Zhang, Y.] US FDA, Nanotechnol Core Facil, Off Sci Coordinat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Ali, S.] US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Mahmood, M (reprint author), Univ Arkansas, Nanotechnol Ctr, 2801 S Univ Ave, Little Rock, AR 72204 USA. EM yxxu@ualr.edu; asbiris@ualr.edu FU Arkansas Science and Technology Authority (ASTA) [08-CAT-03]; US Army TATRC program FX Support for this research received from the Arkansas Science and Technology Authority (ASTA) grant # 08-CAT-03 is greatly appreciated. The financial support provided by the US Army TATRC program is highly appreciated. The editorial assistance of Dr Marinelle Ringer is also acknowledged. NR 45 TC 8 Z9 8 U1 1 U2 32 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0957-4484 J9 NANOTECHNOLOGY JI Nanotechnology PD FEB 1 PY 2013 VL 24 IS 4 AR 045102 DI 10.1088/0957-4484/24/4/045102 PG 11 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Science & Technology - Other Topics; Materials Science; Physics GA 068LA UT WOS:000313367000003 PM 23291321 ER PT J AU Mahmood, I AF Mahmood, Iftekhar TI Prediction of drug concentration-time profiles of therapeutic proteins in humans from animals SO XENOBIOTICA LA English DT Article DE Allometry; pharmacokinetics; therapeutic proteins; concentrations-time profiles; multi-compartment system ID RESPIRATORY SYNCYTIAL VIRUS; ENDOTHELIAL GROWTH-FACTOR; MONOCLONAL-ANTIBODY; DIMERIZATION INHIBITOR; ADVANCED CANCER; SCALE-UP; PHARMACOKINETICS; CLEARANCE; PERTUZUMAB; PARADIGM AB The main objective of this work is to evaluate two methods to predict concentration-time profiles of therapeutic proteins in humans in a multi-compartment system using animal pharmacokinetic parameters. The prediction of concentration-time profiles in humans in a multi-compartment system was based on two proposed methods (volumes of distribution and pharmacokinetic constants) of Mordenti. Seven protein drugs (5 monoclonal antibodies, one epoetin, and one thrombin inhibitor) from the literature were chosen that were described by two-compartment model in both humans and animals. Two- compartment model parameters (CL, V-c, V-ss, V-beta, alpha, A, beta and B) at least from 3 animals were scaled to humans and then were used to predict plasma concentrations-time profiles in humans. The results showed that both the methods provided almost similar concentration-time profiles for most of the drugs. It appears that the proposed methods of Mordenti can be used for reasonably accurate prediction of concentration-time profiles of therapeutic proteins in humans. C1 US FDA, OBRR, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Mahmood, I (reprint author), US FDA, OBRR, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20857 USA. EM iftekhar.mahmood@fda.hhs.gov NR 26 TC 2 Z9 2 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD FEB PY 2013 VL 43 IS 2 BP 153 EP 160 DI 10.3109/00498254.2012.706726 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 067FX UT WOS:000313280700003 PM 22830981 ER PT J AU Labiner-Wolfe, J Fein, SB AF Labiner-Wolfe, Judith Fein, Sara B. TI How US Mothers Store and Handle Their Expressed Breast Milk SO JOURNAL OF HUMAN LACTATION LA English DT Article DE bottle feeding; breast milk; breast milk expression; breast milk storage; breastfeeding; Infant Feeding Practices Study II ID FORMULA AB Background: Many mothers express and store their milk to later feed to their infant. Health organizations provide recommendations on expressed milk storage and handling because these practices can affect milk quality and safety. However, little information exists on US mothers' practices. Objective: To describe how US mothers of healthy infants store and handle their expressed milk and to compare their practices with recommendations. Methods: Mothers participating in the Infant Feeding Practices Study II from 2005-2006 who were expressing milk formed the cohort for this analysis (n = 436-1060, depending on infant age). Participants in this longitudinal mail survey were drawn from a consumer opinion panel and answered questions about milk expression around 2, 5, and 7 months postpartum. Data were analyzed cross sectionally using frequency procedures, and the analysis compared mothers who fed expressed milk with and without also feeding formula. Results: Few mothers stored their milk longer than recommended. Among mothers of the youngest infants in this analysis, 12% heated their milk in a microwave and 17% rinsed bottle nipples with only water before reuse; percentages were similar as infants aged. These practices may pose risks to infant health. Compared with those who fed no formula, mothers who fed both expressed milk and formula were more likely to heat milk in a microwave and, among those with the youngest infants, to rinse bottle nipples with only water between uses. Conclusion: Consumer education should emphasize safe warming and cleaning practices for feeding expressed milk. C1 [Fein, Sara B.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Labiner-Wolfe, Judith] US Dept HHS, Off Womens Hlth, Washington, DC 20201 USA. RP Fein, SB (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 020, College Pk, MD 20740 USA. EM sara.fein@fda.gov FU Food and Drug Administration; Centers for Disease Control and Prevention; National Institutes of Health; Maternal and Child Health Bureau; Office of the Secretary in the US Department of Health and Human Services FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors' work was prepared within the scope of their employment with the U.S. Department of Health and Human Services and is in the public domain. The data collection was funded by the Food and Drug Administration, Centers for Disease Control and Prevention, the National Institutes of Health, the Maternal and Child Health Bureau and the Office of the Secretary in the US Department of Health and Human Services. NR 19 TC 6 Z9 6 U1 0 U2 15 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0890-3344 J9 J HUM LACT JI J. Hum. Lact. PD FEB PY 2013 VL 29 IS 1 BP 54 EP 58 DI 10.1177/0890334412453876 PG 5 WC Nursing; Obstetrics & Gynecology; Pediatrics SC Nursing; Obstetrics & Gynecology; Pediatrics GA 062BA UT WOS:000312892900012 PM 22933609 ER PT J AU Kumar, NB Dhurandhar, M Aggarwal, B Anant, S Daniel, K Deng, G Djeu, J Dou, JH Hawk, E Jayaram, B Jia, LB Joshi, R Kararala, M Karunagaran, D Kucuk, O Kumar, L Malafa, M Samathanam, GJ Sarkar, F Siddiqi, M Singh, RP Srivastava, A White, JD AF Kumar, Nagi B. Dhurandhar, Medha Aggarwal, Bharat Anant, Shrikant Daniel, Kenyon Deng, Gary Djeu, Julie Dou, Jinhui Hawk, Ernest Jayaram, B. Jia, Libin Joshi, Rajendra Kararala, Madhuri Karunagaran, Devarajan Kucuk, Omer Kumar, Lalit Malafa, Mokenge Samathanam, G. J. Sarkar, Fazlul Siddiqi, Maqsood Singh, Rana P. Srivastava, Anil White, Jeffrey D. TI Proceedings of the Indo-US bilateral workshop on accelerating botanicals/biologics agent development research for cancer chemoprevention, treatment, and survival SO CANCER MEDICINE LA English DT Article DE Biologics; botanicals; cancer; chemoprevention; drug development AB With the evolving evidence of the promise of botanicals/biologics for cancer chemoprevention and treatment, an Indo- U. S. collaborative Workshop focusing on "Accelerating Botanicals Agent Development Research for Cancer Chemoprevention and Treatment" was conducted at the Moffitt Cancer Center, 29-31 May 2012. Funded by the Indo- U. S. Science and Technology Forum, a joint initiative of Governments of India and the United States of America and the Moffitt Cancer Center, the overall goals of this workshop were to enhance the knowledge (agents, molecular targets, biomarkers, approaches, target populations, regulatory standards, priorities, resources) of a multinational, multidisciplinary team of researcher's to systematically accelerate the design, to conduct a successful clinical trials to evaluate botanicals/biologics for cancer chemoprevention and treatment, and to achieve efficient translation of these discoveries into the standards for clinical practice that will ultimately impact cancer morbidity and mortality. Expert panelists were drawn from a diverse group of stakeholders, representing the leadership from the National Cancer Institute's Office of Cancer Complementary and Alternative Medicine (OCCAM), NCI Experimental Therapeutics (NExT), Food and Drug Administration, national scientific leadership from India, and a distinguished group of population, basic and clinical scientists from the two countries, including leaders in bioinformatics, social sciences, and biostatisticians. At the end of the workshop, we established four Indo- U. S. working research collaborative teams focused on identifying and prioritizing agents targeting four cancers that are of priority to both countries. Presented are some of the key proceedings and future goals discussed in the proceedings of this workshop. C1 [Kumar, Nagi B.; Daniel, Kenyon; Djeu, Julie; Malafa, Mokenge] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Dhurandhar, Medha] Pune Univ, Ctr Dev Adv Comp, Pune 411007, Maharashtra, India. [Aggarwal, Bharat; Hawk, Ernest] Univ Texas MD Anderson Canc Ctr, Houston, TX 77054 USA. [Anant, Shrikant] Univ Kansas, Med Ctr, Kansas City, KS 66160 USA. [Deng, Gary] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Dou, Jinhui] US FDA, Silver Spring, MD 20993 USA. [Jayaram, B.] India Inst Technol Delhi, New Delhi 110016, India. [Jia, Libin; White, Jeffrey D.] NCI, NIH, Bethesda, MD 20892 USA. [Joshi, Rajendra] Pune Univ, Pune 411007, Maharashtra, India. [Kararala, Madhuri] Univ Michigan, Ann Arbor, MI 48109 USA. [Karunagaran, Devarajan] Indian Inst Technol, Dept Biotechnol, Madras 600036, Tamil Nadu, India. [Kucuk, Omer] Emory Healthcare, Emory Clin, Winship Canc Inst, Ne Atlanta, GA 30322 USA. [Kumar, Lalit] All India Inst Med Sci, IRCH, New Delhi 110029, India. [Samathanam, G. J.] Govt India, Dept & Transfer Div, Dept Sci & Technol, New Delhi, India. [Sarkar, Fazlul] Barbara Ann Karmanos Canc Inst, Detroit, MI 48201 USA. [Siddiqi, Maqsood] Canc Fdn India, Kolkata 700039, India. [Singh, Rana P.] Cent Univ Gujarat, Sch Life Sci, Gandhinagar 382030, Gujarat, India. [Srivastava, Anil] Open Hlth Syst Lab, Rockville, MD 20850 USA. RP Kumar, NB (reprint author), Univ S Florida, Coll Med, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM nagi.kumar@moffitt.org FU Indo-U.S. Science and Technology Forum; National Cancer Institute; Food and Drug Administration; Open Health Systems Laboratory; Moffitt Cancer Center FX This work was supported by Indo-U.S. Science and Technology Forum, the National Cancer Institute, Food and Drug Administration, Open Health Systems Laboratory, and the Moffitt Cancer Center. NR 51 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2045-7634 J9 CANCER MED-US JI Cancer Med. PD FEB PY 2013 VL 2 IS 1 BP 108 EP 115 DI 10.1002/cam4.42 PG 8 WC Oncology SC Oncology GA V36KH UT WOS:000209210500012 PM 24279005 ER PT J AU Patel, S Needleman, KIM AF Patel, Soumya Needleman, Katherine I. Miller TI Funding Grants for Rare Diseases at the Food and Drug Administration SO EXPERT OPINION ON ORPHAN DRUGS LA English DT Editorial Material DE food and drug administration; funding sources; grants; humanitarian device exemption; humanitarian use device designation; investigational new drug; Office of Orphan Products Development; Orphan Products Grants Program; Prescription Drug User Fee Act; rare disease; request for applications; Review Division AB With the availability of various funding sources for studying therapies in rare diseases, choosing the right funding source is often challenging. Assessing the unique aspects of each individual funding source may benefit the applicant as the correct funding source will help ensure that their study receives an appropriate level of support. One such funding source for rare diseases is offered through the Food and Drug Administration (FDA). This paper will discuss the mission, specific program details and achievements of the FDA's Orphan Products Grants Program in an effort to help future grant applicants determine if the program is suited to their needs. C1 [Patel, Soumya] US FDA, Off Orphan Prod Dev, Silver Spring, MD 20993 USA. [Needleman, Katherine I. Miller] US FDA, Off Orphan Prod Dev, Orphan Prod Grants Program, Silver Spring, MD 20993 USA. RP Patel, S (reprint author), US FDA, Off Orphan Prod Dev, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM soumya.patel@fda.hhs.gov NR 7 TC 0 Z9 0 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 2167-8707 J9 EXPERT OPIN ORPHAN D JI Exp. Opin. Orphan Drugs PD FEB PY 2013 VL 1 IS 2 BP 99 EP 102 DI 10.1517/21678707.2013.749181 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AK1VQ UT WOS:000338206300001 ER PT J AU Komatsu, D Fealey, D Filippi, A Schwab, L Fakhoury, J Thanos, P Ferguson, SA AF Komatsu, David Fealey, David Filippi, Alexandra Schwab, Lacey Fakhoury, Jordan Thanos, Panayotis Ferguson, Sherry A. TI Pre- and Early Post-Natal Methylphenidate Exposure and Rat Skeletal Development SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 04-07, 2013 CL Baltimore, MD SP Amer Soc Bone & Mineral Res C1 [Komatsu, David] SUNY Stony Brook, Dept Orthopaed, Stony Brook, NY USA. [Fealey, David; Filippi, Alexandra] SUNY Stony Brook, Sch Med, Stony Brook, NY USA. [Schwab, Lacey] SUNY Stony Brook, Dept Mat Sci & Engn, Stony Brook, NY USA. [Fakhoury, Jordan] SUNY Stony Brook, Dept Biol, Stony Brook, NY USA. [Thanos, Panayotis] Brookhaven Natl Lab, Behav Neuropharmacol & Neuroimaging Lab, Dept Med, Upton, NY 11973 USA. [Ferguson, Sherry A.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2013 VL 28 SU 1 MA SU0032 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8JI UT WOS:000332035804099 ER PT J AU Morton, D Bourcier, T Alden, CL AF Morton, Daniel Bourcier, Todd Alden, Carl L. TI Improving Carcinogenicity Assessment SO TOXICOLOGIC PATHOLOGY LA English DT Article DE bioassay; cancer; NEGCARC; rat; risk ID RAT AB The ICH initiated talks in June 2012 to revise regulatory guidance for carcinogenicity assessment of pharmaceutical products, stimulated in part by a proposal called Negative for Endocrine, Genotoxicity, and Chronic Study Associated Histopathologic Risk Factors for Carcinogenicity in the Rat (NEGCARC) from the Pharmaceutical Research and Manufacturing Association (PhRMA). The 2012 STP Town Hall Meeting focused on the need for change in carcinogenicity assessment strategies for pharmaceuticals. Dr. Todd Bourcier from the Division of Endocrine and Metabolic Products, U.S. FDA and a member of the FDA's Alternative Carcinogenicity Assessment Committee, was the guest speaker and a panelist. Dr. Bourcier is also one of FDA's representatives to the ICH S1 Expert Working Group that is discussing changes to regulatory guidelines for carcinogenicity assessment. Drs. Carl Alden and Dan Morton also participated in the panel discussion. C1 [Morton, Daniel] Pfizer Inc, Groton, CT 06340 USA. [Bourcier, Todd] US FDA, Div Metab & Endocrine Prod, CDER, Silver Spring, MD USA. [Alden, Carl L.] Millennium Pharmaceut Inc, Cambridge, MA USA. RP Morton, D (reprint author), Pfizer Inc, Drug Safety Res & Dev, 35 Cambridge Pk Dr Y2130C, Cambridge, MA 02140 USA. EM dan.g.morton@pfizer.com NR 4 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 EI 1533-1601 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD FEB PY 2013 VL 41 IS 2 BP 263 EP 270 DI 10.1177/0192623312464310 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA AB0DP UT WOS:000331462300007 PM 23076039 ER PT J AU Pouillot, R Hoelzer, K Chen, YH Dennis, S AF Pouillot, Regis Hoelzer, Karin Chen, Yuhuan Dennis, Sherri TI Estimating probability distributions of bacterial concentrations in food based on data generated using the most probable number (MPN) method for use in risk assessment SO FOOD CONTROL LA English DT Article DE MPN; Bacterial concentration; Probability distribution; Likelihood; Risk assessment ID MICROBIOLOGICAL CONTAMINATION DATA; LISTERIA-MONOCYTOGENES; EXPOSURE ASSESSMENT; SERIAL DILUTIONS; ASSESSMENT MODEL; MEAT AB Estimating probability distributions that describe bacterial concentrations in food products is a key element of quantitative microbial risk assessments. Standard bacteriological protocols for bacterial enumeration first apply a detection test to a set of samples. For samples that test positive, bacterial concentrations are quantified using a serial dilution assay such as the most probable number (MPN) method. Estimation of bacterial concentration distributions based on a set of such data, however, represents a considerable statistical challenge. A maximum likelihood approach has been published to estimate bacterial concentrations from this type of data while accounting for the censored nature of the data. In this study, we derived an alternative method, based on complete likelihood maximization from observed MPN pattern data. Both methods were first evaluated in simulation studies, which showed that the latter method generated unbiased estimates of the parameters of the bacterial concentration distribution, while the former method generated biased results. The bias was particularly pronounced when bacterial concentrations were low. Both methods fail to predict accurately low contamination levels at low prevalence (e.g. mean of -7 log(10) for contaminated products and prevalence of 0.2). The methods were then applied to bacteriological data from a food survey of Listeria monocytogenes in the United States. The former method led to approximately 1 log(10) cfu higher estimated mean bacterial concentration compared to estimates generated using the alternative method. The alternative method is preferable, in particular if bacterial concentrations are low. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Pouillot, Regis; Hoelzer, Karin; Chen, Yuhuan; Dennis, Sherri] US FDA, Ctr Food Safety & Appl Nutr HFS 005, College Pk, MD 20740 USA. RP Pouillot, R (reprint author), US FDA, Ctr Food Safety & Appl Nutr HFS 005, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Regis.Pouillot@fda.hhs.gov RI Pouillot, Regis/E-8103-2010 OI Pouillot, Regis/0000-0002-6107-5212 FU U.S. Department of Energy; U.S. Food and Drug Administration FX The authors acknowledge Mark Smith and Robert J. Blodgett for their insights and advice. This work was supported in part by appointments to the Research Participation Program at the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 43 TC 12 Z9 13 U1 1 U2 36 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-7135 J9 FOOD CONTROL JI Food Control PD FEB PY 2013 VL 29 IS 2 SI SI BP 350 EP 357 DI 10.1016/j.foodcont.2012.05.041 PG 8 WC Food Science & Technology SC Food Science & Technology GA 036VB UT WOS:000311059200009 ER PT J AU Allard, MW Luo, Y Strain, E Pettengill, J Timme, R Wang, C Li, C Keys, CE Zheng, J Stones, R Wilson, MR Musser, SM Brown, EW AF Allard, Marc W. Luo, Yan Strain, Errol Pettengill, James Timme, Ruth Wang, Charles Li, Cong Keys, Christine E. Zheng, Jie Stones, Robert Wilson, Mark R. Musser, Steven M. Brown, Eric W. TI On the Evolutionary History, Population Genetics and Diversity among Isolates of Salmonella Enteritidis PFGE Pattern JEGX01.0004 SO PLOS ONE LA English DT Article ID ENTERICA SEROVAR ENTERITIDIS; FIELD GEL-ELECTROPHORESIS; COMPLETE GENOME SEQUENCE; VIRULENCE PLASMIDS; PROVIDES INSIGHTS; ESCHERICHIA-COLI; HOST ADAPTATION; TYPING SCHEME; GENES; STRAINS AB Facile laboratory tools are needed to augment identification in contamination events to trace the contamination back to the source (traceback) of Salmonella enterica subsp. enterica serovar Enteritidis (S. Enteritidis). Understanding the evolution and diversity within and among outbreak strains is the first step towards this goal. To this end, we collected 106 new S. Enteriditis isolates within S. Enteriditis Pulsed-Field Gel Electrophoresis (PFGE) pattern JEGX01.0004 and close relatives, and determined their genome sequences. Sources for these isolates spanned food, clinical and environmental farm sources collected during the 2010 S. Enteritidis shell egg outbreak in the United States along with closely related serovars, S. Dublin, S. Gallinarum biovar Pullorum and S. Gallinarum. Despite the highly homogeneous structure of this population, S. Enteritidis isolates examined in this study revealed thousands of SNP differences and numerous variable genes (n = 366). Twenty-one of these genes from the lineages leading to outbreak-associated samples had nonsynonymous (causing amino acid changes) changes and five genes are putatively involved in known Salmonella virulence pathways. While chromosome synteny and genome organization appeared to be stable among these isolates, genome size differences were observed due to variation in the presence or absence of several phages and plasmids, including phage RE-2010, phage P125109, plasmid pSEEE3072_19 (similar to pSENV), plasmid pOU1114 and two newly observed mobile plasmid elements pSEEE1729_15 and pSEEE0956_35. These differences produced modifications to the assembled bases for these draft genomes in the size range of approximately 4.6 to 4.8 mbp, with S. Dublin being larger (similar to 4.9 mbp) and S. Gallinarum smaller (4.55 mbp) when compared to S. Enteritidis. Finally, we identified variable S. Enteritidis genes associated with virulence pathways that may be useful markers for the development of rapid surveillance and typing methods, potentially aiding in traceback efforts during future outbreaks involving S. Enteritidis PFGE pattern JEGX01.0004. C1 [Allard, Marc W.; Pettengill, James; Timme, Ruth; Wang, Charles; Li, Cong; Keys, Christine E.; Zheng, Jie; Musser, Steven M.; Brown, Eric W.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Luo, Yan; Strain, Errol] US FDA, Off Food Def Commun & Emergency Response, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Stones, Robert] Food & Environm Res Agcy, York, N Yorkshire, England. [Wilson, Mark R.] Western Carolina Univ, Forens Sci Program, Cullowhee, NC 28723 USA. RP Allard, MW (reprint author), US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM marc.allard@fda.hhs.gov FU Food and Drug Administration FX Food and Drug Administration research funds were provided. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 70 TC 46 Z9 47 U1 1 U2 23 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 30 PY 2013 VL 8 IS 1 AR e55254 DI 10.1371/journal.pone.0055254 PG 22 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 098QM UT WOS:000315563800136 PM 23383127 ER PT J AU He, Z Ferguson, SA Cui, L Greenfield, LJ Paule, MG AF He, Zhen Ferguson, Sherry A. Cui, Li Greenfield, L. John, Jr. Paule, Merle G. TI Role of Neural Stem Cell Activity in Postweaning Development of the Sexually Dimorphic Nucleus of the Preoptic Area in Rats SO PLOS ONE LA English DT Article ID SEX-DIFFERENCES; GLOBAL-ISCHEMIA; ADULT RATS; HYPOTHALAMUS; BRAIN; MICE; NEUROGENESIS; APOPTOSIS; DIFFERENTIATION; MIGRATION AB The sexually dimorphic nucleus of the preoptic area (SDN-POA) has received increased attention due to its apparent sensitivity to estrogen-like compounds found in food and food containers. The mechanisms that regulate SDN-POA volume remain unclear as is the extent of postweaning development of the SDN-POA. Here we demonstrate that the female Sprague-Dawley SDN-POA volume increased from weaning to adulthood, although this increase was not statistically significant as it was in males. The number of cells positive for Ki67, a marker of cell proliferation, in both the SDN-POA and the hypothalamus was significantly higher at weaning than at adulthood in male rats. In contrast, the number of Ki67-positive cells was significantly higher in the hypothalamus but not in the SDN-POA (p>0.05) at weaning than at adulthood in female rats. A subset of the Ki67-positive cells in the SDN-POA displayed the morphology of dividing cells. Nestin-immunoreactivity delineated a potential macroscopic neural stem cell niche in the rostral end of the 3rd ventricle. In conclusion, stem cells may partially account for the sexually dimorphic postweaning development of the SDN-POA. C1 [He, Zhen; Ferguson, Sherry A.; Paule, Merle G.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [He, Zhen; Cui, Li; Greenfield, L. John, Jr.] Univ Arkansas Med Sci, Dept Neurol, Little Rock, AR 72205 USA. RP He, Z (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM zhen.he@fda.hhs.gov FU National Center for Toxicological Research/FDA [Protocol P00710, Protocol P00706]; National Institutes of Health [R01-NS049389]; UAMS FX This study was supported by the National Center for Toxicological Research/FDA (Protocol P00710 to ZH and Protocol P00706 to SAF). LC was supported by National Institutes of Health, Grant R01-NS049389 and UAMS institutional funds to LJG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 4 Z9 4 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 30 PY 2013 VL 8 IS 1 AR e54927 DI 10.1371/journal.pone.0054927 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 098QM UT WOS:000315563800089 PM 23383001 ER PT J AU Garber, L Gray, RA Matysiak, SR AF Garber, Libet Gray, Richard A. Matysiak, Silvina R. TI Modeling the Structure and Function of L-Type Calcium Channel (Cav1.2) to Understand its Effect in Cardiac Propagation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 57th Annual Meeting of the Biophysical-Society CY FEB 02-06, 2013 CL Philadelphia, PA SP Biophys Soc C1 [Garber, Libet; Matysiak, Silvina R.] Univ Maryland Coll Pk, College Pk, MD USA. [Garber, Libet; Gray, Richard A.] US FDA, Silver Spring, MD USA. RI Gray, Richard/F-3916-2015 OI Gray, Richard/0000-0003-2798-6378 NR 2 TC 0 Z9 0 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 29 PY 2013 VL 104 IS 2 SU 1 BP 460A EP 460A PG 1 WC Biophysics SC Biophysics GA 105MI UT WOS:000316074304337 ER PT J AU Osmulski, PA Gaczynska, M Karpowicz, P Stuart, C Jong, W Mikolajczyk, M Anderson, MC Marszal, E AF Osmulski, Pawel A. Gaczynska, Maria Karpowicz, Przemyslaw Stuart, Christine Jong, Wesley Mikolajczyk, Malgorzata Anderson, Martha C. Marszal, Ewa TI Atomic Force Microscopy reveals Diversity of Serpin Polymers SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 57th Annual Meeting of the Biophysical-Society CY FEB 02-06, 2013 CL Philadelphia, PA SP Biophys Soc C1 [Osmulski, Pawel A.; Gaczynska, Maria; Karpowicz, Przemyslaw] UTHSCSA, San Antonio, TX USA. [Stuart, Christine; Jong, Wesley; Mikolajczyk, Malgorzata; Anderson, Martha C.; Marszal, Ewa] US FDA, Bethesda, MD 20014 USA. RI Anderson, Martha/C-1720-2015 OI Anderson, Martha/0000-0003-0748-5525 NR 0 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 29 PY 2013 VL 104 IS 2 SU 1 BP 513A EP 513A PG 1 WC Biophysics SC Biophysics GA 105MI UT WOS:000316074305111 ER PT J AU Jha, P Landsman, V Rostron, B Thun, M Anderson, RN McAfee, T Peto, R AF Jha, Prabhat Landsman, Victoria Rostron, Brian Thun, Michael Anderson, Robert N. McAfee, Tim Peto, Richard TI 21st-Century Hazards of Smoking and Benefits of Cessation in the United States SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CIGARETTE; EPIDEMIC; TOBACCO AB Background Extrapolation from studies in the 1980s suggests that smoking causes 25% of deaths among women and men 35 to 69 years of age in the United States. Nationally representative measurements of the current risks of smoking and the benefits of cessation at various ages are unavailable. Methods We obtained smoking and smoking-cessation histories from 113,752 women and 88,496 men 25 years of age or older who were interviewed between 1997 and 2004 in the U. S. National Health Interview Survey and related these data to the causes of deaths that occurred by December 31, 2006 (8236 deaths in women and 7479 in men). Hazard ratios for death among current smokers, as compared with those who had never smoked, were adjusted for age, educational level, adiposity, and alcohol consumption. Results For participants who were 25 to 79 years of age, the rate of death from any cause among current smokers was about three times that among those who had never smoked (hazard ratio for women, 3.0; 99% confidence interval [CI], 2.7 to 3.3; hazard ratio for men, 2.8; 99% CI, 2.4 to 3.1). Most of the excess mortality among smokers was due to neoplastic, vascular, respiratory, and other diseases that can be caused by smoking. The probability of surviving from 25 to 79 years of age was about twice as great in those who had never smoked as in current smokers (70% vs. 38% among women and 61% vs. 26% among men). Life expectancy was shortened by more than 10 years among the current smokers, as compared with those who had never smoked. Adults who had quit smoking at 25 to 34, 35 to 44, or 45 to 54 years of age gained about 10, 9, and 6 years of life, respectively, as compared with those who continued to smoke. Conclusions Smokers lose at least one decade of life expectancy, as compared with those who have never smoked. Cessation before the age of 40 years reduces the risk of death associated with continued smoking by about 90%. C1 [Jha, Prabhat] Univ Toronto, Ctr Global Hlth Res, St Michaels Hosp, Toronto, ON M5C 1N8, Canada. [Rostron, Brian] US FDA, Rockville, MD 20857 USA. [Anderson, Robert N.] Ctr Dis Control & Prevent, Hyattsville, MD USA. [Thun, Michael] Amer Canc Soc, Atlanta, GA 30329 USA. [McAfee, Tim] Ctr Dis Control & Prevent, Atlanta, GA USA. [Peto, Richard] Univ Oxford, Clin Trial & Epidemiol Serv Unit, Oxford, England. RP Jha, P (reprint author), Univ Toronto, Ctr Global Hlth Res, St Michaels Hosp, Toronto, ON M5C 1N8, Canada. FU Fogarty International Center [TW007939-01]; National Institutes of Health; Canadian Institutes of Health Research [IEG-53506]; Disease Control Priorities Project; Bill and Melinda Gates Foundation FX Supported by a grant (TW007939-01) from the Fogarty International Center, National Institutes of Health; by a grant (IEG-53506) from the Canadian Institutes of Health Research; and by the Disease Control Priorities Project, Bill and Melinda Gates Foundation. Dr. Jha holds an endowed faculty position at the University of Toronto. NR 29 TC 358 Z9 363 U1 3 U2 58 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 24 PY 2013 VL 368 IS 4 BP 341 EP 350 DI 10.1056/NEJMsa1211128 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 075KX UT WOS:000313885900007 PM 23343063 ER PT J AU Seaworth, BJ Field, K Flood, J Saliba, J Mase, SR Cronin, A Shah, N Jereb, J Chorba, T AF Seaworth, Barbara J. Field, Kim Flood, Jennifer Saliba, Jouhayna Mase, Sundari R. Cronin, Ann Shah, Neha Jereb, John Chorba, Terence TI Interruptions in Supplies of Second-Line Antituberculosis Drugs - United States, 2005-2012 SO MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT LA English DT Article ID SHORTAGE C1 [Seaworth, Barbara J.] Univ Texas Hlth Sci Ctr, Houston, TX USA. [Field, Kim] San Diego Cty TB Control Program, San Diego, CA USA. [Saliba, Jouhayna] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Mase, Sundari R.; Cronin, Ann; Shah, Neha; Jereb, John; Chorba, Terence] CDC, Div TB Eliminat, Natl Ctr HIV Viral Hepatitis STD & TB Prevent, Atlanta, GA 30333 USA. RP Mase, SR (reprint author), CDC, Div TB Eliminat, Natl Ctr HIV Viral Hepatitis STD & TB Prevent, Atlanta, GA 30333 USA. EM smase@cdc.gov NR 9 TC 6 Z9 6 U1 0 U2 1 PU CENTER DISEASE CONTROL & PREVENTION PI ATLANTA PA MAILSTOP E-90, ATLANTA, GA 30333 USA SN 0149-2195 EI 1545-861X J9 MMWR-MORBID MORTAL W JI MMWR-Morb. Mortal. Wkly. Rep. PD JAN 18 PY 2013 VL 62 IS 2 BP 23 EP 26 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 188DO UT WOS:000322172500002 ER PT J AU Woo, EJ AF Woo, Emily Jane TI Expedited Review of New Drugs SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Woo, EJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM jane.woo@fda.hhs.gov NR 5 TC 0 Z9 0 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 16 PY 2013 VL 309 IS 3 BP 236 EP 237 DI 10.1001/jama.2012.56911 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 070XG UT WOS:000313546800016 PM 23321756 ER PT J AU Parveen, S DaSilva, L DePaola, A Bowers, J White, C Munasinghe, KA Brohawn, K Mudoh, M Tamplin, M AF Parveen, Salina DaSilva, Ligia DePaola, Angelo Bowers, John White, Chanelle Munasinghe, Kumudini Apsara Brohawn, Kathy Mudoh, Meshack Tamplin, Mark TI Development and validation of a predictive model for the growth of Vibrio parahaemolyticus in post-harvest shellstock oysters SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE Vibrio parahaemolyticus; Predictive microbiology; Secondary model; Eastern oyster; Asian oyster ID UNITED-STATES; BACTERIAL-GROWTH; TEMPERATURE; SURVIVAL; HARVEST; STORAGE; WATERS; BAY AB Information is limited about the growth and survival of naturally-occurring Vibrio parahaemolyticus in live oysters under commercially relevant storage conditions harvested from different regions and in different oyster species. This study produced a predictive model for the growth of naturally-occurring V. parahaemolyticus in live Eastern oysters (Crassostrea virginica) harvested from the Chesapeake Bay, MD, USA and stored at 5-30 degrees C until oysters gapped. The model was validated with model-independent data collected from Eastern oysters harvested from the Chesapeake Bay and Mobile Bay, AL, USA and Asian (C. ariakensis) oysters from the Chesapeake Bay, VA, USA. The effect of harvest season, region and water condition on growth rate (GR) was also tested. At each time interval, two samples consisting of six oysters each were analyzed by a direct-plating method for total V. parahaemolyticus. The Baranyi D-model was fitted to the total V. parahaemolyticus growth and survival data. A secondary model was produced using the square root model. V. parahaemolyticus slowly inactivated at 5 and 10 degrees C with average rates of -0.002 and -0.001 log cfu/h, respectively. The average GRs at 15, 20, 25, and 30 degrees C were 0.038, 0.082, 0.228, and 0.219 log cfu/h, respectively. The bias and accuracy factors of the secondary model for model-independent data were 1.36 and 1.46 for Eastern oysters from Mobile Bay and the Chesapeake Bay, respectively. V. parahaemolyticus GRs were markedly lower in Asian oysters. Harvest temperature, salinity, region and season had no effect on GRs. The observed GRs were less than those predicted by the U.S. Food and Drug Administration's V. parahaemolyticus quantitative risk assessment. (c) 2012 Elsevier B.V. All rights reserved. C1 [Parveen, Salina; DaSilva, Ligia; White, Chanelle; Munasinghe, Kumudini Apsara; Mudoh, Meshack] Univ Maryland Eastern Shore, Dept Agr Food & Resource Sci, Food Sci & Technol PhD Program, Princess Anne, MD 21853 USA. [DePaola, Angelo] US FDA, Div Seafood Sci & Technol, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. [Bowers, John] US FDA, Div Publ Hlth & Biostat, College Pk, MD 20740 USA. [Brohawn, Kathy] Maryland Dept Environm, Baltimore, MD 21230 USA. [Tamplin, Mark] Univ Tasmania, Food Safety Ctr, Tasmanian Inst Agr Sci, Hobart, Tas 7001, Australia. RP Parveen, S (reprint author), Univ Maryland Eastern Shore, Ctr Food Sci & Technol 2116, Princess Anne, MD 21853 USA. EM sparveen@umes.edu FU National Research Initiative of the United States Department of Agriculture, Cooperative State Research, Education and Extension Service [2006-35201-16644]; University of Maryland Eastern Shore Advanced Curriculum Technology-Based Instructional Opportunities Network (ACTION) FX This research was supported by the National Research Initiative of the United States Department of Agriculture, Cooperative State Research, Education and Extension Service, grant #2006-35201-16644 and University of Maryland Eastern Shore Advanced Curriculum Technology-Based Instructional Opportunities Network (ACTION). NR 37 TC 15 Z9 17 U1 4 U2 46 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 JAN 15 PY 2013 VL 161 IS 1 BP 1 EP 6 DI 10.1016/j.ijfoodmicro.2012.11.010 PG 6 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 083EI UT WOS:000314445100001 PM 23246606 ER PT J AU Uehara, T Kosyk, O Jeannot, E Bradford, BU Tech, K Macdonald, JM Boorman, GA Chatterjee, S Mason, RP Melnyk, SB Tryndyak, VP Pogribny, IP Rusyn, I AF Uehara, Takeki Kosyk, Oksana Jeannot, Emmanuelle Bradford, Blair U. Tech, Katherine Macdonald, Jeffrey M. Boorman, Gary A. Chatterjee, Saurabh Mason, Ronald P. Melnyk, Stepan B. Tryndyak, Volodymyr P. Pogribny, Igor P. Rusyn, Ivan TI Acetaminophen-induced acute liver injury in HCV transgenic mice SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Hepatitis C virus; Acetaminophen; Liver; Mouse; Mitochondria; Oxidative stress ID HEPATITIS-C VIRUS; UNFOLDED PROTEIN RESPONSE; INDUCED HEPATOTOXICITY; UNITED-STATES; VIRAL HEPATOCARCINOGENESIS; MOUSE-LIVER; GLUTATHIONE; EXPRESSION; INFECTION; ALCOHOL AB The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. (C) 2012 Elsevier Inc. All rights reserved. C1 [Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle; Bradford, Blair U.; Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. [Tech, Katherine; Macdonald, Jeffrey M.] Univ N Carolina, Dept Biomed Engn, Chapel Hill, NC 27599 USA. [Boorman, Gary A.] Covance, Chantilly, VA 20151 USA. [Chatterjee, Saurabh; Mason, Ronald P.] NIEHS, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27713 USA. [Melnyk, Stepan B.] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72201 USA. [Tryndyak, Volodymyr P.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Rusyn, I (reprint author), Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. EM iir@unc.edu RI Rusyn, Ivan/S-2426-2016 FU National Institutes of Health [P42 ES005948, R01 ES015241]; NIH [ES019875] FX Supported, in part, by grants from the National Institutes of Health P42 ES005948 and R01 ES015241. Saurabh Chatterjee was a recipient of NIH K99/R00 award ES019875. The authors wish to acknowledge technical assistance from Drs. John Grimes, Marc ter Horst, and Thomas O'Connell. We are also grateful to Dr. Steven Weinman for providing the HCV-Tg animals and for fruitful discussions. NR 60 TC 6 Z9 7 U1 1 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JAN 15 PY 2013 VL 266 IS 2 BP 224 EP 232 DI 10.1016/j.taap.2012.11.019 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 073QS UT WOS:000313758200006 PM 23200774 ER PT J AU He, XS Sasaki, S Baer, J Khurana, S Golding, H Treanor, JJ Topham, DJ Sangster, MY Jin, H Dekker, CL Subbarao, K Greenberg, HB AF He, Xiao-Song Sasaki, Sanae Baer, Jane Khurana, Surender Golding, Hana Treanor, John J. Topham, David J. Sangster, Mark Y. Jin, Hong Dekker, Cornelia L. Subbarao, Kanta Greenberg, Harry B. TI Heterovariant Cross-Reactive B-Cell Responses Induced by the 2009 Pandemic Influenza Virus A Subtype H1N1 Vaccine SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE influenza; vaccine; antibody; cross-reactivity ID ANTIBODY-RESPONSE; A H1N1; HUMANS; HEMAGGLUTININ; DIVERSITY; EMERGENCE; SWINE AB Background. The generation of heterovariant immunity is a highly desirable feature of influenza vaccines. The goal of this study was to compare the heterovariant B-cell response induced by the monovalent inactivated 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) vaccine with that induced by the 2009 seasonal trivalent influenza vaccine (sTIV) containing a seasonal influenza A virus subtype H1N1 (A[H1N1]) component in young and elderly adults. Methods. Plasmablast-derived polyclonal antibodies (PPAb) from young and elderly recipients of A(H1N1) pdm09 vaccine or sTIV were tested for binding activity to various influenza antigens. Results. In A(H1N1)pdm09 recipients, the PPAb titers against homotypic A(H1N1)pdm09 vaccine were similar to those against the heterovariant seasonal A(H1N1) vaccine and were similar between young and elderly subjects. The PPAb avidity was higher among elderly individuals, compared with young individuals. In contrast, the young sTIV recipients had 10-fold lower heterovariant PPAb titers against the A(H1N1)pdm09 vaccine than against the homotypic seasonal A(H1N1) vaccine. In binding assays with recombinant head and stalk domains of hemagglutinin, PPAb from the A(H1N1)pdm09 recipients but not PPAb from the sTIV recipients bound to the conserved stalk domain. Conclusion. The A(H1N1)pdm09 vaccine induced production of PPAb with heterovariant reactivity, including antibodies targeting the conserved hemagglutinin stalk domain. C1 [He, Xiao-Song; Greenberg, Harry B.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Sasaki, Sanae; Greenberg, Harry B.] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA. [Dekker, Cornelia L.] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. [He, Xiao-Song; Sasaki, Sanae; Greenberg, Harry B.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Jin, Hong] MedImmune, Mountain View, CA USA. [Baer, Jane; Topham, David J.; Sangster, Mark Y.] Univ Rochester, Med Ctr, Dept Microbiol & Immunol, New York, NY USA. [Treanor, John J.] Univ Rochester, Med Ctr, Dept Med, New York, NY USA. [Khurana, Surender; Golding, Hana] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP He, XS (reprint author), VA Med Ctr 154C, 3801 Miranda Ave, Palo Alto, CA 94304 USA. EM xiaosong@stanford.edu FU VA Palo Alto Health Care System; National Institutes of Health [AI090019, AI057229, UL1 RR025744]; New York Influenza Center of Excellence [HHSN266200700008C]; National Center for Immunization and Respiratory Diseases [5U18IP000172 03]; National Institute of Allergy and Infectious Diseases; Department of Health and Human Services [HHSN272200900026C]; Medical Countermeasures Initiative; Food and Drug Administration FX We thank our study subjects, for their participation; P. Dormitzer, for providing critical reagents; C. Zhang, for technical assistance; W. Wang, A. Hussain, R. Vepachedu, and A. Suguitan Jr, for producing the headless HA; S. Mackey, for coordinating the clinical study; S. Swope, S. Cathey, C. Walsh, S. French, and M. Ugur (Stanford University School of Medicine) and the Vaccine Research Unit in the University of Rochester, for enrolling subjects, administering vaccine, and collecting samples and clinical data; T. Quan, K. Spann, S. Batra, and B. Tse, for scheduling subjects and providing clinical data management; and VA Palo Alto Health Care System, for supporting this study.; This work was supported by the National Institutes of Health (AI090019, AI057229, and UL1 RR025744), the New York Influenza Center of Excellence (HHSN266200700008C), the National Center for Immunization and Respiratory Diseases (5U18IP000172 03), the intramural research program of the National Institute of Allergy and Infectious Diseases, the Department of Health and Human Services (HHSN272200900026C), and the Medical Countermeasures Initiative and the Pandemic Influenza Funding of the Food and Drug Administration. NR 28 TC 8 Z9 9 U1 0 U2 14 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 15 PY 2013 VL 207 IS 2 BP 288 EP 296 DI 10.1093/infdis/jis664 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 061YO UT WOS:000312886400015 PM 23107783 ER PT J AU Obolensky, OI Wu, WW Shen, RF Yu, YK AF Obolensky, O. I. Wu, Wells W. Shen, Rong-Fong Yu, Yi-Kuo TI Using dissociation energies to predict observability of b- and y-peaks in mass spectra of short peptides. II. Results for hexapeptides with non-polar side chains SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID COLLISION-INDUCED DISSOCIATION; DENSITY-FUNCTIONAL THEORY; AMIDE BOND-CLEAVAGE; FRAGMENTATION PATHWAYS; GAS-PHASE; PROTONATED PEPTIDES; MOBILE PROTON; IONS; SPECTROMETRY; ISOMERIZATION AB RATIONALE The hypothesis that dissociation energies can serve as a predictor of observability of b- and y-peaks is tested for seven hexapeptides. If the hypothesis holds true for large classes of peptides, one would be able to improve the scoring accuracy of peptide identification tools by excluding theoretical peaks that cannot be observed in practical product ion spectra due to various physical, chemical or thermodynamic considerations. METHODS Product ion m/z spectra of hexapeptides AAAAAA, AAAFAA, AAAVAA, AAFAAA, AAVAAA, AAFFAA and AAVVAA have been acquired on a Finnigan LTQ XL mass spectrometer in the collision-induced dissociation (CID) activation mode on a grid of activation times 0.05 to 100?ms and normalized collision energy 10 to 35%. Dissociation energies were calculated for all fragmentation channels leading to b- and y-fragments at the TPSS/6-31G(d,p) level of the density functional theory. RESULTS It was demonstrated that the m/z peaks observed in the product ion spectra correspond to the fragmentation channels with dissociation energies below a certain threshold value. However, there is no direct correlation between the most intense m/z peaks and the lowest dissociation energies. Using the dissociation energies, it was predicted that out of 63 theoretically possible peaks in the b- and y-series of the seven hexapeptides, 19 should not be observable in practical spectra. In the experiments, 24 peaks were not observed, including all 19 predicted. CONCLUSIONS Dissociation energies alone are not sufficient for predicting ion intensity relationships in product ion m/z spectra. Nevertheless, the present data suggest that dissociation energies appear to be good predictors of observability of b- and y-peaks and potentially very useful for filtering theoretical peaks of each candidate peptide in peptide identification tools. Published 2012. This article is a US Government work and is in the public domain in the USA. C1 [Obolensky, O. I.; Yu, Yi-Kuo] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Wu, Wells W.; Shen, Rong-Fong] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Obolensky, OI (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM obolensk@ncbi.nlm.nih.gov; yyu@ncbi.nlm.nih.gov RI Obolensky, Oleg/A-5839-2008 OI Obolensky, Oleg/0000-0003-3315-1828 FU National Institutes of Health, National Library of Medicine FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Library of Medicine. The computations were carried out on the Biowulf computer cluster at the NIH (http://biowulf.nih.gov). NR 26 TC 0 Z9 0 U1 3 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PD JAN 15 PY 2013 VL 27 IS 1 BP 152 EP 156 DI 10.1002/rcm.6451 PG 5 WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA 057BL UT WOS:000312536700016 PM 23239328 ER PT J AU Mindaye, ST Ra, M Lo Surdo, J Bauer, SR Alterman, MA AF Mindaye, Samuel T. Ra, Moonjin Lo Surdo, Jessica Bauer, Steven R. Alterman, Michail A. TI Improved proteomic profiling of the cell surface of culture-expanded human bone marrow multipotent stromal cells SO JOURNAL OF PROTEOMICS LA English DT Article DE Human bone marrow; Multipotent stromal cells; Proteomics; Membrane proteins; ESI MS/MS; MALDI MS/MS ID MESENCHYMAL STEM-CELLS; UMBILICAL-CORD BLOOD; GENE-EXPRESSION; MEMBRANE-PROTEINS; MASS-SPECTROMETRY; OSTEOBLAST DIFFERENTIATION; OSTEOGENIC DIFFERENTIATION; HETEROGENEITY; IDENTIFICATION; POPULATIONS AB A comprehensive analysis of the membrane proteome is essential to explain the biology of multipotent stromal cells and identify reliable protein biomarkers for the isolation as well as tracking of cells during differentiation and maturation. However, proteomic analysis of membrane proteins is challenging and they are noticeably under-represented in numerous proteomic studies. Here we introduce new approach, which includes high pressure-assisted membrane protein extraction, protein fractionation by gel-eluted liquid fraction entrapment electrophoresis (GELFREE), and combined use of liquid chromatography MALDI and ESI tandem mass spectrometry. This report presents the first comprehensive proteomic analysis of membrane proteome of undifferentiated and culture-expanded human bone marrow multipotent stromal cells (hBM-MSC) obtained from different human donors. Gene ontology mapping using the Ingenuity Pathway Analysis and DAVID programs revealed the largest membrane proteomic dataset for hBM-MSC reported to date. Collectively, the new workflow enabled us to identify at least two-fold more membrane proteins compared to published results on hBM-MSC. A total of 84 CDs were identified including 14 CDs identified for the first time. This dataset can serve as a basis for further exploration of self-renewal, differentiation and characterization of hBM-MSC. Published by Elsevier B.V. C1 [Mindaye, Samuel T.; Ra, Moonjin; Alterman, Michail A.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Lo Surdo, Jessica; Bauer, Steven R.] US FDA, Cellular & Tissue Therapies Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Alterman, MA (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM Michail.Alterman@fda.hhs.gov OI Bauer, Steven/0000-0003-2831-846X FU Center for Biologics Evaluation and Research, US Food and Drug Administration FX This project was supported by the Modernizing Science Initiative funds provided by the Center for Biologics Evaluation and Research, US Food and Drug Administration. We appreciate critical reading of the manuscript by Syed Husain, Raj Puri and John Cipollo. NR 64 TC 17 Z9 17 U1 0 U2 26 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-3919 J9 J PROTEOMICS JI J. Proteomics PD JAN 14 PY 2013 VL 78 BP 1 EP 14 DI 10.1016/j.jprot.2012.10.028 PG 14 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 113YY UT WOS:000316706800001 PM 23153793 ER PT J AU Khodakovskaya, MV Kim, BS Kim, JN Alimohammadi, M Dervishi, E Mustafa, T Cernigla, CE AF Khodakovskaya, Mariya V. Kim, Bong-Soo Kim, Jong Nam Alimohammadi, Mohammad Dervishi, Enkeleda Mustafa, Thikra Cernigla, Carl E. TI Carbon Nanotubes as Plant Growth Regulators: Effects on Tomato Growth, Reproductive System, and Soil Microbial Community SO SMALL LA English DT Article DE tomato plants; carbon nanotubes; plant growth regulators; soil microbes; metagenomic analysis ID DELIVERY-SYSTEMS; NANOPARTICLES; NANOMATERIALS; TRANSLOCATION; IMPACT; CELLS; DNA AB Multi-walled carbon nanotubes (CNTs) can affect plant phenotype and the composition of soil microbiota. Tomato plants grown in soil supplemented with CNTs produce two times more flowers and fruit compared to plants grown in control soil. The effect of carbon nanotubes on microbial community of CNT-treated soil is determined by denaturing gradient gel electrophoresis and pyrosequencing analysis. Phylogenetic analysis indicates that Proteobacteria and Bacteroidetes are the most dominant groups in the microbial community of soil. The relative abundances of Bacteroidetes and Firmicutes are found to increase, whereas Proteobacteria and Verrucomicorbia decrease with increasing concentration of CNTs. The results of comparing diversity indices and species level phylotypes (OTUs) between samples showed that there is not a significant affect on bacterial diversity. C1 [Khodakovskaya, Mariya V.; Alimohammadi, Mohammad] Univ Arkansas, Dept Appl Sci, Little Rock, AR 72204 USA. [Kim, Bong-Soo; Kim, Jong Nam; Cernigla, Carl E.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Dervishi, Enkeleda; Mustafa, Thikra] Univ Arkansas, Ctr Integrat Nanotechnol Sci, Little Rock, AR 72204 USA. RP Khodakovskaya, MV (reprint author), Univ Arkansas, Dept Appl Sci, Little Rock, AR 72204 USA. EM mvkhodakovsk@ualr.edu RI Kim, Bong-Soo/L-4779-2013 OI Kim, Bong-Soo/0000-0003-1243-8280 FU EPSCoR-NSF-P3 Center MVK [P3-202] FX The authors are grateful to Center for Integrative Nanotechnology Sciences (CINS), UALR and especially to Director of CINS Prof. A. S. Biris for detection of carbon nanotubes in flowers of tomato plants using Raman spectroscopy. Funding from EPSCoR-NSF-P3 Center MVK (Grant P3-202 to MVK) is appreciated. NR 36 TC 64 Z9 67 U1 16 U2 135 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1613-6810 J9 SMALL JI Small PD JAN 14 PY 2013 VL 9 IS 1 BP 115 EP 123 DI 10.1002/smll.201201225 PG 9 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 063IE UT WOS:000312988900014 PM 23019062 ER PT J AU Liu, M Fan, J Wang, S Wang, ZJ Wang, C Zuo, Z Chow, MSS Shi, LM Wen, ZN Huang, Y AF Liu, Mandy Fan, Jeffery Wang, Steven Wang, Zhijun Wang, Charles Zuo, Zhong Chow, Moses S. S. Shi, Leming Wen, Zhining Huang, Ying TI Transcriptional profiling of Chinese medicinal formula Si-Wu-Tang on breast cancer cells reveals phytoestrogenic activity SO BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Article DE Phytoestrogens; Microarrays; Genomics; Chemoprevention; Breast cancer; Herbal medicines; Transcriptional profiling ID ESTROGEN-RESPONSIVE GENES; CUSTOMIZED DNA MICROARRAY; ALPHA-BINDING-SITES; JUZEN-TAIHO-TO; ENDOMETRIAL CARCINOGENESIS; EXPRESSION; CONSTITUENTS; MICE; CHEMOPREVENTION; PREVENTION AB Background: Si-Wu-Tang (SWT), comprising the combination of four herbs, Paeoniae, Angelicae, Chuanxiong and Rehmanniae, is one of the most popular traditional oriental medicines for women's diseases. In our previous study, the microarray gene expression profiles of SWT on breast cancer cell line MCF-7 were found similar to the effect of beta-estradiol (E2) on MCF-7 cells in the Connectivity Map database. Methods: Further data analysis was conducted to find the main similarities and differences between the effects of SWT and E2 on MCF-7 gene expression. The cell proliferation assay on MCF-7 (ER-positive) and MDA-MB-231 (ER-negative) cells were used to examine such estrogenic activity. The estrogenic potency of SWT was further confirmed by estrogen-responsive element (ERE) luciferase reporter assay in MCF-7 cells. Results: Many estrogen regulated genes strongly up-regulated by E2 were similarly up-regulated by SWT, e.g., GREB1, PGR and EGR3. Of interest with regard to safety of SWT, the oncogenes MYBL1 and RET were strongly induced by E2 but not by SWT. Quantitative RT-PCR analysis revealed a highly concordant expression change in selected genes with data obtained by microarrays. Further supporting SWT's estrogenic activity, in MCF-7 but not in MDA-MB-231 cells, SWT stimulated cell growth at lower concentrations (<3.0 mg/ml), while at high concentrations, it inhibits the growth of both cell lines. The growth inhibitory potency of SWT was significantly higher in MDA-MB-231 than in MCF-7 cells. The SWT-induced cell growth of MCF-7 could be blocked by addition of the estrogen receptor antagonist tamoxifen. In addition, SWT was able to activate the ERE activity at lower concentrations. The herbal components Angelicae, Chuanxiong and Rehmanniae at lower concentrations (<3.0 mg/ml) also showed growth-inducing and ERE-activating activity in MCF-7 cells. Conclusions: These results revealed a new mechanism to support the clinical use of SWT for estrogen related diseases and possibly for cancer prevention. This study also demonstrated the feasibility of using microarray transcriptional profiling to discover phytoestrogenic components that are present in natural products. C1 [Liu, Mandy; Fan, Jeffery; Wang, Steven; Wang, Zhijun; Chow, Moses S. S.; Huang, Ying] Western Univ Hlth Sci, Coll Pharm, Dept Pharmaceut Sci, Pomona, CA USA. [Liu, Mandy; Fan, Jeffery; Wang, Steven; Wang, Zhijun; Chow, Moses S. S.; Huang, Ying] Western Univ Hlth Sci, Coll Pharm, Ctr Adv Drug Res, Pomona, CA USA. [Wang, Charles] City Hope Comprehens Canc Ctr, Beckman Res Inst, Funct Genom Core, Duarte, CA USA. [Zuo, Zhong] Chinese Univ Hong Kong, Fac Med, Sch Pharm, Shatin, Hong Kong, Peoples R China. [Shi, Leming; Wen, Zhining] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Shi, Leming] Fudan Univ, Sch Pharm, Dept Clin Pharm, Shanghai 200433, Peoples R China. [Shi, Leming] Fudan Univ, Sch Pharm, Ctr Pharmacogenom, Shanghai 200433, Peoples R China. [Wen, Zhining] Sichuan Univ, Coll Chem, Chengdu 610064, Sichuan, Peoples R China. RP Wen, ZN (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM w_zhining@163.com; yhuang@westernu.edu RI Zuo, Zhong/B-6884-2008 FU U.S. Food and Drug Administration; Innovation and Technology Commission of the Hong Kong Special Administrative Region of the People's Republic of China [ITS/112/07, ITS/446/09] FX We thank Dr. David Sanchez at Western University of Health Sciences for providing the ERE-luc construct. This work was partly supported by the U.S. Food and Drug Administration (LS and ZW) and the innovation and Technology Grant (ITS/112/07 and ITS/446/09) from the Innovation and Technology Commission of the Hong Kong Special Administrative Region of the People's Republic of China (ZW, ZZ, MC and YH). NR 50 TC 6 Z9 7 U1 1 U2 31 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6882 J9 BMC COMPLEM ALTERN M JI BMC Complement. Altern. Med. PD JAN 10 PY 2013 VL 13 AR 11 DI 10.1186/1472-6882-13-11 PG 18 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 138GL UT WOS:000318496900001 PM 23305139 ER PT J AU Vaque, JP Dorsam, RT Feng, XD Iglesias-Bartolome, R Forsthoefel, DJ Chen, QM Debant, A Seeger, MA Ksander, BR Teramoto, H Gutkind, JS AF Vaque, Jose P. Dorsam, Robert T. Feng, Xiaodong Iglesias-Bartolome, Ramiro Forsthoefel, David J. Chen, Qianming Debant, Anne Seeger, Mark A. Ksander, Bruce R. Teramoto, Hidemi Gutkind, J. Silvio TI A Genome-wide RNAi Screen Reveals a Trio-Regulated Rho GTPase Circuitry Transducing Mitogenic Signals Initiated by G Protein-Coupled Receptors SO MOLECULAR CELL LA English DT Article ID NUCLEOTIDE EXCHANGE FACTOR; VASCULAR SMOOTH-MUSCLE; UVEAL MELANOMA; PH DOMAINS; CANCER; G-ALPHA(Q); ACTIVATION; MUTATIONS; KINASE; CELLS AB Activating mutations in GNAQ and GNA11, encoding members of the G alpha(q) family of G protein alpha subunits, are the driver oncogenes in uveal melanoma, and mutations in Gq-linked G protein-coupled receptors have been identified recently in numerous human malignancies. How G alpha(q) and its coupled receptors transduce mitogenic signals is still unclear because of the complexity of signaling events perturbed upon Gq activation. Using a synthetic-biology approach and a genome-wide RNAi screen, we found that a highly conserved guanine nucleotide exchange factor, Trio, is essential for activating Rhoand Rac-regulated signaling pathways acting on JNK and p38, and thereby transducing proliferative signals from G alpha(q) to the nucleus independently of phospholipase C-beta. Indeed, whereas many biological responses elicited by Gq depend on the transient activation of second-messenger systems, Gq utilizes a hard-wired protein-protein-interaction-based signaling circuitry to achieve the sustained stimulation of proliferative pathways, thereby controlling normal and aberrant cell growth. C1 [Vaque, Jose P.; Feng, Xiaodong; Iglesias-Bartolome, Ramiro; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. [Dorsam, Robert T.] Ctr Drug Evaluat & Res, Food & Drug Adm, Silver Spring, MD 20993 USA. [Feng, Xiaodong; Chen, Qianming] Sichuan Univ, State Key Lab Oral Dis, Chengdu 610041, Sichuan, Peoples R China. [Forsthoefel, David J.; Seeger, Mark A.] Ohio State Univ, Dept Mol Genet, Columbus, OH 43210 USA. [Debant, Anne] Univ Montpellier I, CNRS, Ctr Rech Biochim Macromol, UMR 5237, F-34293 Montpellier 5, France. [Debant, Anne] Univ Montpellier 2, CNRS, Ctr Rech Biochim Macromol, UMR 5237, F-34293 Montpellier 5, France. [Ksander, Bruce R.] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. [Teramoto, Hidemi] Kojin Hosp, Nagoya, Aichi 4638530, Japan. RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. EM sg39v@nih.gov RI Iglesias-Bartolome, Ramiro/H-4460-2014; Vaque, Jose/H-8413-2015 OI Iglesias-Bartolome, Ramiro/0000-0002-0792-1254; Vaque, Jose/0000-0002-3913-2495 FU Intramural Research Program of the National Institutes of Health; National Institute of Dental and Craniofacial Research FX The authors acknowledge the extensive support, guidance, and help from the DRSC at Harvard Medical School (www.flymai.org), as well as from all members of the Gutkind laboratory and the Oral and Pharyngeal Cancer Branch (OPCB) for their generous contributions and thoughtful suggestions throughout these studies. We thank Dr. Bryan Roth for providing the Sy-Rq construct and fruitful discussions, Dr. Jurgen Wess and members of his laboratory for assistance with binding assays and for their analysis, Dr. Cheuk Leung for advice and DNA vectors for the tetracycline-regulated expression of Sy-Rq, and Dr. Thomas Bugge for insightful advice and for critically reading our manuscript. We thank the entire OPCB team for their encouragement and support. This research was supported by the Intramural Research Program of the National Institutes of Health and the National Institute of Dental and Craniofacial Research. We apologize to all of our colleagues for not citing some of their original studies due to space limitations. NR 44 TC 41 Z9 41 U1 0 U2 18 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JAN 10 PY 2013 VL 49 IS 1 BP 94 EP 108 DI 10.1016/j.molcel.2012.10.018 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 071PS UT WOS:000313607300010 PM 23177739 ER PT J AU Wang, B Yin, JJ Zhou, XY Kurash, I Chai, ZF Zhao, YL Feng, WY AF Wang, Bing Yin, Jun-Jie Zhou, Xiaoyan Kurash, Ibrahim Chai, Zhifang Zhao, Yuliang Feng, Weiyue TI Physicochemical Origin for Free Radical Generation of Iron Oxide Nanoparticles in Biomicroenvironment: Catalytic Activities Mediated by Surface Chemical States SO JOURNAL OF PHYSICAL CHEMISTRY C LA English DT Article ID ELECTRONIC-STRUCTURE; TIO2 NANOPARTICLES; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; NANOMATERIALS; DECOMPOSITION; INFLAMMATION; DEGRADATION; MECHANISM; TOXICITY AB A wide range of nanoparticles (NPs) have been found to generate free radicals in biological systems. Hence, it is hypothesized that free radical generation may play a key role in the mechanism of nanomaterial toxicity in vivo. However, the main physicochemical basis for the free radical generation particularly in the biomicroenvironment has not yet been fully established. In this study, we performed comprehensive spectroscopic techniques to probe the physicochemical origin of free radical generation induced by iron oxide nanoparticles in biomicroenvironment. We demonstrated that alpha-Fe2O3 and gamma-Fe2O3 NPs induced hydroxyl radical ((OH)-O-center dot) via homogeneous and heterogeneous Fenton process, depending on the biological microenvironment of pH and reducing agent presence. The physicochemical structures such as chemical states of oxygen and iron on nanosurface are the key factors in the homogeneous and heterogeneous catalytic reactions. A noteworthy finding was that in situ surface reduction of Fe2O3 NPs occurred in the presence of a physiological amount of biological reducing agents (L-cysteine or NADPH), which could enhance and even reverse the capacity of (OH)-O-center dot generation by alpha-Fe2O3 and gamma-Fe2O3 NPs under low pH 1.2 condition. The present study demonstrates that exploration of the physicochemical basis at the nanobio interface in biomicroenvironments may help to understand the mechanism of nanotoxicity and guide safe design of nanomaterials for biomedical application C1 [Wang, Bing; Zhou, Xiaoyan; Chai, Zhifang; Zhao, Yuliang; Feng, Weiyue] Chinese Acad Sci, Inst High Energy Phys, Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100049, Peoples R China. [Wang, Bing; Zhou, Xiaoyan; Chai, Zhifang; Zhao, Yuliang; Feng, Weiyue] Chinese Acad Sci, Inst High Energy Phys, Key Lab Nucl Analyt Tech, Beijing 100049, Peoples R China. [Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Kurash, Ibrahim] Chinese Acad Sci, Inst High Energy Phys, Beijing Synchrotron Radiat Facil, Beijing 100049, Peoples R China. [Zhao, Yuliang] Natl Ctr Nanosci & Technol China, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China. RP Zhao, YL (reprint author), Chinese Acad Sci, Inst High Energy Phys, Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100049, Peoples R China. EM zhaoyuliang@ihep.ac.cn; fengwy@ihep.ac.cn RI Yin, Jun Jie /E-5619-2014; Feng, Wei-Yue/H-3390-2016 FU National Basic Research Program (973 program) [2011CB933403, 2012CB930000]; National Natural Science Foundation of China [10905064, 11275214, 10975148]; FY11 FDA Nanotechnology CORES Program FX The authors are grateful to the support of the National Basic Research Program (973 program, 2011CB933403 and 2012CB930000), the National Natural Science Foundation of China (10905064, 11275214 and 10975148) and a regulatory science grant under the FY11 FDA Nanotechnology CORES Program (J.J.Y.). NR 42 TC 29 Z9 30 U1 7 U2 70 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1932-7447 J9 J PHYS CHEM C JI J. Phys. Chem. C PD JAN 10 PY 2013 VL 117 IS 1 BP 383 EP 392 DI 10.1021/jp3101392 PG 10 WC Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 066KW UT WOS:000313220700051 ER PT J AU Gray, RA Mashburn, DN Sidorov, VY Wikswo, JP AF Gray, Richard A. Mashburn, David N. Sidorov, Veniamin Y. Wikswo, John P. TI Quantification of Transmembrane Currents during Action Potential Propagation in the Heart SO BIOPHYSICAL JOURNAL LA English DT Article ID VENTRICULAR-FIBRILLATION; CONDUCTION-VELOCITY; MEASURING CURVATURE; CARDIAC TISSUE; SODIUM CURRENT; MUSCLE; MECHANISM; MEMBRANE; CELLS; STIMULATION AB The measurement, quantitative analysis, theory, and mathematical modeling of transmembrane potential and currents have been an integral part of the field of electrophysiology since its inception. Biophysical modeling of action potential propagation begins with detailed ionic current models for a patch of membrane within a distributed cable model. Voltage-clamp techniques have revolutionized clinical electrophysiology via the characterization of the transmembrane current gating variables; however, this kinetic information alone is insufficient to accurately represent propagation. Other factors, including channel density, membrane area, surface/volume ratio, axial conductivities, etc., are also crucial determinants of transmembrane currents in multicellular tissue but are extremely difficult to measure. Here, we provide, to our knowledge, a novel analytical approach to compute transmembrane currents directly from experimental data, which involves high-temporal (200 kHz) recordings of intra- and extracellular potential with glass microelectrodes from the epicardial surface of isolated rabbit hearts during propagation. We show for the first time, to our knowledge, that during stable planar propagation the biphasic total transmembrane current (I-m) dipole density during depolarization was similar to 0.25 ms in duration and asymmetric in amplitude (peak outward current was similar to 95 mu A/cm(2) and peak inward current was similar to 140 mu A/cm(2)), and the peak inward ionic current (I-ion) during depolarization was similar to 260 mu A/cm(2) with duration of similar to 1.0 ms. Simulations of stable propagation using the ionic current versus transmembrane potential relationship fit from the experimental data reproduced these values better than traditional ionic models. During ventricular fibrillation, peak I-m was decreased by 50% and peak I-ion, was decreased by 70%. Our results provide, to our knowledge, novel quantitative information that complements voltage- and patch-clamp data. C1 [Gray, Richard A.] US FDA, Div Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Gray, Richard A.] Univ Alabama Birmingham, Dept Biomed Engn, Birmingham, AL 35294 USA. [Gray, Richard A.; Sidorov, Veniamin Y.; Wikswo, John P.] Vanderbilt Univ, Vanderbilt Inst Integrat Biosyst Res & Educ, Nashville, TN USA. [Mashburn, David N.; Wikswo, John P.] Vanderbilt Univ, Dept Phys & Astron, Nashville, TN 37235 USA. [Sidorov, Veniamin Y.; Wikswo, John P.] Vanderbilt Univ, Dept Biomed Engn, Nashville, TN 37235 USA. [Wikswo, John P.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. RP Gray, RA (reprint author), US FDA, Div Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. EM Richard.Gray@fda.hhs.gov RI Gray, Richard/F-3916-2015 OI Gray, Richard/0000-0003-2798-6378 FU National Institutes of Health (NIH) [R01-HL58241]; American Heart Association [0635037N]; Vanderbilt Institute for Integrative Biosystems Research and Education FX This work was supported in part by National Institutes of Health (NIH) grant R01-HL58241, the American Heart Association (0635037N), and the Vanderbilt Institute for Integrative Biosystems Research and Education. NR 41 TC 7 Z9 7 U1 0 U2 16 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 8 PY 2013 VL 104 IS 1 BP 268 EP 278 DI 10.1016/j.bpj.2012.11.007 PG 11 WC Biophysics SC Biophysics GA 070VM UT WOS:000313541200029 PM 23332079 ER PT J AU Schmidt, AG Xu, HF Khan, AR O'Donnell, T Khurana, S King, LR Manischewitz, J Golding, H Suphaphiphat, P Carfi, A Settembre, EC Dormitzer, PR Kepler, TB Zhang, RJ Moody, MA Haynes, BF Liao, HX Shaw, DE Harrison, SC AF Schmidt, Aaron G. Xu, Huafeng Khan, Amir R. O'Donnell, Timothy Khurana, Surender King, Lisa R. Manischewitz, Jody Golding, Hana Suphaphiphat, Pirada Carfi, Andrea Settembre, Ethan C. Dormitzer, Philip R. Kepler, Thomas B. Zhang, Ruijun Moody, M. Anthony Haynes, Barton F. Liao, Hua-Xin Shaw, David E. Harrison, Stephen C. TI Preconfiguration of the antigen-binding site during affinity maturation of a broadly neutralizing influenza virus antibody SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE immunity; antigen recognition; X-ray crystallography ID GERMINAL-CENTERS; IMMUNE-RESPONSE; FORCE-FIELD; B-CELLS; DYNAMICS; HEMAGGLUTININ; CONVERGENCE; INTEGRATORS; SIMULATION; MOLECULES AB Affinity maturation refines a naive B-cell response by selecting mutations in antibody variable domains that enhance antigen binding. We describe a B-cell lineage expressing broadly neutralizing influenza virus antibodies derived from a subject immunized with the 2007 trivalent vaccine. The lineage comprises three mature antibodies, the unmutated common ancestor, and a common intermediate. Their heavy-chain complementarity determining region inserts into the conserved receptor-binding pocket of influenza HA. We show by analysis of structures, binding kinetics and long time-scale molecular dynamics simulations that antibody evolution in this lineage has rigidified the initially flexible heavy-chain complementarity determining region by two nearly independent pathways and that this preconfiguration accounts for most of the affinity gain. The results advance our understanding of strategies for developing more broadly effective influenza vaccines. C1 [Schmidt, Aaron G.; Khan, Amir R.; Harrison, Stephen C.] Harvard Univ, Childrens Hosp, Mol Med Lab, Sch Med, Boston, MA 02115 USA. [Schmidt, Aaron G.; Khan, Amir R.; Harrison, Stephen C.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Xu, Huafeng; O'Donnell, Timothy; Shaw, David E.] DE Shaw Res, New York, NY 10036 USA. [Khurana, Surender; King, Lisa R.; Manischewitz, Jody; Golding, Hana] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Carfi, Andrea; Settembre, Ethan C.; Dormitzer, Philip R.] Novartis Vaccines & Diagnost, Cambridge, MA 02139 USA. [Kepler, Thomas B.] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA. [Zhang, Ruijun; Moody, M. Anthony; Haynes, Barton F.; Liao, Hua-Xin] Duke Univ, Duke Human Vaccine Inst, Sch Med, Durham, NC 27710 USA. [Shaw, David E.] Columbia Univ, Ctr Computat Biol & Bioinformat, New York, NY 10032 USA. RP Harrison, SC (reprint author), Harvard Univ, Childrens Hosp, Mol Med Lab, Sch Med, Boston, MA 02115 USA. EM harrison@crystal.harvard.edu RI Chiang, Vincent, Ming-Hsien/D-4312-2016; OI Chiang, Vincent, Ming-Hsien/0000-0002-2029-7863; O'Donnell, Timothy/0000-0002-9949-069X; Kepler, Thomas/0000-0002-1383-6865; Moody, Tony/0000-0002-3890-5855 FU National Institute of Allergy and Infectious Diseases of the National Institutes of Health [P01AI089618] FX We thank James Whittle, Junhua Pan, and Marco Morelli for help with cloning and purification of HA head construct and the beam line staff at Advanced Photon Source 24-ID-E and Advanced Light Source 8.2.2. We also thank Ansgar Philippsen for creating some of the molecular graphics and figures. Research reported in this publication was supported by National Institute of Allergy and Infectious Diseases of the National Institutes of Health Grant P01AI089618. NR 37 TC 63 Z9 63 U1 1 U2 25 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 2 PY 2013 VL 110 IS 1 BP 264 EP 269 DI 10.1073/pnas.1218256109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 071XI UT WOS:000313630300061 PM 23175789 ER PT B AU Seeff, L Stickel, F Navarro, VJ AF Seeff, Leonard Stickel, Felix Navarro, Victor J. BE Kaplowitz, N Deleve, LD TI Hepatotoxicity of Herbals and Dietary Supplements SO DRUG-INDUCED LIVER DISEASE, 3RD EDITION LA English DT Article; Book Chapter ID CHRONIC HEPATITIS-C; SHO-SAIKO-TO; FULMINANT LIVER-FAILURE; CELANDINE CHELIDONIUM-MAJUS; OF-THE-LITERATURE; HERBALIFE(R) NUTRITIONAL SUPPLEMENTS; RANDOMIZED CONTROLLED-TRIALS; IMPILA CALLILEPIS-LAUREOLA; PLACEBO-CONTROLLED TRIAL; ALTERNATIVE MEDICINE USE C1 [Seeff, Leonard] Hill Grp, Bethesda, MD 20817 USA. [Seeff, Leonard] US FDA, Silver Spring, MD USA. [Stickel, Felix] Univ Bern, Inselspital, Dept Visceral Surg & Med, CH-3010 Bern, Switzerland. [Navarro, Victor J.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. RP Seeff, L (reprint author), Hill Grp, Bethesda, MD 20817 USA. NR 271 TC 4 Z9 4 U1 2 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-387818-2; 978-0-12-387817-5 PY 2013 BP 631 EP 657 DI 10.1016/B978-0-12-387817-5.00035-2 PG 27 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BA8AE UT WOS:000337919800035 ER PT B AU Avigan, MI AF Avigan, Mark I. BE Kaplowitz, N Deleve, LD TI Regulatory Perspectives SO DRUG-INDUCED LIVER DISEASE, 3RD EDITION LA English DT Article; Book Chapter ID INDUCED LIVER-INJURY; CAUSALITY ASSESSMENT METHOD; ADVERSE DRUG-REACTIONS; AUTOIMMUNE HEPATITIS; CLINICAL-TRIALS; HEPATOTOXICITY; TROGLITAZONE; FAILURE; DISEASE; SAFETY C1 US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Avigan, MI (reprint author), US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 104 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-387818-2; 978-0-12-387817-5 PY 2013 BP 689 EP 712 DI 10.1016/B978-0-12-387817-5.00038-8 PG 24 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BA8AE UT WOS:000337919800038 ER PT S AU Wildt, B Malinauskas, RA Brown, RP AF Wildt, Bridget Malinauskas, Richard A. Brown, Ronald P. BE Dobrovolskaia, MA McNeil, SE TI The Effects of Engineered Nanomaterials on Erythrocytes SO HANDBOOK OF IMMUNOLOGICAL PROPERTIES OF ENGINEERED NANOMATERIALS SE Frontiers in Nanobiomedical Research LA English DT Article; Book Chapter ID RED-BLOOD-CELLS; POLY(PROPYLENE IMINE) DENDRIMERS; SOLID LIPID NANOPARTICLES; IRON-OXIDE NANOPARTICLES; IN-VITRO CYTOTOXICITY; SPRAGUE-DAWLEY RATS; TUMOR-BEARING MICE; SILVER NANOPARTICLES; OXIDATIVE STRESS; GOLD NANOPARTICLES AB Both engineered and naturally occurring nanomaterials (NMs) may come in contact with blood through different pathways, either directly (e.g., as nanoparticles carrying chemotherapy agents injected intravenously, imbedded in a coating on a vascular graft, or as wear debris released from an orthopedic device) or indirectly (e.g., through inhalation, oral, or topical exposure routes). Due to the ubiquitous importance of red blood cells in sustaining the different tissues of the body, in this chapter, we review the possible adverse effects of NMs on erythrocytes and the experimental techniques which have been applied to evaluate and better understand their mechanisms of interaction. This chapter provides a comprehensive overview of the current literature, outlines practical approaches to study nanoparticle interaction with erythrocytes, describes challenges, and suggests solutions to overcome them. C1 [Wildt, Bridget; Malinauskas, Richard A.; Brown, Ronald P.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Brown, RP (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM ronald.brown@fda.hhs.gov NR 190 TC 0 Z9 0 U1 0 U2 1 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE SN 2251-3965 BN 978-981-4390-26-2; 978-981-4390-25-5 J9 FRONT NANOBIOMED RES PY 2013 VL 1 BP 173 EP 206 D2 10.1142/8390 PG 34 WC Immunology; Nanoscience & Nanotechnology; Medicine, Research & Experimental; Materials Science, Biomaterials SC Immunology; Science & Technology - Other Topics; Research & Experimental Medicine; Materials Science GA BB1SW UT WOS:000341327400008 ER PT S AU Simak, J AF Simak, Jan BE Dobrovolskaia, MA McNeil, SE TI The Effects of Engineered Nanomaterials on Cultured Endothelial Cells SO HANDBOOK OF IMMUNOLOGICAL PROPERTIES OF ENGINEERED NANOMATERIALS SE Frontiers in Nanobiomedical Research LA English DT Article; Book Chapter ID IRON-OXIDE NANOPARTICLES; INFLAMMATORY RESPONSE SYNDROME; WATER-SOLUBLE FULLERENE; INDUCED VASCULAR INJURY; WALL CARBON NANOTUBES; SILICA NANOPARTICLES; IN-VITRO; OXIDATIVE STRESS; MEMBRANE MICROPARTICLES; SILVER NANOPARTICLES AB The vascular endothelium forms the inner lining of the vasculature and is an essential system in multicellular organisms that delivers nutrients and oxygen, removes CO2 and waste products, and facilitates interorgan communication. Endothelial dysfunctions may lead to life-threatening vascular disorders, including hypoperfusion and organ damage, and thrombotic and/or bleeding pathologies. As various engineered nanomaterials are being designed for biomedical applications for intravascular use and other nanomaterials may reach the vasculature as a result of occupational, environmental, or other types of exposure, it is necessary to evaluate the effects of engineered nanomaterials on the vascular endothelium. In the introduction of this chapter, the physiology of endothelial cells (ECs) and the pathophysiology of the possible adverse effects of nanomaterials on ECs are briefly described. Next, the methods that are used for the in vitro evaluation of the effects of nanomaterials on ECs are reviewed. Investigations of the effects of nanomaterials on ECs are primarily based on the observation of structural and functional changes in the different types of cultured ECs upon (usually) short-term exposure (up to 72 h) to various doses of nanomaterials. Numerous microscopic methods are employed to study morphological and structural changes of ECs and nanomaterial uptake. Different cell biology assays are used to assess the cytotoxicity of nanomaterials and their effects on proliferation and induction of apoptosis, necrosis, and autophagy. In addition, assays of various EC activation markers, nitric oxide (NO) and reactive oxygen species (ROS) production or functional EC mobility and morphogenesis, monolayer permeability, and vasoactivity assays also provide valuable information on nanomaterial effects on the vascular intima. Lastly, a summary of the published results regarding the in vitro effects of various nanomaterials on ECs, as well as selected assay protocols used in our laboratory are presented. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Simak, J (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 335, Rockville, MD 20852 USA. EM jan.simak@fda.hhs.gov NR 137 TC 1 Z9 1 U1 1 U2 4 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE SN 2251-3965 BN 978-981-4390-26-2; 978-981-4390-25-5 J9 FRONT NANOBIOMED RES PY 2013 VL 1 BP 207 EP 261 D2 10.1142/8390 PG 55 WC Immunology; Nanoscience & Nanotechnology; Medicine, Research & Experimental; Materials Science, Biomaterials SC Immunology; Science & Technology - Other Topics; Research & Experimental Medicine; Materials Science GA BB1SW UT WOS:000341327400009 ER PT S AU Simak, J AF Simak, Jan BE Dobrovolskaia, MA McNeil, SE TI The Effects of Engineered Nanomaterials on the Plasma Coagulation System SO HANDBOOK OF IMMUNOLOGICAL PROPERTIES OF ENGINEERED NANOMATERIALS SE Frontiers in Nanobiomedical Research LA English DT Article; Book Chapter ID DISSEMINATED INTRAVASCULAR COAGULATION; MOLECULAR-WEIGHT HEPARIN; KALLIKREIN-KININ SYSTEM; HEMOPHILIA-A MICE; IN-VITRO; PROTEIN ADSORPTION; TARGETED THROMBOLYSIS; BLOOD PROTEINS; PERFLUOROCARBON NANOPARTICLES; CHITOSAN/DNA NANOPARTICLES AB The plasma coagulation system (PCS) consists of plasma proteins and other factors that, together with platelets and vascular endothelial cells, maintain hemocoagulation balance. Under physiological conditions, these systems prevent blood clotting and, in cases of vascular injury, facilitate hemostasis to prevent blood loss. The dysregulation of hemocoagulation may lead to life-threatening thrombotic and/or bleeding pathologies. Since 1) various engineered nanomaterials are being designed for biomedical applications that will come into contact with the blood and 2) other nanomaterials may reach the circulation as a result of occupational, environmental, or other types of exposure, it is necessary to evaluate the effects of engineered nanomaterials on the PCS. In the introduction of this chapter, the components and mechanisms of the kallikrein-kinin system (KKS), the PCS, fibrinolysis, and the pathophysiology of the possible adverse effects of nanomaterials on these systems are briefly described. Next, the methods that are used for the in vitro evaluation of the effects of nanomaterials on the KKS, PCS, and fibrinolysis are reviewed. Screenings for the effects of nanomaterials are primarily based on their preincubation with citrated platelet-poor plasma (PPP). The PPP is subsequently subjected to clotting tests, including measurements of the activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), and recalcification time. In certain studies, plasmas that are deficient in specific plasma coagulation factors are used for comparison purposes. The activities of certain specific coagulation factors can be assayed photometrically using chromogenic or fluorogenic substrates, while antigens can be detected using ELISAs. Thromboelastography is another technique that is used for the complex analysis of the effects of nanomaterials on blood clotting and fibrinolysis. Gravimetric in vitro thrombolytic assays have also been used to this end. Lastly, a summary of the published results regarding the in vitro effects of various nanomaterials on the KKS, the PCS, and fibrinolysis is presented. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Simak, J (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 335, Rockville, MD 20852 USA. NR 117 TC 0 Z9 0 U1 2 U2 3 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE SN 2251-3965 BN 978-981-4390-26-2; 978-981-4390-25-5 J9 FRONT NANOBIOMED RES PY 2013 VL 1 BP 263 EP 291 D2 10.1142/8390 PG 29 WC Immunology; Nanoscience & Nanotechnology; Medicine, Research & Experimental; Materials Science, Biomaterials SC Immunology; Science & Technology - Other Topics; Research & Experimental Medicine; Materials Science GA BB1SW UT WOS:000341327400010 ER PT S AU Simak, J AF Simak, Jan BE Dobrovolskaia, MA McNeil, SE TI The Effects of Engineered Nanomaterials on Platelets SO HANDBOOK OF IMMUNOLOGICAL PROPERTIES OF ENGINEERED NANOMATERIALS SE Frontiers in Nanobiomedical Research LA English DT Article; Book Chapter ID CELL-MEMBRANE MICROPARTICLES; NANOTUBES ACTIVATE PLATELETS; EXTRACELLULAR CA2+ INFLUX; CORONARY-ARTERY-DISEASE; CARBON NANOTUBES; IN-VITRO; ANIMAL-MODELS; BLOOD COMPATIBILITY; DRUG-DELIVERY; SILVER NANOPARTICLES AB Platelets (PLTs) are small discoidal cells that are anucleated in mammals and circulate in the blood, where they play a critical role in hemostasis and thrombosis. PLT adhesion at the site of vascular injury and their activation and aggregation result in the formation of the primary hemostatic plug. This plug is enforced by a fibrin network structure as a result of the activation of the plasma coagulation system (PCS). Thus, PLTs, together with the PCS and vascular endothelial cells, maintain the hemocoagulation balance. Under physiological conditions, these systems prevent blood clotting, while in cases of vascular injury, they facilitate hemostasis to prevent blood loss. The dysregulation of hemocoagulation can lead to life-threatening thrombotic and/or bleeding pathologies. As various engineered nanomaterials that will come into contact with the blood are being designed for biomedical applications and other nanomaterials may reach the circulation as a result of occupational, environmental, or other routes of exposure, it is necessary to evaluate the effects of engineered nanomaterials on PLTs. In the introduction of this chapter, both the physiology of PLTs and the pathophysiology of the possible adverse effects of nanomaterials on PLTs are briefly described. Next, the methods that are used for the in vitro evaluation of the effects of nanomaterials on PLTs are reviewed. Screenings for the effects of nanomaterials on PLTs are generally based on PLT aggregation assays. These tests include cell counter-based assays, light transmission aggregometry, and impedance aggregometry. The adhesion of PLTs to nanomaterial surfaces is frequently monitored by scanning electron microscopy or light microscopy. Ultrastructural changes are examined using transmission electron microscopy. PLT membrane activation markers (CD62P, CD63, PAC-1) and the release of PLT membrane microparticles are analyzed by flow cytometry or via immunomicroscopic techniques. Soluble activation markers that are released by PLTs (e.g., beta TG, PF4, and TSP-1) are analyzed using ELISA. PLT integrity is assayed using a colorimetric lactate dehydrogenase (LDH) assay in the PLT supernatant. Other techniques are used to investigate the effects of nanomaterials on specific signaling pathways. Lastly, a summary of the published results regarding the in vitro effects of various nanomaterials on PLTs is presented. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Simak, J (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 335, Rockville, MD 20852 USA. EM jan.simak@fda.hhs.gov NR 158 TC 0 Z9 0 U1 3 U2 6 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE SN 2251-3965 BN 978-981-4390-26-2; 978-981-4390-25-5 J9 FRONT NANOBIOMED RES PY 2013 VL 1 BP 293 EP 356 D2 10.1142/8390 PG 64 WC Immunology; Nanoscience & Nanotechnology; Medicine, Research & Experimental; Materials Science, Biomaterials SC Immunology; Science & Technology - Other Topics; Research & Experimental Medicine; Materials Science GA BB1SW UT WOS:000341327400011 ER PT S AU Bancos, S Tyner, KM Weaver, JL AF Bancos, Simona Tyner, Katherine M. Weaver, James L. BE Dobrovolskaia, MA McNeil, SE TI Immunotoxicity Testing for Drug-Nanoparticle Conjugates: Regulatory Considerations SO HANDBOOK OF IMMUNOLOGICAL PROPERTIES OF ENGINEERED NANOMATERIALS SE Frontiers in Nanobiomedical Research LA English DT Article; Book Chapter ID IN-VIVO BIODISTRIBUTION; GOLD NANOPARTICLES; TITANIUM-DIOXIDE; PARTICLE-SIZE; COMPLEMENT; ACTIVATION; INJECTION; RATS; MICE AB Nanoscale materials are being developed for use in a wide variety of products including pharmaceuticals that are regulated by the U. S. Food and Drug Administration (FDA). Some of these represent reformulations of existing drugs or slow release degradable systems. A different category are drugs conjugated to durable nanoparticles (NPs), which do not degrade in the body. In all cases, these novel materials are subject to the same rules and regulations concerning drug development that apply to small molecules and therapeutic proteins. All drugs, including NP-drug conjugates, should be evaluated for immunotoxicity during development. This evaluation is governed by the ICH S8 guidance for small molecule drugs or by the ICH S6 guidance for protein drugs. These guidances continue to apply for drugs conjugated to NPs. Under S8, the primary level of evaluation is a weight of evidence review of the data collected in standard toxicology studies. If data suggestive of immunotoxicity are found, further focused studies may be needed. For proteins, the primary issue is drug hypersensitivity and samples should be collected from non-clinical studies to fully evaluate the role of any anti-drug antibodies. Several studies from CDER/FDA laboratories are used to illustrate how the principles described in the guidance documents could be applied in a real-world situation. C1 [Bancos, Simona; Tyner, Katherine M.; Weaver, James L.] US FDA, Div Drug Safety Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Weaver, JL (reprint author), US FDA, Div Drug Safety Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM james.weaver@fda.hhs.gov NR 38 TC 4 Z9 4 U1 0 U2 3 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE SN 2251-3965 BN 978-981-4390-26-2; 978-981-4390-25-5 J9 FRONT NANOBIOMED RES PY 2013 VL 1 BP 671 EP 685 D2 10.1142/8390 PG 15 WC Immunology; Nanoscience & Nanotechnology; Medicine, Research & Experimental; Materials Science, Biomaterials SC Immunology; Science & Technology - Other Topics; Research & Experimental Medicine; Materials Science GA BB1SW UT WOS:000341327400022 ER PT S AU Pfefer, J Fouad, A Chen, CW Gong, W Tomlins, P Woolliams, P Drezek, R Agrawal, A Chen, Y AF Pfefer, Joshua Fouad, Anthony Chen, Chao-Wei Gong, Wei Tomlins, Peter Woolliams, Peter Drezek, Rebekah Agrawal, Anant Chen, Yu BE Raghavachari, R Liang, R TI Multi-system Comparison of Optical Coherence Tomography Performance with Point Spread Function Phantoms SO DESIGN AND QUALITY FOR BIOMEDICAL TECHNOLOGIES VI SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Design and Quality for Biomedical Technologies VI CY FEB 02-03, 2013 CL San Francisco, CA SP SPIE DE image quality; optical coherence tomography; point spread function; phantom; spatial resolution ID OCT AB Point spread function (PSF) phantoms based on unstructured distributions of sub-resolution particles in a transparent matrix have proven effective for evaluating resolution and its spatial variation in optical coherence tomography (OCT) systems. Measurements based on PSF phantoms have the potential to become a standard test method for consistent, objective and quantitative inter-comparison of OCT system performance. Towards this end, we have evaluated three PSF phantoms and investigated their ability to compare the performance of four OCT systems. The phantoms are based on 260-nm-diameter gold nanoshells, submicron-diameter iron oxide particles and 1.5-micron-diameter silica particles. The OCT systems included spectral-domain and swept source systems in free-beam geometries as well as a time-domain system in both free-beam and fiberoptic probe geometries. Results indicated that iron oxide particles and gold nanoshells were most effective for measuring spatial variations in the magnitude and shape of PSFs across the image volume. The intensity of individual particles was also used to evaluate spatial variations in signal intensity uniformity. Significant system-to-system differences in resolution and signal intensity and their spatial variation were readily quantified. The phantoms proved useful for identification and characterization of irregularities such as astigmatism. Particle concentrations of 5000 per cubic millimeter or greater provided accurate determination of performance metrics. Our multi-system inter-comparison provides evidence of the effectiveness of PSF-phantom-based test methods for comparison of OCT system resolution and signal uniformity. C1 [Pfefer, Joshua; Fouad, Anthony; Chen, Chao-Wei; Gong, Wei; Agrawal, Anant] Food & Drug Adm, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Fouad, Anthony; Chen, Chao-Wei; Gong, Wei; Chen, Yu] Univ Maryland, Dept Bioengn, College Pk, MD 20742 USA. [Gong, Wei] Fujian Normal Univ, Coll Photon & Elect Engn, Fuzhou, Peoples R China. [Tomlins, Peter] Queen Mary Univ London, Barts & London Sch Med & Dent, London, England. [Woolliams, Peter] Natl Phys Lab, Nano & Multfunct Mat Grp, Teddington, Middx, England. [Drezek, Rebekah] Rice Univ, Dept Bioengn, Houston, TX 77251 USA. RP Pfefer, J (reprint author), Food & Drug Adm, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM joshua.pfefer@fda.hhs.gov FU NSF-FDA [CBET 1135514] FX This research was funded in part by the NSF-FDA Scholar in Residence Program (CBET 1135514). NR 17 TC 1 Z9 1 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9342-2 J9 PROC SPIE PY 2013 VL 8573 AR UNSP 85730C DI 10.1117/12.2007005 PG 10 WC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BB0RZ UT WOS:000340666700007 ER PT S AU Wang, QZ Le, D Ramella-Roman, JC Pfefer, J AF Wang, Quanzeng Le, Du Ramella-Roman, Jessica C. Pfefer, Joshua BE Raghavachari, R Liang, R TI Spectral Variations in Narrow Band Imaging Depth-Selectivity: Mucosal Scattering vs. Hemoglobin Absorption SO DESIGN AND QUALITY FOR BIOMEDICAL TECHNOLOGIES VI SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Design and Quality for Biomedical Technologies VI CY FEB 02-03, 2013 CL San Francisco, CA SP SPIE ID OPTICAL COHERENCE TOMOGRAPHY; BARRETTS-ESOPHAGUS; TISSUE; ENDOSCOPY; CANCER; SYSTEM; DISEASE; LESIONS; MODEL AB Spectral variations in contrast enhancement of mucosal vasculature are a key feature of narrow band imaging (NBI) devices. In prior NBI studies, the enhanced visualization of larger, deeper vessels with green light (e. g., 540 nm) relative to violet light (e. g., 415 nm) has often been attributed to the well-known monotonic decrease in scattering coefficient with wavelength in biological tissues. We have developed and implemented numerical and experimental approaches to elucidate and quantify this and other light-tissue interaction effects relevant to NBI. A Monte Carlo model incorporating vessel-like inclusions with a range of diameters (20 to 400 microns) and depths (20 to 400 microns) was used to predict reflectance and fluence distributions in the tissue and calculate vessel contrast values. These results were compared to experimental measurements based on a liquid phantom with a hemoglobin-filled capillary. By comparing results for cases representing mucosa regions with and without blood, we were able to evaluate the relative significance of absorption and scattering on spectral variations in depth-selectivity. Results indicate that at 415 nm, detection of superficial vasculature with NBI was almost entirely dependent on the absorption coefficient of the blood in the vessel of interest. The enhanced visualization of deep vessels at 540 nm bands relative to 415 nm was due primarily to absorption by the superficial vasculature rather than a decrease in scattering coefficient. While computationally intensive, our numerical modeling approach provides unique insights into the light propagation mechanisms underlying this emerging clinical imaging technology. C1 [Wang, Quanzeng; Le, Du; Pfefer, Joshua] Food & Drug Adm, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Le, Du; Ramella-Roman, Jessica C.] Catholic Univ Amer, Dept Biomed Engn, Washington, DC 20064 USA. RP Wang, QZ (reprint author), Food & Drug Adm, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM quanzeng.wang@fda.hhs.gov NR 28 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9342-2 J9 PROC SPIE PY 2013 VL 8573 AR UNSP 85730N DI 10.1117/12.2008768 PG 8 WC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BB0RZ UT WOS:000340666700009 ER PT J AU Blehar, MC Spong, C Grady, C Goldkind, SF Sahin, L Clayton, JA AF Blehar, Mary C. Spong, Catherine Grady, Christine Goldkind, Sara F. Sahin, Leyla Clayton, Janine A. TI Enrolling Pregnant Women: Issues in Clinical Research SO WOMENS HEALTH ISSUES LA English DT Article ID PEDIATRIC RESEARCH; PHARMACOKINETICS; STANDARDS; FRAMEWORK; ASSENT; HEALTH AB Background: Despite the fact that many pregnant women are affected by a range of serious health conditions and take medications for these conditions, there is widespread reticence to include them in clinical intervention research. Hence, their clinical care is typically not informed by evidence derived from pregnant populations. Method: In October 2010, the National Institutes of Health Office of Research on Women's Health convened a workshop to address ethical, regulatory, and scientific issues raised by the enrollment of pregnant women in clinical research. This report summarizes three areas that emerged from that meeting as important next steps to be taken to promote ethically responsible and scientifically sound research during pregnancy. Findings: The three areas are: 1) Reclassify pregnant women from their current status in regulations as a "vulnerable" population to a scientifically "complex" population and change the presumption of exclusion to one of inclusion; 2) examine the institutional review boards' (IRB) gatekeeper role in interpreting regulations governing pregnancy research and identify steps to facilitate IRB approval of ethically informed pregnancy research; and 3) develop a pregnancy-focused research agenda that addresses pressing clinical needs, identifies opportunities to gather information from existing resources and studies, and encourages important new research areas. Conclusion: Research is needed to address the therapeutic needs of pregnant women and to study pregnancy as it may shed light on a pregnant woman's later health and the health of her child. Published by Elsevier Inc. C1 [Blehar, Mary C.; Clayton, Janine A.] NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA. [Spong, Catherine] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Grady, Christine] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. [Goldkind, Sara F.] US FDA, Off Good Clin Practice, Off Commissioner, Silver Spring, MD USA. [Sahin, Leyla] US FDA, Maternal Hlth Team, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Blehar, MC (reprint author), NIH, Off Res Womens Hlth, US Dept HHS, 6707 Democracy Blvd,Suite 400,MSC 5484, Bethesda, MD 20892 USA. EM mary.blehar@nih.gov FU Intramural NIH HHS [Z99 OD999999] NR 30 TC 29 Z9 29 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JAN-FEB PY 2013 VL 23 IS 1 BP E39 EP E45 DI 10.1016/j.whi.2012.10.003 PG 7 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA AO1VX UT WOS:000341104700006 PM 23312713 ER PT J AU Powley, MW AF Powley, Mark W. BE Brock, WJ Hastings, KL McGown, KM TI Genetic Toxicology SO NONCLINICAL SAFETY ASSESSMENT: A GUIDE TO INTERNATIONAL PHARMACEUTICAL REGULATIONS LA English DT Article; Book Chapter ID GENOTOXICITY; SENSITIVITY; IMPURITIES; TESTS; ASSAY C1 US FDA, Off New Drugs, CDER, Silver Spring, MD 20993 USA. RP Powley, MW (reprint author), US FDA, Off New Drugs, CDER, Silver Spring, MD 20993 USA. NR 18 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-0-470-74591-5 PY 2013 BP 255 EP 264 D2 10.1002/9781118517000 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BA5WO UT WOS:000337044000015 ER PT S AU Hussain, AS AF Hussain, Ajaz S. BE Aguilar, JE TI Formulation tools for pharmaceutical development Foreword SO FORMULATION TOOLS FOR PHARMACEUTICAL DEVELOPMENT SE Woodhead Publishing Series in Biomedicine LA English DT Editorial Material; Book Chapter ID PRODUCT DEVELOPMENT C1 [Hussain, Ajaz S.] PMI, Newtown Sq, PA USA. [Hussain, Ajaz S.] Sandoz, Princeton, NJ USA. [Hussain, Ajaz S.] US FDA, Rockville, MD 20857 USA. [Hussain, Ajaz S.] Univ Cincinnati, Cincinnati, OH 45221 USA. [Hussain, Ajaz S.] Ohio No Univ, Lima, OH 45805 USA. [Hussain, Ajaz S.] Amer Assoc Pharmaceut Scientists, Arlington, VA USA. RP Hussain, AS (reprint author), Wockhardt Ltd, Bombay, Maharashtra, India. EM a2zpharmsci@msn.com NR 3 TC 0 Z9 0 U1 1 U2 1 PU WOODHEAD PUBL LTD PI CAMBRIDGE PA ABINGTON HALL ABINGTON, CAMBRIDGE CB1 6AH, CAMBS, ENGLAND SN 2050-0289 BN 978-1-908818-50-8; 978-1-907568-99-2 J9 WOODH PUB SER BIOMED PY 2013 IS 44 BP XXIII EP XXV D2 10.1533/9781908818508 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BA9NL UT WOS:000339617000001 ER PT J AU Tassinari, MS De Schaepdrijver, LM Hurtt, ME AF Tassinari, Melissa S. De Schaepdrijver, Luc M. Hurtt, Mark E. BE Brock, WJ Hastings, KL McGown, KM TI Juvenile Animal Toxicity Studies: Regulatory Expectations, Decision Strategies and Role in Paediatric Drug Development SO NONCLINICAL SAFETY ASSESSMENT: A GUIDE TO INTERNATIONAL PHARMACEUTICAL REGULATIONS LA English DT Article; Book Chapter ID SYSTEM; CHALLENGES; GROWTH; RATS C1 [Tassinari, Melissa S.] US FDA, Off New Drugs, CDER, Silver Spring, MD 20993 USA. [De Schaepdrijver, Luc M.] Johnson & Johnson Consumer Prod Inc, Antwerp, Belgium. [Hurtt, Mark E.] Pfizer, Groton, CT USA. RP Tassinari, MS (reprint author), US FDA, Off New Drugs, CDER, Silver Spring, MD 20993 USA. NR 34 TC 1 Z9 1 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-0-470-74591-5 PY 2013 BP 297 EP 311 D2 10.1002/9781118517000 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BA5WO UT WOS:000337044000017 ER PT J AU Ellis, CE Hartsough, MT Green, MD Ghantous, H AF Ellis, Christopher E. Hartsough, Melanie T. Green, Martin D. Ghantous, Hanan BE Brock, WJ Hastings, KL McGown, KM TI Nonclinical Safety Assessment: Biotechnology-Derived Pharmaceuticals SO NONCLINICAL SAFETY ASSESSMENT: A GUIDE TO INTERNATIONAL PHARMACEUTICAL REGULATIONS LA English DT Article; Book Chapter ID HUMANIZED ANTI-CD3 ANTIBODY; RECEPTOR; BINDING; CARCINOGENICITY; ARRESTINS; HUM291; CELLS; GRKS C1 [Ellis, Christopher E.; Ghantous, Hanan] US FDA, Off New Drugs, CDER, Silver Spring, MD 20993 USA. [Hartsough, Melanie T.] Biol Consulting Grp Inc, Derwood, MD USA. [Green, Martin D.] WOC2, DVRPA, OVRR, CBER FDA, Rockville, MD USA. RP Ellis, CE (reprint author), US FDA, Off New Drugs, CDER, Silver Spring, MD 20993 USA. NR 43 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-0-470-74591-5 PY 2013 BP 347 EP 379 D2 10.1002/9781118517000 PG 33 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BA5WO UT WOS:000337044000019 ER PT J AU Osterberg, RE Powley, MW AF Osterberg, Robert E. Powley, Mark W. BE Brock, WJ Hastings, KL McGown, KM TI Degradants, Impurities, Excipients and Metabolites SO NONCLINICAL SAFETY ASSESSMENT: A GUIDE TO INTERNATIONAL PHARMACEUTICAL REGULATIONS LA English DT Article; Book Chapter ID DRUG METABOLITES; SAFETY C1 [Osterberg, Robert E.] Osterberg Pharm Tox Consulting, Rockville, MD 20850 USA. [Powley, Mark W.] US FDA, Off New Drugs, CDER, Silver Spring, MD USA. RP Osterberg, RE (reprint author), Osterberg Pharm Tox Consulting, Rockville, MD 20850 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-0-470-74591-5 PY 2013 BP 431 EP 447 D2 10.1002/9781118517000 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BA5WO UT WOS:000337044000022 ER PT B AU Teixeira, A Ghai, G Almonacid, S AF Teixeira, Arthur Ghai, Gaurav Almonacid, Sergio BE Yanniotis, S Taoukis, P Stoforos, NG Karathanos, VT TI Advances and Challenges in Thermal Processing with Flexible Packages SO ADVANCES IN FOOD PROCESS ENGINEERING RESEARCH AND APPLICATIONS SE Food Engineering Series LA English DT Article; Book Chapter C1 [Teixeira, Arthur] Univ Florida, Gainesville, FL 32611 USA. [Ghai, Gaurav] US FDA, College Pk, MD USA. [Almonacid, Sergio] Univ Tecn Federico Santa Maria, Valparaiso, Chile. RP Teixeira, A (reprint author), Univ Florida, Gainesville, FL 32611 USA. EM atex@ufl.edu NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-7906-2; 978-1-4614-7905-5 J9 FOOD ENG SER PY 2013 BP 197 EP 207 DI 10.1007/978-1-4614-7906-2_11 D2 10.1007/978-1-4614-7906-2 PG 11 WC Food Science & Technology SC Food Science & Technology GA BA7CH UT WOS:000337395100012 ER PT S AU Gupta, A Khan, MA AF Gupta, Abhay Khan, Mansoor A. BE Repka, MA Langley, N DiNunzio, J TI Consistency of Pharmaceutical Products: An FDA Perspective on Hot-Melt Extrusion Process SO MELT EXTRUSION: MATERIALS, TECHNOLOGY AND DRUG PRODUCT DESIGN SE AAPS Advances in the Pharmaceutical Sciences Series LA English DT Article; Book Chapter ID RAMAN-SPECTROSCOPY; EXTRUDED FILMS; DRUG; LINE AB Hot-melt extrusion represents an efficient technology to formulate drugs with poor aqueous solubility into safe and effective drug delivery systems. The interest in this technology continues to grow as it is suitable for both high dose and potent low dose compounds. It is amenable to real-time monitoring and control of the consistency of the product with respect to content uniformity and crystalline conversion. Quality-by-design (QbD) has become an essential part of modern pharmaceutical quality systems since it incorporates an enhanced product and process understanding. It encourages real-time monitoring and control of critical material attributes and process parameters. The QbD paradigm can be easily incorporated into hot-melt processes. It has the potential to replace traditional batch processes due to its continuous nature and ease of scale-up from laboratory scale to commercial scale. C1 [Gupta, Abhay; Khan, Mansoor A.] US FDA, Div Prod Qual Res, Off Pharmaceut Scil, Silver Spring, MD USA. RP Khan, MA (reprint author), US FDA, Div Prod Qual Res, Off Pharmaceut Scil, Silver Spring, MD USA. EM mansoor.khan@fda.hhs.gov NR 23 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ARLINGTON PA 2107 WILSON BLVD, STE 700, ARLINGTON, VA 22201 USA SN 2210-7371 BN 978-1-4614-8431-8 J9 AAPS ADV PHARM SCI PY 2013 VL 9 BP 435 EP 445 DI 10.1007/978-1-4614-8432-5_17 D2 10.1007/978-1-4614-8432-5 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BA5OZ UT WOS:000336912000018 ER PT J AU Brown, R White, S Goode, J Pradeep, P Merrill, S AF Brown, Ronald White, Shannon Goode, Jennifer Pradeep, Prachi Merrill, Stephen GP ASME TI Use of QSAR Modeling to Predict the Carcinogenicity of Color Additives SO ASME 2013 CONFERENCE ON FRONTIERS IN MEDICAL DEVICES: APPLICATIONS OF COMPUTER MODELING AND SIMULATION LA English DT Proceedings Paper CT ASME Conference on Frontiers in Medical Devices - Applications of Computer Modeling and Simulation (FMD) CY SEP 11-13, 2013 CL Washington, DC SP ASME, Bioengineering Div ID DATABASES; FOOD AB Patients may be exposed to potentially carcinogenic color additives released from polymers used to manufacture medical devices; therefore, the need exists to adequately assess the safety of these compounds. The US FDA Center for Devices and Radiological Health (CDRH) recently issued draft guidance that, when final, will include FDA's recommendations for the safety evaluation of color additives and other potentially toxic chemical entities that may be released from device materials. Specifically, the draft guidance outlines an approach that calls for evaluating the potential for the color additive to be released from the device in concert with available toxicity information about the additive to determine what types of toxicity information, if any, are necessary. However, when toxicity data are not available from the literature for the compounds of interest, a scientific rationale can sometimes be provided for omission of these tests. Although the FDA has issued draft guidance on this topic, the Agency continues to explore alternative approaches to understand when additional toxicity testing is needed to assure the safety of medical devices that contain color additives. An emerging approach that may be useful for determining the need for further testing of compounds released from device materials is Quantitative Structure Activity Relationship (QSAR) modeling. In this paper, we have shown how three publically available QSAR models (OpenTox/Lazar, Toxtree, and the OECD Toolbox) are able to successfully predict the carcinogenic potential of a set of color additives with a wide range of structures. As a result, this computational modeling approach may serve as a useful tool for determining the need to conduct carcinogenicity testing of color additives intended for use in medical devices. C1 [Brown, Ronald; White, Shannon; Goode, Jennifer; Merrill, Stephen] US FDA, CDRH, Silver Spring, MD 20993 USA. RP Brown, R (reprint author), US FDA, CDRH, Silver Spring, MD 20993 USA. OI Pradeep, Prachi/0000-0002-9219-4249 NR 6 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-5600-0 PY 2013 AR V001T10A044 DI 10.1115/FMD2013-16161 PG 2 WC Engineering, Biomedical; Engineering, Mechanical SC Engineering GA BA6CX UT WOS:000337098700076 ER PT J AU Donaldson, FE Coburn, JC AF Donaldson, Finn E. Coburn, James C. GP ASME TI STOCHASTIC SIMULATION OF MODULAR CONNECTIONS IN TOTAL HIP REPLACEMENT SO ASME 2013 CONFERENCE ON FRONTIERS IN MEDICAL DEVICES: APPLICATIONS OF COMPUTER MODELING AND SIMULATION LA English DT Proceedings Paper CT ASME Conference on Frontiers in Medical Devices - Applications of Computer Modeling and Simulation (FMD) CY SEP 11-13, 2013 CL Washington, DC SP ASME, Bioengineering Div ID MORSE TAPER; IMPLANTS C1 [Donaldson, Finn E.; Coburn, James C.] US FDA, Div Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth,Off Med Prod & Tobacco, Silver Spring, MD 20993 USA. RP Donaldson, FE (reprint author), US FDA, Div Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth,Off Med Prod & Tobacco, Silver Spring, MD 20993 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-5600-0 PY 2013 AR V001T11A001 DI 10.1115/FMD2013-16078 PG 2 WC Engineering, Biomedical; Engineering, Mechanical SC Engineering GA BA6CX UT WOS:000337098700087 ER PT J AU Duraiswamy, N Ekrami, Y Weaver, J Retta, S Wu, CF AF Duraiswamy, Nandini Ekrami, Yasamin Weaver, Jason Retta, Stephen Wu, Changfu GP ASME TI NON-CIRCULAR CONFIGURATIONS INCREASE HEART VALVE LEAFLET STRESSES AND ALTER LEAFLET KINEMATICS - A COMPUTATIONAL APPROACH SO ASME 2013 CONFERENCE ON FRONTIERS IN MEDICAL DEVICES: APPLICATIONS OF COMPUTER MODELING AND SIMULATION LA English DT Proceedings Paper CT ASME Conference on Frontiers in Medical Devices - Applications of Computer Modeling and Simulation (FMD) CY SEP 11-13, 2013 CL Washington, DC SP ASME, Bioengineering Div C1 [Duraiswamy, Nandini; Ekrami, Yasamin; Weaver, Jason; Retta, Stephen; Wu, Changfu] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Off Device Evaluat, Silver Spring, MD 20993 USA. RP Duraiswamy, N (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Off Device Evaluat, Silver Spring, MD 20993 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-5600-0 PY 2013 AR V001T10A050 DI 10.1115/FMD2013-16191 PG 2 WC Engineering, Biomedical; Engineering, Mechanical SC Engineering GA BA6CX UT WOS:000337098700082 ER PT J AU Kar, D Saylor, DM AF Kar, Debashis Saylor, David M. GP ASME TI A DIFFUSE INTERFACE MODEL TO SIMULATE ELECTROCHEMICAL RESPONSE OF MEDICAL IMPLANT MATERIALS SO ASME 2013 CONFERENCE ON FRONTIERS IN MEDICAL DEVICES: APPLICATIONS OF COMPUTER MODELING AND SIMULATION LA English DT Proceedings Paper CT ASME Conference on Frontiers in Medical Devices - Applications of Computer Modeling and Simulation (FMD) CY SEP 11-13, 2013 CL Washington, DC SP ASME, Bioengineering Div C1 [Kar, Debashis; Saylor, David M.] US FDA, Div Chem & Mat Sci, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Kar, D (reprint author), US FDA, Div Chem & Mat Sci, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Debashis.Kar@fda.hhs.gov NR 2 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-5600-0 PY 2013 AR V001T10A003 DI 10.1115/FMD2013-16020 PG 2 WC Engineering, Biomedical; Engineering, Mechanical SC Engineering GA BA6CX UT WOS:000337098700035 ER PT J AU Park, BS Rajan, SS Angelone, LM AF Park, Bu S. Rajan, Sunder S. Angelone, Leonardo M. GP ASME TI A New Method to Concentrate Electromagnetic Field within ROI Using a High Dielectric Material in 3T Body MRI SO ASME 2013 CONFERENCE ON FRONTIERS IN MEDICAL DEVICES: APPLICATIONS OF COMPUTER MODELING AND SIMULATION LA English DT Proceedings Paper CT ASME Conference on Frontiers in Medical Devices - Applications of Computer Modeling and Simulation (FMD) CY SEP 11-13, 2013 CL Washington, DC SP ASME, Bioengineering Div AB We present numerical simulation results showing that high dielectric materials (HDMs) when placed between the human body model and the body coil significantly alter the electromagnetic field inside the body. The numerical simulation results show that the electromagnetic field (E, B, and SAR) within a region of interest (ROI) is concentrated (increased). In addition, the average electromagnetic fields decreased significantly outside the region of interest. The calculation results using a human body model and HDM of Barium Strontium Titanate (BST) show that the mean local SAR was decreased by about 56% (i.e., 18.7 vs. 8.2 W/kg) within the body model. C1 [Park, Bu S.; Rajan, Sunder S.; Angelone, Leonardo M.] US FDA, Silver Spring, MD 20993 USA. RP Park, BS (reprint author), US FDA, Silver Spring, MD 20993 USA. EM bu.park@fda.hhs.gov OI Angelone, Leonardo/0000-0002-1105-021X NR 6 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-5600-0 PY 2013 AR V001T10A034 DI 10.1115/FMD2013-16135 PG 2 WC Engineering, Biomedical; Engineering, Mechanical SC Engineering GA BA6CX UT WOS:000337098700066 ER PT J AU Park, BS Guag, JW Angelone, LM Rajan, SS AF Park, Bu S. Guag, Joshua W. Angelone, Leonardo M. Rajan, Sunder S. GP ASME TI A Novel Method to Decrease Electric Field and SAR using an External High Dielectric Sleeve at 3T Head MRI : Numerical and Experimental Results SO ASME 2013 CONFERENCE ON FRONTIERS IN MEDICAL DEVICES: APPLICATIONS OF COMPUTER MODELING AND SIMULATION LA English DT Proceedings Paper CT ASME Conference on Frontiers in Medical Devices - Applications of Computer Modeling and Simulation (FMD) CY SEP 11-13, 2013 CL Washington, DC SP ASME, Bioengineering Div AB We present experimental and numerical simulation results showing that high dielectric materials (HDMs) located outside of a RF head coil decrease the electric field (E-field, |E|) with minimum change of the RF magnetic field (B-1(+)) at 3T MRI imaging. Compared to previous research using HDMs located between the RF coil and sample, our method locating the HDM outside the coil allowed an increased sample size and more flexibility of HDM thickness optimization. Numerical simulation results showed more than 30% decrease in the local SAR at the boundary region of the head model. Validating experimental results showed a 21% decrease in the maximum |E-total| using a HDM made of distilled water. C1 [Park, Bu S.; Guag, Joshua W.; Angelone, Leonardo M.; Rajan, Sunder S.] US FDA, Silver Spring, MD 20993 USA. RP Park, BS (reprint author), US FDA, Silver Spring, MD 20993 USA. EM bu.park@fda.hhs.gov OI Angelone, Leonardo/0000-0002-1105-021X NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-5600-0 PY 2013 AR V001T05A004 DI 10.1115/FMD2013-16133 PG 2 WC Engineering, Biomedical; Engineering, Mechanical SC Engineering GA BA6CX UT WOS:000337098700016 ER PT S AU Woods, JW Burkhardt, W AF Woods, J. W. Burkhardt, W., III BE Cook, N TI Preventing and controlling viral contamination of shellfish SO VIRUSES IN FOOD AND WATER: RISKS, SURVEILLANCE AND CONTROL SE Woodhead Publishing in Food Science Technology and Nutrition LA English DT Article; Book Chapter DE enteric viruses; shellfish; norovirus; detection; mitigation ID HEPATITIS-A VIRUS; ENTERIC VIRUSES; UNITED-STATES; MOLLUSCAN SHELLFISH; FOODBORNE OUTBREAK; ESCHERICHIA-COLI; OYSTERS; GASTROENTERITIS; NOROVIRUS; DEPURATION AB A significant proportion of infectious foodborne illnesses worldwide can be attributed to human enteric viruses. Bivalve molluscan shellfish can act as vehicles for transmission of enteric viruses. Viruses accumulate in shellfish digestive diverticula and can infect humans upon ingestion of raw or undercooked shellfish meat. The use of indicator bacteria as an index of fecal contamination in shellfish growing areas reduced bacterial gastrointestinal infections but this practice is believed to have limited predictive value for enteric viral pathogen contamination. Mitigation strategies such as depuration or relaying exist to reduce or eliminate potential enteric virus hazards associated with consumption of raw or undercooked shellfish. C1 [Woods, J. W.; Burkhardt, W., III] US FDA, Ctr Food Safety & Appl Nutr, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Woods, JW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Gulf Coast Seafood Lab, 1 Iberville Dr, Dauphin Isl, AL 36528 USA. EM Jacquelina.woods@fda.hhs.gov NR 43 TC 1 Z9 1 U1 0 U2 2 PU WOODHEAD PUBL LTD PI CAMBRIDGE PA ABINGTON HALL ABINGTON, CAMBRIDGE CB1 6AH, CAMBS, ENGLAND SN 2042-8049 BN 978-0-85709-887-0; 978-0-85709-430-8 J9 WOODHEAD PUBL FOOD S JI Woodhead Publ. Food Sci. Technol. Nutr. PY 2013 IS 249 BP 281 EP 292 DI 10.1533/9780857098870.3.281 PG 12 WC Food Science & Technology; Virology SC Food Science & Technology; Virology GA BA2TQ UT WOS:000333896700014 ER PT J AU Bennett, RW Hait, JM Tallent, SM AF Bennett, Reginald W. Hait, Jennifer M. Tallent, Sandra M. BE Labbe, RG Garcia, S TI Staphylococcus aureus SO GUIDE TO FOODBORNE PATHOGENS, 2ND EDITION LA English DT Article; Book Chapter C1 [Bennett, Reginald W.] US FDA, Off Regulatory Sci, College Pk, MD 20740 USA. [Hait, Jennifer M.; Tallent, Sandra M.] US FDA, Div Microbiol, College Pk, MD USA. RP Bennett, RW (reprint author), US FDA, Off Regulatory Sci, College Pk, MD 20740 USA. NR 27 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-67142-9 PY 2013 BP 26 EP 44 D2 10.1002/9781118684856 PG 19 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BA1JE UT WOS:000332637700002 ER PT J AU Ricke, SC Koo, OK Foley, S Nayak, R AF Ricke, Steven C. Koo, Ok-Kyung Foley, Steven Nayak, Rajesh BE Labbe, RG Garcia, S TI Salmonella SO GUIDE TO FOODBORNE PATHOGENS, 2ND EDITION LA English DT Article; Book Chapter ID ENTERICA SEROVAR TYPHIMURIUM; CHAIN FATTY-ACIDS; REAL-TIME PCR; SEROTYPE JAVIANA INFECTIONS; FIELD GEL-ELECTROPHORESIS; ENTERITIDIS PHAGE TYPE-4; HEP-2 CELL ASSOCIATION; TANDEM REPEAT ANALYSIS; ESCHERICHIA-COLI O157; III SECRETION SYSTEM C1 [Ricke, Steven C.; Koo, Ok-Kyung] Univ Arkansas, Dept Food Sci, Fayetteville, AR 72703 USA. [Koo, Ok-Kyung] Korea Food Res Inst, Food Safety Res Grp, Songnam, Gyeonggi Do, South Korea. [Foley, Steven; Nayak, Rajesh] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Ricke, SC (reprint author), Univ Arkansas, Dept Food Sci, Fayetteville, AR 72703 USA. NR 285 TC 6 Z9 6 U1 1 U2 3 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-67142-9 PY 2013 BP 112 EP 137 D2 10.1002/9781118684856 PG 26 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BA1JE UT WOS:000332637700007 ER PT J AU Lampel, KA AF Lampel, Keith A. BE Labbe, RG Garcia, S TI Shigella species SO GUIDE TO FOODBORNE PATHOGENS, 2ND EDITION LA English DT Article; Book Chapter ID ENTEROINVASIVE-ESCHERICHIA-COLI; MOLECULAR EVOLUTIONARY HISTORY; COMPLETE GENOME SEQUENCE; LARGE VIRULENCE PLASMID; FLEXNERI 2A; DYSENTERY; SPP.; PATHOGENICITY; CHILDREN; SONNEI C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Lampel, KA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 33 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-67142-9 PY 2013 BP 138 EP 147 D2 10.1002/9781118684856 PG 10 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BA1JE UT WOS:000332637700008 ER PT J AU Feng, P AF Feng, Peter BE Labbe, RG Garcia, S TI Escherichia coli SO GUIDE TO FOODBORNE PATHOGENS, 2ND EDITION LA English DT Article; Book Chapter ID O157-H-STRAINS; GENE; IDENTIFICATION; PATHOGENESIS; INFECTION; SEROTYPE; ANTIGEN; PRODUCE C1 US FDA, College Pk, MD 20740 USA. RP Feng, P (reprint author), US FDA, College Pk, MD 20740 USA. NR 29 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-67142-9 PY 2013 BP 222 EP 240 D2 10.1002/9781118684856 PG 19 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BA1JE UT WOS:000332637700014 ER PT J AU Yan, QQ Power, KA Tall, BD Fanning, S AF Yan, Qiongqiong Power, Karen A. Tall, Ben D. Fanning, Seamus BE Labbe, RG Garcia, S TI Cronobacter spp. (formerly Enterobacter sakazakii) SO GUIDE TO FOODBORNE PATHOGENS, 2ND EDITION LA English DT Article; Book Chapter ID POWDERED INFANT FORMULA; MICROVASCULAR ENDOTHELIAL-CELLS; LIPOPOLYSACCHARIDE O-ANTIGEN; COMPLETE GENOME SEQUENCE; INTENSIVE-CARE-UNIT; MEMBRANE PROTEIN-A; DUBLINENSIS SP-NOV; 16S RIBOSOMAL-RNA; REAL-TIME-PCR; FAMILY ENTEROBACTERIACEAE C1 [Yan, Qiongqiong; Power, Karen A.; Fanning, Seamus] Univ Coll Dublin, UCD Ctr Food Safety, Sch Publ Hlth Physiotherapy & Populat Sci, Dublin 2, Ireland. [Tall, Ben D.] US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. RP Yan, QQ (reprint author), Univ Coll Dublin, UCD Ctr Food Safety, Sch Publ Hlth Physiotherapy & Populat Sci, Dublin 2, Ireland. NR 110 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-67142-9 PY 2013 BP 241 EP 256 D2 10.1002/9781118684856 PG 16 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BA1JE UT WOS:000332637700015 ER PT J AU Hungerford, JM AF Hungerford, James M. BE Labbe, RG Garcia, S TI Seafood toxins SO GUIDE TO FOODBORNE PATHOGENS, 2ND EDITION LA English DT Article; Book Chapter C1 US FDA, Appl Technol Ctr, Pacific Reg Lab Northwest, Bothell, WA 98021 USA. RP Hungerford, JM (reprint author), US FDA, Appl Technol Ctr, Pacific Reg Lab Northwest, Bothell, WA 98021 USA. NR 7 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-67142-9 PY 2013 BP 377 EP 398 D2 10.1002/9781118684856 PG 22 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BA1JE UT WOS:000332637700023 ER PT S AU Pogribny, IP Rusyn, I AF Pogribny, Igor P. Rusyn, Ivan BE Karpf, AR TI Environmental Toxicants, Epigenetics, and Cancer SO EPIGENETIC ALTERATIONS IN ONCOGENESIS SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID ACTIVE DNA DEMETHYLATION; GENE O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; INDUCED MALIGNANT-TRANSFORMATION; HELICOBACTER-PYLORI INFECTION; TERM TAMOXIFEN EXPOSURE; PROMOTER HYPERMETHYLATION; ARSENIC EXPOSURE; HEPATOCELLULAR-CARCINOMA; GENOMIC HYPOMETHYLATION; GASTRIC MUCOSAE AB Tumorigenesis, a complex and multifactorial progressive process of transformation of normal cells into malignant cells, is characterized by the accumulation of multiple cancer-specific heritable phenotypes triggered by the mutational and/or non-mutational (i.e., epigenetic) events. Accumulating evidence suggests that environmental and occupational exposures to natural substances, as well as man-made chemical and physical agents, play a causative role in human cancer. In a broad sense, carcinogenesis may be induced through either genotoxic or non-genotoxic mechanisms; however, both genotoxic and non-genotoxic carcinogens also cause prominent epigenetic changes. This review presents current evidence of the epigenetic alterations induced by various chemical carcinogens, including arsenic, 1,3-butadine, and pharmaceutical and biological agents, and highlights the potential for epigenetic changes to serve as markers for carcinogen exposure and cancer risk assessment. C1 [Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 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 NIEHS NIH HHS [R01 ES023195] NR 143 TC 30 Z9 34 U1 0 U2 24 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4419-9966-5; 978-1-4419-9967-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2013 VL 754 BP 215 EP 232 DI 10.1007/978-1-4419-9967-2_11 D2 10.1007/978-1-4419-9967-2 PG 18 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA BA2EY UT WOS:000333353300012 PM 22956504 ER PT S AU Hunter, GW AF Hunter, Gregory W. BE Kolhe, P Shah, M Rathore, N TI Basics of Sterilization Methods SO STERILE PRODUCT DEVELOPMENT: FORMULATION, PROCESS, QUALITY AND REGULATORY CONSIDERATIONS SE AAPS Advances in the Pharmaceutical Sciences Series LA English DT Article; Book Chapter ID ETHYLENE-OXIDE; TEMPERATURE AB The manufacturing of parenteral formulations should include a sterilization step in order to maintain product quality. How the most common sterilization techniques are performed and some of the advantages and disadvantages of each type will be summarized. Sterilization methods that will be covered include the fundamentals of steam, radiation, and ethylene oxide terminal sterilizations, as well as aseptic processing. Once a sterilization cycle or procedure has been chosen and developed, its effectiveness should be validated according to the guidelines of the respective authorities. Some of the documentation that regulators may review to decide whether they believe a method is acceptable is summarized in this chapter. While regional regulatory authorities may differ on what types of information should be submitted to their agencies and what should be reviewed during field inspections of a manufacturing facility, the focus for this chapter will be validation information and Good Manufacturing Practices aspects of sterilization techniques. C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Hunter, GW (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl, Rockville, MD 20855 USA. EM Gregory.Hunter@fda.hhs.gov NR 48 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2210-7371 BN 978-1-4614-7978-9; 978-1-4614-7977-2 J9 AAPS ADV PHARM SCI PY 2013 VL 6 BP 475 EP 500 DI 10.1007/978-1-4614-7978-9_18 D2 10.1007/978-1-4614-7978-9 PG 26 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BA1NC UT WOS:000332725800019 ER PT J AU Taylor, DR AF Taylor, Deborah R. TI Evolution of cell culture systems for HCV SO ANTIVIRAL THERAPY LA English DT Review ID HEPATITIS-C-VIRUS; DENSITY-LIPOPROTEIN RECEPTOR; LONG-TERM CULTURES; INFECTED IN-VITRO; RNA REPLICATION; EFFICIENT REPLICATION; DC-SIGN; INTERFERON SENSITIVITY; SUBGENOMIC REPLICON; CANDIDATE RECEPTOR AB Many challenges exist for the study of HCV in the laboratory. Therapy using interferon (IFN) is expensive, not well tolerated and ineffective for many patients. HCV research has been hampered by the lack of a robust tissue culture system, but recent advances have made virus growth in culture possible. Cell culture systems using genetically engineered viruses have been reviewed extensively, but here we review recent advances made in the use of natural isolates and the molecular challenges that have been used to overcome the limitations in their growth. Six major genotypes have been identified for HCV that are further divided into numerous subtypes. Combination therapy utilizing IFN-alpha and ribavirin is the standard of care, but is successful in only one-half of patients. The reasons for IFN resistance may be viral-or host-related and may be due to multiple factors. Recently, telaprevir and boceprevir, together with IFN-alpha and ribavirin, have been added to the standard of care in patients infected with IFN-resistant genotypes. A major obstacle in the development of effective vaccines and improved therapeutics has been the lack of a reproducible and efficient tissue culture system for propagation of HCV. Many cell culture systems have used genetically-engineered viruses to gain growth in culture through the use of replicons, but recent advances using natural isolates may improve the outlook for progress in HCV research. C1 US FDA, Ctr Biol & Evaluat, Bethesda, MD 20014 USA. RP Taylor, DR (reprint author), US FDA, Ctr Biol & Evaluat, Bethesda, MD 20014 USA. EM Deborah.Taylor@FDA.HHS.gov NR 52 TC 5 Z9 6 U1 0 U2 5 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2013 VL 18 IS 3 BP 523 EP 530 DI 10.3851/IMP2593 PN B PG 8 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA AG2FM UT WOS:000335231500014 PM 23792335 ER PT S AU Wang, QZ Desai, VN Ngo, YZ Cheng, WC Pfefer, J AF Wang, Quanzeng Desai, Viraj N. Ngo, Ying Z. Cheng, Wei-Chung Pfefer, Joshua BE Wang, Y Yuan, X Sheng, Y Tatsuno, K TI Towards Standardized Assessment of Endoscope Optical Performance: Geometric Distortion SO 2013 INTERNATIONAL CONFERENCE ON OPTICAL INSTRUMENTS AND TECHNOLOGY: OPTICAL SYSTEMS AND MODERN OPTOELECTRONIC INSTRUMENTS SE Proceedings of SPIE LA English DT Proceedings Paper CT International Conference on Optical Instruments and Technology - Optical Systems and Modern Optoelectronic Instruments CY NOV 17-19, 2013 CL Beijing, PEOPLES R CHINA SP China Instrument & Control Soc, SPIE DE endoscope; radial distortion; spatial resolution; optical performance; USAF 1951 target; slanted edge; optical imaging; standardization AB Technological advances in endoscopes, such as capsule, ultrathin and disposable devices, promise significant improvements in safety, clinical effectiveness and patient acceptance. Unfortunately, the industry lacks test methods for preclinical evaluation of key optical performance characteristics (OPCs) of endoscopic devices that are quantitative, objective and well-validated. As a result, it is difficult for researchers and developers to compare image quality and evaluate equivalence to, or improvement upon, prior technologies. While endoscope OPCs include resolution, field of view, and depth of field, among others, our focus in this paper is geometric image distortion. We reviewed specific test methods for distortion and then developed an objective, quantitative test method based on well-defined experimental and data processing steps to evaluate radial distortion in the full field of view of an endoscopic imaging system. Our measurements and analyses showed that a second-degree polynomial equation could well describe the radial distortion curve of a traditional endoscope. The distortion evaluation method was effective for correcting the image and can be used to explain other widely accepted evaluation methods such as picture height distortion. Development of consensus standards based on promising test methods for image quality assessment, such as the method studied here, will facilitate clinical implementation of innovative endoscopic devices. C1 [Wang, Quanzeng; Desai, Viraj N.; Ngo, Ying Z.; Cheng, Wei-Chung; Pfefer, Joshua] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Wang, QZ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM quanzeng.wang@fda.hhs.gov NR 14 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9960-8 J9 PROC SPIE PY 2013 VL 9042 AR 904205 DI 10.1117/12.2044103 PG 8 WC Engineering, Electrical & Electronic; Instruments & Instrumentation; Optics SC Engineering; Instruments & Instrumentation; Optics GA BA1SK UT WOS:000333046400005 ER PT B AU Yin, JJ Zhao, BZ Xia, QS Fu, PP AF Yin, Jun-Jie Zhao, Baozhong Xia, Qingsu Fu, Peter P. BE Liang, XJ TI Electron Spin Resonance Spectroscopy for Studying the Generation and Scavenging of Reactive Oxygen Species by Nanomaterials SO NANOPHARMACEUTICS: THE POTENTIAL APPLICATION OF NANOMATERIALS LA English DT Article; Book Chapter DE Electron spin resonance; nanomaterials; reactive oxygen species; free radical ID SINGLET OXYGEN; LIPID-PEROXIDATION; OXIDATIVE STRESS; FREE-RADICALS; CONCENTRATION PRODUCTS; POLYHYDROXYLATED C-60; UVA PHOTOIRRADIATION; WHEAT ANTIOXIDANTS; CANCER-THERAPY; IN-VITRO AB One fundamental mechanism widely described for nanotoxicity involves oxidative damage due to generation of free radicals and other reactive oxygen species. Indeed, the ability of nanoscale materials to facilitate the transfer of electrons, and thereby promote oxidative damage or in some instances provide antioxidant protection, may be a fundamental property of these materials. Any assessment of a nanoscale material's safety must therefore consider the potential for toxicity arising from oxidative damage. Therefore, rapid and predictive methods are needed to assess oxidative damage elicited by nanoscale materials. The use of electron spin resonance (ESR) to study free radical related bioactivity of nanomaterials has several advantages for free radical determination and identification. Specifically it can directly assess antioxidant quenching or prooxidant generation of relevant free radicals and reactive oxygen species. In this chapter, we have reported some nonclassical behaviors of the electron spin relaxation properties of unpaired electrons in different fullerenes and the investigation of anti/prooxidant activity by various types of nanomaterials using ESR. In addition, we have reviewed the mechanisms of free radical formation photosensitized by different nanomaterials. This chapter also included the use of spin labels, spin traps and ESR oximetry to systematically examine the enzymatic mimetic activities of nanomaterials. C1 [Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Zhao, Baozhong; Fu, Peter P.] NIEHS, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA. [Xia, Qingsu] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Yin, JJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM junjie.yin@fda.hhs.gov NR 86 TC 1 Z9 1 U1 0 U2 4 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 978-981-4368-67-4; 978-981-4368-66-7 PY 2013 BP 375 EP 400 PG 26 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology; Materials Science, Biomaterials; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics; Materials Science; Pharmacology & Pharmacy GA BA2AS UT WOS:000333214900015 ER PT S AU Zhang, L Huang, SM AF Zhang, Lei Huang, Shiew-Mei BE Sugiyama, Y Steffansen, B TI The Role of Transporters in Drug Development: Regulatory Science Perspectives from the FDA SO TRANSPORTERS IN DRUG DEVELOPMENT: DISCOVERY, OPTIMIZATION, CLINICAL STUDY AND REGULATION SE AAPS Advances in the Pharmaceutical Sciences Series LA English DT Article; Book Chapter ID SALT EXPORT PUMP; FAMILIAL INTRAHEPATIC CHOLESTASIS; CANCER RESISTANCE PROTEIN; GP INHIBITION DATA; HEALTHY-VOLUNTEERS; BREAST-CANCER; BILE-ACID; CLINICAL PHARMACOKINETICS; TRANSPLANT RECIPIENTS; SUBSTRATE-SPECIFICITY AB Pharmacokinetic drug interactions can lead to altered systemic exposure and varied drug response. Evaluation of a new molecular entity's (NME's) drug-drug interaction (DDI) potential is therefore an integral part of drug development and regulatory review prior to its market approval. Transporters are expressed in varying abundance in all tissues in the body where they govern the access of molecules to cells or their exit from cells, thereby controlling the overall distribution of drugs to their intracellular site of action. Clinically relevant interactions mediated by transporters are of increasing interest in drug development. Research in this emerging area has revealed that drug transporters, acting alone or in concert with drug metabolizing enzymes, can play an important role in modulating drug absorption, distribution, metabolism, and excretion, thus affecting the pharmacokinetics and/or pharmacodynamics of a drug. The newly published draft drug interaction guidance by the Food and Drug Administration (FDA) in 2012 includes updated recommendations in addressing transporter-mediated drug interactions with various decision trees to help guide drug development and regulatory review. This chapter discusses, from a scientific perspective, role of transporters in drug development with a focus on transporter-mediated DDIs. First, transporter-related recommendations in the recent FDA's draft drug interaction guidance are discussed. Second, additional transporters that are emerging to be important in drug disposition are discussed. Third, recent review examples and transporter-related labelings are presented. Finally, future directions are discussed. C1 [Zhang, Lei; Huang, Shiew-Mei] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Zhang, L (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM leik.zhang@fda.hhs.gov NR 66 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2210-7371 BN 978-1-4614-8229-1; 978-1-4614-8228-4 J9 AAPS ADV PHARM SCI PY 2013 VL 7 BP 249 EP 275 DI 10.1007/978-1-4614-8229-1_11 D2 10.1007/978-1-4614-8229-1 PG 27 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BA0CC UT WOS:000331001600012 ER PT J AU Mulberg, AE Mathis, LL Dunne, J Murphy, D AF Mulberg, Andrew E. Mathis, Lisa L. Dunne, Julia Murphy, Dianne BE Mulberg, AE Murphy, D Dunne, J Mathis, LL TI Introduction: Pediatric Drug Development and Therapeutics: Continued Progress for Better Drugs for Children SO PEDIATRIC DRUG DEVELOPMENT: CONCEPTS AND APPLICATIONS, 2ND EDITION LA English DT Editorial Material; Book Chapter C1 [Mulberg, Andrew E.] US FDA, Div Gastroenterol & Inborn Error Prod, Off Drug Evaluat 3, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Mathis, Lisa L.] Amgen Inc, Thousand Oaks, CA 91320 USA. [Dunne, Julia] Regulatory Agcy, VRMM, Med & Healthcare Prod, London, England. [Murphy, Dianne] US FDA, Off Pediat, Off Commissioner, Silver Spring, MD USA. RP Mulberg, AE (reprint author), US FDA, Div Gastroenterol & Inborn Error Prod, Off Drug Evaluat 3, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-31206-3 PY 2013 BP 3 EP 5 D2 10.1002/9781118312087 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJR82 UT WOS:000329855800002 ER PT J AU Mulberg, AE AF Mulberg, Andrew E. BE Mulberg, AE Murphy, D Dunne, J Mathis, LL TI Pediatric Drug Development Concepts and Applications Preface SO PEDIATRIC DRUG DEVELOPMENT: CONCEPTS AND APPLICATIONS, 2ND EDITION LA English DT Editorial Material; Book Chapter C1 [Mulberg, Andrew E.] US FDA, Div Gastroenterol & Inborn Error Prod, Off Drug Evaluat 3, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Mulberg, AE (reprint author), US FDA, Div Gastroenterol & Inborn Error Prod, Off Drug Evaluat 3, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 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, WEST SUSSEX, ENGLAND BN 978-1-118-31206-3 PY 2013 BP XIII EP XIV D2 10.1002/9781118312087 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJR82 UT WOS:000329855800001 ER PT J AU Roth-Cline, MD Nelson, RM AF Roth-Cline, Michelle D. Nelson, Robert M. BE Mulberg, AE Murphy, D Dunne, J Mathis, LL TI Ethical and Practical Considerations in Conducting Neonatal Research SO PEDIATRIC DRUG DEVELOPMENT: CONCEPTS AND APPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter ID RANDOMIZED CONTROLLED-TRIALS; ADVERSE DRUG-REACTIONS; INTENSIVE-CARE-UNIT; OFF-LABEL; INFORMED-CONSENT; RESUSCITATION RESEARCH; CLINICAL ANESTHESIA; SURGERY RESEARCH; PRETERM INFANTS; CHILDREN C1 [Roth-Cline, Michelle D.] US FDA, Off Pediat Therapeut, Silver Spring, MD 20993 USA. [Nelson, Robert M.] US FDA, Off Pediat Therapeut, Off Commissioner, Silver Spring, MD USA. RP Roth-Cline, MD (reprint author), US FDA, Off Pediat Therapeut, Silver Spring, MD 20993 USA. NR 56 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-31206-3 PY 2013 BP 73 EP 82 D2 10.1002/9781118312087 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJR82 UT WOS:000329855800008 ER PT J AU Roth-Cline, MD Nelson, RM AF Roth-Cline, Michelle D. Nelson, Robert M. BE Mulberg, AE Murphy, D Dunne, J Mathis, LL TI Ethical Considerations in Conducting Pediatric Research SO PEDIATRIC DRUG DEVELOPMENT: CONCEPTS AND APPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter ID CHILD ASSENT; CONSENT; RISK C1 [Roth-Cline, Michelle D.] US FDA, Off Pediat Therapeut, Silver Spring, MD 20993 USA. [Nelson, Robert M.] US FDA, Off Pediat Therapeut, Off Commissioner, Silver Spring, MD USA. RP Roth-Cline, MD (reprint author), US FDA, Off Pediat Therapeut, Silver Spring, MD 20993 USA. NR 30 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-31206-3 PY 2013 BP 83 EP 93 D2 10.1002/9781118312087 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJR82 UT WOS:000329855800009 ER PT J AU Dunne, J Rodriguez, WJ Murphy, D AF Dunne, Julia Rodriguez, William J. Murphy, Dianne BE Mulberg, AE Murphy, D Dunne, J Mathis, LL TI FDA Experience of Extrapolation of Efficacy to the Pediatric Population from Adult and Other Data SO PEDIATRIC DRUG DEVELOPMENT: CONCEPTS AND APPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter C1 [Dunne, Julia] Med & Healthcare Prod Regulatory Agcy, VRMM, London, England. [Rodriguez, William J.] US FDA, Off Pediat Therapeut, Off Commissioner, Washington, DC 20204 USA. [Rodriguez, William J.] George Washington Med Sch, Dept Pediat, Washington, DC USA. [Murphy, Dianne] US FDA, Off Pediat Therapeut, Off Commissioner, Silver Spring, MD USA. RP Dunne, J (reprint author), Med & Healthcare Prod Regulatory Agcy, VRMM, London, England. NR 9 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-31206-3 PY 2013 BP 110 EP 122 D2 10.1002/9781118312087 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJR82 UT WOS:000329855800012 ER PT J AU Cvetkovich, T AF Cvetkovich, Therese BE Mulberg, AE Murphy, D Dunne, J Mathis, LL TI Accelerated Approval and Other Regulatory Approaches to Drug Development for Serious Diseases in Pediatrics SO PEDIATRIC DRUG DEVELOPMENT: CONCEPTS AND APPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter C1 US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Div Risk Assessment, Silver Spring, MD 20993 USA. RP Cvetkovich, T (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Div Risk Assessment, Silver Spring, MD 20993 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-31206-3 PY 2013 BP 123 EP 129 D2 10.1002/9781118312087 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJR82 UT WOS:000329855800013 ER PT J AU Pariser, AR Yao, LP AF Pariser, Anne R. Yao, Lynne P. BE Mulberg, AE Murphy, D Dunne, J Mathis, LL TI Rare Diseases and Orphan Drugs SO PEDIATRIC DRUG DEVELOPMENT: CONCEPTS AND APPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter ID POMPE DISEASE; NEUTRALIZING ANTIBODIES; GAUCHER-DISEASE; APPROVAL; VENTILATION; DISORDERS; SURVIVAL; EFFICACY; THERAPY; IMPACT C1 [Pariser, Anne R.; Yao, Lynne P.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Pariser, AR (reprint author), US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 60 TC 3 Z9 3 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-31206-3 PY 2013 BP 130 EP 148 D2 10.1002/9781118312087 PG 19 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJR82 UT WOS:000329855800014 ER PT J AU Venkataraman-Rao, P Samuels-Reid, JH AF Venkataraman-Rao, Priya Samuels-Reid, Joy H. BE Mulberg, AE Murphy, D Dunne, J Mathis, LL TI Pediatric Device Development in the United States SO PEDIATRIC DRUG DEVELOPMENT: CONCEPTS AND APPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter ID VAGUS NERVE-STIMULATION; BACTERIAL-CONTAMINATION; CIRCULATORY SUPPORT; CHILDREN C1 [Venkataraman-Rao, Priya] US FDA, DRGUD, Silver Spring, MD 20993 USA. [Samuels-Reid, Joy H.] US FDA, Div Anesthesiol Gen Hosp Resp Infect Control & De, Off Device Evaluat, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Venkataraman-Rao, P (reprint author), US FDA, DRGUD, Silver Spring, MD 20993 USA. NR 45 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-31206-3 PY 2013 BP 177 EP 191 D2 10.1002/9781118312087 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJR82 UT WOS:000329855800018 ER PT J AU Coogan, TP Tassinari, MS AF Coogan, Timothy P. Tassinari, Melissa S. BE Mulberg, AE Murphy, D Dunne, J Mathis, LL TI Preclinical Safety Assessment: Introduction and Overview SO PEDIATRIC DRUG DEVELOPMENT: CONCEPTS AND APPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter C1 [Coogan, Timothy P.] Janssen Res & Dev LLC, Biol Toxicol, Spring House, PA 19477 USA. [Tassinari, Melissa S.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Coogan, TP (reprint author), Janssen Res & Dev LLC, Biol Toxicol, Spring House, PA 19477 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-31206-3 PY 2013 BP 195 EP 200 D2 10.1002/9781118312087 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJR82 UT WOS:000329855800019 ER PT J AU Davis-Bruno, KL Carleer, J Lima, BS Tassinari, MS AF Davis-Bruno, Karen L. Carleer, Jacqueline Lima, Beatriz Silva Tassinari, Melissa S. BE Mulberg, AE Murphy, D Dunne, J Mathis, LL TI A Global Regulatory Perspective SO PEDIATRIC DRUG DEVELOPMENT: CONCEPTS AND APPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter ID LABEL DRUG-USE C1 [Davis-Bruno, Karen L.] US FDA, Div Metab & Endocrinol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Lima, Beatriz Silva] Univ Lisbon, Fac Pharm, Dept Pharmacol Sci, Nonclin Safety & Regulatory Sci Res Grp,iMED UL, P-1699 Lisbon, Portugal. [Tassinari, Melissa S.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Davis-Bruno, KL (reprint author), US FDA, Div Metab & Endocrinol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-31206-3 PY 2013 BP 246 EP 256 D2 10.1002/9781118312087 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJR82 UT WOS:000329855800022 ER PT J AU Mehta, NR King, ST AF Mehta, Niraj R. King, Sruthi Tallapragada BE Mulberg, AE Murphy, D Dunne, J Mathis, LL TI Disease-Specific Models to Enhance Pediatric Drug Development SO PEDIATRIC DRUG DEVELOPMENT: CONCEPTS AND APPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter ID LECITHIN-CHOLESTEROL ACYLTRANSFERASE; NIEMANN-PICK-DISEASE; SPHINGOMYELINASE-DEFICIENT MICE; HUMAN ACID SPHINGOMYELINASE; MUSCULAR-DYSTROPHY; ANIMAL-MODELS; ALPHA-GLUCOSIDASE; TRANSGENIC MICE; POMPE DISEASE; MDX C1 [Mehta, Niraj R.] US FDA, Div Bioequivalence & GLP Compliance, Off Sci Invest, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [King, Sruthi Tallapragada] US FDA, Div Gastroenterol & Inborn Error Prod, Off Drug Evaluat 3, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Mehta, NR (reprint author), US FDA, Div Bioequivalence & GLP Compliance, Off Sci Invest, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 45 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-31206-3 PY 2013 BP 257 EP 267 D2 10.1002/9781118312087 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJR82 UT WOS:000329855800023 ER PT J AU Burckart, GJ Momper, JD AF Burckart, Gilbert J. Momper, Jeremiah D. BE Mulberg, AE Murphy, D Dunne, J Mathis, LL TI Pediatric Clinical Pharmacology in Regulatory and Drug Development Sciences: Lessons Learned and the Path Forward SO PEDIATRIC DRUG DEVELOPMENT: CONCEPTS AND APPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter ID CLOPIDOGREL PICOLO TRIAL; PLATELET INHIBITION; YOUNG-CHILDREN; MIGRAINE; PHARMACOKINETICS; EXCRETION; INFANTS C1 [Burckart, Gilbert J.] US FDA, Pediat Clin Pharmacol Grp, Off Clin Pharmacol, Off Translat Sci,CDER, Silver Spring, MD 20993 USA. [Momper, Jeremiah D.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Burckart, GJ (reprint author), US FDA, Pediat Clin Pharmacol Grp, Off Clin Pharmacol, Off Translat Sci,CDER, Silver Spring, MD 20993 USA. NR 20 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-31206-3 PY 2013 BP 271 EP 280 D2 10.1002/9781118312087 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJR82 UT WOS:000329855800024 ER PT J AU Momper, JD Burckart, GJ Jadhav, P AF Momper, Jeremiah D. Burckart, Gilbert J. Jadhav, Pravin BE Mulberg, AE Murphy, D Dunne, J Mathis, LL TI Applications of Population Pharmacokinetics for Pediatric Drug Development SO PEDIATRIC DRUG DEVELOPMENT: CONCEPTS AND APPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter ID DRIED BLOOD SPOTS; SCAVENGED SAMPLES; PRETERM INFANTS; CHILDREN; SIZE; SIMULATION; CLEARANCE; DESIGN; ADULT; MODEL C1 [Momper, Jeremiah D.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Burckart, Gilbert J.] US FDA, Pediat Clin Pharmacol Grp, Off Clin Pharmacol, Off Translat Sci,CDER, Silver Spring, MD USA. [Jadhav, Pravin] Merck Sharp & Dohme Ltd, Upper Gwynedd, PA USA. RP Momper, JD (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 42 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-31206-3 PY 2013 BP 306 EP 315 D2 10.1002/9781118312087 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJR82 UT WOS:000329855800027 ER PT J AU Burckart, GJ Green, D Mummaneni, P AF Burckart, Gilbert J. Green, Dionna Mummaneni, Padmaja BE Mulberg, AE Murphy, D Dunne, J Mathis, LL TI Applications of Pharmacogenomics to Pediatric Drug Development SO PEDIATRIC DRUG DEVELOPMENT: CONCEPTS AND APPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter ID METABOLIZING-ENZYMES; ONTOGENY; CHILDREN; FOOD; INFORMATION; MEDICINE; LABELS C1 [Burckart, Gilbert J.; Green, Dionna] US FDA, Pediat Clin Pharmacol Grp, Off Clin Pharmacol, Off Translat Sci,CDER, Silver Spring, MD 20993 USA. [Mummaneni, Padmaja] US FDA, Genom Grp, Off Clin Pharmacol OTS, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Burckart, GJ (reprint author), US FDA, Pediat Clin Pharmacol Grp, Off Clin Pharmacol, Off Translat Sci,CDER, Silver Spring, MD 20993 USA. NR 27 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-31206-3 PY 2013 BP 316 EP 331 D2 10.1002/9781118312087 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJR82 UT WOS:000329855800028 ER PT J AU Illoh, K AF Illoh, Kachi BE Mulberg, AE Murphy, D Dunne, J Mathis, LL TI Brain and Central Nervous System Development: Physiological Considerations for Assessment of Long-Term Safety SO PEDIATRIC DRUG DEVELOPMENT: CONCEPTS AND APPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter ID CHILD-DEVELOPMENT INVENTORY; YOUNG-CHILDREN; CEREBRAL-PALSY; INFANTS; DELAY; RISK; VALIDATION; CHECKLIST; DENVER C1 US FDA, Div Neurol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Illoh, K (reprint author), US FDA, Div Neurol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 40 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-31206-3 PY 2013 BP 345 EP 354 D2 10.1002/9781118312087 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJR82 UT WOS:000329855800030 ER PT J AU Sylvester, FA Wynn, EL AF Sylvester, Francisco A. Wynn, Erica L. BE Mulberg, AE Murphy, D Dunne, J Mathis, LL TI Pediatric Bone and Adult Bone - Physiological Differences SO PEDIATRIC DRUG DEVELOPMENT: CONCEPTS AND APPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter ID PROTON PUMP INHIBITORS; ANTIEPILEPTIC DRUG MONOTHERAPY; GLUCOCORTICOID-INDUCED OSTEOPOROSIS; TERM OMEPRAZOLE TREATMENT; GASTRIC-ACID SECRETION; VITAMIN-D METABOLISM; MINERAL DENSITY; HIP FRACTURE; ANTICONVULSANT THERAPY; CALCIUM-ABSORPTION C1 [Sylvester, Francisco A.] Univ Connecticut, Ctr Hlth, Farmington, CT 06030 USA. [Sylvester, Francisco A.] Connecticut Childrens Med Ctr, Hartford, CT USA. [Wynn, Erica L.] US FDA, Div Gastroenterol & Inborn Errors Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Sylvester, FA (reprint author), Univ Connecticut, Ctr Hlth, Farmington, CT 06030 USA. NR 101 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-31206-3 PY 2013 BP 395 EP 408 D2 10.1002/9781118312087 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJR82 UT WOS:000329855800033 ER PT J AU Snyder, KM Donoghue, M Helms, WS Reaman, G AF Snyder, Kristen M. Donoghue, Martha Helms, Whitney S. Reaman, Gregory BE Mulberg, AE Murphy, D Dunne, J Mathis, LL TI Development of Drugs for Pediatric Cancers SO PEDIATRIC DRUG DEVELOPMENT: CONCEPTS AND APPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter ID CHILDHOOD-CANCER; CLINICAL-TRIALS; PROGRAMS; LEUKEMIA C1 [Snyder, Kristen M.] Monroe Carell Jr Childrens Hosp Vanderbilt, Dept Pediat, Div Pediat Hematol Oncol, Nashville, TN 37232 USA. [Donoghue, Martha] US FDA, Off Hematol & Oncol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Helms, Whitney S.] US FDA, Div Hematol, Off Hematol & Oncol Prod, Silver Spring, MD USA. [Reaman, Gregory] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Reaman, Gregory] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA. RP Snyder, KM (reprint author), Monroe Carell Jr Childrens Hosp Vanderbilt, Dept Pediat, Div Pediat Hematol Oncol, Nashville, TN 37232 USA. NR 27 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-31206-3 PY 2013 BP 438 EP 452 D2 10.1002/9781118312087 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJR82 UT WOS:000329855800036 ER PT J AU Mulberg, AE Hausman, ED AF Mulberg, Andrew E. Hausman, Ethan D. BE Mulberg, AE Murphy, D Dunne, J Mathis, LL TI Clinical Laboratory Testing in Clinical Trials for Pediatric Subjects SO PEDIATRIC DRUG DEVELOPMENT: CONCEPTS AND APPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter ID REFERENCE RANGES; CHILDREN; VALUES C1 [Mulberg, Andrew E.] US FDA, Div Gastroenterol & Inborn Error Prod, Off Drug Evaluat 3, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Hausman, Ethan D.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Mulberg, AE (reprint author), US FDA, Div Gastroenterol & Inborn Error Prod, Off Drug Evaluat 3, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 23 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-31206-3 PY 2013 BP 517 EP 529 D2 10.1002/9781118312087 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJR82 UT WOS:000329855800041 ER PT J AU Papadopoulos, EJ Patrick, DL Tassinari, MS Mulberg, AE Epps, C Pariser, AR Burke, LB AF Papadopoulos, Elektra J. Patrick, Donald L. Tassinari, Melissa S. Mulberg, Andrew E. Epps, Carla Pariser, Anne R. Burke, Laurie B. BE Mulberg, AE Murphy, D Dunne, J Mathis, LL TI Clinical Outcome Assessments for Clinical Trials in Children SO PEDIATRIC DRUG DEVELOPMENT: CONCEPTS AND APPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter ID TASK-FORCE; EOSINOPHILIC ESOPHAGITIS; PRO INSTRUMENTS C1 [Papadopoulos, Elektra J.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Patrick, Donald L.] Univ Washington, Seattle, WA 98195 USA. [Patrick, Donald L.] Seattle Qual Life Grp, Seattle, WA USA. [Tassinari, Melissa S.; Pariser, Anne R.; Burke, Laurie B.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Mulberg, Andrew E.] US FDA, Div Gastroenterol & Inborn Error Prod, Off Drug Evaluat 3, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Epps, Carla] US FDA, Div Gastroenterol & Inborn Errors Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Papadopoulos, EJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 8 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-31206-3 PY 2013 BP 539 EP 548 D2 10.1002/9781118312087 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJR82 UT WOS:000329855800043 ER PT J AU McMahon, AW Feudtner, C Murphy, D AF McMahon, Ann W. Feudtner, Chris Murphy, Dianne BE Mulberg, AE Murphy, D Dunne, J Mathis, LL TI Challenges Evaluating the Safety of Pediatric Therapeutic Agents in Clinical Trials and Post-Marketing Surveillance SO PEDIATRIC DRUG DEVELOPMENT: CONCEPTS AND APPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter ID ADVERSE EVENTS; CLASSIFICATION; CHILDREN; DRUGS C1 [McMahon, Ann W.; Murphy, Dianne] US FDA, Off Pediat Therapeut, Off Commissioner, Silver Spring, MD 20993 USA. [Feudtner, Chris] Univ Penn, Childrens Hosp Philadelphia, Dept Med Eth, Philadelphia, PA 19104 USA. RP McMahon, AW (reprint author), US FDA, Off Pediat Therapeut, Off Commissioner, Silver Spring, MD 20993 USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-31206-3 PY 2013 BP 549 EP 556 D2 10.1002/9781118312087 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJR82 UT WOS:000329855800044 ER PT J AU Yao, LP Pariser, AR AF Yao, Lynne P. Pariser, Anne R. BE Mulberg, AE Murphy, D Dunne, J Mathis, LL TI Biomarkers and Endpoints in Rare Diseases SO PEDIATRIC DRUG DEVELOPMENT: CONCEPTS AND APPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter ID CLINICAL-TRIALS; SURROGATE; CRITERIA C1 [Yao, Lynne P.; Pariser, Anne R.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Yao, LP (reprint author), US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-31206-3 PY 2013 BP 557 EP 561 D2 10.1002/9781118312087 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJR82 UT WOS:000329855800045 ER PT J AU Edwards, GB Ruiz, GRS AF Edwards, G. B. Ruiz, Gustavo R. S. TI Freya ambigua (Araneae: Salticidae) introduced to the continental United States, with new synonyms SO JOURNAL OF ARACHNOLOGY LA English DT Article DE Florida; jumping spider; South America; systematics; Texas AB Euophrys ambigua C.L. Koch 1846 is again transferred, becoming Freya ambigua, COMBINATION RESTORED. This jumping spider species, native to northern South America, has been found in North America in the southern parts of two of the states of the USA: Florida (Broward, Hillsborough, Manatee, Miami-Dade, and Pinellas counties) and Texas (Cameron and Hidalgo counties). Previously known from Colombia, Suriname, Trinidad and Tobago, and Venezuela, it is now also recorded from Brazil and French Guiana. Two other names are reported as NEW SYNONYMS: Menemerus fannae Peckham & Peckham 1896 and Freya perelegans Simon 1902. A lectotype is designated for Menemerus fannae. The female of F. ambigua is described for the first time. C1 [Edwards, G. B.] FDACS, Div Plant Ind, Gainesville, FL 32614 USA. [Ruiz, Gustavo R. S.] Fed Univ Para, Inst Ciencias Biol, BR-66075110 Belem, Para, Brazil. RP Edwards, GB (reprint author), FDACS, Div Plant Ind, POB 147100, Gainesville, FL 32614 USA. EM GB.Edwards@freshfromflorida.com NR 17 TC 3 Z9 3 U1 0 U2 0 PU AMER ARACHNOLOGICAL SOC PI COLLEGE PARK PA UNIV MARYLAND, DEPT ENTOMOLOGY, 4112 PLANT SCIENCES BLDG, COLLEGE PARK, MD 20742-4454 USA SN 0161-8202 EI 1937-2396 J9 J ARACHNOL JI J. Arachnol. PY 2013 VL 41 IS 1 BP 11 EP 17 PG 7 WC Entomology SC Entomology GA AA3YB UT WOS:000331030000002 ER PT J AU Mustafa, T Zhang, YB Watanabe, F Karmakar, A Asar, MP Little, R Hudson, MK Xu, Y Biris, AS AF Mustafa, Thikra Zhang, Yongbin Watanabe, Fumiya Karmakar, Alokita Asar, Madhu P. Little, Reginald Hudson, M. Keith Xu, Yang Biris, Alexandru S. TI Iron oxide nanoparticle-based radio-frequency thermotherapy for human breast adenocarcinoma cancer cells SO BIOMATERIALS SCIENCE LA English DT Article ID AC-MAGNETIC-FIELD; CELLULAR UPTAKE; HYPERTHERMIA; CYTOTOXICITY; THERAPY; OXYGEN; BLOOD; SIZE AB Iron oxide nanoparticles (IONPs) with diameters of 15, 25, and 41 nm were evaluated as mediators of thermal cytotoxicity under radio-frequency (RF) exposure. The 25 nm IONPs were found to be the most efficient of the three in killing cancer cells at 350 kHz low-frequency RF irradiation. However, at a higher frequency of 13.56 MHz, 15 nm IONPs produced the highest percentage of cell death. Moreover, the killing effect was concentration-dependent in that a higher concentration of IONPs resulted in increased cellular death. Size-dependent internalization of IONPs in MCF-7 cells was quantified by using inductively coupled-plasma mass spectrometry (ICP-MS). Dark-field microscopy and transmission electron microscopy (TEM) revealed that MCF-7 cells internalize IONPs through endocytosis after 24 hours of incubation. In addition, after RF treatment, the cancer cells underwent the apoptosis process, and the level of reactive oxygen species (ROS) increased significantly after hyperthermia. Scanning electron microscopy (SEM) and TEM further established that the ultrastructure morphological changes in the cancer cells originated from the apoptosis process. C1 [Mustafa, Thikra; Watanabe, Fumiya; Karmakar, Alokita; Asar, Madhu P.; Xu, Yang; Biris, Alexandru S.] Univ Arkansas, Ctr Integrat Nanotechnol Sci, Little Rock, AR 72204 USA. [Zhang, Yongbin] USDA, Nanotechnol Core Facil, Off Sci Coordinat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Little, Reginald] South Carolina State Univ, Dept Biol & Phys Sci, Orangeburg, SC 29117 USA. [Hudson, M. Keith] Univ Arkansas, Dept Appl Sci, Little Rock, AR 72204 USA. RP Mustafa, T (reprint author), Univ Arkansas, Ctr Integrat Nanotechnol Sci, 2801 S Univ Ave, Little Rock, AR 72204 USA. EM yxxu@ualr.edu; asbiris@ualr.edu FU Arkansas Science and Technology Authority (ASTA) [08-CAT-03]; US Army TATRC program; Office of Experimental Program to Stimulate Competitive Research (EPSCoR) of National Science Foundation of USA; South Carolina State University FX The support for this research received from the Arkansas Science and Technology Authority (ASTA) through grant no. 08-CAT-03 is acknowledged. The financial support provided by the US Army TATRC program is acknowledged. The supports for this work received from The Office of Experimental Program to Stimulate Competitive Research (EPSCoR) of National Science Foundation of USA and South Carolina State University are acknowledged. The editorial assistance by Dr Marinelle Ringer is also acknowledged. Ocean NanoTech is acknowledged for supplying the iron nanoparticle samples for the XRD analysis. NR 43 TC 12 Z9 12 U1 4 U2 18 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2047-4830 EI 2047-4849 J9 BIOMATER SCI-UK JI Biomater. Sci. PY 2013 VL 1 IS 8 BP 870 EP 880 DI 10.1039/c3bm60015g PG 11 WC Materials Science, Biomaterials SC Materials Science GA 295ST UT WOS:000330136500009 ER PT B AU Carey, CC AF Carey, Carole C. BA Wong, J Tong, RKY BF Wong, J Tong, RKY TI United States Medical Device Regulatory Framework SO HANDBOOK OF MEDICAL DEVICE REGULATORY AFFAIRS IN ASIA LA English DT Article; Book Chapter C1 US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Carey, CC (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD USA. EM carole.carey@fda.hhs.gov NR 1 TC 0 Z9 0 U1 0 U2 1 PU PAN STANFORD PUBLISHING PTE LTD PI SINGAPORE PA PENTHOUSE LEVEL, SUNTEC TOWER 3, 8 TEMASEK BLVD, SINGAPORE, 038988, SINGAPORE BN 978-981-4411-22-6; 978-981-4411-21-9 PY 2013 BP 211 EP 231 PG 21 WC Health Policy & Services; Law SC Health Care Sciences & Services; Government & Law GA BJJ94 UT WOS:000328543900021 ER PT B AU Weiner, JB Nguyen, TX AF Weiner, John Barlow Nguyen, Thinh X. BA Wong, J Tong, RKY BF Wong, J Tong, RKY TI Regulation of Combination Products in the United States SO HANDBOOK OF MEDICAL DEVICE REGULATORY AFFAIRS IN ASIA LA English DT Article; Book Chapter C1 [Weiner, John Barlow; Nguyen, Thinh X.] US FDA, Off Combinat Prod, Silver Spring, MD 20993 USA. RP Weiner, JB (reprint author), US FDA, Off Combinat Prod, WO32,Hub Mail Room 5129,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM John.Weiner@fda.hhs.gov; THUYNTT@its.jnj.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU PAN STANFORD PUBLISHING PTE LTD PI SINGAPORE PA PENTHOUSE LEVEL, SUNTEC TOWER 3, 8 TEMASEK BLVD, SINGAPORE, 038988, SINGAPORE BN 978-981-4411-22-6; 978-981-4411-21-9 PY 2013 BP 275 EP 285 PG 11 WC Health Policy & Services; Law SC Health Care Sciences & Services; Government & Law GA BJJ94 UT WOS:000328543900023 ER PT J AU Whichard, JM Gay, K Tate, H Chiller, TM AF Whichard, Jean M. Gay, Kathryn Tate, Heather Chiller, Tom M. BE Mikanatha, NM Lynfield, R VanBeneden, CA DeValk, H TI Surveillance for foodborne diseases PART 3: Surveillance for antimicrobial resistance among foodborne bacteria-the US approach SO INFECTIOUS DISEASE SURVEILLANCE, 2ND EDITION LA English DT Article; Book Chapter ID UNITED-STATES; VETERINARY-MEDICINE; ESCHERICHIA-COLI; FOOD ANIMALS; SALMONELLA; INFECTIONS; SUSCEPTIBILITY; CAMPYLOBACTER; HUMANS C1 [Whichard, Jean M.; Chiller, Tom M.] Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, Atlanta, GA 30333 USA. [Gay, Kathryn] Philadelphia Anim Welf Soc, Philadelphia, PA USA. [Tate, Heather] US FDA, Ctr Vet Med, Laurel, MD USA. RP Whichard, JM (reprint author), Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, Atlanta, GA 30333 USA. NR 39 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-65467-5 PY 2013 BP 129 EP 142 D2 10.1002/9781118543504 PG 14 WC Infectious Diseases SC Infectious Diseases GA BJK54 UT WOS:000328679500016 ER PT J AU Kuehnert, MJ Wise, RP Holmberg, JA AF Kuehnert, Matthew J. Wise, Robert P. Holmberg, Jerry A. BE Mikanatha, NM Lynfield, R VanBeneden, CA DeValk, H TI Biovigilance: designing and implementing surveillance systems for the safety and quality of blood, organs, and tissues SO INFECTIOUS DISEASE SURVEILLANCE, 2ND EDITION LA English DT Article; Book Chapter ID RESISTANT STREPTOCOCCUS-PNEUMONIAE; UNITED-STATES; EUROPEAN COUNTRIES; STAPHYLOCOCCUS-AUREUS; ANTIBIOTIC-RESISTANCE; ANTIBIOGRAMS; PREVALENCE; HOSPITALS C1 [Kuehnert, Matthew J.] Ctr Dis Control & Prevent, Off Blood Organ & Other Tissue Safety, Div Healthcare Qual Promot, Atlanta, GA 30333 USA. [Wise, Robert P.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Holmberg, Jerry A.] Dept Hlth & Human Serv, Off Publ Hlth & Sci, Rockville, MD USA. RP Kuehnert, MJ (reprint author), Ctr Dis Control & Prevent, Off Blood Organ & Other Tissue Safety, Div Healthcare Qual Promot, Atlanta, GA 30333 USA. NR 38 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-65467-5 PY 2013 BP 261 EP 287 D2 10.1002/9781118543504 PG 27 WC Infectious Diseases SC Infectious Diseases GA BJK54 UT WOS:000328679500026 ER PT S AU Gould, T Wang, QZ Kim, DH Pfefer, J AF Gould, Taylor Wang, Quanzeng Kim, Do-Hyun Pfefer, Joshua BE Cullum, BM McLamore, ES TI Near-infrared photoacoustic diagnostics in biomedicine: Analysis of thermal safety and light-tissue interactions SO SMART BIOMEDICAL AND PHYSIOLOGICAL SENSOR TECHNOLOGY X SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Smart Biomedical and Physiological Sensor Technology X CY MAY 01-02, 2013 CL Baltimore, MD SP SPIE DE Photoacoustics; Monte Carlo modeling; laser-tissue interactions; thermal damage; laser safety ID SENTINEL LYMPH-NODES; PORT-WINE STAINS; IN-VIVO; BIOLOGICAL TISSUES; OPTICAL-PROPERTIES; OXYGEN-SATURATION; LASER TREATMENT; BREAST-CANCER; HUMAN SKIN; TOMOGRAPHY AB Medical diagnostic devices based on photoacoustics represent an emerging area with significant potential for evaluation of brain injury and chemical agent exposure, as well as detection of pandemic diseases and cancer. However, few studies have addressed photothermal safety of these devices which emit high-power laser pulses to generate rapid, selective, yet non-destructive heating of subsurface structures. Towards elucidation of laser-tissue interactions and factors of safety for photothermal injury, we have developed a three-dimensional numerical model including light propagation, heat transfer and thermal damage algorithms. Literature surveys were performed to identify appropriate optical properties and the range of device exposure levels implemented in prior in vivo studies. Initial simulations provided model validation against results from the literature. Simulations were then performed based on breast tissue with discrete blood vessels irradiated by a train of laser pulses (10 Hz) at 800 and 1064 nm. For a constant exposure level, increasing beam diameter from 0.2 to 2.0 cm led to a factor of 2.5 increase in subsurface heat generation rates. Our preliminary modeling results indicate that for a 10 second tissue exposure under standard photoacoustic imaging conditions, irradiance-based safety limits should provide a factor of safety of 6 or greater over exposure levels that induce thermal coagulation. Optical-thermal modeling represents a powerful tool for elucidating photothermal effects relevant to the safety and effectiveness of photoacoustic systems. C1 [Gould, Taylor; Wang, Quanzeng; Kim, Do-Hyun; Pfefer, Joshua] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Gould, T (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. NR 42 TC 0 Z9 0 U1 1 U2 9 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9510-5 J9 PROC SPIE PY 2013 VL 8719 AR 87190X DI 10.1117/12.2018311 PG 12 WC Engineering, Biomedical; Optics; Physics, Applied SC Engineering; Optics; Physics GA BJQ21 UT WOS:000329624600023 ER PT S AU Wang, JT Coburn, J Liang, CP Woolsey, N Le, D Ramella-Roman, J Chen, Y Pfefer, J AF Wang, Jianting Coburn, James Liang, Chia-Pin Woolsey, Nicholas Le, Du Ramella-Roman, Jessica Chen, Yu Pfefer, Joshua BE Cullum, BM McLamore, ES TI Characterization and Application of 3D Printed Phantoms for Biophotonic Imaging SO SMART BIOMEDICAL AND PHYSIOLOGICAL SENSOR TECHNOLOGY X SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Smart Biomedical and Physiological Sensor Technology X CY MAY 01-02, 2013 CL Baltimore, MD SP SPIE DE 3D printing; rapid proto-typing; Acrylonitrile Butadiene Styrene (ABS); geometric phantoms; biophotonic imaging; microfluidic channel; hyperspectral reflectance imaging ID OPTICAL-PROPERTIES; TISSUES; RANGE AB The emerging technique of three-dimensional (3D) printing provides a simple, fast, and flexible way to fabricate structures with arbitrary spatial features and may prove useful in the development of standardized, phantom-based performance test methods for biophotonic imaging. Acrylonitrile Butadiene Styrene (ABS) is commonly used in the printing process, given its low cost and strength. In this study, we evaluate 3D printing as an approach for fabricating biologically-relevant optical phantoms for hyperspectral reflectance imaging (HRI). The initial phase of this work involved characterization of absorption and scattering coefficients using spectrophotometry. The morphology of phantoms incorporating vessel-like channels with diameters on the order of hundreds of microns was examined by microscopy and OCT. A near-infrared absorbing dye was injected into channels located at a range of depths within the phantom and imaged with a near-infrared HRI system (650-1100 nm). ABS was found to have scattering coefficients comparable to biological tissue and low absorption throughout much of the visible and infrared range. Channels with dimensions on the order of the resolution limit of the 3D printer (similar to 0.2 mm) exhibited pixelation effects as well as a degree of distortion along their edges. Furthermore, phantom porosity sometimes resulted in leakage from channel regions. Contrast-enhanced channel visualization with HRI was possible to a depth of nearly 1 mm - a level similar to that seen previously in biological tissue. Overall, our ABS phantoms demonstrated a high level of optical similarity to biological tissue. While limitations in printer resolution, matrix homogeneity and optical property tunability remain challenging, 3D printed phantoms have significant promise as samples for objective, quantitative evaluation of performance for biophotonic imaging modalities such as HRI. C1 [Wang, Jianting; Liang, Chia-Pin; Woolsey, Nicholas; Chen, Yu] Univ Maryland, College Pk, MD 20742 USA. [Wang, Jianting; Coburn, James; Woolsey, Nicholas; Le, Du; Ramella-Roman, Jessica; Chen, Yu; Pfefer, Joshua] Food & Drug Adm, Silver Spring, MD 10903 USA. [Le, Du; Ramella-Roman, Jessica] Catholic Univ Amer, Washington, DC 20064 USA. RP Wang, JT (reprint author), Univ Maryland, College Pk, MD 20742 USA. FU National Science Foundation [CBET-1238407]; University of Maryland Center for Excellence in Regulatory Science and Innovation (CERSI) FX The authors acknowledge the support from National Science Foundation (NSF, CBET-1238407) and the University of Maryland Center for Excellence in Regulatory Science and Innovation (CERSI). NR 12 TC 1 Z9 1 U1 2 U2 15 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9510-5 J9 PROC SPIE PY 2013 VL 8719 AR UNSP 87190Y DI 10.1117/12.2018285 PG 9 WC Engineering, Biomedical; Optics; Physics, Applied SC Engineering; Optics; Physics GA BJQ21 UT WOS:000329624600024 ER PT B AU Boerlin, P White, DG AF Boerlin, Patrick White, David G. BE Giguere, S Prescott, JF Dowling, PM TI Antimicrobial Resistance and Its Epidemiology SO ANTIMICROBIAL THERAPY IN VETERINARY MEDICINE, 5TH EDITION LA English DT Article; Book Chapter ID SALMONELLA-ENTERICA SEROVAR; URINARY-TRACT-INFECTIONS; INTENSIVE-CARE-UNIT; EXTRAINTESTINAL ESCHERICHIA-COLI; HORIZONTAL GENE-TRANSFER; ANTIBIOTIC-RESISTANCE; STAPHYLOCOCCUS-AUREUS; COMPANION ANIMALS; ENTEROCOCCUS-FAECIUM; FOOD ANIMALS C1 [Boerlin, Patrick] Univ Guelph, Ontario Vet Coll, Dept Pathobiol, Guelph, ON N1G 2W1, Canada. [White, David G.] US FDA, Res Off, Ctr Vet Med, Laurel, MD USA. RP Boerlin, P (reprint author), Univ Guelph, Ontario Vet Coll, Dept Pathobiol, Guelph, ON N1G 2W1, Canada. NR 146 TC 4 Z9 4 U1 1 U2 3 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-67510-6; 978-0-470-96302-9 PY 2013 BP 21 EP 40 PG 20 WC Veterinary Sciences SC Veterinary Sciences GA BJI81 UT WOS:000328360400004 ER PT B AU Martinez, MN Toutain, PL Turnidge, J AF Martinez, Marilyn N. Toutain, Pierre-Louis Turnidge, John BE Giguere, S Prescott, JF Dowling, PM TI The Pharmacodynamics of Antimicrobial Agents SO ANTIMICROBIAL THERAPY IN VETERINARY MEDICINE, 5TH EDITION LA English DT Article; Book Chapter ID RESISTANT STAPHYLOCOCCUS-AUREUS; MUTANT SELECTION WINDOW; EPITHELIAL LINING FLUID; COAGULASE-NEGATIVE STAPHYLOCOCCI; PSEUDOMONAS-AERUGINOSA BIOFILMS; HEMOLYTIC-UREMIC SYNDROME; SLOWLY GROWING BACTERIA; MONTE-CARLO-SIMULATION; IN-VITRO; ESCHERICHIA-COLI C1 [Martinez, Marilyn N.] US FDA, Off New Anim Drug Evaluat, Ctr Vet Med, Rockville, MD 20857 USA. [Toutain, Pierre-Louis] Ecole Natl Vet Toulouse, Toulouse, France. [Turnidge, John] Univ Adelaide, Fac Hlth Sci, Adelaide, SA 5005, Australia. RP Martinez, MN (reprint author), US FDA, Off New Anim Drug Evaluat, Ctr Vet Med, Rockville, MD 20857 USA. NR 140 TC 6 Z9 6 U1 1 U2 5 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-67510-6; 978-0-470-96302-9 PY 2013 BP 79 EP 103 PG 25 WC Veterinary Sciences SC Veterinary Sciences GA BJI81 UT WOS:000328360400006 ER PT B AU Reimschuessel, R Miller, RA Gieseker, CM AF Reimschuessel, Renate Miller, Ron A. Gieseker, Charles M. BE Giguere, S Prescott, JF Dowling, PM TI Antimicrobial Drug Use in Aquaculture SO ANTIMICROBIAL THERAPY IN VETERINARY MEDICINE, 5TH EDITION LA English DT Article; Book Chapter ID TROUT ONCORHYNCHUS-MYKISS; MINIMUM INHIBITORY CONCENTRATIONS; FISH-PATHOGENIC BACTERIA; SALMON SALMO-SALAR; OXOLINIC ACID; RAINBOW-TROUT; AEROMONAS-SALMONICIDA; IN-VITRO; FRESH-WATER; CHANNEL CATFISH C1 [Reimschuessel, Renate] US FDA, Vet Lab Response Network, Ctr Vet Med, Laurel, MD USA. [Miller, Ron A.] US FDA, Off New Anim Drug Evaluat, Ctr Vet Med, Rockville, MD 20857 USA. [Gieseker, Charles M.] US FDA, Res Off, Ctr Vet Med, Laurel, MD USA. RP Reimschuessel, R (reprint author), US FDA, Vet Lab Response Network, Ctr Vet Med, Laurel, MD USA. NR 91 TC 0 Z9 0 U1 2 U2 2 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-67510-6; 978-0-470-96302-9 PY 2013 BP 645 EP 661 PG 17 WC Veterinary Sciences SC Veterinary Sciences GA BJI81 UT WOS:000328360400040 ER PT J AU Moon, H Lopez, KL Lin, GI Chen, JJ AF Moon, Hojin Lopez, Karen L. Lin, Grace I. Chen, James J. TI Sex-Specific Genomic Biomarkers for Individualized Treatment of Life-Threatening Diseases SO DISEASE MARKERS LA English DT Article ID GENE SELECTION; CLASSIFICATION; CANCER AB Numerous studies have demonstrated sex differences in drug reactions to the same drug treatment, steering away from the traditional view of one-size-fits-all medicine. A premise of this study is that the sex of a patient influences difference in disease characteristics and risk factors. In this study, we intend to exploit and to obtain better sex-specific biomarkers from gene-expression data. We propose a procedure to isolate a set of important genes as sex-specific genomic biomarkers, which may enable more effective patient treatment. A set of sex-specific genes is obtained by a variable importance ranking using a combination of cross-validation methods. The proposed procedure is applied to three gene-expression datasets. C1 [Moon, Hojin; Lopez, Karen L.] Calif State Univ Long Beach, Dept Math & Stat, Long Beach, CA 90840 USA. [Lin, Grace I.] Univ Calif Santa Cruz, Dept Comp Sci, Santa Cruz, CA 95064 USA. [Chen, James J.] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Chen, James J.] China Med Univ, Grad Inst Biostat, Taichung, Taiwan. [Chen, James J.] China Med Univ, Biostat Ctr, Taichung, Taiwan. RP Moon, H (reprint author), Calif State Univ Long Beach, Dept Math & Stat, 1250 Bellflower Blvd, Long Beach, CA 90840 USA. EM hojin.moon@csulb.edu FU Research, Scholarship, and Creative Activity (RSCA) Award from California State University, Long Beach FX Hojin Moon's research was partially supported by the Research, Scholarship, and Creative Activity (RSCA) Award from California State University, Long Beach, and was partially supported by the Faculty Research Participation Program at the NCTR administered by the Oak Ridge Institute for Science and Education through an interagency agreement between USDOE and USFDA. The views presented in this paper are those of the authors and do not necessarily represent those of the U.S. Food and Drug Administration. NR 17 TC 1 Z9 1 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 0278-0240 EI 1875-8630 J9 DIS MARKERS JI Dis. Markers PY 2013 BP 661 EP 667 DI 10.1155/2013/393020 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 286FO UT WOS:000329451900001 PM 24302811 ER PT B AU Grim, CJ AF Grim, Christopher J. BE Morris, JG Potter, ME TI Aeromonas and Plesiomonas SO FOODBORNE INFECTIONS AND INTOXICATIONS, 4TH EDITION LA English DT Article; Book Chapter ID GENUS AEROMONAS; SHIGELLOIDES DIARRHEA; TRAVELERS-DIARRHEA; UNITED-STATES; INFECTIONS; HYDROPHILA; EPIDEMIOLOGY; DISEASE; MICROBIOLOGY; AMPICILLIN C1 USDA, Ctr Food Safety & Appl Nutr, Laurel, MD USA. RP Grim, CJ (reprint author), USDA, Ctr Food Safety & Appl Nutr, Laurel, MD USA. NR 42 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-391476-7; 978-0-12-416041-5 PY 2013 BP 229 EP 237 PG 9 WC Food Science & Technology; Public, Environmental & Occupational Health SC Food Science & Technology; Public, Environmental & Occupational Health GA BID68 UT WOS:000327740900016 ER PT B AU Tall, BD Grim, CJ Franco, AA Jarvis, KG Hu, L Kothary, MH Sathyamoorthy, V Gopinath, G Fanning, S AF Tall, B. D. Grim, C. J. Franco, A. A. Jarvis, K. G. Hu, L. Kothary, M. H. Sathyamoorthy, V. Gopinath, G. Fanning, S. BE Morris, JG Potter, ME TI Cronobacter Species (formerly Enterobacter sakazakii) SO FOODBORNE INFECTIONS AND INTOXICATIONS, 4TH EDITION LA English DT Article; Book Chapter ID POWDERED INFANT FORMULA; EPITHELIAL-CELL INJURY; TURICENSIS SP-NOV; NECROTIZING ENTEROCOLITIS; ENVIRONMENTAL-SAMPLES; FRUIT POWDER; RAT MODEL; IDENTIFICATION; CELLULOSE; INFECTIONS C1 [Tall, B. D.; Franco, A. A.; Jarvis, K. G.; Hu, L.; Kothary, M. H.; Sathyamoorthy, V.; Gopinath, G.] USDA, Laurel, MD USA. [Grim, C. J.] USDA, Ctr Food Safety & Appl Nutr, Laurel, MD USA. [Fanning, S.] Univ Coll Dublin, UCD Ctr Food Safety, WHO Collaborating Ctr Res Reference & Training Cr, Sch Publ Hlth Physiotherapy & Populat Sci,UCD Vet, Dublin 2, Ireland. RP Tall, BD (reprint author), USDA, Laurel, MD USA. OI Fanning, Seamus/0000-0002-1922-8836; Tall, Ben/0000-0003-0399-3629 NR 45 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-391476-7; 978-0-12-416041-5 PY 2013 BP 251 EP 258 PG 8 WC Food Science & Technology; Public, Environmental & Occupational Health SC Food Science & Technology; Public, Environmental & Occupational Health GA BID68 UT WOS:000327740900018 ER PT B AU Glass, K Marshall, K AF Glass, Kathleen Marshall, Kristin BE Morris, JG Potter, ME TI Clostridium botulinum SO FOODBORNE INFECTIONS AND INTOXICATIONS, 4TH EDITION LA English DT Article; Book Chapter ID NEUROTOXIN COMPLEX GENES; FOODBORNE BOTULISM; INFANT BOTULISM; TOXIN PRODUCTION; STRAINS; HONEY; FOOD; DIVERSITY; GROWTH; PREVALENCE C1 [Glass, Kathleen] Univ Wisconsin, Food Res Inst, Madison, WI 53706 USA. [Marshall, Kristin] US FDA, Bedford Pk, IL USA. RP Glass, K (reprint author), Univ Wisconsin, Food Res Inst, Madison, WI 53706 USA. NR 59 TC 1 Z9 1 U1 1 U2 8 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-391476-7; 978-0-12-416041-5 PY 2013 BP 371 EP 387 PG 17 WC Food Science & Technology; Public, Environmental & Occupational Health SC Food Science & Technology; Public, Environmental & Occupational Health GA BID68 UT WOS:000327740900028 ER PT J AU Hutt, PB Temple, R AF Hutt, Peter Barton Temple, Robert TI Commemorating the 50th Anniversary of the Drug Amendments of 1962 SO FOOD AND DRUG LAW JOURNAL LA English DT Article ID FDA C1 [Hutt, Peter Barton] Covington & Burling LLP, Washington, DC USA. [Temple, Robert] US FDA, Clin Scienceat Ctr Drug Evaluat & Res CDER, Rockville, MD 20857 USA. RP Hutt, PB (reprint author), Covington & Burling LLP, Washington, DC USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2013 VL 68 IS 4 BP 449 EP 465 PG 17 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 276BQ UT WOS:000328723500005 PM 24552082 ER PT J AU Timme, RE Pettengill, JB Allard, MW Strain, E Barrangou, R Wehnes, C Van Kessel, JS Karns, JS Musser, SM Brown, EW AF Timme, Ruth E. Pettengill, James B. Allard, Marc W. Strain, Errol Barrangou, Rodolphe Wehnes, Chris Van Kessel, JoAnn S. Karns, Jeffrey S. Musser, Steven M. Brown, Eric W. TI Phylogenetic Diversity of the Enteric Pathogen Salmonella enterica subsp enterica Inferred from Genome-Wide Reference-Free SNP Characters SO GENOME BIOLOGY AND EVOLUTION LA English DT Article DE H antigens; serovar; O antigens; CRISPR; lineage-through-time plot; comparative method ID ESCHERICHIA-COLI STRAINS; MULTILOCUS GENOTYPE DATA; POPULATION-STRUCTURE; HOST ADAPTATION; EVOLUTION; PARATYPHI; DIVERGENCE; INFERENCE; SEROVARS; LINEAGE AB The enteric pathogen Salmonella enterica is one of the leading causes of foodborne illness in the world. The species is extremely diverse, containing more than 2,500 named serovars that are designated for their unique antigen characters and pathogenicity profiles-some are known to be virulent pathogens, while others are not. Questions regarding the evolution of pathogenicity, significance of antigen characters, diversity of clustered regularly interspaced short palindromic repeat (CRISPR) loci, among others, will remain elusive until a strong evolutionary framework is established. We present the first large-scale S. enterica subsp. enterica phylogeny inferred from a new reference-free k-mer approach of gathering single nucleotide polymorphisms (SNPs) from whole genomes. The phylogeny of 156 isolates representing 78 serovars (102 were newly sequenced) reveals two major lineages, each with many strongly supported sublineages. One of these lineages is the S. Typhi group; well nested within the phylogeny. Lineage-through-time analyses suggest there have been two instances of accelerated rates of diversification within the subspecies. We also found that antigen characters and CRISPR loci reveal different evolutionary patterns than that of the phylogeny, suggesting that a horizontal gene transfer or possibly a shared environmental acquisition might have influenced the present character distribution. Our study also shows the ability to extract reference-free SNPs from a large set of genomes and then to use these SNPs for phylogenetic reconstruction. This automated, annotation-free approach is an important step forward for bacterial disease tracking and in efficiently elucidating the evolutionary history of highly clonal organisms. C1 [Timme, Ruth E.; Pettengill, James B.; Allard, Marc W.; Strain, Errol; Musser, Steven M.; Brown, Eric W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Barrangou, Rodolphe] N Carolina State Univ, Dept Food Bioproc & Nutr Sci, Raleigh, NC 27695 USA. [Wehnes, Chris] DuPont Nutr & Hlth, Madison, WI USA. [Van Kessel, JoAnn S.; Karns, Jeffrey S.] ARS, Environm Microbial & Food Safety Lab, USDA, Beltsville, MD USA. RP Timme, RE (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM ruth.timme@fda.hhs.gov RI Barrangou, Rodolphe/I-2878-2014 OI Barrangou, Rodolphe/0000-0002-0648-3504 FU Center for Food Safety and Applied Nutrition at the US Food and Drug Administration FX The authors thank Shea Gardner at Lawrence Livermore National Laboratory for the development of kSNP v. 2. They would also like to sincerely thank several people at FDA-CFAN: Charles Wang, Cong Li, and Andrea Ottesen for generating draft Salmonella genomes; David W. Weingaertner for assistance with fig. 4; Lili Velez and Barbara Berman for manuscript editing. Wesley Morovic at DuPont contributed helpful CRISPR sequence analyses, and Philippe Horvath provided the CRISPR DB II macro. And finally, the manuscript was greatly improved by critical comments from the reviewers. No human subjects or animals were used in this study. All authors have read the manuscript and agreed to its contents, subject matter, and author line order. These data are novel and have not been previously published elsewhere. Disclosure forms provided by the authors will be available with the full text of this article. This work was supported by the Center for Food Safety and Applied Nutrition at the US Food and Drug Administration. NR 47 TC 27 Z9 27 U1 0 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PY 2013 VL 5 IS 11 BP 2109 EP 2123 DI 10.1093/gbe/evt159 PG 15 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 271RZ UT WOS:000328410600012 PM 24158624 ER PT J AU Calleo, J Williams, JR Amspoker, AB Swearingen, L Hirsch, ES Anderson, K Goldstein, SR Grill, S Lehmann, S Little, JT Margolis, RL Palanci, J Pontone, GM Weiss, H Rabins, P Marsh, L AF Calleo, Jessica Williams, James R. Amspoker, Amber B. Swearingen, Leah Hirsch, Elaina S. Anderson, Karen Goldstein, Susanne R. Grill, Stephen Lehmann, Susan Little, John T. Margolis, Russell L. Palanci, Justin Pontone, Gregory M. Weiss, Howard Rabins, Peter Marsh, Laura TI Application of Depression Rating Scales in Patients with Parkinson's Disease with and without Co-Occurring Anxiety SO JOURNAL OF PARKINSONS DISEASE LA English DT Article DE Parkinson's disease; depression; anxiety; psychiatric disorder; rating scale ID COMORBID ANXIETY; DISORDERS; SYMPTOMATOLOGY; PREVALENCE; VALIDATION; INVENTORY; LIFE AB Background: In patients with Parkinson's disease (PD), depressive symptom rating scales facilitate identification of depressive disorders, which are common and disabling. Anxiety disturbances in PD, which lack valid assessment scales, frequently co-occur with PD-depression, are under-recognized, and require different interventions than depressive disorders. Whether high anxiety rates in PD confound depression scale performance or if any depression scales also predict anxiety disturbances is not known. Objective: To test the impact of co-occurring anxiety disorders on psychometric properties of depression rating scales in depressed PD patients and compare disability between PD patients with anxiety, depression, and comorbid anxiety and depressive disorders. Methods: PD subjects (n = 229) completed self-report and clinician-administered depression scales. Receiver operating characteristic curves were developed to estimate psychometric properties of each scale in those with depression alone, anxiety alone, and comorbid depression and anxiety. Between-group differences on all measures were examined. Results: Comorbid anxiety did not affect the psychometric properties of any scale when identifying depressive disorders, but is associated with greater symptom severity and disability. Depression-scale scores were not significantly different between subjects with anxiety disorders only and those without depressive or anxiety diagnoses. Conclusions: Co-occurring anxiety disorders do not impact performance of depression rating scales in depressed PD patients. However, depression rating scales do not adequately identify anxiety disturbances alone or in patients with depression. C1 [Calleo, Jessica; Amspoker, Amber B.] Houston VA HSR&D Ctr Innovat Qual Effectiveness &, Houston, TX USA. [Calleo, Jessica; Amspoker, Amber B.; Marsh, Laura] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Calleo, Jessica; Amspoker, Amber B.; Marsh, Laura] Baylor Coll Med, Houston, TX 77030 USA. [Williams, James R.] Biogen Idec Inc, Cambridge, MA USA. [Williams, James R.; Swearingen, Leah; Hirsch, Elaina S.; Goldstein, Susanne R.; Grill, Stephen; Lehmann, Susan; Little, John T.; Margolis, Russell L.; Palanci, Justin; Pontone, Gregory M.; Weiss, Howard; Rabins, Peter; Marsh, Laura] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Anderson, Karen] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. [Goldstein, Susanne R.] US FDA, Silver Spring, MD USA. [Goldstein, Susanne R.; Grill, Stephen] Parkinsons & Movement Disorder Ctr Maryland, Elkridge, MD USA. [Little, John T.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. [Little, John T.] Vet Affairs Med Ctr, Washington, DC 20422 USA. RP Marsh, L (reprint author), Michael E DeBakey VAMC, Mental Hlth Care Line 116A,2002 Holcombe Blvd, Houston, TX 77005 USA. EM laura.marsh2@va.gov FU National Institute of Mental Health (NIMH) [RO1-MH069666]; National Institute of Neurological Disorders and Stroke [P50-NS-58377]; National Institute on Aging [T32-AG-027668]; Department of Veterans Affairs; Donna Jeanne Gault Baumann Fund; Weldon Hall Trust; VA HSR&D Houston Center for Innovations in Quality, Effectiveness and Safety [CIN 13-413] FX The Methods of Optimal Depression Detection in PD (MOOD-PD) Study was funded by the National Institute of Mental Health (NIMH) grant RO1-MH069666. Co-authors were also supported by National Institute of Neurological Disorders and Stroke grant P50-NS-58377 (the Morris K. Udall Parkinson's Disease Research Center of Excellence at Johns Hopkins), National Institute on Aging grant T32-AG-027668, the Department of Veterans Affairs, the Donna Jeanne Gault Baumann Fund, and the Weldon Hall Trust. This work was also partly supported by the VA HSR&D Houston Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413). The views expressed reflect those of the authors and not necessarily those of the Department of Veterans Affairs, Baylor College of Medicine the NIMH, the US Food and Drug Administration or the US government. The NIMH had no role in the design and conduct of the study; the collection, management, analysis and interpretation of the data; or the preparation, review or approval of the manuscript. NR 28 TC 2 Z9 2 U1 1 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1877-7171 EI 1877-718X J9 J PARKINSON DIS JI J. Parkinsons Dis. PY 2013 VL 3 IS 4 BP 603 EP 608 DI 10.3233/JPD-130264 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 270PY UT WOS:000328332100013 PM 24275604 ER PT J AU Daneshian, M Botana, LM Bottein, MYD Buckland, G Campas, M Dennison, N Dickey, RW Diogene, J Fessard, V Hartung, T Humpage, A Leist, M Molgo, J Quilliam, MA Rovida, C Suarez-Isla, BA Tubaro, A Wagner, K Zoller, O Dietrich, D AF Daneshian, Mardas Botana, Luis M. Bottein, Marie-Yasmine Dechraoui Buckland, Gemma Campas, Monica Dennison, Ngaire Dickey, Robert W. Diogene, Jorge Fessard, Valerie Hartung, Thomas Humpage, Andrew Leist, Marcel Molgo, Jordi Quilliam, Michael A. Rovida, Costanza Suarez-Isla, Benjamin A. Tubaro, Aurelia Wagner, Kristina Zoller, Otmar Dietrich, Daniel TI A Roadmap for Hazard Monitoring and Risk Assessment of Marine Biotoxins on the Basis of Chemical and Biological Test Systems SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION LA English DT Article DE marine biotoxins; risk assessment; consumer protection; regulatory toxicology ID PARALYTIC SHELLFISH TOXINS; RECEPTOR-BINDING ASSAY; ALEXANDRIUM-OSTENFELDII DINOPHYCEAE; TANDEM MASS-SPECTROMETRY; LC-MS/MS ANALYSIS; PERFORMANCE LIQUID-CHROMATOGRAPHY; SINGLE-LABORATORY VALIDATION; OYSTER CRASSOSTREA-VIRGINICA; LINKED-IMMUNOSORBENT-ASSAY; CEREBELLAR GRANULE NEURONS AB Aquatic food accounts for over 40% of global animal food products, and the potential contamination with toxins of algal origin - marine biotoxins - poses a health threat for consumers, The gold standards to assess toxins in aquatic food have traditionally been in vivo methods, i.e., the mouse as well as the rat bioassay. Besides ethical concerns, there is also a need for more reliable test methods because of low inter-species comparability, high intra-species variability, the high number of false positive and negative results as well as questionable extrapolation of quantitative risk to humans. For this reason, a transatlantic group of experts in the field of marine biotoxins was convened from academia and regulatory safety authorities to discuss future approaches to marine biotoxin testing. In this report they provide a background on the toxin classes, on their chemical characterization, the epidemiology, on risk assessment and management, as well as on their assumed mode of action. Most importantly, physiological functional assays such as in vitro bioassays and also analytical techniques, e.g., liquid chromatography coupled mass spectrometry (LC-MS), as substitutes for the rodent bioassay are reviewed. This forms the basis for recommendations on methodologies for hazard monitoring and risk assessment, establishment of causality of intoxications in human cases, a roadmap for research and development of human-relevant functional assays, as well as new approaches for a consumer directed safety concept. C1 [Daneshian, Mardas; Hartung, Thomas; Leist, Marcel; Rovida, Costanza; Dietrich, Daniel] Univ Konstanz, CAAT Europe, D-78457 Constance, Germany. [Botana, Luis M.] USC Campus Lugo, Dept Pharmacol, Fac Vet Sci, Lugo, Spain. [Bottein, Marie-Yasmine Dechraoui] NOAA, Ctr Human Hlth Risk, Hollings Marine Lab, Charleston, SC USA. [Buckland, Gemma] Humane Soc Int, Washington, DC USA. [Campas, Monica; Diogene, Jorge] IRTA, Marine Monitoring & Food Safety Subprogram, San Carlos de la Rapita, Spain. [Dennison, Ngaire] Home Off, Anim Sci Regulat Unit, Dundee, Scotland. [Dickey, Robert W.] FDA Ctr Food Safety & Appl Nutr, Div Seafood Sci & Technol, Dauphin Isl, AL USA. [Fessard, Valerie] French Agcy Food Environm & Occupat Hlth & Safety, Lab Fougeres, Fougeres, France. [Hartung, Thomas] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, CAAT, Baltimore, MD USA. [Humpage, Andrew] Australian Water Qual Ctr, Adelaide, SA, Australia. [Leist, Marcel] Univ Konstanz, Doerenkamp Zbinden Chair Invitro Toxicol & Biomed, D-78457 Constance, Germany. [Molgo, Jordi] CNRS, Inst Neurobiol Alfred Fessard, Gif Sur Yvette, France. [Quilliam, Michael A.] Natl Res Council Canada, Halifax, NS, Canada. [Suarez-Isla, Benjamin A.] Univ Chile, Fac Med, Santiago, Chile. [Tubaro, Aurelia] Univ Trieste, Dept Life Sci, Trieste, Italy. [Wagner, Kristina] German Anim Welf Federat, Anim Welf Acad, Neubiberg, Germany. [Zoller, Otmar] Swiss Fed Off Publ Hlth, Consumer Protect Directorate, Food Safety Div, Bern, Switzerland. [Dietrich, Daniel] Univ Konstanz, Chair Human & Environm Toxicol, D-78457 Constance, Germany. RP Dietrich, D (reprint author), Univ Konstanz, Chair Human & Environm Toxicol, POB X 918, D-78457 Constance, Germany. RI Campas, Monica/J-9900-2013; Leist, Marcel/D-2133-2010 OI Campas, Monica/0000-0002-1220-7100; Leist, Marcel/0000-0002-3778-8693 NR 638 TC 6 Z9 6 U1 0 U2 24 PU SPEKTRUM AKADEMISCHER VERLAG-SPRINGER-VERLAG GMBH PI HEILDEBERG PA TIERGARTENSTRASSE 17, HEILDEBERG, 69121, GERMANY SN 1868-596X EI 1868-8551 J9 ALTEX-ALTERN ANIM EX JI ALTEX-Altern. Anim. Exp. PY 2013 VL 30 IS 4 BP 487 EP 545 PG 59 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 264TE UT WOS:000327903100006 PM 24173170 ER PT J AU Lomonaco, S Verghese, B Gerner-Smidt, P Tarr, C Gladney, L Joseph, L Katz, L Turnsek, M Frace, M Chen, Y Brown, E Meinersmann, R Berrang, M Knabel, S AF Lomonaco, Sara Verghese, Bindhu Gerner-Smidt, Peter Tarr, Cheryl Gladney, Lori Joseph, Lavin Katz, Lee Turnsek, Maryann Frace, Michael Chen, Yi Brown, Eric Meinersmann, Richard Berrang, Mark Knabel, Stephen TI Novel Epidemic Clones of Listeria monocytogenes, United States, 2011 SO EMERGING INFECTIOUS DISEASES LA English DT Article ID PROCESSING PLANT; OUTBREAK; POULTRY; STRAINS; MEAT AB We identified a novel serotype 1/2a outbreak strain and 2 hovel epidemic clones of Listeria monocytogenes while investigating a foodborne outbreak of listeriosis associated with consumption of cantaloupe during 2011 in the United States. Comparative analyses of strains worldwide are essential to identification of novel outbreak strains and epidemic clones. C1 [Lomonaco, Sara] Univ Turin, Dept Anim Pathol, Turin, Italy. [Verghese, Bindhu] Accugenix, Newark, DE USA. [Verghese, Bindhu; Knabel, Stephen] Penn State Univ, University Pk, PA 16802 USA. [Gerner-Smidt, Peter; Tarr, Cheryl; Gladney, Lori; Joseph, Lavin; Katz, Lee; Turnsek, Maryann; Frace, Michael] Ctr Dis Control & Prevent, Atlanta, GA USA. [Chen, Yi; Brown, Eric] US FDA, College Pk, MD USA. [Meinersmann, Richard; Berrang, Mark] USDA, Athens, GA USA. RP Knabel, S (reprint author), Penn State Univ, Dept Food Sci, 405 Food Sci Bldg, University Pk, PA 16802 USA. EM sjk9@psu.edu OI Lomonaco, Sara/0000-0001-8242-6280 FU USDA FX S.L. conducted this research while she was a visiting scientist at Pennsylvania State University during September 5-October 15, 2011. This study was partially funded by a USDA Special Grant on Milk Safety. NR 15 TC 47 Z9 50 U1 1 U2 14 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 EI 1080-6059 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JAN PY 2013 VL 19 IS 1 BP 147 EP 150 DI 10.3201/eid1901.121167 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 268LS UT WOS:000328172800025 PM 23260778 ER PT J AU Botsis, T Ball, R AF Botsis, T. Ball, R. TI Automating case definitions using literature-based reasoning SO APPLIED CLINICAL INFORMATICS LA English DT Article DE Case definition; safety surveillance; semantic networks; literature-based reasoning; anaphylaxis; similarity ID EVENTS FOLLOWING IMMUNIZATION; WORD SENSE DISAMBIGUATION; CLINICAL CASE-DEFINITION; RELATION EXTRACTION; BIOMEDICAL DOMAIN; REPORTING SYSTEM; NEURAL-NETWORK; HEALTH DATA; TEXT; VALIDATION AB Background: Establishing a Case Definition (CDef) is a first step in many epidemiological, clinical, surveillance, and research activities. The application of CDefs still relies on manual steps and this is a major source of inefficiency in surveillance and research. Objective: Describe the need and propose an approach for automating the useful representation of CDefs for medical conditions. Methods: We translated the existing Brighton Collaboration CDef for anaphylaxis by mostly relying on the identification of synonyms for the criteria of the CDef using the NLM MetaMap tool. We also generated a CDef for the same condition using all the related PubMed abstracts, processing them with a text mining tool, and further treating the synonyms with the above strategy. The co-occurrence of the anaphylaxis and any other medical term within the same sentence of the abstracts supported the construction of a large semantic network. The 'islands' algorithm reduced the network and revealed its densest region including the nodes that were used to represent the key criteria of the CDef. We evaluated the ability of the "translated" and the "generated" CDef to classify a set of 6034 H1N1 reports for anaphylaxis using two similarity approaches and comparing them with our previous semi-automated classification approach. Results: Overall classification performance across approaches to producing CDefs was similar, with the generated CDef and vector space model with cosine similarity having the highest accuracy (0.825+/-0.003) and the semi-automated approach and vector space model with cosine similarity having the highest recall (0.809+/-0.042). Precision was low for all approaches. Conclusion: The useful representation of CDefs is a complicated task but potentially offers substantial gains in efficiency to support safety and clinical surveillance. C1 [Botsis, T.; Ball, R.] US FDA, Off Biostat & Epidemiol, CBER, Rockville, MD 20852 USA. [Botsis, T.] Univ Tromso, Dept Comp Sci, Tromso, Norway. RP Botsis, T (reprint author), US FDA, Off Biostat & Epidemiol, CBER, Woodmont Off Complex 1,Rm 306N,1401 Rockville Pik, Rockville, MD 20852 USA. EM Taxiarchis.Botsis@fda.hhs.gov FU Center for Biologics Evaluation and Research FX This project was supported in part by the appointment of Taxiarchis Botsis to the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U. S. Department of Energy and the U.S. Food and Drug Administration. The authors would like to thank Michael D. Nguyen for the insightful review of the manuscript and his constructive comments. NR 61 TC 3 Z9 3 U1 1 U2 2 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 1869-0327 J9 APPL CLIN INFORM JI Appl. Clin. Inform. PY 2013 VL 4 IS 4 BP 515 EP 527 DI 10.4338/ACI-2013-04-RA-0028 PG 13 WC Medical Informatics SC Medical Informatics GA 262HM UT WOS:000327725000005 PM 24454579 ER PT J AU Ferlin, KM Kaplan, DS Fisher, JP AF Ferlin, Kimberly M. Kaplan, David S. Fisher, John P. BE Ramalingam, M Jabbari, E Ramakrishna, S Khademhosseini, A TI CHARACTERIZATION OF THE ADHESIVE INTERACTIONS BETWEEN CELLS AND BIOMATERIALS SO MICRO AND NANOTECHNOLOGIES IN ENGINEERING STEM CELLS AND TISSUES LA English DT Article; Book Chapter ID MESENCHYMAL STEM-CELLS; SYNTHETIC BIODEGRADABLE POLYMERS; PHOTOCROSSLINKED HYALURONIC-ACID; SILK-BASED BIOMATERIALS; SMOOTH-MUSCLE-CELLS; BONE-MARROW-CELLS; EXTRACELLULAR-MATRIX; POLY(PROPYLENE FUMARATE); POLY(ETHYLENE GLYCOL); OSTEOGENIC DIFFERENTIATION C1 [Ferlin, Kimberly M.; Fisher, John P.] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. [Ferlin, Kimberly M.; Kaplan, David S.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Ferlin, KM (reprint author), Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. NR 132 TC 1 Z9 1 U1 1 U2 5 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-14042-0 PY 2013 BP 159 EP 182 D2 10.1002/9781118574775 PG 24 WC Cell & Tissue Engineering; Nanoscience & Nanotechnology SC Cell Biology; Science & Technology - Other Topics GA BID80 UT WOS:000327746900008 ER PT J AU Lee, SL Brown, P Wang, J Dorsam, RT AF Lee, Shwu-Luan Brown, Paul Wang, Jian Dorsam, Robert T. BE Cheng, K Mahato, RI TI Nonclinical Safety Assessments and Clinical Pharmacokinetics for Oligonucleotide Therapeutics: A Regulatory Perspective SO ADVANCED DELIVERY AND THERAPEUTIC APPLICATIONS OF RNAI LA English DT Article; Book Chapter ID ANTISENSE OLIGONUCLEOTIDE; PHARMACOLOGY; TOXICOLOGY; BCL-2; DRUGS; RATS C1 [Lee, Shwu-Luan; Brown, Paul; Dorsam, Robert T.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Wang, Jian] US FDA, Off Translat Sci, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Lee, SL (reprint author), US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 15 TC 4 Z9 4 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-119-97686-8 PY 2013 BP 63 EP 81 D2 10.1002/9781118610749 PG 19 WC Engineering, Biomedical; Pharmacology & Pharmacy SC Engineering; Pharmacology & Pharmacy GA BIC99 UT WOS:000327435600005 ER PT S AU Fatas, E Vicente, J Latorre, B Lera, F Vinals, V Lopez, MV Blanco, N Pena, C Gonzalez-Cebollada, C Moret-Fernandez, D AF Fatas, E. Vicente, J. Latorre, B. Lera, F. Vinals, V. Lopez, M. V. Blanco, N. Pena, C. Gonzalez-Cebollada, C. Moret-Fernandez, D. BE Romano, N DUrso, G Severino, G Chirico, GB Palladino, M TI TDR-LAB 2.0 Improved TDR Software for soil water content and electrical conductivity measurements SO FOUR DECADES OF PROGRESS IN MONITORING AND MODELING OF PROCESSES IN THE SOIL-PLANT-ATMOSPHERE SYSTEM: APPLICATIONS AND CHALLENGES SE Procedia Environmental Sciences LA English DT Proceedings Paper CT International Conference on Four Decades of Progress in Monitoring and Modeling of Processes in the Soil-Plant-Atmosphere System CY JUN 19-21, 2013 CL Naples, ITALY DE Time Domain Reflectometry; Software; Waveform ID TIME-DOMAIN REFLECTOMETRY; PROBE AB Time Domain Reflectometry is a technique widely used in hydrology and agronomy that allows real time estimation of soil volumetric water content (0), which is related to soil's apparent permittivity (epsilon a) and bulk electrical conductivity (sigma). This work presents an enhanced release of TDR-Lab, software which controls instrumentation for field measurements of theta and sigma, enabling a convenient recording and retrieving of data. TDR-Lab 2.0 supports Tektronics 1502C, TDR-100 Campbell Sci. and TRASE Soil-moisture Equipment Corp., which can be connected to a multiplexing system (SDMX50, Campbell Sci) allowing automated scheduled measurements from up to 251 different probes. This new release, when connected to TDR-100, allows increasing the waveform accuracy up to 2048 points/waveform. Multiple comparison of TDR waveform within the same TDR screen is now allowed. Graphical or numerical methods can he used for the estimation of 0 and a from soil measurements coming taken with different probes. Additional features to carry out water-surface-level measurements such as matric potential and soil solution electrical conductivity are also available when measurements are made using the corresponding specific probes. Two different versions, a lite and a full release, for field and laboratory applications have been developed. The light version with a reduced set of features (TDR-Lab Lite) was designed to run in low-end ultraportable devices. TDR-Lab Lite works with XML-files instead of the SQL database engine of the extended TDR-Lab, and has lower system requirements and a faster boot-up time. A robust import/export graphical user interface (GUI) facilitates transferring projects between the centralized SQL database and XML files. A new project manager window has been implemented, where the bar menu has been complemented with a useful set of icons. The display system projects has been improved and simplified. Within the project, a new friendly configuration manager for cables and TDR probes has been developed. Finally, an improved calibration procedure for TDR probes has been implemented. TDR Lab 2.0 supports more devices and provides additional estimated features from soil's measurements. Besides, the low hardware requirement of TDR-Lab Lite facilitates faster in-the-field tests and measurements. (C) 2013 The Authors. Published by Elsevier B.V C1 [Fatas, E.; Lera, F.; Vinals, V.; Lopez, M. V.; Blanco, N.; Pena, C.] Univ Zaragoza, ICMA CSIC, Dept Ingn Elect & Comunicac, C Maria de Luna 1, Zaragoza 50018, Spain. [Vicente, J.] US FDA, Ctr Devices & Radiol Hlth, Div Phys, Off Sci & Engn Labs, Silver Spring, MD USA. [Latorre, B.; Moret-Fernandez, D.] CSIC, Dept Suelo & Agua Estac Expt Aula Det, E-50080 Zaragoza, Spain. [Gonzalez-Cebollada, C.] Univ Zaragoza, Area Mecan Fluidos, E-50009 Zaragoza, Spain. RP Fatas, E (reprint author), Univ Zaragoza, ICMA CSIC, Dept Ingn Elect & Comunicac, C Maria de Luna 1, Zaragoza 50018, Spain. EM efatas@gmail.com RI Moret-Fernandez, David/K-8876-2014; Pena-Sancho, Carolina/B-5205-2015; Latorre, Borja/L-1749-2014; Lera, Francisco/H-4526-2015; Vinals, Victor/F-6451-2016; OI Moret-Fernandez, David/0000-0002-6674-0453; Pena-Sancho, Carolina/0000-0003-4444-9806; Latorre, Borja/0000-0002-6720-3326; Lera, Francisco/0000-0002-1568-1481; Vinals, Victor/0000-0002-5976-1352; Vicente, Jose/0000-0001-9963-1205 NR 15 TC 3 Z9 3 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1878-0296 J9 PROCEDIA ENVIRON SCI PY 2013 VL 19 BP 474 EP 483 DI 10.1016/j.proenv.2013.06.054 PG 10 WC Plant Sciences; Environmental Sciences; Soil Science SC Plant Sciences; Environmental Sciences & Ecology; Agriculture GA BHX21 UT WOS:000326900300053 ER PT S AU Balan, KV Babu, US Godar, DE Calvo, MS AF Balan, K. V. Babu, U. S. Godar, D. E. Calvo, M. S. BE Watson, RR TI Vitamin D and respiratory infections in infants and toddlers: a nutri-shine perspective SO HANDBOOK OF VITAMIN D IN HUMAN HEALTH: PREVENTION, TREATMENT AND TOXICITY SE Human Health Handbooks LA English DT Article; Book Chapter DE vitamin D deficiency; infants; vitamin D supplementation; wheezing; skeletal health; respiratory infections; breast fed infants ID D DEFICIENCY; CORD-BLOOD; 25-HYDROXYVITAMIN D; D SUPPLEMENTATION; EARLY-CHILDHOOD; 1,25-DIHYDROXYVITAMIN D-3; TRACT INFECTIONS; VIRUS-INFECTION; HIGH PREVALENCE; D REQUIREMENTS AB There is compelling evidence of a global problem of poor vitamin D status in expecting mothers and postnatal life; and even more critical, is the evidence showing the association of vitamin D deficiency with increased morbidity and mortality risks from respiratory infections. Viral and bacterial pneumonia kills more children than any other illness, accounting for 19% of all deaths in children less than five years of age worldwide; and under-nutrition, which includes vitamin D insufficiency/deficiency, has been implicated in 53% of all these deaths. Poor vitamin D status is a result of insufficient sunlight exposure and/or poor dietary intake. Greater understanding of the role of vitamin D deficiency in precipitating lung infections grew from the use of rodent models and observational and intervention studies in infants and toddlers. Vitamin D adequacy is important to maintaining the key protective mechanism of developing lungs since it mediates the synthesis of antimicrobial peptides, the lungs strongest defense against viral and bacterial pathogens. If vitamin D intervention currently under study in several clinical trials is proven successful, then implementation of new fortification practices, revised guidelines for healthy sun exposure and public health programs for vitamin D supplementation of pregnant/lactating women and their infants may be effective strategies to aide in preventing neonates and children under five from developing pneumonia. Globally, there is potential to save more than a million young lives with preventive treatment, a compelling reason why the efficacy of optimizing vitamin D mediated defense against respiratory pathogens in infants and children merits further study. C1 [Balan, K. V.; Babu, U. S.; Calvo, M. S.] US FDA, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Godar, D. E.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Balan, KV (reprint author), US FDA, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd,HFS 025-MOD1, Laurel, MD 20708 USA. EM kannan.balan@fda.hhs.gov NR 85 TC 0 Z9 0 U1 0 U2 0 PU WAGENINGEN ACAD PUBL PI WAGENINGEN PA POSTBUS 220, 6700 AE WAGENINGEN, NETHERLANDS SN 2212-375X BN 978-90-8686-765-3; 978-90-8686-210-8 J9 HUM HEALT HANDB PY 2013 IS 4 BP 277 EP 298 D2 10.3920/978-908686-765-3 PG 22 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BIC84 UT WOS:000327428200016 ER PT J AU Fu, PP Xia, QS Zhao, YW Wang, SG Yu, HT Chiang, HM AF Fu, Peter P. Xia, Qingsu Zhao, Yuewei Wang, Shuguang Yu, Hongtao Chiang, Hsiu-Mei TI Phototoxicity of Herbal Plants and Herbal Products SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE phototoxicity; phytochemicals; herbal; mechanism of action; photocarcinogenicity; photogenotoxicity; PUVA therapy ID POLYCYCLIC AROMATIC-HYDROCARBONS; ST-JOHNS-WORT; HYDRASTIS-CANADENSIS-L.; MOUSE LYMPHOMA-CELLS; HACAT KERATINOCYTES-GENERATION; PIGMENT EPITHELIAL-CELLS; PHOTOINDUCED DNA-DAMAGE; VIVO MICRONUCLEUS TEST; SUCTION BLISTER FLUID; SIMULATED SOLAR LIGHT AB Plants are used by humans in daily life in many different ways, including as food, herbal medicines, and cosmetics. Unfortunately, many natural plants and their chemical constituents are photocytotoxic and photogenotoxic, and these phototoxic phytochemicals are widely present in many different plant families. To date, information concerning the phototoxicity and photogenotoxicity of many plants and their chemical constituents is limited. In this review, we discuss phototoxic plants and their major phototoxic constituents; routes of human exposure; phototoxicity of these plants and their constituents; general mechanisms of phototoxicity of plants and phototoxic components; and several representative phototoxic plants and their photoactive chemical constituents. C1 [Fu, Peter P.; Xia, Qingsu; Zhao, Yuewei; Wang, Shuguang] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Yu, Hongtao] Jackson State Univ, Dept Chem & Biochem, Jackson, MS USA. [Chiang, Hsiu-Mei] China Med Univ, Dept Cosmeceut, Taichung, Taiwan. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM peter.fu@fda.hhs.gov; hmchiang@mail.cmu.edu.tw RI Chiang, Hsiu-Mei/L-8150-2013 NR 291 TC 5 Z9 5 U1 4 U2 28 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1059-0501 EI 1532-4095 J9 J ENVIRON SCI HEAL C JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev. PD JAN 1 PY 2013 VL 31 IS 3 BP 213 EP 255 DI 10.1080/10590501.2013.824206 PG 43 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 217LC UT WOS:000324360000003 PM 24024520 ER PT S AU Combs, GF Trumbo, PR McKinley, MC Milner, J Studenski, S Kimura, T Watkins, SM Raiten, DJ AF Combs, Gerald F., Jr. Trumbo, Paula R. McKinley, Michelle C. Milner, John Studenski, Stephanie Kimura, Takeshi Watkins, Steven M. Raiten, Daniel J. GP Annals NY Acad Sci TI Biomarkers in nutrition: new frontiers in research and application SO ANNALS MEETING REPORTS SE Annals of the New York Academy of Sciences LA English DT Article DE biomarkers; nutrition; nutrients ID SELENIUM SUPPLEMENTATION; CANCER PREVENTION; ADULTS; TRIAL; MALNUTRITION; SARCOPENIA AB Nutritional biomarkers-biochemical, functional, or clinical indices of nutrient intake, status, or functional effects-are needed to support evidence-based clinical guidance and effective health programs and policies related to food, nutrition, and health. Such indices can reveal information about biological or physiological responses to dietary behavior or pathogenic processes, and can be used to monitor responses to therapeutic interventions and to provide information on interindividual differences in response to diet and nutrition. Many nutritional biomarkers are available; yet there has been no formal mechanism to establish consensus regarding the optimal biomarkers for particular nutrients and applications. C1 [Combs, Gerald F., Jr.] USDA ARS, Grand Forks Human Nutr Res Ctr, Grand Forks, ND 58202 USA. [Trumbo, Paula R.] US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. [McKinley, Michelle C.] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Belfast, Antrim, North Ireland. [Milner, John] NCI, NIH, US Dept Hlth & Human Serv, Rockville, MD USA. [Studenski, Stephanie] Univ Pittsburgh, Pittsburgh, PA USA. [Kimura, Takeshi] Ajinomoto Co Inc, Tokyo, Japan. [Watkins, Steven M.] Tethys Biosci Inc, Emeryville, CA USA. [Raiten, Daniel J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, US Dept Hlth & Human Serv, Rockville, MD USA. RP Combs, GF (reprint author), USDA ARS, Grand Forks Human Nutr Res Ctr, Grand Forks, ND 58202 USA. EM annals@nyas.org FU Medical Research Council [MR/K023241/1] NR 26 TC 8 Z9 8 U1 2 U2 13 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2013 VL 1278 BP 1 EP 10 DI 10.1111/nyas.12069 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BHO53 UT WOS:000326100700001 PM 23488557 ER PT S AU Uribarri, J Calvo, MS AF Uribarri, Jaime Calvo, Mona S. BE Uribarri, J TI Introduction to Dietary Phosphorus Excess and Health SO DIETARY PHOSPHORUS EXCESS AND HEALTH SE Annals of the New York Academy of Sciences LA English DT Editorial Material CT Symposium on Current Dietary Phosphorus Intake - Are There Potential Implications for Public Health CY FEB 26, 2013 CL New York Acad Sci, New York, NY SP New York Acad Sci, Sackler Inst Nutr Sci HO New York Acad Sci C1 [Uribarri, Jaime] Icahn Sch Med Mt Sinai, Dept Med, New York, NY USA. [Calvo, Mona S.] US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Laurel, MD USA. RP Uribarri, J (reprint author), Icahn Sch Med Mt Sinai, Dept Med, New York, NY USA. NR 0 TC 1 Z9 1 U1 2 U2 5 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2013 VL 1301 BP III EP IV DI 10.1111/nyas.12302 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BHM48 UT WOS:000325922600001 PM 24472075 ER PT S AU Calvo, MS Tucker, KL AF Calvo, Mona S. Tucker, Katherine L. BE Uribarri, J TI Is phosphorus intake that exceeds dietary requirements a risk factor in bone health? SO DIETARY PHOSPHORUS EXCESS AND HEALTH SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Symposium on Current Dietary Phosphorus Intake - Are There Potential Implications for Public Health CY FEB 26, 2013 CL New York Acad Sci, New York, NY SP New York Acad Sci, Sackler Inst Nutr Sci HO New York Acad Sci DE phosphorus food additives; PTH; FGF-23; calcitriol; Ca:P intake ratio; serum phosphorus circadian rhythm; phosphoric acid; cola soft drinks; bone mineral density; dietary acid load; PRAL; bone turnover markers ID PARATHYROID-HORMONE CONCENTRATION; CONTAINING FOOD-ADDITIVES; CHRONIC KIDNEY-DISEASE; RENAL ACID LOAD; YOUNG-WOMEN; MINERAL DENSITY; CALCIUM; MEN; METABOLISM; SECRETION AB Phosphorus intake in excess of the nutrient needs of healthy adults is thought to disrupt hormonal regulation of phosphorus (P), calcium (Ca), and vitamin D, contributing to impaired peak bone mass, bone resorption, and greater risk of fracture. Elevation of extracellular phosphorus due to excessive intake is thought to be the main stimulus disrupting phosphorus homeostasis in healthy individuals, as it is in renal disease even when intake is modest. If high serum phosphorus is the critical link to the effect of high phosphorus intake on bone health, the issue could be addressed through epidemiologic or dietary studies. However, several confounding factors, including problems estimating accurate phosphorus intake, the influence of a low dietary Ca:P ratio, the acidic nature of phosphorus, the rapid rate of absorption and greater phosphorus bioavailability from processed food such as cola drinks, and circadian fluctuation in serum phosphorus, make this question difficult to address using conventional study designs. These confounding factors are considered in this review, exploring whether phosphorus intake exceeding nutrient needs in healthy individuals disrupts phosphorus regulation and negatively affects bone accretion or loss. Specific attention is given to phosphorus intake from processed foods rich in phosphorus additives, which significantly contribute to phosphorus intake. C1 [Calvo, Mona S.] US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Laurel, MD 20708 USA. [Tucker, Katherine L.] Univ Massachusetts, Dept Clin Lab & Nutrit Sci, Lowell, MA USA. RP Calvo, MS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, MOD-1,HFS-025,8301 Muirkirk Rd, Laurel, MD 20708 USA. EM mona.calvo@FDA.HHS.gov OI Tucker, Katherine/0000-0001-7640-662X NR 38 TC 16 Z9 16 U1 2 U2 24 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2013 VL 1301 BP 29 EP 35 DI 10.1111/nyas.12300 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BHM48 UT WOS:000325922600005 PM 24472074 ER PT S AU Schisler, MR Moore, MM Gollapudi, BB AF Schisler, Melissa R. Moore, Martha M. Gollapudi, B. Bhaskar BE Dhawan, A Bajpayee, M TI In Vitro Mouse Lymphoma (L5178Y Tk(+/-)-3.7.2C) Forward Mutation Assay SO GENOTOXICITY ASSESSMENT: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Mouse lymphoma; Genetic toxicology; Thymidine kinase; Forward mutation assay; L5178Y (Tk(+/-)-3.7.2C) cells ID DISCRIMINATE RODENT CARCINOGENS; INTERNATIONAL WORKSHOP; GENOTOXICITY TESTS; CELL-LINE; RELATIVE PREDICTIVITY; CYTOGENETIC ANALYSIS; GENE; MUTAGENICITY; SYSTEM; NONCARCINOGENS AB The in vitro mouse lymphoma assay (MLA) is one of the most widely practiced assays in genetic toxicology. MLA detects forward mutations at the thymidine kinase (Tk) locus of the L5178Y (Tk(+/-) -3.7.2C) cell line derived from a mouse thymic lymphoma. This assay is capable of detecting a wide range of genetic events including point mutations, deletions (intragenic) and multilocus, chromosomal rearrangements, mitotic recombination, and nondisjunction. There are two equally accepted versions of the assay, one using soft agar cloning and the second method using liquid media cloning in 96-microwell plates. There are two morphologically distinct types of mutant colonies recovered in the MLA: small-and large-colony mutants. The induction of small-colony mutants is associated with chemicals inducing gross chromosomal aberrations whereas the induction of large mutant colonies is generally associated with chemicals inducing point mutations. The source and karyotype of the cell line as well as the culture conditions are important variables that could influence the assay performance. The assay when performed according to the standards recommended by the International Workshops on Genotoxicity Testing is capable of providing valuable genotoxicity hazard information as part of the overall safety assessment process of various classes of test substances. C1 [Schisler, Melissa R.; Gollapudi, B. Bhaskar] Dow Chem Co USA, Toxicol & Environm Res & Consulting, Midland, MI 48674 USA. [Moore, Martha M.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Schisler, MR (reprint author), Dow Chem Co USA, Toxicol & Environm Res & Consulting, Midland, MI 48674 USA. NR 29 TC 3 Z9 3 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-529-3; 978-1-62703-528-6 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1044 BP 27 EP 50 DI 10.1007/978-1-62703-529-3_2 D2 10.1007/978-1-62703-529-3 PG 24 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA BHJ04 UT WOS:000325571800004 PM 23896870 ER PT S AU Dobrovolsky, VN Shaddock, JG Mittelstaedt, RA Miura, D Heflich, RH AF Dobrovolsky, Vasily N. Shaddock, Joseph G. Mittelstaedt, Roberta A. Miura, Daishiro Heflich, Robert H. BE Dhawan, A Bajpayee, M TI Detection of In Vivo Mutation in the Hprt and Pig-a Genes of Rat Lymphocytes SO GENOTOXICITY ASSESSMENT: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Hprt; Pig-a; alamarBlue (TM); Mutation; 6-Thioguanine; Proaerolysin ID CELLS AB Assays for in vivo mutation are used to identify genotoxic hazards and phenotypes prone to genomic instability and cancer. The hypoxanthine guanine phosphoribosyl transferase (Hprt) gene and the phosphatidyl inositol glycan, class A (Pig-a) gene are endogenous X-linked genes that can be used as reporters of mutation in peripheral blood lymphocytes from most mammals. Here we describe methodology for measuring Hprt and Pig-a mutation in rat T-lymphocytes. The identification and selective expansion of mutant lymphocytes are based upon the phenotypic properties of Hprt- and Pig-a-deficient cells, i.e., resistance to the purine analog, 6-thioguanine, or to the bacterial toxin, proaerolysin. Expanded mutants can be further analyzed by sequencing cDNA from the target transcripts for identification of small sequence alterations and by multiplex PCR analysis of genomic DNA for the detection of deletions. C1 [Dobrovolsky, Vasily N.; Shaddock, Joseph G.; Mittelstaedt, Roberta A.; Heflich, Robert H.] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Miura, Daishiro] Teijin Pharma Ltd, Strateg Planning Dept, Tokyo, Japan. RP Dobrovolsky, VN (reprint author), US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. NR 9 TC 7 Z9 7 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-529-3; 978-1-62703-528-6 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1044 BP 79 EP 95 DI 10.1007/978-1-62703-529-3_4 D2 10.1007/978-1-62703-529-3 PG 17 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA BHJ04 UT WOS:000325571800006 PM 23896872 ER PT S AU Manjanatha, MG Cao, XF Shelton, SD Mittelstaedt, RA Heflich, RH AF Manjanatha, Mugimane G. Cao, Xuefei Shelton, Sharon D. Mittelstaedt, Roberta A. Heflich, Robert H. BE Dhawan, A Bajpayee, M TI In Vivo cII, gpt, and Spi(-) Gene Mutation Assays in Transgenic Mice and Rats SO GENOTOXICITY ASSESSMENT: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Big Blue (R); gpt-delta; cII mutants; gpt mutants; cII; gpt and Spi(-) assays AB Transgenic mutation assays are used to identify and characterize genotoxic hazards and for determining the mode of action for carcinogens. The three most popular transgenic mutational models are Big Bluer (rats or mice), Muta T mouse (mice), and gpt-delta (rats or mice). The Big Blue (R) and Muta T mouse models use the cII gene as a reporter of mutation whereas gpt-delta rodents use the gpt gene and the red/gam genes (Spi(-) selection) as mutation reporter genes. Here we describe methodology for conducting mutation assays with these transgenes. Transgenes recovered from tissue DNA are packaged into infectious lambda phage, bacteria are infected with the phage, and cII-mutant and Spi(-) plaques and gpt-mutant colonies are isolated using selective conditions and quantified. Selected mutants can be further analyzed for identification of small sequence alterations in the cII and gpt genes and large deletions at the Spi(-) locus. C1 [Manjanatha, Mugimane G.; Cao, Xuefei; Shelton, Sharon D.; Mittelstaedt, Roberta A.; Heflich, Robert H.] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Manjanatha, MG (reprint author), US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. NR 6 TC 2 Z9 2 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-529-3; 978-1-62703-528-6 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2013 VL 1044 BP 97 EP 119 DI 10.1007/978-1-62703-529-3_5 D2 10.1007/978-1-62703-529-3 PG 23 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA BHJ04 UT WOS:000325571800007 PM 23896873 ER PT J AU Jiang, J Zhang, LZ Li, H He, WW Yin, JJ AF Jiang, Jing Zhang, Lizhi Li, Hao He, Weiwei Yin, Jun Jie TI Self-doping and surface plasmon modification induced visible light photocatalysis of BiOCl SO NANOSCALE LA English DT Article ID ACTIVITY ENHANCEMENT; TITANIUM-DIOXIDE; HOT-ELECTRONS; THIN-FILMS; GOLD; SEMICONDUCTOR; NANOPARTICLES; OXIDE; WATER; NANOSTRUCTURES AB In this study we demonstrate that self-doping and surface plasmon resonance could endow a wide-band-gap ternary semiconductor BiOCl with remarkable visible light driven photocatalytic activity on the degradation of organic pollutants and photocurrent generation properties. The self-doped BiOCl with plasmonic silver modification was synthesized by a facile one-pot nonaqueous approach and systematically characterized using X-ray diffraction, scanning electron microscopy, transmission electron microscopy, UV-visible diffuse reflectance spectra, electron spin resonance, and X-ray photoelectron spectroscopy. The photocurrent enhancement was found to be intimately dependent on the irradiation wavelength and matched well with the intensity of the absorption of the Ag nanoparticles. Reactive species trapping experiments and electron spin resonance spectroscopy with 5,5-dimethyl-1-pyrroline-Noxide spin-trapping adducts confirmed that more oxidative species could be generated from the photogenerated electrons due to the plasmon-excitation of the metallic Ag in the self-doped BiOCl with plasmonic silver modification, which is responsible for the great enhancement of photocatalytic activity and photocurrent. Surface photovoltage spectroscopy and time-resolved photoluminescence spectroscopy results revealed the transfer of plasmon-band-induced electrons from Ag nanoparticles into BiOCl and the acceleration effect of surface plasmon resonance-induced intense oscillating electric fields on this electron transfer. This study would not only provide direct evidence of plasmonic photocatalysis, but also shed light on the design of highly efficient metal-semiconductor composite photocatalysts. C1 [Jiang, Jing; Zhang, Lizhi; Li, Hao] Cent China Normal Univ, Coll Chem, Inst Environm Chem, Key Lab Pesticide & Chem Biol,Minist Educ, Wuhan 430079, Peoples R China. [Jiang, Jing] China West Normal Univ, Coll Chem & Chem Engn, Nanchong 637002, Peoples R China. [He, Weiwei; Yin, Jun Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Zhang, LZ (reprint author), Cent China Normal Univ, Coll Chem, Inst Environm Chem, Key Lab Pesticide & Chem Biol,Minist Educ, Wuhan 430079, Peoples R China. EM zhanglz@mail.ccnu.edu.cn RI Yin, Jun Jie /E-5619-2014 FU National Basic Research Program of China (973 Program) [2013CB632402]; National Science Foundation of China [21073069, 91023010, 21177048, 21103141] FX This work was supported by National Basic Research Program of China (973 Program) (Grant 2013CB632402) and National Science Foundation of China (Grants 21073069, 91023010, 21177048, and 21103141). NR 64 TC 65 Z9 65 U1 25 U2 204 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 EI 2040-3372 J9 NANOSCALE JI Nanoscale PY 2013 VL 5 IS 21 BP 10573 EP 10581 DI 10.1039/c3nr03597b PG 9 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 235ZH UT WOS:000325762000063 PM 24056871 ER PT S AU Calhoun, WR Beylin, A Weiblinger, R Ilev, I AF Calhoun, William R., III Beylin, Alexander Weiblinger, Richard Ilev, Ilko BE Manns, F Soderberg, PG Ho, A TI Quantification of phase retardation in corneal tissues using a femtosecond laser SO OPHTHALMIC TECHNOLOGIES XXIII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Ophthalmic Technologies XXIII as a part of the SPIE Photonics West BiOS Meeting CY FEB 02-03, 2013 CL San Francisco, CA SP SPIE DE Femtosecond laser; cornea; phase rotation; retardation; birefringence; ophthalmic ID MECHANISMS; ABLATION AB The use of femtosecond lasers (FSL) in ophthalmic procedures, such as LASIK, lens replacement (cataract surgery), as well as several other treatments, is growing rapidly. The treatment effect is based on photo ablation of ocular tissues by a series of ultra-short laser pulses. However, the laser beam characteristics change dynamically due to interactions with birefringent corneal tissue, which may affect the outcome of the laser treatment. To better understand the effect the cornea has on the laser characteristics, we developed a system for measuring retardation and validated it with precise, standard phase retarders. Then we measured the phase retardation of FSLs through bovine corneas and found that there is a considerable, location dependent, variation in retardation values. This information can potentially help optimize FSL parameters to make their application in ophthalmic procedures safer and more effective. C1 [Calhoun, William R., III; Ilev, Ilko] US FDA, Ctr Devices & Radiol Hlth, Opt Therapeut & Med Nanophoton Lab, Off Sci & Engn Labs, Silver Spring, MD USA. [Beylin, Alexander; Weiblinger, Richard] U S Food & Drug Adm, Ctr Devices & Radiol Hlth, Off Device Evaluat, Silver Spring, MD USA. RP Calhoun, WR (reprint author), US FDA, Ctr Devices & Radiol Hlth, Opt Therapeut & Med Nanophoton Lab, Off Sci & Engn Labs, Silver Spring, MD USA. EM william.calhoun@fda.hhs.gov NR 7 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9336-1 J9 PROC SPIE PY 2013 VL 8567 AR 85672B DI 10.1117/12.2005954 PG 5 WC Ophthalmology; Optics SC Ophthalmology; Optics GA BHH46 UT WOS:000325430800035 ER PT J AU Nelson, MA Ondov, JM VanDerveer, MC Buchholz, BA AF Nelson, Michael A. Ondov, John M. VanDerveer, Michael C. Buchholz, Bruce A. TI CONTEMPORARY FRACTION OF BIS(2-ETHYLHEXYL) PHTHALATE IN STILTON CHEESE BY ACCELERATOR MASS SPECTROMETRY SO RADIOCARBON LA English DT Article; Proceedings Paper CT 21st International Radiocarbon Conference CY 2012 CL Paris, FRANCE ID ACID ESTERS; C-14 DATA; EXPOSURE; AMS; GRAPHITE; SAMPLES; MILK; DBP AB Measurements of the radiocarbon abundance in 5 samples of bis(2-ethylhexyl) phthalate (DEHP) isolated from Stilton cheese were made by accelerator mass spectrometry (AMS) to determine the fraction of carbon originating from contemporary biogenic sources. DEHP is classified as a "priority hazardous substance" by the European Union, a probable human carcinogen by the United States Environmental Protection Agency, and is suspected to be a human endocrine disrupter. Measurement of its C-14 abundance in a specific food indicates whether its presence is due to contamination from industrially synthesized DEHP or a naturally inherent component. A method was developed to determine the contemporary carbon fraction of DEHP in a fatty food matrix at concentrations of approximate to 0.14 mg/kg. Five 90-mu g quantities of DEHP were extracted from 12 kg of Stilton cheese and isolated by silica gel, size exclusion, and high-performance liquid chromatography (HPLC). Masses of samples were determined by gas chromatography mass spectrometry (GC-MS) analyses prior to combustion and manometry afterwards. The purity of DEHP carbon mass in each isolate was determined by multivariate deconvolution of GCMS fragmentation spectra obtained from measurements of standards and isolates, and ranged from 88.0 +/- 1.8% to 92.3 +/- 1.1% (n = 5, 1 sigma). Concurrently processed isolation method blanks contained from 0.15 +/- 0.04 to 1.52 +/- 0.06 mu g (n = 3, 1 sigma) DEHP per sample and significant quantities of pre- and post-chromatographic extraneous carbon contamination. The mean C-14-corrected contemporary carbon fraction of DEHP in the isolates was 0.235 +/- 0.073 (1 sigma; and +/- 0.091 at the 95% confidence level), revealing that the majority of DEHP in Stilton cheese results from anthropogenic sources, but with a significant naturally occurring component. C1 [Nelson, Michael A.; Ondov, John M.] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. [Nelson, Michael A.] NIST, Div Analyt Chem, Mat Measurement Lab, Gaithersburg, MD 20899 USA. [VanDerveer, Michael C.] US FDA, Univ Stn, College Pk, MD 20740 USA. [Buchholz, Bruce A.] Lawrence Livermore Natl Lab, Ctr Accelerator Mass Spectrometry, Livermore, CA 94551 USA. RP Nelson, MA (reprint author), Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. EM manelson@umd.edu FU US Food and Drug Administration's Office of Food Additive Safety (Division of Food Contact Notification) [U01FD001418]; US Department of Energy by Lawrence Livermore National Laboratory [DE-AC52-07NA27344] FX This work was performed with funding from the US Food and Drug Administration's Office of Food Additive Safety (Division of Food Contact Notification) under grant number U01FD001418; and in part under the auspices of the US Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. We thank Michele Schantz of the NIST Analytical Chemistry Division for providing guidance and training; and Professor Alan Kaufman, Dept. of Geology at the University of Maryland College Park, for performing 13C/12C isotope ratio measurements in his Stable Isotope Laboratory. Certain commercial equipment, instruments, or materials are identified in this paper to specify adequately the experimental procedure. Such identification does not imply recommendation or endorsement by the National Institute of Standards and Technology or the US Food and Drug Administration, nor does it imply that the materials or equipment identified are necessarily the best available for the purpose. NR 21 TC 1 Z9 1 U1 0 U2 12 PU UNIV ARIZONA DEPT GEOSCIENCES PI TUCSON PA RADIOCARBON 4717 E FORT LOWELL RD, TUCSON, AZ 85712 USA SN 0033-8222 EI 1945-5755 J9 RADIOCARBON JI Radiocarbon PY 2013 VL 55 IS 2-3 BP 686 EP 697 PG 12 WC Geochemistry & Geophysics SC Geochemistry & Geophysics GA 235WK UT WOS:000325752100056 ER PT J AU Kanungo, J AF Kanungo, Jyotshna TI DNA-dependent protein kinase and DNA repair: relevance to Alzheimer's disease SO ALZHEIMERS RESEARCH & THERAPY LA English DT Review ID DOUBLE-STRAND BREAKS; BASE EXCISION-REPAIR; NEURONAL CELL-DEATH; RNA-POLYMERASE-I; V(D)J RECOMBINATION; REPLICATION STRESS; HOMOLOGOUS RECOMBINATION; ATAXIA-TELANGIECTASIA; COGNITIVE IMPAIRMENT; MAMMALIAN-CELLS AB The pathological hallmark of Alzheimer's disease (AD), the leading cause of senile dementia, involves region-specific neuronal death and an accumulation of neuronal and extracellular lesions termed neurofibrillary tangles and senile plaques, respectively. One of the biochemical abnormalities observed in AD is reduced DNA end-joining activity. The reduced capacity of post-mitotic neurons for some types of DNA repair is further compromised by aging. The predominant mechanism to repair double-strand DNA (dsDNA) breaks (DSB) is non-homologous end joining (NHEJ), which requires DNA-dependent protein kinase (DNA-PK) activity. DNA-PK is a holoenzyme comprising the p460 kDa DNA-PK catalytic subunit (DNA-PKcs) and the Ku heterodimer consisting of p86 (Ku 80) and p70 (Ku 70) subunits. Ku binds to DNA ends first and then recruits DNA-PKcs during NHEJ. However, in AD brains, reduced NHEJ activity has been reported along with reduced levels of DNA-PKcs and the Ku proteins, indicating a potential link between AD and dsDNA damage. Since age-matched control brains also show a reduction in these protein levels, whether there is a direct link between NHEJ ability and AD remains unknown. Possible mechanisms involving the role of DNA-PK in neurodegeneration, a benchmark of AD, are the focus of this review. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Kanungo, J (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM jyotshnabala.kanungo@fda.hhs.gov FU National Center for Toxicological Research of the US Food and Drug Administration (FDA) FX The author's research is supported by funds from the National Center for Toxicological Research of the US Food and Drug Administration (FDA). This document has been reviewed in accordance with FDA policy and has been approved for publication. Approval does not signify that the contents necessarily reflect the position or opinions of the FDA, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. The findings and conclusions in this report are those of the author and do not necessarily represent the views of the FDA. NR 98 TC 7 Z9 7 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-9193 J9 ALZHEIMERS RES THER JI Alzheimers Res. Ther. PY 2013 VL 5 IS 2 AR 13 DI 10.1186/alzrt167 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 229RT UT WOS:000325285700003 PM 23566654 ER PT J AU Ness, GL Sheehan, AH Snyder, ME Jordan, J Cunningham, JE Gettig, JP AF Ness, Genevieve Lynn Sheehan, Amy Heck Snyder, Margie E. Jordan, Joseph Cunningham, Jean E. Gettig, Jacob P. TI Graduating Pharmacy Students' Perspectives on E-Professionalism and Social Media SO AMERICAN JOURNAL OF PHARMACEUTICAL EDUCATION LA English DT Article DE social media; pharmacy students; e-professionalism; social networking ID FACEBOOK AB Objective. To determine the use patterns of social media among graduating pharmacy students, characterize students' views and opinions of professionalism on popular social media sites, and compare responses about social media behavior among students seeking different types of employment. Methods. All graduating pharmacy students (n=516) at Purdue University, The University of Findlay, Butler University, and Midwestern University were invited to complete a survey instrument during the fall semester of 2011. Results. Of 212 (41%) students who responded to the survey, 93% (194/209) had a social media profile. Seventy-four percent (120/162) of participants felt they should edit their social media profiles prior to applying for a job. Conclusions. Many graduating pharmacy students use social media; however, there appears to be a growing awareness of the importance of presenting a more professional image online as they near graduation and begin seeking employment as pharmacists. C1 [Ness, Genevieve Lynn; Sheehan, Amy Heck; Snyder, Margie E.] Purdue Univ, Coll Pharm, Indianapolis, IN USA. [Ness, Genevieve Lynn] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Ness, Genevieve Lynn] US FDA, Silver Spring, MD USA. [Jordan, Joseph] Butler Univ, Coll Pharm & Hlth Sci, Indianapolis, IN 46208 USA. [Cunningham, Jean E.] Univ Findlay, Coll Pharm, Findlay, OH USA. [Gettig, Jacob P.] Midwestern Univ, Chicago Coll Pharm, Downers Grove, IL 60515 USA. RP Ness, GL (reprint author), 1900 Belmont Blvd, Nashville, TN 37212 USA. EM gness2011@gmail.com FU Gloria Niemeyer Francke Grant Program; [KL2RR025760] FX Dr. Snyder's effort was supported in part by KL2RR025760 (A. Shekhar, PI). Dr. Ness and Dr. Sheehan's efforts were supported in part by the Gloria Niemeyer Francke Grant Program. NR 17 TC 6 Z9 6 U1 1 U2 17 PU AMER ASSOC COLL PHARMACY PI ALEXANDRIA PA 1426 PRINCE STREET, ALEXANDRIA, VA 22314-2815 USA SN 0002-9459 J9 AM J PHARM EDUC JI Am. J. Pharm. Educ. PY 2013 VL 77 IS 7 AR 146 PG 6 WC Education, Scientific Disciplines; Pharmacology & Pharmacy SC Education & Educational Research; Pharmacology & Pharmacy GA 217RZ UT WOS:000324379300011 PM 24052649 ER PT J AU Salminen, WF Greenhaw, J Fowler, JM AF Salminen, William F. Greenhaw, James Fowler, Joe M. BE Salminen, WF Fowler, JM Greenhaw, J TI NONCLINICAL STUDY CONTRACTING AND MONITORING: A PRACTICAL GUIDE Introduction SO NONCLINICAL STUDY CONTRACTING AND MONITORING: A PRACTICAL GUIDE LA English DT Editorial Material; Book Chapter C1 [Salminen, William F.] PAREXEL Int, Sarasota, FL USA. [Greenhaw, James] FDA, Ctr Excellence Hepatotox, Natl Ctr Toxicol Res, Jefferson, AR USA. [Fowler, Joe M.] FDA, Qual Assurance Unit, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Salminen, WF (reprint author), PAREXEL Int, Sarasota, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-397831-8 PY 2013 BP 1 EP 17 DI 10.1016/B978-0-12-397829-5.00001-6 PG 17 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BGO59 UT WOS:000323647100001 ER PT J AU Fowler, JM Salminen, WF Greenhaw, J AF Fowler, Joe M. Salminen, William F. Greenhaw, James BE Salminen, WF Fowler, JM Greenhaw, J TI Good Laboratory Practices SO NONCLINICAL STUDY CONTRACTING AND MONITORING: A PRACTICAL GUIDE LA English DT Article; Book Chapter C1 [Fowler, Joe M.] FDA, Qual Assurance Unit, Natl Ctr Toxicol Res, Jefferson, AR USA. [Greenhaw, James] FDA, Ctr Excellence Hepatotox, Natl Ctr Toxicol Res, Jefferson, AR USA. [Salminen, William F.] PAREXEL Int, Sarasota, FL USA. RP Fowler, JM (reprint author), FDA, Qual Assurance Unit, Natl Ctr Toxicol Res, Jefferson, AR USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-397831-8 PY 2013 BP 19 EP 58 DI 10.1016/B978-0-12-397829-5.00002-8 PG 40 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BGO59 UT WOS:000323647100002 ER PT J AU Babb, A Ambroso, J Davis, K Greenhaw, J Salminen, WF AF Babb, Amy Ambroso, Jeffrey Davis, Kelly Greenhaw, James Salminen, William F. BE Salminen, WF Fowler, JM Greenhaw, J TI Study Design SO NONCLINICAL STUDY CONTRACTING AND MONITORING: A PRACTICAL GUIDE LA English DT Article; Book Chapter C1 [Babb, Amy; Davis, Kelly] FDA, Natl Ctr Toxicol Res, Jefferson, AR USA. [Greenhaw, James] FDA, Ctr Excellence Hepatotox, Natl Ctr Toxicol Res, Jefferson, AR USA. [Ambroso, Jeffrey] GlaxoSmithKline, Dept Safety Assessment, Res Triangle Pk, NC USA. [Salminen, William F.] PAREXEL Int, Sarasota, FL USA. RP Babb, A (reprint author), FDA, Natl Ctr Toxicol Res, Jefferson, AR USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-397831-8 PY 2013 BP 59 EP 79 DI 10.1016/B978-0-12-397829-5.00003-X PG 21 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BGO59 UT WOS:000323647100003 ER PT J AU Gopee, N Carraway, J Groves, LA Salminen, WF AF Gopee, Neera Carraway, Jeff Groves, Lady Ashley Salminen, William F. BE Salminen, WF Fowler, JM Greenhaw, J TI Animal Welfare SO NONCLINICAL STUDY CONTRACTING AND MONITORING: A PRACTICAL GUIDE LA English DT Article; Book Chapter C1 [Gopee, Neera; Carraway, Jeff; Groves, Lady Ashley] FDA, Natl Ctr Toxicol Res, Jefferson, AR USA. [Salminen, William F.] PAREXEL Int, Sarasota, FL USA. RP Gopee, N (reprint author), FDA, Natl Ctr Toxicol Res, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-397831-8 PY 2013 BP 81 EP 101 DI 10.1016/B978-0-12-397829-5.00004-1 PG 21 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BGO59 UT WOS:000323647100004 ER PT J AU Ambroso, J Babb, A VanLare, K Greenhaw, J Davis, K Fowler, JM Salminen, WF AF Ambroso, Jeffrey Babb, Amy VanLare, Karen Greenhaw, James Davis, Kelly Fowler, Joe M. Salminen, William F. BE Salminen, WF Fowler, JM Greenhaw, J TI Study Protocol Preparation, Review, and Approval SO NONCLINICAL STUDY CONTRACTING AND MONITORING: A PRACTICAL GUIDE LA English DT Review; Book Chapter C1 [Ambroso, Jeffrey] GlaxoSmithKline, Dept Safety Assessment, Res Triangle Pk, NC USA. [Babb, Amy; Davis, Kelly] FDA, Natl Ctr Toxicol Res, Jefferson, AR USA. [Greenhaw, James] FDA, Ctr Excellence Hepatotox, Natl Ctr Toxicol Res, Jefferson, AR USA. [Fowler, Joe M.] FDA, Qual Assurance Unit, Natl Ctr Toxicol Res, Jefferson, AR USA. [VanLare, Karen] Novartis Anim Hlth, Greensboro, NC USA. [Salminen, William F.] PAREXEL Int, Sarasota, FL USA. RP Ambroso, J (reprint author), GlaxoSmithKline, Dept Safety Assessment, Res Triangle Pk, NC USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-397831-8 PY 2013 BP 149 EP 172 DI 10.1016/B978-0-12-397829-5.00008-9 PG 24 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BGO59 UT WOS:000323647100008 ER PT J AU Babb, A Salminen, WF Fowler, JM AF Babb, Amy Salminen, William F. Fowler, Joe M. BE Salminen, WF Fowler, JM Greenhaw, J TI Test Article SO NONCLINICAL STUDY CONTRACTING AND MONITORING: A PRACTICAL GUIDE LA English DT Article; Book Chapter C1 [Babb, Amy] FDA, Natl Ctr Toxicol Res, Jefferson, AR USA. [Fowler, Joe M.] FDA, Qual Assurance Unit, Natl Ctr Toxicol Res, Jefferson, AR USA. [Salminen, William F.] PAREXEL Int, Sarasota, FL USA. RP Babb, A (reprint author), FDA, Natl Ctr Toxicol Res, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-397831-8 PY 2013 BP 173 EP 180 DI 10.1016/B978-0-12-397829-5.00009-0 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BGO59 UT WOS:000323647100009 ER PT J AU Babb, A Greenhaw, J Salminen, WF AF Babb, Amy Greenhaw, James Salminen, William F. BE Salminen, WF Fowler, JM Greenhaw, J TI Study Start Through End of In-Life SO NONCLINICAL STUDY CONTRACTING AND MONITORING: A PRACTICAL GUIDE LA English DT Article; Book Chapter C1 [Babb, Amy] FDA, Natl Ctr Toxicol Res, Jefferson, AR USA. [Greenhaw, James] FDA, Ctr Excellence Hepatotox, Natl Ctr Toxicol Res, Jefferson, AR USA. [Salminen, William F.] PAREXEL Int, Sarasota, FL USA. RP Babb, A (reprint author), FDA, Natl Ctr Toxicol Res, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-397831-8 PY 2013 BP 181 EP 191 DI 10.1016/B978-0-12-397829-5.00010-7 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BGO59 UT WOS:000323647100010 ER PT J AU Salminen, WF Yang, X AF Salminen, William F. Yang, Xi BE Salminen, WF Fowler, JM Greenhaw, J TI Study Communication and Data Management SO NONCLINICAL STUDY CONTRACTING AND MONITORING: A PRACTICAL GUIDE LA English DT Article; Book Chapter C1 [Salminen, William F.] PAREXEL Int, Sarasota, FL USA. [Yang, Xi] FDA, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Salminen, WF (reprint author), PAREXEL Int, Sarasota, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-397831-8 PY 2013 BP 193 EP 203 DI 10.1016/B978-0-12-397829-5.00011-9 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BGO59 UT WOS:000323647100011 ER PT J AU Salminen, WF Fowler, JM Greenhaw, J AF Salminen, William F. Fowler, Joe M. Greenhaw, James BE Salminen, WF Fowler, JM Greenhaw, J TI Draft Report SO NONCLINICAL STUDY CONTRACTING AND MONITORING: A PRACTICAL GUIDE LA English DT Article; Book Chapter C1 [Salminen, William F.] PAREXEL Int, Sarasota, FL USA. [Fowler, Joe M.] FDA, Qual Assurance Unit, Natl Ctr Toxicol Res, Jefferson, AR USA. [Greenhaw, James] FDA, Ctr Excellence Hepatotox, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Salminen, WF (reprint author), PAREXEL Int, Sarasota, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-397831-8 PY 2013 BP 217 EP 236 DI 10.1016/B978-0-12-397829-5.00013-2 PG 20 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BGO59 UT WOS:000323647100013 ER PT J AU Salminen, WF Greenhaw, J Fowler, JM AF Salminen, William F. Greenhaw, James Fowler, Joe M. BE Salminen, WF Fowler, JM Greenhaw, J TI Final Report, Study Close-Out, and Conclusions SO NONCLINICAL STUDY CONTRACTING AND MONITORING: A PRACTICAL GUIDE LA English DT Editorial Material; Book Chapter C1 [Salminen, William F.] PAREXEL Int, Sarasota, FL USA. [Greenhaw, James] FDA, Ctr Excellence Hepatotox, Natl Ctr Toxicol Res, Jefferson, AR USA. [Fowler, Joe M.] FDA, Qual Assurance Unit, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Salminen, WF (reprint author), PAREXEL Int, Sarasota, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-397831-8 PY 2013 BP 237 EP 240 DI 10.1016/B978-0-12-397829-5.00014-4 PG 4 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BGO59 UT WOS:000323647100014 ER PT S AU Bai, JPF Abernethy, DR AF Bai, Jane P. F. Abernethy, Darrell R. BE Insel, PA TI Systems Pharmacology to Predict Drug Toxicity: Integration Across Levels of Biological Organization SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 53, 2013 SE Annual Review of Pharmacology and Toxicology LA English DT Review; Book Chapter DE adverse drug effects; bioinformatics; systems analysis ID MITOCHONDRIAL PERMEABILITY TRANSITION; ACTIVATED PROTEIN-KINASE; FATTY-ACID OXIDATION; INDUCED LIVER-INJURY; INDUCED HEPATOTOXICITY; IN-VITRO; GENE-EXPRESSION; TRANSLATIONAL BIOINFORMATICS; MOUSE MODEL; CELLS AB To achieve sensitive and specific mechanism-based prediction of drug toxicity, the tools of systems pharmacology will be integrated using structured ontological approaches, analytics, mathematics, and statistics. Success of this effort is based on the assumption that a systems network that consists of drug-induced perturbations of physiological functions can be characterized. This network spans the hierarchy of biological organization, from gene to mRNA to protein to intracellular organelle to cell to organ to organism. It is populated with data from each of these levels of biological organization. These data, from disparate sources, include the published literature, drug development archives of all approved drugs and drug candidates that did not complete development, and various toxicity databases and adverse event reporting systems. The network contains interrelated genomics, transcriptomics, and metabolomics data, as well as organ and physiological functional data that are derived from the universe of information that describes and analyzes drug toxicity. Here we describe advances in bioinformatics, computer sciences, next-generation sequencing, and systems biology that create the opportunity for integrated systems pharmacology-based prediction of drug safety. C1 [Bai, Jane P. F.; Abernethy, Darrell R.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Bai, JPF (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM darrell.abernethy@fda.hhs.gov NR 144 TC 53 Z9 54 U1 5 U2 83 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0362-1642 BN 978-0-8243-0453-9 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 2013 VL 53 BP 451 EP 473 DI 10.1146/annurev-pharmtox-011112-140248 PG 23 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BGH79 UT WOS:000323040100022 PM 23140241 ER PT J AU Cavallari, LH Klein, TE Huang, SM AF Cavallari, Larisa H. Klein, Teri E. Huang, Shiew-Mei BE Lam, YWF Cavallari, LH TI Governmental and Academic Efforts to Advance the Field of Pharmacogenomics SO PHARMACOGENOMICS: CHALLENGES AND OPPORTUNITIES IN THERAPEUTIC IMPLEMENTATION LA English DT Article; Book Chapter ID IMPLEMENTATION CONSORTIUM GUIDELINES; GENOME-WIDE ASSOCIATION; ELECTRONIC MEDICAL-RECORDS; ADVERSE DRUG-REACTIONS; REGULATORY SCIENCE; CLINICAL UTILITY; DATA SUBMISSIONS; RESEARCH NETWORK; CRITICAL PATH; PERSONALIZED MEDICINE C1 [Cavallari, Larisa H.] Univ Illinois, Dept Pharm Practice, Chicago, IL 60607 USA. [Klein, Teri E.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Huang, Shiew-Mei] US FDA, Off Clin Pharmacol, Silver Spring, MD USA. RP Cavallari, LH (reprint author), Univ Illinois, Dept Pharm Practice, Chicago, IL 60607 USA. NR 82 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-398303-9 PY 2013 BP 63 EP 88 DI 10.1016/B978-0-12-391918-2.00003-2 PG 26 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA BGQ38 UT WOS:000323772400004 ER PT S AU Leighton, J Koehler, KM Kavanaugh, C Heintz, K AF Leighton, Jessica Koehler, Kathleen M. Kavanaugh, Claudine Heintz, Kasey BE Stumbo, P McNutt, S TI Nutrient databases: critical tools for policy development SO 36TH NATIONAL NUTRIENT DATABANK CONFERENCE SE Procedia Food Science LA English DT Proceedings Paper CT 36th National Nutrient Databank Conference CY MAR 25-28, 2012 CL Univ Texas, Sch Publ Hlth, Houston, TX SP Michael & Susan Dell Ctr Hlth Living HO Univ Texas, Sch Publ Hlth DE Nutrient databases; policy; USDA; trans fat; sodium ID UNITED-STATES; FOLIC-ACID; PREVALENCE AB Nutrient databases provide critical tools for developing effective government policies to promote healthy diets and a nutritionally healthy food supply. This paper highlights the role of nutrient databases in various phases of policy development referencing folic acid as a historical illustration and providing more recent examples of trans fat and sodium reduction in the food supply. Limitations of both public and proprietary nutrient databases are considered and improvements to enhance nutrient databases to support policy efforts are suggested. (C) 2013 The Authors. Published by Elsevier Ltd. C1 [Leighton, Jessica; Kavanaugh, Claudine] US FDA, Silver Spring, MD 20993 USA. RP Leighton, J (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM jessica.leighton@fda.hhs.gov NR 35 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2211-601X J9 PROC FOOD SCI PY 2013 VL 2 BP 187 EP 194 DI 10.1016/j.profoo.2013.04.027 PG 8 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA BGQ00 UT WOS:000323754000025 ER PT J AU Green, MD Al-Humadi, NH AF Green, Martin David Al-Humadi, Nabil Hussain BE Faqi, AS TI Preclinical Toxicology of Vaccines SO COMPREHENSIVE GUIDE TO TOXICOLOGY IN PRECLINICAL DRUG DEVELOPMENT LA English DT Article; Book Chapter ID HERPES-SIMPLEX-VIRUS; ALUMINUM-CONTAINING ADJUVANTS; MURINE CUTANEOUS LEISHMANIASIS; YELLOW-FEVER VACCINATION; RECURRENT GENITAL HERPES; UNITED-STATES-ARMY; INFLUENZA-VIRUS; IMMUNE-RESPONSES; ANIMAL-MODELS; PROTECTIVE IMMUNITY C1 [Green, Martin David; Al-Humadi, Nabil Hussain] US FDA, CBER, Rockville, MD 20857 USA. RP Green, MD (reprint author), US FDA, CBER, Rockville, MD 20857 USA. NR 213 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-387815-1 PY 2013 BP 619 EP 645 DI 10.1016/B978-0-12-387815-1.00025-3 PG 27 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BGH59 UT WOS:000323013200026 ER PT S AU Witters, D Bassen, H Guag, J Addissie, B LaSorte, N Rafai, H AF Witters, Donald Bassen, Howard Guag, Joshua Addissie, Bisrat LaSorte, Nickolas Rafai, Hazem BE Carapezza, EM TI Assessment of Risks of EMI for Personal Medical Electronic Devices (PMEDs) from Emissions of Millimeter Wave Security Screening Systems SO SENSORS, AND COMMAND, CONTROL, COMMUNICATIONS, AND INTELLIGENCE (C3I) TECHNOLOGIES FOR HOMELAND SECURITY AND HOMELAND DEFENSE XII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Sensors, and Command, Control, Communications, and Intelligence (C3I) Technologies for Homeland Security and Homeland Defense XII CY APR 29-MAY 01, 2013 CL Baltimore, MD SP SPIE DE Personal medical electronic medical devices; PMED; medical devices; millimeter wave; security systems; electromagnetic interference; electromagnetic compatibility AB This paper describes research and testing of a representative group of high priority body worn and implantable personal medical electronic devices (PMEDs) for exposure to millimeter wave (MMW) advanced imaging technology (AIT) security systems used at airports. The sample PMEDs included in this study were implantable cardiac pacemakers, ICDs, neurostimulators and insulin pumps. These PMEDs are designed and tested for susceptibility to electromagnetic interference (EMI) under the present standards for medical device electromagnetic compatibility (EMC). However, the present standards for medical equipment do not address exposure to the much higher frequency fields that are emitted by MMW security systems. Initial AIT emissions measurements were performed to assess the PMED and passenger exposures. Testing protocols were developed and testing methods were tailored to the type of PMED. In addition, a novel exposure simulation system was developed to allow controlled EMC testing without the need of the MMW AIT system. Methodology, test results, and analysis are presented, along with an assessment of the human exposure and risks for PMED users. The results on this study reveal no effects on the medical devices from the exposure to the MMW security system. Furthermore, the human exposure measurements and analysis showed levels well below applicable standard, and the risks for PMED users and others we assessed to be very low. These findings apply to the types of PMEDs used in the study though these findings might suggest that the risks for other, similar PMEDs would likely be similar. C1 [Witters, Donald; Bassen, Howard; Guag, Joshua; Addissie, Bisrat] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. [LaSorte, Nickolas; Rafai, Hazem] Univ Oklahoma, Tulsa, OK 74135 USA. RP Witters, D (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. NR 11 TC 0 Z9 0 U1 0 U2 5 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9502-0 J9 PROC SPIE PY 2013 VL 8711 AR UNSP 87110I DI 10.1117/12.2021543 PG 10 WC Engineering, Electrical & Electronic; Optics; Telecommunications SC Engineering; Optics; Telecommunications GA BGM80 UT WOS:000323522600011 ER PT J AU Leviton, MP Lacayo, JC Choi, KY Hernandez-Alvarado, N Wey, A Schleiss, MR AF Leviton, Michael P. Lacayo, Juan C. Choi, K. Yeon Hernandez-Alvarado, Nelmary Wey, Andrew Schleiss, Mark R. TI An Attenuated Cytomegalovirus Vaccine with a Deletion of a Viral Chemokine Gene Is Protective against Congenital CMV Transmission in a Guinea Pig Model SO CLINICAL & DEVELOPMENTAL IMMUNOLOGY LA English DT Article ID BACTERIAL ARTIFICIAL CHROMOSOME; ENDOTHELIAL-CELLS; MOUSE CYTOMEGALOVIRUS; IMMUNE EVASION; GPCMV GENOME; INFECTION; HOMOLOG; STRATEGIES; CLONING; VIRUS AB Development of a vaccine against congenital cytomegalovirus (CMV) infection is a public health priority, but CMVs encode immune evasion genes that complicate live virus vaccine design. To resolve this problem, this study employed guanosyl phosphoribosyl transferase (gpt) mutagenesis to generate a recombinant guinea pig CMV (GPCMV) with a knockout of a viral chemokine gene, GPCMV MIP (gp1). MIP deletion virus replicated with wild-type kinetics in cell culture but was attenuated in nonpregnant guinea pigs, demonstrating reduced viremia and reduced inflammation and histopathology (compared to a control virus with an intact GPCMV MIP gene) following footpad inoculation. In spite of attenuation, the vaccine was immunogenic, eliciting antibody responses comparable to those observed in natural infection. To assess its protective potential as a vaccine, either recombinant virus or placebo was used to immunize seronegative female guinea pigs. Dams were challenged in the early 3rd trimester with salivary gland-adapted GPCMV. Immunization protected against DNAemia (1/15 in vaccine group versus 12/13 in the control group, P < 0.01). Mean birth weights were significantly higher in pups born to vaccinated dams compared to controls (98.7 g versus 71.2 g, P < 0.01). Vaccination reduced pup mortality, from 35/50 (70%) in controls to 8/52 (15%) in the immunization group. Congenital GPCMV infection was also reduced, from 35/50 (70%) in controls to 9/52 (17%) in the vaccine group (P < 0.0001). We conclude that deletion of an immune modulation gene can attenuate the pathogenicity of GPCMV while resulting in a viral vaccine that retains immunogenicity and demonstrates efficacy against congenital infection and disease. C1 [Leviton, Michael P.; Lacayo, Juan C.; Choi, K. Yeon; Hernandez-Alvarado, Nelmary; Schleiss, Mark R.] Univ Minnesota, Sch Med, Ctr Infect Dis & Microbiol Translat Res, Div Pediat Infect Dis & Immunol,Dept Pediat, Minneapolis, MN 55455 USA. [Lacayo, Juan C.] US FDA, Regulatory Review Off, Rockville, MD 20852 USA. [Choi, K. Yeon] Texas A&M Hlth Sci Ctr, College Stn, TX 77843 USA. [Wey, Andrew] Univ Minnesota, Biostat Design & Anal Ctr, Clin & Translat Sci Inst, Minneapolis, MN 55455 USA. RP Schleiss, MR (reprint author), Univ Minnesota, Sch Med, Ctr Infect Dis & Microbiol Translat Res, Div Pediat Infect Dis & Immunol,Dept Pediat, 2001 6th St SE, Minneapolis, MN 55455 USA. EM schleiss@umn.edu FU NIH [R01HD044864, R01HD038416] FX The assistance of Jodi Anderson, Janine Gessner, Adam Gilbertsen, and Katherine Schleiss is gratefully acknowledged. This work was supported by grants R01HD044864 and R01HD038416 from the NIH and a diversity supplement to HD044864 to Nelmary Hernandez-Alvarado. NR 43 TC 3 Z9 3 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1740-2522 J9 CLIN DEV IMMUNOL JI Clin. Dev. Immunol. PY 2013 AR 906948 DI 10.1155/2013/906948 PG 12 WC Immunology SC Immunology GA 205KU UT WOS:000323443900001 ER PT J AU Abdalla, AA Smith, RE AF Abdalla, Amir A. Smith, Robert E. TI Determination of Mercury in Ayurvedic Dietary Supplements That Are Not Rasa Shastra Using the Hydra-C Direct Mercury Analyzer SO INTERNATIONAL JOURNAL OF ANALYTICAL CHEMISTRY LA English DT Article ID PLASMA-MASS SPECTROMETRY; MEDICINES; LEAD AB Mercury has been determined in Ayurvedic dietary supplements (Trifala, Trifala Guggulu, Turmeric, Mahasudarshan, Yograj, Shatawari, Hingwastika, Shatavari, and Shilajit) by inductively coupled plasma-mass spectrometry (ICP-MS) and direct mercury analysis using the Hydra-C direct mercury analyzer (Teledyne Leeman Labs Hudson, NH, USA). Similar results were obtained from the two methods, but the direct mercury analysis method was much faster and safer and required no microwave digestion (unlike ICP-MS). Levels of mercury ranged from 0.002 to 56 mu g/g in samples of dietary supplements. Standard reference materials Ephedra 3240 and tomato leaves that were from the National Institute of Standard and Technology (NIST) and dogfish liver (DOLT3) that was from the Canadian Research Council were analyzed using Hydra-C method. Average mercury recoveries were 102% (RSD% 0.0018), 100% (RSD% 0.0009), and 101% (RSD% 0.0729), respectively. Hydra-C method Limit Of Quantitation was 0.5 ng. C1 [Abdalla, Amir A.; Smith, Robert E.] US FDA, Total Diet & Pesticide Res Ctr, Lenexa, KS 66214 USA. RP Smith, RE (reprint author), US FDA, Total Diet & Pesticide Res Ctr, 11510 W 80th St, Lenexa, KS 66214 USA. EM robert.smith@fda.hhs.gov NR 21 TC 1 Z9 1 U1 2 U2 14 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-8760 J9 INT J ANAL CHEM JI Int. J. Anal. Chem. PY 2013 AR 628397 DI 10.1155/2013/628397 PG 4 WC Chemistry, Analytical SC Chemistry GA 205OT UT WOS:000323454600001 ER PT S AU Cheng, WC Keay, T Flaherty, NO Wang, J Ivansky, A Gavrielides, MA Gallas, BD Badano, A AF Cheng, Wei-Chung Keay, Tyler Flaherty, Neil O. Wang, Joel Ivansky, Adam Gavrielides, Marios A. Gallas, Brandon D. Badano, Aldo BE Gurcan, MN Madabhushi, A TI Assessing Color Reproducibility of Whole-Slide Imaging Scanners SO MEDICAL IMAGING 2013: DIGITAL PATHOLOGY SE Proceedings of SPIE LA English DT Proceedings Paper CT 9th Conference on Digital Pathology at the SPIE Medical Imaging Symposium CY FEB 10-11, 2013 CL Lake Buena Vista, FL SP SPIE, Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ DE Digital pathology; whole-slide imaging; color reproducibility; color phantom; color management; ICC profile AB A new method for assessing color reproducibility of whole-slide imaging (WSI) systems is introduced. A color phantom is used to evaluate the difference between the input to and the output from a WSI system. The method consists of four components: (a) producing the color phantom, (b) establishing the truth of the color phantom, (c) retrieving the digital display data from the WSI system, and (d) calculating the color difference. The method was applied to a WSI system and used to evaluate the color characteristics with and without color management. C1 [Cheng, Wei-Chung; Keay, Tyler; Flaherty, Neil O.; Wang, Joel; Ivansky, Adam; Gavrielides, Marios A.; Gallas, Brandon D.; Badano, Aldo] US FDA, Div Imaging & Appl Math, CDRH, Silver Spring, MD 20993 USA. RP Cheng, WC (reprint author), US FDA, Div Imaging & Appl Math, CDRH, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. OI Gallas, Brandon/0000-0001-7332-1620; badano, aldo/0000-0003-3712-6670 NR 4 TC 0 Z9 0 U1 0 U2 4 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9450-4 J9 PROC SPIE PY 2013 VL 8676 AR 86760O DI 10.1117/12.2007215 PG 5 WC Optics; Pathology; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Pathology; Radiology, Nuclear Medicine & Medical Imaging GA BGH42 UT WOS:000322982800024 ER PT S AU He, X Samuelson, F Gallas, BD Sahiner, B Myers, K AF He, Xin Samuelson, Frank Gallas, Brandon D. Sahiner, Berkman Myers, Kyle BE Abbey, CK MelloThoms, CR TI The Equivalence of a Human Observer and an Ideal Observer in Binary Diagnostic Tasks SO MEDICAL IMAGING 2013: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND TECHNOLOGY ASSESSMENT SE Proceedings of SPIE LA English DT Proceedings Paper CT Image Perception, Observer Performance, and Technology Assessment Conference, part of the SPIE Medical Imaging Symposium CY FEB 10-11, 2013 CL Lake Buena Vista, FL SP SPIE, Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ ID IMAGE QUALITY AB The Ideal Observer (IO) is "ideal" for given data populations. In the image perception process, as the raw images are degraded by factors such as display and eye optics, there is an equivalent IO (EIO). The EIO uses the statistical information that exits the perception/cognitive degradations as the data. We assume a human observer who received sufficient training, e.g., radiologists, and hypothesize that such a human observer can be modeled as if he is an EIO. To measure the likelihood ratio (LR) distributions of an EIO, we formalize experimental design principles that encourage rationality based on von Neumann and Morgenstern's (vNM) axioms. We present examples to show that many observer study design refinements, although motivated by empirical principles explicitly, implicitly encourage rationality. Our hypothesis is supported by a recent review paper on ROC curve convexity by Pesce, Metz, and Berbaum. We also provide additional evidence based on a collection of observer studies in medical imaging. EIO theory shows that the "sub-optimal" performance of a human observer can be mathematically formalized in the form of an IO, and measured through rationality encouragement. C1 [He, Xin; Samuelson, Frank; Gallas, Brandon D.; Sahiner, Berkman; Myers, Kyle] US FDA, Rockville, MD 20857 USA. RP He, X (reprint author), US FDA, Rockville, MD 20857 USA. OI Gallas, Brandon/0000-0001-7332-1620 NR 29 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9447-4 J9 PROC SPIE PY 2013 VL 8673 AR 86730E DI 10.1117/12.2007921 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BGH44 UT WOS:000322986700012 ER PT S AU Zhang, GZ Myers, KJ Park, S AF Zhang, George Z. Myers, Kyle J. Park, Subok BE Abbey, CK MelloThoms, CR TI Investigating the feasibility of using partial least squares as a method of extracting salient information for the evaluation of digital breast tomosynthesis SO MEDICAL IMAGING 2013: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND TECHNOLOGY ASSESSMENT SE Proceedings of SPIE LA English DT Proceedings Paper CT Image Perception, Observer Performance, and Technology Assessment Conference, part of the SPIE Medical Imaging Symposium CY FEB 10-11, 2013 CL Lake Buena Vista, FL SP SPIE, Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ DE Hotelling observer; channelized Hotelling observer; partial least squares; efficient channels; digital breast tomosynthesis (DBT) ID IMAGE ACQUISITION; 3D SIMULATION; OBSERVERS; MODEL AB Digital breast tomosynthesis (DBT) has shown promise for improving the detection of breast cancer, but it has not yet been fully optimized due to a large space of system parameters to explore. A task-based statistical approach(1) is a rigorous method for evaluating and optimizing this promising imaging technique with the use of optimal observers such as the Hotelling observer (HO). However, the high data dimensionality found in DBT has been the bottleneck for the use of a task-based approach in DBT evaluation. To reduce data dimensionality while extracting salient information for performing a given task, efficient channels have to be used for the HO. In the past few years, 2D Laguerre-Gauss (LG) channels, which are a complete basis for stationary backgrounds and rotationally symmetric signals, have been utilized for DBT evaluation(2,3). But since background and signal statistics from DBT data are neither stationary nor rotationally symmetric, LG channels may not be efficient in providing reliable performance trends as a function of system parameters. Recently, partial least squares (PLS) has been shown to generate efficient channels for the Hotelling observer in detection tasks involving random backgrounds and signals. 4 In this study, we investigate the use of PLS as a method for extracting salient information from DBT in order to better evaluate such systems. C1 [Zhang, George Z.; Myers, Kyle J.; Park, Subok] US FDA, Div Imaging & Appl Math, OSEL, CDRH, Rockville, MD 20857 USA. RP Park, S (reprint author), 10903 New Hampshire Ave,Bldg 62,Rm 3109, Silver Spring, MD 20993 USA. EM Subok.Park@fda.hhs.gov NR 18 TC 3 Z9 3 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9447-4 J9 PROC SPIE PY 2013 VL 8673 AR 867311 DI 10.1117/12.2008018 PG 11 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BGH44 UT WOS:000322986700035 ER PT S AU Badal, A Zafar, F Dong, H Badano, A AF Badal, Andreu Zafar, Fahad Dong, Han Badano, Aldo BE Nishikawa, RM Whiting, BR Hoeschen, C TI A real-time radiation dose monitoring system for patients and staff during interventional fluoroscopy using a GPU-accelerated Monte Carlo simulator and an automatic 3D localization system based on a depth camera SO MEDICAL IMAGING 2013: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Physics of Medical Imaging CY FEB 11-14, 2013 CL Lake Buena Vista, FL SP SPIE, Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ DE Monte Carlo; dosimetry; GPU; depth camera; fluoroscopy ID RADIOLOGY PROCEDURES; PHOTON TRANSPORT; RAD-IR; SKIN; PENELOPE; CODE AB Radiation monitoring systems able to accurately track the radiation dose received by the patient and the medical staff during interventional fluoroscopy can be used to minimize the likelihood and severity of radiation-induced skin injuries and estimate the accumulated organ doses. We describe a method to monitor doses in real time using automatic sensors in the imaging room and a GPU-accelerated computer simulator. The Monte Carlo simulation code MC-GPU is used to estimate patient and staff doses due to primary and scattered radiation, along with the associated statistical uncertainties. The geometrical configuration of the irradiation is automatically determined and updated using data from a depth camera that tracks the location and posture of each person in the imaging room. A virtual x-ray source graphical interface is used to manually trigger the simulations. The implemented computational framework separates the simulation of the x-ray transport through the patient and the operator bodies into two coupled, sequential simulations. The initial simulation uses the patient anatomy and a c-arm source model with a collimated cone beam emitted from a point focal spot. During this simulation a large phase space file with the energy, position and direction of x rays scattered in the direction of the operator is created. The phase space file is then used as the input radiation source for the following simulation with the operator anatomy model. Particle recycling is employed as a variance reduction technique to maximize the information obtained from the limited number of particles scattered towards the operator. For a typical image acquisition, a patient skin dose map can be displayed at the operator's monitor within 10 seconds with a peak skin dose error below 1%. This work demonstrates that a dose monitoring system based on accurate Monte Carlo simulations can be used to estimate in real-time the average and peak organ doses for both the patient and the staff in interventional fluoroscopy, and provide timely information regarding possible overdoses while the imaging procedure is being performed. C1 [Badal, Andreu; Zafar, Fahad; Dong, Han; Badano, Aldo] US FDA, Div Imaging & Appl Math, OSEL, CDRH, Silver Spring, MD 20993 USA. RP Badal, A (reprint author), US FDA, Div Imaging & Appl Math, OSEL, CDRH, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Andreu.Badal-Soler@fda.hhs.gov NR 14 TC 0 Z9 0 U1 5 U2 12 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9442-9 J9 PROC SPIE PY 2013 VL 8668 AR 866828-1 DI 10.1117/12.2008031 PG 11 WC Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BFZ77 UT WOS:000322002700076 ER PT S AU Badano, A Samuelson, FW AF Badano, Aldo Samuelson, Frank W. BE Nishikawa, RM Whiting, BR Hoeschen, C TI Uncertainty of Monte Carlo variance estimates: application to the simulation of x-ray imaging detectors SO MEDICAL IMAGING 2013: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Physics of Medical Imaging CY FEB 11-14, 2013 CL Lake Buena Vista, FL SP SPIE, Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ AB Knowledge of the uncertainty associated with Monte Carlo estimates is useful for determining when to stop a simulation run when statistical fluctuations fall below a desired tolerance level, and for designing and analyzing variance reduction techniques. In this work, we discuss how to analytically calculate the uncertainty of Monte Carlo variance estimates from higher order moments of the distribution of events. In addition, we show how these expressions can be incorporated in the study of x-ray imaging detectors to manage runtime and precision of the simulation. Our analysis can be used to design variance reduction techniques for Monte Carlo simulations when, as in many cases in imaging, the variance and not the mean, is the quantity of interest. C1 [Badano, Aldo; Samuelson, Frank W.] US FDA, Div Imaging & Appl Math, Offf Sci & Radiol Hlth, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Badano, A (reprint author), US FDA, Div Imaging & Appl Math, Offf Sci & Radiol Hlth, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. OI badano, aldo/0000-0003-3712-6670 NR 5 TC 1 Z9 1 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9442-9 J9 PROC SPIE PY 2013 VL 8668 AR 86680L DI 10.1117/12.2007432 PG 4 WC Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BFZ77 UT WOS:000322002700018 ER PT S AU Chui, JH Zeng, RP Pokrajac, DD Park, S Myers, KJ Maidment, ADA Bakic, PR AF Chui, Joseph H. Zeng, Rongping Pokrajac, David D. Park, Subok Myers, Kyle J. Maidment, Andrew D. A. Bakic, Predrag R. BE Nishikawa, RM Whiting, BR Hoeschen, C TI Two Methods for Simulation of Dense Tissue Distribution in Software Breast Phantoms SO MEDICAL IMAGING 2013: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Physics of Medical Imaging CY FEB 11-14, 2013 CL Lake Buena Vista, FL SP SPIE, Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ DE Breast cancer imaging; anthropomorphic breast phantoms; software breast phantoms; validation; fibroglandular tissue distribution; Beta functions ID DIGITIZED MAMMOGRAMS; CANCER; RISK; PATTERNS AB Software breast phantoms have been developed for use in evaluation of novel breast imaging systems. Software phantoms are flexible allowing the simulation of wide variations in breast anatomy, and provide ground truth for the simulated tissue structures. Different levels of phantom realism are required depending on the intended application. Realistic simulation of dense (fibroglandular) tissue is of particular importance; the properties of dense tissue breast percent density and the spatial distribution have been related to the risk of breast cancer. In this work, we have compared two methods for simulation of dense tissue distribution in a software breast phantom previously developed at the University of Pennsylvania. The methods compared are: (1) the previously used Gaussian distribution centered at the phantom nipple point, and (2) the proposed combination of two Beta functions, one modeling the dense tissue distribution along the chest wall-to-nipple direction, and the other modeling the radial distribution in each coronal section of the phantom. Dense tissue distributions obtained using these methods have been compared with distributions reported in the literature estimated from the analysis of breast CT images. Qualitatively, the two methods produced rather similar dense tissue distributions. The simulation based upon the use of Beta functions provides more control over the simulated distributions through the selection of the various Beta function parameters. Both methods showed good agreement to the clinical data, suggesting both provide a high level of realism. C1 [Chui, Joseph H.; Maidment, Andrew D. A.; Bakic, Predrag R.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Zeng, Rongping; Park, Subok; Myers, Kyle J.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Pokrajac, David D.] Delaware State Univ, Comp & Informat Sci Dept, Dover, DE USA. RP Chui, JH (reprint author), Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. EM Joseph.Chui@uphs.upenn.edu; Rongping.Zeng@fda.hhs.gov; DPokrajac@desu.edu; Subok.Park@fda.hhs.gov; Kyle.Myers@fda.hhs.gov; Andrew.Maidment@uphs.upenn.edu; Predrag.Bakic@uphs.upenn.edu FU US Department of Defense Breast Cancer Research Program [BC083639]; US National Institutes of Health [CA154444]; US National Science Foundation [0630388]; US Department of Defense/Department of Army [45395-MA-ISP, 54412-CI-ISP] FX This work was supported in part by the US Department of Defense Breast Cancer Research Program (HBCU Partnership Training Award #BC083639), the US National Institutes of Health (R01 grant #CA154444), the US National Science Foundation (CREOSA grant #HRD-0630388), and the US Department of Defense/Department of Army (45395-MA-ISP, #54412-CI-ISP). The authors are grateful to Dr. Ingrid Reiser for fruitful discussions. NR 13 TC 1 Z9 1 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9442-9 J9 PROC SPIE PY 2013 VL 8668 AR 86680M DI 10.1117/12.2008104 PG 10 WC Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BFZ77 UT WOS:000322002700019 ER PT S AU Fang, Y Badal, A Badano, A Karim, KS AF Fang, Yuan Badal, Andreu Badano, Aldo Karim, Karim S. BE Nishikawa, RM Whiting, BR Hoeschen, C TI Spatial resolution characteristics of a-Se imaging detectors using Monte Carlo methods with detailed spatiotemporal transport of x rays, electrons, and electron-hole pairs under applied bias SO MEDICAL IMAGING 2013: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Physics of Medical Imaging CY FEB 11-14, 2013 CL Lake Buena Vista, FL SP SPIE, Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ DE Monte Carlo simulation; amorphous selenium; ARTEMIS AB Detectability of microcalcifications and small lesions in mammography has driven the development of high spatial resolution imagers with small pixel pitch. In this work, we study the detector resolution limits of amorphous selenium (a-Se) with a detailed Monte Carlo transport code for simulation of direct x-ray detectors. The model takes into account generation and re-absorption of characteristic x rays, spreading due to Compton scattering and high-energy secondary electron transport, and drift and diffusion of electron-hole pairs under the applied external electric field. The transport of electron-hole pairs is achieved with a spatiotemporal model that accounts for recombination and trapping of carriers and Coulombic effects of 3D spatial charge distribution. The location information for each detected electron and hole over millions of simulation histories are used to build the detector point response. A range of incident x-ray energies are simulated from 10 to 100 keV. The simulated detector point response can be used to study the spatial resolution characteristics of detectors at different energies ranges and for calculation of the modulation transfer function and image quality metrics. C1 [Fang, Yuan; Badal, Andreu; Badano, Aldo] OSEL CDRH FDA, Div Imaging & Appl Math, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. [Fang, Yuan; Karim, Karim S.] Univ Waterloo, Dept Elect & Comp Engn, Waterloo, ON N2L 3G1, Canada. RP Fang, Y (reprint author), OSEL CDRH FDA, Div Imaging & Appl Math, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM yuan.fang@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 FU Natural Sciences and Engineering Research Council of Canada (NSERC); Center for Device and Radiological Health; Oak Ridge Institute for Science and Education; U.S. Department of Energy; U.S. Food and Drug Administration FX This work was financially supported in part by the Natural Sciences and Engineering Research Council of Canada (NSERC). Y.F. acknowledges funding by an appointment to the Research Participation Program at the Center for Device and Radiological Health administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and U.S. Food and Drug Administration. NR 5 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9442-9 J9 PROC SPIE PY 2013 VL 8668 AR 86683R DI 10.1117/12.2007436 PG 6 WC Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BFZ77 UT WOS:000322002700128 ER PT S AU Sharma, D Dong, H Fang, Y Badano, A AF Sharma, Diksha Dong, Han Fang, Yuan Badano, Aldo BE Nishikawa, RM Whiting, BR Hoeschen, C TI A compendium of publicly available Monte Carlo transport codes (including new tools) for the simulation of radiation imaging detectors SO MEDICAL IMAGING 2013: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Physics of Medical Imaging CY FEB 11-14, 2013 CL Lake Buena Vista, FL SP SPIE, Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ ID X-RAY; MANTIS AB Simulations play a vital role in the understanding and analysis of existing and emerging medical imaging technologies. Over the last years, Monte Carlo simulations have become increasingly necessary tools for studying the fundamental limitations and for the design and optimization of medical imaging systems. We compare available open-source software packages from the Division of Imaging and Applied Mathematics at the FDA for modeling scintillator- and semiconductor-based radiation imaging detectors for applications in x-ray and nuclear imaging including MANTIS, hybridMANTIS, cartesianDETEcT2, and ARTEMIS. We describe the significant features of these packages and discuss their advantages or disadvantages. We also introduce a graphical user interface which greatly facilitates the set up of simple experiments involving scintillator structures with columnar geometries. C1 [Sharma, Diksha; Dong, Han; Fang, Yuan; Badano, Aldo] US FDA, Div Imaging & Appl Math, Off Sci & Radiol Hlth, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Sharma, D (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Radiol Hlth, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. OI badano, aldo/0000-0003-3712-6670 NR 11 TC 0 Z9 0 U1 0 U2 4 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9442-9 J9 PROC SPIE PY 2013 VL 8668 AR 866858 DI 10.1117/12.2007434 PG 5 WC Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BFZ77 UT WOS:000322002700177 ER PT S AU Sahiner, B He, X Chen, WJ Chan, HP Hadjiiski, L Petrick, N AF Sahiner, Berkman He, Xin Chen, Weijie Chan, Heang-Ping Hadjiiski, Lubomir Petrick, Nicholas BE Novak, CL Aylward, S TI Neural Network Training by Maximization of the Area Under the ROC Curve: Application to Characterization of Masses on Breast Ultrasound as Malignant or Benign SO MEDICAL IMAGING 2013: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Computer-Aided Diagnosis CY FEB 12-14, 2013 CL Lake Buena Vista, FL SP SPIE, Aeroflex Inc, Univ Cent Florida, CREOL Coll Opt & Photon, DQE Instruments Inc, Medtronic Inc, PIXELTEQ DE Artificial neural networks; overtraining; simulation; breast mass characterization; ultrasound AB Back-propagation neural networks (BPNs) are traditionally trained using error measures such as sum-of-squares or cross-entropy. If the training sample size is small, and the neural network has a large number of hidden layer nodes, the BPN may be overtrained, i.e., it may fit the training data well, but may generalize poorly to independent test data. In this study, we investigated a training technique that maximized the approximate area under the ROC curve (AUC) to reduce overtraining. In general, the non-parametric AUC is a discontinuous and non-differentiable function of the neural network output, which makes it unsuitable for gradient descent algorithms such as back-propagation. We used a semi-differentiable approximation to AUC, which appeared to provide reasonable training for the data sets explored in this study. We performed a simulation study using synthetic data sets consisting of Gaussian mixtures to investigate the behavior of this new technique with respect to overtraining. Our results indicated that an artificial neural network trained using the AUC-maximization method is less prone to overtraining. The advantage of the AUC-maximization method was consistently observed over different values of hidden layer BPN nodes, training sample sizes, and the dimensionality of the feature spaces evaluated in our simulation study. For a five-hidden-node BPN trained using 50 training samples per class, the average test AUC was 0.896 (standard deviation (SD): 0.026) with AUC-maximization and 0.856 (SD: 0.028) with the sum-of-squares method. The gain in test performance by the AUC-maximization method over the traditional BPN training was greater when the training sample size was smaller. We also applied this new method to a data set previously acquired for characterization of masses on breast ultrasound as malignant or benign. Our results with this real-world data set had the same trend as with our simulation data sets in that the AUC-maximization technique was less prone to overtraining than the sum-of-squares method. C1 [Sahiner, Berkman; He, Xin; Chen, Weijie; Petrick, Nicholas] US FDA, CDRH, Silver Spring, MD 20993 USA. RP Sahiner, B (reprint author), US FDA, CDRH, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Berkman.sahiner@fda.hhs.gov NR 9 TC 0 Z9 0 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9444-3 J9 PROC SPIE PY 2013 VL 8670 AR 86701M DI 10.1117/12.2007615 PG 7 WC Engineering, Electrical & Electronic; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BGC32 UT WOS:000322261500056 ER PT J AU Iacono, MI Makris, N Mainardi, L Angelone, LM Bonmassar, G AF Iacono, Maria Ida Makris, Nikos Mainardi, Luca Angelone, Leonardo M. Bonmassar, Giorgio TI MRI-Based Multiscale Model for Electromagnetic Analysis in the Human Head with Implanted DBS SO COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE LA English DT Article ID DEEP BRAIN-STIMULATION; STEREOTACTIC FUNCTIONAL NEUROSURGERY; METALLIC IMPLANTS; DIELECTRIC-PROPERTIES; SUBTHALAMIC NUCLEUS; ATLAS; ABSORPTION; FIELD; REGISTRATION; EXPOSURE AB Deep brain stimulation (DBS) is an established procedure for the treatment of movement and affective disorders. Patients with DBS may benefit from magnetic resonance imaging (MRI) to evaluate injuries or comorbidities. However, the MRI radio-frequency (RF) energy may cause excessive tissue heating particularly near the electrode. This paper studies how the accuracy of numerical modeling of the RF field inside a DBS patient varies with spatial resolution and corresponding anatomical detail of the volume surrounding the electrodes. A multiscale model (MS) was created by an atlas-based segmentation using a 1 mm(3) head model (mRes) refined in the basal ganglia by a 200 mu m(2) ex-vivo dataset. Four DBS electrodes targeting the left globus pallidus internus were modeled. Electromagnetic simulations at 128 MHz showed that the peak of the electric field of the MS doubled (18.7 kV/m versus 9.33 kV/m) and shifted 6.4 mm compared to the mRes model. Additionally, the MS had a sixfold increase over the mRes model in peak-specific absorption rate (SAR of 43.9 kW/kg versus 7 kW/kg). The results suggest that submillimetric resolution and improved anatomical detail in the model may increase the accuracy of computed electric field and local SAR around the tip of the implant. C1 [Iacono, Maria Ida; Makris, Nikos; Angelone, Leonardo M.; Bonmassar, Giorgio] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Med Sch, Charlestown, MA 02129 USA. [Iacono, Maria Ida; Angelone, Leonardo M.] US FDA, Div Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Makris, Nikos] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Morphometr Anal,Dept Psychiat & Neurol, Boston, MA 02129 USA. [Mainardi, Luca] Politecn Milan, Dept Bioengn, I-20133 Milan, Italy. RP Bonmassar, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Med Sch, Charlestown, MA 02129 USA. EM giorgio@nmr.mgh.harvard.edu OI Angelone, Leonardo/0000-0002-1105-021X FU National Institutes of Health [1R21EY020961-01, 1R43NS071988-01A, 15P41RR014075-13]; NIDA [1R01DA027804-01]; NIMH [1R21MH084041-01A1] FX Preparation of this paper was supported by Grants 1R21EY020961-01, 1R43NS071988-01A, and 15P41RR014075-13 from the National Institutes of Health and, in part, by Grants from NIDA 1R01DA027804-01 and NIMH 1R21MH084041-01A1. The authors give special thanks to A. Mareyam, J. R. Polimeni, L. L. Wald, and B. Fischl for providing them with the mu Res human brain dataset, to A. Van der Kouwe for his scientific support, and to Remcom's technical support. NR 71 TC 2 Z9 2 U1 0 U2 12 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 1748-670X EI 1748-6718 J9 COMPUT MATH METHOD M JI Comput. Math. Method Med. PY 2013 AR UNSP 694171 DI 10.1155/2013/694171 PG 12 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 192HH UT WOS:000322474400001 ER PT J AU Ruiz, P Yang, XX Lumen, A Fisher, J AF Ruiz, Patricia Yang, Xiaoxia Lumen, Annie Fisher, Jeff BE Fowler, BA TI Quantitative Structure-Activity Relationship (QSAR) Models, Physiologically Based Pharmacokinetic (PBPK) Models, Biologically Based Dose Response (BBDR) and Toxicity Pathways Computational Tools for Public Health SO COMPUTATIONAL TOXICOLOGY: METHODS AND APPLICATIONS FOR RISK ASSESSMENT LA English DT Article; Book Chapter ID SPRAGUE-DAWLEY RATS; MERCURY FOLLOWING EXPOSURE; BISPHENOL-A; RISK-ASSESSMENT; DRINKING-WATER; CANCER-RISK; ENVIRONMENTAL-POLLUTANTS; PERCUTANEOUS-ABSORPTION; LACTATIONAL TRANSFER; TOXICOKINETIC MODEL C1 [Ruiz, Patricia] US Ctr Dis Control, ATSDR, Chamblee, GA USA. [Yang, Xiaoxia; Lumen, Annie; Fisher, Jeff] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Ruiz, P (reprint author), US Ctr Dis Control, ATSDR, Chamblee, GA USA. NR 107 TC 2 Z9 2 U1 1 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-396508-0 PY 2013 BP 5 EP 21 PG 17 WC Mathematical & Computational Biology; Toxicology SC Mathematical & Computational Biology; Toxicology GA BFR29 UT WOS:000321041500003 ER PT J AU Valerio, LG AF Valerio, Luis G., Jr. BE Fowler, BA TI Computational Translation and Integration of Test Data to Meet Risk Assessment Goals SO COMPUTATIONAL TOXICOLOGY: METHODS AND APPLICATIONS FOR RISK ASSESSMENT LA English DT Article; Book Chapter ID IN-SILICO METHODS; AMES TEST MUTAGENICITY; JOINT RESEARCH-CENTER; RODENT CARCINOGENICITY; QSAR MODELS; MDL-QSAR; PHARMACEUTICAL IMPURITIES; REPRODUCTIVE TOXICITY; CHEMICAL-STRUCTURE; TOXICOLOGY MODELS C1 US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Valerio, LG (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 111 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-396508-0 PY 2013 BP 85 EP 112 PG 28 WC Mathematical & Computational Biology; Toxicology SC Mathematical & Computational Biology; Toxicology GA BFR29 UT WOS:000321041500007 ER PT J AU Fang, H Hong, HX Liu, ZC Perkins, R Kelly, R Beresney, J Tong, WD Fowler, BA AF Fang, Hong Hong, Huixiao Liu, Zhichao Perkins, Roger Kelly, Reagan Beresney, John Tong, Weida Fowler, Bruce A. BE Fowler, BA TI Omics Biomarkers in Risk Assessment A Bioinformatics Perspective SO COMPUTATIONAL TOXICOLOGY: METHODS AND APPLICATIONS FOR RISK ASSESSMENT LA English DT Article; Book Chapter ID GENE-EXPRESSION DATA; INDUCED LIVER-INJURY; DECISION FOREST; MICROARRAY DATA; DRUG DISCOVERY; MOLECULAR CLASSIFICATION; CANCER CLASSIFICATION; TUMOR CLASSIFICATION; PROTEOMIC PATTERNS; CLASS PREDICTION C1 [Fang, Hong] US FDA, Off Sci Coordinat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Hong, Huixiao; Liu, Zhichao; Perkins, Roger; Kelly, Reagan; Tong, Weida] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR USA. [Beresney, John; Fowler, Bruce A.] ICF Int, Fairfax, VA USA. RP Fang, H (reprint author), US FDA, Off Sci Coordinat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 50 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-396508-0 PY 2013 BP 195 EP 213 PG 19 WC Mathematical & Computational Biology; Toxicology SC Mathematical & Computational Biology; Toxicology GA BFR29 UT WOS:000321041500012 ER PT J AU Scheineson, MJ Cuevas, G AF Scheineson, Marc J. Cuevas, Guillermo TI United States v. Caronia The Increasing Strength of Commercial Free Speech and Potential New Emphasis on Classifying Off-Label Promotion as "False and Misleading" SO FOOD AND DRUG LAW JOURNAL LA English DT Article ID 1ST-AMENDMENT; PHYSICIANS; CALL C1 [Scheineson, Marc J.] US FDA, Rockville, MD 20857 USA. NR 38 TC 2 Z9 2 U1 0 U2 2 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2013 VL 68 IS 2 BP 201 EP 216 PG 16 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 180KS UT WOS:000321594700005 PM 24640469 ER PT S AU Deng, L Luo, M Velikovsky, A Mariuzza, RA AF Deng, Lu Luo, Ming Velikovsky, Alejandro Mariuzza, Roy A. BE Dill, KA TI Structural Insights into the Evolution of the Adaptive Immune System SO ANNUAL REVIEW OF BIOPHYSICS, VOL 42 SE Annual Review of Biophysics LA English DT Review; Book Chapter DE antibody; T cell receptor; variable lymphocyte receptor; jawless vertebrate; immunoglobulin fold; leucine-rich repeat ID VARIABLE LYMPHOCYTE RECEPTORS; T-CELL-RECEPTOR; CHITIN-BINDING PROTEINS; ANTIGEN-RECEPTOR; SOMATIC DIVERSIFICATION; MONOCLONAL-ANTIBODIES; IMMUNOLOGIC RESPONSES; CRYSTAL-STRUCTURE; AMPHIOXUS GENOME; SEA LAMPREY AB The adaptive immune system, which is based on highly diverse antigen receptors that are generated by somatic recombination, arose approximately 500 Mya at the dawn of vertebrate evolution. In jawed vertebrates, adaptive immunity is mediated by antibodies and T cell receptors (TCRs), which are composed of immunoglobulin (Ig) domains containing hypervariable loops that bind antigen. In striking contrast, the adaptive immune receptors of jawless vertebrates, termed variable lymphocyte receptors (VLRs), are constructed from leucine-rich repeat (LRR) modules. Structural studies of VLRs have shown that these LRR-based receptors bind antigens though their concave surface, in addition to a unique hypervariable loop in the C-terminal LRR capping module. These studies have revealed a remarkable example of convergent evolution in which jawless vertebrates adopted the LRR scaffold to recognize as broad a spectrum of antigens as the Ig-based antibodies and TCRs of jawed vertebrates, with altogether comparable affinity and specificity. C1 [Deng, Lu] US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Luo, Ming; Velikovsky, Alejandro; Mariuzza, Roy A.] Univ Maryland, Inst Biosci & Biotechnol Res, WM Keck Lab Struct Biol, Rockville, MD 20850 USA. [Luo, Ming] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China. [Luo, Ming] Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China. [Velikovsky, Alejandro; Mariuzza, Roy A.] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. RP Deng, L (reprint author), US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM mariuzz@umd.edu FU NIAID NIH HHS [AI073654, R01 AI036900, AI036900] NR 85 TC 17 Z9 18 U1 0 U2 33 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1936-122X BN 978-0-8243-1842-0 J9 ANNU REV BIOPHYS JI Annu. Rev. Biophys. PY 2013 VL 42 BP 191 EP 215 DI 10.1146/annurev-biophys-083012-130422 PG 25 WC Biophysics SC Biophysics GA BFW68 UT WOS:000321695700010 PM 23451889 ER PT J AU Simeonova, R Vitcheva, V Kondeva-Burdina, M Krasteva, I Manov, V Mitcheva, M AF Simeonova, Rumyana Vitcheva, Vessela Kondeva-Burdina, Magdalena Krasteva, Ilina Manov, Vassil Mitcheva, Mitka TI Hepatoprotective and Antioxidant Effects of Saponarin, Isolated from Gypsophila trichotoma Wend. on Paracetamol-Induced Liver Damage in Rats SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID OXIDATIVE STRESS; LIPID-PEROXIDATION; HUMAN HEPATOCYTES; HEPATOTOXICITY; DRUG; GLUTATHIONE; TOXICITY; MECHANISMS; FLAVONOIDS; MICROSOMES AB The hepatoprotective potential of saponarin, isolated from Gypsophila trichotoma, was evaluated in vitro/in vivo using a hepatotoxicity model of paracetamol-induced liver injury. In freshly isolated rat hepatocytes, paracetamol (100 mu mol) led to a significant decrease in cell viability, increased LDH leakage, decreased levels of cellular GSH, and elevated MDA quantity. Saponarin (60-0.006 mu g/mL) preincubation, however, significantly ameliorated paracetamol-induced hepatotoxicity in a concentration-dependent manner. The beneficial effect of saponarin was also observed in vivo. Rats were challenged with paracetamol alone (600 mg/kg, i.p.) and after 7-day pretreatment with saponarin (80 mg/kg, oral gavage). Paracetamol toxicity was evidenced by increase in MDA quantity and decrease in cell GSH levels and antioxidant defence system. No changes in phase I enzyme activities of AH and EMND and cytochrome P 450 quantity were detected. Saponarin pretreatment resulted in significant increase in cell antioxidant defence system and GSH levels and decrease in lipid peroxidation. The biochemical changes are in good correlation with the histopathological data. Protective activity of saponarin was similar to the activity of positive control silymarin. On the basis of these results, it can be concluded that saponarin exerts antioxidant and hepatoprotective activity against paracetamol liver injury in vitro/in vivo. C1 [Simeonova, Rumyana; Vitcheva, Vessela; Kondeva-Burdina, Magdalena; Mitcheva, Mitka] Med Univ, Fac Pharm, Dept Pharmacol Pharmacotherapy & Toxicol, Lab Drug Metab & Drug Tox, Sofia 1000, Bulgaria. [Vitcheva, Vessela] US FDA, CFSAN, Pkwy Coll Pk, MD 20740 USA. [Krasteva, Ilina] Med Univ, Fac Pharm, Dept Pharmacognosy, Sofia 1000, Bulgaria. [Manov, Vassil] Univ Forestry, Fac Vet Med, Dept Obstet Gynecol Biotechnol Reprod Pathol Anat, Sofia 1756, Bulgaria. RP Vitcheva, V (reprint author), Med Univ, Fac Pharm, Dept Pharmacol Pharmacotherapy & Toxicol, Lab Drug Metab & Drug Tox, 2 Dunav St, Sofia 1000, Bulgaria. EM vesselavitcheva@yahoo.com FU Medical Science Committee through Concurs Grant [42/2011] FX The authors would like to thank the Medical Science Committee for funding this research (Project no. 42/2011) through Concurs Grant 2011. NR 45 TC 12 Z9 14 U1 1 U2 7 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 J9 BIOMED RES INT JI Biomed Res. Int. PY 2013 AR 757126 DI 10.1155/2013/757126 PG 10 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 181EW UT WOS:000321651800001 ER PT B AU Kahook, MY Van Buskirk, EM AF Kahook, Malik Y. Van Buskirk, E. Michael BE Kahook, MY Schuman, JS Epstein, DL TI Anatomy SO CHANDLER AND GRANT'S GLAUCOMA, FIFTH EDITION LA English DT Article; Book Chapter ID OPTIC-NERVE HEAD; TRABECULAR MESHWORK; LAMINA-CRIBROSA; LASER TRABECULOPLASTY; PRIMATE EYE; OUTFLOW; NEUROPATHY; GLAUCOMA; SCHLEMM; MONKEY C1 [Kahook, Malik Y.] Univ Colorado, Dept Ophthalmol, Boulder, CO 80309 USA. [Van Buskirk, E. Michael] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Kahook, MY (reprint author), US FDA, Ophthalm Device Div, Rockville, MD 20857 USA. NR 41 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-55642-954-5 PY 2013 BP 7 EP 15 PG 9 WC Ophthalmology SC Ophthalmology GA BFM72 UT WOS:000320564900004 ER PT B AU Kahook, MY Schuman, JS AF Kahook, Malik Y. Schuman, Joel S. BE Kahook, MY Schuman, JS Epstein, DL TI CHANDLER and GRANT'S GLAUCOMA FIFTH EDITION INTRODUCTION SO CHANDLER AND GRANT'S GLAUCOMA, FIFTH EDITION LA English DT Editorial Material; Book Chapter C1 [Kahook, Malik Y.] Univ Colorado, Dept Ophthalmol, Boulder, CO 80309 USA. [Schuman, Joel S.] Univ Pittsburgh, Sch Med, Inst Eye & Ear, Pittsburgh, PA 15260 USA. [Schuman, Joel S.] Univ Pittsburgh, Swanson Sch Engn, Pittsburgh, PA 15260 USA. [Schuman, Joel S.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Schuman, Joel S.] Massachusetts Eye & Ear Infirm, Boston, MA USA. [Schuman, Joel S.] Tufts Univ, New England Med Ctr, Medford, MA USA. RP Kahook, MY (reprint author), US FDA, Ophthalm Device Div, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-55642-954-5 PY 2013 BP XXIIII EP XXIIII PG 1 WC Ophthalmology SC Ophthalmology GA BFM72 UT WOS:000320564900002 ER PT J AU Yavlovich, A Viard, M Gupta, K Sine, J Vu, M Blumenthal, R Tata, DB Puri, A AF Yavlovich, Amichai Viard, Mathias Gupta, Kshitij Sine, Jessica Vu, Mylinh Blumenthal, Robert Tata, Darrell B. Puri, Anu TI Low-visibility light-intensity laser-triggered release of entrapped calcein from 1,2-bis (tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine liposomes is mediated through a type I photoactivation pathway SO INTERNATIONAL JOURNAL OF NANOMEDICINE LA English DT Article DE visible laser-triggered payload release; photo-agents; photopolymerizable phospholipids; photodynamic actions; reactive oxygen species ID PHOTODYNAMIC THERAPY; BIOLOGICAL-SYSTEMS; LIPID-BILAYERS; SINGLET OXYGEN; SOLUTE RELEASE; CELLS; DELIVERY; PHOSPHATIDYLCHOLINE; VESICLES; MECHANISMS AB We recently reported on the physical characteristics of photo-triggerable liposomes containing dipalmitoylphosphatidylcholine (DPPC), and 1,2-bis (tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) carrying a photo agent as their payload. When exposed to a low-intensity 514 nm wavelength (continuous-wave) laser light, these liposomes were observed to release entrapped calcein green (Cal-G; Ex/Em 490/517 nm) but not calcein blue (Cal-B; Ex/Em 360/460 nm). In this study, we have investigated the mechanism for the 514 nm laser-triggered release of the Cal-G payload using several scavengers that are known specifically to inhibit either type I or type II photoreaction pathways. Liposomes containing DPPC:DC8,9PC: distearoylphosphatidylethanolamine (DSPE)-polyethylene glycol (PEG)-2000 (86:10:04 mole ratio) were loaded either with fluorescent (calcein) or nonfluorescent (H-3-inulin) aqueous markers. In addition, a non-photo-triggerable formulation (1-palmitoyl-2-oleoyl phosphatidylcholine [POPC]:DC8,9PC:DSPE-PEG2000) was also studied with the same payloads. The 514 nm wavelength laser exposure on photo-triggerable liposomes resulted in the release of Cal-G but not that of Cal-B or H-3-inulin, suggesting an involvement of a photoactivated state of Cal-G due to the 514 nm laser exposure. Upon 514 nm laser exposures, substantial hydrogen peroxide (H2O2, approximate to 100 mu M) levels were detected from only the Cal-G loaded photo-triggerable liposomes but not from Cal-B-loaded liposomes (<= 10 mu M H2O2). The Cal-G release from photo-triggerable liposomes was found to be significantly inhibited by ascorbic acid (AA), resulting in a 70%-80% reduction in Cal-G release. The extent of AA-mediated inhibition of Cal-G release from the liposomes also correlated with the consumption of AA. No AA consumption was detected in the 514 nm laser-exposed Cal B-loaded liposomes, thus confirming a role of photoactivation of Cal-G in liposome destabilization. Inclusion of 100 mM K3Fe(CN)(6) (a blocker of electron transfer) in the liposomes substantially inhibited Cal-G release, whereas inclusion of 10 mM sodium azide (a blocker of singlet oxygen of type II photoreaction) in the liposomes failed to block 514 nm laser-triggered Cal-G release. Taken together, we conclude that low-intensity 514 nm laser-triggered release of Cal-G from photo-triggerable liposomes involves the type I photoreaction pathway. C1 [Yavlovich, Amichai; Viard, Mathias; Gupta, Kshitij; Sine, Jessica; Vu, Mylinh; Blumenthal, Robert; Puri, Anu] NCI, Nanobiol Program, Ctr Canc Res, Ft Detrick, MD 21702 USA. [Viard, Mathias] SAIC Frederick Inc, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD USA. [Tata, Darrell B.] US FDA, CDRH, OSEL, Div Phys, White Oak, MD USA. RP Puri, A (reprint author), NCI, Membrane Struct & Funct Sect, Nanobiol Program, Ctr Canc Res, Bldg 469,Room 216A, Ft Detrick, MD 21702 USA. EM puria@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX This project was funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. We thank Alex Haber and Christopher Connor for their help with the experiments. NR 40 TC 2 Z9 2 U1 0 U2 16 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2013 J9 INT J NANOMED JI Int. J. Nanomed. PY 2013 VL 8 BP 2575 EP 2587 DI 10.2147/IJN.S44993 PG 13 WC Nanoscience & Nanotechnology; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA 185XI UT WOS:000322003800001 PM 23901274 ER PT J AU Lee, EC Ha, E Singh, S Legesse, L Ahmad, S Karnaukhova, E Donaldson, RP Jeremic, AM AF Lee, Elizabeth C. Ha, Emmeline Singh, Sanghamitra Legesse, Linda Ahmad, Sana Karnaukhova, Elena Donaldson, Robert P. Jeremic, Aleksandar M. TI Copper(II)-human amylin complex protects pancreatic cells from amylin toxicity SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS LA English DT Article ID ISLET AMYLOID POLYPEPTIDE; TYPE-2 DIABETES-MELLITUS; ALZHEIMERS-DISEASE; HYDROXYL RADICALS; OXIDATIVE STRESS; MEMBRANE INTERACTIONS; REDOX REACTIONS; BETA-CELLS; COPPER; CYTOTOXICITY AB Human amylin-derived oligomers and aggregates are believed to play an important role in the pathogenesis of type II diabetes mellitus (T2DM). In addition to amylin-evoked cell attrition, T2DM is often accompanied by elevated serum copper levels. Although previous studies have shown that human amylin, in the course of its aggregation, produces hydrogen peroxide (H2O2) in solution, and that this process is exacerbated in the presence of copper(II) ions (Cu2+), very little is known about the mechanism of interaction between Cu2+ and amylin in pancreatic beta-cells, including its pathological significance. Hence, in this study we investigated the mechanism by which Cu2+ and human amylin catalyze formation of reactive oxygen species (ROS) in cells and in vitro, and examined the modulatory effect of Cu2+ on amylin aggregation and toxicity in pancreatic rat insulinoma (RIN-m5F) beta-cells. Our results indicate that Cu2+ interacts with human and rat amylin to form metalo-peptide complexes with low aggregative and oxidative properties. Human and non-amyloidogenic rat amylin produced minute (nM) amounts of H2O2, the accumulation of which was slightly enhanced in the presence of Cu2+. In a marked contrast to human and rat amylin, and in the presence of the reducing agents glutathione and ascorbate, Cu2+ produced mu M concentrations of H2O2 surpassing the amylin effect by several fold. The current study shows that human and rat amylin not only produce but also quench H2O2, and that human but not rat amylin significantly decreases the amount of H2O2 in solution produced by Cu2+ and glutathione. Similarly, human amylin was found to also decrease hydroxyl radical formation elicited by Cu2+ and glutathione. Furthermore, Cu2+ mitigated the toxic effect of human amylin by inhibiting activation of pro-apoptotic caspase-3 and stress-kinase signaling pathways in rat pancreatic insulinoma cells in part by stabilizing human amylin in its native conformational state. This sacrificial quenching of metal-catalyzed ROS by human amylin and copper's anti-aggregative and anti-apoptotic properties suggest a novel and protective role for the copper-amylin complex. C1 [Lee, Elizabeth C.; Ha, Emmeline; Singh, Sanghamitra; Legesse, Linda; Ahmad, Sana; Donaldson, Robert P.; Jeremic, Aleksandar M.] George Washington Univ, Dept Biol Sci, Washington, DC 20052 USA. [Karnaukhova, Elena] Food & Drug Adm, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Jeremic, AM (reprint author), George Washington Univ, Dept Biol Sci, 340 Lisner Hall,2023 G St NW, Washington, DC 20052 USA. EM jerema@gwu.edu FU GWU CCFF research grant FX This work was supported by the GWU CCFF research grant. NR 62 TC 20 Z9 20 U1 4 U2 20 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1463-9076 J9 PHYS CHEM CHEM PHYS JI Phys. Chem. Chem. Phys. PY 2013 VL 15 IS 30 BP 12558 EP 12571 DI 10.1039/c3cp44542a PG 14 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 180TW UT WOS:000321622500022 PM 23793354 ER PT J AU Anez, G Rios, M AF Anez, German Rios, Maria TI Dengue in the United States of America: A Worsening Scenario? SO BIOMED RESEARCH INTERNATIONAL LA English DT Review ID PUERTO-RICO; HEMORRHAGIC-FEVER; AEDES-ALBOPICTUS; PUBLIC-HEALTH; BLOOD-DONORS; VIRUS; TRANSMISSION; CULICIDAE; DIPTERA; SURVEILLANCE AB Dengue is a febrile illness caused by any of the four dengue virus types (DENV-1 to -4, genus Flavivirus, family Flaviviridae) mainly transmitted by the mosquito Aedes aegypti. DENV can be transmitted by blood transfusion. Dengue has been historically present in the continental United States (US), in the state of Hawaii, and in the US insular territories in the Caribbean and the Pacific. During the second half of the 20th century, most of the cases reported in the US were imported cases brought to the country by travelers. Since 2009, cases of autochthonous dengue have been recognized in the state of Florida after 75 years of absence, followed by intensification of transmission in endemic places including the US territories of US Virgin Islands and Puerto Rico, which experienced a large dengue epidemic in 2010. The widespread distribution of dengue mosquito vectors, deficient mosquito control measures and increased frequency of DENV-infected visitors to the US coming from dengue-endemic locations or places experiencing epidemics appear to be jointly responsible for the emergence and reemergence of dengue in the US and its territories. C1 [Anez, German; Rios, Maria] US FDA, Lab Emerging Pathogens, DETTD OBRR CBER, Bethesda, MD 20892 USA. RP Anez, G (reprint author), US FDA, Lab Emerging Pathogens, DETTD OBRR CBER, Bethesda, MD 20892 USA. EM german.anez@fda.hhs.gov; maria.rios@fda.hhs.gov OI Anez, German/0000-0001-5361-3001 NR 83 TC 13 Z9 13 U1 2 U2 16 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 J9 BIOMED RES INT JI Biomed Res. Int. PY 2013 AR 678645 DI 10.1155/2013/678645 PG 13 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 177BD UT WOS:000321349600001 ER PT J AU Simhadri, VR Mariano, JL Gil-Krzewska, A Zhou, Q Borrego, F AF Simhadri, Venkateswara R. Mariano, John L. Gil-Krzewska, Aleksandra Zhou, Qing Borrego, Francisco TI CD300c is an Activating Receptor Expressed on Human Monocytes SO JOURNAL OF INNATE IMMUNITY LA English DT Article DE CD300; CD300a; CD300c; Cell surface receptors; Paired receptors ID INHIBITORY RECEPTOR; NK CELLS; FUNCTIONAL-CHARACTERIZATION; IMMUNOGLOBULIN RECEPTOR; DENDRITIC CELLS; IMMUNE-SYSTEM; MEMBER; MAST; PATHWAYS; IRP60 AB Human CD300 molecules comprise a family of receptors that regulate many immune cell processes. They are mostly expressed on myeloid cells, although expression of two members, CD300a and CD300c, has also been described on lymphocytes. However, due to the lack of specific antibodies that distinguish between these two receptors, it has been difficult to determine the expression pattern and function of CD300a and CD300c in primary cells. Here, we have identified a specific monoclonal antibody, clone TX45, that recognizes only CD300c and show that within freshly isolated blood leukocytes, monocytes are the only cells that express CD300c on the cell surface. In vitro differentiation experiments revealed that CD300c is differentially expressed on different monocyte-derived cells, including macrophages and dendritic cells. Furthermore, TLR ligands LPS and flagellin dynamically regulate the expression of CD300c. Crosslinking of this receptor with clone TX45 monoclonal antibody induced calcium mobilization, upregulation of the costimulatory molecule CD86 and the production of inflammatory cytokines. Importantly, LPS-mediated production of inflammatory cytokines by monocytes was further enhanced if CD300c was simultaneously engaged by the agonist antibody. Altogether, our results show that human CD300c is an activating receptor expressed on monocytes and that it has a potential role in inflammatory responses. Copyright (C) 2013 S. Karger AG, Basel C1 [Simhadri, Venkateswara R.; Mariano, John L.; Gil-Krzewska, Aleksandra; Zhou, Qing; Borrego, Francisco] US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Borrego, F (reprint author), US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, OBP,CDER, Bldg 29B,Room 3NN18 29 Lincoln Dr,HFD-123, Bethesda, MD 20892 USA. EM Francisco.Borrego@fda.hhs.gov FU Food and Drug Administration FX The authors would like to thank Dr. Akira Shibuya for the generous gift of clone TX49 antibody. This work was funded by the intramural program of the Food and Drug Administration. NR 39 TC 6 Z9 6 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-811X J9 J INNATE IMMUN JI J. Innate Immun. PY 2013 VL 5 IS 4 BP 389 EP 400 DI 10.1159/000350523 PG 12 WC Immunology SC Immunology GA 168CA UT WOS:000320682100010 PM 23571507 ER PT J AU Potnis, PA Mitkus, R Elnabawi, A Squibb, K Powell, JL AF Potnis, Pushya A. Mitkus, Robert Elnabawi, Ahmed Squibb, Katherine Powell, Jan L. TI Role of NF-kappa B in the oxidative stress-induced lung inflammatory response to iron and selenium at ambient levels SO TOXICOLOGY RESEARCH LA English DT Article ID PARTICULATE AIR-POLLUTION; REACTIVE OXYGEN; TRANSCRIPTION FACTORS; EPITHELIAL-CELLS; GENE-TRANSCRIPTION; REDOX REGULATION; DNA-DAMAGE; TNF-ALPHA; IN-VITRO; ACTIVATION AB Metals enriched in ambient air fine particulate matter (PM2.5) are thought to contribute to the pathogenesis of PM2.5-induced inflammatory lung diseases. An important mechanism involved in metal-induced lung injury involves increased oxidative stress due to generation of reactive oxygen species. The redox sensitive transcription factor, nuclear factor kappa B (NF-kappa B) converts extracellular oxidative stress signals into changes in expression of genes associated with diverse cellular activities. The purpose of this study was to determine the mechanism by which exposure to Fe or Se, at environmentally relevant concentrations, leads to an increased release of chemokines by cultured human lung epithelial cells (A549). We tested the hypothesis that NF-kappa B signaling pathway is involved in the metal induced IL-8 and MCP-1 release by Fe and Se. Exposure to Fe or Se induced an enhanced release of chemokines at 6 and 24 h, and mediated nuclear translocation of NF-kappa B. Levels of chemokines in response to Fe were significantly suppressed in the presence of BMS-345541, a specific inhibitor of NF-kappa B. Similar effects were seen in response to Se, indicating the involvement of NF-kappa B in the metal-induced chemokine release, while not affecting the AP-1 c-Jun-DNA binding activity. Overall, results indicate that both Fe and Se, at ambient levels, possess the potential for inducing lung inflammation via an oxidative stress pathway in lung epithelial cells. C1 [Potnis, Pushya A.; Mitkus, Robert; Elnabawi, Ahmed; Squibb, Katherine; Powell, Jan L.] Univ Maryland, Sch Med, Toxicol Program, Baltimore, MD 21201 USA. RP Potnis, PA (reprint author), US FDA, Div Biol, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. EM pushya.potnis@fda.hhs.gov FU school University of Maryland at Baltimore (UMAB), School of Medicine Program in Toxicology FX The authors would like to thank graduate school University of Maryland at Baltimore (UMAB), School of Medicine Program in Toxicology for providing funding support. NR 48 TC 3 Z9 3 U1 2 U2 10 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2045-452X J9 TOXICOL RES-UK JI Toxicol. Res. PY 2013 VL 2 IS 4 BP 259 EP 269 DI 10.1039/c3tx50012h PG 11 WC Toxicology SC Toxicology GA 162NU UT WOS:000320272700004 ER PT B AU Buratto, L Brint, SF Romano, MR AF Buratto, Lucio Brint, Stephen F. Romano, Mario R. BA Burratto, L Brint, SF Romano, MR BF Burratto, L Brint, SF Romano, MR TI The Corneal Incision SO CATARACT SURGERY COMPLICATIONS LA English DT Article; Book Chapter ID TRAUMATIC WOUND DEHISCENCE; HYDROGEL OCULAR BANDAGE; CATARACT-SURGERY; CONSTRUCTION; ASTIGMATISM; MANAGEMENT; PATIENT C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Buratto, Lucio] ESCRS, Paris, France. [Brint, Stephen F.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Romano, Mario R.] ESCRS, Paris, France. [Romano, Mario R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Romano, Mario R.] Royal Liverpool Univ Hosp, Liverpool, Merseyside, England. [Romano, Mario R.] Ist Clin & Ric Humanitas, Vitreoretinal Serv, Milan, Italy. EM bookspublishing@wyanokegroup.com NR 20 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-608-7 PY 2013 BP 11 EP 17 PG 7 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BDO78 UT WOS:000314254200002 ER PT J AU Keire, DA Buhse, LF Al-Hakim, A AF Keire, David A. Buhse, Lucinda F. Al-Hakim, Ali TI Characterization of currently marketed heparin products: composition analysis by 2D-NMR SO ANALYTICAL METHODS LA English DT Article ID MAGNETIC-RESONANCE-SPECTROSCOPY; MOLECULAR-WEIGHT HEPARINS; NMR-SPECTROSCOPY; QUANTITATIVE NMR; H-1; PATTERNS; HSQC AB Each type of heparin has a unique pattern of signals in their NMR spectra because of the effects of the process specific chemical reactions used to manufacture them. Thus, for heparin sodium, 1D-H-1-NMR identification tests are part of the United States Pharmacopeia (USP) and European Pharmacopeia (EP) monographs. Previous work has shown that two-dimensional (2D) NMR data can be used to identify heparin types and be used to calculate heparin composition. Therefore, in this study, we applied a 2D H-1-C-13-heteronuclear single quantum coherence (HSQC) spectroscopy experiment to characterize the normal variation of intact heparin sodium or low molecular weight heparin (LMWH) molecular composition in USP grade sample lots which were available on the US market in the summer of 2009. We tested 7 heparin sodium active pharmaceutical ingredient (API) samples by the 2D method representing lots from 6 manufacturers and the USP heparin sodium identification standard. In addition, we tested 10 LMWH API samples from 3 manufactures of different types of LMWH and the USP enoxaparin identification standard. Using the integrated volumes of HSQC cross-peaks assigned to specific heparin species the monosaccharide or disaccharide percent compositions were calculated. These data establish the composition and normal range of variability for each of the heparin types in the 2D assay across manufacturers supplying the US market. The values obtained from the NMR test were similar to those obtained from mass spectrometric analysis of heparin digests on the same sample set. The robustness of the assay was tested by varying the acquisition time from similar to 3 to similar to 68 h by changing the number of transients co-added or the relaxation delay; across these changes the percent composition values obtained did not vary significantly. We conclude that the manner in which the calculations are performed minimizes experimental errors that arise from differences in spectral signal-to-noise, heparin (1)J(CH) through bond coupling constants or relaxation times. C1 [Keire, David A.; Buhse, Lucinda F.] US FDA, CDER, Div Pharmaceut Anal, St Louis, MO 63101 USA. [Al-Hakim, Ali] US FDA, CDER, Off New Drug Qual Assessment, Silver Spring, MD USA. RP Keire, DA (reprint author), US FDA, CDER, Div Pharmaceut Anal, 1114 Market St, St Louis, MO 63101 USA. EM David.Keire@fda.hhs.gov; ali.alhakim@fda.hhs.gov FU FDA Critical Path Program funds FX Suggestion by Drs Torri and Guerrini of the Ronzoni Institute regarding this work are gratefully acknowledged. In part this study was supported by the FDA Critical Path Program funds. NR 30 TC 18 Z9 19 U1 1 U2 35 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1759-9660 J9 ANAL METHODS-UK JI Anal. Methods PY 2013 VL 5 IS 12 BP 2984 EP 2994 DI 10.1039/c3ay40226f PG 11 WC Chemistry, Analytical; Food Science & Technology; Spectroscopy SC Chemistry; Food Science & Technology; Spectroscopy GA 156JW UT WOS:000319819000012 ER PT J AU Easter, R Barry, C Caruso, J Limbach, P AF Easter, Renee Barry, Colin Caruso, Joseph Limbach, Patrick TI Separation and identification of phosphorothioate oligonucleotides by HILIC-ESIMS SO ANALYTICAL METHODS LA English DT Article ID IONIZATION MASS-SPECTROMETRY AB A combined hydrophilic interaction chromatography (HILIC) electrospray ionization mass spectrometry (ESI-MS) approach for the separation and identification of phosphorothioate oligonucleotides is described. Phosphorothioate 21-mer and 23-mer were separated by HILIC and detected using selected ion monitoring (SIM) ESI-MS. Phosphorothioates could be detected from 50 nM solutions suggesting effectiveness comparable to ion pairing reversed phase chromatography approaches. C1 [Easter, Renee; Caruso, Joseph; Limbach, Patrick] Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. [Easter, Renee; Barry, Colin] US FDA, Forens Chem Ctr, Cincinnati, OH USA. RP Caruso, J (reprint author), Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. EM carusoja@ucmail.uc.edu; Pat.Limbach@uc.edu RI Limbach, Patrick/A-9188-2009 OI Limbach, Patrick/0000-0003-1526-4546 FU National Institutes of Health [GM58843]; United States Food and Drug Administration FX Financial support for this work was provided by the National Institutes of Health (GM58843 to P.A.L.). R.N.E. was supported through the Student Temporary Employment Program (STEP) offered by the United States Food and Drug Administration. NR 17 TC 4 Z9 4 U1 6 U2 28 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1759-9660 J9 ANAL METHODS-UK JI Anal. Methods PY 2013 VL 5 IS 11 BP 2657 EP 2659 DI 10.1039/c3ay26519f PG 3 WC Chemistry, Analytical; Food Science & Technology; Spectroscopy SC Chemistry; Food Science & Technology; Spectroscopy GA 145HB UT WOS:000319004800003 ER PT J AU Yamasaki, T Edwards, GB AF Yamasaki, Takeshi Edwards, G. B. TI The genus Myrmarachne (Araneae, Salticidae) in Flores, Indonesia SO ZOOKEYS LA English DT Article DE New species; ant-mimicking jumping spiders; Java; Malay Archipelago ID REDESCRIPTION AB Two new species of the genus Myrmarachne are described (M. acutidens sp. n., M. epigealis sp. n.), and M. macrognatha and M. melanocephala are redescribed from Flores specimens. The females of M. macrognatha are recorded for the first time. C1 [Yamasaki, Takeshi] Kagoshima Univ, Grad Sch Sci & Engn, Kagoshima 8900065, Japan. [Edwards, G. B.] FDACS Div Plant Ind, Florida State Collect Arthropods, Gainesville, FL 32614 USA. RP Yamasaki, T (reprint author), Kagoshima Univ, Grad Sch Sci & Engn, Kagoshima 8900065, Japan. EM k0468874@kadai.jp FU JSPS International Training Program, Kagoshima University (Leader: Prof. Eizi Suzuki) FX We would like to express our deep gratitude to Prof. Seiki Yamane (Kagoshima University, Japan), Dr. Sadaharu Morinaka (Kawaguchi- shi, Japan), Mr. I Ketut Ginarsa (Bali, Indonesia), Prof. Dahermi (Andalas University, Indonesia), Dr. Henny Herwina (Andalas University, Indonesia) and Mr. Rijal Satria (Kagoshima University, Japan) for arranging the field trip to Flores, and to Ms. Marika K llsen (NRM, Sweden) for offering the type material to us. This work was supported by the JSPS International Training Program, Kagoshima University (Leader: Prof. Eizi Suzuki). NR 25 TC 2 Z9 3 U1 7 U2 11 PU PENSOFT PUBL PI SOFIA PA GEO MILEV STR 13A, SOFIA, 1111, BULGARIA SN 1313-2989 EI 1313-2970 J9 ZOOKEYS JI ZooKeys PY 2013 IS 299 BP 1 EP 20 DI 10.3897/zookeys.299.4970 PG 20 WC Zoology SC Zoology GA 143BU UT WOS:000318842100001 PM 23794886 ER PT J AU Avital, I Langan, RC Summers, TA Steele, SR Waldman, SA Backman, V Yee, J Nissan, A Young, P Womeldorph, C Mancusco, P Mueller, R Noto, K Grundfest, W Bilchik, AJ Protic, M Daumer, M Eberhardt, J Man, YG Brucher, BLDM Stojadinovic, A AF Avital, Itzhak Langan, Russell C. Summers, Thomas A. Steele, Scott R. Waldman, Scott A. Backman, Vadim Yee, Judy Nissan, Aviram Young, Patrick Womeldorph, Craig Mancusco, Paul Mueller, Renee Noto, Khristian Grundfest, Warren Bilchik, Anton J. Protic, Mladjan Daumer, Martin Eberhardt, John Man, Yan Gao Bruecher, Bjoern L. D. M. Stojadinovic, Alexander TI Evidence-Based Guidelines for Precision Risk Stratification-Based Screening (PRSBS) for Colorectal Cancer: Lessons Learned from the US Armed Forces: Consensus and Future Directions SO JOURNAL OF CANCER LA English DT Review DE cancer screening; risk identification; colon; rectal; colorectal cancer; evidence-based medicine; consensus ID HEAT-STABLE ENTEROTOXIN; GUANYLYL CYCLASE-C; CONTRAST BARIUM ENEMA; COLON-CANCER; STEM-CELLS; COMPUTED-TOMOGRAPHY; VIRTUAL COLONOSCOPY; PROSPECTIVE MULTICENTER; METHYLATION MARKERS; RACIAL DISPARITIES AB Colorectal cancer (CRC) is the third most common cause of cancer-related death in the United States (U. S.), with estimates of 143,460 new cases and 51,690 deaths for the year 2012. Numerous organizations have published guidelines for CRC screening; however, these numerical estimates of incidence and disease-specific mortality have remained stable from years prior. Technological, genetic profiling, molecular and surgical advances in our modern era should allow us to improve risk stratification of patients with CRC and identify those who may benefit from preventive measures, early aggressive treatment, alternative treatment strategies, and/or frequent surveillance for the early detection of disease recurrence. To better negotiate future economic constraints and enhance patient outcomes, ultimately, we propose to apply the principals of personalized and precise cancer care to risk-stratify patients for CRC screening (Precision Risk Stratification-Based Screening, PRSBS). We believe that genetic, molecular, ethnic and socioeconomic disparities impact oncological outcomes in general, those related to CRC, in particular. This document highlights evidence-based screening recommendations and risk stratification methods in response to our CRC working group private-public consensus meeting held in March 2012. Our aim was to address how we could improve CRC risk stratification-based screening, and to provide a vision for the future to achieving superior survival rates for patients diagnosed with CRC. C1 [Avital, Itzhak; Bruecher, Bjoern L. D. M.; Stojadinovic, Alexander] Bon Secours Canc Inst, Richmond, VA USA. [Avital, Itzhak; Steele, Scott R.; Bruecher, Bjoern L. D. M.; Stojadinovic, Alexander] Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. [Avital, Itzhak; Summers, Thomas A.; Steele, Scott R.; Nissan, Aviram; Bilchik, Anton J.; Protic, Mladjan; Stojadinovic, Alexander] United States Mil Canc Inst, Bethesda, MD USA. [Avital, Itzhak; Nissan, Aviram; Bilchik, Anton J.; Protic, Mladjan; Daumer, Martin; Bruecher, Bjoern L. D. M.; Stojadinovic, Alexander] Theodor Billroth Acad, Int Consortium Res Excellence, INCORE, Munich, Germany. [Langan, Russell C.] Georgetown Univ Hosp, Washington, DC 20007 USA. [Summers, Thomas A.] Walter Reed Natl Mil Med Ctr, Dept Pathol, Bethesda, MD 20889 USA. [Steele, Scott R.] Madigan Army Med Ctr, Dept Surg, Tacoma, WA 98431 USA. [Waldman, Scott A.] Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. [Waldman, Scott A.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Pharmacol & Expt Therapeut, Philadelphia, PA 19107 USA. [Backman, Vadim] Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA. [Yee, Judy] Univ Calif San Francisco, San Francisco Sch Med Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Nissan, Aviram] Hadassah Hebrew Univ, Med Ctr, Dept Surg, Jerusalem, Israel. [Young, Patrick; Womeldorph, Craig] Walter Reed Natl Mil Med Ctr, Dept Med, Div Gastroenterol, Bethesda, MD 20889 USA. [Mancusco, Paul; Mueller, Renee; Noto, Khristian] MD Anderson Canc Ctr Orlando, Orlando, FL USA. [Grundfest, Warren] Telemed & Adv Technol Res Ctr West, Los Angeles, CA USA. [Grundfest, Warren] US FDA, Los Angeles, CA USA. [Bilchik, Anton J.] John Wayne Canc Inst, Santa Monica, CA USA. [Bilchik, Anton J.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Bilchik, Anton J.] Calif Oncol Res Ctr, CA Diagnost, Los Angeles, CA USA. [Protic, Mladjan] Clin Ctr Vojvodina, Clin Abdominal Endocrine & Transplantat Surg, Novi Sad, Serbia. [Protic, Mladjan] Univ Novi Sad, Fac Med, Novi Sad 21000, Serbia. [Daumer, Martin] Sylvia Lawry Ctr MS Res, Munich, Germany. [Eberhardt, John] DecisionQ Corp, Washington, DC USA. [Man, Yan Gao] Henry Jackson Fdn Adv Mil Med, Diagnost & Translat Res Ctr, Gaithersburg, MD USA. [Bruecher, Bjoern L. D. M.] Theodor Billroth Acad, Munich, Germany. [Stojadinovic, Alexander] Walter Reed Natl Mil Med Ctr, Dept Surg, Div Surg Oncol, Bethesda, MD 20889 USA. [Grundfest, Warren] Univ Calif Los Angeles, Los Angeles, CA USA. RP Stojadinovic, A (reprint author), Walter Reed Natl Mil Med Ctr, 8901 Wisconsin Ave,Bldg 9,Room 1272, Bethesda, MD 20889 USA. EM Stojadinovicmd2011@gmail.com RI Backman, Vadim/B-6689-2009; OI Brucher, Bjorn/0000-0002-3930-6416 FU Telemedicine and Advanced Technology Research Center; Henry M. Jackson Foundation for the Advancement of Military Medicine; California Oncology Research Institute; INCORE; International Consortium of Research Excellence of the Theodor-Billroth-Academy [TBA (R)]; United States Military Cancer Institute FX This work is supported by the Telemedicine and Advanced Technology Research Center, the Henry M. Jackson Foundation for the Advancement of Military Medicine, the California Oncology Research Institute, INCORE, International Consortium of Research Excellence of the Theodor-Billroth-Academy [TBA (R)], and the United States Military Cancer Institute. NR 114 TC 7 Z9 8 U1 0 U2 7 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2013 VL 4 IS 3 BP 172 EP 192 DI 10.7150/jca.5834 PG 21 WC Oncology SC Oncology GA 135QG UT WOS:000318303000002 PM 23459409 ER PT J AU Kropp, TJ Rosario, LA DeHaven, S Houser, W Kramer, LA Nath, S Smyrnios, T Wally, JL AF Kropp, Timothy J. Rosario, Lilliam A. DeHaven, Susan Houser, William Kramer, Lou Ann Nath, Shree Smyrnios, Troy Wally, Jeremy L. TI FDA Engages Collaborators to Address Nonclinical Data Challenges SO THERAPEUTIC INNOVATION & REGULATORY SCIENCE LA English DT Article DE Standard for Exchange of Nonclinical Data; SEND standard; data management; computational science; collaboration framework AB FDA and PhUSE cohosted a Computational Science Symposium (CSS) in 2012 that brought stakeholders from the pharmaceutical industry and government to work collaboratively to solve common needs and challenges. A nonclinical informatics workgroup was formed, dedicated to improving nonclinical assessments and regulatory science by identifying, collecting, and prioritizing key needs and challenges in the field and then establishing an innovative framework for addressing them in a collaborative manner. This paper discusses the process and outcomes of the nonclinical informatics workgroup during the CSS and describes an approach which crossed organizational barriers to optimize computational science for nonclinical assessment. C1 [Kropp, Timothy J.; Rosario, Lilliam A.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [DeHaven, Susan] Sanofi Aventis, Bridgewater, NJ USA. [Houser, William] Bristol Myers Squibb Co, Evansville, IN USA. [Kramer, Lou Ann] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Nath, Shree] PointCross Life Sci Inc, Foster City, CA USA. [Smyrnios, Troy] MPI Res, Mattawan, MI USA. [Wally, Jeremy L.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Kropp, TJ (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51,Room 2278, Silver Spring, MD 20993 USA. EM Timothy.Kropp@fda.hhs.gov NR 11 TC 2 Z9 2 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2168-4790 J9 THER INNOV REGUL SCI JI Ther. Innov. Regul. Sci. PD JAN PY 2013 VL 47 IS 1 BP 41 EP 45 DI 10.1177/0092861512466398 PG 5 WC Medical Informatics; Pharmacology & Pharmacy SC Medical Informatics; Pharmacology & Pharmacy GA 136DP UT WOS:000318341700007 ER PT J AU Zhang, LJ Ko, CW Tang, SH Sridhara, R AF Zhang, Lijun Ko, Chia-Wen Tang, Shenghui Sridhara, Rajeshwari TI Relationship Between Progression-Free Survival and Overall Survival Benefit: A Simulation Study SO THERAPEUTIC INNOVATION & REGULATORY SCIENCE LA English DT Article DE clinical trial; overall survival; progression-free survival; crossover; survival post progression ID CLINICAL-TRIALS; END-POINTS AB This study evaluated the circumstances under which the observed progression-free survival (PFS) benefit may translate into an overall survival (OS) benefit. Methods: A simulation study, based on PFS and OS joint model decomposition, was conducted to evaluate the impact of crossover rates, survival post progression (SPP) lengths, and magnitudes of difference in median PFS on OS. Under different simulation scenarios, the degree of impact was investigated based on the probability of observing a significant OS benefit given an observed PFS benefit. Results: Using simulation parameters defined based on historical NDA datasets, the probability of detecting an OS benefit given the observed PFS benefit depends largely on crossover rate and SPP length (ie, SPP median times). Compared to no crossover, a crossover rate of <= 50% decreases the probability of detecting an OS benefit by at most 15% regardless of the SPP length. A crossover rate of > 50% decreases the probability of detecting an OS benefit much further, and the extent of decrease is proportional to the length of SPP. Conclusion: Crossover rate and SPP length are important factors affecting the benefit translating from PFS to OS. This simulation study identified a threshold, of 50%, for crossover rate that is likely to confound OS effect. With a greater than 50% crossover rate, longer SPP further decreases the probability of translating a PFS benefit to OS. C1 [Zhang, Lijun; Ko, Chia-Wen; Tang, Shenghui; Sridhara, Rajeshwari] US FDA, Ctr Drug Evaluat & Res, Div Biometr 5, Off Biostat,Off Translat Sci, Silver Spring, MD USA. RP Zhang, LJ (reprint author), Off Biostat, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM lijun.zhang2@fda.hhs.gov NR 8 TC 6 Z9 6 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2168-4790 J9 THER INNOV REGUL SCI JI Ther. Innov. Regul. Sci. PD JAN PY 2013 VL 47 IS 1 BP 95 EP 100 DI 10.1177/0092861512459180 PG 6 WC Medical Informatics; Pharmacology & Pharmacy SC Medical Informatics; Pharmacology & Pharmacy GA 136DP UT WOS:000318341700015 ER PT J AU Zhou, Y Song, KJ Painter, RG Aiken, M Reiser, J Stanton, BA Nauseef, WM Wang, GS AF Zhou, Yun Song, Kejing Painter, Richard G. Aiken, Martha Reiser, Jakob Stanton, Bruce A. Nauseef, William M. Wang, Guoshun TI Cystic Fibrosis Transmembrane Conductance Regulator Recruitment to Phagosomes in Neutrophils SO JOURNAL OF INNATE IMMUNITY LA English DT Article DE Host defense; Immune response; Neutrophils; Oxidative burst; Phagocytosis; Hypochlorous acid; Myeloperoxidase; Chloride channel; Cystic fibrosis transmembrane conductance regulator ID PSEUDOMONAS-AERUGINOSA; MICE DEFICIENT; CF NEUTROPHILS; HOST-DEFENSE; MYELOPEROXIDASE; TRAFFICKING; OXIDANTS; CELLS; INFLAMMATION; RESISTANCE AB Optimal microbicidal activity of human polymorphonuclear leukocytes (PMN) relies on the generation of toxic agents such as hypochlorous acid (HOCl) in phagosomes. HOCl formation requires H2O2 produced by the NADPH oxidase, myeloperoxidase derived from azurophilic granules, and chloride ion. Chloride transport from cytoplasm into phagosomes requires chloride channels which include cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel. However, the phagosomal targeting of CFTR in PMN has not been defined. Using human peripheral blood PMN, we determined that 95-99% of lysosomal-associated membrane protein 1 (LAMP-1)-positive mature phagosomes were CFTR positive, as judged by immunostaining and flow cytometric analysis. To establish a model cell system to evaluate CFTR phagosomal recruitment, we stably expressed enhanced green fluorescent protein (EGFP) alone, EGFP-wt-CFTR and EGFP-Delta F508-CFTR fusion proteins in promyelocytic PLB-985 cells, respectively. After differentiation into neutrophil-like cells, CFTR presentation to phagosomes was examined. EGFP-wt-CFTR was observed to associate with phagosomes and colocalize with LAMP-1. Flow cytometric analysis of the isolated phagosomes indicated that such a phagosomal targeting was determined by the CFTR portion of the fusion protein. In contrast, significantly less EGFP-Delta F508-CFTR was found in phagosomes, indicating a defective targeting of the molecule to the organelle. Importantly, the CFTR corrector compound VRT-325 facilitated the recruitment of Delta F508-CFTR to phagosomes. These data demonstrate the possibility of pharmacologic correction of impaired recruitment of mutant CFTR, thereby providing a potential means to augment chloride supply to the phagosomes of PMN in patients with cystic fibrosis to enhance their microbicidal function. Copyright (C) 2013 S. Karger AG, Basel C1 [Zhou, Yun; Song, Kejing; Painter, Richard G.; Aiken, Martha; Wang, Guoshun] Louisiana State Univ, Hlth Sci Ctr, Dept Microbiol, New Orleans, LA 70112 USA. [Zhou, Yun; Song, Kejing; Painter, Richard G.; Aiken, Martha; Wang, Guoshun] Louisiana State Univ, Hlth Sci Ctr, Dept Genet, New Orleans, LA 70112 USA. [Zhou, Yun; Song, Kejing; Painter, Richard G.; Aiken, Martha; Wang, Guoshun] Louisiana State Univ, Hlth Sci Ctr, Dept Med, New Orleans, LA 70112 USA. [Reiser, Jakob] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Stanton, Bruce A.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Microbiol & Immunol, Hanover, NH 03756 USA. [Stanton, Bruce A.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Physiol, Hanover, NH 03756 USA. [Nauseef, William M.] Univ Iowa, Inflammat Program, Coralville, IA USA. [Nauseef, William M.] Univ Iowa, Dept Med, Roy J & Lucille A Carver Coll Med, Coralville, IA USA. RP Wang, GS (reprint author), Louisiana State Univ, Hlth Sci Ctr, Gene Therapy Program, Dept Microbiol, CSRB 642,533 Bolivar St, New Orleans, LA 70112 USA. EM gwang@lsuhsc.edu FU National Institutes of Health [1R01AI72327]; CF RDP [STANTO07R0]; NIH [R01 HL074175] FX The authors would like to thank the volunteers who donated their blood and the Cystic Fibrosis Foundation for providing the CFTR corrector compound VRT-325. We also thank Dr. Nick Lanson for his critical reading of the manuscript. This work was supported by a grant from the National Institutes of Health (1R01AI72327) to G.W. B.A.S. was supported by a CF RDP (STANTO07R0) and NIH R01 HL074175. NR 40 TC 26 Z9 26 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-811X J9 J INNATE IMMUN JI J. Innate Immun. PY 2013 VL 5 IS 3 BP 219 EP 230 DI 10.1159/000346568 PG 12 WC Immunology SC Immunology GA 131NB UT WOS:000317999300004 PM 23486169 ER PT J AU Wang, B Gucinski, AC Keire, DA Buhse, LF Boyne, MT AF Wang, Bo Gucinski, Ashley C. Keire, David A. Buhse, Lucinda F. Boyne, Michael T., II TI Structural comparison of two anti-CD20 monoclonal antibody drug products using middle-down mass spectrometry SO ANALYST LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ELECTRON-TRANSFER DISSOCIATION; HIGH-RESOLUTION; TOP-DOWN; LC-MS; STREPTOCOCCAL ENDOPEPTIDASE; PROTEIN-THERAPEUTICS; LIMITED PROTEOLYSIS; CYSTEINE PROTEINASE; STRICT SPECIFICITY AB Liquid chromatography-mass spectrometry (LC-MS) is an information rich analytical tool that can provide fast, robust and sensitive characterization of protein therapeutics for quality assurance and structural comparison. Herein, structural characterization of two anti-CD20 monoclonal antibodies obtained from two different sources was performed using a middle-down LC-MS strategy to determine if they can be analytically differentiated. Through the use of a specific enzymatic digestion method using IdeS with subsequent LC-MS analysis, we show that the anti-CD20 monoclonal antibody that has been approved by the FDA can be partially characterized and differentiated analytically from an Indian sourced product that lacks FDA approval. In comparison to the FDA-approved product, differential modifications to both the N- and C-termini result in increased charge heterogeneity for the Indian product. In addition, significant differences in the intensities of the observed glycoforms between the two antibodies were detected. While this study assesses only one lot of each of a FDA approved drug product and the Indian sourced drug product, the observed differences may represent process specific fingerprints that could be useful for surveillance purposes. C1 [Wang, Bo; Gucinski, Ashley C.; Keire, David A.; Buhse, Lucinda F.; Boyne, Michael T., II] US FDA, Div Pharmaceut Res, Off Testing & Res, Ctr Drug Evaluat & Res, St Louis, MO 63101 USA. RP Boyne, MT (reprint author), US FDA, Div Pharmaceut Res, Off Testing & Res, Ctr Drug Evaluat & Res, 1114 Market St,Room 1002, St Louis, MO 63101 USA. EM Michael.Boyne@fda.hhs.gov FU U.S. Food and Drug Administration; FDA Center for Drug Evaluation and Research Critical Path Program; Regulatory Science and Review Enhancement (RSR) Program; Oak Ridge Institute for Science and Engineering FX This project was supported by appointments to the Research Participation Program at the Center for Drug Evaluation and Research administered by the Oak Ridge Institute for Science and Engineering and the U.S. Food and Drug Administration for B. W. and A. C. G. This work was funded by the FDA Center for Drug Evaluation and Research Critical Path Program and Regulatory Science and Review Enhancement (RSR) Program. The authors thank and acknowledge the Office of International Programs for their assistance in procuring foreign sourced drug products. NR 42 TC 21 Z9 21 U1 2 U2 21 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0003-2654 J9 ANALYST JI Analyst PY 2013 VL 138 IS 10 BP 3058 EP 3065 DI 10.1039/c3an36524g PG 8 WC Chemistry, Analytical SC Chemistry GA 129UF UT WOS:000317867400039 PM 23579346 ER PT J AU Botsis, T Woo, EJ Ball, R AF Botsis, T. Woo, E. J. Ball, R. TI The contribution of the Vaccine adverse event Text Mining system to the classification of possible Guillain-Barre Syndrome reports SO APPLIED CLINICAL INFORMATICS LA English DT Article DE Biosurveillance and case reporting; data repositories; data mining; natural language processing; data access; integration; analysis ID SAFETY; MEDDRA AB Background: We previously demonstrated that a general purpose text mining system, the Vaccine adverse event Text Mining (VaeTM) system, could be used to automatically classify reports of anaphylaxis for post-marketing safety surveillance of vaccines. Objective: To evaluate the ability of VaeTM to classify reports to the Vaccine Adverse Event Reporting System (VAERS) of possible Guillain-Barre Syndrome (GBS). Methods: We used VaeTM to extract the key diagnostic features from the text of reports in VAERS. Then, we applied the Brighton Collaboration (BC) case definition for GBS, and an information retrieval strategy (i.e. the vector space model) to quantify the specific information that is included in the key features extracted by VaeTM and compared it with the encoded information that is already stored in VAERS as Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms (PTs). We also evaluated the contribution of the primary (diagnosis and cause of death) and secondary (second level diagnosis and symptoms) diagnostic VaeTM-based features to the total VaeTM-based information. Results: MedDRA captured more information and better supported the classification of reports for GBS than VaeTM (AUC: 0.904 vs. 0.777); the lower performance of VaeTM is likely due to the lack of extraction by VaeTM of specific laboratory results that are included in the BC criteria for GBS. On the other hand, the VaeTM-based classification exhibited greater specificity than the MedDRA-based approach (94.96% vs. 87.65%). Most of the VaeTM-based information was contained in the secondary diagnostic features. Conclusion: For GBS, clinical signs and symptoms alone are not sufficient to match MedDRA coding for purposes of case classification, but are preferred if specificity is the priority. C1 [Botsis, T.; Woo, E. J.; Ball, R.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Botsis, T.] Univ Tromso, Dept Comp Sci, N-9001 Tromso, Norway. RP Botsis, T (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Woodmont Off Complex 1,Rm 306N, Rockville, MD 20852 USA. EM Taxiarchis.Botsis@fda.hhs.gov FU Oak Ridge Institute for Science and Education; U.S. Department of Energy; U.S. Food and Drug Administration FX This project was supported in part by the appointment of Taxiarchis Botsis to the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. MedDRA is a registered trademark owned by the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) on behalf of the International Conference on Harmonization (ICH). NR 21 TC 3 Z9 3 U1 0 U2 8 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 1869-0327 J9 APPL CLIN INFORM JI Appl. Clin. Inform. PY 2013 VL 4 IS 1 BP 88 EP 99 DI 10.4338/ACI-2012-11-RA-0049 PG 12 WC Medical Informatics SC Medical Informatics GA 120PX UT WOS:000317184500008 PM 23650490 ER PT J AU Neal, AP Guilarte, TR AF Neal, April P. Guilarte, Tomas R. TI Mechanisms of lead and manganese neurotoxicity SO TOXICOLOGY RESEARCH LA English DT Review ID NUTRITION EXAMINATION SURVEY; LONG-TERM POTENTIATION; CHILDRENS INTELLECTUAL FUNCTION; DIVALENT METAL TRANSPORTER; NERVOUS-SYSTEM TOXICITY; ELEMENT-BINDING PROTEIN; VARIANT MESSENGER-RNA; CHRONIC LIVER-FAILURE; D-ASPARTATE RECEPTORS; 2ND NATIONAL-HEALTH AB Human exposure to neurotoxic metals is a global public health problem. Metals which cause neurological toxicity, such as lead (Pb) and manganese (Mn), are of particular concern due to the long-lasting and possibly irreversible nature of their effects. Pb exposure in childhood can result in cognitive and behavioural deficits in children. These effects are long-lasting and persist into adulthood even after Pb exposure has been reduced or eliminated. While Mn is an essential element of the human diet and serves many cellular functions in the human body, elevated Mn levels can result in a Parkinson's disease (PD)-like syndrome and developmental Mn exposure can adversely affect childhood neurological development. Due to the ubiquitous presence of both metals, reducing human exposure to toxic levels of Mn and Pb remains a world-wide public health challenge. In this review we summarize the toxicokinetics of Pb and Mn, describe their neurotoxic mechanisms, and discuss common themes in their neurotoxicity. C1 [Neal, April P.] US FDA, College Pk, MD 20740 USA. [Guilarte, Tomas R.] Columbia Univ, Dept Environm Hlth Sci, Mailman Sch Publ Hlth, New York, NY 10032 USA. RP Neal, AP (reprint author), US FDA, College Pk, MD 20740 USA. EM april.neal@fda.hhs.gov; trguilarte@columbia.edu FU NIEHS [ES006189, ES010975, ES020465] FX This work was originally prepared in partial fulfillment for the doctoral degree requirements for APN. Current email contact information for APN is: april.neal@fda.hhs.gov. Some of the studies described in this review were funded by NIEHS grant number ES006189, ES010975, and ES020465 to TRG. NR 271 TC 25 Z9 26 U1 11 U2 54 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2045-452X J9 TOXICOL RES-UK JI Toxicol. Res. PY 2013 VL 2 IS 2 BP 99 EP 114 DI 10.1039/c2tx20064c PG 16 WC Toxicology SC Toxicology GA 126BM UT WOS:000317586200002 PM 25722848 ER PT J AU Schmued, LC Raymick, J Paule, MG Dumas, M Sarkar, S AF Schmued, Larry C. Raymick, James Paule, Merle G. Dumas, Melanie Sarkar, Sumit TI Characterization of Myelin Pathology in the Hippocampal Complex of a Transgenic Mouse Model of Alzheimer's Disease SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE Alzheimer's disease; amyloid plaques; Black-Gold II; demyelination; hippocampus; AD-Tg mouse ID CEREBRAL AMYLOID ANGIOPATHY; WHITE-MATTER INTEGRITY; MICE; ABNORMALITIES; DEPOSITION; PATHWAYS AB We have characterized the myelin changes observed within the hippocampal complex (HC) of a transgenic (Tg) mouse model of Alzheimer's disease (AD). Individual myelinated fibers were labeled with Black-Gold II while amyloid plaques were labeled with either Congo Red or Pan-A-beta immunofluoresence. Myelinated fibers were never seen passing through amyloid plaques in any region, while conspicuous myelin pathology was seen within, and immediately adjacent to, the amyloid plaques in the HC of the AD-Tg mouse. This pathology consisted of a complete disruption of myelinated fibers passing through the plaque and the region immediately adjacent to the plaques exhibited an edematous swelling of the fibers. This pathology was most frequently observed within the molecular and polymorph layers of the dentate gyrus and the molecular layer of Ammon's horn. The remaining layers of Ammon's horn exhibited minimal myelin pathology, while moderate myelinopathy was observed in the subiculum. Since the HC is integral for memory function, these findings may help account for the memory problems so characteristic of the disease process. Because the molecular layers of the dentate gyrus and Ammon's horn are the sites of inputs to the HC, the extensive myelin pathology observed in these regions would imply functional deafferentation of the HC. The appearance of some Black-Gold II positive debris within the plaques may reflect a possible cascade mechanism whereby the presence of plaques results in myelin degeneration, some of which is incorporated within the plaque, causing it to further expand in a self-perpetuating fashion. C1 [Schmued, Larry C.; Paule, Merle G.; Sarkar, Sumit] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Raymick, James] Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Dumas, Melanie] Prior One, Jefferson, AR 72709 USA. RP Schmued, LC (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. EM larry.schmued@fda.hhs.gov FU FDA [E-7273] FX The authors would like to thank Ms. Florene Lewis for her help with the care and dosing of mice used in this study. This work was supported by FDA protocol E-7273. The findings and conclusions are those of the authors and do not necessarily represent the views of the FDA. The mention of trade names or commercial products does not constitute endorsement. NR 27 TC 10 Z9 10 U1 1 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD JAN PY 2013 VL 10 IS 1 BP 30 EP 37 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 121VE UT WOS:000317271800005 PM 23157338 ER PT J AU Hu, XN Saran, A Hou, S Wen, T Ji, YL Liu, WQ Zhang, H He, WW Yin, JJ Wu, XC AF Hu, Xiaona Saran, Aditya Hou, Shuai Wen, Tao Ji, Yinglu Liu, Wenqi Zhang, Hui He, Weiwei Yin, Jun-Jie Wu, Xiaochun TI Au@PtAg core/shell nanorods: tailoring enzyme-like activities via alloying SO RSC ADVANCES LA English DT Article ID IRON-OXIDE NANOPARTICLES; PEROXIDASE-LIKE ACTIVITY; ARTIFICIAL ENZYMES; GLUCOSE DETECTION; SUPEROXIDE ANION; PLATINUM NANOPARTICLES; CATALYTIC ANTIBODIES; NANOSTRUCTURES; OXYGEN; OXIDATION AB Pt nanoparticles (NPs) have been reported to demonstrate four kinds of enzyme-like activity including superoxide dismutase (SOD), catalase, oxidase and peroxidase. Some of these activities interfere with each other. For instance, as antioxidant enzyme mimics, their SOD and catalase activities are very helpful in scavenging related reactive oxygen species (ROSs). However, their oxidase-like and/or peroxidase-like activities may simultaneously oxidize some natural antioxidants, thus compromising the final anti-oxidation efficacy. Fine tuning different enzyme-like activities is therefore very important to realize the optimization of their functions. In this paper, our effort is focused in this direction by tailoring the electronic structure of Pt NPs via alloying with Ag. All four enzyme-like activities are found to be weakened by an increased Ag percentage in the alloy, as witnessed by decreased values of K-cat. The variation in the electronic structure also changes the substrate affinity. Introducing silver into Pt weakens the affinity for H2O2, which affects the limit of detection (LOD) for H2O2 and products with H2O2 involved. In contrast to Fe3O4 MNPs, for peroxidase-like activity, hydroxyl radicals are not involved in the oxidation of chromogenic substrates for the alloy nanostructures. C1 [Hu, Xiaona; Saran, Aditya; Hou, Shuai; Wen, Tao; Ji, Yinglu; Liu, Wenqi; Zhang, Hui; Wu, Xiaochun] Natl Ctr Nanosci & Technol, CAS Key Lab Standardizat & Measurement Nanotechno, Beijing 100190, Peoples R China. [He, Weiwei; Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Hu, XN (reprint author), Natl Ctr Nanosci & Technol, CAS Key Lab Standardizat & Measurement Nanotechno, Beijing 100190, Peoples R China. EM JunJie.Yin@fda.hhs.gov; wuxc@nanoctr.cn RI Yin, Jun Jie /E-5619-2014 FU National Natural Science Foundation of China [21173056]; National Key Basic Research Program of China [2012CB934001, 2011CB932802]; FDA Nanotechnology CORES Program [FY11] FX The work was supported by the National Natural Science Foundation of China (grant no. 21173056) and the National Key Basic Research Program of China (2012CB934001 and 2011CB932802).; This article is not an official US Food and Drug Administration (FDA) guidance or policy statement. No official support or endorsement by the US FDA is intended or should be inferred. This work was supported by a regulatory science grant under the FY11 FDA Nanotechnology CORES Program (J. J. Yin). NR 63 TC 20 Z9 20 U1 15 U2 91 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2046-2069 J9 RSC ADV JI RSC Adv. PY 2013 VL 3 IS 17 BP 6095 EP 6105 DI 10.1039/c3ra23215h PG 11 WC Chemistry, Multidisciplinary SC Chemistry GA 117PO UT WOS:000316965800049 ER PT J AU Plant, EP Sims, AC Baric, RS Dinman, JD Taylor, DR AF Plant, Ewan P. Sims, Amy C. Baric, Ralph S. Dinman, Jonathan D. Taylor, Deborah R. TI Altering SARS Coronavirus Frameshift Efficiency Affects Genomic and Subgenomic RNA Production SO VIRUSES-BASEL LA English DT Article DE SARS; severe acute respiratory syndrome; pseudoknot; ribosomal frameshifting; viral replication ID RESPIRATORY SYNDROME CORONAVIRUS; MESSENGER-RNA; PSEUDOKNOT; SIGNAL; POLYMERASE; REPLICATION; TRANSLATION; TRANSCRIPTION; TEMPLATE AB In previous studies, differences in the amount of genomic and subgenomic RNA produced by coronaviruses with mutations in the programmed ribosomal frameshift signal of ORF1a/b were observed. It was not clear if these differences were due to changes in genomic sequence, the protein sequence or the frequency of frameshifting. Here, viruses with synonymous codon changes are shown to produce different ratios of genomic and subgenomic RNA. These findings demonstrate that the protein sequence is not the primary cause of altered genomic and subgenomic RNA production. The synonymous codon changes affect both the structure of the frameshift signal and frameshifting efficiency. Small differences in frameshifting efficiency result in dramatic differences in genomic RNA production and TCID50 suggesting that the frameshifting frequency must stay above a certain threshold for optimal virus production. The data suggest that either the RNA sequence or the ratio of viral proteins resulting from different levels of frameshifting affects viral replication. C1 [Plant, Ewan P.; Taylor, Deborah R.] US FDA, Lab Emerging Pathogens, Div Transfus Transmitted Dis, Bethesda, MD 20892 USA. [Sims, Amy C.; Baric, Ralph S.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Baric, Ralph S.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. [Dinman, Jonathan D.] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. RP Taylor, DR (reprint author), US FDA, Lab Emerging Pathogens, Div Transfus Transmitted Dis, Bethesda, MD 20892 USA. EM Ewan.Plant@fda.hhs.gov; sims0018@ad.unc.edu; rbaric@email.unc.edu; dinman@umd.edu; deborah.taylor@fda.hhs.gov OI Plant, Ewan/0000-0003-0166-5939; Dinman, Jonathan/0000-0002-2402-9698 FU National Institutes of Health [AI064307] FX This work was supported by a grant from the National Institutes of Health to J.D.D. (AI064307). 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 36 TC 6 Z9 7 U1 0 U2 9 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1999-4915 J9 VIRUSES-BASEL JI Viruses-Basel PD JAN PY 2013 VL 5 IS 1 BP 279 EP 294 DI 10.3390/v5010279 PG 16 WC Virology SC Virology GA 096HC UT WOS:000315393800014 PM 23334702 ER PT J AU Verma, A McNichol, B Dominguez-Castillo, RI Amador-Molina, JC Arciniega, JL Reiter, K Meade, BD Ngundi, MM Stibitz, S Burns, DL AF Verma, Anita McNichol, Beth Dominguez-Castillo, Rocio I. Amador-Molina, Juan C. Arciniega, Juan L. Reiter, Karine Meade, Bruce D. Ngundi, Miriam M. Stibitz, Scott Burns, Drusilla L. TI Use of Site-Directed Mutagenesis To Model the Effects of Spontaneous Deamidation on the Immunogenicity of Bacillus anthracis Protective Antigen SO INFECTION AND IMMUNITY LA English DT Article ID ASPARAGINE DEAMIDATION; ISOASPARTATE FORMATION; MOLECULAR CLOCKS; GUINEA-PIGS; PROTEINS; TOXIN; DETERMINANTS; CHALLENGE; RESIDUES; EFFICACY AB Long-term stability is a desired characteristic of vaccines, especially anthrax vaccines, which must be stockpiled for large-scale use in an emergency situation; however, spontaneous deamidation of purified vaccine antigens has the potential to adversely affect vaccine immunogenicity over time. In order to explore whether spontaneous deamidation of recombinant protective antigen (rPA)-the major component of new-generation anthrax vaccines-affects vaccine immunogenicity, we created a "genetically deamidated" form of rPA using site-directed mutagenesis to replace six deamidation-prone asparagine residues, at positions 408, 466, 537, 601, 713, and 719, with either aspartate, glutamine, or alanine residues. We found that the structure of the six-Asp mutant rPA was not significantly altered relative to that of the wild-type protein as assessed by circular dichroism (CD) spectroscopy and biological activity. In contrast, immunogenicity of aluminum-adjuvanted six-Asp mutant rPA, as measured by induction of toxin-neutralizing antibodies, was significantly lower than that of the corresponding wild-type rPA vaccine formulation. The six-Gln and six-Ala mutants also exhibited lower immunogenicity than the wild type. While the wild-type rPA vaccine formulation exhibited a high level of immunogenicity initially, its immunogenicity declined significantly upon storage at 25 degrees C for 4 weeks. In contrast, the immunogenicity of the six-Asp mutant rPA vaccine formulation was low initially but did not change significantly upon storage. Taken together, results from this study suggest that spontaneous deamidation of asparagine residues predicted to occur during storage of rPA vaccines would adversely affect vaccine immunogenicity and therefore the storage life of vaccines. C1 [Verma, Anita; McNichol, Beth; Dominguez-Castillo, Rocio I.; Amador-Molina, Juan C.; Arciniega, Juan L.; Ngundi, Miriam M.; Stibitz, Scott; Burns, Drusilla L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Reiter, Karine] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD USA. [Meade, Bruce D.] Meade Biol, Hillsborough, NC USA. RP Burns, DL (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. EM drusilla.burns@fda.hhs.gov FU National Institute of Allergy and Infectious Diseases; National Institutes of Health; Center for Biologics Evaluation and Research, Food and Drug Administration FX This work was supported by the Intramural Research Programs of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and the Center for Biologics Evaluation and Research, Food and Drug Administration, as well as an interagency agreement between the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and the Food and Drug Administration. NR 29 TC 9 Z9 9 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2013 VL 81 IS 1 BP 278 EP 284 DI 10.1128/IAI.00863-12 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 108MQ UT WOS:000316298000028 PM 23115046 ER PT J AU Hu, Y Meng, JH Shi, CL Hervin, K Fratamico, PM Shi, XM AF Hu, Yu Meng, Jianghong Shi, Chunlei Hervin, Kirstin Fratamico, Pina M. Shi, Xianming TI Characterization and comparative analysis of a second thermonuclease from Staphylococcus aureus SO MICROBIOLOGICAL RESEARCH LA English DT Article DE Characterization; Comparative analysis; Thermonuclease activity; nuc gene expression; Staphylococcal nuclease ID CONTEMPORARY ENZYMOLOGY; ESCHERICHIA-COLI; NUCLEASE; PROTEINS; STRAIN; ACID; IDENTIFICATION; EXPRESSION; PREDICTION; STABILITY AB Staphylococcal nuclease (here termed as Nucl) is considered an important virulence factor and a unique marker widely used in the detection of Staphylococcus aureus. A second functional thermostable nuclease (here termed as Nuc2) in S. aureus was characterized after recombinant expression in Escherichia coll. Sequence alignment and phylogenetic analysis revealed that Nuc2 was a more conserved protein in the staphylococci group compared with Nucl. Recombinant Nuc2 showed nuclease activity in the zymogram test and was able to degrade various types of nucleic acids. The optimal reaction temperature and pH for Nuc2 were 50 C and pH 10, respectively. The enzymatic activity of Nuc2 was stimulated in the presence of Ca2+ (0.05 mM), Mg2+ (0.5 mM), dithiothreitol, beta-mecaptoethanol, TritonX-100, Tween-20, and urea; however, activity decreased sharply when exposed to heavy metals such as Zn2+ and Mn2+, and in the presence of EDTA or SDS. Nuc2 showed weaker activity, lower thermostability and different sensitivity to these chemical agents compared with Nucl, which was consistent with differences in the sequence pattern and structure predicted. Furthermore, a nuc1 and nuc2 double deletion mutant of S. aureus and respective complementation experiments suggest a major role for nuc1 in terms of thermonuclease activity in S. aureus. (C) 2012 Elsevier GmbH. All rights reserved. C1 [Hu, Yu; Shi, Chunlei; Hervin, Kirstin; Shi, Xianming] Shanghai Jiao Tong Univ, Sch Agr & Biol, MOST USDA Joint Res Ctr Food Safety, Shanghai 200240, Peoples R China. [Hu, Yu; Shi, Chunlei; Hervin, Kirstin; Shi, Xianming] Shanghai Jiao Tong Univ, Sch Agr & Biol, Bor Luh Food Safety Ctr, Shanghai 200240, Peoples R China. [Meng, Jianghong] Univ Maryland, Joint Inst Food Safety & Appl Nutr, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Fratamico, Pina M.] USDA, ARS, Eastern Reg Res Ctr, Wyndmoor, PA 19038 USA. RP Shi, XM (reprint author), Shanghai Jiao Tong Univ, Sch Agr & Biol, MOST USDA Joint Res Ctr Food Safety, Shanghai 200240, Peoples R China. EM xmshi@sjtu.edu.cn FU Ministry of Science and Technology of China [2011DFA31220, 2012AA101601, 2012BAK17B10]; National Natural Science Foundation of China [31171690, 31000779] FX This work was jointly supported by the Ministry of Science and Technology of China (Grant nos. 2011DFA31220, 2012AA101601, 2012BAK17B10) and National Natural Science Foundation of China (Grant nos. 31171690, 31000779). The authors would like to thank DrGuRuoxu (College of life science and biotechnology, Shanghai Jiao Tong University) for the drawing of the superposition structure. NR 37 TC 6 Z9 7 U1 3 U2 27 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0944-5013 J9 MICROBIOL RES JI Microbiol. Res. PY 2013 VL 168 IS 3 BP 174 EP 182 DI 10.1016/j.micres.2012.09.003 PG 9 WC Microbiology SC Microbiology GA 111EP UT WOS:000316504400007 PM 23295145 ER PT J AU Pandey, GS Tseng, SC Howard, TE Sauna, ZE AF Pandey, Gouri Shankar Tseng, Sandra C. Howard, Tom E. Sauna, Zuben E. TI Detection of Intracellular Factor VIII Protein in Peripheral Blood Mononuclear Cells by Flow Cytometry SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID HEMOPHILIA-A; MONOCLONAL-ANTIBODIES; GENE; INHIBITORS; EXPRESSION; COAGULATION AB Flow cytometry is widely used in cancer research for diagnosis, detection of minimal residual disease, as well as immune monitoring and profiling following immunotherapy. Detection of specific host proteins for diagnosis predominantly uses quantitative PCR and western blotting assays. In this study, we optimized a flow cytometry-based detection assay for Factor VIII protein in peripheral blood mononuclear cells (PBMCs). An indirect intracellular staining (ICS) method was standardized using monoclonal antibodies to different domains of human Factor VIII protein. The FVIII protein expression level was estimated by calculating the mean and median fluorescence intensities (MFI) values for each monoclonal antibody. ICS staining of transiently transfected cell lines supported the method's specificity. Intracellular FVIII protein expression was also detected by the monoclonal antibodies used in the study in PBMCs of five blood donors. In summary, our data suggest that intracellular FVIII detection in PBMCs of hemophilia A patients can be a rapid and reliable method to detect intracellular FVIII levels. C1 [Pandey, Gouri Shankar; Tseng, Sandra C.; Sauna, Zuben E.] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Howard, Tom E.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA 90073 USA. RP Pandey, GS (reprint author), US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, 29 Lincoln Dr, Bethesda, MD 20892 USA. EM gouri.pandey@fda.hhs.gov; zuben.sauna@fda.hhs.gov FU National Heart, Lung and Blood Institute; NIH [1RC2-HL101851, HL-71130, HL-72533]; Bayer Healthcare Corporation; Bayer Haemophilia Awards Program; Baxter Healthcare Corporation; Clinical Translational Science Institute at the University of Southern California's Keck School of Medicine FX The research conducted in the laboratory of Z. E. Sauna is funded by the Modernization of Science Program of the Center for Biologics Evaluation and Research, Food and Drug Administration. Research conducted in the laboratory of T. E. Howard is funded by Grants from the National Heart, Lung and Blood Institute, NIH, (1RC2-HL101851, HL-71130, and HL-72533) as well as from Bayer Healthcare Corporation, Bayer Haemophilia Awards Program, Baxter Healthcare Corporation, and the Clinical Translational Science Institute at the University of Southern California's Keck School of Medicine. NR 26 TC 2 Z9 2 U1 0 U2 4 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 J9 BIOMED RES INT JI Biomed Res. Int. PY 2013 AR 793502 DI 10.1155/2013/793502 PG 8 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 102YR UT WOS:000315881100001 ER PT B AU Buratto, L Brint, SF Romano, MR AF Buratto, Lucio Brint, Stephen F. Romano, Mario R. BA Burratto, L Brint, SF Romano, MR BF Burratto, L Brint, SF Romano, MR TI Anesthesia by Injection SO CATARACT SURGERY COMPLICATIONS LA English DT Article; Book Chapter ID SUB-TENON ANESTHESIA; RETROBULBAR ANESTHESIA; SUBARACHNOID INJECTION; SCLERAL PERFORATION; COMPLICATION; PERIBULBAR; BLOCK C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Buratto, Lucio] ESCRS, Paris, France. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Romano, Mario R.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Romano, Mario R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Romano, Mario R.] Royal Liverpool Univ Hosp, Liverpool, Merseyside, England. [Romano, Mario R.] Ist Clin & Ric Humanitas, Vitreoretinal Serv, Milan, Italy. EM bookspublishing@wyanokegroup.com NR 22 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-608-7 PY 2013 BP 3 EP 9 PG 7 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BDO78 UT WOS:000314254200001 ER PT B AU Buratto, L Brint, SF Romano, MR AF Buratto, Lucio Brint, Stephen F. Romano, Mario R. BA Burratto, L Brint, SF Romano, MR BF Burratto, L Brint, SF Romano, MR TI Capsulorrhexis SO CATARACT SURGERY COMPLICATIONS LA English DT Article; Book Chapter ID CONTINUOUS CURVILINEAR CAPSULORHEXIS; PRIMARY POSTERIOR CAPSULORHEXIS; CATARACT-SURGERY; INTRAOCULAR-LENS; PHACOEMULSIFICATION; CAPSULOTOMY; COMPLICATIONS; IMPLANTATION C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Buratto, Lucio] ESCRS, Paris, France. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Romano, Mario R.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Romano, Mario R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Romano, Mario R.] Royal Liverpool Univ Hosp, Liverpool, Merseyside, England. [Romano, Mario R.] Ist Clin & Ric Humanitas, Vitreoretinal Serv, Milan, Italy. EM bookspublishing@wyanokegroup.com NR 25 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-608-7 PY 2013 BP 19 EP 27 PG 9 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BDO78 UT WOS:000314254200003 ER PT B AU Buratto, L Brint, SF Romano, MR AF Buratto, Lucio Brint, Stephen F. Romano, Mario R. BA Burratto, L Brint, SF Romano, MR BF Burratto, L Brint, SF Romano, MR TI Hydroseparation Maneuvers SO CATARACT SURGERY COMPLICATIONS LA English DT Article; Book Chapter ID POSTERIOR POLAR CATARACT; CORTICAL CLEAVING HYDRODISSECTION; PHACOEMULSIFICATION; SURGERY; NUCLEUS; RUPTURE; EYES C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Buratto, Lucio] ESCRS, Paris, France. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Romano, Mario R.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Romano, Mario R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Romano, Mario R.] Royal Liverpool Univ Hosp, Liverpool, Merseyside, England. [Romano, Mario R.] Ist Clin & Ric Humanitas, Vitreoretinal Serv, Milan, Italy. EM bookspublishing@wyanokegroup.com NR 13 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-608-7 PY 2013 BP 29 EP 33 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BDO78 UT WOS:000314254200004 ER PT B AU Buratto, L Brint, SF Romano, MR AF Buratto, Lucio Brint, Stephen F. Romano, Mario R. BA Burratto, L Brint, SF Romano, MR BF Burratto, L Brint, SF Romano, MR TI Complications of Phacoemulsification SO CATARACT SURGERY COMPLICATIONS LA English DT Article; Book Chapter ID DIVIDE-AND-CONQUER; PHACO-CHOP TECHNIQUES; DENSITY; ENERGY; FLIP C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Buratto, Lucio] ESCRS, Paris, France. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Romano, Mario R.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Romano, Mario R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Romano, Mario R.] Royal Liverpool Univ Hosp, Liverpool, Merseyside, England. [Romano, Mario R.] Ist Clin & Ric Humanitas, Vitreoretinal Serv, Milan, Italy. EM bookspublishing@wyanokegroup.com NR 11 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-608-7 PY 2013 BP 35 EP 45 PG 11 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BDO78 UT WOS:000314254200005 ER PT B AU Buratto, L Brint, SF Romano, MR AF Buratto, Lucio Brint, Stephen F. Romano, Mario R. BA Burratto, L Brint, SF Romano, MR BF Burratto, L Brint, SF Romano, MR TI Complications With Intraocular Lens Implantation SO CATARACT SURGERY COMPLICATIONS LA English DT Article; Book Chapter ID INCISION CATARACT-SURGERY; OPACIFICATION; CALCIUM; HYPHEMA C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Buratto, Lucio] ESCRS, Paris, France. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Brint, Stephen F.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Romano, Mario R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Romano, Mario R.] Royal Liverpool Univ Hosp, Liverpool, Merseyside, England. [Romano, Mario R.] Ist Clin & Ric Humanitas, Vitreoretinal Serv, Milan, Italy. EM bookspublishing@wyanokegroup.com NR 15 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-608-7 PY 2013 BP 47 EP 56 PG 10 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BDO78 UT WOS:000314254200006 ER PT B AU Buratto, L Brint, SF Romano, MR AF Buratto, Lucio Brint, Stephen F. Romano, Mario R. BA Burratto, L Brint, SF Romano, MR BF Burratto, L Brint, SF Romano, MR TI Complications Arising From Equipment and Tubing SO CATARACT SURGERY COMPLICATIONS LA English DT Article; Book Chapter ID COAXIAL PHACOEMULSIFICATION; BIMANUAL MICROINCISION; CATARACT-SURGERY; TIP C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Buratto, Lucio] ESCRS, Paris, France. [Brint, Stephen F.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Romano, Mario R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Romano, Mario R.] Royal Liverpool Univ Hosp, Liverpool, Merseyside, England. [Romano, Mario R.] Ist Clin & Ric Humanitas, Vitreoretinal Serv, Milan, Italy. EM bookspublishing@wyanokegroup.com NR 14 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-608-7 PY 2013 BP 57 EP 62 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BDO78 UT WOS:000314254200007 ER PT B AU Buratto, L Brint, SF Romano, MR AF Buratto, Lucio Brint, Stephen F. Romano, Mario R. BA Burratto, L Brint, SF Romano, MR BF Burratto, L Brint, SF Romano, MR TI Posterior Capsule Rupture SO CATARACT SURGERY COMPLICATIONS LA English DT Article; Book Chapter ID CATARACT-SURGERY; VITREOUS LOSS; OUTCOMES; IMPLANTATION; RISK; LENS C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Buratto, Lucio] ESCRS, Paris, France. [Brint, Stephen F.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Romano, Mario R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Romano, Mario R.] Royal Liverpool Univ Hosp, Liverpool, Merseyside, England. [Romano, Mario R.] Ist Clin & Ric Humanitas, Vitreoretinal Serv, Milan, Italy. EM bookspublishing@wyanokegroup.com NR 11 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-608-7 PY 2013 BP 63 EP 74 PG 12 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BDO78 UT WOS:000314254200008 ER PT B AU Buratto, L Brint, SF Romano, MR AF Buratto, Lucio Brint, Stephen F. Romano, Mario R. BA Burratto, L Brint, SF Romano, MR BF Burratto, L Brint, SF Romano, MR TI Anterior Vitrectomy SO CATARACT SURGERY COMPLICATIONS LA English DT Article; Book Chapter ID 25-GAUGE VITREOUS CUTTERS; PHACOEMULSIFICATION; MANAGEMENT C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Buratto, Lucio] ESCRS, Paris, France. [Brint, Stephen F.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Romano, Mario R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Romano, Mario R.] Royal Liverpool Univ Hosp, Liverpool, Merseyside, England. [Romano, Mario R.] Ist Clin & Ric Humanitas, Vitreoretinal Serv, Milan, Italy. EM bookspublishing@wyanokegroup.com NR 12 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-608-7 PY 2013 BP 75 EP 80 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BDO78 UT WOS:000314254200009 ER PT B AU Buratto, L Brint, SF Romano, MR AF Buratto, Lucio Brint, Stephen F. Romano, Mario R. BA Burratto, L Brint, SF Romano, MR BF Burratto, L Brint, SF Romano, MR TI Posterior Vitrectomy SO CATARACT SURGERY COMPLICATIONS LA English DT Article; Book Chapter ID 25-GAUGE VITREOUS CUTTERS; PARS-PLANA VITRECTOMY; ASSISTED LEVITATION; CATARACT-SURGERY; PHACOEMULSIFICATION; FRAGMENTS C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Buratto, Lucio] ESCRS, Paris, France. [Brint, Stephen F.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Romano, Mario R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Romano, Mario R.] Royal Liverpool Univ Hosp, Liverpool, Merseyside, England. [Romano, Mario R.] Ist Clin & Ric Humanitas, Vitreoretinal Serv, Milan, Italy. EM bookspublishing@wyanokegroup.com NR 13 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-608-7 PY 2013 BP 81 EP 87 PG 7 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BDO78 UT WOS:000314254200010 ER PT B AU Buratto, L Brint, SF Romano, MR AF Buratto, Lucio Brint, Stephen F. Romano, Mario R. BA Burratto, L Brint, SF Romano, MR BF Burratto, L Brint, SF Romano, MR TI Endophthalmitis Following Cataract Surgery SO CATARACT SURGERY COMPLICATIONS LA English DT Article; Book Chapter ID INTRAOCULAR-LENS IMPLANTATION; OF-THE-LITERATURE; POSTOPERATIVE ENDOPHTHALMITIS; BACTERIAL ENDOPHTHALMITIS; STAPHYLOCOCCUS-AUREUS; INFECTIOUS ENDOPHTHALMITIS; INTRACAMERAL CEFUROXIME; INTRAVITREAL VANCOMYCIN; EUROPEAN MULTICENTER; AQUEOUS PENETRATION C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Buratto, Lucio] ESCRS, Paris, France. [Brint, Stephen F.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Romano, Mario R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Romano, Mario R.] Royal Liverpool Univ Hosp, Liverpool, Merseyside, England. [Romano, Mario R.] Ist Clin & Ric Humanitas, Vitreoretinal Serv, Milan, Italy. EM bookspublishing@wyanokegroup.com NR 48 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-608-7 PY 2013 BP 89 EP 95 PG 7 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BDO78 UT WOS:000314254200011 ER PT B AU Buratto, L Brint, SF Romano, MR AF Buratto, Lucio Brint, Stephen F. Romano, Mario R. BA Burratto, L Brint, SF Romano, MR BF Burratto, L Brint, SF Romano, MR TI Cystoid Macular Edema Following Cataract Surgery SO CATARACT SURGERY COMPLICATIONS LA English DT Article; Book Chapter ID OPTICAL COHERENCE TOMOGRAPHY; ANTERIOR-CHAMBER LENS; IRVINE-GASS SYNDROME; DIABETIC-RETINOPATHY; IMPLANTATION; EFFICACY; PSEUDOPHAKIA; CEFUROXIME; EXTRACTION; VITRECTOMY C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Buratto, Lucio] ESCRS, Paris, France. [Brint, Stephen F.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Romano, Mario R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Romano, Mario R.] Royal Liverpool Univ Hosp, Liverpool, Merseyside, England. [Romano, Mario R.] Ist Clin & Ric Humanitas, Vitreoretinal Serv, Milan, Italy. EM bookspublishing@wyanokegroup.com NR 39 TC 0 Z9 0 U1 0 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-608-7 PY 2013 BP 97 EP 101 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BDO78 UT WOS:000314254200012 ER PT B AU Buratto, L Brint, SF Romano, MR AF Buratto, Lucio Brint, Stephen F. Romano, Mario R. BA Burratto, L Brint, SF Romano, MR BF Burratto, L Brint, SF Romano, MR TI Complications in Cataract Surgery With Femtosecond Laser SO CATARACT SURGERY COMPLICATIONS LA English DT Article; Book Chapter ID IN-SITU KERATOMILEUSIS; INTRAOPERATIVE COMPLICATIONS; MICROKERATOME SUCTION; LASIK FLAPS; BENCHMARK; AUDIT; RING C1 [Buratto, Lucio] US FDA, Rockville, MD 20857 USA. [Buratto, Lucio] ESCRS, Paris, France. [Brint, Stephen F.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Brint, Stephen F.] Amer Coll Surg, Chicago, IL USA. [Romano, Mario R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Romano, Mario R.] Royal Liverpool Univ Hosp, Liverpool, Merseyside, England. [Romano, Mario R.] Ist Clin & Ric Humanitas, Vitreoretinal Serv, Milan, Italy. EM bookspublishing@wyanokegroup.com NR 19 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-608-7 PY 2013 BP 103 EP 107 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BDO78 UT WOS:000314254200013 ER PT J AU Delmonte, P Barrientos, S Rader, JI AF Delmonte, Pierluigi Barrientos, Steven Rader, Jeanne I. TI Modifications of AOAC Official Method 999.15 to Improve the Quantitation of Vitamin K-1 in Complex Formulated Nutritional Products SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LIQUID-CHROMATOGRAPHY; CIS-PHYLLOQUINONE; INFANT FORMULAS; PHASE; MILK; METABOLISM; FOODS AB Vitamin K-1 (phylloquinone) occurs in foods in relatively low concentrations. It is synthesized for addition to formulated nutritional products (infant formulas, medical foods, and adult nutritional products). In recent years, nutritional products formulated with free amino acids and partially hydrolyzed proteins have been introduced in the market. Schimpf et al. demonstrated that the current AOAC Official Method 999.15 for determination of vitamin K in milk and infant formula is not adequate to quantitatively extract vitamin K-1 from such products. We developed a modification of AOAC 999.15 for the analysis of vitamin K-1 in these products that provides quantitative extraction by increasing the sample size, volume of extraction solvents, time of liquid/liquid partitioning, and order of the addition of solvents. This modified procedure showed extraction efficiency comparable to that of the original AOAC 999.15 procedure for analyzing infant formula matrixes and to the modified procedure of Schimpf et al. for the analysis of samples containing limited amounts of free amino acids and/or partially hydrolyzed proteins. Extraction efficiency increased more than 10% using the modified extraction procedure for samples containing higher amounts of these components. The chromatographic separation was improved by using a Dionex Acclaim triacontanol-bonded C30 column (250x3.0 mm id, 3 mu m particle size) maintained at 15 degrees C, with acetonitrile methanol (50+50, v/v) mobile phase at a flow rate of 0.5 mL/min, which provided baseline separation of the cis and trans isomers of vitamin K-1 from each other and from other compounds contained in the sample extracts. C1 [Delmonte, Pierluigi; Barrientos, Steven; Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. RP Delmonte, P (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. EM Pierluigi.Delmonte@fda.hhs.gov NR 16 TC 2 Z9 2 U1 1 U2 22 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2013 VL 96 IS 1 BP 91 EP 101 DI 10.5740/jaoacint.12-191 PG 11 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 094HT UT WOS:000315254300016 PM 23513963 ER PT J AU Murphy, CJ MacNeil, JD Capar, SG AF Murphy, Cory J. MacNeil, James D. Capar, Stephen G. TI Best Practices for Single-Laboratory Validation of Chemical Methods for Trace Elements in Foods. Part I-Background and General Considerations SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID INDUCTIVELY-COUPLED-PLASMA; SPECTROMETRY ICP-MS; ANALYTICAL-CHEMISTRY LABORATORIES; ATOMIC-ABSORPTION-SPECTROMETRY; VESSEL MICROWAVE DIGESTION; IUPAC TECHNICAL REPORT; MASS-SPECTROMETRY; HARMONIZED GUIDELINES; ENVIRONMENTAL-ANALYSIS; EMISSION-SPECTROMETRY AB The metals subgroup of AOAC INTERNATIONAL's Community on Chemical Contaminants and Residues in Food has been engaged for the past several years in discussions concerning the requirements for the single-laboratory validation (SLV) of methods for the determination of trace elements in foods. This paper reviews the general guidance currently available related to validation of chemical analytical methods and current typical validation practices found in publications on the analysis of elements in food and other matrixes, such as environmental and clinical samples. Based on the available guidance on SLV requirements and a review of current practices in elemental analysis, a general approach based on best practices is proposed for put of a method for elements in food to demonstrate the method as "fit-for-purpose." C1 [Murphy, Cory J.; MacNeil, James D.] Canadian Food Inspect Agcy, Dartmouth Lab, Dartmouth, NS B3B 1Y9, Canada. [Capar, Stephen G.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, Div Bioanalyt Chem, College Pk, MD 20740 USA. RP Murphy, CJ (reprint author), Canadian Food Inspect Agcy, Dartmouth Lab, 1992 Agcy Dr, Dartmouth, NS B3B 1Y9, Canada. EM Cory.Murphy@inspection.gc.ca NR 142 TC 5 Z9 5 U1 2 U2 21 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2013 VL 96 IS 1 BP 190 EP 203 DI 10.5740/jaoacint.12-204 PG 14 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 094HT UT WOS:000315254300030 PM 23513977 ER PT J AU Le, DVN Wang, QZ Ramella-Roman, JC Pfefer, TJ AF Le, Du V. N. Wang, Quanzeng Ramella-Roman, Jessica C. Pfefer, T. Joshua TI Monte Carlo modeling of light-tissue interactions in narrow band imaging SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE Monte Carlo; computational modeling; narrow band imaging; optical properties; tissue phantom ID OPTICAL-PROPERTIES AB Light-tissue interactions that influence vascular contrast enhancement in narrow band imaging (NBI) have not been the subject of extensive theoretical study. In order to elucidate relevant mechanisms in a systematic and quantitative manner we have developed and validated a Monte Carlo model of NBI and used it to study the effect of device and tissue parameters, specifically, imaging wavelength (415 versus 540 nm) and vessel diameter and depth. Simulations provided quantitative predictions of contrast-including up to 125% improvement in small, superficial vessel contrast for 415 over 540 nm. Our findings indicated that absorption rather than scattering-the mechanism often cited in prior studies-was the dominant factor behind spectral variations in vessel depth-selectivity. Narrow-band images of a tissue-simulating phantom showed good agreement in terms of trends and quantitative values. Numerical modeling represents a powerful tool for elucidating the factors that affect the performance of spectral imaging approaches such as NBI. (c) 2013 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.JBO.18.1.010504] C1 [Le, Du V. N.; Wang, Quanzeng; Pfefer, T. Joshua] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Le, Du V. N.; Ramella-Roman, Jessica C.] Catholic Univ Amer, Dept Biomed Engn, Washington, DC 20064 USA. RP Le, DVN (reprint author), Catholic Univ Amer, Dept Biomed Engn, Washington, DC 20064 USA. EM 10le@cardinalmail.cua.edu RI Le, Vinh Nguyen Du/E-3859-2015 OI Le, Vinh Nguyen Du/0000-0002-4054-4200 NR 9 TC 1 Z9 1 U1 0 U2 5 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JAN PY 2013 VL 18 IS 1 AR 010504 DI 10.1117/1.JBO.18.1.010504 PG 3 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 092XT UT WOS:000315157000004 ER PT J AU Rao, SS Mohan, KVK Gao, YM Atreya, CD AF Rao, Shilpakala Sainath Mohan, Ketha V. Krishna Gao, Yamei Atreya, Chintamani D. TI Identification and evaluation of a novel peptide binding to the cell surface of Staphylococcus aureus SO MICROBIOLOGICAL RESEARCH LA English DT Article DE Microbial detection; Peptides; Phage-display; Quantum dots; S. aureus ID PHAGE-DISPLAY; SALMONELLA-TYPHIMURIUM; PLATELET TRANSFUSION; BACILLUS-ANTHRACIS; LIGANDS; SPORES; STRAIN; PROBE AB Identification of short peptides that serve as specific ligands to biological materials such as microbial cell surfaces has major implications in better understanding the molecular recognition of cell surfaces. In this study we screened a commercially available random phage-display library against Staphylococcus aureus cells and identified peptides specifically binding to the bacteria. A synthetic peptide (SA5-1) representing the consensus sequence (VPHNPGLISLQG) of the bacteria-binding peptide was evaluated for its binding potential against S. aureus. Dot-blot, immunoblot assay and ELISA results revealed the SA5-1 peptide to be highly specific to S. aureus. The SA5-1 peptide binding was optimal between pH 6.0 and 8.0. Nanogold Transmission Electron Microscopy demonstrated that the SA5-1 binds to the outer membrane surface of S. aureus. Diagnostic potential of the SA5-1 peptide was evaluated in human platelet samples spiked with S. aureus and specific detection of the bacteria by biotinylated-SA5-1 and streptavidin-conjugated fluorescent quantum dots. Fluorometry results indicated that the peptide was able to detect similar to 100 organisms per ml in a spiked biological sample providing a proof-of-concept towards potential of this peptide as a S. aureus diagnostic tool that can be of use in different detection platforms. Published by Elsevier GmbH. C1 [Rao, Shilpakala Sainath; Mohan, Ketha V. Krishna; Atreya, Chintamani D.] US FDA, Sect Cell Biol, Lab Cellular Hematol, Div Hematol,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Gao, Yamei] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Atreya, CD (reprint author), Bldg 29A,Room 2C-11,NIH Campus,8800 Rockville Pik, Bethesda, MD 20892 USA. EM chintamani.atreya@fda.hhs.gov FU Center for Biologics Evaluation and Research (CBER) FX SSR is a recipient of a postdoctoral fellowship at the Center for Biologics Evaluation and Research (CBER) administered by the Oak Ridge Institute for Science and Education (ORISE) through an intra agency agreement between the U. S. Department of Energy and the U.S. Food and Drug Administration. Review of the manuscript by Drs. Salim Haddad and Xuan Chi, CBER is highly appreciated. NR 30 TC 7 Z9 9 U1 3 U2 37 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0944-5013 J9 MICROBIOL RES JI Microbiol. Res. PY 2013 VL 168 IS 2 BP 106 EP 112 DI 10.1016/j.micres.2012.07.004 PG 7 WC Microbiology SC Microbiology GA 093GJ UT WOS:000315179400007 PM 23017232 ER PT J AU Warner, AW Bienfait, KL Bledsoe, M Burckart, G Flamion, B Knoppers, B Nelsen, AJ Rudman, A Sieffert, NJ Uyama, Y AF Warner, Amelia Wall Bienfait, Karina L. Bledsoe, Marianna Burckart, Gilbert Flamion, Bruno Knoppers, Bartha Nelsen, Anita J. Rudman, Allen Sieffert, Nicole J. Uyama, Yoshiaki TI Improving clinical trial sampling for future research - an international approach: outcomes and next steps from the DIA future use sampling workshop 2011 SO PHARMACOGENOMICS LA English DT Article DE clinical trials; data privacy; drug development; EU EMA; future use sampling; Japan PMDA; pharmacogenetics; pharmacogenomics; regulatory agencies; US FDA ID PHARMACOGENOMICS WORKING GROUP; ETHICS COMMITTEES; INDUSTRY; PERSPECTIVE AB Clinical trial samples collected for pharmacogenomic and future research are vital resources for the development of safe and effective drugs, yet collecting adequate, representative sample sets in global trials is challenging. The Drug Information Association (DIA) sponsored a workshop on future use sampling in September 2011, bringing together experts from regulatory agencies, academia and industry to discuss challenges to future use sample collection and identify actions to improve collection. Several common themes and associated action items emerged, including the need for international guidance on the collection of samples for future research; additional discussion related to coding, scope of research, and return of research results; and additional education about pharmacogenomic/future research and the importance of long-term storage of specimens. C1 [Warner, Amelia Wall; Bienfait, Karina L.] Merck & Co Inc, Clin Pharmacogen & Clin Specimen Management, Upper Gwynedd, PA 19454 USA. [Bledsoe, Marianna] Dept Vet Affairs, Biorepository & Tissue Banking Biomed Lab R&D Ser, Off Res & Dev, Washington, DC 20420 USA. [Burckart, Gilbert; Rudman, Allen] US FDA, Off Clin Pharmacol, Off Translat Sci, CDER, Silver Spring, MD 20993 USA. [Flamion, Bruno] Univ Namur, Physiol & Pharmacol Unit, Namur, Belgium. [Knoppers, Bartha] McGill Univ, Fac Med, Dept Human Genet, Montreal, PQ H3A 0G1, Canada. [Nelsen, Anita J.] GlaxoSmithKline, Genet, Res Triangle Pk, NC 27709 USA. [Sieffert, Nicole J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Uyama, Yoshiaki] PMDA, Regulatory Sci Res Div, Off Regulatory Sci, Tokyo 1000013, Japan. [Uyama, Yoshiaki] Chiba Univ, Grad Sch Med & Pharmaceut Sci, Dept Regulatory Sci & Publ Adm Med, Chiba 2608677, Japan. RP Warner, AW (reprint author), Merck & Co Inc, Clin Pharmacogen & Clin Specimen Management, 351 N Sumneytown Pike,UGD4-34, Upper Gwynedd, PA 19454 USA. EM amelia.warner@merck.com NR 11 TC 4 Z9 4 U1 0 U2 4 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD JAN PY 2013 VL 14 IS 1 BP 103 EP 112 DI 10.2217/PGS.12.193 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 090PQ UT WOS:000314991700018 PM 23252952 ER PT J AU Judson, R Kavlock, R Martin, M Reif, D Houck, K Knudsen, T Richard, A Tice, RR Whelan, M Xia, MH Huang, RL Austin, C Daston, G Hartung, T Fowle, JR Wooge, W Tong, WD Dix, D AF Judson, Richard Kavlock, Robert Martin, Matthew Reif, David Houck, Keith Knudsen, Thomas Richard, Ann Tice, Raymond R. Whelan, Maurice Xia, Menghang Huang, Ruili Austin, Christopher Daston, George Hartung, Thomas Fowle, John R., III Wooge, William Tong, Weida Dix, David TI Perspectives on Validation of High-Throughput Assays Supporting 21st Century Toxicity Testing SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION LA English DT Article; Proceedings Paper CT Workshop on Evidence-Based Toxicology for the 21st Century - Opportunities and Challenges CY JAN 24-25, 2012 CL Environm Protect Agcy Campus, NC HO Environm Protect Agcy Campus DE validation; in vitro; high-throughput screening ID APPLICABILITY DOMAIN; TOXICOLOGY; FRAMEWORK; CHEMICALS; THOUGHT; FOOD; RECOMMENDATIONS; TOXICOGENOMICS; PRINCIPLES; RELEVANCE AB In vitro high-throughput screening (HTS) assays are seeing increasing use in toxicity testing. HTS assays can simultaneously test many chemicals but have seen limited use in the regulatory arena, in part because of the need to undergo rigorous, time-consuming formal validation. Here we discuss streamlining the validation process, specifically for prioritization applications. By prioritization, we mean a process in which less complex, less expensive, and faster assays are used to prioritize which chemicals are subjected first to more complex, expensive, and slower guideline assays. Data from the HTS prioritization assays is intended to provide a priori evidence that certain chemicals have the potential to lead to the types of adverse effects that the guideline tests are assessing. The need for such prioritization approaches is driven by the fact that there are tens of thousands of chemicals to which people are exposed, but the yearly throughput of most guideline assays is small in comparison. The streamlined validation process would continue to ensure the reliability and relevance of assays for this application. We discuss the following practical guidelines: (1) follow current validation practice to the extent possible and practical; (2) make increased use of reference compounds to better demonstrate assay reliability and relevance; (3) de-emphasize the need for cross-laboratory testing; and (4) implement a web-based, transparent, and expedited peer review process. C1 [Judson, Richard; Kavlock, Robert; Martin, Matthew; Reif, David; Houck, Keith; Knudsen, Thomas; Richard, Ann; Dix, David] US EPA, Res Triangle Pk, NC 27711 USA. [Tice, Raymond R.] NIEHS, Res Triangle Pk, NC 27709 USA. [Whelan, Maurice] Commiss European Communities, Joint Res Ctr, EURL ECVAM, I-21020 Ispra, Italy. [Xia, Menghang; Huang, Ruili; Austin, Christopher] Natl Ctr Adv Translat Sci, Rockville, MD USA. [Daston, George] Procter & Gamble Co, Cincinnati, OH USA. [Hartung, Thomas] Johns Hopkins Univ, Baltimore, MD USA. [Wooge, William] US EPA, Washington, DC 20460 USA. [Tong, Weida] US FDA, Jefferson, AR USA. RP Judson, R (reprint author), US EPA, Natl Ctr Computat Toxicol, Off Res & Dev, 109 TW Alexander Dr,B205-01, Res Triangle Pk, NC 27711 USA. EM judson.richard@epa.gov OI Judson, Richard/0000-0002-2348-9633; Reif, David/0000-0001-7815-6767 FU Intramural NIH HHS [Z99 ES999999] NR 67 TC 52 Z9 53 U1 5 U2 23 PU SPEKTRUM AKADEMISCHER VERLAG-SPRINGER-VERLAG GMBH PI HEILDEBERG PA TIERGARTENSTRASSE 17, HEILDEBERG, 69121, GERMANY SN 1868-596X J9 ALTEX-ALTERN ANIM EX JI ALTEX-Altern. Anim. Exp. PY 2013 VL 30 IS 1 BP 51 EP 66 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 090XH UT WOS:000315012800005 PM 23338806 ER PT J AU Stephens, ML Andersen, M Becker, RA Betts, K Boekelheide, K Carney, E Chapin, R Devlin, D Fitzpatrick, S Fowle, JR Harlow, P Hartung, T Hoffmann, S Holsapple, M Jacobs, A Judson, R Naidenko, O Pastoor, T Patlewicz, G Rowan, A Scherer, R Shaikh, R Simon, T Wolf, D Zurlo, J AF Stephens, Martin L. Andersen, Melvin Becker, Richard A. Betts, Kellyn Boekelheide, Kim Carney, Ed Chapin, Robert Devlin, Dennis Fitzpatrick, Suzanne Fowle, John R., III Harlow, Patricia Hartung, Thomas Hoffmann, Sebastian Holsapple, Michael Jacobs, Abigail Judson, Richard Naidenko, Olga Pastoor, Tim Patlewicz, Grace Rowan, Andrew Scherer, Roberta Shaikh, Rashid Simon, Ted Wolf, Douglas Zurlo, Joanne TI Evidence-based Toxicology for the 21st Century: Opportunities and Challenges SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION LA English DT Article DE evidence-based toxicology; evidence-based medicine; systematic review; validation; test method assessment ID EVIDENCE-BASED MEDICINE; BIOMARKER QUALIFICATION; EPIDEMIOLOGIC EVIDENCE; URINARY BIOMARKERS; KIDNEY INJURY; FRAMEWORK; TOXICITY; EXPOSURE; SCIENCE AB The Evidence-based Toxicology Collaboration (EBTC) was established recently to translate evidence-based approaches from medicine and health care to toxicology in an organized and sustained effort. The EBTC held a workshop on "Evidence-based Toxicology for the 21st Century: Opportunities and Challenges" in Research Triangle Park, North Carolina, USA on January 24-25, 2012. The presentations largely reflected two EBTC priorities: to apply evidence-based methods to assessing the performance of emerging pathway-based testing methods consistent with the 2007 National Research Council report on "Toxicity Testing in the 21st Century" as well as to adopt a governance structure and work processes to move that effort forward. The workshop served to clarify evidence-based approaches and to provide food for thought on substantive and administrative activities for the EBTC. Priority activities include conducting pilot studies to demonstrate the value of evidence-based approaches to toxicology, as well as conducting educational outreach on these approaches. C1 [Stephens, Martin L.; Hartung, Thomas; Scherer, Roberta; Zurlo, Joanne] Johns Hopkins Univ, Baltimore, MD USA. [Andersen, Melvin] Hamner Inst Hlth Sci, Res Triangle Pk, NC USA. [Becker, Richard A.] Amer Chem Council, Washington, DC USA. [Boekelheide, Kim] Brown Univ, Providence, RI 02912 USA. [Carney, Ed] Dow Chem, Midland, MI USA. [Chapin, Robert] Pfizer Global R&D, Groton, CT USA. [Devlin, Dennis] ExxonMobil, Irving, TX USA. [Fitzpatrick, Suzanne] US FDA, College Pk, MD USA. [Fowle, John R., III] US EPA, Pittsboro, NC USA. [Harlow, Patricia; Jacobs, Abigail] US FDA, Silver Spring, MD USA. [Hoffmann, Sebastian] Seh Consulting Serv, Paderborn, Germany. [Holsapple, Michael] Battelle Mem Inst, Columbus, OH USA. [Judson, Richard; Wolf, Douglas] US EPA, Res Triangle Pk, NC 27711 USA. [Naidenko, Olga] Environm Working Grp, Washington, DC USA. [Pastoor, Tim] Syngenta, Greensboro, NC USA. [Patlewicz, Grace] DuPont Haskell Global Ctr Hlth & Environm Sci, Newark, DE USA. [Rowan, Andrew] Humane Soc Int, Gaithersburg, MD USA. [Shaikh, Rashid] Hlth Effects Inst, Boston, MA USA. [Simon, Ted] Ted Simon LLC, Winston, GA USA. RP Stephens, ML (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Alternat Anim Testing, 615 N Wolfe St,W7032, Baltimore, MD 21205 USA. EM mstephen@jhsph.edu OI Andersen, Melvin/0000-0002-3894-4811; Simon, Ted/0000-0001-9405-3020; Judson, Richard/0000-0002-2348-9633; Patlewicz, Grace/0000-0003-3863-9689 FU Doerenkamp-Zbinden Foundation FX The Evidence-based Toxicology Collaboration would like to thank the following in connection with its January 2012 workshop: Robert Kavlock and the Environmental Protection Agency for hosting the workshop; Marilyn Principe of the Johns Hopkins Center for Alternatives to Animal Testing for logistical support; Kellyn Betts for summarizing the comments from the workshop; the American Chemistry Council, American Cleaning Institute, ExxonMobil, and the transatlantic think tank for toxicology (t4) sponsored by the Doerenkamp-Zbinden Foundation for financial support; and the Society of Toxicology for its endorsement of the workshop. NR 43 TC 21 Z9 21 U1 4 U2 17 PU SPEKTRUM AKADEMISCHER VERLAG-SPRINGER-VERLAG GMBH PI HEILDEBERG PA TIERGARTENSTRASSE 17, HEILDEBERG, 69121, GERMANY SN 1868-596X EI 1868-8551 J9 ALTEX-ALTERN ANIM EX JI ALTEX-Altern. Anim. Exp. PY 2013 VL 30 IS 1 BP 74 EP 103 PG 30 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 090XH UT WOS:000315012800007 PM 23338808 ER PT J AU Bandele, O Camacho, L Ferguson, M Reimschuessel, R Stine, C Black, T Olejnik, N Keltner, Z Scott, M da Costa, GG Sprando, R AF Bandele, Omari Camacho, Luisa Ferguson, Martine Reimschuessel, Renate Stine, Cynthia Black, Thomas Olejnik, Nicholas Keltner, Zachary Scott, Michael da Costa, Goncalo Gamboa Sprando, Robert TI Performance of urinary and gene expression biomarkers in detecting the nephrotoxic effects of melamine and cyanuric acid following diverse scenarios of co-exposure SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Nephrotoxicity; Biomarkers; Melamine; Cyanuric acid, Luminex (R) bead-based immunoassays ID ACUTE KIDNEY INJURY; DOSE-RESPONSE ASSESSMENT; ACUTE-RENAL-FAILURE; F344 RATS; COMBINED-EXPOSURE; IN-VITRO; TOXICITY; CATS; OSTEOPONTIN; MOLECULE-1 AB Although standard nephrotoxicity assessments primarily detect impaired renal function, KIM-1, clusterin, NGAL, osteopontin and TIMP-1 were recently identified biomarkers proposed to indicate earlier perturbations in renal integrity. The recent adulteration of infant and pet food with melamine (MEL) and structurally-related compounds revealed that co-ingestion of MEL and cyanuric acid (CYA) could form melamine-cyanurate crystals which obstruct renal tubules and induce acute renal failure. This study concurrently evaluated the ability of multiplexed urinary biomarker immunoassays and biomarker gene expression analysis to detect nephrotoxicity in F344 rats co-administered 60 ppm each of MEL and CYA in feed or via gavage for 28 days. The biomarkers were also evaluated for the ability to differentiate the effects of the compounds when co-administered using diverse dosing schedules (i.e., consecutive vs. staggered gavage) and dosing matrixes (i.e., feed vs. gavage). Our results illustrate the ability of both methods to detect and differentiate the severity of adverse effects in the staggered and consecutive gavage groups at much lower doses than previously observed in animals co-exposed to the compounds in feed. We also demonstrate that these urinary biomarkers outperform traditional diagnostic methods and represent a powerful, non-invasive indicator of chemical-induced nephrotoxicity prior to the onset of renal dysfunction. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Bandele, Omari; Black, Thomas; Olejnik, Nicholas; Keltner, Zachary; Scott, Michael; Sprando, Robert] US FDA, Div Toxicol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Camacho, Luisa; da Costa, Goncalo Gamboa] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Ferguson, Martine] US FDA, Div Publ Hlth & Biostat, Off Food Def, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Reimschuessel, Renate; Stine, Cynthia] US FDA, Div Appl Vet Res, Off Res, Ctr Vet Med, Laurel, MD 20708 USA. RP Bandele, O (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd,MOD 1 Labs,HFS 025, Laurel, MD 20807 USA. EM omari.bandele@fda.hhs.gov FU FDA; National Toxicology Program at the National Institute of Environmental Health Sciences [FDA IAG:224-12-0003, NIH AES12013] FX This study was supported in part through an interagency agreement between the FDA and the National Toxicology Program at the National Institute of Environmental Health Sciences (FDA IAG:224-12-0003; NIH AES12013). O.J.B. was supported by an appointment to the Research Participation Program at the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the US Department of Energy and the US Food and Drug Administration. We would like to also thank Sarah M. Nemser and Andriy Tkachenko for their assistance with the animal necropsies. The opinions expressed in this paper do not necessarily represent those of the US Food and Drug Administration or National Toxicology Program. NR 58 TC 5 Z9 7 U1 0 U2 19 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD JAN PY 2013 VL 51 BP 106 EP 113 DI 10.1016/j.fct.2012.09.022 PG 8 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 091VQ UT WOS:000315078300014 PM 23022069 ER PT J AU Beland, FA Mellick, PW Olson, GR Mendoza, MCB Marques, MM Doerge, DR AF Beland, Frederick A. Mellick, Paul W. Olson, Greg R. Mendoza, Maria C. B. Marques, M. Matilde Doerge, Daniel R. TI Carcinogenicity of acrylamide in B6C3F(1) mice and F344/N rats from a 2-year drinking water exposure SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Acrylamide; Glycidamide; Tumorigenicity; Mice; Rats; Bioassay ID DNA ADDUCT FORMATION; BIG-BLUE MICE; DIETARY ACRYLAMIDE; FISCHER-344 RATS; HEMOGLOBIN ADDUCTS; CANCER-RISK; METABOLITE GLYCIDAMIDE; N-METHYLOLACRYLAMIDE; PROSPECTIVE COHORT; MAILLARD REACTION AB Acrylamide is a component of roasted coffee and certain baked and fried carbohydrate-rich foods prepared at high temperatures. We have assessed the carcinogenicity of acrylamide in male and female B6C3F(1) mice and F344/N rats administered 0, 0.0875, 0.175, 0.35, or 0.70 mM acrylamide in the drinking water ad libitum for 2 years. Acrylamide caused significant dose-related decreasing trends in the body weights of F344/N rats. Acrylamide administration resulted in significant dose-related decreasing trends in survival in both sexes of B6C3F(1) mice and in female F344/N rats. Histopathological analyses indicated significant dose-related increases in Harderian gland and lung tumors in male and female B6C3F(1) mice. Male B6C3F(1) mice also had a significantly increased incidence of forestomach tumors, while female B6C3F(1) mice had significant dose-related increases in mammary gland, ovary, and skin tumors. In male and female F344/N rats, there were significant increases in thyroid tumors. Male F344/N rats also had significant dose-related increases in testes, heart, and pancreas tumors, while female F344 rats demonstrated significant increases in clitoral gland, mammary gland, oral cavity, and skin tumors. These results, combined with previous mechanistic studies, provide strong support for the concept that acrylamide is activated to a carcinogen through metabolism to glycidamide. Published by Elsevier Ltd. C1 [Beland, Frederick A.; Doerge, Daniel R.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Mellick, Paul W.; Olson, Greg R.] Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Mendoza, Maria C. B.] Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. [Marques, M. Matilde] Univ Tecn Lisboa, Inst Super Tecn, Ctr Quim Estrutural, P-1049001 Lisbon, Portugal. RP Beland, FA (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 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 of Environmental Health Sciences, National Toxicology Program (NTP); U.S. Food and Drug Administration, National Center for Toxicological Research [224-12-0003, AES12013]; Fundacao para a Ciencia e a Tecnologia, Portugal [PTDC/SAU-OSM/105572/2008] FX We thank L. Patrice McDaniel for serving as the study coordinator, and James Carson, Andy Matson, and Michelle Vanlandingham for providing animal diets and care. This work was supported by an Interagency Agreement between the National Institute of Environmental Health Sciences, National Toxicology Program (NTP), and the U.S. Food and Drug Administration, National Center for Toxicological Research (NCTR/FDA IAG #224-12-0003; NIH/NTP IAG #AES12013), and formed the basis for NTP Technical Report 575. Financial support was also provided by a research grant from Fundacao para a Ciencia e a Tecnologia (PTDC/SAU-OSM/105572/2008), Portugal. The opinions expressed in this paper do not necessarily represent those of the U.S. Food and Drug Administration. NR 59 TC 26 Z9 27 U1 11 U2 52 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 EI 1873-6351 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD JAN PY 2013 VL 51 BP 149 EP 159 DI 10.1016/j.fct.2012.09.017 PG 11 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 091VQ UT WOS:000315078300019 PM 23009883 ER PT J AU Yauk, CL Argueso, JL Auerbach, SS Awadalla, P Davis, SR DeMarini, DM Douglas, GR Dubrova, YE Elespuru, RK Glover, TW Hales, BF Hurles, ME Klein, CB Lupski, JR Manchester, DK Marchetti, F Montpetit, A Mulvihill, JJ Robaire, B Robbins, WA Rouleau, GA Shaughnessy, DT Somers, CM Taylor, JG Trasler, J Waters, MD Wilson, TE Witt, KL Bishop, JB AF Yauk, Carole Lyn Argueso, J. Lucas Auerbach, Scott S. Awadalla, Philip Davis, Sean R. DeMarini, David M. Douglas, George R. Dubrova, Yuri E. Elespuru, Rosalie K. Glover, Thomas W. Hales, Barbara F. Hurles, Matthew E. Klein, Catherine B. Lupski, James R. Manchester, David K. Marchetti, Francesco Montpetit, Alexandre Mulvihill, John J. Robaire, Bernard Robbins, Wendie A. Rouleau, Guy A. Shaughnessy, Daniel T. Somers, Christopher M. Taylor, James G. Trasler, Jacquetta Waters, Michael D. Wilson, Thomas E. Witt, Kristine L. Bishop, Jack B. TI Harnessing genomics to identify environmental determinants of heritable disease SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH LA English DT Editorial Material DE Germ cell; Heritable mutation; Next generation sequencing; Copy number variants ID GERM-CELL MUTAGENS; ANTICANCER DRUGS; MUTATION-RATES; AIR-POLLUTION; VARIANTS; EXPOSURE; SPECTRUM; TOBACCO; HUMANS; SMOKE AB Next-generation sequencing technologies can now be used to directly measure heritable de novo DNA sequence mutations in humans. However, these techniques have not been used to examine environmental factors that induce such mutations and their associated diseases. To address this issue, a working group on environmentally induced germline mutation analysis (ENIGMA) met in October 2011 to propose the necessary foundational studies, which include sequencing of parent-offspring trios from highly exposed human populations, and controlled dose-response experiments in animals. These studies will establish background levels of variability in germline mutation rates and identify environmental agents that influence these rates and heritable disease. Guidance for the types of exposures to examine come from rodent studies that have identified agents such as cancer chemotherapeutic drugs, ionizing radiation, cigarette smoke, and air pollution as germ-cell mutagens. Research is urgently needed to establish the health consequences of parental exposures on subsequent generations. Published by Elsevier B.V. C1 [Yauk, Carole Lyn; Douglas, George R.; Marchetti, Francesco] Hlth Canada, Toronto, ON, Canada. [Argueso, J. Lucas] Colorado State Univ, Ft Collins, CO 80523 USA. [Awadalla, Philip; Rouleau, Guy A.] Univ Montreal, Montreal, PQ H3C 3J7, Canada. [Davis, Sean R.] NIH, Bethesda, MD 20892 USA. [Dubrova, Yuri E.] Univ Leicester, Leicester LE1 7RH, Leics, England. [Elespuru, Rosalie K.] US FDA, Rockville, MD 20857 USA. [Glover, Thomas W.; Wilson, Thomas E.] Univ Michigan, Ann Arbor, MI 48109 USA. [Hales, Barbara F.; Montpetit, Alexandre; Robaire, Bernard; Trasler, Jacquetta] McGill Univ, Montreal, PQ H3A 2T5, Canada. [Hurles, Matthew E.] Wellcome Trust Sanger Inst, Hinxton, England. [Klein, Catherine B.] NYU, Sch Med, New York, NY 10003 USA. [Lupski, James R.] Baylor Coll Med, Houston, TX 77030 USA. [Manchester, David K.] Childrens Hosp Colorado, Aurora, CO USA. [Mulvihill, John J.] Univ Oklahoma, Hlth Sci Ctr, Norman, OK 73019 USA. [Robbins, Wendie A.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Somers, Christopher M.] Univ Regina, Regina, SK S4S 0A2, Canada. [Taylor, James G.] NHLBI, Bethesda, MD 20892 USA. RP Yauk, CL (reprint author), Hlth Canada, Toronto, ON, Canada. EM carole.yauk@hc-sc.gc.ca OI Argueso, Juan Lucas/0000-0002-7157-1519; Dubrova, Yuri/0000-0001-5281-7539; Marchetti, Francesco/0000-0002-9435-4867; Taylor, James/0000-0002-4421-1809; Yauk, Carole/0000-0003-4919-876X; Davis, Sean/0000-0002-8991-6458 FU Intramural NIH HHS [ZIA HL006160-01] NR 30 TC 8 Z9 8 U1 0 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5742 J9 MUTAT RES-REV MUTAT JI Mutat. Res.-Rev. Mutat. Res. PD JAN-MAR PY 2013 VL 752 IS 1 BP 6 EP 9 DI 10.1016/j.mrrev.2012.08.002 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 091TN UT WOS:000315072800002 PM 22935230 ER PT J AU Johnson, ES Bartman, BA Briesacher, BA Fleming, NS Gerhard, T Kornegay, CJ Nourjah, P Sauer, B Schumock, GT Sedrakyan, A Sturmer, T West, SL Schneeweiss, S AF Johnson, Eric S. Bartman, Barbara A. Briesacher, Becky A. Fleming, Neil S. Gerhard, Tobias Kornegay, Cynthia J. Nourjah, Parivash Sauer, Brian Schumock, Glen T. Sedrakyan, Art Stuermer, Til West, Suzanne L. Schneeweiss, Sebastian TI The incident user design in comparative effectiveness research SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Review DE inception cohort; incident interventions; study design; comparative effectiveness; pharmacoepidemiology ID POSTMENOPAUSAL HORMONE-THERAPY; CORONARY-HEART-DISEASE; DRUG UTILIZATION; RISK; EPIDEMIOLOGY; TRIALS AB Comparative effectiveness research includes cohort studies and registries of interventions. When investigators design such studies, how important is it to follow patients from the day they initiated treatment with the study interventions? Our article considers this question and related issues to start a dialogue on the value of the incident user design in comparative effectiveness research. By incident user design, we mean a study that sets the cohort's inception date according to patients' new use of an intervention. In contrast, most epidemiologic studies enroll patients who were currently or recently using an intervention when follow-up began. We take the incident user design as a reasonable default strategy because it reduces biases that can impact non-randomized studies, especially when investigators use healthcare databases. We review case studies where investigators have explored the consequences of designing a cohort study by restricting to incident users, but most of the discussion has been informed by expert opinion, not by systematic evidence. Published 2012. This article is a U.S. Government work and is in the public domain in the USA. C1 [Johnson, Eric S.] Kaiser Permanente, Ctr Hlth Res, Portland, OR USA. [Bartman, Barbara A.; Nourjah, Parivash] Agcy Healthcare Res & Qual, Ctr Outcomes & Evidence, Rockville, MD USA. [Briesacher, Becky A.] Univ Massachusetts, Sch Med, Div Geriatr Med, Worcester, MA USA. [Fleming, Neil S.] Baylor Hlth Care Syst, Ctr Hlth Care Res, Dallas, TX USA. [Gerhard, Tobias] Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, New Brunswick, NJ 08903 USA. [Kornegay, Cynthia J.] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. [Sauer, Brian] Salt Lake City Hlth Care Syst, Salt Lake City IDEAS Ctr Vet Affairs, Salt Lake City, UT USA. [Schumock, Glen T.] Univ Illinois, Sch Pharm, Dept Pharm Practice, Chicago, IL USA. [Sedrakyan, Art] Weill Cornell Med Coll, Div Outcomes & Effectiveness Res, New York, NY USA. [Stuermer, Til] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [West, Suzanne L.] Res Triangle Inst Int, Hlth Social & Econ Res, Res Triangle Pk, NC USA. [Schneeweiss, Sebastian] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. RP Johnson, ES (reprint author), Kaiser Permanente, Ctr Hlth Res, Portland, OR USA. EM Eric.S.Johnson@kpchr.org RI Schneeweiss, Sebastian/C-2125-2013 FU Agency for Healthcare Research and Quality, US Department of Health and Human Services FX This project was funded by the Agency for Healthcare Research and Quality, US Department of Health and Human Services, as part of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) program. The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the US Department of Health and Human Services. NR 30 TC 40 Z9 40 U1 2 U2 14 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JAN PY 2013 VL 22 IS 1 BP 1 EP 6 DI 10.1002/pds.3334 PG 6 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 088FE UT WOS:000314818400001 PM 23023988 ER PT J AU Andrade, SE Scott, PE Davis, RL Li, DK Getahun, D Cheetham, TC Raebel, MA Toh, S Dublin, S Pawloski, PA Hammad, TA Beaton, SJ Smith, DH Dashevsky, I Haffenreffer, K Cooper, WO AF Andrade, Susan E. Scott, Pamela E. Davis, Robert L. Li, De-Kun Getahun, Darios Cheetham, T. Craig Raebel, Marsha A. Toh, Sengwee Dublin, Sascha Pawloski, Pamala A. Hammad, Tarek A. Beaton, Sarah J. Smith, David H. Dashevsky, Inna Haffenreffer, Katherine Cooper, William O. TI Validity of health plan and birth certificate data for pregnancy research SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE administrative databases; birth certificate; positive predictive value; pregnancy; validation; pharmacoepidemiology ID ASTHMA; RELIABILITY; VALIDATION; RECORDS; WOMEN AB Purpose To evaluate the validity of health plan and birth certificate data for pregnancy research. Methods A retrospective study was conducted using administrative and claims data from 11 U. S. health plans and corresponding birth certificate data from state health departments. Diagnoses, drug dispensings, and procedure codes were used to identify infant outcomes (cardiac defects, anencephaly, preterm birth, and neonatal intensive care unit [NICU] admission) and maternal diagnoses (asthma and systemic lupus erythematosus [SLE]) recorded in the health plan data for live born deliveries between January 2001 and December 2007. A random sample of medical charts (n = 802) was abstracted for infants and mothers identified with the specified outcomes. Information on newborn, maternal, and paternal characteristics (gestational age at birth, birth weight, previous pregnancies and live births, race/ethnicity) was also abstracted and compared to birth certificate data. Positive predictive values (PPVs) were calculated with documentation in the medical chart serving as the gold standard. Results PPVs were 71% for cardiac defects, 37% for anencephaly, 87% for preterm birth, and 92% for NICU admission. PPVs for algorithms to identify maternal diagnoses of asthma and SLE were >= 93%. Our findings indicated considerable agreement (PPVs > 90%) between birth certificate and medical record data for measures related to birth weight, gestational age, prior obstetrical history, and race/ethnicity. Conclusions Health plan and birth certificate data can be useful to accurately identify some infant outcomes, maternal diagnoses, and newborn, maternal, and paternal characteristics. Other outcomes and variables may require medical record review for validation. Copyright (C) 2012 John Wiley & Sons, Ltd. C1 [Andrade, Susan E.] Meyers Primary Care Inst, Worcester, MA 01605 USA. [Andrade, Susan E.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Scott, Pamela E.; Hammad, Tarek A.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Davis, Robert L.] Kaiser Permanente Georgia, Ctr Hlth Res, Atlanta, GA USA. [Li, De-Kun] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Getahun, Darios] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA USA. [Cheetham, T. Craig] Kaiser Permanente, Pharm Analyt Serv, Downey, CA USA. [Raebel, Marsha A.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Toh, Sengwee; Dashevsky, Inna; Haffenreffer, Katherine] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Toh, Sengwee; Dashevsky, Inna; Haffenreffer, Katherine] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Dublin, Sascha] Grp Hlth Res Inst, Seattle, WA USA. [Pawloski, Pamala A.] HealthPartners Res Fdn, Bloomington, MN USA. [Beaton, Sarah J.] LCF Res, Albuquerque, NM USA. [Smith, David H.] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA. [Cooper, William O.] Vanderbilt Univ, Sch Med, Dept Pediat & Prevent Med, Nashville, TN 37212 USA. RP Andrade, SE (reprint author), Meyers Primary Care Inst, 630 Plantat St, Worcester, MA 01605 USA. EM sandrade@meyersprimary.org RI Toh, Sengwee/D-7567-2017 OI Toh, Sengwee/0000-0002-5160-0810 FU U.S. FDA (Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research) [HHSF223200510012C, HHSF223200510009C, HHSF223200510008C]; National Institute on Aging [K23AG028954] FX This study was supported through funding from contracts HHSF223200510012C, HHSF223200510009C, and HHSF223200510008C from the U.S. FDA (Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research). Dr. Dublin was supported by National Institute on Aging grant K23AG028954. The views expressed in this paper are those of the authors and are not intended to convey official US FDA policy or guidance. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Aging or the National Institutes of Health. NR 20 TC 28 Z9 28 U1 0 U2 5 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JAN PY 2013 VL 22 IS 1 BP 7 EP 15 DI 10.1002/pds.3319 PG 9 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 088FE UT WOS:000314818400002 PM 22753079 ER PT J AU Cutrona, SL Toh, S Iyer, A Foy, S Daniel, GW Nair, VP Ng, D Butler, MG Boudreau, D Forrow, S Goldberg, R Gore, J McManus, D Racoosin, JA Gurwitz, JH AF Cutrona, Sarah L. Toh, Sengwee Iyer, Aarthi Foy, Sarah Daniel, Gregory W. Nair, Vinit P. Ng, Daniel Butler, Melissa G. Boudreau, Denise Forrow, Susan Goldberg, Robert Gore, Joel McManus, David Racoosin, Judith A. Gurwitz, Jerry H. TI Validation of acute myocardial infarction in the Food and Drug Administration's Mini-Sentinel program SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE myocardial infarction; coronary artery disease; validation; administrative data; Food and Drug Administration; Mini-Sentinel; pharmacoepidemiology ID POSITIVE PREDICTIVE-VALUE; MEDICAL-PRODUCT-SAFETY; CORONARY-HEART-DISEASE; UNIVERSAL DEFINITION; CASE-FATALITY; POPULATION; DIAGNOSIS; DATABASE; RISK; ORGANIZATION AB Purpose To validate an algorithm based upon International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) codes for acute myocardial infarction (AMI) documented within the Mini-Sentinel Distributed Database (MSDD). Methods Using an ICD-9-CM-based algorithm (hospitalized patients with 410.x0 or 410.x1 in primary position), we identified a random sample of potential cases of AMI in 2009 from four Data Partners participating in the Mini-Sentinel Program. Cardiologist reviewers used information abstracted from hospital records to assess the likelihood of an AMI diagnosis based on criteria from the Joint European Society of Cardiology and American College of Cardiology Global Task Force. Positive predictive values (PPVs) of the ICD-9-based algorithm were calculated. Results Of the 153 potential cases of AMI identified, hospital records for 143 (93%) were retrieved and abstracted. Overall, the PPV was 86.0% (95% confidence interval; 79.2%, 91.2%). PPVs ranged from 76.3% to 94.3% across the four Data Partners. Conclusions The overall PPV of potential AMI cases, as identified using an ICD-9-CM-based algorithm, may be acceptable for safety surveillance; however, PPVs do vary across Data Partners. This validation effort provides a contemporary estimate of the reliability of this algorithm for use in future surveillance efforts conducted using the Food and Drug Administration's MSDD. Copyright (C) 2012 John Wiley & Sons, Ltd. C1 [Cutrona, Sarah L.; Foy, Sarah; Goldberg, Robert; Gurwitz, Jerry H.] Reliant Med Grp, Meyers Primary Care Inst, Worcester, MA USA. [Cutrona, Sarah L.; Foy, Sarah; Goldberg, Robert; Gurwitz, Jerry H.] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. [Toh, Sengwee; Iyer, Aarthi; Forrow, Susan] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Toh, Sengwee; Iyer, Aarthi; Forrow, Susan] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Gore, Joel; McManus, David] Univ Massachusetts, Sch Med, Div Cardiovasc Med, Worcester, MA 01605 USA. [Racoosin, Judith A.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Daniel, Gregory W.] Brookings Inst, Engelberg Ctr Hlth Care Reform, Washington, DC 20036 USA. [Nair, Vinit P.] Humana Inc, Louisville, KY USA. [Butler, Melissa G.] Kaiser Permanente Georgia Ctr Hlth Res SE, Atlanta, GA USA. [Boudreau, Denise] Grp Hlth Res Inst, Seattle, WA USA. RP Cutrona, SL (reprint author), Univ Massachusetts, Sch Med, 377 Plantat St,Biotech 4,Suite 315, Worcester, MA 01605 USA. EM Sarah.cutrona@umassmemorial.org RI Toh, Sengwee/D-7567-2017 OI Toh, Sengwee/0000-0002-5160-0810 FU U.S. Food and Drug Administration (FDA) [HHSF223200910006I]; National Center for Research Resources (NCRR) [KL2RR031981] FX This project was supported through funding from contract HHSF223200910006I from the U.S. Food and Drug Administration (FDA). Dr. Sarah Cutrona is supported by Award Number KL2RR031981 from the National Center for Research Resources (NCRR). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NCRR or the National Institutes of Health. NR 37 TC 16 Z9 15 U1 0 U2 2 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JAN PY 2013 VL 22 IS 1 BP 40 EP 54 DI 10.1002/pds.3310 PG 15 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 088FE UT WOS:000314818400006 PM 22745038 ER PT J AU Conrado, DJ Rogers, HL Zineh, I Pacanowski, MA AF Conrado, Daniela J. Rogers, Hobart L. Zineh, Issam Pacanowski, Michael A. TI Consistency of drug-drug and gene-drug interaction information in US FDA-approved drug labels SO PHARMACOGENOMICS LA English DT Article DE CYP450 metabolism; drug labels; drug-drug interaction; FDA; genotype-based dosing; pharmacogenetics ID PHARMACOGENETICS; UPDATE; POLYMORPHISMS; HALOPERIDOL; CAUCASIANS; GUIDELINES; CILOSTAZOL; WITHDRAWN; ENZYMES; MARKET AB Aim: To characterize concordance between clinically relevant drug-drug interactions (DDIs) related to CYP2C19, CYP2D6 and CYP2C9 and their analogous gene-drug interactions (GDIs) in US FDA-approved drug labeling. Methods: We selected prototypical CYP2C19, CYP2D6 and CYP2C9 inhibitors and abstracted all respective interacting drugs via a tertiary resource used in the clinical setting. We then selected only CYP2C19, CYP2D6 and CYP2C9 metabolism-related DDIs requiring enhanced clinical monitoring, dose adjustment or use of alternative drugs. Labeling and management strategies on DDIs and GDIs were compared. Results: Among the drug labels with DDI information, 73% of them describe the analogous GDI. Of the 65 drug labels, 43 and 17% had specific management recommendations for DDIs and GDIs, respectively. In general, GDI management recommendations were concordant with DDI management recommendations in terms of specific dose adjustments or use of alternative drugs. Conclusion: The FDA has recognized genetic differences in drug metabolism where clinically relevant DDIs trigger dose adjustment or use of alternative drugs. C1 [Conrado, Daniela J.; Rogers, Hobart L.; Zineh, Issam; Pacanowski, Michael A.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Conrado, Daniela J.] Univ Florida, Coll Pharm, Dept Pharmaceut, Gainesville, FL 32610 USA. RP Pacanowski, MA (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,White Oak Bldg 51,Room 31, Silver Spring, MD 20993 USA. EM michael.pacanowski@fda.hhs.gov FU Oak Ridge Institute for Science and Education (US Department of Energy); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, Brazil) FX DJ Conrado would like to thank the financial support given by the Oak Ridge Institute for Science and Education (US Department of Energy) and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, Brazil). 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 41 TC 11 Z9 12 U1 1 U2 7 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD JAN PY 2013 VL 14 IS 2 BP 215 EP 223 DI 10.2217/PGS.12.203 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 090PV UT WOS:000314992200018 PM 23327581 ER PT J AU Giberson, SF AF Giberson, Scott F. TI MILLION HEARTS (TM): PHARMACIST-DELIVERED CARE TO IMPROVE CARDIOVASCULAR HEALTH SO PUBLIC HEALTH REPORTS LA English DT Editorial Material ID PATIENT OUTCOMES; INTERVENTIONS; METAANALYSIS; SENSITIVITY; MANAGEMENT C1 Care of Tsai Y, US Publ Hlth Serv, US FDA, Silver Spring, MD 20993 USA. RP Giberson, SF (reprint author), Care of Tsai Y, US Publ Hlth Serv, US FDA, Silver Spring, MD 20993 USA. NR 16 TC 4 Z9 4 U1 0 U2 1 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1900 M ST NW, STE 710, WASHINGTON, DC 20036 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JAN-FEB PY 2013 VL 128 IS 1 BP 2 EP 6 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 079SU UT WOS:000314193300002 PM 23277654 ER PT J AU Calvo, MS Uribarri, J AF Calvo, Mona S. Uribarri, Jaime TI Contributions to Total Phosphorus Intake: All Sources Considered SO SEMINARS IN DIALYSIS LA English DT Review ID CONTAINING FOOD-ADDITIVES; CHRONIC KIDNEY-DISEASE; DIETARY PHOSPHORUS; SERUM PHOSPHORUS; YOUNG-WOMEN; PHOSPHATE; CALCIUM; PRODUCTS; RISK; BONE AB High serum phosphorus is linked to poor health outcome and mortality in chronic kidney disease (CKD) patients before or after the initiation of dialysis. Dietary intake of phosphorus, a major determinant of serum phosphorus, seems to be systematically underestimated using the available software tools and generalized nutrient content databases. Several sources of dietary phosphorus including the addition of phosphorus ingredients in food processing, and phosphorus content of vitamin and mineral supplements and commonly used over-the-counter or prescription medications are not fully accounted for by the nutrient content databases and software programs in current clinical use or used in large population studies. In this review, we explore the many unknown sources of phosphorus in the food supply to identify all possible contributors to total phosphorus intake of Americans that have escaped inclusion in past intake estimates. Our goal is to help delineate areas for future interventions that will enable tighter control of dietary phosphorus intake, a critical factor to maintaining health and quality of life in CKD and dialysis patients. C1 [Calvo, Mona S.] US FDA, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Dept Hlth & Human Serv, Laurel, MD USA. [Uribarri, Jaime] Mt Sinai Sch Med, Dept Med, New York, NY USA. RP Uribarri, J (reprint author), 1 Gustave Levy Pl, New York, NY 10029 USA. EM jaime.uribarri@mssm.edu NR 44 TC 21 Z9 21 U1 1 U2 42 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD JAN-FEB PY 2013 VL 26 IS 1 BP 54 EP 61 DI 10.1111/sdi.12042 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 077SY UT WOS:000314049500015 PM 23278245 ER PT J AU Stagg, NJ Ghantous, HN Ladics, GS House, RV Gendel, SM Hastings, KL AF Stagg, Nicola J. Ghantous, Hanan N. Ladics, Gregory S. House, Robert V. Gendel, Steven M. Hastings, Kenneth L. TI Workshop Proceedings: Challenges and Opportunities in Evaluating Protein Allergenicity Across Biotechnology Industries SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article DE biotechnology; allergenicity; immunotoxicity; protein ID HYPERSENSITIVITY; CULTIVARS; EVENTS AB A workshop entitled "Challenges and Opportunities in Evaluating Protein Allergenicity across Biotechnology Industries" was held at the 51st Annual Meeting of the Society of Toxicology (SOT) in San Francisco, California. The workshop was sponsored by the Biotechnology Specialty Section of SOT and was designed to present the science-based approaches used in biotechnology industries to evaluate and regulate protein allergenicity. A panel of experts from industry and government highlighted the allergenicity testing requirements and research in the agricultural, pharmaceutical/biopharma, and vaccine biotechnology industries and addressed challenges and opportunities for advancing the science of protein allergenicity. The main learning from the workshop was that immunoglobulin E-mediated allergenicity of biotechnology-derived products is difficult to assess without human data. The approaches currently being used to evaluate potential for allergenicity across biotechnology industries are very different and range from bioinformatics, in vitro serology, in vivo animal testing, in vitro and in vivo functional assays, and "biosimilar" assessments (ie, biotherapeutic equivalents to innovator products). The challenge remains with regard to the different or lack of regulatory requirements for allergenicity testing across industries, but the novel approaches being used with bioinformatics and biosimilars may lead to opportunities in the future to collaborate across biotechnology industries. C1 [Stagg, Nicola J.] Agensys, Santa Monica, CA 90404 USA. [Ghantous, Hanan N.] FDA, Silver Spring, MD USA. [Ladics, Gregory S.] DuPont Co Inc, Wilminton, DE USA. [House, Robert V.] DynPort Vaccine Co LLC, Frederick, MD USA. [Gendel, Steven M.] FDA, College Pk, MD USA. [Hastings, Kenneth L.] Sanofi SA, Bethesda, MA USA. RP Stagg, NJ (reprint author), Agensys, 1800 Stewart St, Santa Monica, CA 90404 USA. EM Nicola.Stagg@Agensys.com NR 31 TC 3 Z9 4 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD JAN-FEB PY 2013 VL 32 IS 1 BP 4 EP 10 DI 10.1177/1091581812471864 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 085BW UT WOS:000314586700002 PM 23324160 ER PT J AU Word, B Lyn-Cook, LE Mwamba, B Wang, HG Lyn-Cook, B Hammons, G AF Word, Beverly Lyn-Cook, Lascelles E., Jr. Mwamba, BiBi Wang, Honggang Lyn-Cook, Beverly Hammons, George TI Cigarette Smoke Condensate Induces Differential Expression and Promoter Methylation Profiles of Critical Genes Involved in Lung Cancer in NL-20 Lung Cells In Vitro: Short-Term and Chronic Exposure SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article DE cigarette smoke condensate; human lung cells; DNA methylation ID TUMOR-SUPPRESSOR; DNA METHYLATION; CPG ISLAND; TOBACCO SMOKING; DAP-KINASE; HYPERMETHYLATION; HYPOMETHYLATION; STAGE; TRANSFORMATION; ASSOCIATION AB Establishing early diagnostic markers of harm is critical for effective prevention programs and regulation of tobacco products. This study examined effects of cigarette smoke condensate (CSC) on expression and promoter methylation profile of critical genes (DAPK, ECAD, MGMT, and RASSF1A) involved in lung cancer development in different human lung cell lines. NL-20 cells were treated with 0.1-100 mu g/ml of CSC for 24 to 72 hrs for short-term exposures. DAPK expression or methylation status was not significantly affected. However, CSC treatment resulted in changes in expression and promoter methylation profile of ECAD, MGMT, and RASSF1A. For chronic studies, cells were exposed to 1 or 10 mu g/ml CSC up to 28 days. Cells showed morphological changes associated with transformation and changes in invasion capacities and global methylation status. This study provides critical data suggesting that epigenetic changes could serve as an early biomarker of harm due to exposure to cigarette smoke. C1 [Word, Beverly; Lyn-Cook, Lascelles E., Jr.; Mwamba, BiBi; Wang, Honggang; Lyn-Cook, Beverly; Hammons, George] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Hammons, G (reprint author), Natl Ctr Toxicol Res, Off Regulatory Act, HFT 100, Jefferson, AR 72079 USA. EM ghammons@nctr.fda.gov NR 32 TC 10 Z9 11 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD JAN-FEB PY 2013 VL 32 IS 1 BP 23 EP 31 DI 10.1177/1091581812465902 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 085BW UT WOS:000314586700004 PM 23174910 ER PT J AU Stavitskaya, L Kruhlak, NL Cross, KP Minnier, BL Bower, DA Chakravarti, S Saiakhov, RD Benz, RD AF Stavitskaya, Lidiya Kruhlak, Naomi L. Cross, Kevin P. Minnier, Barbara L. Bower, David A. Chakravarti, Suman Saiakhov, Roustem D. Benz, R. Daniel TI Development of Improved In Silico Models for Predicting Rodent Carcinogenicity SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting of the American-College-of-Toxicology CY NOV 04-07, 2012 CL FL SP Amer Coll Toxicol C1 [Stavitskaya, Lidiya; Kruhlak, Naomi L.; Minnier, Barbara L.; Benz, R. Daniel] FDA Ctr Drug Evaluat & Res CDER, Silver Spring, MD USA. [Cross, Kevin P.; Bower, David A.] Leadscope Inc, Columbus, OH USA. [Chakravarti, Suman; Saiakhov, Roustem D.] MultiCASE Inc, Beachwood, OH USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD JAN-FEB PY 2013 VL 32 IS 1 BP 72 EP 72 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 085BW UT WOS:000314586700047 ER PT J AU Taylor, K Maslov, Y AF Taylor, Kellie Maslov, Yelena TI ACCIDENTAL PEDIATRIC EXPOSURE TO IMIDAZOLINE DERIVATIVES SO JOURNAL OF EMERGENCY NURSING LA English DT Editorial Material C1 [Taylor, Kellie; Maslov, Yelena] US FDA, Div Medicat Error Prevent & Anal, Silver Spring, MD 20993 USA. RP Taylor, K (reprint author), US FDA, Div Medicat Error Prevent & Anal, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Kellie.Taylor@fda.hhs.gov NR 4 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 0099-1767 J9 J EMERG NURS JI J. Emerg. Nurs. PD JAN PY 2013 VL 39 IS 1 BP 59 EP 60 DI 10.1016/j.jen.2012.10.007 PG 2 WC Emergency Medicine; Nursing SC Emergency Medicine; Nursing GA 083IK UT WOS:000314456700018 PM 23295088 ER PT J AU Zhou, YT He, WW Wamer, WG Hu, XN Wu, XC Lo, YM Yin, JJ AF Zhou, Yu-Ting He, Weiwei Wamer, Wayne G. Hu, Xiaona Wu, Xiaochun Lo, Y. Martin Yin, Jun-Jie TI Enzyme-mimetic effects of gold@platinum nanorods on the antioxidant activity of ascorbic acid SO NANOSCALE LA English DT Article ID PEROXIDASE-LIKE ACTIVITY; CATALYTIC-ACTIVITY; HYDROGEN-PEROXIDE; SUPEROXIDE ANION; NANOPARTICLES; OXIDASE; STRESS; ESR; NANOSTRUCTURES; GENERATION AB Au@Pt nanorods were prepared by growing platinum nanodots on gold nanorods. Using electron spin resonance (ESR), we determined that the mechanisms for oxidation of ascorbic acid (AA) by Au@Pt nanorods and ascorbic acid oxidase (AAO) were kinetically similar and yielded similar products. In addition we observed that Au@Pt nanorods were stable with respect to temperature and pH. Using UV-VIS spectroscopy, the apparent kinetics of enzyme-mimetic activity of Au@Pt nanorods were studied and compared with the activity of AAO. With the help of ESR, we found that Au@Pt nanorods did not scavenge hydroxyl radicals but inhibited the antioxidant ability of AA for scavenging hydroxyl radicals produced by photoirradiating solutions containing titanium dioxide and zinc oxide. Moreover, the Au@Pt nanorods reduced the ability of AA to scavenge DPPH radicals and superoxide radicals. These results demonstrate that Au@Pt nanorods can reduce the antioxidant activity of AA. Therefore, it is necessary to consider the effects of using Pt nanoparticles together with other reducing agents or antioxidants such as AA due to the oxidase-like property of Au@Pt nanorods. C1 [Zhou, Yu-Ting; He, Weiwei; Wamer, Wayne G.; Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Zhou, Yu-Ting; Lo, Y. Martin] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [He, Weiwei] Xuchang Univ, Inst Surface Micro & Nanomat, Key Lab Micronano Energy Storage & Convers Mat He, Xuchang 461000, Peoples R China. [Hu, Xiaona; Wu, Xiaochun] Natl Ctr Nanosci & Technol, CAS Key Lab Standardizat & Measurement Nanotechol, Beijing 100190, Peoples R China. RP Lo, YM (reprint author), Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. EM ymlo@umd.edu; junjie.yin@fda.hhs.gov RI Yin, Jun Jie /E-5619-2014 FU regulatory science grant under the FY11 FDA Nanotechnology CORES Program FX We thank Dr John Callahan for his valuable discussion and comments. This article is not an official US Food and Drug Administration (FDA) guidance or policy statement. No official support or endorsement by the US FDA is intended or should be inferred. This work was supported by a regulatory science grant under the FY11 FDA Nanotechnology CORES Program. NR 41 TC 21 Z9 21 U1 10 U2 98 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 J9 NANOSCALE JI Nanoscale PY 2013 VL 5 IS 4 BP 1583 EP 1591 DI 10.1039/c2nr33072e PG 9 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 083PM UT WOS:000314477300044 PM 23329011 ER PT J AU Xie, HG Wang, SK Cao, CC Harpur, E AF Xie, Hong-Guang Wang, Shu-Kui Cao, Chang-Chun Harpur, Ernie TI Qualified kidney biomarkers and their potential significance in drug safety evaluation and prediction SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE Drug safety; Drug-induced nephrotoxicity; Biomarker; Acute kidney injury; Renal safety biomarker; Biomarker qualification ID ACUTE-RENAL-FAILURE; SERUM CYSTATIN-C; URINARY BIOMARKERS; TUBULAR DYSFUNCTION; PAPILLARY NECROSIS; INJURY MOLECULE-1; 2 STRAINS; NEPHROTOXICITY; ALBUMIN; MARKER AB The kidney is one of the major organs drug toxicity may target. Some renal safety biomarkers have been proposed to measure kidney injury and function accordingly. Despite the widespread use for diagnosis and monitoring of renal injury and function for decades, serum creatinine and blood urea nitrogen are nonspecific biomarkers with insensitive and delayed response in the clinical setting. There is an urgent need to identify and qualify novel kidney safety biomarkers that would be used to detect and predict drug-induced nephrotoxicity in preclinical toxicological studies, clinical trials and patient care in sequence. To do that, eight novel renal safety biomarkers have been well characterized and qualified for preclinical drug safety screening, and their clinical bridging validation is underway as well. Of them, some are used to detect or predict proximal tubular injury, and others are used to diagnose and monitor glomerular damage. Thus, measurement of a panel of kidney safety biomarkers in parallel would help maximally capture all potential safety signals for a more informative decision to be made in drug research and development as well as for optimal selection of the drug and its dose in clinical practice. Published by Elsevier Inc. C1 [Xie, Hong-Guang; Wang, Shu-Kui] Nanjing Med Univ, Nanjing Hosp, Gen Clin Res Ctr, Nanjing, Jiangsu, Peoples R China. [Xie, Hong-Guang] Nanjing Med Univ, Sch Pharm, Dept Pharmacol, Nanjing, Jiangsu, Peoples R China. [Xie, Hong-Guang] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Cao, Chang-Chun] Nanjing Med Univ, Nanjing Hosp, Dept Med, Div Nephrol, Nanjing, Jiangsu, Peoples R China. [Harpur, Ernie] Newcastle Univ, Sch Med, Inst Cellular Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. RP Xie, HG (reprint author), Nanjing First Hosp, Cent Lab, 68 Changle Rd, Nanjing 210006, Jiangsu, Peoples R China. EM hongg.xie@gmail.com; ernieharpur@gmail.com FU Nanjing First Hospital, Nanjing Medical University, China; [31010300010339] FX Dr. Xie was supported in part by an appointment to the Research Participation Program at the Center for Drug Evaluation and Research (CDER) administrated by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy and the U.S. FDA, and also supported in part by the starting research grant No. 31010300010339, funded by the Nanjing First Hospital, Nanjing Medical University, China. NR 82 TC 11 Z9 12 U1 1 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD JAN PY 2013 VL 137 IS 1 BP 100 EP 107 DI 10.1016/j.pharmthera.2012.09.004 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 081MO UT WOS:000314326500007 PM 23017937 ER PT J AU Handy, SM Yakes, BJ DeGrasse, JA Campbell, K Elliott, CT Kanyuck, KM DeGrasse, SL AF Handy, Sara M. Yakes, Betsy Jean DeGrasse, Jeffrey A. Campbell, Katrina Elliott, Christopher T. Kanyuck, Kelsey M. DeGrasse, Stacey L. TI First report of the use of a saxitoxin-protein conjugate to develop a DNA aptamer to a small molecule toxin SO TOXICON LA English DT Article DE Aptamer; Saxitoxin; Marine toxin; Paralytic shellfish toxins; Surface plasmon resonance ID SELECTION; LIGANDS; SELEX; ACID; ANTIBODIES; ENRICHMENT; EVOLUTION; BINDING AB Saxitoxin (STX) is a low molecular weight neurotoxin mainly produced by certain marine dinoflagellates that, along with its family of similarly related paralytic shellfish toxins, may cause the potentially fatal intoxication known as paralytic shellfish poisoning. Illness and fatality rates are low due to the effective monitoring programs that determine when toxins exceed the established regulatory action level and effectuate shellfish harvesting closures accordingly. Such monitoring programs rely on the ability to rapidly screen large volumes of samples. Many of the screening assays currently available employ antibodies or live animals. This research focused on developing an analytical recognition element that would eliminate the challenges associated with the limited availability of antibodies and the use of animals. Here we report the discovery of a DNA aptamer that targets STX. Concentration-dependent and selective binding of the aptamer to STX was determined using a surface plasmon resonance sensor. Not only does this work represent the first reported aptamer to SIX, but also the first aptamer to any marine biotoxin. A novel strategy of using a toxin protein conjugate for DNA aptamer selection was successfully implemented to overcome the challenges associated with aptamer selection to small molecules. Taking advantage of such an approach could lead to increased diversity and accessibility of aptamers to low molecular weight toxins, which could then be incorporated as analytical recognition elements in diagnostic assays for foodborne toxin detection. The selected STX aptamer sequence is provided here, making it available to any investigator for use in assay development for the detection of SIX. Published by Elsevier Ltd. C1 [Handy, Sara M.; Yakes, Betsy Jean; DeGrasse, Jeffrey A.; DeGrasse, Stacey L.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Campbell, Katrina; Elliott, Christopher T.] Queens Univ Belfast, IAFLU, Sch Biol Sci, Belfast BT9 5AG, Antrim, North Ireland. [Kanyuck, Kelsey M.] Univ Maryland, JIFSAN, College Pk, MD 20742 USA. RP Handy, SM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM sara.handy@fda.hhs.gov RI Handy, Sara/C-6195-2008; Yakes, Betsy/K-2646-2012; DeGrasse, Jeffrey/J-1151-2014; OI DeGrasse, Jeffrey/0000-0003-3178-6301; DeGrasse, Stacey/0000-0001-7808-4193 FU Department of Employment and Learning via the All-island Research Initiative (ASSET Project) FX The authors would like to thank Sarah Stadig for technical assistance, and Dr. John Callahan for guidance and review of the manuscript, and funding for the work in Belfast from the Department of Employment and Learning via the All-island Research Initiative (ASSET Project). Thank you also to Titan Fan from Beacon Analytical for providing purified anti-STX for SPR experiments. NR 24 TC 24 Z9 27 U1 3 U2 88 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD JAN PY 2013 VL 61 BP 30 EP 37 DI 10.1016/j.toxicon.2012.10.015 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 079BY UT WOS:000314146400005 PM 23142073 ER PT J AU Lin, WJ Chen, JJ AF Lin, Wei-Jiun Chen, James J. TI Class-imbalanced classifiers for high-dimensional data SO BRIEFINGS IN BIOINFORMATICS LA English DT Article DE class-imbalanced prediction; feature selection; lack of data; performance metrics; threshold adjustment; under-sampling ensemble ID SUPPORT VECTOR MACHINES; CANCER CLASSIFICATION; PREDICTIVE TOXICOLOGY; BREAST-CANCER; CLASS SIZES; EXPRESSION; ALGORITHMS; MICROARRAY; PROFILES; LYMPHOMA AB A class-imbalanced classifier is a decision rule to predict the class membership of new samples from an available data set where the class sizes differ considerably. When the class sizes are very different, most standard classification algorithms may favor the larger (majority) class resulting in poor accuracy in the minority class prediction. A class-imbalanced classifier typically modifies a standard classifier by a correction strategy or by incorporating a new strategy in the training phase to account for differential class sizes. This article reviews and evaluates some most important methods for class prediction of high-dimensional imbalanced data. The evaluation addresses the fundamental issues of the class-imbalanced classification problem: imbalance ratio, small disjuncts and overlap complexity, lack of data and feature selection. Four class-imbalanced classifiers are considered. The four classifiers include three standard classification algorithms each coupled with an ensemble correction strategy and one support vector machines (SVM)-based correction classifier. The three algorithms are (i) diagonal linear discriminant analysis (DLDA), (ii) random forests (RFs) and (ii) SVMs. The SVM-based correction classifier is SVM threshold adjustment (SVM-THR). A Monte-Carlo simulation and five genomic data sets were used to illustrate the analysis and address the issues. The SVM-ensemble classifier appears to perform the best when the class imbalance is not too severe. The SVM-THR performs well if the imbalance is severe and predictors are highly correlated. The DLDA with a feature selection can perform well without using the ensemble correction. C1 [Lin, Wei-Jiun] Feng Chia Univ, Dept Appl Math, Taichung, Taiwan. [Lin, Wei-Jiun; Chen, James J.] US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. [Chen, James J.] China Med Univ, Grad Inst Biostat, Shenyang, Taiwan. [Chen, James J.] China Med Univ, Ctr Biostat, Shenyang, Taiwan. RP Chen, JJ (reprint author), HFT-20,3900 NCTR Rd, Jefferson, AR 72079 USA. EM jamesj.chen@fda.hhs.gov FU National Science Council, Taiwan [NSC 100-2119-M-035-002-] FX This research was supported in part by the National Science Council, Taiwan, under contract NSC 100-2119-M-035-002-. NR 49 TC 43 Z9 44 U1 5 U2 52 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1467-5463 J9 BRIEF BIOINFORM JI Brief. Bioinform. PD JAN PY 2013 VL 14 IS 1 BP 13 EP 26 DI 10.1093/bib/bbs006 PG 14 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 073DL UT WOS:000313723600002 PM 22408190 ER PT J AU Shields, JM Joo, J Kim, R Murphy, HR AF Shields, Joan M. Joo, Jane Kim, Richard Murphy, Helen R. TI Assessment of three commercial DNA extraction kits and a laboratory-developed method for detecting Cryptosporidium and Cyclospora in raspberry wash, basil wash and pesto SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE Cyclospora cayetanensis; Cyptosporidium parvum; DNA extraction; Foods; PCR ID REAL-TIME PCR; CAYETANENSIS; OUTBREAK; INFECTION; PATHOGEN; LETTUCE; PARVUM; HSP70 AB Polymerase chain reaction (PCR) methods are often used to identify the parasitic protozoa Cryptosporidium parvum and Cyclospora cayetanensis in foods although little has been published regarding the efficacy of available DNA extraction methods. This study reviewed three commonly used commercial DNA extraction kits: FastDNA SPIN Kit for soil, QBiogene (FastDNA), UltraClean (TM) Soil DNA Isolation Kit, MO BIO Laboratories (MoBio), and QIAamp DNA Mini Stool Kit, Qiagen (QIAamp), as well as a 'homebrew' Universal Nucleic Acid Extraction (UNEX) method. Washes from raspberry and basil as well as commercial pesto samples were seeded with 5000, 500, or 50 C parvum and C cayetanensis oocysts. The protocols were assessed for: quantity and quality of the extracted DNA, time to completion, presence of PCR inhibitors and the percentage of samples correctly identified as positive for the two parasites. Real-time and conventional nested PCR assays were used to detect the seeded pathogens. Of the commercial kits, PCR results of samples extracted using FastDNA were statistically similar to QIAamp and both were superior to MoBio. Differences in PCR results among FastDNA, QIAamp and UNEX for detection of Cyclospora were not statistically significant although the UNEX method proved best with Cryptosporidium. Real-time PCR assays targeted the 18S rRNA and the hsp70 genes of C. cayetanensis; overall results were similar to those found using conventional nested PCR targeting the 18S rRNA gene. Published by Elsevier B.V. C1 [Shields, Joan M.; Murphy, Helen R.] US FDA, Div Virulence Assessment, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. [Joo, Jane] Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. [Kim, Richard] KNU, Taegu, South Korea. RP Shields, JM (reprint author), US FDA, Div Virulence Assessment, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. EM Joan.Shields@fda.hhs.gov NR 29 TC 10 Z9 11 U1 2 U2 49 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 JAN PY 2013 VL 92 IS 1 BP 51 EP 58 DI 10.1016/j.mimet.2012.11.001 PG 8 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 078BR UT WOS:000314073600008 PM 23147278 ER PT J AU Thudium, K Bilic, S Leipold, D Mallet, W Kaur, S Meibohm, B Erickson, H Tibbitts, J Zhao, H Gupta, M AF Thudium, Karen Bilic, Sanela Leipold, Douglas Mallet, William Kaur, Surinder Meibohm, Bernd Erickson, Hans Tibbitts, Jay Zhao, Hong Gupta, Manish TI American Association of Pharmaceutical Scientists National Biotechnology Conference Short Course: Translational Challenges in Developing Antibody-Drug Conjugates May 24, 2012, San Diego, CA SO MABS LA English DT Article DE ADC; pharmacokinetics; linker; trastuzumab emtansine; brentuximab vedotin ID TRASTUZUMAB EMTANSINE T-DM1; METASTATIC BREAST-CANCER; MODEL AB The American Association of Pharmaceutical Scientists (AAPS) National Biotechnology Conference Short Course "Translational Challenges in Developing Antibody-Drug Conjugates (ADCs)," held May 24, 2012 in San Diego, CA, was organized by members of the Pharmacokinetics, Pharmacodynamics and Drug Metabolism section of AAPS. Representatives from the pharmaceutical industry, regulatory authorities, and academia in the US and Europe attended this short course to discuss the translational challenges in ADC development and the importance of characterizing these molecules early in development to achieve therapeutic utility in patients. Other areas of discussion included selection of target antigens; characterization of absorption, distribution, metabolism, and excretion; assay development and hot topics like regulatory perspectives and the role of pharmacometrics in ADC development. MUC16-targeted ADCs were discussed to illustrate challenges in preclinical development; experiences with trastuzumab emtansine (T-DM1; Genentech) and the recently approved brentuximab vedotin (Adcetris (R); Seattle Genetics) were presented in depth to demonstrate considerations in clinical development. The views expressed in this report are those of the participants and do not necessarily represent those of their affiliations. C1 [Thudium, Karen; Bilic, Sanela] Novartis Pharmaceut, Clin Pharmacol, Oncol Business Unit, Florham Pk, NJ USA. [Leipold, Douglas; Kaur, Surinder; Tibbitts, Jay] Genentech Inc, San Francisco, CA USA. [Mallet, William] Novartis Inst BioMed Res, Emeryville, CA USA. [Meibohm, Bernd] Univ Tennessee, Ctr Hlth Sci, Coll Pharm, Memphis, TN 38163 USA. [Erickson, Hans] ImmunoGen Inc, Waltham, MA USA. [Zhao, Hong] US FDA, Silver Spring, MD USA. [Gupta, Manish] Bristol Myers Squibb Co, New Brunswick, NJ USA. RP Thudium, K (reprint author), Novartis Pharmaceut, Clin Pharmacol, Oncol Business Unit, Florham Pk, NJ USA. EM karen.thudium@novartis.com; Sanela.Bilic@Novartis.com FU AAPS-NBC FX The authors acknowledge and thank AAPS-NBC for supporting the short-course and recognize the scientists dedicated to the defining the ADC development path. The authors would like to acknowledge Benjamin Guiastrennec who assisted in the preparation of Figure 1. NR 11 TC 9 Z9 9 U1 0 U2 10 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1942-0862 EI 1942-0870 J9 MABS-AUSTIN JI mAbs PD JAN-FEB PY 2013 VL 5 IS 1 BP 5 EP 12 DI 10.4161/mabs.22909 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 078PX UT WOS:000314112800002 PM 23255090 ER PT J AU Zoratto, F Fiore, M Ali, SF Laviola, G Macri, S AF Zoratto, Francesca Fiore, Marco Ali, Syed F. Laviola, Giovanni Macri, Simone TI Neonatal tryptophan depletion and corticosterone supplementation modify emotional responses in adult male mice SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Mouse; Depression; Validity; Tryptophan; Corticosterone; Anhedonia ID PROGRESSIVE RATIO SCHEDULE; CORTICOTROPIN-RELEASING-FACTOR; MAJOR DEPRESSIVE DISORDER; ANXIETY-LIKE BEHAVIORS; TAIL SUSPENSION TEST; FACTOR MESSENGER-RNA; CHRONIC MILD STRESS; EARLY-LIFE STRESS; SEROTONIN TRANSPORTER; ANIMAL-MODELS AB The serotonergic system and the hypothalamic-pituitary-adrenal (HPA) axis are crucially involved in the regulation of emotions. Specifically, spontaneous and/or environmentally mediated modulations of the functionality of these systems early in development may favour the onset of depressive- and anxiety-related phenotypes. While the independent contribution of each of these systems to the emergence of abnormal phenotypes has been detailed in clinical and experimental studies, only rarely has their interaction been systematically investigated. Here, we addressed the effects of reduced serotonin and environmental stress during the early stages of postnatal life on emotional regulations in mice. To this aim, we administered, to outbred CD1 mouse dams, during their first week of lactation, a tryptophan deficient diet (T) and corticosterone via drinking water (C; 80 mu g/ml). Four groups of dams (animal facility rearing, AFR; T treated, T; C treated, C; T and C treated, TC) and their male offspring were used in the study. Maternal care was scored throughout treatment and adult offspring were tested for: anhedonia (progressive ratio schedule); anxiety-related behaviour (approach-avoidance conflict paradigm); BDNF, dopamine and serotonin concentrations in selected brain areas. T, C and TC treatments reduced active maternal care compared to AFR. Adult IC offspring showed significantly increased anxiety- and anhedonia-related behaviours, reduced striatal and increased hypothalamic BDNF and reduced dopamine and serotonin in the prefrontal cortex and their turnover in the hippocampus. Thus, present findings support the view that neonatal variations in the functionality of the serotonergic system and of HPA axis may jointly contribute to induce emotional disturbances in adulthood. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Zoratto, Francesca; Laviola, Giovanni; Macri, Simone] Ist Super Sanita, Sect Behav Neurosci, Dept Cell Biol & Neurosci, I-00161 Rome, Italy. [Fiore, Marco] CNR, Inst Cell Biol & Neurobiol, Rome, Italy. [Fiore, Marco] IRCCS Fdn Santa Lucia, Rome, Italy. [Ali, Syed F.] Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Macri, S (reprint author), Ist Super Sanita, Sect Behav Neurosci, Dept Cell Biol & Neurosci, Viale Regina Elena 299,Block 19,Floor D,Room 11, I-00161 Rome, Italy. EM simone.macri@iss.it RI Laviola, Giovanni/K-4392-2016; Zoratto, Francesca/K-6031-2016; Fiore, Marco/B-6112-2015; OI Laviola, Giovanni/0000-0003-0388-0835; Zoratto, Francesca/0000-0002-3626-8928; Macri, Simone/0000-0003-2946-4784 FU NARSAD young investigator award; ISS-NIH [0F14]; ERARE-EuroRett Network [ERAR/6] FX S. Macri was supported by a NARSAD young investigator award. G. Laviola's research was supported by ISS-NIH (0F14) grant and by ERARE-EuroRett Network (ERAR/6). NR 111 TC 6 Z9 6 U1 2 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JAN PY 2013 VL 38 IS 1 BP 24 EP 39 DI 10.1016/j.psyneuen.2012.04.015 PG 16 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 073RU UT WOS:000313761000003 PM 22613034 ER PT J AU Alayash, AI Andersen, CBF Moestrup, SK Bulow, L AF Alayash, Abdu I. Andersen, Christian Brix Folsted Moestrup, Soren Kragh Bulow, Leif TI Haptoglobin: the hemoglobin detoxifier in plasma SO TRENDS IN BIOTECHNOLOGY LA English DT Letter ID GUINEA-PIG; OXYGENATION; OXIDATION; COMPLEX AB Hemoglobin (Hb) is one of the most studied proteins. However, oxidative toxicity associated with free Hb in circulation and its contribution to inflammation and complications of transfusion have only recently become active areas of research. New insights into the protective mechanisms of haptoglobin (Hp), a plasma protein, and a timely resolution of the crystal structure of the Hb-Hp complex made it possible to definitively link the functional and structural interplay between the two proteins. Here, we summarize current knowledge of the interactions between Hb and Hp under oxidative stress conditions, and how Hb's own damaging radicals are harnessed by complex formation. Potential therapeutic benefits of using Hp for inactivation and clearance of free Hb under a number of clinical settings are considered. C1 [Alayash, Abdu I.] US FDA, Lab Biochem & Vasc Biol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Andersen, Christian Brix Folsted; Moestrup, Soren Kragh] Aarhus Univ, Dept Biomed, DK-8000 Aarhus, Denmark. [Bulow, Leif] Lund Univ, Dept Pure & Appl Biochem, Lund, Sweden. RP Alayash, AI (reprint author), US FDA, Lab Biochem & Vasc Biol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM abdu.alayash@fda.hhs.gov RI Moestrup, Soren Kragh/A-1403-2014 OI Moestrup, Soren Kragh/0000-0003-3862-2107 FU NHLBI NIH HHS [P01 HL110900] NR 12 TC 18 Z9 20 U1 1 U2 16 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD JAN PY 2013 VL 31 IS 1 BP 2 EP 3 DI 10.1016/j.tibtech.2012.10.003 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 077FZ UT WOS:000314014600002 PM 23140673 ER PT J AU Durmowicz, AG Witzmann, KA Rosebraugh, CJ Chowdhury, BA AF Durmowicz, Anthony G. Witzmann, Kimberly A. Rosebraugh, Curtis J. Chowdhury, Badrul A. TI Change in Sweat Chloride as a Clinical End Point in Cystic Fibrosis Clinical Trials The Ivacaftor Experience SO CHEST LA English DT Article ID MUTATION; LUNG AB Cystic fibrosis (CF) is a life-shortening inherited disease caused by mutations in the CF transmembrane conductance regulator gene (CFTR), which encodes for the CF transmenibrane conductance regulator (CFTR) ion channel that regulates chloride and water transport across the surface of epithelial cells. Ivacaftor, a drug recently approved by the US Food and Drug Administration, represents the first mutation-specific therapy for CF. It is a CFTR channel modulator and improves CFTR function in patients with CF who have a G551D mutation. A clinical trial performed to support ivacaftor dose selection demonstrated a dose-response relationship between improvement in FEV1 and decrease in sweat chloride, a measure of CFTR function. Validation of such a relationship between FEV1 and sweat chloride would facilitate development of new drugs that target the defective CFTR. Subsequently, in phase 3 studies, ivacaftor 150 mg hid resulted in significant improvements in FEV1 (10%42%) and reduction in sweat chloride (approximately 50 mmol/L). However, a decrease in sweat chloride did not correlate with improvement in FEV1, nor did there appear to be a threshold level for change in sweat chloride above which an improvement in FEV1 was apparent. The lack of correlation of sweat chloride with improvement in FEV1 speaks to the multiplicity of factors, physiologic, environmental, and genetic, that likely modulate. CF disease severity. Future clinical trials of drugs that are directed to the defective CFTR will need take into account the uncertainty of using even,established measurements, such as sweat chloride, as clinical end points. CHEST 2013; 143(1):14-18 C1 [Durmowicz, Anthony G.; Witzmann, Kimberly A.; Chowdhury, Badrul A.] US FDA, Div Pulm Allergy & Rheumatol Prod, Off New Drugs, Silver Spring, MD 20993 USA. [Rosebraugh, Curtis J.] US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 2, Silver Spring, MD 20993 USA. RP Durmowicz, AG (reprint author), US FDA, Div Pulm Allergy & Rheumatol Prod, Off New Drugs, White Oak Bldg 22,Room 3318,10903 New Hampshire A, Silver Spring, MD 20993 USA. EM anthony.durmowicz@fda.hhs.gov NR 13 TC 45 Z9 45 U1 1 U2 13 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2013 VL 143 IS 1 BP 14 EP 18 DI 10.1378/chest.12-1430 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 070SL UT WOS:000313531200008 PM 23276841 ER PT J AU Tadesse, DA Bahnson, PB Funk, JA Morrow, WEM Abley, MJ Ponte, VA Thakur, S Wittum, T DeGraves, FJ Rajala-Schultz, PJ Gebreyes, WA AF Tadesse, Daniel A. Bahnson, Peter B. Funk, Julie A. Morrow, W. E. Morgan Abley, Melanie J. Ponte, Valeria A. Thakur, Siddhartha Wittum, Thomas DeGraves, Fred J. Rajala-Schultz, Paivi J. Gebreyes, Wondwossen A. TI Yersinia enterocolitica of Porcine Origin: Carriage of Virulence Genes and Genotypic Diversity SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID FIELD GEL-ELECTROPHORESIS; MOLECULAR EPIDEMIOLOGY; SEROVAR TYPHIMURIUM; PREVALENCE; PIGS; STRAINS; SWINE; SUSCEPTIBILITY; IDENTIFICATION; SLAUGHTER AB Yersinia enterocolitica is an important foodborne pathogen, and pigs are recognized as a major reservoir and potential source of pathogenic strains to humans. A total of 172 Y. enterocolitica recovered from conventional and antimicrobial-free pig production systems from different geographic regions (North Carolina, Ohio, Michigan, Wisconsin, and Iowa) were investigated to determine their pathogenic significance to humans. Phenotypic and genotypic diversity of the isolates was assessed using antibiogram, serogrouping, and amplified fragment length polymorphism (AFLP). Carriage of chromosomal and plasmid-borne virulence genes were investigated using polymerase chain reaction. A total of 12 antimicrobial resistance patterns were identified. More than two-thirds (67.4%) of Y. enterocolitica were pan-susceptible, and 27.9% were resistant against beta-lactams. The most predominant serogroup was O:3 (43%), followed by O:5 (25.6%) and O:9 (4.1%). Twenty-two of 172 (12.8%) isolates were found to carry Yersinia adhesion A (yadA), a virulence gene encoded on the Yersinia virulence plasmid. Sixty-nine (40.1%) isolates were found to carry ail gene. The ystA and ystB genes were detected in 77% and 26.2% of the strains, respectively. AFLP genotyping of isolates showed wide genotypic diversity and were grouped into nine clades with an overall genotypic similarity of 66.8-99.3%. AFLP analysis revealed that isolates from the same production system showed clonal relatedness, while more than one genotype of Y. enterocolitica circulates within a farm. C1 [Tadesse, Daniel A.] US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD USA. [Bahnson, Peter B.] Univ Wisconsin, Sch Vet Med, Madison, WI 53706 USA. [Funk, Julie A.] Michigan State Univ, Coll Vet Med, E Lansing, MI 48824 USA. [Morrow, W. E. Morgan] N Carolina State Univ, Coll Agr & Life Sci, Raleigh, NC 27695 USA. [Thakur, Siddhartha] N Carolina State Univ, Coll Vet Med, Raleigh, NC USA. [Gebreyes, Wondwossen A.] Ohio State Univ, Coll Vet Med, Dept Vet Prevent Med, Columbus, OH 43210 USA. RP Gebreyes, WA (reprint author), Ohio State Univ, Coll Vet Med, Dept Vet Prevent Med, 1920 Coffey Rd, Columbus, OH 43210 USA. EM Wondwossen.Gebreyes@cvm.osu.edu FU U.S. Department of Agriculture, National Integrated Food Safety Initiative (NIF-SI) [2002-51110-01508]; Ohio State University FX We thank Dr. Brian Ahmer, Ohio State University Department of Microbiology, for providing us Y. enterocolitica control strains for the aesculin hydrolysis test. We wish to also thank the producers and processors that participated in this research. This study was funded by U.S. Department of Agriculture, National Integrated Food Safety Initiative (NIF-SI; grant 2002-51110-01508) and internal grants from Ohio State University. NR 34 TC 5 Z9 5 U1 1 U2 19 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1535-3141 J9 FOODBORNE PATHOG DIS JI Foodborne Pathog. Dis. PD JAN PY 2013 VL 10 IS 1 BP 80 EP 86 DI 10.1089/fpd.2011.1120 PG 7 WC Food Science & Technology SC Food Science & Technology GA 071CJ UT WOS:000313563000013 PM 23320426 ER PT J AU He, Y Abid, A Fisher, R Eller, N Mikolajczyk, M Welliver, RC Bonner, AB Scott, DE Reed, JL AF He, Yong Abid, Afsheen Fisher, Robert Eller, Nancy Mikolajczyk, Malgorzata Welliver, Robert C., Sr. Bonner, Aleta B. Scott, Dorothy E. Reed, Jennifer L. TI Mucosal antibody responses are directed by viral burden in children with acute influenza infection SO INFLUENZA AND OTHER RESPIRATORY VIRUSES LA English DT Article DE Mucosal antibody response; pandemic influenza pediatric; lower respiratory infection; neutralizing antibody response ID RESPIRATORY SYNCYTIAL VIRUS; INNATE IMMUNE SIGNALS; PANDEMIC INFLUENZA; H1N1 INFLUENZA; UNITED-STATES; VACCINE; CELLS; PSEUDOTYPES; SECRETIONS AB Please cite this paper as: He et al. (2012) Mucosal antibody responses are directed by viral burden in children with acute influenza infection. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2012.00346.x. Background Influenza infection causes excess hospitalizations and deaths in younger patients, but susceptibility to severe disease is poorly understood. While mucosal antibodies can limit influenza-associated infection and disease, little is known about acute mucosal antibody responses to influenza infection. Objectives These studies characterize mucosal antiviral antibody production in children during lower respiratory infection (LRI) with H1N1 influenza versus other viral LRI and examine the relationship between mucosal antiviral antibodies and protection against severe disease. Methods B lymphocytes were assessed by immunohistochemistry in lung tissue from infants with fatal acute seasonal influenza infection. Nasopharyngeal secretions (NPS) were obtained at presentation from children with acute respiratory illness, including H1N1 (2009) influenza infection. Total and antiviral antibodies, and inflammatory and immune mediators, were quantified by ELISA. Neutralizing activity in NPS was detected using a pseudotyped virus assay. Viral burden was assessed by qPCR. Results and conclusions B lymphocytes were abundant in lung tissue of infants with fatal acute influenza LRI. Among surviving children with H1N1 infection, only a small subset (11%) demonstrated H1N1 neutralizing activity in NPS. H1N1 neutralizing activity coincided with high local levels of antiviral IgM, IgG and IgA, greater detection of inflammatory mediators, and higher viral burden (P = 0.016). Patients with mucosal antiviral antibody responses demonstrated more severe respiratory symptoms including greater hypoxia (P = 0.0018) and pneumonia (P = 0.038). These patients also trended toward younger age, longer duration of illness and longer hospital stays. Prophylaxis strategies that heighten neutralizing antibody production in the mucosa are likely to benefit both older and younger children. C1 [He, Yong; Fisher, Robert; Eller, Nancy; Mikolajczyk, Malgorzata; Scott, Dorothy E.; Reed, Jennifer L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Abid, Afsheen] SUNY Buffalo, Dept Pediat, Buffalo, NY 14260 USA. [Welliver, Robert C., Sr.] SUNY Buffalo, Div Infect Dis, Buffalo, NY 14260 USA. [Bonner, Aleta B.] Dell Childrens Med Ctr Cent Texas, Dept Emergency Med, Austin, TX USA. RP Reed, JL (reprint author), US FDA, Ctr Biol Evaluat & Res, 8800 Rockville Pike,HFM 345, Bethesda, MD 20892 USA. EM dorothy.scott@fda.hhs.gov; jennifer.reed@fda.hhs.gov FU Alere Scarborough, Inc; BD Diagnostics; Quidel Corporation; bioMeriux Inc.; Response Biomedical Corporation; Remel, Inc.; FDA CBER FX Potential conflicts of interest: R. C. W. is a consultant to MedImmune. A. B. has received influenza research funding from Alere Scarborough, Inc, BD Diagnostics, Quidel Corporation, bioMeriux Inc., Response Biomedical Corporation, and Remel, Inc. No conflicts of interest are identified for Y.H., A. A., R. F., N.E., M. M, D. E. S., and J.L.R. This study was supported by FDA CBER operating funds. The findings and conclusions in this manuscript have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy. NR 34 TC 1 Z9 2 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1750-2640 J9 INFLUENZA OTHER RESP JI Influenza Other Respir. Viruses PD JAN PY 2013 VL 7 IS 1 BP 46 EP 54 DI 10.1111/j.1750-2659.2012.00346.x PG 9 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA 058QZ UT WOS:000312650000009 PM 22405508 ER PT J AU Tsong, Y Chen, J AF Tsong, Yi Chen, Jie TI Editors' Note on Special Issue on Medical Product Safety SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Editorial Material C1 [Tsong, Yi] US FDA, Silver Spring, MD USA. [Chen, Jie] Merck Serono Beijing Pharmaceut R&D Co, Beijing, Peoples R China. RP Tsong, Y (reprint author), US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 9 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PD JAN 1 PY 2013 VL 23 IS 1 SI SI BP 1 EP 2 DI 10.1080/10543406.2013.735760 PG 2 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 072OK UT WOS:000313681500001 PM 23331217 ER PT J AU Tsong, Y AF Tsong, Yi TI On the Designs of Thorough QT/QTc Clinical Trials SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Adaptive designs; Assay sensitivity; Imbalanced clinical trial; Sample size determination ID ISSUES AB A thorough QT trial is typically designed to test for two set of hypotheses. The primary set of hypotheses is for demonstrating that the test treatment will not prolong QT interval. The second set of hypotheses is to demonstrate the assay sensitivity of the positive control treatment in the study population. The conventional designs of thorough QT studies are parallel arms and crossover trials. Although the sample size requirements, the time points of analysis, and the durations of drug administration to reach a steady stage are all different between the test and positive control treatments, the trials are often designed with equal study duration and sample size for the different treatment arms or periods. In order to reduce the number of subjects needed for the parallel-arm thorough QT clinical trial, unconventional designs were proposed and used in the recent years. In this article, we review and discuss a few of the designs and propose some additional designs in the form of unbalanced, group sequential, and adaptive designs with the objective to improve trial efficiency or to reduce the risk of unnecessarily exposure of subjects to the potentially harmful positive control treatment. C1 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, Room 4628,Bldg 21,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM yi.tsong@cder.hhs.gov NR 13 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PD JAN 1 PY 2013 VL 23 IS 1 SI SI BP 43 EP 56 DI 10.1080/10543406.2013.735762 PG 14 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 072OK UT WOS:000313681500004 PM 23331220 ER PT J AU Tsong, Y Sun, AN Kang, SH AF Tsong, Yi Sun, Anna Kang, Seung-Ho TI Sample Size of Thorough QTc Clinical Trial Adjusted for Multiple Comparisons SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Assay sensitivity; Sample size determination; Type I error rate adjustment; Type II error rate adjustment ID MEASURED RESPONSE ISSUES; END-POINTS; QT/QTC; POWER; DESIGN AB A thorough QT trial is typically designed to test for two sets of hypotheses. The primary set of hypotheses is for demonstrating that the test treatment will not prolong QT interval. The second set of hypotheses is to demonstrate the assay sensitivity of the positive control treatment in the study population. Both analyses require multiple comparisons by testing the treatment difference measured repeatedly at multiple selected time points. Tsong and Zhong (2010) indicated that for prolongation testing, this involves an intersection-union test that leads to the reduction of study power. It requires type II error rate adjustment in order to maintain proper sample size and power of the test. Tsong et al. (2010) indicated also that the assay sensitivity analysis is carried out using a union-intersection test that leads to the inflation of the family-wise type I error rate. Type I error rate adjustment is required to control the family-wise type I error rate. Zhang and Machado () proposed the sample size calculation of test-placebo QT response difference based on simulation with a multivariate normal distribution model. Even though the results are generally used as guidance for sample size determination for balanced arm TQT trials, they are limited in generalization to various advanced and adaptive designs of TQT trials (Zhang, ; Tsong, ). In this article, we propose a power equation based on multivariate normal distribution of TQT trials. Sample sizes of various TQT designs can be obtained through numerical iteration of the equation. C1 [Tsong, Yi] US FDA, Div Biometr 6, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Sun, Anna] Univ Maryland Baltimore Cty, Dept Stat, Baltimore, MD 21228 USA. [Kang, Seung-Ho] Yonsei Univ, Dept Stat, Seoul 120749, South Korea. RP Tsong, Y (reprint author), US FDA, Div Biometr 6, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Room 4628,Bldg 21,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM yi.tsong@cder.hhs.gov NR 15 TC 1 Z9 1 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PD JAN 1 PY 2013 VL 23 IS 1 SI SI BP 57 EP 72 DI 10.1080/10543406.2013.735763 PG 16 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 072OK UT WOS:000313681500005 PM 23331221 ER PT J AU Dong, XY Ding, X Tsong, Y AF Dong, Xiaoyu Ding, Xiao Tsong, Yi TI Bayesian Approach to Assay Sensitivity Analysis of Thorough QT Trials SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Assay sensitivity; Bayesian; Bayesian significance; QT trial; Sample size AB One of the analyses recommended in ICH E14 Guidance (International Conference on Harmonisation, ) after the test drug is shown to be negative in QT interval prolongation after subjects treated with the test drug is an assay sensitivity analysis of a positive control drug with known effect on QT prolongation. The assay sensitivity is validated if the response profile is shown to be expected and the QT interval after administration of the positive control drug is shown to be at least 5 ms more than placebo. The negative result of the test treatment is validated if the prolongation of the positive control is verified among the study subjects. One of the most frequently used positive control drugs in thorough QT (TQT) trials is moxifloxacin. In order to improve the efficiency of the study and to reduce the number of subjects exposed to moxifloxacin, we explore the potential sample size reduction with a Bayesian approach to the assay sensitivity utilizing the data of historical TQT trials. We derived the distribution of moxifloxacin-induced QT prolongation based on 14 crossover trials and six parallel trials. The estimated distribution is used as a prior distribution to assess the posterior probability that the moxifloxacin-induced QT prolongation is larger than 5 ms. Sample size based on such Bayesian approach will be compared with the conventional frequentist approach for efficiency assessment. C1 [Dong, Xiaoyu] US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Dong, XY (reprint author), US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Room 3617,Bldg 21,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM xiaoyu.dong@fda.hhs.gov NR 6 TC 2 Z9 2 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PD JAN 1 PY 2013 VL 23 IS 1 SI SI BP 73 EP 81 DI 10.1080/10543406.2013.735764 PG 9 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 072OK UT WOS:000313681500006 PM 23331222 ER PT J AU Tsong, Y Yuan, MD Dong, XY Wu, YT Shen, MY AF Tsong, Yi Yuan, Mengdie Dong, Xiaoyu Wu, Yu-te Shen, Meiyu TI Comparing the Response Rates for Superiority, Noninferiority and Equivalence Testing with Multiple-to-One Matched Binary Data SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Adaptive; Discordant sets; McNamar test; Multiple-to-one matched binary data ID CONTROLLED CLINICAL-TRIALS; NON-INFERIORITY HYPOTHESES; SAMPLE-SIZE AB Paired and multiple-to-one matched data have often been collected in clinical trials and epidemiological safety studies. When the response is binary, the sample size and power are determined by the discordant pairs or matched sets. Fixed sample size determination in assessing response rate difference of superiority, noninferiority, and equivalence tests of paired binary data has been discussed by Lu and Bean ()Nam (), and Liu et al. (). We extend the results of Lu and Bean ()Nam (), and Liu et al. () to more general cases of multiple-to-one matched binary data. We further examine two issues regarding such tests. First, we examine the issue of simultaneous test and two-stage test for both superiority and noninferiority/equivalence hypotheses. Although, as discussed in Nam () and Liu et al. (), the standard errors restricted to null hypothesis are different between superiority and noninferiority test, the monotonic property of the two tests makes the simultaneous testing and switching between the hypotheses valid. Second, in practice, the joint distribution of matched responses is often unknown, and thus determining the sample size using only the background information of the control group could be inefficient. Furthermore, for noninferiority or equivalence tests, the sample sizes are often determined using the unrealistic alternative hypothesis that the response rates of both treatments are identical. We propose to use a two-stage adaptive design strategy for sample size reestimation that uses the interim information to improve the efficiency. C1 [Tsong, Yi] US FDA, Div Biometr 6, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Yuan, Mengdie] George Mason Univ, Dept Stat, Fairfax, VA 22030 USA. RP Tsong, Y (reprint author), US FDA, Div Biometr 6, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Room 4628,Bldg 21,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM yi.tsong@fda.hhs.gov NR 9 TC 0 Z9 0 U1 3 U2 11 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PD JAN 1 PY 2013 VL 23 IS 1 SI SI BP 98 EP 109 DI 10.1080/10543406.2013.735766 PG 12 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 072OK UT WOS:000313681500008 PM 23331224 ER PT J AU Levenson, MS Yue, LQ AF Levenson, Mark S. Yue, Lilly Q. TI Regulatory Issues of Propensity Score Methodology Application to Drug and Device Safety Studies SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Devices; Drugs; Observational study; Propensity scores; Safety evaluation ID CARDIAC-SURGERY; APROTININ; RISK; BIAS AB While randomized, well-controlled, clinical trials have been viewed as the gold standard in the evaluation of medical products, including drugs, biological products, and medical devices, it is not uncommon for safety assessment to be performed using observational studies, for ethical or practical reasons. In observational studies, various biases could be introduced in every stage and aspect of study, and consequently the resulting statistical inference may carry a lower level of scientific assurance, compared to randomized trials. To ensure the objectivity of study design and interpretability of the results, it is critical to address the challenges of such studies. In this paper, we share regulatory considerations on the prospective design of observational studies to address safety issues using propensity score methodology. C1 [Levenson, Mark S.; Yue, Lilly Q.] US FDA, Silver Spring, MD 20993 USA. RP Levenson, MS (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM mark.levenson@fda.hhs.gov; lilly.yue@fda.hhs.gov NR 30 TC 2 Z9 2 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PD JAN 1 PY 2013 VL 23 IS 1 SI SI BP 110 EP 121 DI 10.1080/10543406.2013.735778 PG 12 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 072OK UT WOS:000313681500009 PM 23331225 ER PT J AU McEvoy, BW Frimpong, EY AF McEvoy, Bradley W. Frimpong, Eric Y. TI Testing A Noninferiority Hypothesis: What to Anticipate when the Adverse Event is Rare SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Approximations; Drug safety; Noninferiority; Rare events; Sample size AB While randomized controlled trials may not be considered efficient for investigating rare adverse events based on their size, biases associated with other epidemiological designs may justify the additional resources. In certain contexts it may be appropriate, for example, to inflate the noninferiority (NI) margin to decrease the sample size, provided the excess risk that will be ruled out remains clinically relevant. The implication of a reduced sample size on the number of events anticipated from the trial is often not considered at the study design phase but may have important ramifications. To assess the implications of modifying study design parameters, approximations are presented for (a) how likely it is that no events will be observed, (b) how many events should be anticipated, and (c) how likely it is that v or more events will be observed. The approximations presented are intended to serve as tangible a priori expectations from the study. This work is motivated from an FDA Advisory Committee meeting regarding a discussion at the association between long-acting beta-agonists and asthma-related deaths. C1 [McEvoy, Bradley W.] US FDA, Div Biometr 7, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP McEvoy, BW (reprint author), US FDA, Div Biometr 7, Off Biostat, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Bradley.McEvoy@fda.hhs.gov NR 7 TC 0 Z9 0 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PD JAN 1 PY 2013 VL 23 IS 1 SI SI BP 122 EP 128 DI 10.1080/10543406.2013.735779 PG 7 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 072OK UT WOS:000313681500010 PM 23331226 ER PT J AU Chen, HC Tsong, Y Chen, JJ AF Chen, Hung-Chia Tsong, Yi Chen, James J. TI Data Mining for Signal Detection of Adverse Event Safety Data SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Biclustering and clustering analysis; Drug safety; Postmarketing surveillance ID GENE-EXPRESSION DATA; SPONTANEOUS REPORTING SYSTEMS; SINGULAR-VALUE DECOMPOSITION; MICROARRAY DATA; DRUG-REACTIONS; MATRIX; RATIOS AB The Adverse Event Reporting System (AERS) is the primary database designed to support the Food and Drug Administration (FDA) postmarketing safety surveillance program for all approved drugs and therapeutic biologic products. Most current disproportionality analysis focuses on the detection of potential adverse events (AE) involving a single drug and a single AE only. In this paper, we present a data mining biclustering technique based on the singular value decomposition to extract local regions of association for a safety study. The analysis consists of collection of biclusters, each representing an association between a set of drugs with the corresponding set of adverse events. Significance of each bicluster can be tested using disproportionality analysis. Individual drugevent combination can be further tested. A safety data set consisting of 193 drugs with 8453 adverse events is analyzed as an illustration. C1 [Chen, Hung-Chia; Chen, James J.] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR USA. [Chen, Hung-Chia] China Med Univ, Grad Inst Biostat, Taichung, Taiwan. [Chen, Hung-Chia] China Med Univ, Ctr Biostat, Taichung, Taiwan. [Tsong, Yi] US FDA, Off Biostat, DB6, Ctr Drug Evaluat Res, Silver Spring, MD USA. RP Chen, JJ (reprint author), 3900 NCTR Rd,HFT 20, Jefferson, AR 72079 USA. EM jamesj.chen@fda.hhs.gov NR 27 TC 3 Z9 3 U1 2 U2 18 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PD JAN 1 PY 2013 VL 23 IS 1 SI SI BP 146 EP 160 DI 10.1080/10543406.2013.735780 PG 15 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 072OK UT WOS:000313681500012 PM 23331228 ER PT J AU Huang, L Zalkikar, J Tiwari, RC AF Huang, Lan Zalkikar, Jyoti Tiwari, Ram C. TI Likelihood Ratio Test-Based Method for Signal Detection in Drug Classes Using FDA's AERS Database SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Drug class; Gadolinium drugs; Safety signals; Simplified Bayesian; Statin drugs; Weight matrix ID CERIVASTATIN; GENERATION; EVENTS AB In 1968 the Food and Drug Administration (FDA) established the Adverse Event Reporting System (AERS) database containing data on adverse events (AEs) reported by patients, health care providers, and other sources through a spontaneous reporting system. FDA uses AERS for monitoring the safety of the drugs on the market after approval. Most statistical methods that are available in the literature to analyze large postmarket drug safety data for identifying drugevent combinations with disproportionately high frequencies are designed to explore signals of a single drugAE combination, but not signals including a drug class or a group of AEs simultaneously. Those methods are also not designed to control type I error and are subject to high false discovery rates. In this paper, we first briefly review a recently developed method, known as the likelihood ratio test (LRT)-based method, which has been demonstrated to control the family-wise type I error and false discovery rates. By introducing a concept of weight matrix for the drugs (or for AEs), we then extend the LRT method for detecting signals including a class of drugs (or AEs) in addition to detecting signals of single drug (or AE). A simplified Bayesian method is also proposed and compared with LRT method. The proposed methods are applied to study the signal patterns of drug classes, namely, the gadolinium drug class for magnetic resonance imaging (MRI) and statins for hypercholesterolemia, over different time periods, using the datasets with only suspect drugs and with both suspect and concomitant drugs from the AERS database. The signals detected by the statistical methods can be confirmed by signals detected across different databases, existing medical evidence from research or regulatory resources, prospective biological studies, and also through simulation as illustrated in the application. C1 [Huang, Lan] US FDA, DBV, OB, CDER, Silver Spring, MD 20993 USA. RP Huang, L (reprint author), US FDA, DBV, OB, CDER, Silver Spring, MD 20993 USA. EM lan.huang@fda.hhs.gov NR 12 TC 4 Z9 4 U1 0 U2 9 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PD JAN 1 PY 2013 VL 23 IS 1 SI SI BP 178 EP 200 DI 10.1080/10543406.2013.736810 PG 23 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 072OK UT WOS:000313681500014 PM 23331230 ER PT J AU Kodell, RL Chen, JJ AF Kodell, Ralph L. Chen, James J. TI Quantitative Benefit-Risk Analysis for Evaluating Drug Therapies SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Adverse event; AUC; Drug withdrawal; ROC curve; Sensitive subpopulation AB Despite the fact that benefitrisk analysis is a necessary component of the review of new drugs for potential regulatory approval in the presence of known adverse side effects, and of the review of already-approved drugs for possible withdrawal from the market when unanticipated adverse events are discovered, formal quantitative tools for benefitrisk analysis are few. This paper proposes a quantitative method that utilizes receiver operating characteristic (ROC) curves to find an optimal dose of a drug that maximizes the differential between the benefit of the intended effect and the risk of adverse side effects, where costs associated with lack of benefit and risk can be incorporated. The method can be applied separately to subpopulations of different sensitivities and to different adverse events to give a full picture of the trade-offs between the benefit afforded by the drug and the risk it incurs, and potentially to allow the drug to be approved only selectively for specific subpopulations, or at different doses for different subpopulations. C1 [Kodell, Ralph L.] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. [Chen, James J.] Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. RP Kodell, RL (reprint author), Univ Arkansas Med Sci, Dept Biostat, 4301 W Markham St, Little Rock, AR 72205 USA. EM rlkodell@uams.edu FU FDA [HHSF223201010733P] FX The first author's work was supported by FDA purchase order no. HHSF223201010733P. NR 16 TC 1 Z9 1 U1 2 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PD JAN 1 PY 2013 VL 23 IS 1 SI SI BP 231 EP 238 DI 10.1080/10543406.2013.735785 PG 8 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 072OK UT WOS:000313681500017 PM 23331233 ER PT J AU McLawhorn, MW Goulding, MR Gill, RK Michele, TM AF McLawhorn, Melinda W. Goulding, Margie R. Gill, Rajdeep K. Michele, Theresa M. TI Analysis of Benzonatate Overdoses Among Adults and Children from 1969-2010 by the United States Food and Drug Administration SO PHARMACOTHERAPY LA English DT Article DE benzonatate; Tessalon; antitussive agents; poisoning; overdose; prevention; child; infant; accidental ingestion ID COUGH AB Study Objective To augment the December 2010 United States Food and Drug Administration (FDA) Drug Safety Communication on accidental ingestion of benzonatate in children less than 10 years old by summarizing data on emergency department visits, benzonatate exposure, and reports of benzonatate overdoses from several data sources. Design Retrospective review of adverse-event reports and drug utilization data of benzonatate. Data Sources The FDA Adverse Event Reporting System (AERS) database (19692010), the National Electronic Injury Surveillance SystemCooperative Adverse Drug Event Surveillance Project (NEISS-CADES, 20042009), and the IMS commercial data vendor (20042009). Patients Any patient who reported an adverse event with benzonatate captured in the AERS or NEISS-CADES database or received a prescription for benzonatate according to the IMS commercial data vendor. Measurements and Main Results Postmarketing adverse events with benzonatate were collected from the AERS database, emergency department visits due to adverse events with benzonatate were collected from the NEISS-CADES database, and outpatient drug utilization data were collected from the IMS commercial data vendor. Of 31 overdose cases involving benzonatate reported in the AERS database, 20 had a fatal outcome, and five of these fatalities occurred from accidental ingestions in children 2 years of age and younger. The NEISS-CADES database captured emergency department visits involving 12 cases of overdose from accidental benzonatate ingestions in children aged 13 years. Signs and symptoms of overdose included seizures, cardiac arrest, coma, brain edema or anoxic encephalopathy, apnea, tachycardia, and respiratory arrest and occurred in some patients within 15 minutes of ingestion. Dispensed benzonatate prescriptions increased by approximately 52% from 2004 to 2009. Conclusion Although benzonatate has a long history of safe use, accumulating cases of fatal overdose, especially in children, prompted the FDA to notify health care professionals about the risks of benzonatate overdose. Pharmacists may have a role in preventing benzonatate overdoses by counseling patients on signs and symptoms of benzonatate overdose, the need for immediate medical care, and safe storage and disposal of benzonatate. C1 [McLawhorn, Melinda W.] US FDA, Div Pharmacovigilance 1, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Goulding, Margie R.; Gill, Rajdeep K.] US FDA, Div Epidemiol 2, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Michele, Theresa M.] US FDA, Off Pharmacovigilance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Michele, Theresa M.] US FDA, Div Pulm Allergy & Rheumatol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP McLawhorn, MW (reprint author), LCDR US Publ Hlth Serv, Div Prescript Drug Promot, US FDA, Ctr Drug Evaluat & Res,Off Prescript Drug Promot, 10903 New Hampshire Ave,Bldg 51,Room 3254, Silver Spring, MD 20993 USA. EM melinda.mclawhorn@fda.hhs.gov FU United States Food and Drug Administration FX This study was supported by the United States Food and Drug Administration. NR 12 TC 5 Z9 5 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD JAN PY 2013 VL 33 IS 1 BP 38 EP 43 DI 10.1002/phar.1153 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 070PW UT WOS:000313523400008 PM 23307543 ER PT J AU Miller, MA Tong, WD Fan, XH Slikker, W AF Miller, Margaret A. Tong, Weida Fan, Xiaohui Slikker, William, Jr. TI 2012 Global Summit on Regulatory Science (GSRS-2012) - Modernizing Toxicology SO TOXICOLOGICAL SCIENCES LA English DT Editorial Material DE regulatory science; food safety; toxicogenomics; global public health AB Regulatory science encompasses the tools, models, techniques, and studies needed to assess and evaluate product safety, efficacy, quality, and performance. Several recent publications have emphasized the role of regulatory science in improving global health, supporting economic development and fostering innovation. As for other scientific disciplines, research in regulatory science is the critical element underpinning the development and advancement of regulatory science as a modern scientific discipline. As a regulatory agency in the 21st century, the Food and Drug Administration (FDA) has an international component that underpins its domestic mission; foods, drugs, and devices are developed and imported to the United States from across the world. The Global Summit on Regulatory Science, an international conference for discussing innovative technologies, approaches, and partnerships that enhance the translation of basic science into regulatory applications, is providing leadership for the advancement of regulatory sciences within the global context. Held annually, this international conference provides a platform where regulators, policy makers, and bench scientists from various countries can exchange views on how to develop, apply, and implement innovative methodologies into regulatory assessments in their respective countries, as well as developing a harmonized strategy to improve global public health through global collaboration. C1 [Miller, Margaret A.; Tong, Weida; Slikker, William, Jr.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Fan, Xiaohui] Zhejiang Univ, Sch Pharmaceut Sci, Pharmaceut Informat Inst, Hangzhou 310058, Peoples R China. RP Slikker, W (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Dr,HFT 1, Jefferson, AR 72079 USA. EM william.slikker@fda.hhs.gov NR 2 TC 3 Z9 4 U1 0 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JAN PY 2013 VL 131 IS 1 BP 9 EP 12 DI 10.1093/toxsci/kfs254 PG 4 WC Toxicology SC Toxicology GA 072EV UT WOS:000313652900002 PM 22923489 ER PT J AU Boudreau, MD Mellick, PW Olson, GR Felton, RP Thorn, BT Beland, FA AF Boudreau, Mary D. Mellick, Paul W. Olson, Greg R. Felton, Robert P. Thorn, Brett T. Beland, Frederick A. TI Clear Evidence of Carcinogenic Activity by a Whole-Leaf Extract of Aloe barbadensis Miller (Aloe vera) in F344/N Rats SO TOXICOLOGICAL SCIENCES LA English DT Article DE natural products; metabolism; histopathology; chronic; gastrointestinal; carcinogenesis; dietary supplement; Aloe vera; Aloe barbadensis Miller; colon cancer; rodents ID VAR. NATALENSIS BERGER; ABERRANT CRYPT FOCI; INTESTINAL BACTERIA; TRANSFORMING BARBALOIN; GASTROINTESTINAL-TRACT; ANTHRANOID LAXATIVES; COLORECTAL-CANCER; CHRONIC TOXICITY; EMODIN ANTHRONE; LYMPHOID-TISSUE AB Aloe barbadensis Miller (Aloe vera) is an herbal remedy promoted to treat a variety of illnesses; however, only limited data are available on the safety of this dietary supplement. Drinking water exposure of F344/N rats and B6C3F1 mice to an Aloe vera whole-leaf extract (1, 2, and 3%) for 13 weeks resulted in goblet cell hyperplasia of the large intestine in both species. Based upon this observation, 2-year drinking water studies were conducted to assess the carcinogenic potential of an Aloe vera whole-leaf extract when administered to F344/N rats (48 per sex per group) at 0.5, 1, and 1.5%, and B6C3F1 mice (48 per sex per group) at 1, 2, and 3%. Compared with controls, survival was decreased in the 1.5% dose group of female rats. Treatment-related neoplasms and nonneoplastic lesions in both species were confined primarily to the large intestine. Incidences of adenomas and/or carcinomas of the ileo-cecal and cecal-colic junction, cecum, and ascending and transverse colon were significantly higher than controls in male and female rats in the 1 and 1.5% dose groups. There were no neoplasms of the large intestine in mice or in the 0 or 0.5% dose groups of rats. Increased incidences of mucosa hyperplasia of the large intestine were observed in F344/N rats, and increased incidences of goblet cell hyperplasia of the large intestine occurred in B6C3F1 mice. These results indicate that Aloe vera whole-leaf extract is an intestinal irritant in F344/N rats and B6C3F1 mice and a carcinogen of the large intestine in F344/N rats. C1 [Boudreau, Mary D.; Beland, Frederick A.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Mellick, Paul W.; Olson, Greg R.] US FDA, Toxicol Pathol Associates, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Felton, Robert P.; Thorn, Brett T.] US FDA, Div Bioinformat & Biostatist, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Boudreau, MD (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM mary.boudreau@fda.hhs.gov FU National Center for Toxicological Research/Food and Drug Administration [224-12-0003, AES12013]; National Institute of Environmental Health Sciences [224-12-0003, AES12013] FX Interagency Agreement Nos. 224-12-0003 and AES12013 between the National Center for Toxicological Research/Food and Drug Administration and the National Institute of Environmental Health Sciences/National Toxicology Program. NR 89 TC 12 Z9 12 U1 0 U2 27 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JAN PY 2013 VL 131 IS 1 BP 26 EP 39 DI 10.1093/toxsci/kfs275 PG 14 WC Toxicology SC Toxicology GA 072EV UT WOS:000313652900004 PM 22968693 ER PT J AU Desai, VG Herman, EH Moland, CL Branham, WS Lewis, SM Davis, KJ George, NI Lee, T Kerr, S Fuscoe, JC AF Desai, Varsha G. Herman, Eugene H. Moland, Carrie L. Branham, William S. Lewis, Sherry M. Davis, Kelly J. George, Nysia I. Lee, Taewon Kerr, Susan Fuscoe, James C. TI Development of doxorubicin-induced chronic cardiotoxicity in the B6C3F(1) mouse model SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Doxorubicin; Cardiac troponin T; Cardiac lesions; Hematotoxicity; Male B6C3F(1) mice ID CARDIAC TROPONIN-T; MITOCHONDRIA-RELATED GENES; BREAST-CANCER PATIENTS; INDUCED CARDIOMYOPATHY; MYOCARDIAL DAMAGE; ANTHRACYCLINE CARDIOMYOPATHY; ADRIAMYCIN CARDIOTOXICITY; HEPATOCELLULAR-CARCINOMA; EXPRESSION PROFILE; HYPERTENSIVE-RATS AB Serum levels of cardiac troponins serve as biomarkers of myocardial injury. However, troponins are released into the serum only after damage to cardiac tissue has occurred. Here, we report development of a mouse model of doxorubicin (DOX)-induced chronic cardiotoxicity to aid in the identification of predictive biomarkers of early events of cardiac tissue injury. Male B6C3F(1) mice were administered intravenous DOX at 3 mg/kg body weight, or an equivalent volume of saline, once a week for 4, 6, 8, 10, 12, and 14 weeks, resulting in cumulative DOX doses of 12, 18, 24, 30, 36, and 42 mg/kg, respectively. Mice were sacrificed a week following the last dose. A significant reduction in body weight gain was observed in mice following exposure to a weekly DOX dose for 1 week and longer compared to saline-treated controls. DOX treatment also resulted in declines in red blood cell count, hemoglobin level, and hematocrit compared to saline-treated controls after the 2nd weekly dose until the 8th and 9th doses, followed by a modest recovery. All DOX-treated mice had significant elevations in cardiac troponin T concentrations in plasma compared to saline-treated controls, indicating cardiac tissue injury. Also, a dose-related increase in the severity of cardiac lesions was seen in mice exposed to 24 mg/kg DOX and higher cumulative doses. Mice treated with cumulative DOX doses of 30 mg/kg and higher showed a significant decline in heart rate, suggesting drug-induced cardiac dysfunction. Altogether, these findings demonstrate the development of DOX-induced chronic cardiotoxicity in B6C3F(1) mice. Published by Elsevier Inc. C1 [Desai, Varsha G.; Moland, Carrie L.; Branham, William S.; Fuscoe, James C.] US FDA, Personalized Med Branch, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Herman, Eugene H.] US FDA, Div Drug Safety Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Lewis, Sherry M.] US FDA, Off Sci Coordinat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Toxicol Pathol Associates, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [George, Nysia I.] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Lee, Taewon] Korea Univ, Dept Math & Informat, Jochiwon 339700, Chungnam, South Korea. [Kerr, Susan] Arkansas Heart Hosp, Little Rock, AR 72211 USA. RP Desai, VG (reprint author), US FDA, Personalized Med Branch, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM varsha.desai@fda.hhs.gov NR 94 TC 25 Z9 25 U1 0 U2 14 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 JAN 1 PY 2013 VL 266 IS 1 BP 109 EP 121 DI 10.1016/j.taap.2012.10.025 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 069YY UT WOS:000313474200013 PM 23142469 ER PT J AU Mahmood, I AF Mahmood, Iftekhar TI Evaluation of Sigmoidal Maturation and Allometric Models: Prediction of Propofol Clearance in Neonates and Infants SO AMERICAN JOURNAL OF THERAPEUTICS LA English DT Article DE allometry; maturation model; pediatrics; clearance ID UNIVERSAL METABOLIC ALLOMETRY; DRUG CLEARANCE; PHARMACOKINETICS; CHILDREN; EXPONENT; ONTOGENY; PATHWAYS; ADULTS; RATES; SIZE AB The main objectives of this report are to predict propofol clearance in neonates and infants by a maturation model that includes age and weight and to compare the predictive performance of propofol maturation model with a simple allometric model (clearance vs. body weight). Age, weight, and propofol clearance data were obtained from the literature. A maturation model for propofol was developed using data from neonates, toddlers, children, adolescents, and adults (N = 71). The allometric model was developed using the same data as the maturation model. The predicted clearance of propofol in an individual neonate or infant from these models was compared with the observed clearance (16 neonates and 22 infants) in that individual neonate or infant. The prediction of propofol clearance in most of the individual neonates or infants by both maturation and allometric models was poor. However, the mean predicted propofol clearance in the neonates by both models was comparable with the observed clearance, but the mean predicted propofol clearance in the infants was underpredicted by both models. The propofol maturation and simple allometric model performed poorly for the prediction of propofol clearance in individual neonate and infant. C1 US FDA, Off Blood Review & Res, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Off Blood Review & Res, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM iftekhar.mahmood@fda.hhs.gov NR 24 TC 4 Z9 4 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1075-2765 J9 AM J THER JI Am. J. Ther. PD JAN PY 2013 VL 20 IS 1 BP 21 EP 28 DI 10.1519/JSC.0b013e31823b087a PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 069BO UT WOS:000313410100004 PM 23299229 ER PT J AU Kuhn, JH Bao, YM Bavari, S Becker, S Bradfute, S Brister, JR Bukreyev, AA Chandran, K Davey, RA Dolnik, O Dye, JM Enterlein, S Hensley, LE Honko, AN Jahrling, PB Johnson, KM Kobinger, G Leroy, EM Lever, MS Muhlberger, E Netesov, SV Olinger, GG Palacios, G Patterson, JL Paweska, JT Pitt, L Radoshitzky, SR Saphire, EO Smither, SJ Swanepoel, R Towner, JS van der Groen, G Volchkov, VE Wahl-Jensen, V Warren, TK Weidmann, M Nichol, ST AF Kuhn, Jens H. Bao, Yiming Bavari, Sina Becker, Stephan Bradfute, Steven Brister, J. Rodney Bukreyev, Alexander A. Chandran, Kartik Davey, Robert A. Dolnik, Olga Dye, John M. Enterlein, Sven Hensley, Lisa E. Honko, Anna N. Jahrling, Peter B. Johnson, Karl M. Kobinger, Gary Leroy, Eric M. Lever, Mark S. Muehlberger, Elke Netesov, Sergey V. Olinger, Gene G. Palacios, Gustavo Patterson, Jean L. Paweska, Janusz T. Pitt, Louise Radoshitzky, Sheli R. Saphire, Erica Ollmann Smither, Sophie J. Swanepoel, Robert Towner, Jonathan S. van der Groen, Guido Volchkov, Viktor E. Wahl-Jensen, Victoria Warren, Travis K. Weidmann, Manfred Nichol, Stuart T. TI Virus nomenclature below the species level: a standardized nomenclature for natural variants of viruses assigned to the family Filoviridae SO ARCHIVES OF VIROLOGY LA English DT Article ID TAXONOMY; NAMES; IDENTIFICATION; VIROLOGISTS; EBOLAVIRUS; PROPOSAL AB The task of international expert groups is to recommend the classification and naming of viruses. The International Committee on Taxonomy of Viruses Filoviridae Study Group and other experts have recently established an almost consistent classification and nomenclature for filoviruses. Here, further guidelines are suggested to include their natural genetic variants. First, this term is defined. Second, a template for full-length virus names (such as "Ebola virus H.sapiens-tc/COD/1995/Kikwit-9510621") is proposed. These names contain information on the identity of the virus (e.g., Ebola virus), isolation host (e.g., members of the species Homo sapiens), sampling location (e.g., Democratic Republic of the Congo (COD)), sampling year, genetic variant (e.g., Kikwit), and isolate (e.g., 9510621). Suffixes are proposed for individual names that clarify whether a given genetic variant has been characterized based on passage zero material (-wt), has been passaged in tissue/cell culture (-tc), is known from consensus sequence fragments only (-frag), or does (most likely) not exist anymore (-hist). We suggest that these comprehensive names are to be used specifically in the methods section of publications. Suitable abbreviations, also proposed here, could then be used throughout the text, while the full names could be used again in phylograms, tables, or figures if the contained information aids the interpretation of presented data. The proposed system is very similar to the well-known influenzavirus nomenclature and the nomenclature recently proposed for rotaviruses. If applied consistently, it would considerably simplify retrieval of sequence data from electronic databases and be a first important step toward a viral genome annotation standard as sought by the National Center for Biotechnology Information (NCBI). Furthermore, adoption of this nomenclature would increase the general understanding of filovirus-related publications and presentations and improve figures such as phylograms, alignments, and diagrams. Most importantly, it would counter the increasing confusion in genetic variant naming due to the identification of ever more sequences through technological breakthroughs in high-throughput sequencing and environmental sampling. C1 [Kuhn, Jens H.; Jahrling, Peter B.; Wahl-Jensen, Victoria] NIAID, Integrated Res Facil Ft Detrick IRF Frederick, Div Clin Res DCR, NIH, Frederick, MD USA. [Bao, Yiming; Brister, J. Rodney] Natl Lib Med, Informat Engn Branch, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD USA. [Bavari, Sina; Dye, John M.; Honko, Anna N.; Olinger, Gene G.; Palacios, Gustavo; Pitt, Louise; Radoshitzky, Sheli R.; Warren, Travis K.] USA, Med Res Inst Infect Dis, Frederick, MD USA. [Becker, Stephan; Dolnik, Olga] Univ Marburg, Inst Virol, D-35032 Marburg, Germany. [Bradfute, Steven] Univ New Mexico, Albuquerque, NM 87131 USA. [Bukreyev, Alexander A.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Chandran, Kartik] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. [Davey, Robert A.; Patterson, Jean L.] Texas Biomed Res Inst, Dept Virol & Immunol, San Antonio, TX USA. [Enterlein, Sven] Integrated BioTherapeut Inc, Gaithersburg, MD USA. [Hensley, Lisa E.] Fed Drug Adm, Med Countermeasure Initiat, Silver Spring, MD USA. [Kobinger, Gary] Publ Hlth Agcy Canada, Natl Microbiol Lab, Special Pathogens Program, Winnipeg, MB, Canada. [Leroy, Eric M.] Ctr Int Rech Med Franceville, Franceville, Gabon. [Lever, Mark S.; Smither, Sophie J.] Dstl, Dept Biomed Sci, Porton Down, Salisbury, Wilts, England. [Muehlberger, Elke] Univ Sch Med, Natl Emerging Infect Dis Lab, Boston, MA USA. [Netesov, Sergey V.] Novosibirsk State Univ, Novosibirsk 630090, Novosibirsk Obl, Russia. [Paweska, Janusz T.] Natl Hlth Lab Serv, Natl Inst Communicable Dis, Ctr Emerging & Zoonot Dis, Johannesburg, Gauteng, South Africa. [Saphire, Erica Ollmann] Scripps Res Inst, Dept Immunol & Microbial Sci, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. [Swanepoel, Robert] Univ Pretoria, Zoonoses Res Unit, ZA-0002 Pretoria, South Africa. [Towner, Jonathan S.; Nichol, Stuart T.] Ctr Dis Control & Prevent, Viral Special Pathogens Branch, Div High Consequence Pathogens Pathol, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA. [van der Groen, Guido] Prins Leopold Inst Trop Geneeskunde, Antwerp, Belgium. [Volchkov, Viktor E.] Univ Lyon, Lab Filovirus, Ecole Normale Super Lyon, INSERM,U758,UCB Lyon 1, Lyon, France. [Weidmann, Manfred] Univ Med Gottingen, Abt Virol, Gottingen, Germany. RP Kuhn, JH (reprint author), NIAID, Integrated Res Facil Ft Detrick IRF Frederick, Div Clin Res DCR, NIH, B-8200 Res Plaza, Frederick, MD USA. EM kuhnjens@mail.nih.gov; stn1@cdc.gov RI LEROY, Eric/I-4347-2016; Netesov, Sergey/A-3751-2013; Volchkov, Viktor/M-7846-2014; Kuhn, Jens H./B-7615-2011; Becker, Stephan/A-1065-2010; Palacios, Gustavo/I-7773-2015; Weidmann, Manfred/G-1817-2015; OI Honko, Anna/0000-0001-9165-148X; LEROY, Eric/0000-0003-0022-0890; Muhlberger, Elke/0000-0003-3547-9376; Netesov, Sergey/0000-0002-7786-2464; Volchkov, Viktor/0000-0001-7896-8706; Kuhn, Jens H./0000-0002-7800-6045; Becker, Stephan/0000-0002-2794-5659; Palacios, Gustavo/0000-0001-5062-1938; Weidmann, Manfred/0000-0002-7063-7491; Olinger, Gene/0000-0001-7338-0292 FU Joint Science and Technology Office for Chem Bio Defense [TMTI0048_09_RD_T]; NIAID [HHSN272200200016I]; NIH, National Library of Medicine FX The content of this publication does not necessarily reflect the views or policies of the US Department of the Army, the US Department of Defense or the US Department of Health and Human Services or of the institutions and companies affiliated with the authors. This work was funded in part by the Joint Science and Technology Office for Chem Bio Defense (proposal #TMTI0048_09_RD_T to SB). JHK and VWJ performed this work as employees of Tunnell Consulting, Inc., a subcontractor to Battelle Memorial Institute under its prime contract with NIAID, under Contract No. HHSN272200200016I. This research was also supported in part by the Intramural Research Program of the NIH, National Library of Medicine (YB and JRB). NR 36 TC 49 Z9 50 U1 2 U2 32 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0304-8608 EI 1432-8798 J9 ARCH VIROL JI Arch. Virol. PD JAN PY 2013 VL 158 IS 1 BP 301 EP 311 DI 10.1007/s00705-012-1454-0 PG 11 WC Virology SC Virology GA 067KY UT WOS:000313294200042 PM 23001720 ER PT J AU Crossman, LC Chen, H Cerdeno-Tarraga, AM Brooks, K Quail, MA Pineiro, SA Hobley, L Sockett, RE Bentley, SD Parkhill, J Williams, HN Stine, OC AF Crossman, Lisa C. Chen, Huan Cerdeno-Tarraga, Ana-M Brooks, Karen Quail, Michael A. Pineiro, Silvia A. Hobley, Laura Sockett, R. Elizabeth Bentley, Stephen D. Parkhill, Julian Williams, Henry N. Stine, O. Colin TI A small predatory core genome in the divergent marine Bacteriovorax marinus SJ and the terrestrial Bdellovibrio bacteriovorus SO ISME JOURNAL LA English DT Article DE Bacteriovorax; Bdellovibrio; genome sequence; BALO; subtractive hybridization; host-interaction locus ID ESCHERICHIA-COLI; LIFE-CYCLE; INTRAPERIPLASMIC GROWTH; PREY INTERACTIONS; COMB. NOV.; IV PILI; SEQUENCE; DIVERSITY; IDENTIFICATION; SYSTEM AB Bacteriovorax marinus SJ is a predatory delta-proteobacterium isolated from a marine environment. The genome sequence of this strain provides an interesting contrast to that of the terrestrial predatory bacterium Bdellovibrio bacteriovorus HD100. Based on their predatory lifestyle, Bacteriovorax were originally designated as members of the genus Bdellovibrio but subsequently were re-assigned to a new genus and family based on genetic and phenotypic differences. B. marinus attaches to Gram-negative bacteria, penetrates through the cell wall to form a bdelloplast, in which it replicates, as shown using microscopy. Bacteriovorax is distinct, as it shares only 30% of its gene products with its closest sequenced relatives. Remarkably, 34% of predicted genes over 500 nt in length were completely unique with no significant matches in the databases. As expected, Bacteriovorax shares several characteristic loci with the other delta-proteobacteria. A geneset shared between Bacteriovorax and Bdellovibrio that is not conserved among other delta-proteobacteria such as Myxobacteria (which destroy prey bacteria externally via lysis), or the non-predatory Desulfo-bacteria and Geobacter species was identified. These 291 gene orthologues common to both Bacteriovorax and Bdellovibrio may be the key indicators of host-interaction predatory-specific processes required for prey entry. The locus from Bdellovibrio bacteriovorus is implicated in the switch from predatory to prey/host-independent growth. Although the locus is conserved in B. marinus, the sequence has only limited similarity. The results of this study advance understanding of both the similarities and differences between Bdellovibrio and Bacteriovorax and confirm the distant relationship between the two and their separation into different families. The ISME Journal (2013) 7, 148-160; doi:10.1038/ismej.2012.90; published online 6 September 2012 C1 [Crossman, Lisa C.] Genome Anal Ctr, Dept Bioinformat, Norwich NR4 7UH, Norfolk, England. [Crossman, Lisa C.] Univ E Anglia, Sch Biol Sci, Norwich NR4 7TJ, Norfolk, England. [Chen, Huan; Williams, Henry N.] Florida A&M Univ, Sch Environm, Tallahassee, FL 32307 USA. [Cerdeno-Tarraga, Ana-M] European Bioinformat Inst, ENA, Hinxton, England. [Brooks, Karen; Quail, Michael A.; Bentley, Stephen D.; Parkhill, Julian] Wellcome Trust Sanger Inst, Hinxton, England. [Pineiro, Silvia A.] US FDA, Rockville, MD 20857 USA. [Hobley, Laura; Sockett, R. Elizabeth] Univ Nottingham, Sch Biol, Nottingham NG7 2RD, England. [Stine, O. Colin] Univ Maryland, Dept Epidemiol, Baltimore, MD 21201 USA. RP Crossman, LC (reprint author), Genome Anal Ctr, Dept Bioinformat, Norwich Res Pk, Norwich NR4 7UH, Norfolk, England. EM lisa.crossman@bbsrc.ac.uk RI Parkhill, Julian/G-4703-2011; OI Parkhill, Julian/0000-0002-7069-5958; Cerdeno-Tarraga, Ana M./0000-0001-6635-3237 FU Wellcome Trust; National Science Foundation award [HRD 0932137]; BBSRC UK [G003092/1]; BBSRC; East of England Development Agency, Norfolk County, Norwich City; South Norfolk Councils; Greater Norwich Development Partnership, UK FX Sequencing and annotation of Bacteriovorax marinus SJ was funded by the Wellcome Trust. Microscopy was supported by National Science Foundation award HRD 0932137 to HW and by BBSRC UK G003092/1 to RES. LC is funded by BBSRC in partnership with East of England Development Agency, Norfolk County, Norwich City and South Norfolk Councils and the Greater Norwich Development Partnership, UK. The complete manually annotated chromosome of Bacteriovorax marinus SJ is available at FQ312005; plasmid pBMS1 has been assigned accession number HE610506. NR 73 TC 18 Z9 19 U1 3 U2 28 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1751-7362 J9 ISME J JI ISME J. PD JAN PY 2013 VL 7 IS 1 BP 148 EP 160 DI 10.1038/ismej.2012.90 PG 13 WC Ecology; Microbiology SC Environmental Sciences & Ecology; Microbiology GA 066QT UT WOS:000313236000013 PM 22955231 ER PT J AU Van Kessel, JS Sonnier, J Zhao, S Karns, JS AF Van Kessel, J. S. Sonnier, J. Zhao, S. Karns, J. S. TI Antimicrobial Resistance of Salmonella enterica Isolates from Bulk Tank Milk and Milk Filters in the United States SO JOURNAL OF FOOD PROTECTION LA English DT Article ID FIELD GEL-ELECTROPHORESIS; LACTATING DAIRY-CATTLE; ESCHERICHIA-COLI O157-H7; RAW-MILK; LISTERIA-MONOCYTOGENES; FOOD ANIMALS; US DAIRIES; FOODBORNE ILLNESS; PREVALENCE; TYPHIMURIUM AB Salmonella isolates were recovered from bulk tank milk as part of the National Animal Health Monitoring System (NAHMS) Dairy 2002 and 2007 surveys. In-line milk filters were also tested in the 2007 survey. The objective of this study was to determine the prevalence of antimicrobial resistance among Salmonella enterica isolates from bulk milk and milk filters in the NAHMS Dairy 2002 and. 2007 surveys and to further characterize resistant isolates. Susceptibilities to 15 antibiotics were determined for 176 Salmonella isolates of 26 serotypes using an automated antimicrobial susceptibility system. Resistant isolates were screened by PCR for the presence of the extended-spectrum beta-lactamase (bla(CMY)) gene and class I integrons and further characterized by pulsed-field gel electrophoresis. Thirty isolates (17.0%) representing six S. enterica serotypes exhibited resistance to at least one antimicrobial agent (serotypes Newport [14 of 14 isolates exhibited resistance], Dublin [7 of 7], Typhimurium [3 of 5], Kentucky [4 of 22], Anatum [1 of 13], and Infantis [1 of 2]). Twenty isolates (11.4%), including all 14 Newport, 3 Dublin, 2 Typhimurium, and 1 Infantis isolate, displayed the typical multidrug-resistant, bla(CMY)-positive (MDR-AmpC) phenotype which included resistance to ampicillin, chloramphenicol, streptomycin, sulfonamide, and tetracycline, plus resistance to amoxicillin-clavulanic acid and extended-spectrum cephalosporins. Five of the MDR-AmpC isolates carried class I integrons (2.8%). Two-enzyme (XbaI and BlnI) pulsed-field gel electrophoresis discerned clades within serotypes and, together with the resistance profiles, identified strains that appeared to have persisted temporally and geographically. These results suggest that there is a low but appreciable risk of infection with MDR Salmonella from consumption of nonpasteurized milk and dairy products. C1 [Van Kessel, J. S.; Sonnier, J.; Karns, J. S.] USDA ARS, Environm Microbial & Food Safety Lab, Anim & Nat Resources Inst, Beltsville, MD 20705 USA. [Zhao, S.] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Van Kessel, JS (reprint author), USDA ARS, Environm Microbial & Food Safety Lab, Anim & Nat Resources Inst, 10300 Baltimore Ave,BARC E Bldg 173, Beltsville, MD 20705 USA. EM joann.vankessel@ars.usda.gov NR 55 TC 6 Z9 6 U1 1 U2 37 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JAN PY 2013 VL 76 IS 1 BP 18 EP 25 DI 10.4315/0362-028X.JFP-12-263 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 068UM UT WOS:000313391700003 PM 23317852 ER PT J AU Jones, YL Peters, SM Weland, C Ivanova, NV Yancy, HF AF Jones, Yolanda L. Peters, Sharla M. Weland, Chris Ivanova, Natalia V. Yancy, Haile F. TI Potential Use of DNA Barcodes in Regulatory Science: Identification of the US Food and Drug Administration's "Dirty 22," Contributors to the Spread of Foodborne Pathogens SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ACTION CRITERIA; FISH; ACARI; TAXONOMY; SEQUENCES; DIFFERENTIATION; CLASSIFICATION; POLYMORPHISM; LEPIDOPTERA; DISTINGUISH AB The U.S. Food, Drug, and Cosmetic Act prohibits the distribution of food that is adulterated, and the regulatory mission of the U.S. Food and Drug Administration (FDA) is to enforce this Act. FDA field laboratories have identified the 22 most common pests that contribute to the spread of foodborne disease (the "Dirty 22"). The current method of detecting filth and extraneous material (tails, legs, carcasses, etc.) is visual inspection using microscopy. Because microscopy can be time-consuming and may yield inaccurate and/or nonspecific results due to lack of expertise, an alternative method of detecting these adulterants is needed. In this study, we sequenced DNA from the 5' region of the cytochrome oxidase I gene of these 22 common pests that contribute to the spread of foodborne pathogens. Here, we describe the generation of DNA barcodes for all 22 species. To date, this is the first attempt to develop a sequence-based regulatory database and systematic primer strategy to identify these FDA-targeted species. DNA barcoding can be a powerful tool that can aid the FDA in promoting the protection and safety of the U.S. food supply. C1 [Jones, Yolanda L.; Peters, Sharla M.; Yancy, Haile F.] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. [Weland, Chris; Ivanova, Natalia V.] Univ Guelph, Biodivers Inst Ontario, Canadian Ctr DNA Barcoding, Guelph, ON N1G 2W1, Canada. RP Jones, YL (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM yolanda.jones@fda.hhs.gov NR 61 TC 5 Z9 6 U1 1 U2 36 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X EI 1944-9097 J9 J FOOD PROTECT JI J. Food Prot. PD JAN PY 2013 VL 76 IS 1 BP 144 EP 149 DI 10.4315/0362-028X.JFP-12-168 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 068UM UT WOS:000313391700022 PM 23317871 ER PT J AU Calvo, MS Babu, US Garthoff, LH Woods, TO Dreher, M Hill, G Nagaraja, S AF Calvo, M. S. Babu, U. S. Garthoff, L. H. Woods, T. O. Dreher, M. Hill, G. Nagaraja, S. TI Vitamin D-2 from light-exposed edible mushrooms is safe, bioavailable and effectively supports bone growth in rats SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE Bioavailability; Microarchitecture; Microcomputed tomography; Safety; Trabecular bone; Vitamin D2; White button mushrooms ID SERUM 25-HYDROXYVITAMIN D; ULTRAVIOLET-IRRADIATION; AGARICUS-BISPORUS; BUTTON MUSHROOMS; CANCELLOUS BONE; UNITED-STATES; CHOLECALCIFEROL; ERGOCALCIFEROL; METABOLISM; TOXICITY AB Widespread poor vitamin D status, a health risk for bone disease, increases the need for new food sources of vitamin D. Light-exposed edible mushrooms synthesize vitamin D-2. Bioavailability, safety, and efficacy of high levels of vitamin D-2 from mushrooms to support bone health was established in chronically fed growing rats. Poor vitamin D status from reduced sun exposure is made worse by limited access to vitamin D-containing foods. Exposing white button mushrooms to ultraviolet B (UVB) light markedly increases their vitamin D-2 content, creating a new food source of vitamin D. We used a growing rat model to determine safety, bioavailability, and efficacy in support of bone growth by vitamin D-2 from UVB-exposed mushrooms. We fed 150 weanling female rats one of five diets for 10 weeks, all formulated on AIN-93 G. Control diets contained no mushrooms either with or without vitamin D-3. Other diets contained 2.5% and 5.0% of UVB-exposed or -unexposed mushrooms. Safety of the high levels of vitamin D-2 from mushrooms was assessed by animal growth and by Von Kossa staining for soft tissue calcification. Bioavailability was determined from changes in circulating levels of 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH). Efficacy in support of bone growth was determined from measures of femur bending properties, size, mineralization, and microarchitecture. Diets containing 2.5% and 5.0% light-exposed mushrooms significantly raised 25(OH)D and suppressed PTH levels compared to control-fed rats or rats fed 5.0% mushroom unexposed to light. Microarchitecture and trabecular mineralization were only modestly higher in the light-treated mushroom-fed rats compared to the controls. Von Kossa staining revealed no soft tissue calcification despite very high plasma 25(OH)D. Vitamin D-2 from UVB-exposed mushrooms is bioavailable, safe, and functional in supporting bone growth and mineralization in a growing rat model without evidence of toxicity. C1 [Calvo, M. S.; Babu, U. S.; Garthoff, L. H.] US FDA, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Woods, T. O.; Dreher, M.; Hill, G.; Nagaraja, S.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Calvo, MS (reprint author), US FDA, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM mona.calvo@fda.hhs.gov FU Mushroom Council; US FDA Centers for Food Safety and Applied Nutrition; Devices and Radiological Health FX The Mushroom Council, and the US FDA Centers for Food Safety and Applied Nutrition and Devices and Radiological Health. NR 43 TC 13 Z9 14 U1 1 U2 36 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD JAN PY 2013 VL 24 IS 1 BP 197 EP 207 DI 10.1007/s00198-012-1934-9 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 065PS UT WOS:000313161400016 PM 22358317 ER PT J AU Epstein, JS Vostal, JG AF Epstein, Jay S. Vostal, Jaroslav G. TI FDA contributions to reduction of bacterial contamination in platelet products within the United States SO TRANSFUSION LA English DT Letter ID APHERESIS PLATELETS; DIVERSION C1 [Epstein, Jay S.; Vostal, Jaroslav G.] US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Review, Rockville, MD 20857 USA. RP Epstein, JS (reprint author), US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Review, Rockville, MD 20857 USA. EM jaroslav.vostal@fda.hhs.gov NR 7 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JAN PY 2013 VL 53 IS 1 BP 232 EP 233 DI 10.1111/j.1537-2995.2012.03809.x PG 2 WC Hematology SC Hematology GA 068ET UT WOS:000313348900034 PM 23294211 ER PT J AU Weber, B Hochhaus, G Adams, W Lionberger, R Li, B Tsong, Y Lee, SL AF Weber, Benjamin Hochhaus, Guenther Adams, Wallace Lionberger, Robert Li, Bing Tsong, Yi Lee, Sau L. TI A Stability Analysis of a Modified Version of the Chi-Square Ratio Statistic: Implications for Equivalence Testing of Aerodynamic Particle Size Distribution SO AAPS JOURNAL LA English DT Article DE aerodynamic particle size distribution; bioequivalence; cascade impactor; chi-square ratio statistic; orally inhaled drug products AB Demonstration of equivalence in aerodynamic particle size distribution (APSD; e.g., by comparing cascade impactor (CI) profiles) constitutes one of key in vitro tests for supporting bioequivalence between test (T) and reference (R) orally inhaled drug products (OIDPs). A chi-square ratio statistic (CSRS) was previously proposed for equivalence testing of CI profiles. However, it was reported that the CSRS could not consistently discriminate between equivalent and inequivalent CI profiles. The objective of the overall project was to develop a robust and sensitive methodology for assessing equivalence of APSD profiles of T and R OIDPs. We propose here a modified version of the CSRS (mCSRS) and evaluated systematically its behavior when T and R CI profiles were identical. Different scenarios comprising CI profiles with different number of deposition sites and shapes were generated by Monte-Carlo simulation. For each scenario, the mCSRS was applied to 20,000 independent sets of 30 T and 30 R CI profiles that were identical. Different metrics (including mean and median) of the distribution of 900 mCSRSs (30 T x 30 R) were then evaluated for their suitability as a test statistic (i.e., independent of the number of sites and shape of the CI profile) for APSD equivalence testing. The median of the distribution of 900 mCSRSs (MmCSRS) was one regardless of the number of sites and shape of the CI profile. Hence, the MmCSRS is a robust metric for CI profile equivalence testing when T and R CI profiles are identical and potentially useful for APSD equivalence testing. C1 [Adams, Wallace; Lionberger, Robert; Li, Bing; Lee, Sau L.] US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Weber, Benjamin; Hochhaus, Guenther] Univ Florida, Coll Pharm, Dept Pharmaceut, Ctr Pharmacometr & Syst Pharmacol, Gainesville, FL 32610 USA. [Tsong, Yi] US FDA, Div Biometr 6, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Lee, Sau L.] MPN II, Rockville, MD 20855 USA. RP Lee, SL (reprint author), US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. EM Sau.Lee@fda.hhs.gov NR 19 TC 7 Z9 7 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD JAN PY 2013 VL 15 IS 1 BP 1 EP 9 DI 10.1208/s12248-012-9410-1 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 063RJ UT WOS:000313017300001 PM 23008161 ER PT J AU Li, BV Davit, BM Lee, CH Pabba, SK Mahadevan, C Caramenico, HT Haidar, SH Sanchez, AL Sigler, AW Stier, EM Conner, DP AF Li, Bing V. Davit, Barbara M. Lee, Christina H. Pabba, Santhosh K. Mahadevan, Chitra Caramenico, Hoainhon T. Haidar, Sam H. Sanchez, Aida L. Sigler, Aaron W. Stier, Ethan M. Conner, Dale P. TI Common Reasons for "For-Cause" Inspections in Bioequivalence Studies Submitted to the Food and Drug Administration SO AAPS JOURNAL LA English DT Article DE bioequivalence; FDA; inspection AB "For-cause" inspections are initiated during the review of bioequivalence (BE) data submitted to Abbreviated New Drug Applications when possible scientific misconduct and study irregularities are discovered. We investigated the common reasons for initiating "for-cause" inspections related to the clinical, analytical, and dissolution study sites associated with BE studies. This information may help the pharmaceutical industry to understand the root causes of compliance failures in BE studies and help them to improve compliance with FDA's regulations, thereby facilitating more rapid approval of safe and effective generic drugs. C1 [Li, Bing V.; Davit, Barbara M.; Lee, Christina H.; Pabba, Santhosh K.; Mahadevan, Chitra; Caramenico, Hoainhon T.; Sanchez, Aida L.; Sigler, Aaron W.; Stier, Ethan M.; Conner, Dale P.] US FDA, Div Bioequivalence, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20855 USA. [Haidar, Sam H.] US FDA, Off Compliance, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Li, BV (reprint author), US FDA, Div Bioequivalence, Off Gener Drugs, Ctr Drug Evaluat & Res, 7520 Standish Pl, Rockville, MD 20855 USA. EM bing.li@fda.hhs.gov NR 3 TC 0 Z9 0 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD JAN PY 2013 VL 15 IS 1 BP 10 EP 14 DI 10.1208/s12248-012-9415-9 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 063RJ UT WOS:000313017300002 PM 23054974 ER PT J AU Chang, RK Raw, A Lionberger, R Yu, L AF Chang, Rong-Kun Raw, Andre Lionberger, Robert Yu, Lawrence TI Generic Development of Topical Dermatologic Products: Formulation Development, Process Development, and Testing of Topical Dermatologic Products SO AAPS JOURNAL LA English DT Article DE dermatologic product; generic; semi-solid; topical product; quality by design ID IN-VITRO; DRUG-RELEASE AB This review presents considerations which can be employed during the development of a semi-solid topical generic product. This includes a discussion on the implementation of quality by design concepts during development to ensure the generic drug product has similar desired quality attributes to the reference-listed drug (RLD) and ensure batch to batch consistency through commercial production. This encompasses the concept of reverse-engineering to copy the RLD as a strategy during product development to ensure qualitative (Q1) and quantitative (Q2) formulation similarity, as well as similarity in formulation microstructure (Q3). The concept of utilizing in vitro skin permeation studies as a tool to justify formulation differences between the test generic product and the RLD to ensure a successful pharmacodynamic or clinical endpoint bioequivalence study is discussed. The review concludes with a discussion on drug product evaluation and quality tests as well as in vivo bioequivalence studies. C1 [Chang, Rong-Kun; Raw, Andre; Lionberger, Robert; Yu, Lawrence] US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20855 USA. RP Raw, A (reprint author), US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, 7500 Standish Pl, Rockville, MD 20855 USA. EM andre.raw@fda.hhs.gov NR 24 TC 30 Z9 30 U1 3 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD JAN PY 2013 VL 15 IS 1 BP 41 EP 52 DI 10.1208/s12248-012-9411-0 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 063RJ UT WOS:000313017300005 PM 23054971 ER PT J AU Meyer, TE Taylor, LG Xie, SJ Graham, DJ Mosholder, AD Williams, JR Moeny, D Ouellet-Hellstrom, RP Coster, TS AF Meyer, Tamra E. Taylor, Lockwood G. Xie, Suji Graham, David J. Mosholder, Andrew D. Williams, James R. Moeny, David Ouellet-Hellstrom, Rita P. Coster, Trinka S. TI Neuropsychiatric events in varenicline and nicotine replacement patch users in the Military Health System SO ADDICTION LA English DT Article DE Claims analysis; cohort studies; nicotine patch; nicotine replacement products; pharmacoepidemiology; propensity score; psychiatric diagnosis; survival rate; tobacco use cessation products; varenicline ID RECEPTOR PARTIAL AGONIST; MENTAL-ILLNESS; SMOKING-CESSATION; CONTROLLED-TRIAL; DOUBLE-BLIND; PLACEBO; POPULATION; PREVALENCE; BUPROPION; DISORDER AB Aim To determine the rate ratio of neuropsychiatric hospitalizations in new users of varenicline compared to new users of nicotine replacement therapy (NRT) patch in the Military Health System (MHS). Design, setting and participants Varenicline (n?=?19?933) and NRT patch (n?=?15?867) users who initiated therapy from 1 August 2006 to 31 August 2007 within the MHS were included in this retrospective cohort study. After matching according to propensity scores, 10?814 users remained in each cohort. The study population included those with and without a history of neuropsychiatric disease. Measurements Patients were followed for neuropsychiatric hospitalizations defined by primary neuropsychiatric discharge diagnosis using ICD-9 codes from in-patient administrative claims. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated after propensity score matching on exposure for socio-demographic factors, health-care utilization, comorbidities, medication history and neuropsychiatric history. Findings There was no increase in the rate of neuropsychiatric hospitalizations in patients treated with varenicline compared to NRT patch when followed for 30 days (propensity-score matched HR?=?1.14, 95% CI:?0.562.34). Results were similar after 60 days of follow-up. Conclusions There does not appear to be an increase in neuropsychiatric hospitalizations with varenicline compared with nicotine replacement therapy patch over 30 or 60 days after drug initiation. C1 [Meyer, Tamra E.; Taylor, Lockwood G.; Xie, Suji; Coster, Trinka S.] Pharmacovigilance Ctr, Dept Army, Off Surg Gen, Falls Church, VA 22042 USA. [Graham, David J.; Mosholder, Andrew D.; Williams, James R.; Moeny, David; Ouellet-Hellstrom, Rita P.] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Meyer, TE (reprint author), Pharmacovigilance Ctr, Dept Army, Off Surg Gen, 7700 Arlington Blvd,Suite 5142, Falls Church, VA 22042 USA. EM Tamra.E.Meyer@us.army.mil FU FDA FX Funds from the FDA were used to support this study under an inter-agency agreement between the FDA and MEDCOM. NR 25 TC 23 Z9 23 U1 2 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0965-2140 J9 ADDICTION JI Addiction PD JAN PY 2013 VL 108 IS 1 BP 203 EP 210 DI 10.1111/j.1360-0443.2012.04024.x PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 061XU UT WOS:000312884400032 PM 22812921 ER PT J AU ElZarrad, MK Eckstein, ET Glasgow, RE AF ElZarrad, M. Khair Eckstein, Erin T. Glasgow, Russell E. TI Applying Chronic Illness Care, Implementation Science, and Self-Management Support to HIV SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Review ID ANTIRETROVIRAL THERAPY; PREEXPOSURE PROPHYLAXIS; IMPROVE ADHERENCE; HEALTH-SERVICES; PREVENTION; INTERVENTIONS; MODEL; LITERACY; TRANSMISSION; INFECTION C1 [ElZarrad, M. Khair; Eckstein, Erin T.; Glasgow, Russell E.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. [ElZarrad, M. Khair] NCI, Canc Prevent Fellowship Program, Rockville, MD 20852 USA. [ElZarrad, M. Khair] US FDA, Interagcy Oncol Task Force Joint Fellowship Progr, Silver Spring, MD USA. RP Glasgow, RE (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,Room 6144, Rockville, MD 20852 USA. EM glasgowre@mail.nih.gov FU Division of Cancer Control and Population Sciences; Cancer Prevention Fellowship Program; National Cancer Institute, Rockville; Interagency Oncology Task Force Joint Fellowship Program; U.S. Food and Drug Administration, Silver Spring, Maryland; CDC through the Association for Prevention Teaching and Research (CDC-APTR) [11-NCHHSTP-01] FX From the Division of Cancer Control and Population Sciences (ElZarrad, Eckstein, Glasgow) and the Cancer Prevention Fellowship Program (ElZarrad), National Cancer Institute, Rockville; and Interagency Oncology Task Force Joint Fellowship Program (ElZarrad), U.S. Food and Drug Administration, Silver Spring, Maryland; Publication of this article was supported by the CDC through the Association for Prevention Teaching and Research (CDC-APTR) Cooperative Agreement number 11-NCHHSTP-01. NR 60 TC 8 Z9 8 U1 3 U2 21 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD JAN PY 2013 VL 44 IS 1 SU 2 BP S99 EP S107 DI 10.1016/j.amepre.2012.09.046 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 056YL UT WOS:000312528000008 PM 23253770 ER PT J AU Compton, WM Volkow, ND Throckmorton, DC Lurie, P AF Compton, Wilson M. Volkow, Nora D. Throckmorton, Douglas C. Lurie, Peter TI Expanded Access to Opioid Overdose Intervention: Research, Practice, and Policy Needs SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID UNITED-STATES; NALOXONE; ABUSE; PAIN C1 [Compton, Wilson M.; Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA. [Throckmorton, Douglas C.; Lurie, Peter] US FDA, Silver Spring, MD USA. RP Compton, WM (reprint author), NIDA, 6001 Execut Blvd,MSC 9589, Bethesda, MD 20892 USA. EM wcompton@nida.nih.gov NR 13 TC 15 Z9 15 U1 0 U2 5 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 1 PY 2013 VL 158 IS 1 BP 65 EP U147 DI 10.7326/0003-4819-158-1-201301010-00013 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 065AV UT WOS:000313119900011 PM 23277902 ER PT J AU Kim, DW Feng, JH Chen, HZ Kweon, O Gao, Y Yu, LR Burrowes, VJ Sutherland, JB AF Kim, Dae-Wi Feng, Jinhui Chen, Huizhong Kweon, Ohgew Gao, Yuan Yu, Li-Rong Burrowes, Vanessa J. Sutherland, John B. TI Identification of the Enzyme Responsible for N-Acetylation of Norfloxacin by Microbacterium sp Strain 4N2-2 SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID WATER TREATMENT-PLANT; MYCOBACTERIUM-TUBERCULOSIS; GLUTAMINE-SYNTHETASE; QUINOLONE RESISTANCE; ESCHERICHIA-COLI; WASTE-WATER; ACETYLTRANSFERASE GENES; ANTIBACTERIAL AGENTS; TRANSFERABLE PLASMID; NITROGEN-METABOLISM AB Microbacterium sp. 4N2-2, isolated from a wastewater treatment plant, converts the antibacterial fluoroquinolone norfloxacin to N-acetylnorfloxacin and three other metabolites. Because N-acetylation results in loss of antibacterial activity, identification of the enzyme responsible is important for understanding fluoroquinolone resistance. The enzyme was identified as glutamine synthetase (GS); N-acetylnorfloxacin was produced only under conditions associated with GS expression. The GS gene (glnA) was cloned, and the protein (53 kDa) was heterologously expressed and isolated. Optimal conditions and biochemical properties (K-m and V-max) of purified GS were characterized; the purified enzyme was inhibited by Mn2+, Mg2+, ATP, and ADP. The contribution of GS to norfloxacin resistance was shown by using a norfloxacin-sensitive Escherichia coli strain carrying glnA derived from Microbacterium sp. 4N2-2. The GS of Microbacterium sp. 4N2-2 was shown to act as an N-acetyltransferase for norfloxacin, which produced low-level norfloxacin resistance. Structural and docking analysis identified potential binding sites for norfloxacin at the ADP binding site and for acetyl coenzyme A (acetyl-CoA) at a cleft in GS. The results suggest that environmental bacteria whose enzymes modify fluoroquinolones may be able to survive in the presence of low fluoroquinolone concentrations. C1 [Kim, Dae-Wi; Feng, Jinhui; Chen, Huizhong; Kweon, Ohgew; Burrowes, Vanessa J.; Sutherland, John B.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Gao, Yuan; Yu, Li-Rong] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Kim, Dae-Wi] Chung Ang Univ, Dept Biotechnol, Program BK21, Anseong, South Korea. [Kim, Dae-Wi] Chung Ang Univ, Inst Microbiom, Anseong, South Korea. RP Sutherland, JB (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM john.sutherland@fda.hhs.gov FU Research Participation Program; National Center for Toxicological Research FX This research was supported in part by the appointments of D.-W. Kim and J. Feng to the Research Participation Program and that of V.J. Burrowes to the Summer Student Research Program at the National Center for Toxicological Research, administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 48 TC 2 Z9 2 U1 0 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JAN PY 2013 VL 79 IS 1 BP 314 EP 321 DI 10.1128/AEM.02347-12 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 062PK UT WOS:000312931600034 PM 23104417 ER PT J AU Carter, L Lindsey, LA Grim, CJ Sathyamoorthy, V Jarvis, KG Gopinath, G Lee, C Sadowski, JA Trach, L Pava-Ripoll, M McCardell, BA Tall, BD Hu, L AF Carter, L. Lindsey, L. A. Grim, C. J. Sathyamoorthy, V. Jarvis, K. G. Gopinath, G. Lee, C. Sadowski, J. A. Trach, L. Pava-Ripoll, M. McCardell, B. A. Tall, B. D. Hu, L. TI Multiplex PCR Assay Targeting a Diguanylate Cyclase-Encoding Gene, cgcA, To Differentiate Species within the Genus Cronobacter SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID ENTEROBACTER-SAKAZAKII; SEQUENCE AB In a comparison to the widely used Cronobacter rpoB PCR assay, a highly specific multiplexed PCR assay based on cgcA, a diguanylate cyclase gene, that identified all of the targeted six species among 305 Cronobacter isolates was designed. This assay will be a valuable tool for identifying suspected Cronobacter isolates from food-borne investigations. C1 [Carter, L.; Lindsey, L. A.; Grim, C. J.; Sathyamoorthy, V.; Jarvis, K. G.; Gopinath, G.; Lee, C.; Sadowski, J. A.; Trach, L.; McCardell, B. A.; Tall, B. D.; Hu, L.] US FDA, CFSAN, Laurel, MD USA. [Grim, C. J.; Hu, L.] Oak Ridge Inst Sci & Educ, Oak Ridge, TN USA. [Pava-Ripoll, M.] US FDA, CFSAN, College Pk, MD USA. RP Hu, L (reprint author), US FDA, CFSAN, Laurel, MD USA. EM lan16686@yahoo.com OI Tall, Ben/0000-0003-0399-3629 FU National Association for Equal Opportunity in Higher Education internship program fellowship, Washington, DC; oint Institute of Food Safety and Applied Nutrition student internship program, University of Maryland, College Park, MD FX L. A. Lindsey was a recipient of a 2011 National Association for Equal Opportunity in Higher Education internship program fellowship, Washington, DC. C. Lee, L. Trach, and J. A. Sadowski were supported by the Joint Institute of Food Safety and Applied Nutrition student internship program, University of Maryland, College Park, MD. NR 19 TC 16 Z9 17 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JAN PY 2013 VL 79 IS 2 BP 734 EP 737 DI 10.1128/AEM.02898-12 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 062SI UT WOS:000312941800039 PM 23144142 ER PT J AU Haynes, K Beukelman, T Curtis, JR Newcomb, C Herrinton, LJ Graham, DJ Solomon, DH Griffin, MR Chen, L Liu, LY Saag, KG Lewis, JD AF Haynes, Kevin Beukelman, Timothy Curtis, Jeffrey R. Newcomb, Craig Herrinton, Lisa J. Graham, David J. Solomon, Daniel H. Griffin, Marie R. Chen, Lang Liu, Liyan Saag, Kenneth G. Lewis, James D. CA SABER Collaboration TI Tumor necrosis factor a inhibitor therapy and cancer risk in chronic immune-mediated diseases SO ARTHRITIS AND RHEUMATISM LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; RANDOMIZED CONTROLLED-TRIALS; NONMELANOMA SKIN CANCERS; RHEUMATOID-ARTHRITIS; CROHNS-DISEASE; FACTOR ANTAGONISTS; LYMPHOMA RISK; METAANALYSIS; INFLIXIMAB; MALIGNANCIES AB Objective To compare the incidence of cancer following tumor necrosis factor a (TNFa) inhibitor therapy to that with commonly used alternative therapies across multiple immune-mediated diseases. Methods The Safety Assessment of Biological Therapeutics study used data from 4 sources: national Medicaid and Medicare databases, Tennessee Medicaid, pharmacy benefits plans for Medicare beneficiaries in New Jersey and Pennsylvania, and Kaiser Permanente Northern California. Propensity scoreadjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) were computed to estimate the relative rates of cancer, comparing those treated with TNFa inhibitors to those treated with alternative disease-modifying therapies. The cancer-finding algorithm had a positive predictive value ranging from 31% for any leukemia to 89% for female breast cancer. Results We included 29,555 patients with rheumatoid arthritis (RA) (13,102 person-years), 6,357 patients with inflammatory bowel disease (1,508 person-years), 1,298 patients with psoriasis (371 person-years), and 2,498 patients with psoriatic arthritis (618 person-years). The incidence of any solid cancer was not elevated in RA (HR 0.80 [95% CI 0.591.08]), inflammatory bowel disease (HR 1.42 [95% CI 0.474.26]), psoriasis (HR 0.58 [95% CI 0.103.31]), or psoriatic arthritis (HR 0.74 [95% CI 0.202.76]) during TNFa inhibitor therapy compared to disease-specific alternative therapy. Among RA patients, the incidence of any of the 10 most common cancers in the US and of nonmelanoma skin cancer was not increased with TNFa inhibitor therapy compared to treatment with comparator drugs. Conclusion Short-term cancer risk was not elevated among patients treated with TNFa inhibitor therapy relative to commonly used therapies for immune- mediated chronic inflammatory diseases in this study. C1 [Haynes, Kevin] Univ Penn, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Beukelman, Timothy; Curtis, Jeffrey R.; Chen, Lang; Saag, Kenneth G.] Univ Alabama Birmingham, Birmingham, AL USA. [Herrinton, Lisa J.; Liu, Liyan] Kaiser Permanente No Calif, Oakland, CA USA. [Graham, David J.] FDA, White Oak, MD USA. [Solomon, Daniel H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Solomon, Daniel H.] Harvard Univ, Sch Med, Boston, MA USA. [Griffin, Marie R.] Vanderbilt Univ, Nashville, TN USA. [Griffin, Marie R.] VA Tennessee Valley Hlth Care Syst, MidSouth Geriatr Res Educ & Clin Ctr, Nashville, TN USA. RP Haynes, K (reprint author), Univ Penn, Dept Epidemiol & Biostat, 713 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM khaynes@upenn.edu FU AHRQ [R01-HS-018517]; FDA/DHHS [1U18-HS-017919-0]; NIH through the University of Alabama at Birmingham Center for Clinical and Translational Science [5KL2-RR-025776]; NIH [AR-053351, K24-DK07822806]; Novartis; Genentech; Pfizer; Bristol-Myers Squibb; Crescendo Bioscience; Abbott; Roche/Genentech; UCB; Centocor; Amgen; Consortium of Rheumatology Researchers of North America (CORRONA) registry; CORRONA; Proctor Gamble; Eli Lilly FX Supported by the AHRQ and the FDA/DHHS as part of grant 1U18-HS-017919-0, administered through the AHRQ Centers for Education and Research on Therapeutics Program. Dr. Beukelman's work was supported by NIH grant 5KL2-RR-025776 through the University of Alabama at Birmingham Center for Clinical and Translational Science. Dr. Curtis' work was supported by NIH grant AR-053351 and AHRQ grant R01-HS-018517. Dr. Lewis' work was supported by NIH grant K24-DK07822806.; Dr. Beukelman has received consulting fees, speaking fees, and/or honoraria from Novartis and Genentech (less than $10,000 each) and research funding from Pfizer. Dr. Curtis has received consulting fees, speaking fees, and/or honoraria from Pfizer, Bristol-Myers Squibb, Crescendo Bioscience, and Abbott (less than $10,000 each) and from Roche/Genentech, UCB, Centocor, Amgen, and the Consortium of Rheumatology Researchers of North America (CORRONA) registry (more than $10,000 each); he has received research grants from Pfizer, Bristol-Myers Squibb, Crescendo Bioscience, Abbott, Roche/Genentech, UCB, Centocor, CORRONA, and Amgen. Dr. Herrinton has received research contracts from Proctor & Gamble, Genentech, and Centocor. Dr. Solomon has received consulting fees from CORRONA (more than $10,000) and research grants from Amgen, Abbott, and Eli Lilly and has served in uncompensated roles on clinical trials related to rheumatoid arthritis for the VA Health System and Pfizer. Dr. Saag has received consulting fees, speaking fees, and/or honoraria from Eli Lilly, Merck, Savient, Ardea Biosciences, Regeneron, URL Pharma, and Abbott (less than $10,000 each) and from Amgen (more than $10,000). Dr. Lewis has received consulting fees, speaking fees, and/or honoraria from GlaxoSmithKline, Millennium Pharmaceuticals, Allos Therapeutics, Amgen, Pfizer, and Abbott (less than $10,000 each) and research grants from Centocor, Takeda, and Shire. NR 38 TC 36 Z9 36 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD JAN PY 2013 VL 65 IS 1 BP 48 EP 58 DI 10.1002/art.37740 PG 11 WC Rheumatology SC Rheumatology GA 062RD UT WOS:000312938100007 PM 23055441 ER PT J AU He, WW Zhou, YT Warner, WG Hu, XN Wu, XC Zheng, Z Boudreau, MD Yin, JJ AF He, Weiwei Zhou, Yu-Ting Warner, Wayne G. Hu, Xiaona Wu, Xiaochun Zheng, Zhi Boudreau, Mary D. Yin, Jun-Jie TI Intrinsic catalytic activity of Au nanoparticles with respect to hydrogen peroxide decomposition and superoxide scavenging SO BIOMATERIALS LA English DT Article DE Au nanoparticles; Hydroxyl radicals; Oxygen; ROS; Nanosafety; ESR ID GOLD NANOPARTICLES; DEPENDENT GENERATION; OXIDE NANOPARTICLES; FREE-RADICALS; CYTOTOXICITY; SIZE; CELLS; NANORODS; GLUCOSE; BIOLOGY AB Gold nanoparticles have received a great deal of interest due to their unique optical and catalytic properties and biomedical applications. Developing applications as well as assessing associated risks requires an understanding of the interactions between Au nanoparticles (NPs) and biologically active substances. In this paper, electron spin resonance spectroscopy (ESR) was used to investigate the catalytic activity of Au NPs in biologically relevant reactions. We report here that Au NPs can catalyze the rapid decomposition of hydrogen peroxide. Decomposition of hydrogen peroxide is accompanied by the formation of hydroxyl radicals at lower pH and oxygen at higher pH. In addition, we found that, mimicking SOD, Au NPs efficiently catalyze the decomposition of superoxide. These results demonstrate that Au NPs can act as SOD and catalase mimetics. Since reactive oxygen species are biologically relevant products being continuously generated in cells, these results obtained under conditions resembling different biological microenvironments may provide insights for evaluating risks associated with Au NPs. Published by Elsevier Ltd. C1 [He, Weiwei; Zhou, Yu-Ting; Warner, Wayne G.; Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [He, Weiwei; Zheng, Zhi] Xuchang Univ, Inst Surface Micro & Nano Mat, Key Lab Micronano Mat Energy Storage & Convers He, Xuchang 461000, Henan, Peoples R China. [Hu, Xiaona; Wu, Xiaochun] Natl Ctr Nanosci & Technol, CAS Key Lab Standardizat & Measurement Nanotechno, Beijing 100190, Peoples R China. [Boudreau, Mary D.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Zhou, Yu-Ting] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. RP Yin, JJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM junjie.yin@fda.hhs.gov RI Yin, Jun Jie /E-5619-2014 FU regulatory science grant under FDA Nanotechnology CORES Program [FY11]; Research Project of Basic and Advanced Technology of Henan Province [112300410106]; Natural Science Foundation of Henan Province [2011B150035] FX This article is not an official US Food and Drug Administration (FDA) guidance or policy statement. No official support or endorsement by the US FDA is intended or should be inferred. This work was supported by a regulatory science grant under the FY11 FDA Nanotechnology CORES Program. Dr. W. He and Z. Zheng thank Research Project of Basic and Advanced Technology of Henan Province (Grant NO. 112300410106) and Natural Science Foundation of Henan Province (2011B150035) for financial support. We thank Dr. John H. Callahan (CFSAN/FDA) for valuable suggestions and comments on this manuscript. NR 44 TC 51 Z9 54 U1 11 U2 151 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 JAN PY 2013 VL 34 IS 3 BP 765 EP 773 DI 10.1016/j.biomaterials.2012.10.010 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 060ER UT WOS:000312759800017 PM 23103160 ER PT J AU Sidney, S Cheetham, TC Connell, FA Ouellet-Hellstrom, R Graham, DJ Davis, D Sorel, M Quesenberry, CP Cooper, WO AF Sidney, Stephen Cheetham, T. Craig Connell, Frederick A. Ouellet-Hellstrom, Rita Graham, David J. Davis, Daniel Sorel, Michael Quesenberry, Charles P., Jr. Cooper, William O. TI Recent combined hormonal contraceptives (CHCs) and the risk of thromboembolism and other cardiovascular events in new users SO CONTRACEPTION LA English DT Article DE Contraceptives; Venous thromboembolism; Cardiovascular disease; Epidemiology ID NONFATAL VENOUS THROMBOEMBOLISM; CONTAINING ORAL-CONTRACEPTIVES; MYOCARDIAL-INFARCTION; TRANSDERMAL PATCH; ETHINYL ESTRADIOL; WOMEN; STROKE; NORGESTIMATE; THROMBOSIS; COHORT AB Background: Combined hormonal contraceptives (CHCs) place women at increased risk of venous thromboembolic events (VTEs) and arterial thrombotic events (ATEs), including acute myocardial infarction and ischemic stroke. There is concern that three recent CHC preparations [drospirenone-containing pills (DRSPs), the norelgestromin-containing transdermal patch (NGMN) and the etonogestrel vaginal ring (ETON)] may place women at even higher risk of thrombosis than other older low-dose CHCs with a known safety profile. Study Design: All VTEs and all hospitalized ATEs were identified in women, ages 10-55 years, from two integrated health care programs and two state Medicaid programs during the time period covering their new use of DRSP, NGMN, ETON or one of four low-dose estrogen comparator CHCs. The relative risk of thrombotic and thromboembolic outcomes associated with the newer CHCs in relation to the comparators was assessed with Cox proportional hazards regression models adjusting for age, site and year of entry into the study. Results: The hazards ratio for DRSP in relation to low-dose estrogen comparators among new users was 1.77 (95% confidence interval 1.33-2.35) for VTE and 2.01 (1.06-3.81) for ATE. The increased risk of DRSP was limited to the 10-34-year age group for VTE and the 35-55-year group for ATE. Use of the NGMN patch and ETON vaginal ring was not associated with increased risk of either thromboembolic or thrombotic outcomes. Conclusions: In new users, DRSP was associated with higher risk of thrombotic events (VTE and ATE) relative to low-dose estrogen comparator CHCs, while the use of the NGMN patch and ETON vaginal ring was not. (c) 2013 Elsevier Inc. All rights reserved. C1 [Sidney, Stephen; Sorel, Michael; Quesenberry, Charles P., Jr.] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. [Cheetham, T. Craig] Kaiser Permanente So Calif, Pharm Analyt Serv, Downey, CA USA. [Connell, Frederick A.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Ouellet-Hellstrom, Rita; Graham, David J.; Davis, Daniel] FDA Off Surveillance & Epidemiol, Silver Spring, MD USA. [Cooper, William O.] Vanderbilt Univ, Dept Pediat, Nashville, TN USA. RP Sidney, S (reprint author), Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. EM steve.sidney@kp.org FU U.S. Food and Drug Administration, Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research [HHSF223200510008C, HHSF223200510009C] FX This study was supported through contracts HHSF223200510008C and HHSF223200510009C (U.S. Food and Drug Administration, Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research). NR 21 TC 46 Z9 46 U1 0 U2 28 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0010-7824 J9 CONTRACEPTION JI Contraception PD JAN PY 2013 VL 87 IS 1 BP 93 EP 100 DI 10.1016/j.contraception.2012.09.015 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 060AT UT WOS:000312748400017 PM 23083525 ER PT J AU Gollapudi, BB Johnson, GE Hernandez, LG Pottenger, LH Dearfield, KL Jeffrey, AM Julien, E Kim, JH Lovell, DP MacGregor, JT Moore, MM van Benthem, J White, PA Zeiger, E Thybaud, V AF Gollapudi, B. B. Johnson, G. E. Hernandez, L. G. Pottenger, L. H. Dearfield, K. L. Jeffrey, A. M. Julien, E. Kim, J. H. Lovell, D. P. MacGregor, J. T. Moore, M. M. van Benthem, J. White, P. A. Zeiger, E. Thybaud, V. TI Quantitative approaches for assessing dose-response relationships in genetic toxicology studies SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE mutagenicity; risk assessment; low-dose; benchmark dose; point of departure; no-observed-genotoxic-effect-level; dose-response ID IN-VITRO; RISK-ASSESSMENT; FOLLOW-UP; MUTAGENICITY; CELLS; THRESHOLDS; ASSAY; CARCINOGENS; CHEMICALS; TOXICANTS AB Genetic toxicology studies are required for the safety assessment of chemicals. Data from these studies have historically been interpreted in a qualitative, dichotomous yes or no manner without analysis of doseresponse relationships. This article is based upon the work of an international multi-sector group that examined how quantitative doseresponse relationships for in vitro and in vivo genetic toxicology data might be used to improve human risk assessment. The group examined three quantitative approaches for analyzing doseresponse curves and deriving point-of-departure (POD) metrics (i.e., the no-observed-genotoxic-effect-level (NOGEL), the threshold effect level (Td), and the benchmark dose (BMD)), using data for the induction of micronuclei and gene mutations by methyl methanesulfonate or ethyl methanesulfonate in vitro and in vivo. These results suggest that the POD descriptors obtained using the different approaches are within the same order of magnitude, with more variability observed for the in vivo assays. The different approaches were found to be complementary as each has advantages and limitations. The results further indicate that the lower confidence limit of a benchmark response rate of 10% (BMDL10) could be considered a satisfactory POD when analyzing genotoxicity data using the BMD approach. The models described permit the identification of POD values that could be combined with mode of action analysis to determine whether exposure(s) below a particular level constitutes a significant human risk. Subsequent analyses will expand the number of substances and endpoints investigated, and continue to evaluate the utility of quantitative approaches for analysis of genetic toxicity doseresponse data. Environ. Mol. Mutagen., 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Kim, J. H.] ILSI Hlth & Environm Sci Inst, Washington, DC 20005 USA. [Gollapudi, B. B.; Pottenger, L. H.] Dow Chem Co USA, Midland, MI 48674 USA. [Johnson, G. E.] Swansea Univ, Coll Med, Inst Life Sci, Swansea SA2 8PP, W Glam, Wales. [Hernandez, L. G.; van Benthem, J.] Natl Inst Publ Hlth & Environm RIVM, Lab Hlth Protect Res, NL-3720 BA Bilthoven, Netherlands. [Dearfield, K. L.] US Food Safety & Inspect Serv, USDA, Washington, DC 20250 USA. [Jeffrey, A. M.] New York Med Coll, Dept Pathol, Valhalla, NY 10595 USA. [Julien, E.] LifeSci Res Serv, Rockville, MD USA. [Lovell, D. P.] St Georges Univ London, Div Biomed Sci, London SW17 0RE, England. [MacGregor, J. T.] Toxicol Consulting Serv, Arnold, MD USA. [Moore, M. M.] Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [White, P. A.] Hlth Canada, Hlth Environm & Consumer Safety Branch, Environm Hlth Sci & Res Bur, Ottawa, ON K1A 0K9, Canada. [Zeiger, E.] Errol Zeiger Consulting, Chapel Hill, NC USA. [Thybaud, V.] Sanofi Rech, Vitry Alfortville Res Ctr, Drug Disposit Preclin Safety & Anim Res, Vitry Sur Seine, France. RP Kim, JH (reprint author), ILSI Hlth & Environm Sci Inst, Washington, DC 20005 USA. EM jkim@hesiglobal.org OI white, paul/0000-0001-5853-4759; Johnson, George/0000-0001-5643-9942 NR 40 TC 47 Z9 47 U1 2 U2 29 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JAN PY 2013 VL 54 IS 1 BP 8 EP 18 DI 10.1002/em.21727 PG 11 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 063IX UT WOS:000312991300002 PM 22987251 ER PT J AU Brookmire, L Chen, JJ Levy, DD AF Brookmire, Lauren Chen, James J. Levy, Dan D. TI Evaluation of the highest concentrations used in the in vitro chromosome aberrations assay SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE genetic toxicity; regulatory; cytotoxicity ID MAMMALIAN-CELLS; RODENT CARCINOGENS; TOP CONCENTRATION; TESTS; CLASTOGENICITY; MUTAGENICITY AB There is controversy over the highest concentration to which an article should be tested in in vitro mammalian cell assays of genetic toxicity. Until recently, most guidelines specified the use of concentrations of up to 10 mM or 5,000 mu g/ml (whichever is lower) when not limited by the toxicity of the test article to the cells used for the test. Several recent publications have called for lowering those limits. We examined concentration/response curves for in vitro chromosome aberrations assays. Data was extracted from two published databases to evaluate the lowest dose at which a positive response was reported. Concentration/response curves were simulated using Monte Carlo procedures on log normal distributions of the data. These curves were then used to predict the loss in assay sensitivity that would be incurred by arbitrarily lowering the highest concentration to which the assay is conducted. The simulations suggest that lowering the current high concentration limit from 10 mM would dramatically impact the sensitivity of the assay. In contrast, lowering the high concentration limit using the mu g/ml scale, the most commonly applied scale in regulatory submissions, would not have a similar impact on assay sensitivity until the limit concentration was lowered to more than half of the current 5,000 mu g/ml limit. This analysis suggests that the current limits of 10 mM and 5,000 mu g/ml are not equivalent to one another and challenges the assumption that lowering the 10 mM limit will not decrease assay sensitivity. Environ. Mol. Mutagen., 2013. Published 2012 Wiley Periodicals, Inc. C1 [Brookmire, Lauren; Levy, Dan D.] US FDA, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Chen, James J.] Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. RP Levy, DD (reprint author), 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM dan.levy@fda.hhs.gov NR 17 TC 2 Z9 2 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JAN PY 2013 VL 54 IS 1 BP 36 EP 43 DI 10.1002/em.21738 PG 8 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 063IX UT WOS:000312991300004 PM 23076808 ER PT J AU Ou, W Marino, MP Lu, C Reiser, J AF Ou, W. Marino, M. P. Lu, C. Reiser, J. TI Rapid titration of retroviral vectors using a beta-lactamase protein fragment complementation assay SO GENE THERAPY LA English DT Article DE gamma retrovirus; lentivirus; titration; protein fragment complementation; beta-lactamase ID HUMAN-IMMUNODEFICIENCY-VIRUS; LENTIVIRAL-VECTORS; REVERSE-TRANSCRIPTASE; T-LYMPHOCYTES; TARGET-CELLS; EXPRESSION; GLYCOPROTEIN; VIRIONS; FUSION; ENTRY AB The availability of rapid and quantitative titration assays for retroviral vectors is important, especially in the context of clinical applications. In this report, we describe a novel assay to titrate lentiviral and gamma retroviral vectors. This rapid assay is based on protein fragment complementation involving the N-terminal (Bla1) and the C-terminal (Bla2) fragments of TEM-1 beta-lactamase (BLAK). The Bla1 protein fragment is incorporated in the vector's envelope during vector production. Bla1-bearing vectors are titrated on Bla2-expressing cells. Upon transduction, Bla1 and Bla2 heterodimerize and restore BLAK's enzymatic function. The enzymatic activity of BLAK is quantified by flow cytometry using the green fluorescent CCF2/AM substrate, which is converted into a blue fluorescent product. The enzymatic conversion of the CCF2/AM substrate was found to be directly related to vector entry, as a neutralizing antibody completely blocked the conversion. The titers obtained using this rapid assay correlated well with the titers measured by functional transduction assays. The whole assay can be finished within 8 h. Thus, it is considerably less time consuming compared with other transduction-based titration assays for lentiviral and gamma retroviral vectors. Gene Therapy (2013) 20, 43-50; doi:10.1038/gt.2011.212; published online 19 January 2012 C1 [Reiser, J.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, CBER, Rockville, MD 20852 USA. RP Reiser, J (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, CBER, 1401 Rockville Pike,HFM 725, Rockville, MD 20852 USA. EM Jakob.Reiser@fda.hhs.gov NR 39 TC 0 Z9 1 U1 1 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD JAN PY 2013 VL 20 IS 1 BP 43 EP 50 DI 10.1038/gt.2011.212 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 064EG UT WOS:000313053900006 PM 22257933 ER PT J AU Oakley, MS Gerald, N Anantharaman, V Gao, YM Majam, V Mahajan, B Pham, PT Lotspeich-Cole, L Myers, TG McCutchan, TF Morris, SL Aravind, L Kumar, S AF Oakley, Miranda S. Gerald, Noel Anantharaman, Vivek Gao, Yamei Majam, Victoria Mahajan, Babita Phuong Thao Pham Lotspeich-Cole, Leda Myers, Timothy G. McCutchan, Thomas F. Morris, Sheldon L. Aravind, L. Kumar, Sanjai TI Radiation-Induced Cellular and Molecular Alterations in Asexual Intraerythrocytic Plasmodium falciparum SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE NOD2; IL-17; Th17; T lymphocytes; ocular toxoplasmosis; Toxoplasma gondii ID MALARIA VACCINE; TOPOISOMERASE-II; EXPRESSION; DEATH; PARASITES; PATHWAYS; INVASION; IMMUNITY; BERGHEI; STRESS AB Background. gamma-irradiation is commonly used to create attenuation in Plasmodium parasites. However, there are no systematic studies on the survival, reversion of virulence, and molecular basis for gamma-radiation-induced cell death in malaria parasites. Methods. The effect of gamma-irradiation on the growth of asexual Plasmodium falciparum was studied in erythrocyte cultures. Cellular and ultrastructural changes within the parasite were studied by fluorescence and electron microscopy, and genome-wide transcriptional profiling was performed to identify parasite biomarkers of attenuation and cell death. Results. gamma-radiation induced the death of P. falciparum in a dose-dependent manner. These parasites had defective mitosis, sparse cytoplasm, fewer ribosomes, disorganized and clumped organelles, and large vacuoles-observations consistent with "distressed" or dying parasites. A total of 185 parasite genes were transcriptionally altered in response to gamma-irradiation (45.9% upregulated, 54.1% downregulated). Loss of parasite survival was correlated with the downregulation of genes encoding translation factors and with upregulation of genes associated with messenger RNA-sequestering stress granules. Genes pertaining to cell-surface interactions, host-cell remodeling, and secreted proteins were also altered. Conclusions. These studies provide a framework to assess the safety of gamma-irradiation attenuation and promising targets for genetic deletion to produce whole parasite-based attenuated vaccines. C1 [Oakley, Miranda S.; Lotspeich-Cole, Leda; Morris, Sheldon L.] US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Gerald, Noel; Majam, Victoria; Mahajan, Babita; Phuong Thao Pham; Kumar, Sanjai] US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Gao, Yamei] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Anantharaman, Vivek; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Myers, Timothy G.] NIH, Microarray Res Facil, Res & Technol Branch, Bethesda, MD 20892 USA. [McCutchan, Thomas F.] NIH, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. RP Kumar, S (reprint author), 5516 Nicholson Ln, Kensington, MD 20895 USA. EM sanjai.kumar@fda.hhs.gov OI Anantharaman, Vivek/0000-0001-8395-0009 FU Food and Drug Administration; National Institutes of Health FX This work was supported by the intramural grants from the Food and Drug Administration and National Institutes of Health. NR 34 TC 6 Z9 6 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2013 VL 207 IS 1 BP 164 EP 174 DI 10.1093/infdis/jis645 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 057ZU UT WOS:000312604200021 PM 23100570 ER PT J AU Chan-Tack, KM Gao, A Himaya, AC Thompson, EG Singer, ME Uyeki, TM Birnkrant, DB AF Chan-Tack, Kirk M. Gao, Arlene Himaya, Amalia C. Thompson, Elizabeth G. Singer, Mary E. Uyeki, Timothy M. Birnkrant, Debra B. TI Clinical Experience With Intravenous Zanamivir Under an Emergency Investigational New Drug Program in the United States SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID CRITICALLY-ILL PATIENTS; 2009 H1N1 INFLUENZA C1 [Chan-Tack, Kirk M.; Gao, Arlene; Himaya, Amalia C.; Thompson, Elizabeth G.; Singer, Mary E.; Birnkrant, Debra B.] US FDA, Div Antiviral Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Uyeki, Timothy M.] Ctr Dis Control & Prevent, Influenza Div, Atlanta, GA USA. RP Chan-Tack, KM (reprint author), 10903 New Hampshire Ave,Bldg 22,Room 6337, Silver Spring, MD 20993 USA. EM kirk.chan-tack@fda.hhs.gov NR 8 TC 9 Z9 9 U1 2 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2013 VL 207 IS 1 BP 196 EP 198 DI 10.1093/infdis/jis637 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 057ZU UT WOS:000312604200024 PM 23089591 ER PT J AU Jain, L Parks, MH Sahajwalla, C AF Jain, Lokesh Parks, Mary H. Sahajwalla, Chandrahas TI Determination of time to onset and rate of action of insulin products: Importance and new approaches SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE insulin; comparability; absorption; time to onset of action; rate of action; regulatory science; pharmacokinetics; pharmacodynamics; bioequivalence ID REGULAR HUMAN INSULIN; ORAL INSULIN AB One important aspect of insulin drug development is to ascertain that short-acting insulins mimic the normal mealtime insulin release in healthy subjects. Therefore, it is important to identify metrics that allow identification of unique characteristics of insulin products based on pharmacokinetic (PK) (timeconcentration) or glucodynamic (time course of action) profiles. Current development programs use metrics such as onset of action to characterize insulin products, in addition to peak and area under the curve parameters for PK and glucodynamic profiles. However, in current practice, onset of action parameter is often interchangeably used with rate of action for insulin products, which points to existence of confusion about their definitions and methods of determination. In this paper, we discuss these two parameters with an underlying objective to prompt discussion on development of a quantitative standard for insulin products based on the onset and/or rate of action. This paper presents euglycemic clamp and meal challenge study data using a hypothetical insulin product and attempts to clear confusion by emphasizing on the distinct properties of these parameters. (c) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:271279, 2013 C1 [Jain, Lokesh; Sahajwalla, Chandrahas] US Food & Drug Adm FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Parks, Mary H.] US Food & Drug Adm FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Jain, L (reprint author), US Food & Drug Adm FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM Lokesh.Jain@fda.hhs.gov NR 13 TC 2 Z9 2 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD JAN PY 2013 VL 102 IS 1 BP 271 EP 279 DI 10.1002/jps.23355 PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 051RV UT WOS:000312145900028 PM 23132625 ER PT J AU Yang, X Greenhaw, J Shi, Q Roberts, DW Hinson, JA Muskhelishvili, L Davis, K Salminen, WF AF Yang, Xi Greenhaw, James Shi, Qiang Roberts, Dean W. Hinson, Jack A. Muskhelishvili, Levan Davis, Kelly Salminen, William F. TI Mouse Liver Protein Sulfhydryl Depletion after Acetaminophen Exposure SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID MITOCHONDRIAL PERMEABILITY TRANSITION; N-ACETYLCYSTEINE; OXIDANT STRESS; ISCHEMIA-REPERFUSION; INJURY; MICE; HEPATOTOXICITY; THIOL; GLUTATHIONE; TOXICITY AB Acetaminophen (APAP)-induced liver injury is the leading cause of acute liver failure in many countries. This study determined the extent of liver protein sulfhydryl depletion not only in whole liver homogenate but also in the zonal pattern of sulfhydryl depletion within the liver lobule. A single oral gavage dose of 150 or 300 mg/kg APAP in B6C3F1 mice produced increased serum alanine aminotransferase levels, liver necrosis, and glutathione depletion in a dose-dependent manner. Free protein sulfhydryls were measured in liver protein homogenates by labeling with maleimide linked to a near infrared fluorescent dye followed by SDS-polyacrylamide gel electrophoresis. Global protein sulfhydryl levels were decreased significantly (48.4%) starting at 1 hour after the APAP dose and maintained at this reduced level through 24 hours. To visualize the specific hepatocytes that had reduced protein sulfhydryl levels, frozen liver sections were labeled with maleimide linked to horseradish peroxidase. The centrilobular areas exhibited dramatic decreases in free protein sulfhydryls while the periportal regions were essentially spared. These protein sulfhydryl-depleted regions correlated with areas exhibiting histopathologic injury and APAP binding to protein. The majority of protein sulfhydryl depletion was due to reversible oxidation since the global-and lobule-specific effects were essentially reversed when the samples were reduced with tris(2-carboxyethy) phosphine before maleimide labeling. These temporal and zonal pattern changes in protein sulfhydryl oxidation shed new light on the importance that changes in protein redox status might play in the pathogenesis of APAP hepatotoxicity. C1 [Salminen, William F.] PAREXEL Int, Bethesda, MD 20814 USA. [Yang, Xi; Greenhaw, James; Shi, Qiang] Natl Ctr Toxicol Res, Div Syst Biol, Jefferson, AR 72079 USA. [Roberts, Dean W.] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. [Hinson, Jack A.] Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. [Muskhelishvili, Levan; Davis, Kelly] Toxicol Pathol Associates, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Salminen, WF (reprint author), PAREXEL Int, 4600 East West Highway,Suite 350, Bethesda, MD 20814 USA. EM willie.salminen@parexel.com FU National Center for Toxicological Research; U.S. Department of Energy; U.S. Food and Drug Administration; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [DK081406]; Arkansas Children's Hospital Research Institute; Arkansas Biosciences Institute, the major research component of the Tobacco Settlement Proceeds Act; National Institutes of Health [R01-DK079008] FX This work was supported by the Research Participation Program at the National Center for Toxicological Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration (to X.Y.); in part by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grant DK081406] (to D. W. R.); by the Arkansas Children's Hospital Research Institute and the Arkansas Biosciences Institute, the major research component of the Tobacco Settlement Proceeds Act of 2000; and by a grant from the National Institutes of Health [Grant R01-DK079008] (to J.A.H.). NR 30 TC 5 Z9 5 U1 0 U2 6 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2013 VL 344 IS 1 BP 286 EP 294 DI 10.1124/jpet.112.199067 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 060VE UT WOS:000312805500030 PM 23093024 ER PT J AU Cho, HC Hadjiiski, L Sahiner, B Chan, HP Helvie, M Paramagul, C Nees, AV AF Cho, Hyun-chong Hadjiiski, Lubomir Sahiner, Berkman Chan, Heang-Ping Helvie, Mark Paramagul, Chintana Nees, Alexis V. TI A similarity study of content-based image retrieval system for breast cancer using decision tree SO MEDICAL PHYSICS LA English DT Article DE breast masses; computer-aided diagnosis; content-based image retrieval; decision tree; ultrasonography ID COMPUTER-AIDED DIAGNOSIS; HIGH FAMILIAL RISK; ULTRASOUND IMAGES; CLUSTERED MICROCALCIFICATIONS; SCREENING MAMMOGRAPHY; SONOGRAPHIC FEATURES; BI-RADS; MASSES; CLASSIFICATION; LESIONS AB Purpose: We are developing a decision tree content-based image retrieval (DTCBIR) CADx system to assist radiologists in characterization of breast masses on ultrasound images. Methods: Three DTCBIR configurations, including decision tree with boosting (DTb), decision tree with full leaf features (DTL), and decision tree with selected leaf features (DTLs) were compared. For DTb, features of a query mass were combined first into a merged feature score and then masses with similar scores were retrieved. For DTL and DTLs, similar masses were retrieved based on the Euclidean distance between feature vectors of the query and those of selected references. For each DTCBIR configuration, we investigated the use of full feature set and subset of features selected by the stepwise linear discriminant analysis (LDA) and simplex optimization method, resulting in six retrieval methods and selected five, DTb-lda, DTL-lda, DTb-full, DTL-full, and DTLs-full, for the observer study. Three MQSA radiologists rated similarities between the query mass and computer-retrieved three most similar masses using nine-point similarity scale (9 = very similar). Results: For DTb-lda, DTL-lda, DTb-full, DTL-full, and DTLs-full, average A(z) values were 0.90 +/- 0.03, 0.85 +/- 0.04, 0.87 +/- 0.04, 0.79 +/- 0.05, and 0.71 +/- 0.06, respectively, and average similarity ratings were 5.00, 5.41, 4.96, 5.33, and 5.13, respectively. Conclusions: The DTL-lda is a promising DTCBIR CADx configuration which had simple tree structure, good classification performance, and highest similarity rating. (C) 2013 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4770277] C1 [Cho, Hyun-chong; Hadjiiski, Lubomir; Sahiner, Berkman; Chan, Heang-Ping; Helvie, Mark; Paramagul, Chintana; Nees, Alexis V.] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Sahiner, Berkman] US FDA, Silver Spring, MD 20993 USA. RP Hadjiiski, L (reprint author), Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. EM lhadjisk@umich.edu FU USPHS [CA 118305] FX This work is supported by USPHS Grant No. CA 118305. The authors are grateful to Charles E. Metz for the LABROC program. NR 57 TC 4 Z9 4 U1 0 U2 16 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JAN PY 2013 VL 40 IS 1 AR 012901 DI 10.1118/1.4770277 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 063WR UT WOS:000313033200051 PM 23298117 ER PT J AU Rostron, B AF Rostron, Brian TI Smoking-Attributable Mortality by Cause in the United States: Revising the CDC's Data and Estimates SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID DEATHS; TOBACCO; RISK AB Smoking is the leading cause of preventable mortality in the United States, but the methods and data used in the Centers for Disease Control and Prevention's (CDC) published estimates of adult smoking-attributable mortality have not been substantially revised since their introduction in the 1980s. We employed the CDC's general methodology for estimating smoking-attributable mortality but produced improved estimates by using recent, nationally representative relative risk data from the National Health Interview Survey-Linked Mortality Files and adjusting for confounding risk factors. We also produced estimates by smoking status and over time. Our use of more recent and nationally representative relative risks tended to decrease estimates of smoking deaths for men and increased estimates for women compared with the CDC's estimates. Adjustment for confounding factors further refined the estimates, particularly by smoking status. We estimated 200,000 smoking-attributable deaths for men and 180,000 smoking-attributable deaths for women in the United States in 2004. Estimated smoking-attributable mortality has finally begun to decline for both U.S. men and women. Our approach offers several substantive improvements in the estimation of smoking-attributable mortality by cause for the United States. Cigarette smoking remains a leading cause of preventable mortality in the United States, but we estimate that the number of smoking-attributable deaths has begun to decline. C1 US FDA, Ctr Tobacco Prod, Rockville, MD 20850 USA. RP Rostron, B (reprint author), US FDA, Ctr Tobacco Prod, 9200 Corp Blvd,Room 300G, Rockville, MD 20850 USA. EM brian.rostron@fda.hhs.gov NR 30 TC 18 Z9 18 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD JAN PY 2013 VL 15 IS 1 BP 238 EP 246 DI 10.1093/ntr/nts120 PG 9 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 061WM UT WOS:000312880900030 PM 22592446 ER PT J AU Salari, R Kimchi-Sarfaty, C Gottesman, MM Przytycka, TM AF Salari, Raheleh Kimchi-Sarfaty, Chava Gottesman, Michael M. Przytycka, Teresa M. TI Sensitive measurement of single-nucleotide polymorphism-induced changes of RNA conformation: application to disease studies SO NUCLEIC ACIDS RESEARCH LA English DT Article ID EUKARYOTIC MESSENGER-RNAS; IRON-RESPONSIVE ELEMENT; SECONDARY STRUCTURE; SYNONYMOUS MUTATIONS; PROTEIN EXPRESSION; ESCHERICHIA-COLI; L-FERRITIN; STABILITY; SEQUENCE; DATABASE AB Single-nucleotide polymorphisms (SNPs) are often linked to critical phenotypes such as diseases or responses to vaccines, medications and environmental factors. However, the specific molecular mechanisms by which a causal SNP acts is usually not obvious. Changes in RNA secondary structure emerge as a possible explanation necessitating the development of methods to measure the impact of single-nucleotide variation on RNA structure. Despite the recognition of the importance of considering the changes in Boltzmann ensemble of RNA conformers in this context, a formal method to perform directly such comparison was lacking. Here, we solved this problem and designed an efficient method to compute the relative entropy between the Boltzmann ensembles of the native and a mutant structure. On the basis of this theoretical progress, we developed a software tool, remuRNA, and investigated examples of its application. Comparing the impact of common SNPs naturally occurring in populations with the impact of random point mutations, we found that structural changes introduced by common SNPs are smaller than those introduced by random point mutations. This suggests a natural selection against mutations that significantly change RNA structure and demonstrates, surprisingly, that randomly inserted point mutations provide inadequate estimation of random mutations effects. Subsequently, we applied remuRNA to determine which of the disease-associated non-coding SNPs are potentially related to RNA structural changes. C1 [Salari, Raheleh; Przytycka, Teresa M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Kimchi-Sarfaty, Chava] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Gottesman, Michael M.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Przytycka, TM (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM przytyck@mail.nih.gov FU National Institutes of Health, National Library of Medicine and National Cancer Institute; Center for Biologics Evaluation and Research FDA; NSERC PDF; National Institutes of Health, National Library of Medicine FX The Intramural Research Program of the National Institutes of Health, National Library of Medicine and National Cancer Institute; the Research Participation program at the Center for Biologics Evaluation and Research FDA; NSERC PDF (in part, to R. S.). The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy. Funding for open access charge: Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 36 TC 21 Z9 21 U1 1 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2013 VL 41 IS 1 BP 44 EP 53 DI 10.1093/nar/gks1009 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 061ZW UT WOS:000312889900037 PM 23125360 ER PT J AU Lawrence, JM Andrade, SE Avalos, LA Beaton, SJ Chiu, VY Davis, RL Dublin, S Pawloski, PA Raebel, MA Smith, DH Toh, S Wang, JQ Kaplan, S Amini, T Hampp, C Hammad, TA Scott, PE Cheetham, TC AF Lawrence, Jean M. Andrade, Susan E. Avalos, Lyndsay A. Beaton, Sarah J. Chiu, Vicki Y. Davis, Robert L. Dublin, Sascha Pawloski, Pamala A. Raebel, Marsha A. Smith, David H. Toh, Sengwee Wang, Jean Q. Kaplan, Sigal Amini, Thushi Hampp, Christian Hammad, Tarek A. Scott, Pamela E. Cheetham, T. Craig CA Medication Exposure Pregnancy Risk TI Prevalence, Trends, and Patterns of Use of Antidiabetic Medications Among Pregnant Women, 2001-2007 SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID GESTATIONAL DIABETES-MELLITUS; INCREASING PREVALENCE; METFORMIN; POPULATION; METAANALYSIS; ALGORITHMS; EXPOSURE; OUTCOMES; YOUTH; DATE AB OBJECTIVE: To describe the prevalence, trends, and patterns in use of antidiabetic medications to treat hyperglycemia and insulin resistance before and during pregnancy in a large U. S. cohort of insured pregnant women. METHODS: Pregnancies resulting in live births were identified (N=437,950) from 2001 to 2007 among 372,543 females 12-50 years of age at delivery from 10 health maintenance organizations participating in the Medication Exposure in Pregnancy Risk Evaluation Program. Information for these descriptive analyses, including all antidiabetic medications dispensed during this period, was extracted from electronic health records and newborn birth certificates. RESULTS: A little more than 1% (1.21%) of deliveries were to women dispensed antidiabetic medication in the 120 days before pregnancy. Use of antidiabetic medications before pregnancy increased from 0.66% of deliveries in 2001 to 1.66% of deliveries in 2007 (P<.001) because of an increase in metformin use. Most women using metformin before pregnancy had a diagnosis code for polycystic ovaries or female infertility (67.2%), whereas only 13.6% had a diagnosis code for diabetes. The use of antidiabetic medications during the second or third trimester of pregnancy increased from 2.8% of deliveries in 2001 to 3.6% in 2007 (P<.001). Approximately two thirds (68%) of women using metformin before pregnancy did not use any antidiabetic medications during pregnancy. CONCLUSIONS: Antidiabetic medication use before and during pregnancy increased from 2001 to 2007, possibly because of increasing prevalence of gestational diabetes mellitus, type 1 and type 2 diabetes, and other conditions associated with insulin resistance. (Obstet Gynecol 2013;121:106-14) DOI: http://10.1097/AOG.0b013e318278ce86 C1 [Lawrence, Jean M.] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA. Meyers Primary Care Inst, Worcester, MA USA. Univ Massachusetts, Sch Med, Worcester, MA USA. Kaiser Permanente No Calif, Div Res, Oakland, CA USA. LCF Res, Albuquerque, NM USA. Kaiser Permanente Georgia, Ctr Hlth Res, Atlanta, GA USA. Grp Hlth Res Inst, Seattle, WA USA. Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA. Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. Harvard Pilgrim Hlth Care Inst, Boston, MA USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. Kaiser Permanente So Calif, Pharm Analyt Serv, Downey, CA USA. RP Lawrence, JM (reprint author), Kaiser Permanente So Calif, Dept Res & Evaluat, 100 S Los Robles,4th Floor, Pasadena, CA 91101 USA. EM Jean.M.Lawrence@kp.org RI Toh, Sengwee/D-7567-2017 OI Toh, Sengwee/0000-0002-5160-0810 FU United States Food and Drug Administration (Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research) [HHSF223200510012C, HHSF223200510009C, HHSF223200510008C]; National Institute on Aging [K23AG028954]; American Geriatrics Society FX This study was supported through funding from contracts HHSF223200510012C, HHSF223200510009C, and HHSF223200510008C from the United States Food and Drug Administration (Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research). We acknowledge the State Health Departments for providing the birth certificate data for this paper.; Dr. Dublin was supported by National Institute on Aging grant K23AG028954.; Dr. Dublin has received a Merck New Investigator Award from the American Geriatrics Society for work unrelated to this project. The other authors did not report any potential conflicts of interest. NR 31 TC 10 Z9 10 U1 0 U2 7 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 JAN PY 2013 VL 121 IS 1 BP 106 EP 114 DI 10.1097/AOG.0b013e318278ce86 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 060LN UT WOS:000312779500016 PM 23262934 ER PT J AU Dworkin, RH Allen, R Kopko, S Lu, Y Turk, DC Burke, LB Desjardins, P Etropolski, M Hewitt, DJ Jayawardena, S Lin, AH Malamut, R Michel, D Ottinger, J Peloso, P Pucino, F Rappaport, BA Skljarevski, V St Peter, D Timinski, S West, CR Wilson, HD AF Dworkin, Robert H. Allen, Robert Kopko, Stephen Lu, Yun Turk, Dennis C. Burke, Laurie B. Desjardins, Paul Etropolski, Mila Hewitt, David J. Jayawardena, Shyamalie Lin, Allison H. Malamut, Richard Michel, Denis Ottinger, James Peloso, Paul Pucino, Frank Rappaport, Bob A. Skljarevski, Vladimir St Peter, David Timinski, Susan West, Christine R. Wilson, Hilary D. TI A standard database format for clinical trials of pain treatments: An ACTTION-CDISC initiative SO PAIN LA English DT Review ID IMMPACT RECOMMENDATIONS; PERSONALIZED MEDICINE; OUTCOME MEASURES C1 [Dworkin, Robert H.] Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY 14642 USA. [Allen, Robert] Afferent Pharmaceut, San Mateo, CA USA. [Kopko, Stephen] Clin Data Interchange Stand Consortium, Austin, TX USA. [Lu, Yun] KAI Res Inc, Rockville, MD USA. [Turk, Dennis C.; Wilson, Hilary D.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [Burke, Laurie B.; Lin, Allison H.; Pucino, Frank; Rappaport, Bob A.] US FDA, Silver Spring, MD USA. [Desjardins, Paul] Desjardins Associates, Maplewood, NJ USA. [Etropolski, Mila; Michel, Denis] Johnson & Johnson Consumer Prod Inc, Titusville, NJ USA. [Hewitt, David J.; Peloso, Paul] Merck & Co Inc, Whitehouse Stn, NJ USA. [Jayawardena, Shyamalie; West, Christine R.] Pfizer Inc, Groton, CT 06340 USA. [Malamut, Richard] AstraZeneca, Wilmington, DE USA. [Ottinger, James] Cephalon, Frazer, PA USA. [Skljarevski, Vladimir] Eli Lilly & Co, Indianapolis, IN 46285 USA. [St Peter, David] Pacira Pharmaceut Inc, Parsippany, NJ USA. [Timinski, Susan] Teva Pharmaceut, Frazer, PA USA. RP Dworkin, RH (reprint author), Univ Rochester, Sch Med & Dent, Dept Anesthesiol, 601 Elmwood Ave,Box 604, Rochester, NY 14642 USA. EM robert_dworkin@urmc.rochester.edu FU FDA [HHSF 223201000078C]; ACTTION public-private partnership FX No official endorsement by the U.S. Food and Drug Administration or the pharmaceutical companies that provided unrestricted grants to support the activities of ACTTION should be inferred. Financial support for this project was provided by a research contract (HHSF 223201000078C) from the FDA to the University of Rochester, and by the ACTTION public-private partnership, which has received research grants or other revenue from the FDA, various pharmaceutical companies, and other sources. We appreciate thoughtful comments on a draft of this manuscript by Ian Gilron, MD, and the support of AstraZeneca, Cephalon, Johnson & Johnson, Lilly, Pacira, and Pfizer in providing materials that were used in the preparation of the pain database standards. The views expressed in this article are those of the authors, none of whom have financial conflicts of interest related to the issues examined in this article. NR 15 TC 2 Z9 2 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JAN PY 2013 VL 154 IS 1 BP 11 EP 14 DI 10.1016/j.pain.2012.10.014 PG 4 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 061AF UT WOS:000312818800006 PM 23218970 ER PT J AU Mirza, T Bykadi, SA Ellison, CD Yang, YS Davit, BM Khan, MA AF Mirza, Tahseen Bykadi, Srikant A. Ellison, Christopher D. Yang, Yongsheng Davit, Barbara M. Khan, Mansoor A. TI Use of In Vitro-In Vivo Correlation to Predict the Pharmacokinetics of Several Products Containing a BCS Class 1 Drug in Extended Release Matrices SO PHARMACEUTICAL RESEARCH LA English DT Article DE BCS Class 1 drug; convolution; deconvolution; dissolution; IVIVC ID METOPROLOL TARTRATE; SUSTAINED-RELEASE; FORMULATION; TABLETS AB To determine if an IVIVC model can predict PK profiles of varying formulations of a BCS Class 1 drug that is a salt of a weak base. An IVIVC model (Level A) was created by correlating deconvoluted in vivo absorption data obtained from oral administration of 50 mg, 100 mg, and 200 mg fast and slow extended release formulations with in vitro percent dissolved using residual regression analysis. The model was then used to predict the in vivo profile of five test products that varied in formulation characteristics. The model passed internal validation for predicted Cmax and AUC. For external validation, in vitro data of five different test formulations was utilized. The model passed external validation for two test formulations that were different but belonging to the same release mechanism as that of the reference formulation. Three formulations failed external validation because they belonged to either a mixed or different release mechanism. The model and results were further confirmed using GatstroPlus (TM) simulation software. These observations indicate that an IVIVC model for a BCS class I drug may be applicable to varying formulations if the principle of the drug release is similar. C1 [Mirza, Tahseen; Bykadi, Srikant A.; Ellison, Christopher D.; Yang, Yongsheng; Khan, Mansoor A.] US FDA, Div Prod Qual Res CDER OPS OTR DPQR, Silver Spring, MD 20993 USA. [Davit, Barbara M.] US FDA, Div Bioequivalence CDER OPS OGD DBII 2, Rockville, MD 20855 USA. RP Mirza, T (reprint author), US FDA, Div Prod Qual Res CDER OPS OTR DPQR, LS Bldg 64,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Tahseen.mirza@fda.hhs.gov NR 19 TC 8 Z9 9 U1 0 U2 24 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORDR JI Pharm. Res. PD JAN PY 2013 VL 30 IS 1 BP 179 EP 190 DI 10.1007/s11095-012-0861-y PG 12 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 058MG UT WOS:000312637300016 PM 22910891 ER PT J AU Zirkelbach, JF Jackson, AJ Wang, YN Schuirmann, DJ AF Zirkelbach, Jeanne Fourie Jackson, Andre J. Wang, Yaning Schuirmann, Donald J. TI Use of Partial AUC (PAUC) to Evaluate Bioequivalence-A Case Study with Complex Absorption: Methylphenidate SO PHARMACEUTICAL RESEARCH LA English DT Article DE bioequivalance; curve shape; methylphenidate; modified release product; partial AUC ID CURVE COMPARISON METRICS; PROFILES; MODEL AB Methylphenidate modified-release products produce early and late peak concentrations critical for treatment of morning and afternoon symptoms of attention deficit hyperactivity disorder (ADHD). Standard bioequivalence (BE) criteria cannot be applied to these products. The performance of partial area under the drug concentration-time curve (PAUC), Cmax and AUCINF to assess BE were independently evaluated for two products. A two-stage analysis was performed on plasma data for two methylphenidate modified-release products (Product 1 and 2). Simulations using the fitted parameters determined how changes in fast absorption rate constant (K0Fast) and fraction available (F1) affected curve shape and BE determination using Cmax, AUCINF and PAUC. The sensitivity of the mean PAUC(test)/PAUC(reference) ratios to changes in K0Fast(test) are product dependent. Product 1 mean PAUC(test)/PAUC(reference) ratios for PAUC0-4h are more responsive to both decreases and increases in K0Fast(test) than Product 2. Product 2 showed a greater response in the mean PAUC(test)/PAUC(reference) ratio for PAUC0-4h when the K0Fast(test) is decreased and less response as the value is increased. PAUC estimated curve shape is sensitive to changes in absorption and are product specific, and may require a new PAUC metric for each drug. A non-product specific metric to assess curve shape is warranted. C1 [Zirkelbach, Jeanne Fourie; Jackson, Andre J.; Wang, Yaning] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Schuirmann, Donald J.] US FDA, Off Bioastatist, Off Translat Sci, Ctr Drug Evaluat Res, Silver Spring, MD 20993 USA. RP Jackson, AJ (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Andre.Jackson@fda.hhs.gov NR 28 TC 3 Z9 4 U1 1 U2 10 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORDR JI Pharm. Res. PD JAN PY 2013 VL 30 IS 1 BP 191 EP 202 DI 10.1007/s11095-012-0862-x PG 12 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 058MG UT WOS:000312637300017 ER PT J AU Sorbello, A Jones, SC Birnkrant, D Dal Pan, G AF Sorbello, Alfred Jones, S. Christopher Birnkrant, Debra Dal Pan, Gerald TI Response to Several Recent Publications Related to Safety and Efficacy of Peramivir From the Emergency Use Authorization Experience Reply SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 [Sorbello, Alfred; Jones, S. Christopher; Dal Pan, Gerald] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Birnkrant, Debra] US FDA, Off Antimicrobial Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Sorbello, A (reprint author), US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM alfred.sorbello@fda.hhs.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2013 VL 56 IS 1 BP 165 EP 165 DI 10.1093/cid/cis801 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 058AE UT WOS:000312605500033 PM 22972860 ER PT J AU Xu, L Elkahloun, AG Candotti, F Grajkowski, A Beaucage, SL Petricoin, EF Calvert, V Juhl, H Mills, F Mason, K Shastri, N Chik, J Xu, C Rosenberg, AS AF Xu, Lai Elkahloun, Abdel G. Candotti, Fabio Grajkowski, Andrzej Beaucage, Serge L. Petricoin, Emanuel F. Calvert, Valerie Juhl, Hartmut Mills, Frederick Mason, Karen Shastri, Neal Chik, Josh Xu, Cynthia Rosenberg, Amy S. TI A Novel Function of RNAs Arising From the Long Terminal Repeat of Human Endogenous Retrovirus 9 in Cell Cycle Arrest SO JOURNAL OF VIROLOGY LA English DT Article ID HISTONE DEACETYLASE INHIBITOR; P53 TUMOR-SUPPRESSOR; GENE-EXPRESSION; GERM-LINE; NF-Y; ACTIVATION; SP1; IDENTIFICATION; TRANSCRIPTION; PROMOTER AB The human genome contains approximately 50 copies of the replication-defective human endogenous retrovirus 9 (ERV-9) and thousands of copies of its solitary long term repeat (sLTR) element. While some sLTRs are located upstream of critical genes and have enhancer activity, other sLTRs are located within introns and may be transcribed as RNAs. We found that intronic RNAs arising from U3 sLTRs of ERV-9 were expressed as both sense (S) and antisense (AS) transcripts in all human cells tested but that expression levels differed in malignant versus nonmalignant cells. In nonmalignant cells, AS was expressed at higher levels than S and at higher levels than in malignant cells; in malignant cells, AS was expressed at amounts equivalent to those of S RNA. Critically, U3 AS RNA was found to physically bind to key transcription factors for cellular proliferation, including NF-Y, p53, and sp1, indicating that such RNA transcripts may function as decoy targets or traps for NF-Y and thus inhibit the growth of human cancer cells. Indeed, short U3 oligodeoxynucleotides (ODNs) based on these RNA sequences ably inhibited proliferation of cancer cell lines driven by cyclins B1/B2, the gene targets of NF-Y. C1 [Xu, Lai; Grajkowski, Andrzej; Beaucage, Serge L.; Mills, Frederick; Mason, Karen; Shastri, Neal; Chik, Josh; Xu, Cynthia; Rosenberg, Amy S.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Elkahloun, Abdel G.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Candotti, Fabio] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Petricoin, Emanuel F.; Calvert, Valerie] George Mason Univ, Ctr Appl Prote & Mol Med, Fairfax, VA 22030 USA. [Juhl, Hartmut] Indivumed GmbH, Hamburg, Germany. RP Rosenberg, AS (reprint author), US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM Amy.Rosenberg@fda.hhs.gov FU NHGRI intramural program funds FX This work was supported by NHGRI intramural program funds (to Fabio Candotti). NR 44 TC 5 Z9 5 U1 1 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2013 VL 87 IS 1 BP 25 EP 36 DI 10.1128/JVI.01648-12 PG 12 WC Virology SC Virology GA 055ZB UT WOS:000312455500003 PM 23097441 ER PT J AU Xie, H Lin, ZS Mosier, PD Desai, UR Gao, YM AF Xie, Hang Lin, Zhengshi Mosier, Philip D. Desai, Umesh R. Gao, Yamei TI The Compensatory G88R Change Is Essential in Restoring the Normal Functions of Influenza A/WSN/33 Virus Matrix Protein 1 with a Disrupted Nuclear Localization Signal SO JOURNAL OF VIROLOGY LA English DT Article ID M1 PROTEIN; A VIRUS; MEMBRANE ASSOCIATION; BINDING; DOMAIN; EXPORT; RNA; RIBONUCLEOPROTEINS; OLIGOMERIZATION; GLYCOPROTEINS AB G88R emerged as a compensatory mutation in matrix protein 1 (M1) of influenza virus A/WSN/33 when its nuclear localization signal (NLS) was disrupted by R101S and R105S substitutions. The resultant M1 triple mutant M(NLS-88R) regained replication efficiency in vitro while remaining attenuated in vivo with the potential of being a live vaccine candidate. To understand why G88R was favored by the virus as a compensatory change for the NLS loss and resultant replication deficiency, three more M1 triple mutants with an alternative G88K, G88V, or G88E change in addition to R101S and R105S substitutions in the NLS were generated. Unlike the other M1 triple mutants, M(NLS-88R) replicated more efficiently in vitro and in vivo. The G88R compensatory mutation not only restored normal functions of M1 in the presence of a disrupted NLS but also resulted in a strong association of M1 with viral ribonucleoprotein. Under a transmission electron microscope, only the M1 layer of the M(NLS-88R) virion exhibited discontinuous fingerprint-like patterns with average thicknesses close to that of wild-type A/WSN/33. Computational modeling suggested that the compensatory G88R change could reestablish the integrity of the M1 layer through new salt bridges between adjacent M1 subunits when the original interactions were interrupted by simultaneous R101S and R105S replacements in the NLS. Our results suggested that restoring the normal functions of M1 was crucial for efficient virus replication. C1 [Xie, Hang; Lin, Zhengshi; Gao, Yamei] US FDA, Div Viral Prod, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Mosier, Philip D.; Desai, Umesh R.] Virginia Commonwealth Univ, Dept Med Chem, Richmond, VA 23298 USA. [Mosier, Philip D.; Desai, Umesh R.] Virginia Commonwealth Univ, Inst Struct Biol & Drug Discovery, Richmond, VA USA. RP Xie, H (reprint author), US FDA, Div Viral Prod, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM Hang.Xie@fda.hhs.gov RI Desai, Umesh/D-3741-2013 FU Intramural Research Program of Center for Biologics Evaluation and Research, U.S. Food and Drug Administration FX This work was supported by the Intramural Research Program of Center for Biologics Evaluation and Research, U.S. Food and Drug Administration. NR 33 TC 2 Z9 2 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2013 VL 87 IS 1 BP 345 EP 353 DI 10.1128/JVI.02024-12 PG 9 WC Virology SC Virology GA 055ZB UT WOS:000312455500029 PM 23077315 ER PT J AU Lewis, JP Horenstein, RB Ryan, K O'Connell, JR Gibson, Q Mitchell, BD Tanner, K Chai, S Bliden, KP Tantry, US Peer, CJ Figg, WD Spencer, SD Pacanowski, MA Gurbel, PA Shuldiner, AR AF Lewis, Joshua P. Horenstein, Richard B. Ryan, Kathleen O'Connell, Jeffrey R. Gibson, Quince Mitchell, Braxton D. Tanner, Keith Chai, Sumbul Bliden, Kevin P. Tantry, Udaya S. Peer, Cody J. Figg, William D. Spencer, Shawn D. Pacanowski, Michael A. Gurbel, Paul A. Shuldiner, Alan R. TI The functional G143E variant of carboxylesterase 1 is associated with increased clopidogrel active metabolite levels and greater clopidogrel response SO PHARMACOGENETICS AND GENOMICS LA English DT Article DE carboxylesterase 1; CES1; clopidogrel; percutaneous coronary intervention; pharmacogenetics ID MYOCARDIAL-INFARCTION; PLATELET REACTIVITY; THIOL METABOLITE; CYP2C19 GENOTYPE; GENETIC-VARIANTS; ESTERASE; IDENTIFICATION; OSELTAMIVIR; INHIBITION; ACTIVATION AB Introduction Carboxylesterase 1 (CES1) is the primary enzyme responsible for converting clopidogrel into biologically inactive carboxylic acid metabolites. Methods We genotyped a functional variant in CES1, G143E, in participants of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study (n=566) and in 350 patients with coronary heart disease treated with clopidogrel, and carried out an association analysis of bioactive metabolite levels, on-clopidogrel ADP-stimulated platelet aggregation, and cardiovascular outcomes. Results The levels of clopidogrel active metabolite were significantly greater in CES1 143E-allele carriers (P = 0.001). Consistent with these findings, individuals who carried the CES1 143E-allele showed a better clopidogrel response as measured by ADP-stimulated platelet aggregation in both participants of the PAPI study (P = 0.003) and clopidogrel-treated coronary heart disease patients (P = 0.03). No association was found between this single nucleotide polymorphism and baseline measures of platelet aggregation in either cohort. Conclusion Taken together, these findings suggest, for the first time, that genetic variation in CES1 may be an important determinant of the efficacy of clopidogrel. Pharmacogenetics and Genomics 23:1-8 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. Pharmacogenetics and Genomics 2013, 23: 1-8 C1 [Lewis, Joshua P.; Horenstein, Richard B.; Ryan, Kathleen; O'Connell, Jeffrey R.; Gibson, Quince; Mitchell, Braxton D.; Tanner, Keith; Chai, Sumbul; Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Lewis, Joshua P.; Horenstein, Richard B.; Ryan, Kathleen; O'Connell, Jeffrey R.; Gibson, Quince; Mitchell, Braxton D.; Tanner, Keith; Chai, Sumbul; Shuldiner, Alan R.] Univ Maryland, Sch Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA. [Bliden, Kevin P.; Tantry, Udaya S.; Gurbel, Paul A.] Sinai Hosp Baltimore, Sinai Ctr Thrombosis Res, Baltimore, MD USA. [Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA. [Peer, Cody J.; Figg, William D.] NCI, Clin Pharmacol Program, Bethesda, MD 20892 USA. [Spencer, Shawn D.] NCI, SAIC Frederick Inc, Appl & Dev Res, Frederick, MD USA. [Pacanowski, Michael A.] US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Silver Spring, MD USA. RP Shuldiner, AR (reprint author), Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, 660 W Redwood St,Rm 494, Baltimore, MD 21201 USA. EM ashuldin@medicine.umaryland.edu RI Figg Sr, William/M-2411-2016; OI Mitchell, Braxton/0000-0003-4920-4744 FU National Institutes of Health [U01 GM074518, U01 GM074518-05S1, U01 HL105198]; University of Maryland General Clinical Research Center [M01 RR 16500]; General Clinical Research Centers Program, National Center for Research Resources (NCRR), NIH; Baltimore Veterans Administration Geriatric Research and Education Clinical Center (GRECC); Sinai Hospital of Baltimore; NIH; Astra Zeneca; Daiichi-Sankyo; Bayer Healthcare; Eli Lilly; Haemonetics; Pozen; Sanofi-Aventis FX This investigation was supported by National Institutes of Health grants U01 GM074518, U01 GM074518-05S1, and U01 HL105198, the University of Maryland General Clinical Research Center, Grant M01 RR 16500, General Clinical Research Centers Program, National Center for Research Resources (NCRR), NIH, the Baltimore Veterans Administration Geriatric Research and Education Clinical Center (GRECC), and Sinai Hospital of Baltimore.; Dr Shuldiner receives grant support from NIH to study the pharmacogenomics of antiplatelet therapy. He is also a consultant for United States Diagnostic Standards Inc. Dr Gurbel receives grant support from Astra Zeneca, Daiichi-Sankyo, Bayer Healthcare, Eli Lilly, Haemonetics, Pozen, and Sanofi-Aventis; and Honoraria/Consulting income from Accumetrics, Astra Zeneca, Bayer Healthcare, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Merck, Pozen, Novartis, CSL Limited, and Sanofi-Aventis. For the remaining authors there are no conflicts of interest. NR 32 TC 52 Z9 56 U1 2 U2 31 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1744-6872 J9 PHARMACOGENET GENOM JI Pharmacogenet. Genomics PD JAN PY 2013 VL 23 IS 1 BP 1 EP 8 DI 10.1097/FPC.0b013e32835aa8a2 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 056OJ UT WOS:000312499800001 PM 23111421 ER PT J CA Anim Biotechnology Interdisciplina TI GUIDELINES FOR THE REGULATION OF GENETICALLY ENGINEERED ANIMALS SO REPRODUCTION FERTILITY AND DEVELOPMENT LA English DT Meeting Abstract C1 [Anim Biotechnology Interdisciplina] US FDA, Ctr Vet Med, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU CSIRO PUBLISHING PI COLLINGWOOD PA 150 OXFORD ST, PO BOX 1139, COLLINGWOOD, VICTORIA 3066, AUSTRALIA SN 1031-3613 J9 REPROD FERT DEVELOP JI Reprod. Fertil. Dev. PY 2013 VL 25 IS 1 BP 322 EP 322 PG 1 WC Developmental Biology; Reproductive Biology; Zoology SC Developmental Biology; Reproductive Biology; Zoology GA 047OJ UT WOS:000311850000362 ER PT S AU Galeotti, L Johannesen, L Vicente, J Strauss, DG AF Galeotti, Loriano Johannesen, Lars Vicente, Jose Strauss, David G. GP IEEE TI Measurement of Noise in ECG Signals to Improve Automatic Delineation SO 2013 COMPUTING IN CARDIOLOGY CONFERENCE (CINC) SE Computing in Cardiology Conference LA English DT Proceedings Paper CT 40th Annual Meeting on Computing in Cardiology (CinC) CY SEP 22-25, 2013 CL Zaragoza, SPAIN SP EMB, IEEE, PhysioNet, Mortara, Univ Inst Investigac Ingn Aragon, Univ Zaragoza, Philips, Escuela Ingn Arquitectura, Univ Zaragoza, GE Healthcare Life Sci, Cardiolund, Ciber-BBN, Centro Investigac Biomedica Red Bioingenieria, Biomateriales Nanomedicina, lOP Publishing, Zoll, Museo Ibercaja, Goya Zaragoza, ESC Working Grp, e-Cardiol, Unive Zaragoza, GTC, Commun Technologies Grp,, Unive Zaragoza, European Soc Cardiol AB Evaluation of quality in digital ECG recordings is of importance when analyzing data archives or for automatic patient monitoring. In these settings, using noisy signals may lead to incorrectly measured ECGs or triggering false alarms in patient monitoring. Empirically defined thresholds are usually employed to exclude noisy recordings. We implemented a method to measure and correct the amount of noise in an ECG dividing it in three different categories: baseline wander, power-line and residual noise (e.g. muscular noise). To decide whether a signal is valid for its intended use (e.g. to measure T-offset), we characterized the amount of errors introduced on the ECG measurements as a function of the measured input noise This method allows a generalized approach to evaluate ECG noise levels and to determine if ECGs are of sufficient quality for the intended use. We present an example showing how to select the noise limits to ensure a 10 ms maximum T-offset error using 74 ECGs (28 simulated and 46 real) and 213 different noise patterns. Using the same data we confirm the ability of the method to correctly measure the noise present in the signal. C1 [Galeotti, Loriano; Vicente, Jose; Strauss, David G.] US FDA, Ctr Devices & Radiol Hlth, Div Phys, Off Sci & Engn Labs, Silver Spring, MD USA. [Johannesen, Lars] US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Off Translat Sci,Div Pharmacometr, Silver Spring, MD USA. [Johannesen, Lars] Karolinska Inst, Dept Clin Physiol, S-10401 Stockholm, Sweden. [Johannesen, Lars] Karolinska Univ Hosp, Stockholm, Sweden. RP Galeotti, L (reprint author), 10903 New Hampshire Ave Bldg 62 RM 1111, Silver Spring, MD 20993 USA. EM Loriano.galeotti@fda.hhs.gov RI GALEOTTI, LORIANO/N-4240-2014 OI GALEOTTI, LORIANO/0000-0002-3200-9080 NR 12 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2325-887X BN 978-1-4799-0884-4 J9 COMPUT CARDIOL CONF PY 2013 VL 40 BP 511 EP 514 PG 4 WC Computer Science, Interdisciplinary Applications; Engineering, Multidisciplinary; Engineering, Biomedical SC Computer Science; Engineering GA BC1AL UT WOS:000349898700130 ER PT S AU Vicente, J Johannesen, L Galeotti, L Strauss, DG AF Vicente, Jose Johannesen, Lars Galeotti, Loriano Strauss, David G. GP IEEE TI ECGlab: User Friendly ECG/VCG Analysis Tool for Research Environments SO 2013 COMPUTING IN CARDIOLOGY CONFERENCE (CINC) SE Computing in Cardiology Conference LA English DT Proceedings Paper CT 40th Annual Meeting on Computing in Cardiology (CinC) CY SEP 22-25, 2013 CL Zaragoza, SPAIN SP EMB, IEEE, PhysioNet, Mortara, Univ Inst Investigac Ingn Aragon, Univ Zaragoza, Philips, Escuela Ingn Arquitectura, Univ Zaragoza, GE Healthcare Life Sci, Cardiolund, Ciber-BBN, Centro Investigac Biomedica Red Bioingenieria, Biomateriales Nanomedicina, lOP Publishing, Zoll, Museo Ibercaja, Goya Zaragoza, ESC Working Grp, e-Cardiol, Unive Zaragoza, GTC, Commun Technologies Grp,, Unive Zaragoza, European Soc Cardiol ID LEADS AB We present ECGlab, a cross-platform, user friendly, graphical user interface for assessing results from automated analysis of ECGs in research environments. ECGlab allows visual inspection and adjudication of ECGs. It is part of our recently developed framework to automatically analyze ECGs from clinical studies, including those in the US Food and Drug Administration (FDA) ECG Warehouse. ECGlab is written in C++ using open-source libraries. Supported ECG formats include Physionet, ISHNE and FDA XML HL7. ECG processing and automated analysis is done with ECGlib (ECG analysis library). ECGs can be loaded individually or grouped using ECGlib index format and information such as demographics or signal quality metrics can be loaded from metafiles to navigate through the ECGs and guide their review. The user can graphically adjudicate the ECGs in a semi-automatic or manual fashion. Vectorcardiograms can be assessed as well. A prototype for automatic extraction, based on heart rate stability and signal quality, of 10 seconds ECGs from continuous Holter recordings is also available. ECGlab, which has been successfully tested in Linux and Microsoft Windows, is currently being used to assess ECGs from clinical studies. We are working on making ECGlab open-source in order to facilitate ECG research. C1 [Vicente, Jose; Galeotti, Loriano; Strauss, David G.] US FDA, Div Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Johannesen, Lars] US FDA, Div Pharmacometr, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Johannesen, Lars] Karolinska Inst, Dept Clin Physiol, S-10401 Stockholm, Sweden. [Johannesen, Lars] Karolinska Univ Hosp, Stockholm, Sweden. RP Vicente, J (reprint author), 10903 New Hampshire Ave,WO62-1125B, Silver Spring, MD 20993 USA. EM jose.vicente@fda.hhs.gov RI GALEOTTI, LORIANO/N-4240-2014 OI GALEOTTI, LORIANO/0000-0002-3200-9080 NR 18 TC 5 Z9 5 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2325-887X BN 978-1-4799-0884-4 J9 COMPUT CARDIOL CONF PY 2013 VL 40 BP 775 EP 778 PG 4 WC Computer Science, Interdisciplinary Applications; Engineering, Multidisciplinary; Engineering, Biomedical SC Computer Science; Engineering GA BC1AL UT WOS:000349898700196 ER PT S AU Johannesen, L Vicente, J Galeotti, L Strauss, DG AF Johannesen, Lars Vicente, Jose Galeotti, Loriano Strauss, David G. GP IEEE TI ECGlib: Library for Processing Electrocardiograms SO 2013 COMPUTING IN CARDIOLOGY CONFERENCE (CINC) SE Computing in Cardiology Conference LA English DT Proceedings Paper CT 40th Annual Meeting on Computing in Cardiology (CinC) CY SEP 22-25, 2013 CL Zaragoza, SPAIN SP EMB, IEEE, PhysioNet, Mortara, Univ Inst Investigac Ingn Aragon, Univ Zaragoza, Philips, Escuela Ingn Arquitectura, Univ Zaragoza, GE Healthcare Life Sci, Cardiolund, Ciber-BBN, Centro Investigac Biomedica Red Bioingenieria, Biomateriales Nanomedicina, lOP Publishing, Zoll, Museo Ibercaja, Goya Zaragoza, ESC Working Grp, e-Cardiol, Unive Zaragoza, GTC, Commun Technologies Grp,, Unive Zaragoza, European Soc Cardiol ID ANALYSIS SYSTEM; QT; RECORDINGS; ALGORITHMS; PATTERNS; DATABASE; SAFETY AB To facilitate evaluation of ECGs in the FDA ECG Warehouse, public databases and clinical trials we have developed a C++ library for processing ECGs (ECGlib). ECGlib has a modular design, and is capable of handling files stored in many different formats, e.g. ISHNE, Physionet and FDA HL7. Moreover, ECGlib provides functions to do standard ECG signal processing, such as noise removal, QRS detection, classification, median beat creation and ECG waveform delineation. The performance of the different components of ECGlib has been evaluated using publicly available databases from Physionet (MIT-BIH and QTDB). The performance of ECGlib processing methodologies is comparable to state-of-the-art methods. We have also developed a MATLAB/Octave interface for ECGlib and are working on an interface for Python, R and Julia. Lastly, ECGlib comes with a set of command line tools that utilize parallel processing to quickly enable researchers to process large databases. We believe frameworks such as the one described can be used to facilitate research of ECG signals and we are working on making the library publicly available under an open source license. C1 [Johannesen, Lars] USDA, Div Pharmacometr, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Washington, DC USA. [Johannesen, Lars] Karolinska Inst, Dept Clin Physiol, S-10401 Stockholm, Sweden. [Johannesen, Lars] Karolinska Univ Hosp, Stockholm, Sweden. [Vicente, Jose; Galeotti, Loriano; Strauss, David G.] USDA, Div Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Washington, DC USA. RP Johannesen, L (reprint author), 10903 New Hampshire Ave,Bldg 62 RM2127E, Silver Spring, MD 20910 USA. EM lars.johannesen@fda.hhs.gov RI GALEOTTI, LORIANO/N-4240-2014 OI GALEOTTI, LORIANO/0000-0002-3200-9080 NR 25 TC 8 Z9 8 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2325-887X BN 978-1-4799-0884-4 J9 COMPUT CARDIOL CONF PY 2013 VL 40 BP 951 EP 954 PG 4 WC Computer Science, Interdisciplinary Applications; Engineering, Multidisciplinary; Engineering, Biomedical SC Computer Science; Engineering GA BC1AL UT WOS:000349898700240 ER PT J AU Johnson, LG Gubrij, IB Pangle, AK Pang, L AF Johnson, L. G. Gubrij, I. B. Pangle, A. K. Pang, L. TI Upregulation Of Micrornas 21 And 223 In An Animal Model Of Pulmonary Hypertension SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Johnson, L. G.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Gubrij, I. B.; Pangle, A. K.] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. [Pang, L.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4644 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838401287 ER PT J AU Pereira, C Wang, Y Scott, DE Reed, JL AF Pereira, C. Wang, Y. Scott, D. E. Reed, J. L. TI Autocrine, Cytosolic Alpha-1 Proteinase Inhibitor (a1pi) Regulates Intracellular Reactive Oxygen Species In Human Monocytes SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Pereira, C.; Wang, Y.; Scott, D. E.; Reed, J. L.] US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4136 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838400572 ER PT J AU Wang, Y Scott, DE Reed, JL AF Wang, Y. Scott, D. E. Reed, J. L. TI Cytosolic Alpha-1 Proteinase Inhibitor (a1pi) Promotes Autophagy-Induced Limitation Of Il-1beta Release In Monocytes SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Wang, Y.; Scott, D. E.; Reed, J. L.] US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A5173 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838402001 ER PT B AU Sarkar, S Ray, B Sharma, J Schmued, L Lahiri, DK AF Sarkar, Sumit Ray, Balmiki Sharma, Jay Schmued, Larry Lahiri, Debomoy K. BE Brahmachari, G TI Role of Curcumin in Ameliorating Neuroinflammation and Neurodegeneration Associated with Alzheimer's Disease SO CHEMISTRY AND PHARMACOLOGY OF NATURALLY OCCURRING BIOACTIVE COMPOUNDS LA English DT Article; Book Chapter ID AMYLOID-BETA-PEPTIDE; GAMMA-SECRETASE INHIBITORS; APOLIPOPROTEIN-E GENOTYPE; AGED GARLIC EXTRACT; NF-KAPPA-B; NEUROTROPHIC FACTOR; PRECURSOR PROTEIN; TRANSGENIC MICE; IN-VIVO; PHOTOCHEMICAL STABILITY C1 [Sarkar, Sumit; Schmued, Larry] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Ray, Balmiki; Lahiri, Debomoy K.] Indiana Univ Sch Med, Inst Psychiat Res, Dept Psychiat, Indianapolis, IN 46202 USA. [Sharma, Jay] Celprogen Inc, Dept Pharmacol, San Pedro, CA USA. [Lahiri, Debomoy K.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. RP Sarkar, S (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 98 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-9168-1; 978-1-4398-9167-4 PY 2013 BP 259 EP 271 D2 10.1201/b13867 PG 13 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BD1QM UT WOS:000358281300013 ER PT J AU Fuzery, AK Levin, J Chan, MM Chan, DW AF Fuezery, Anna K. Levin, Joshua Chan, Maria M. Chan, Daniel W. TI Translation of proteomic biomarkers into FDA approved cancer diagnostics: issues and challenges SO CLINICAL PROTEOMICS LA English DT Review DE Proteomic biomarker; Analytical performance; Clinical performance; Food and drug administration AB Tremendous efforts have been made over the past few decades to discover novel cancer biomarkers for use in clinical practice. However, a striking discrepancy exists between the effort directed toward biomarker discovery and the number of markers that make it into clinical practice. One of the confounding issues in translating a novel discovery into clinical practice is that quite often the scientists working on biomarker discovery have limited knowledge of the analytical, diagnostic, and regulatory requirements for a clinical assay. This review provides an introduction to such considerations with the aim of generating more extensive discussion for study design, assay performance, and regulatory approval in the process of translating new proteomic biomarkers from discovery into cancer diagnostics. We first describe the analytical requirements for a robust clinical biomarker assay, including concepts of precision, trueness, specificity and analytical interference, and carryover. We next introduce the clinical considerations of diagnostic accuracy, receiver operating characteristic analysis, positive and negative predictive values, and clinical utility. We finish the review by describing components of the FDA approval process for protein-based biomarkers, including classification of biomarker assays as medical devices, analytical and clinical performance requirements, and the approval process workflow. While we recognize that the road from biomarker discovery, validation, and regulatory approval to the translation into the clinical setting could be long and difficult, the reward for patients, clinicians and scientists could be rather significant. C1 [Fuezery, Anna K.; Chan, Daniel W.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA. [Levin, Joshua; Chan, Maria M.] US FDA, Div Immunol & Hematol Devices, Off In Vitro Diagnost Devices & Radiol Hlth, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Chan, Daniel W.] Johns Hopkins Med Inst, Dept Pathol, Ctr Biomarker Discovery, Baltimore, MD 21231 USA. RP Fuzery, AK (reprint author), Royal Alexandra Hosp, Dept Pathol & Lab Med, Diagnost Treatment Ctr, Room 5047, Edmonton, AB T5H 3V9, Canada. EM anna.fuezery@albertahealthservices.ca NR 84 TC 74 Z9 75 U1 4 U2 21 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1542-6416 EI 1559-0275 J9 CLIN PROTEOM JI Clin. Proteom. PY 2013 VL 10 AR 13 DI 10.1186/1559-0275-10-13 PG 14 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA V42YQ UT WOS:000209649500005 PM 24088261 ER PT S AU Hung, HMJ Wang, SJ O'Neill, R AF Hung, Hsien-Ming James Wang, Sue-Jane O'Neill, Robert BE Liu, JP Chow, SC Hsiao, CF TI Issues of Sample Size in Bridging Trials and Global Clinical Trials SO DESIGN AND ANALYSIS OF BRIDGING STUDIES SE Chapman & Hall-CRC Biostatistics Series LA English DT Article; Book Chapter C1 [Hung, Hsien-Ming James; Wang, Sue-Jane; O'Neill, Robert] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Hung, HMJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA SN 2154-4298 BN 978-1-4398-4635-3; 978-1-4398-4634-6 J9 CH CRC BIOSTAT SER JI Chapman & Hall-CRC Biostat. Ser. PY 2013 BP 105 EP 119 PG 15 WC Mathematical & Computational Biology; Pharmacology & Pharmacy SC Mathematical & Computational Biology; Pharmacology & Pharmacy GA BD7HU UT WOS:000363112800008 ER PT S AU Wang, SJ AF Wang, Sue-Jane BE Liu, JP Chow, SC Hsiao, CF TI Application of Genomic Technologies for Bridging Strategy Involving Different Race and Ethnicity in Pharmacogenomics Clinical Trials SO DESIGN AND ANALYSIS OF BRIDGING STUDIES SE Chapman & Hall-CRC Biostatistics Series LA English DT Article; Book Chapter ID CELL LUNG-CANCER; GROWTH-FACTOR-RECEPTOR; ACUTE CORONARY SYNDROMES; METASTATIC COLORECTAL-CANCER; GEFITINIB ANTITUMOR-ACTIVITY; TYROSINE KINASE INHIBITOR; PHASE-III TRIAL; TIMI 38 TRIAL; BREAST-CANCER; ACTIVATING MUTATIONS C1 [Wang, Sue-Jane] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Wang, SJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 89 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA SN 2154-4298 BN 978-1-4398-4635-3; 978-1-4398-4634-6 J9 CH CRC BIOSTAT SER JI Chapman & Hall-CRC Biostat. Ser. PY 2013 BP 151 EP 196 PG 46 WC Mathematical & Computational Biology; Pharmacology & Pharmacy SC Mathematical & Computational Biology; Pharmacology & Pharmacy GA BD7HU UT WOS:000363112800010 ER PT S AU Tsong, Y Tsou, HH AF Tsong, Yi Tsou, Hsiao-Hui BE Liu, JP Chow, SC Hsiao, CF TI Multiregional Clinical Trials SO DESIGN AND ANALYSIS OF BRIDGING STUDIES SE Chapman & Hall-CRC Biostatistics Series LA English DT Article; Book Chapter ID SAMPLE-SIZE; SUPERIORITY; HYPOTHESES; REGIONS C1 [Tsong, Yi] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Tsou, Hsiao-Hui] Natl Hlth Res Inst, Zhunan Township, Miaoli County, Taiwan. RP Tsong, Y (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 31 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA SN 2154-4298 BN 978-1-4398-4635-3; 978-1-4398-4634-6 J9 CH CRC BIOSTAT SER JI Chapman & Hall-CRC Biostat. Ser. PY 2013 BP 219 EP 234 PG 16 WC Mathematical & Computational Biology; Pharmacology & Pharmacy SC Mathematical & Computational Biology; Pharmacology & Pharmacy GA BD7HU UT WOS:000363112800012 ER PT J AU Pathmanathan, P Gray, RA AF Pathmanathan, Pras Gray, Richard A. TI Ensuring reliability of safety-critical clinical applications of computational cardiac models SO FRONTIERS IN PHYSIOLOGY LA English DT Article DE modeling; software; verification; validation; uncertainty quantification ID ION-CHANNEL; VARIABILITY; POTENTIALS; TISSUE AB Computational models of cardiac electrophysiology have been used for over half a century to investigate physiological mechanisms and generate hypotheses for experimental testing, and are now starting to play a role in clinical applications. There is currently a great deal of interest in using models as diagnostic or therapeutic aids, for example using patient-specific whole-heart simulations to optimize cardiac resynchronization therapy, ablation therapy, and defibrillation. However, if models are to be used in safety-critical clinical decision making, the reliability of their predictions needs to be thoroughly investigated. In engineering and the physical sciences, the field of "verification, validation and uncertainty quantification" (VVUQ) [also known as "verification and validation" (V&V)] has been developed for rigorously evaluating the credibility of computational model predictions. In this article we first discuss why it is vital that cardiac models be developed and evaluated within a VVUQ framework, and then consider cardiac models in the context of each of the stages in VVUQ. We identify some of the major difficulties which may need to be overcome for cardiac models to be used in safely-critical clinical applications. C1 [Pathmanathan, Pras; Gray, Richard A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Pathmanathan, Pras] Univ Oxford, Dept Comp Sci, Oxford, England. RP Pathmanathan, P (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,WO-62,Room 1103, Silver Spring, MD 20993 USA. EM prasanna.pathmanathan@fda.hhs.gov RI Gray, Richard/F-3916-2015 OI Gray, Richard/0000-0003-2798-6378 FU UK EPSRC [EP/I017909/1] FX The authors would like to thank Gary Mirams (University of Oxford) for important discussions leading to this work, and Leonardo Angelone, Tina M. Morrison and David Strauss (Center for Devices and Radiological Health, FDA) for their feedback. Pras Pathmanathan would like to acknowledge support from the UK EPSRC-funded "2020 Science" programme (grant number: EP/I017909/1). NR 34 TC 13 Z9 13 U1 0 U2 5 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-042X J9 FRONT PHYSIOL JI Front. Physiol. PY 2013 VL 4 AR 358 DI 10.3389/fphys.2013.00358 PG 6 WC Physiology SC Physiology GA AX2LA UT WOS:000346774000350 PM 24376423 ER PT B AU Wedam, SB Lipkowitz, S AF Wedam, Suparna B. Lipkowitz, Stanley BE Yand, SX Dancey, JE TI HER-2 as a Prognostic and Predictive Biomarker in Cancer SO HANDBOOK OF THERAPEUTIC BIOMARKERS IN CANCER LA English DT Article; Book Chapter ID EPIDERMAL-GROWTH-FACTOR; METASTATIC BREAST-CANCER; IN-SITU HYBRIDIZATION; TOPOISOMERASE-II-ALPHA; CELL LUNG-CANCER; EPITHELIAL OVARIAN-CANCER; OF-AMERICAN-PATHOLOGISTS; RANDOMIZED PHASE-II; HUMANIZED ANTI-HER2 ANTIBODY; PRIMARY PERITONEAL CARCINOMA C1 [Wedam, Suparna B.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Lipkowitz, Stanley] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Wedam, SB (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM Suparna.Wedam@fda.hhs.gov; lipkowis@mail.nih.gov NR 197 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-981-4364-66-9; 978-981-4364-65-2 PY 2013 BP 77 EP 120 PG 44 WC Oncology SC Oncology GA BC7QB UT WOS:000355142300005 ER PT B AU Hassan, M Kainerstorfer, J Chernomordik, V Vogel, A Gannot, I Little, RF Yarchoan, R Gandjbakhche, AH AF Hassan, Moinuddin Kainerstorfer, Jana Chernomordik, Victor Vogel, Abby Gannot, Israel Little, Richard F. Yarchoan, Robert Gandjbakhche, Amir H. BE Diakides, M Bronzino, JD Peterson, DR TI Noninvasive Infrared Imaging for Functional Monitoring of Disease Processes SO MEDICAL INFRARED IMAGING: PRINCIPLES AND PRACTICES LA English DT Article; Book Chapter ID TISSUE OPTICAL-PROPERTIES; RESOLVED TRANSILLUMINATION EXPERIMENTS; ENDOTHELIAL GROWTH-FACTOR; ANISOTROPIC RANDOM-WALKS; HIGHLY SCATTERING MEDIA; DOMAIN PHOTON MIGRATION; IN-VIVO FLUORESCENCE; SKIN BLOOD-FLOW; KAPOSIS-SARCOMA; QUANTITATIVE ASSESSMENT C1 [Hassan, Moinuddin] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Kainerstorfer, Jana; Chernomordik, Victor; Little, Richard F.; Yarchoan, Robert; Gandjbakhche, Amir H.] NIH, Bethesda, MD 20892 USA. [Vogel, Abby] Georgia Inst Technol, Atlanta, GA 30332 USA. [Gannot, Israel] Tel Aviv Univ, Dept Biomed Engn, IL-69978 Tel Aviv, Israel. RP Hassan, M (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. NR 120 TC 0 Z9 0 U1 0 U2 1 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-7250-5; 978-1-4398-7249-9 PY 2013 PG 31 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BC6MS UT WOS:000354125200020 ER PT J AU Khalaj, M Abbasi, A Yamanishi, H Akiyama, K Kikuchi, S Hirose, M Yuzuriha, M Magari, M Degheidy, H Abe, K Ogura, A Hashimoto, H Kunieda, T AF Khalaj, M. Abbasi, A. Yamanishi, H. Akiyama, K. Kikuchi, S. Hirose, M. Yuzuriha, M. Magari, M. Degheidy, H. Abe, K. Ogura, A. Hashimoto, H. Kunieda, T. TI A missense mutation in Rev7 disrupts formation of Pol zeta and impairs mouse development and replication dependent ICL DNA repair SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Khalaj, M.; Abbasi, A.] NIH, Bethesda, MD 20892 USA. [Khalaj, M.; Abbasi, A.; Yamanishi, H.; Akiyama, K.; Magari, M.; Kunieda, T.] Okayama Univ, Okayama, Japan. [Kikuchi, S.; Hashimoto, H.] Yokohama City Univ, Yokohama, Kanagawa 232, Japan. [Hirose, M.; Yuzuriha, M.; Abe, K.; Ogura, A.] Riken Bioresource Ctr, Tsukuba, Ibaraki, Japan. [Degheidy, H.] FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 987 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348701311 ER PT J AU Iha, MH Barbosa, CB Okada, IA Trucksess, MW AF Iha, Maria Helena Barbosa, Cynara Baltazar Okada, Isaura Akemi Trucksess, Mary W. TI Aflatoxin M-1 in milk and distribution and stability of aflatoxin M-1 during production and storage of yoghurt and cheese SO FOOD CONTROL LA English DT Article DE Aflatoxin M-1; Milk; Cheese; Yoghurt ID BRAZIL; M1; RISK AB The objective of this study was to investigate the incidence and occurrence of aflatoxin M-1 (AFM(1)) in Brazilian milk and infant formula. The distribution and stability of AFM(1) in cheese and yoghurt were also determined. Milk samples and infant formula samples were purchased in Ribeirao Preto-SP, Brazil and were analyzed for AFM(1) using immunoaffinity column purification, liquid chromatography separation and fluorescence detection. AFM(1) was detected in 83% of the milk samples (>3 ng/kg) with levels ranging from 8 to 437 ng/kg for fluid milk, and 20-760 ng/kg for powdered milk. No AFM(1) was found in infant formula. Processing and storage was shown to have little effect on AFM(1) content in milk and milk products. Total AFM(1) mass in milk was reduced by 3.2% in cheese and by 6% in yoghurt (pH 4.4). The mean concentration of AFM(1) in curds was 1.9-fold higher and whey was 0.6-fold lower than in unprocessed milk. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Iha, Maria Helena; Barbosa, Cynara Baltazar; Okada, Isaura Akemi] Adolfo Lutz Inst, Nucleo Ciencias Quim & Bromatol, CLR Ribeirao Preto, BR-14085410 Ribeirao Preto, SP, Brazil. [Trucksess, Mary W.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD USA. RP Iha, MH (reprint author), Adolfo Lutz Inst, Nucleo Ciencias Quim & Bromatol, CLR Ribeirao Preto, Rua Minas 877, BR-14085410 Ribeirao Preto, SP, Brazil. EM mhiha@ial.sp.gov.br FU FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) FX The authors are grateful to FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) for financial support. NR 25 TC 25 Z9 25 U1 6 U2 43 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-7135 J9 FOOD CONTROL JI Food Control PD JAN PY 2013 VL 29 IS 1 BP 1 EP 6 DI 10.1016/j.foodcont.2012.05.058 PG 6 WC Food Science & Technology SC Food Science & Technology GA 020HW UT WOS:000309800600001 ER PT J AU Ryan, PB Madigan, D Stang, PE Overhage, JM Racoosin, JA Hartzema, AG AF Ryan, Patrick B. Madigan, David Stang, Paul E. Overhage, J. Marc Racoosin, Judith A. Hartzema, Abraham G. TI Empirical assessment of methods for risk identification in healthcare data: results from the experiments of the Observational Medical Outcomes Partnership SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT 32nd Annual Conference of the International-Society-for-Clinical-Biostatistics CY AUG 21-25, 2011 CL Ontario, CANADA DE product surveillance; postmarketing; pharmacoepidemiology; epidemiologic methods; causality; electronic health records; adverse drug reactions ID CLINICAL-TRIALS; CASE-CROSSOVER; SURVEILLANCE; SCIENCE; DESIGNS AB Background: Expanded availability of observational healthcare data (both administrative claims and electronic health records) has prompted the development of statistical methods for identifying adverse events associated with medical products, but the operating characteristics of these methods when applied to the real-world data are unknown. Methods: We studied the performance of eight analytic methods for estimating of the strength of association-relative risk (RR) and associated standard error of 53 drugadverse event outcome pairs, both positive and negative controls. The methods were applied to a network of ten observational healthcare databases, comprising over 130 million lives. Performance measures included sensitivity, specificity, and positive predictive value of methods at RR thresholds achieving statistical significance of p < 0.05 or p < 0.001 and with absolute threshold RR > 1.5, as well as threshold-free measures such as area under receiver operating characteristic curve (AUC). Results: Although no specific method demonstrated superior performance, the aggregate results provide a benchmark and baseline expectation for risk identification method performance. At traditional levels of statistical significance (RR > 1, p < 0.05), all methods have a false positive rate >18%, with positive predictive value <38%. The best predictive model, high-dimensional propensity score, achieved an AUC = 0.77. At 50% sensitivity, false positive rate ranged from 16% to 30%. At 10% false positive rate, sensitivity of the methods ranged from 9% to 33%. Conclusions: Systematic processes for risk identification can provide useful information to supplement an overall safety assessment, but assessment of methods performance suggests a substantial chance of identifying false positive associations. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 [Ryan, Patrick B.; Stang, Paul E.] Johnson & Johnson Pharmaceut Res & Dev LLC, Titusville, NJ USA. [Ryan, Patrick B.; Madigan, David; Stang, Paul E.; Overhage, J. Marc; Racoosin, Judith A.; Hartzema, Abraham G.] Fdn Natl Inst Hlth, Bethesda, MD USA. [Ryan, Patrick B.] Univ N Carolina, UNC Eshelman Sch Pharm, Chapel Hill, NC USA. [Madigan, David] Columbia Univ, Dept Stat, New York, NY USA. [Overhage, J. Marc] Indiana Univ Sch Med, Indianapolis, IN USA. [Overhage, J. Marc] Regenstrief Inst Hlth Care, Indianapolis, IN 46202 USA. [Racoosin, Judith A.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Hartzema, Abraham G.] Univ Florida, Coll Pharm, Gainesville, FL USA. RP Ryan, PB (reprint author), Johnson & Johnson Consumer Prod Inc, 1125 Trenton Harbourton Rd,POB 200,MS K304, Titusville, NJ 08560 USA. EM ryan@omop.org FU Foundation for the National Institutes of Health through Abbott; Foundation for the National Institutes of Health through Amgen; Foundation for the National Institutes of Health through AstraZeneca; Foundation for the National Institutes of Health through Bayer Healthcare Pharmaceuticals, Inc.; Foundation for the National Institutes of Health through Pharmaceutical Research Manufacturers of America; Foundation for the National Institutes of Health through Roche; Foundation for the National Institutes of Health through Sanofi; Foundation for the National Institutes of Health through Schering-Plough Corporation; Foundation for the National Institutes of Health through Takeda FX The OMOP is funded by the Foundation for the National Institutes of Health through generous contributions from the following: Abbott, Amgen Inc., AstraZeneca, Bayer Healthcare Pharmaceuticals, Inc., Bristol-Myers Squibb, Eli Lilly & Company, GlaxoSmithKline, Johnson & Johnson, Lundbeck, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc, Pharmaceutical Research Manufacturers of America, Roche, Sanofi, Schering-Plough Corporation, and Takeda. Drs Ryan and Stang are employees of Johnson & Johnson, and Dr. Ryan is a past employee of GlaxoSmithKline. The authors thank and acknowledge the research contributions of the OMOP Distributed Partners, Department of Veterans Affairs Center for Medication Safety/Outcomes Research, Pharmacy Benefits Management Services, Humana Inc., Indiana University-Regenstrief Institute, Massachusetts General Hospital supporting the work of Partners HealthCare System, and SDI Health, who were supported by a grant from the Foundation for the National Institutes of Health. The authors appreciate the thoughtful feedback from the OMOP Executive and Advisory Boards, notably Elizabeth Andrews, Andrew Bate, Jesse Berlin, Jeffrey Brown, Diane MacKinnon, and Judy Staffa. No compensation was given for the reviews. NR 22 TC 77 Z9 77 U1 3 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD DEC 30 PY 2012 VL 31 IS 30 SI SI BP 4401 EP 4415 DI 10.1002/sim.5620 PG 15 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 055XJ UT WOS:000312451000021 PM 23015364 ER PT J AU Lohne, JJ Andersen, WC Clark, SB Turnipseed, SB Madson, MR AF Lohne, Jack J. Andersen, Wendy C. Clark, Susan B. Turnipseed, Sherri B. Madson, Mark R. TI Laser diode thermal desorption mass spectrometry for the analysis of quinolone antibiotic residues in aquacultured seafood SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; FLUORESCENCE DETECTION; CAPILLARY-ELECTROPHORESIS; ELECTROSPRAY-IONIZATION; RAPID-DETERMINATION; AMBIENT CONDITIONS; FISH; CONFIRMATION; THROUGHPUT; HPLC AB RATIONALE Veterinary drug residue analysis of meat and seafood products is an important part of national regulatory agency food safety programs to ensure that consumers are not exposed to potentially dangerous substances. Complex tissue matrices often require lengthy extraction and analysis procedures to identify improper animal drug treatment. Direct and rapid analysis mass spectrometry techniques have the potential to increase regulatory sample analysis speed by eliminating liquid chromatographic separation. METHODS Flumequine, oxolinic acid, and nalidixic acid were extracted from catfish, shrimp, and salmon using acidified acetonitrile. Extracts were concentrated, dried onto metal sample wells, then rapidly desorbed (6 s) with an infrared diode laser for analysis by laser diode thermal desorption atmospheric pressure chemical ionization with tandem mass spectrometry (LDTD-MS/MS). Analysis was conducted in selected reaction monitoring mode using piromidic acid as internal standard. RESULTS Six-point calibration curves for each compound in extracted matrix were linear with r(2) correlation greater than 0.99. The method was validated by analyzing 23 negative samples and 116 fortified samples at concentrations of 10, 20, 50, 100, and 600 ng/g. Average recoveries of fortified samples were greater than 77% with method detection levels ranging from 2 to 7 ng/g. Three product ion transitions were acquired per analyte to identify each residue. CONCLUSIONS A rapid method for quinolone analysis in fish muscle was developed using LDTD-MS/MS. The total analysis time was less than 30 s per sample; quinolone residues were detected below 10 ng/g and in most cases residue identity was confirmed. This represents the first application of LDTD to tissue extract analysis. Published 2012. This article is a US Government work and is in the public domain in the USA. C1 [Lohne, Jack J.; Andersen, Wendy C.; Turnipseed, Sherri B.; Madson, Mark R.] US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Denver, CO 80225 USA. [Clark, Susan B.; Madson, Mark R.] US FDA, Denver Lab, Denver Fed Ctr, Denver, CO 80225 USA. RP Andersen, WC (reprint author), US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Bldg 20,W 6th Ave & Kipling St, Denver, CO 80225 USA. EM wendy.andersen@fda.hhs.gov NR 46 TC 9 Z9 9 U1 9 U2 57 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PD DEC 30 PY 2012 VL 26 IS 24 BP 2854 EP 2864 DI 10.1002/rcm.6414 PG 11 WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA 034KT UT WOS:000310872500002 PM 23136016 ER PT J AU Liu, ST Han, J Nacif, MS Jones, J Kawel, N Kellman, P Sibley, CT Bluemke, DA AF Liu, Songtao Han, Jing Nacif, Marcelo S. Jones, Jacquin Kawel, Nadine Kellman, Peter Sibley, Christopher T. Bluemke, David A. TI Diffuse myocardial fibrosis evaluation using cardiac magnetic resonance T1 mapping: sample size considerations for clinical trials SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Article ID EXTRACELLULAR VOLUME FRACTION; AMERICAN-HEART-ASSOCIATION; INVERSION-RECOVERY MOLLI; GD-DTPA; INTRAINDIVIDUAL ASSESSMENT; ENDOMYOCARDIAL BIOPSY; INTERSTITIAL FIBROSIS; CONTRAST ENHANCEMENT; CARDIOMYOPATHY; DISEASE AB Background: Cardiac magnetic resonance (CMR) T1 mapping has been used to characterize myocardial diffuse fibrosis. The aim of this study is to determine the reproducibility and sample size of CMR fibrosis measurements that would be applicable in clinical trials. Methods: A modified Look-Locker with inversion recovery (MOLLI) sequence was used to determine myocardial T1 values pre-, and 12 and 25min post-administration of a gadolinium-based contrast agent at 3 Tesla. For 24 healthy subjects (8 men; 29 +/- 6 years), two separate scans were obtained a) with a bolus of 0.15mmol/kg of gadopentate dimeglumine and b) 0.1mmol/kg of gadobenate dimeglumine, respectively, with averaged of 51 +/- 34 days between two scans. Separately, 25 heart failure subjects (12 men; 63 +/- 14 years), were evaluated after a bolus of 0.15mmol/kg of gadopentate dimeglumine. Myocardial partition coefficient (lambda) was calculated according to (Delta R1myocardium/Delta R1blood), and ECV was derived from lambda by adjusting (1-hematocrit). Results: Mean ECV and lambda were both significantly higher in HF subjects than healthy (ECV: 0.287 +/- 0.034 vs. 0.267 +/- 0.028, p = 0.002; lambda:0.481 +/- 0.052 vs. 442 +/- 0.037, p < 0.001, respectively). The inter-study ECV and. variation were about 2.8 times greater than the intra-study ECV and lambda variation in healthy subjects (ECV: 0.017 vs. 0.006, lambda:0.025 vs. 0.009, respectively). The estimated sample size to detect ECV change of 0.038 or lambda change of 0.063 (corresponding to similar to 3% increase of histological myocardial fibrosis) with a power of 80% and an alpha error of 0.05 for heart failure subjects using a two group design was 27 in each group, respectively. Conclusion: ECV and. quantification have a low variability across scans, and could be a viable tool for evaluating clinical trial outcome. C1 [Liu, Songtao; Nacif, Marcelo S.; Jones, Jacquin; Kawel, Nadine; Sibley, Christopher T.; Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Liu, Songtao; Nacif, Marcelo S.; Sibley, Christopher T.; Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Mol Biomed Imaging Lab, Bethesda, MD USA. [Han, Jing] US FDA, Rockville, MD 20857 USA. [Kellman, Peter] NHLBI, Cardiac Energet Lab, Bethesda, MD 20892 USA. RP Bluemke, DA (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. EM bluemked@cc.nih.gov RI Sibley, Christopher/C-9900-2013; OI Bluemke, David/0000-0002-8323-8086 FU National Institutes of Health (NIH) FX Funded by the National Institutes of Health (NIH) intramural program. NR 47 TC 32 Z9 32 U1 0 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1097-6647 J9 J CARDIOVASC MAGN R JI J. Cardiov. Magn. Reson. PD DEC 28 PY 2012 VL 14 AR 90 DI 10.1186/1532-429X-14-90 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 096BH UT WOS:000315378200003 PM 23272704 ER PT J AU Hershko, K Simhadri, VL Blaisdell, A Hunt, RC Newell, J Tseng, SC Hershko, AY Choi, JW Sauna, ZE Wu, A Bram, RJ Komar, AA Kimchi-Sarfaty, C AF Hershko, Klilah Simhadri, Vijaya L. Blaisdell, Adam Hunt, Ryan C. Newell, Jordan Tseng, Sandra C. Hershko, Alon Y. Choi, Jae Won Sauna, Zuben E. Wu, Andrew Bram, Richard J. Komar, Anton A. Kimchi-Sarfaty, Chava TI Cyclosporin A Impairs the Secretion and Activity of ADAMTS13 (A Disintegrin and Metalloprotease with Thrombospondin Type 1 Repeat) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID THROMBOTIC THROMBOCYTOPENIC PURPURA; VON-WILLEBRAND-FACTOR; HEMOLYTIC-UREMIC SYNDROME; FACTOR-CLEAVING PROTEASE; BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; PLASMA-EXCHANGE; SURFACE EXPRESSION; MTOR INHIBITORS; CYCLOPHILIN-B AB The protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat) cleaves multimers of von Willebrand factor, thus regulating platelet aggregation. ADAMTS13 deficiency leads to the fatal disorder thrombotic thrombocytopenic purpura (TTP). It has been observed that cyclosporin A (CsA) treatment, particularly in transplant patients, may sometimes be linked to the development of TTP. Until now, the reason for such a link was unclear. Here we provide evidence demonstrating that cyclophilin B (CypB) activity plays an important role in the secretion of active ADAMTS13. We found that CsA, an inhibitor of CypB, reduces the secretion of ADAMTS13 and leads to conformational changes in the protein resulting in diminished ADAMTS13 proteolytic activity. A direct, functional interaction between CypB (which possesses peptidyl-prolyl cis-trans isomerase (PPIase) and chaperone functions) and ADAMTS13 is demonstrated using immunoprecipitation and siRNA knockdown of CypB. Finally, CypB knockout mice were found to have reduced ADAMTS13 levels. Taken together, our findings indicate that cyclophilin-mediated activity is an important factor affecting secretion and activity of ADAMTS13. The large number of proline residues in ADAMTS13 is consistent with the important role of cis-trans isomerization in the proper folding of this protein. These results altogether provide a novel mechanistic explanation for CsA-induced TTP in transplant patients. C1 [Hershko, Klilah; Simhadri, Vijaya L.; Blaisdell, Adam; Hunt, Ryan C.; Newell, Jordan; Tseng, Sandra C.; Sauna, Zuben E.; Wu, Andrew; Kimchi-Sarfaty, Chava] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20982 USA. [Choi, Jae Won; Bram, Richard J.] Mayo Clin, Dept Pediat Hematol Oncol, Rochester, MN 55905 USA. [Hershko, Alon Y.] Meir Med Ctr, Dept Med, IL-44281 Kefar Sava, Israel. [Komar, Anton A.] Cleveland State Univ, Ctr Gene Regulat Hlth & Dis, Dept Biol Geol & Environm Sci, Cleveland, OH 44115 USA. RP Kimchi-Sarfaty, C (reprint author), 29 Lincoln Dr, Bethesda, MD 20892 USA. EM Chava.kimchi-sarfaty@fda.hhs.gov FU United States Food and Drug Administration; National American Heart Association [0730120N] FX This work was supported by the United States Food and Drug Administration and National American Heart Association Grant 0730120N (to A. A. K.). NR 67 TC 6 Z9 6 U1 2 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 28 PY 2012 VL 287 IS 53 BP 44361 EP 44371 DI 10.1074/jbc.M112.383968 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 062RI UT WOS:000312938600033 PM 23144461 ER PT J AU Woodcock, J Khan, M Yu, LX AF Woodcock, Janet Khan, Mansoor Yu, Lawrence X. TI Withdrawal of Generic Budeprion for Nonbioequivalence SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Woodcock, Janet; Khan, Mansoor; Yu, Lawrence X.] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Woodcock, J (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RI Yu, Lawrence/L-6280-2016 NR 1 TC 20 Z9 22 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 DEC 27 PY 2012 VL 367 IS 26 BP 2463 EP 2465 DI 10.1056/NEJMp1212969 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 059OG UT WOS:000312714200002 PM 23216549 ER PT J AU Fernandez, CV Ruccione, K Wells, RJ Long, JB Pelletier, W Hooke, MC Pentz, RD Noll, RB Baker, JN O'Leary, M Reaman, G Adamson, PC Joffe, S AF Fernandez, Conrad V. Ruccione, Kathleen Wells, Robert J. Long, Jay B. Pelletier, Wendy Hooke, Mary C. Pentz, Rebecca D. Noll, Robert B. Baker, Justin N. O'Leary, Maura Reaman, Gregory Adamson, Peter C. Joffe, Steven TI Recommendations for the Return of Research Results to Study Participants and Guardians: A Report From the Children's Oncology Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CLINICAL-TRIAL; INFORMED-CONSENT; CANCER; ATTITUDES; MEDIA; ADOLESCENTS; SURVIVORS; COVERAGE; MEETINGS; PARENTS AB Purpose The Children's Oncology Group (COG) strongly supports the widely recognized principle that research participants should be offered a summary of study results. The mechanism by which to do so in a cooperative research group setting has not been previously described. Methods On the basis of a review of the available empirical and theoretic literature and on iterative, multidisciplinary discussion, a COG Return of Results Task Force (RRTF) offered detailed recommendations for the return of results to research study participants. Results The RRTF established guidelines for the notification of research participants and/or their parents/guardians about the availability of research results, a mechanism for and timing of sharing results via registration on the COG public Web site, the scope of the research to be shared, the target audience, and a process for creating and vetting lay summaries of study results. The RRTF recognized the challenges in adequately conveying complex scientific results to audiences with varying levels of health literacy and recommended that particularly sensitive or complex results be returned using direct personal contact. The RRTF also recommended evaluation of the cost, effectiveness, and impact of sharing results. Conclusion These recommendations provide a framework for the offering and returning of results to participants. They can be used by individual investigators, multi-investigator research collaboratives, and large cooperative groups. J Clin Oncol 30:4573-4579. (C) 2012 by American Society of Clinical Oncology C1 [Fernandez, Conrad V.] Dalhousie Univ, Izaak Walton Killam Hlth Ctr, Halifax, NS, Canada. [Pelletier, Wendy] Alberta Childrens Prov Gen Hosp, Calgary, AB T2T 5C7, Canada. [Ruccione, Kathleen] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Long, Jay B.] Miller Childrens Hosp Long Beach, Long Beach, CA USA. [Wells, Robert J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Hooke, Mary C.] Univ Minnesota, Sch Nursing, Minneapolis, MN 55455 USA. [Pentz, Rebecca D.] Emory Univ, Sch Med, Atlanta, GA USA. [Noll, Robert B.] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. [Adamson, Peter C.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Baker, Justin N.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [O'Leary, Maura] US FDA, Rockville, MD 20857 USA. [Reaman, Gregory] George Washington Univ, Sch Med & Hlth Sci, Childrens Natl Med Ctr, Washington, DC 20052 USA. [Joffe, Steven] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. [Joffe, Steven] Harvard Univ, Sch Med, Boston, MA USA. RP Fernandez, CV (reprint author), Dalhousie Univ, 5850 Univ Ave, Halins, NS B3K 6R8, Canada. EM conrad.fernandez@iwk.nshealth.ca OI Joffe, Steven/0000-0002-0667-7384 FU Children's Oncology Group, National Cancer Institute, National Institutes of Health, Bethesda, MD [U10 CA98543, U10 CA98413] FX Supported by Chair Grant No. U10 CA98543 and Statistics and Data Center Grant No. U10 CA98413 from the Children's Oncology Group, National Cancer Institute, National Institutes of Health, Bethesda, MD. NR 54 TC 5 Z9 5 U1 0 U2 9 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 DEC 20 PY 2012 VL 30 IS 36 BP 4573 EP 4579 DI 10.1200/JCO.2012.45.2086 PG 7 WC Oncology SC Oncology GA 060YT UT WOS:000312815000025 PM 23109703 ER PT J AU Plant, EP Liu, TM Xie, H Ye, ZP AF Plant, Ewan P. Liu, Teresa M. Xie, Hang Ye, Zhiping TI Mutations to A/Puerto Rico/8/34 PB1 gene improves seasonal reassortant influenza A virus growth kinetics SO VACCINE LA English DT Article DE Influenza; Vaccine; Polymerase; Protein yield ID SEGMENT 2; POLYMERASE-ACTIVITY; RNA-POLYMERASE; IDENTIFICATION; PROTEIN; PA; GENERATION; CONTRIBUTE; VACCINE; ORIGIN AB It is desirable for influenza vaccine virus strains to have phenotypes that include good growth and hemagglutinin (HA) protein yield. The quality of these characteristics varies among the vaccine viruses and is usually due to multigenic effects. Many influenza A virus vaccine viruses are made as reassortants of the high yield virus A/Puerto Rico/8/34 (PR/8) and a circulating seasonal virus. Co-infection of eggs with the two viruses, and selection of reassortants with the HA and neuraminidase (NA) segments from the seasonal virus, can result in viruses that contain a mixture of internal genes derived from both the high yield virus and the circulating virus. Segment 2 (PB1), which encodes the RNA-dependent RNA polymerase, frequently cosegregates with the seasonal HA and NA segments. We asked whether mutations based on the seasonal PB1 genes could improve vaccine virus strains. Here we report that mutations to the PR/8 PB1 gene, based on differences observed between seasonal and PR/8 PB1 genes, accelerate egg and cell culture based replication for a reassortant virus containing HA and NA segments from the low yield A/Wyoming/03/2003 (H3N2) vaccine virus. Published by Elsevier Ltd. C1 [Plant, Ewan P.; Liu, Teresa M.; Xie, Hang; Ye, Zhiping] US FDA, Lab Resp Viral Dis, Div Viral Prod, Off Vaccine Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Ye, ZP (reprint author), US FDA, Lab Resp Viral Dis, Div Viral Prod, Off Vaccine Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM Zhiping.Ye@fda.hhs.gov OI Plant, Ewan/0000-0003-0166-5939 FU Biomedical Advanced Research and Development Authority, Department of Health and Human Services FX We would like to thank Dr. Vladimir Lugovtsev for comments and suggestions. This work was supported in part by the Biomedical Advanced Research and Development Authority, Department of Health and Human Services. NR 27 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD DEC 17 PY 2012 VL 31 IS 1 BP 207 EP 212 DI 10.1016/j.vaccine.2012.10.060 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 067PA UT WOS:000313306400030 PM 23116694 ER PT J AU Moratz, C Burton, E Liu, YB Myers, M McCabe, J AF Moratz, Chantal Burton, Ellen Liu, Yumbo Myers, Matthew McCabe, Joseph TI Blood brain barrier alterations and neuro-inflammation after single or repetitive exposures to primary blast using a high-intensity focused ultrasound model of mild traumatic brain injury (mTBI) SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 11th International Congress of Neuroimmunology (ISNI) CY NOV 04-08, 2012 CL Boston, MA SP European Sch Neuroimmunol, Int Soc Neuroimmunol (ISNI) C1 [Moratz, Chantal] Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. [Burton, Ellen] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA. [Liu, Yumbo; Myers, Matthew] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [McCabe, Joseph] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD DEC 15 PY 2012 VL 253 IS 1-2 BP 25 EP 25 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 060GP UT WOS:000312764800065 ER PT J AU Cortazar, P Zhang, L Untch, M Mehta, K Costantino, J Wolmark, N Bonnefoi, H Cameron, D Gianni, L Valagussa, P Zujewski, JA Justice, R Loibl, S Wickerham, L Bogaerts, J Baselga, J Perou, C Blumenthal, G Blohmer, J Mamounas, E Bergh, J Semiglazov, V Prowell, T Eidtmann, H Paik, S Piccart, M Sridhara, R Fasching, P Swain, SM Slaets, L Tang, S Gerber, B Geyer, C Pazdur, R Ditsch, N Rastogi, P Eiermann, W von Mincwitz, G AF Cortazar, P. Zhang, L. Untch, M. Mehta, K. Costantino, J. Wolmark, N. Bonnefoi, H. Cameron, D. Gianni, L. Valagussa, P. Zujewski, J. A. Justice, R. Loibl, S. Wickerham, L. Bogaerts, J. Baselga, J. Perou, C. Blumenthal, G. Blohmer, J. Mamounas, E. Bergh, J. Semiglazov, V. Prowell, T. Eidtmann, H. Paik, S. Piccart, M. Sridhara, R. Fasching, P. Swain, S. M. Slaets, L. Tang, S. Gerber, B. Geyer, C. Pazdur, R. Ditsch, N. Rastogi, P. Eiermann, W. von Mincwitz, G. TI Meta-analysis Results from the Collaborative Trials in Neoadjuvant Breast Cancer (CTNeoBC) SO CANCER RESEARCH LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. HELIOS Klinikum Berlin Buch, Berlin, Germany. NSABP, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA USA. INSERM, Inst Bergonie, U916, Bordeaux, France. Univ Bordeaux Segalen, Bordeaux, France. Univ Edinburgh, Edinburgh, Midlothian, Scotland. Ist Sci San Raffaele, I-20132 Milan, Italy. Fdn Michelangelo, Milan, Italy. NCI, Bethesda, MD 20892 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. GBG Forsch GmbH, Berlin, Germany. Washington Hosp Ctr, Washington, DC 20010 USA. St Gertrauden Hosp, Berlin, Germany. Univ Womens Hosp, Kiel, Germany. Univ Womens Hosp, Erlangen, Germany. Univ Womens Hosp, Rostock, Germany. Univ Womens Hosp, Munich, Germany. Karolinska Inst, Stockholm, Sweden. St Gorans Univ Hosp, S-11281 Stockholm, Sweden. EORTC Headquarters, Brussels, Belgium. Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. NN Petrov Res Inst Oncol, St Petersburg, Russia. Inst Jules Bordet, B-1000 Brussels, Belgium. NR 0 TC 22 Z9 24 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 DEC 15 PY 2012 VL 72 SU 24 MA S1-11 DI 10.1158/0008-5472.SABCS12-S1-11 PG 2 WC Oncology SC Oncology GA V43TY UT WOS:000209704900090 ER PT J AU Ylitalo, GM Krahn, MM Dickhoff, WW Stein, JE Walker, CC Lassitter, CL Garrett, ES Desfosse, LL Mitchell, KM Noble, BT Wilson, S Beck, NB Benner, RA Koufopoulos, PN Dickey, RW AF Ylitalo, Gina M. Krahn, Margaret M. Dickhoff, Walton W. Stein, John E. Walker, Calvin C. Lassitter, Cheryl L. Garrett, E. Spencer Desfosse, Lisa L. Mitchell, Karen M. Noble, Brandi T. Wilson, Steven Beck, Nancy B. Benner, Ronald A. Koufopoulos, Peter N. Dickey, Robert W. TI Federal seafood safety response to the Deepwater Horizon oil spill SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article AB Following the 2010 Deepwater Horizon oil spill, petroleum-related compounds and chemical dispersants were detected in the waters of the Gulf of Mexico. As a result, there was concern about the risk to human health through consumption of contaminated seafood in the region. Federal and Gulf Coast State agencies worked together on a sampling plan and analytical protocols to determine whether seafood was safe to eat and acceptable for sale in the marketplace. Sensory and chemical methods were used to measure polycyclic aromatic hydrocarbons (PAHs) and dispersant in >8,000 seafood specimens collected in federal waters of the Gulf. Overall, individual PAHs and the dispersant component dioctyl sodium sulfosuccinate were found in low concentrations or below the limits of quantitation. When detected, the concentrations were at least two orders of magnitude lower than the level of concern for human health risk. Once an area closed to fishing was free of visibly floating oil and all sensory and chemical results for the seafood species within an area met the criteria for reopening, that area was eligible to be reopened. On April 19, 2011 the area around the wellhead was the last area in federal waters to be reopened nearly 1 y after the spill began. However, as of November 9, 2011, some state waters off the Louisiana coast (Barataria Bay and the Delta region) remain closed to fishing. C1 [Ylitalo, Gina M.; Krahn, Margaret M.; Dickhoff, Walton W.; Stein, John E.] Natl Marine Fisheries Serv, NW Fisheries Sci Ctr, NOAA, Seattle, WA 98112 USA. [Walker, Calvin C.; Lassitter, Cheryl L.; Garrett, E. Spencer] Natl Marine Fisheries Serv, Natl Seafood Inspect Lab, SE Fisheries Sci Ctr, NOAA, Pascagoula, MS 39567 USA. [Desfosse, Lisa L.; Mitchell, Karen M.; Noble, Brandi T.] Natl Marine Fisheries Serv, Mississippi Labs, SE Fisheries Sci Ctr, NOAA, Pascagoula, MS 39567 USA. [Wilson, Steven] Natl Marine Fisheries Serv, Seafood Inspect Program, Silver Spring, MD 20910 USA. [Beck, Nancy B.] Off Management & Budget, Off Informat & Regulatory Affairs, Washington, DC 20503 USA. [Benner, Ronald A.; Dickey, Robert W.] US FDA, Div Seafood Sci & Technol, Gulf Coast Seafood Lab, Ctr Food Safety & Appl Nutr, Dauphin Isl, AL 36528 USA. [Koufopoulos, Peter N.] US FDA, Div Seafood Safety, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Ylitalo, GM (reprint author), Natl Marine Fisheries Serv, NW Fisheries Sci Ctr, NOAA, Seattle, WA 98112 USA. EM gina.ylitalo@noaa.gov NR 18 TC 36 Z9 36 U1 7 U2 88 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 DEC 11 PY 2012 VL 109 IS 50 BP 20274 EP 20279 DI 10.1073/pnas.1108886109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 058AF UT WOS:000312605600035 PM 22315401 ER PT J AU Han, J Lynne, AM David, DE Tang, HL Xu, JS Nayak, R Kaldhone, P Logue, CM Foley, SL AF Han, Jing Lynne, Aaron M. David, Donna E. Tang, Hailin Xu, Joshua Nayak, Rajesh Kaldhone, Pravin Logue, Catherine M. Foley, Steven L. TI DNA Sequence Analysis of Plasmids from Multidrug Resistant Salmonella enterica Serotype Heidelberg Isolates SO PLOS ONE LA English DT Article ID ESCHERICHIA-COLI; ANTIMICROBIAL RESISTANCE; COMPARATIVE GENOMICS; SEROVAR HEIDELBERG; VIRULENCE PLASMID; UNITED-STATES; FOOD ANIMALS; INFECTIONS; PREVALENCE; SYSTEMS AB Salmonella enterica serovar Heidelberg is among the most detected serovars in swine and poultry, ranks among the top five serotypes associated with human salmonellosis and is disproportionately associated with invasive infections and mortality in humans. Salmonella are known to carry plasmids associated with antimicrobial resistance and virulence. To identify plasmid-associated genes in multidrug resistant S. enterica serovar Heidelberg, antimicrobial resistance plasmids from five isolates were sequenced using the 454 LifeSciences pyrosequencing technology. Four of the isolates contained incompatibility group (Inc) A/C multidrug resistance plasmids harboring at least eight antimicrobial resistance genes. Each of these strains also carried a second resistance plasmid including two IncFIB, an IncHI2 and a plasmid lacking an identified Inc group. The fifth isolate contained an IncI1 plasmid, encoding resistance to gentamicin, streptomycin and sulfonamides. Some of the IncA/C plasmids lacked the full concert of transfer genes and yet were able to be conjugally transferred, likely due to the transfer genes carried on the companion plasmids in the strains. Several non-IncA/C resistance plasmids also carried putative virulence genes. When the sequences were compared to previously sequenced plasmids, it was found that while all plasmids demonstrated some similarity to other plasmids, they were unique, often due to differences in mobile genetic elements in the plasmids. Our study suggests that Salmonella Heidelberg isolates harbor plasmids that co-select for antimicrobial resistance and virulence, along with genes that can mediate the transfer of plasmids within and among other bacterial isolates. Prevalence of such plasmids can complicate efforts to control the spread of S. enterica serovar Heidelberg in food animal and human populations. C1 [Han, Jing; Nayak, Rajesh; Foley, Steven L.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Lynne, Aaron M.] Sam Houston State Univ, Dept Biol Sci, Huntsville, TX 77340 USA. [Lynne, Aaron M.; David, Donna E.; Kaldhone, Pravin; Foley, Steven L.] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI 54449 USA. [Tang, Hailin; Xu, Joshua] ICF Int Incorporat NCTR FDA, Jefferson, AR USA. [Logue, Catherine M.] Iowa State Univ, Dept Vet Microbiol & Preventat Med, Ames, IA USA. RP Foley, SL (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR USA. EM Steven.Foley@fda.hhs.gov FU Marshfield Clinic Research Foundation; National Center for Toxicological Research FX This project was internally funded by the Marshfield Clinic Research Foundation and the National Center for Toxicological Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 19 Z9 20 U1 0 U2 23 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 10 PY 2012 VL 7 IS 12 AR e51160 DI 10.1371/journal.pone.0051160 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 052ML UT WOS:000312201900049 PM 23251446 ER PT J AU Moir, S De Ravin, SS Santich, BH Kim, JY Posada, JG Ho, J Buckner, CM Wang, W Kardava, L Garofalo, M Marciano, BE Manischewitz, J King, LR Khurana, S Chun, TW Golding, H Fauci, AS Malech, HL AF Moir, Susan De Ravin, Suk See Santich, Brian H. Kim, Jin Young Posada, Jacqueline G. Ho, Jason Buckner, Clarisa M. Wang, Wei Kardava, Lela Garofalo, Mary Marciano, Beatriz E. Manischewitz, Jody King, Lisa R. Khurana, Surender Chun, Tae-Wook Golding, Hana Fauci, Anthony S. Malech, Harry L. TI Humans with chronic granulomatous disease maintain humoral immunologic memory despite low frequencies of circulating memory B cells SO BLOOD LA English DT Article ID HIV-INFECTION; EXPRESSION; ANTIBODIES; BINDING; RECEPTORS; RESPONSES AB CD27(+) memory B cells are reduced in the blood of patients with chronic granulomatous disease (CGD) for reasons and consequences that remain unclear. Here we confirm not only decreased CD27(+) but also IgG(+) B cells in the blood of CGD patients compared with healthy donors (HDs). However, among IgG(+) B cells, the ratio of CD27(-) to CD27(+) was significantly higher in CGD patients compared with HDs. Similar to conventional memory B cells, CD27(-)IgG(+) B cells of CGD patients expressed activation markers and had undergone somatic hypermutation, albeit at levels lower than their CD27(+) counterparts. Functional analyses revealed slight reductions in frequencies of total IgG but not influenza-specific memory B-cell responses, as measured by Elispot in CGD patients compared with HDs. Serum IgG levels and influenza-specific antibodies were also normal in these CGD patients. Finally, we provide evidence that influenza-specific memory B cells can be present within the CD27(-)IgG(+) B-cell compartment. Together, these findings show that, despite reduced circulating CD27(+) memory B cells, CGD patients maintain an intact humoral immunologic memory, with potential contribution from CD27(-) B cells. (Blood. 2012;120(24):4850-4858) C1 [De Ravin, Suk See; Garofalo, Mary; Malech, Harry L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Moir, Susan; Santich, Brian H.; Kim, Jin Young; Posada, Jacqueline G.; Ho, Jason; Buckner, Clarisa M.; Wang, Wei; Kardava, Lela; Chun, Tae-Wook; Fauci, Anthony S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Marciano, Beatriz E.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Manischewitz, Jody; King, Lisa R.; Khurana, Surender; Golding, Hana] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD USA. RP De Ravin, SS (reprint author), NIAID, Host Def Lab, NIH, 10-CRC-5W-3816,10 Ctr Dr, Bethesda, MD 20892 USA. EM smoir@niaid.nih.gov; sderavin@niaid.nih.gov OI Malech, Harry/0000-0001-5874-5775 FU NIAID, National Institutes of Health FX This work was supported by the Intramural Research Program of NIAID, National Institutes of Health. NR 29 TC 22 Z9 23 U1 0 U2 12 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 DEC 6 PY 2012 VL 120 IS 24 BP 4850 EP 4858 DI 10.1182/blood-2012-05-430959 PG 9 WC Hematology SC Hematology GA 064ZO UT WOS:000313115300028 PM 23074274 ER PT J AU Chang, CY Furlong, LA AF Chang, Christina Y. Furlong, Lesley-Anne TI Microbial Stowaways in Topical Antiseptic Products SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Chang, Christina Y.; Furlong, Lesley-Anne] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Chang, CY (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 4 TC 3 Z9 3 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 DEC 6 PY 2012 VL 367 IS 23 BP 2170 EP 2173 DI 10.1056/NEJMp1212680 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 048DO UT WOS:000311890600003 PM 23215554 ER PT J AU McMurry-Heath, M Hamburg, MA AF McMurry-Heath, Michelle Hamburg, Margaret A. TI Creating a Space for Innovative Device Development SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Editorial Material AB The FDA announces a partnership with a new nonprofit organization-the Medical Device Innovation Consortium-to advance regulatory science in the medical technology arena. C1 [McMurry-Heath, Michelle] US FDA, Off Ctr Director, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Hamburg, Margaret A.] US FDA, Off Commissioner, Silver Spring, MD 20993 USA. RP McMurry-Heath, M (reprint author), US FDA, Off Ctr Director, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM michelle.mcmurry-heath@fda.hhs.gov NR 4 TC 10 Z9 10 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD DEC 5 PY 2012 VL 4 IS 163 AR 163fs43 DI 10.1126/scitranslmed.3005269 PG 2 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 049PU UT WOS:000311996700002 PM 23209277 ER PT J AU Co, CC Ho, CC Kumar, G AF Co, Carlos C. Ho, Chia-Chi Kumar, Girish TI Motility-Based Cell Sorting by Planar Cell Chromatography SO ANALYTICAL CHEMISTRY LA English DT Article ID MIGRATION; SIGNALS; SEPARATION; ANISOTROPY; POLARITY; DENSITY AB We report here a new methodology for sorting mammalian cells based on their intrinsic motility on planar substrates, independent of chemoattractants and external fields. This biological analogue of thin layer chromatography consists of arrays of asymmetric adhesive islands on tissue culture dishes that rectify the random movement of cells and direct their migration in a specific direction. We demonstrated the use of planar cell chromatography in the separation of mixtures of 3T3 fibroblasts that express constitutively active Rac1 or RhoA and mixtures of 3T3 fibroblasts and SH-SY5Y neuroblastoma cells. C1 [Co, Carlos C.; Ho, Chia-Chi; Kumar, Girish] Univ Cincinnati, Chem Engn Program, Cincinnati, OH 45221 USA. [Kumar, Girish] US FDA, Div Biol, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Ho, CC (reprint author), Univ Cincinnati, Chem Engn Program, Cincinnati, OH 45221 USA. EM chiachi.ho@uc.edu FU National Institutes of Health [R01EB010043, R21EB005348]; National Science Foundation [CBET0928219] FX This work was supported by the National Institutes of Health (R01EB010043 and R21EB005348) and the National Science Foundation (CBET0928219). We thank Dr. Yi Zheng's laboratory for providing the constitutively active Rac1 and RhoA fibroblasts. NR 22 TC 2 Z9 2 U1 1 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD DEC 4 PY 2012 VL 84 IS 23 BP 10160 EP 10164 DI 10.1021/ac302855m PG 5 WC Chemistry, Analytical SC Chemistry GA 047CM UT WOS:000311815300003 PM 23140541 ER PT J AU Stantchev, TS Paciga, M Lankford, CR Schwartzkopff, F Broder, CC Clouse, KA AF Stantchev, Tzanko S. Paciga, Mark Lankford, Carla R. Schwartzkopff, Franziska Broder, Christopher C. Clouse, Kathleen A. TI Cell-type specific requirements for thiol/disulfide exchange during HIV-1 entry and infection SO RETROVIROLOGY LA English DT Article DE HIV-1; Virus entry; Protein disulfide isomerase; Thioredoxin; Cell type specificity ID PROTEIN-DISULFIDE-ISOMERASE; IMMUNODEFICIENCY-VIRUS TYPE-1; MEMBRANE-FUSION; ENVELOPE GLYCOPROTEIN; REVERSE-TRANSCRIPTASE; PLASMA THIOREDOXIN; VIRAL ENTRY; CD4; BONDS; MECHANISMS AB Background: The role of disulfide bond remodeling in HIV-1 infection is well described, but the process still remains incompletely characterized. At present, the data have been predominantly obtained using established cell lines and/or CXCR4-tropic laboratory-adapted virus strains. There is also ambiguity about which disulfide isomerases/reductases play a major role in HIV-1 entry, as protein disulfide isomerase (PDI) and/or thioredoxin (Trx) have emerged as the two enzymes most often implicated in this process. Results: We have extended our previous findings and those of others by focusing on CCR5-using HIV-1 strains and their natural targets - primary human macrophages and CD4(+) T lymphocytes. We found that the nonspecific thiol/disulfide exchange inhibitor, 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), significantly reduced HIV-1 entry and infection in cell lines, human monocyte-derived macrophages (MDM), and also phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC). Subsequent studies were performed using specific anti-PDI or Trx monoclonal antibodies (mAb) in HIV-1 envelope pseudotyped and wild type (wt) virus infection systems. Although human donor-to-donor variability was observed as expected, Trx appeared to play a greater role than PDI in HIV-1 infection of MDM. In contrast, PDI, but not Trx, was predominantly involved in HIV-1 entry and infection of the CD4(+)/CCR5(+) T cell line, PM-1, and PHA-stimulated primary human T lymphocytes. Intriguingly, both PDI and Trx were present on the surface of MDM, PM-1 and PHA-stimulated CD4(+) T cells. However, considerably lower levels of Trx were detected on freshly isolated CD4(+) lymphocytes, compared to PHA-stimulated cells. Conclusions: Our findings clearly demonstrate the role of thiol/disulfide exchange in HIV-1 entry in primary T lymphocytes and MDM. They also establish a cell-type specificity regarding the involvement of particular disulfide isomerases/reductases in this process and may provide an explanation for differences among previously published studies. More importantly, from an in vivo perspective, the preferential utilization of PDI may be relevant to the HIV-1 entry and establishment of virus reservoirs in resting CD4(+) cells, while the elevated levels of Trx reported in the chronic stages of HIV-1 infection may facilitate the virus entry in macrophages and help to sustain high viremia during the decline of T lymphocytes. C1 [Stantchev, Tzanko S.; Paciga, Mark; Lankford, Carla R.; Schwartzkopff, Franziska; Clouse, Kathleen A.] US FDA, Cell Biol Lab, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. [Broder, Christopher C.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, F Edward Hebert Sch Med, Bethesda, MD 20814 USA. RP Clouse, KA (reprint author), US FDA, Cell Biol Lab, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. EM Kathleen.clouse@fda.hhs.gov FU NIH Intramural AIDS Targeted Antiviral Program (IATAP); Research Participation Program at the Center for Drug Evaluation and Research FX This work was supported in part by the NIH Intramural AIDS Targeted Antiviral Program (IATAP). It was also partially supported by an appointment of Dr. Mark Paciga to the Research Participation Program at the Center for Drug Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U. S. Department of Energy and the U.S. Food and Drug Administration. The authors would also like to thank Dr. David Frucht, Dr. Francisco Borrego and Dr. Klaus Strebel for the critical reading of the manuscript and Dr. Mate Tolnay for his expert assistance in performing and analyzing the surface plasmon resonance experiments. NR 68 TC 13 Z9 13 U1 1 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD DEC 3 PY 2012 VL 9 AR 97 DI 10.1186/1742-4690-9-97 PG 15 WC Virology SC Virology GA 057RP UT WOS:000312582000001 PM 23206338 ER PT J AU Dunne, J Murphy, MD Rodriguez, WJ AF Dunne, Julia Murphy, M. Dianne Rodriguez, William J. TI The Globalization of Pediatric Clinical Trials SO PEDIATRICS LA English DT Article DE pediatric clinical trials; developing countries; drugs; vaccines; biologicals; globalization ID CHILDREN AB OBJECTIVE: To examine the characteristics of pediatric trials conducted under US legislation and to compare results with data from 2002 to 2007. METHODS: We reviewed all pediatric trials provided to the US Food and Drug Administration in submissions that were approved between September 28, 2007 and December 21, 2010. We extracted data for each trial including age range, therapeutic indication, design, duration, and patient and center enrollment by location. RESULTS: Overall 346 studies on 113 drugs and biologicals enrolled 55 819 pediatric patients. The United States participated in 86% of the studies, providing 71% of the centers and 74% of the patients. Corresponding percentages for non-US countries were 43%, 29%, and 26% respectively. Developing or transition countries participated in 22% of the studies, providing 12% of the centers and 10% of the patients; our earlier analysis found corresponding percentages of 38%, 12%, and 23%. The most common therapeutic areas studied in the latter countries were infectious, neurologic, and pulmonary diseases. Seventy-eight vaccine studies enrolled 147 692 patients. The United States participated in 40% of the studies, providing 39% of the centers and 22% of the patients. Corresponding percentages for non-US countries were 74%, 61%, and 78% respectively. Developing or transition countries participated in 27% of the studies, providing 15% of the centers and 52% of the patients. CONCLUSIONS: The United States remains an important location for pediatric trials. Developing country involvement in pediatric drug development is not increasing, although these countries participate significantly in vaccine trials. Pediatrics 2012;130:e1583-e1591 C1 [Dunne, Julia; Murphy, M. Dianne; Rodriguez, William J.] US FDA, Off Pediat Therapeut, Off Commissioner, Silver Spring, MD USA. [Dunne, Julia] Med & Healthcare Prod Regulatory Author, Special Populat Unit, London SW1W 9SZ, England. RP Dunne, J (reprint author), Med & Healthcare Prod Regulatory Author, Special Populat Unit, 151 Buckingham Palace Rd, London SW1W 9SZ, England. EM julia.dunne@mhra.gsi.gov.uk NR 14 TC 3 Z9 4 U1 0 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 2012 VL 130 IS 6 BP E1583 EP E1591 DI 10.1542/peds.2011-3687 PG 9 WC Pediatrics SC Pediatrics GA 087YZ UT WOS:000314802000021 PM 23129087 ER PT J AU Xiao, R Perveen, Z Paulsen, D Rouse, R Ambalavanan, N Kearney, M Penn, AL AF Xiao, Rui Perveen, Zakia Paulsen, Daniel Rouse, Rodney Ambalavanan, Namasivayam Kearney, Michael Penn, Arthur L. TI In Utero Exposure to Second-Hand Smoke Aggravates Adult Responses to Irritants Adult Second-Hand Smoke SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE second-hand smoke; in utero exposure; airway hyperresponsiveness; lung structure changes; gene expression ID OBSTRUCTIVE PULMONARY-DISEASE; ARYL-HYDROCARBON RECEPTOR; CHILDHOOD LUNG-FUNCTION; TOBACCO-SMOKE; GENE-EXPRESSION; AIRWAY RESPONSIVENESS; CELL-DIFFERENTIATION; MATERNAL SMOKING; EPITHELIAL-CELLS; BALB/C MICE AB In utero exposure to second-hand smoke (SHS) is associated with exacerbated asthmatic responses in children. We tested the hypothesis that in utero SHS will aggravate the lung responses of young adult mice re-exposed to SHS. We exposed Balb/c mice in utero to SHS (S) or filtered air (AIR; A), and re-exposed the male offspring daily from 11-15 weeks of age to either SHS (AS and SS) or AIR (AA and SA). After the adult exposures, we analyzed samples of bronchoalveolar lavage fluid (BALF), examined the results of histopathology, and assessed pulmonary function and gene expression changes in lung samples. In SS mice, compared with the other three groups (AA, AS, and SA), we found decreases in breathing frequency and increases in airway hyperresponsiveness (AHR), as well as low but significantly elevated concentrations of BALF proinflammatory cytokines (IL-1b, IL-6, and keratinocyte-derived chemokine). Lung morphometric analyses revealed enlarged airspaces and arteries in SA and SS mice compared with their in utero AIR counterparts, as well as increased collagen deposition in AS and SS mice. Unique gene expression profiles were found for in utero, adult, and combined exposures, as well as for mice with elevated AHR responses. The profibrotic metalloprotease genes, Adamts9 and Mmp3, were up-regulated in the SS and AHR groups, suggesting a role for in utero SHS exposure on the adult development of chronic obstructive pulmonary disease. Our results indicate that in utero exposures to environmentally relevant concentrations of SHS alter lung structure more severely than do adult SHS exposures of longer duration. These in utero exposures also aggravate AHR and promote a profibrotic milieu in adult lungs. C1 [Xiao, Rui; Perveen, Zakia; Penn, Arthur L.] Louisiana State Univ, Sch Vet Med, Dept Comparat Biomed Sci, Baton Rouge, LA 70803 USA. [Paulsen, Daniel; Kearney, Michael] Louisiana State Univ, Sch Vet Med, Dept Pathobiol Sci, Baton Rouge, LA 70803 USA. [Rouse, Rodney] US FDA, Silver Spring, MD USA. [Ambalavanan, Namasivayam] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA. RP Penn, AL (reprint author), Louisiana State Univ, Sch Vet Med, Dept Comparat Biomed Sci, Skip Bertman Dr,Room 2425, Baton Rouge, LA 70803 USA. EM apenn@vetmed.lsu.edu OI Xiao, Rui/0000-0001-8679-9551; Ambalavanan, Namasivayam/0000-0003-0731-9092 FU Louisiana Governor's Biotechnology Initiative; National Institutes of Health [HL092906] FX This work was supported by the Louisiana Governor's Biotechnology Initiative (A.L.P.) and by National Institutes of Health grant HL092906 (N.A.). NR 44 TC 9 Z9 9 U1 1 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD DEC PY 2012 VL 47 IS 6 BP 843 EP 851 DI 10.1165/rcmb.2012-0241OC PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 082QH UT WOS:000314406800015 PM 22962063 ER PT J AU Li, TW Zhao, HT Hung, GC Han, J Tsai, S Li, BJ Zhang, J Puri, RK Lo, SC AF Li, Tianwei Zhao, Hongtao Hung, Guo-Chiuan Han, Jing Tsai, Shien Li, Bingjie Zhang, Jing Puri, Raj K. Lo, Shyh-Ching TI Differentially expressed genes and pathways induced by organophosphates in human neuroblastoma cells SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article DE organophosphate; neuroblastoma; microarray; pathway analysis; gene regulation ID CHLORPYRIFOS; NEUROTOXICITY; PESTICIDES; MUTATIONS; EXPOSURES; STRESS; AGENTS; RAT AB Organophosphates (OPs) are toxic chemicals commonly used as pesticides and herbicides. Some OPs are highly toxic to humans and have been used in warfare and terrorist attacks. In order to elucidate the molecular mechanisms of injury caused by OPs, the differentially expressed genes were analyzed in human SK-N-SH neuroblastoma cells induced by three OPs. The SK-N-SH cells were treated with one of the three OPs, chlorpyrifos, dichlorvos or methamidophos at LC20 (high-dose), the concentration causing 20% cell death, as well as 1/20 of LC20 (low-dose), a sub-lethal concentration with no detectable cell death, for 24 h. The genome-wide gene changes were identified by Agilent Microarray System, and analyzed by microarray analysis tools. The analysis revealed neuroblastoma cells treated with the high doses of all three OPs markedly activated cell apoptosis and inhibited cell growth and proliferation genes, which would most likely lead to the process of cell death. Interestingly, the analysis also revealed significant decrease in expressions of many genes in a specific spliceosome pathway in cells treated with the low doses of all three different OPs. The change of spliceosome pathway may represent an important mechanism of injury in neuronal cells exposed to low doses of various OPs. In addition to unraveling a potentially different form of OP pathogenesis, this finding could provide a new diagnostic marker in assessing OP-associated injury in cells or tissues. In addition, these results could also contribute to the development of new prevention and/or therapeutic regimens against OP toxicity. C1 [Li, Tianwei; Zhao, Hongtao; Hung, Guo-Chiuan; Tsai, Shien; Li, Bingjie; Zhang, Jing; Lo, Shyh-Ching] US FDA, Tissue Safety Lab Program, Bethesda, MD 20892 USA. [Li, Tianwei; Zhao, Hongtao; Hung, Guo-Chiuan; Han, Jing; Tsai, Shien; Li, Bingjie; Zhang, Jing; Puri, Raj K.; Lo, Shyh-Ching] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Lo, SC (reprint author), US FDA, Tissue Safety Lab Program, NIH Bldg 29B,29 Lincoln Dr, Bethesda, MD 20892 USA. EM shyhching.lo@fda.hhs.gov FU Defense Threat Reduction Agency (DTRA) [CBS.MEDCHEM.01.10.FDA.PP008] FX This research was supported by a grant from Defense Threat Reduction Agency (DTRA: #CBS.MEDCHEM.01.10.FDA.PP008). We thank Dr Amy Yang for her help on microarray experiments and data analysis, Dr Ephrem Tekle for his help on confocal microscope. NR 33 TC 2 Z9 2 U1 2 U2 14 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD DEC PY 2012 VL 237 IS 12 BP 1413 EP 1423 DI 10.1258/ebm.2012.012178 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 082GS UT WOS:000314380900006 PM 23354400 ER PT J AU O'Brien, TR Muchmore, B Tang, W Pfeiffer, R Park, H Dickensheets, H Buckett, D Porter-Gill, P Chen, S Astemborski, J Bonkovsky, HL Edlin, BR Howell, CD Morgan, T Thomas, DL Rehermann, B Donnelly, RP Prokunina-Olsson, L AF O'Brien, Thomas R. Muchmore, Brian Tang, Wei Pfeiffer, Ruth Park, Heiyoung Dickensheets, Harold Buckett, Dianna Porter-Gill, Patricia Chen, Sabrina Astemborski, Jacquie Bonkovsky, Herbert L. Edlin, Brian R. Howell, Charles D. Morgan, Timothy Thomas, David L. Rehermann, Barbara Donnelly, Raymond P. Prokunina-Olsson, Ludmila TI A Novel Frame-Shift Genetic Variant Located Near IL28B Creates an Interferon Analog (IFNAN) Protein and Explains Genetic Associations with Impaired HCV Clearance SO HEPATOLOGY LA English DT Meeting Abstract C1 [O'Brien, Thomas R.; Muchmore, Brian; Tang, Wei; Pfeiffer, Ruth; Buckett, Dianna; Porter-Gill, Patricia; Prokunina-Olsson, Ludmila] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Park, Heiyoung; Rehermann, Barbara] NIDDKD, Liver Dis Branch, Bethesda, MD 20892 USA. [Dickensheets, Harold; Donnelly, Raymond P.] US FDA, Div Therapeut Prot, Bethesda, MD 20014 USA. [Chen, Sabrina] Informat Management Serv Inc, Silver Spring, MD USA. [Astemborski, Jacquie; Thomas, David L.] Johns Hopkins Univ, Baltimore, MD USA. [Bonkovsky, Herbert L.] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Edlin, Brian R.] SUNY Downstate Coll Med, Brooklyn, NY USA. [Howell, Charles D.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Morgan, Timothy] VA Long Beach Healthcare Syst, Long Beach, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 2012 VL 56 IS 6 MA LB7 BP 1520 EP 1521 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 081BD UT WOS:000314288900008 ER PT J AU Zhang, J Suzuki, A Kelly, R Fang, H Li, AP Tong, WD AF Zhang, Jie Suzuki, Ayako Kelly, Reagan Fang, Hong Li, Albert P. Tong, Weida TI A novel biomarker, ROS/ATP ratio, accurately predicts drugs associated with serious drug induced liver injury (sDILI) SO HEPATOLOGY LA English DT Meeting Abstract C1 [Zhang, Jie; Kelly, Reagan; Fang, Hong; Tong, Weida] US FDA, Div Bioinformat & Biostat, NCTR, Jefferson, AR USA. [Suzuki, Ayako] Cent Arkansas Vet Healthcare Syst, Hepatol, Little Rock, AR USA. [Li, Albert P.] In Vitro ADMET Labs LLC, Columbia, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 2012 VL 56 IS 6 MA LB10 BP 1523 EP 1524 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 081BD UT WOS:000314288900011 ER PT J AU Kaplan, S Zhou, EH Iyasu, S AF Kaplan, Sigal Zhou, Esther H. Iyasu, Solomon TI Characterization of Long-Acting Beta(2)-Adrenergic Agonists Utilization in Asthma Patients SO JOURNAL OF ASTHMA LA English DT Article DE asthma; drug concurrency; drug use; fixed-dose combination LABAs; long-acting beta(2)-adrenergic agonists; single-ingredient LABAs ID COMMERCIALLY INSURED POPULATION; COMBINATION THERAPY; CONTROLLER THERAPY; CHILDREN; FDA AB Objective. Because of the serious safety risks, Food and Drug Administration (FDA) has recommended that long-acting beta(2)-adrenergic agonists (LABAs) be reserved for patients whose asthma cannot be adequately managed with asthma control medication. The objective of the study is to assess prescribing patterns for LABAs prior to the FDA's drug safety communication issued on 2 June 2010. Methods. Data were extracted from IMS Health Plan Claims database for asthma patients who had a new LABA therapy during 2005-2009. The proportion of LABA incident episodes preceded by inhaled corticosteroid (ICS) or leukotriene receptor antagonists (LTRAs) was examined. The medication-concurrent ratio (MCR), defined as the ratio of overlapping therapy days of single-ingredient (SI) LABAs and non-LABA products to the total days of SI LABAs, was calculated. Four criteria were used to estimate poorly controlled asthma prior to LABA initiation. Results. Of the 228 047 asthma patients, fixed-dose combination (FDC) LABAs were used by the majority of patients (96%). Prior use of ICS or LTRAs was observed in 64% and 31% of SI and FDC LABA incident episodes, respectively. The median MCR for SI LABAs was 62%. Approximately half of the patients met at least one criterion for poorly controlled asthma prior to LABA use. Conclusions. Substantial proportion of patients was prescribed LABAs without prior use of ICS or LTRAs, or other indicators of poor asthma control. These findings suggest that asthma guidelines were not entirely followed in clinical practice during the study period. C1 [Kaplan, Sigal; Zhou, Esther H.; Iyasu, Solomon] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. RP Iyasu, S (reprint author), US FDA, Div Epidemiol 1, Off Pharmacovigilance & Epidemiol, 10903 New Hampshire Ave,Bldg 22,Rm 2472, Silver Spring, MD 20993 USA. EM Solomon.Iyasu@fda.hhs.gov NR 20 TC 7 Z9 7 U1 0 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0277-0903 J9 J ASTHMA JI J. Asthma PD DEC PY 2012 VL 49 IS 10 BP 1079 EP 1085 DI 10.3109/02770903.2012.733990 PG 7 WC Allergy; Respiratory System SC Allergy; Respiratory System GA 080ZG UT WOS:000314283000011 PM 23106094 ER PT J AU De Feo, CJ Weiss, CD AF De Feo, Christopher J. Weiss, Carol D. TI Escape from Human Immunodeficiency Virus Type 1 (HIV-1) Entry Inhibitors SO VIRUSES-BASEL LA English DT Review DE resistance; entry inhibitor; virus entry; fusion; envelope glycoprotein; HIV ID GP120 ENVELOPE GLYCOPROTEIN; TERMINAL HEPTAD REPEAT; SMALL-MOLECULE INHIBITORS; PEPTIDE FUSION INHIBITOR; CORECEPTOR ANTAGONIST VICRIVIROC; MULTIPLE CONFORMATIONAL STATES; RELATIVE REPLICATIVE FITNESS; ANTI-CD4 MONOCLONAL-ANTIBODY; CHEMOKINE RECEPTOR CXCR4; TREATMENT-NAIVE SUBJECTS AB The human immunodeficiency virus (HIV) enters cells through a series of molecular interactions between the HIV envelope protein and cellular receptors, thus providing many opportunities to block infection. Entry inhibitors are currently being used in the clinic, and many more are under development. Unfortunately, as is the case for other classes of antiretroviral drugs that target later steps in the viral life cycle, HIV can become resistant to entry inhibitors. In contrast to inhibitors that block viral enzymes in intracellular compartments, entry inhibitors interfere with the function of the highly variable envelope glycoprotein as it continuously adapts to changing immune pressure and available target cells in the extracellular environment. Consequently, pathways and mechanisms of resistance for entry inhibitors are varied and often involve mutations across the envelope gene. This review provides a broad overview of entry inhibitor resistance mechanisms that inform our understanding of HIV entry and the design of new inhibitors and vaccines. C1 [De Feo, Christopher J.; Weiss, Carol D.] US FDA, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Weiss, CD (reprint author), US FDA, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM christopher.defeo@fda.hhs.gov; carol.weiss@fda.hhs.gov RI Weiss, Carol/F-6438-2011 OI Weiss, Carol/0000-0002-9965-1289 FU FDA; NIH Intramural AIDS Targeted Antiviral Program FX We thank Ira Berkower and Russell Vassell (US FDA, Bethesda, MD) for critical reading of the manuscript. This work was supported in part by institutional funds from the FDA and the NIH Intramural AIDS Targeted Antiviral Program. NR 350 TC 11 Z9 12 U1 0 U2 27 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1999-4915 J9 VIRUSES-BASEL JI Viruses-Basel PD DEC PY 2012 VL 4 IS 12 BP 3859 EP 3911 DI 10.3390/v4123859 PG 53 WC Virology SC Virology GA 082OO UT WOS:000314401700031 PM 23342377 ER PT J AU Anderson, DL AF Anderson, David L. TI Effect of L-cysteine on drying and neutron irradiation loss of Hg, Se, As, and Br from fish tissue SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS LA English DT Article DE Fish tissue; Mercury; Selenium; Arsenic; Bromine; Neutron activation analysis; L-Cysteine treatment; Irradiation losses; Drying losses; Food safety; Food analysis; Food composition ID ACTIVATION-ANALYSIS; BIOLOGICAL-MATERIALS; MERCURY; STABILITY; STANDARD; SAMPLES AB Powdered, thawed composited, and fresh frozen fish tissues were analyzed for Hg, Se, As, and Br. Experiments were designed to measure or estimate upper limits of long-term storage, drying, and instrumental neutron activation analysis (INAA) irradiation-related analyte losses. Tissue was analyzed as received (dried, if necessary, for INAA) and treated with L-cysteine to determine if such treatment reduces analyte loss, especially for Hg. Untreated tissues experienced large (23-49%) volatile Hg losses during irradiation. L-Cysteine treatment followed by freeze drying reduced Hg losses to 0.9-3.5%. Desiccation over Mg(ClO4)(2) and oven drying at 40 degrees C of treated tissues were less successful at reducing Hg irradiation loss. Irradiation losses for volatile Se, As, and Br species were smaller, ranging from 0.06-0.4%, <0.01-0.11%, and 0.02-1.0%, respectively. Treated tissue drying losses for Fig, Se, As, and Br ranged from about 3-20%, <= 2-6%, <0.2-6%, and <0.3-3%, respectively, depending on drying method. There was some evidence that, unlike for Hg, L-cysteine treatment enhanced Se drying loss. There was little evidence of element loss during long-term storage at -80 degrees C, except for an 8% loss from Hg in desiccator dried, L-cysteine treated powdered fish protein. Published by Elsevier Inc. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, Div Bioanalyt Chem, College Pk, MD 20740 USA. RP Anderson, DL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, Div Bioanalyt Chem, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM david.anderson@fda.hhs.gov NR 30 TC 1 Z9 1 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1575 J9 J FOOD COMPOS ANAL JI J. Food Compos. Anal. PD DEC PY 2012 VL 28 IS 2 BP 88 EP 98 DI 10.1016/j.jfca.2012.08.002 PG 11 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 073VX UT WOS:000313772300003 ER PT J AU Moutsopoulos, NM Kling, HM Angelov, N Jin, WW Palmer, RJ Nares, S Osorio, M Wahl, SM AF Moutsopoulos, Niki M. Kling, Heather M. Angelov, Nikola Jin, Wenwen Palmer, Robert J. Nares, Salvador Osorio, Manuel Wahl, Sharon M. TI Porphyromonas gingivalis promotes Th17 inducing pathways in chronic periodontitis SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE Periodontitis; Th17; P. gingivalis; Host-pathogen interactions; Oral; Mucosal inflammation; Immune-mediated bone loss ID HELPER T-CELLS; OSTEOPROTEGERIN LIGAND; ARTHRITIS PATIENTS; BONE DESTRUCTION; IMMUNE-SYSTEM; RESPONSES; DISEASE; INTERLEUKIN-17; PATHOGENESIS; ACTIVATION AB In periodontitis, a common chronic inflammatory condition, gram-negative-rich bacterial biofilms trigger, in susceptible individuals, perpetuating inflammation that results in extensive tissue damage of tooth supporting structures. To delineate immune cell-dependent menchanisms whereby bacterial challenge drives persistent destructive inflammation in periodontitis and other inflammatory diseases, we studied involved tissues ex vivo and investigated host cell responses to the periodontal pathogen Porphyromonas gingivalis, in vitro. Diseased lesions were populated by abundant Th17 cells, linked to infection, chronic inflammation/autoimmunity and tissue pathology. In vitro, P. gingivalis, particularly the more virulent strain W83, stimulated myeloid antigen presenting cells (APC) to drive Th17 polarization. Supernatants from myeloid APC exposed to P. gingivalis were capable of enhancing Th17 but not Th1 polarization. P. gingivalis.favored the generation of Th17 responses by stimulating the production of Th17 related cytokines IL-1 beta, IL-6 and IL-23, but not Th1 related IL-12. By inducing NF kappa B activation, P. gingivalis promoted IL-1 beta, IL-6 and IL-12p40 production, but not IRF3 phosphorylation, connected to generation of the IL-12p35 chain, ultimately restricting formation of the intact IL-12 molecule. Promotion of Th17 lineage responses was also aided by P. gingivalis proteases, which appeared to differentially degrade pivotal cytokines. In this regard, IL-12 was largely degraded by P. gingivalis, whereas IL-1 beta was more resistant to proteolysis. Our data unveil multiple pathways by which P. gingivalis may orchestrate chronic inflammation, providing insights into interventional strategies. Published by Elsevier Ltd. C1 [Moutsopoulos, Niki M.; Kling, Heather M.; Jin, Wenwen; Palmer, Robert J.; Nares, Salvador; Wahl, Sharon M.] NIDCR, NIH, Bethesda, MD 20892 USA. [Angelov, Nikola] Loma Linda Univ, Sch Dent, Dept Periodont, Loma Linda, CA 92350 USA. [Osorio, Manuel] US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Moutsopoulos, NM (reprint author), NIDCR, NIH, Bldg 30,Room 327,30 Convent Dr,MSC4352, Bethesda, MD 20892 USA. EM nmoutsopoulos@dir.nidr.nih.gov FU NIH, National Institute of Dental and Craniofacial Research FX The authors are grateful to Calley Grace for editorial assistance and Teresa Wild and Sarala Sarah for technical assistance. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Dental and Craniofacial Research. NR 45 TC 46 Z9 51 U1 1 U2 12 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD DEC PY 2012 VL 39 IS 4 BP 294 EP 303 DI 10.1016/j.jaut.2012.03.003 PG 10 WC Immunology SC Immunology GA 069VS UT WOS:000313465800006 PM 22560973 ER PT J AU Hellberg, RS Haney, CJ Shen, YL Cheng, CM Williams-Hill, DM Martin, WB AF Hellberg, Rosalee S. Haney, Christopher J. Shen, Yuelian Cheng, Chorng-Ming Williams-Hill, Donna M. Martin, William B. TI Development of a custom 16S rRNA gene library for the identification and molecular subtyping of Salmonella enterica SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE Salmonella enterica; 16S rRNA gene; DNA sequencing ID REAL-TIME PCR; SEQUENCE DIVERSITY; INTRAGENOMIC HETEROGENEITY; PHYLOGENETIC-RELATIONSHIPS; CLINICAL MICROBIOLOGY; RRN OPERONS; BACTERIA; STRAINS; SEGMENTS; GENOMES AB The use of 16S rRNA gene sequencing within the regulatory workflow may help to reduce the time and labor involved in the identification and differentiation of Salmonella enterica isolates. However, a comprehensive, standardized reference library is needed in order to use this method with regulatory samples. The goal of this project was to acquire 16S rRNA partial and full gene sequences for a variety of S. enterica isolates and to use these sequences to build a custom 16S rRNA reference library. A total of 535 S.. enterica isolates representing over 100 serotypes and 5 subspecies were selected for 16S rRNA partial gene sequencing (similar to 500 bp) and 66 isolates representing 32 serotypes and 2 subspecies were selected for 16S rRNA full gene sequencing (similar to 1500 bp). PCR, sequencing, and automated sequence assembly and editing were carried out using the MicroSEQ ID Microbial Identification System (Applied Biosystems). High quality sequences were obtained for 94.4% and 95.5% of the isolates sequenced over the partial and full genes, respectively. These sequences did not show sufficient divergence to reliably differentiate serotypes; however, they could be differentiated using 16S rRNA sequence typing based on intragenomic heterogeneity. A total of 83 unique 16S sequence types were obtained for use in the partial gene library and 58 unique 16S sequence types were obtained for entry into the full gene library. Preliminary sequencing results with one isolate analyzed in replicate were promising, with consistent matches to a specific 16S type in the custom library. The result of this study is a custom S. enterica 16S rRNA type library for potential use in the identification of isolates at the species, subspecies, and molecular subtype level. Further work will include validating the method for parameters such as exclusivity, sensitivity, and reproducibility. (c) 2012 Elsevier B.V. All rights reserved. C1 [Cheng, Chorng-Ming; Williams-Hill, Donna M.; Martin, William B.] US FDA, Off Regulatory Affairs, Pacific Reg Lab SW PRLSW, Irvine, CA 92612 USA. [Haney, Christopher J.] US FDA, Off Regulatory Affairs, Pacific Reg Lab SW PRLSW, Jefferson, AR 72079 USA. [Shen, Yuelian] US FDA, Off Regulatory Affairs, Off Reg Operat, Div Field Sci, Rockville, MD 20857 USA. [Hellberg, Rosalee S.] Chapman Univ, Sch Earth & Environm Sci, Orange, CA 92866 USA. RP Hellberg, RS (reprint author), Chapman Univ, Sch Earth & Environm Sci, 1 Univ Dr, Orange, CA 92866 USA. EM hellberg@chapman.edu NR 35 TC 1 Z9 1 U1 3 U2 25 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 DEC PY 2012 VL 91 IS 3 BP 448 EP 458 DI 10.1016/j.mimet.2012.09.018 PG 11 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 070AJ UT WOS:000313477900019 PM 23022443 ER PT J AU Fahmy, R Kona, R Dandu, R Xie, W Claycamp, G Hoag, SW AF Fahmy, Raafat Kona, Ravikanth Dandu, Ramesh Xie, Walter Claycamp, Gregg Hoag, Stephen W. TI Quality by Design I: Application of Failure Mode Effect Analysis (FMEA) and Plackett-Burman Design of Experiments in the Identification of "Main Factors" in the Formulation and Process Design Space for Roller-Compacted Ciprofloxacin Hydrochloride Immediate-Release Tablets SO AAPS PHARMSCITECH LA English DT Article DE failure mode effect analysis (FMEA); Plackett-Burman; quality by design (QbD); quality risk management; roller compaction; tablet and ciprofloxacin ID NEAR-INFRARED SPECTROSCOPY; REDUCED TABLETABILITY; GRANULES; STRENGTH; MOISTURE; POWDER AB As outlined in the ICH Q8(R2) guidance, identifying the critical quality attributes (CQA) is a crucial part of dosage form development; however, the number of possible formulation and processing factors that could influence the manufacturing of a pharmaceutical dosage form is enormous obviating formal study of all possible parameters and their interactions. Thus, the objective of this study is to examine how quality risk management can be used to prioritize the number of experiments needed to identify the CQA, while still maintaining an acceptable product risk profile. To conduct the study, immediate-release ciprofloxacin tablets manufactured via roller compaction were used as a prototype system. Granules were manufactured using an Alexanderwerk WP120 roller compactor and tablets were compressed on a Stokes B2 tablet press. In the early stages of development, prior knowledge was systematically incorporated into the risk assessment using failure mode and effect analysis (FMEA). The factors identified using FMEA were then followed by a quantitative assessed using a Plackett-Burman screening design. Results show that by using prior experience, literature data, and preformulation data the number of experiments could be reduced to an acceptable level, and the use of FMEA and screening designs such as the Plackett Burman can rationally guide the process of reducing the number experiments to a manageable level. C1 [Fahmy, Raafat] US FDA, Off New Anim Drug Evaluat, Rockville, MD 20857 USA. [Kona, Ravikanth; Hoag, Stephen W.] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. [Dandu, Ramesh] Sandoz Inc, Wilson, NC 27893 USA. [Xie, Walter] Progen Pharmaceut, Tarrytown, NY 10591 USA. [Claycamp, Gregg] US FDA, Off Compliance, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Hoag, SW (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, 20 N Pine St, Baltimore, MD 21201 USA. EM shoag@rx.umaryland.edu FU Food and Drug Administration FX This work was carried out with the scientific and financial support provided by the Food and Drug Administration. NR 26 TC 20 Z9 21 U1 2 U2 37 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PD DEC PY 2012 VL 13 IS 4 BP 1243 EP 1254 DI 10.1208/s12249-012-9844-x PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 070IT UT WOS:000313500500024 PM 22993122 ER PT J AU Gao, ZM AF Gao, Zongming TI Development of a Continuous Dissolution/Absorption System-a Technical Note SO AAPS PHARMSCITECH LA English DT Article DE absorption; dissolution; permeability ID DRUG ABSORPTION; SOLUBLE DRUGS; MODEL; TRANSIT; FLOW C1 US FDA, Div Pharmaceut Anal, Ctr Drug Evaluat & Res, St Louis, MO 63101 USA. RP Gao, ZM (reprint author), US FDA, Div Pharmaceut Anal, Ctr Drug Evaluat & Res, St Louis, MO 63101 USA. EM zongming.gao@fda.hhs.gov NR 17 TC 6 Z9 6 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 DEC PY 2012 VL 13 IS 4 BP 1287 EP 1292 DI 10.1208/s12249-012-9856-6 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 070IT UT WOS:000313500500028 PM 22996672 ER PT J AU Ge, CC Li, Y Yin, JJ Liu, Y Wang, LM Zhao, YL Chen, CY AF Ge, Cuicui Li, Yang Yin, Jun-Jie Liu, Ying Wang, Liming Zhao, Yuliang Chen, Chunying TI The contributions of metal impurities and tube structure to the toxicity of carbon nanotube materials SO NPG ASIA MATERIALS LA English DT Article DE biological microenvironments; carbon nanotube; metal impurities; reactive oxygen species; toxicity ID LABILE IRON POOL; OXIDATIVE STRESS; PURIFICATION; CELLS; MICE; NANOPARTICLES; CYTOTOXICITY; BIODISTRIBUTION; BIOAVAILABILITY; NANOMATERIALS AB Due to the existence of considerable quantities of metallic and carbonaceous impurities, the key factor and mechanism for the reported toxicity of carbon nanotubes (CNTs) are unclear. Here, we first quantify the contribution of metal residues and fiber structure to the toxicity of CNTs. Significant quantities of metal particles could be mobilized from CNTs into surrounding fluids, depending on the properties and constituents of the biological microenvironment, as well as the properties of metal particles. Furthermore, electron spin resonance measurements confirm that hydroxyl radicals can be generated by both CNTs containing metal impurities and acid-leachable metals from CNTs. Several biomolecules facilitate the generation of free radicals, which might be due to the participation of these biomolecules in redox cycling influenced by pH. Among several major metal residues, Fe has a critical role in generating hydroxyl radicals, reducing cell viability and promoting intracellular reactive oxidative species. Cell viability is highly dependent on the amount of metal residues and iron in particular, but not tube structure, while the negative effect of CNTs themselves on cell viability is very limited in a certain concentration range below 80 mu gml(-1). It is crucial to systematically understand how these exogenous and endogenous factors influence the toxicity of CNTs to avoid their undesirable toxicity. NPG Asia Materials (2012) 4, e32; doi:10.1038/am.2012.60; published online 7 December 2012 C1 [Ge, Cuicui; Li, Yang; Liu, Ying; Wang, Liming; Zhao, Yuliang; Chen, Chunying] Chinese Acad Sci, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Natl Ctr Nanosci & Technol China, Beijing 100190, Peoples R China. [Ge, Cuicui; Li, Yang; Liu, Ying; Wang, Liming; Zhao, Yuliang; Chen, Chunying] Chinese Acad Sci, Inst High Energy Phys, Beijing 100190, Peoples R China. [Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Zhao, YL (reprint author), Chinese Acad Sci, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Natl Ctr Nanosci & Technol China, 11 Beiyijie, Beijing 100190, Peoples R China. EM zhaoyuliang@ihep.ac.cn; chenchy@nanoctr.cn RI Wang, Liming/A-6924-2012; Yin, Jun Jie /E-5619-2014; OI Wang, Liming/0000-0003-1382-9195; Li, Yang/0000-0001-7242-4687 FU National Basic Research Programs in the Ministry of Science and Technology of China [2011CB933401, 2012CB934000]; Natural Science Foundation of China [10975040, 21277037]; Danish Agency for Science Technology and Innovation [09-067185]; Nanotechnology CORES Program [FY11 FDA] FX This work was financially supported by the National Basic Research Programs in the Ministry of Science and Technology of China (2011CB933401, 2012CB934000) and the Natural Science Foundation of China (10975040, 21277037) and the Danish Agency for Science Technology and Innovation (09-067185). This work was partially supported by a regulatory science grant under the FY11 FDA Nanotechnology CORES Program (JY). We gratefully acknowledge the comments of Wayne Wamer (Center for Food Safety and Applied Nutrition/US Food and Drug Administration) during the preparation of this manuscript. This article is not an official US Food and Drug Administration (FDA) guidance or policy statement. No official support or endorsement by the US FDA is intended or should be inferred. NR 40 TC 35 Z9 37 U1 1 U2 68 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1884-4049 J9 NPG ASIA MATER JI NPG Asia Mater. PD DEC PY 2012 VL 4 AR E32 DI 10.1038/am.2012.60 PG 10 WC Materials Science, Multidisciplinary SC Materials Science GA 062ZH UT WOS:000312963200001 ER PT J AU Flack, MN Gross, TP Reid, JS Mills, TT Francis, J AF Flack, Marilyn Neder Gross, Thomas P. Reid, Joy Samuels Mills, Thalia T. Francis, Jacqueline TI FDA Working to Ensure the Safety of Medical Devices Used in the Pediatric Population SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Food and Drug Administration; Center for Devices and Radiological Health; Medical devices; Surveillance; Total product life cycle; Pediatric device safety ID EMERGENCY-DEPARTMENT; ADVERSE EVENTS; VISITS; CT AB Special initiatives exist in FDA's Center for Devices and Radiological Health (CDRH), the Center for Drug Evaluation and Research, and the Center for Biologics Evaluation and Research to ensure the safety and effectiveness of medical products used in the vulnerable pediatric population. This article focuses on the special programs, projects, and special studies implemented by CDRH to ensure this safety and effectiveness in devices used in pediatric patients throughout the devices' total product life-cycles. Pediatricians play a major role in keeping medical devices safe for use in children by reporting device problems to FDA. C1 [Flack, Marilyn Neder; Gross, Thomas P.] US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Reid, Joy Samuels] US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Mills, Thalia T.] US FDA, Off Vitro Diagnost & Radiol Hlth OIR, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Francis, Jacqueline] US FDA, Off Ctr Director, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Flack, MN (reprint author), US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Marilyn.flack@fda.hhs.gov NR 29 TC 0 Z9 0 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD DEC PY 2012 VL 59 IS 6 BP 1355 EP + DI 10.1016/j.pcl.2012.08.003 PG 14 WC Pediatrics SC Pediatrics GA 058FD UT WOS:000312618600012 PM 23116531 ER PT J AU Ma, XW Zhang, LH Wang, LR Xue, X Sun, JH Wu, Y Zou, GZ Wu, X Wang, PC Wamer, WG Yin, JJ Zheng, KY Liang, XJ AF Ma, Xiaowei Zhang, Li-Hua Wang, Li-Rong Xue, Xue Sun, Ji-Hong Wu, Yan Zou, Guozhang Wu, Xia Wang, Paul C. Wamer, Wayne G. Yin, Jun-Jie Zheng, Kaiyuan Liang, Xing-Jie TI Single-Walled Carbon Nanotubes Alter Cytochrome c Electron Transfer and Modulate Mitochondrial Function SO ACS NANO LA English DT Article DE single-walled carbon nanotubes; carboxy; cytochrome c; electron transfer; mitochondrial function; redox activity ID APOPTOSIS; CELLS; TRANSPORTERS; NANOPARTICLES; RESPIRATION; DYSFUNCTION; INHIBITION; DEFICIENCY; PROTEINS; DELIVERY AB Single-walled carbon nanotubes (SWCNTs) are broadly used for various biomedical applications such as drug delivery, in vivo imaging, and cancer photothermal therapy due to their unique physiochemical properties. However, once they enter the cells, the effects of SWCNTs on the intracellular organelles and macromolecules are not comprehensively understood. Cytochrome c (Cyt c), as a key component of the electron transport chain in mitochondria, plays an essential role in cellular energy consumption, growth, and differentiation. In this study, we found the mitochondrial membrane potential and mitochondrial oxygen uptake were greatly decreased in human epithelial KB cells treated with SWCNTs, which accompanies the reduction of Cyt c. SWCNTs deoxidized Cyt c in a pH-dependent manner, as evidenced by the appearance of a 550 nm characteristic absorption peak, the intensity of which increased as the pH increased. Circular dichroism measurement confirmed the pH-dependent conformational change, which facilitated closer association of SWCNTs with the heme pocket of Cyt c and thus expedited the reduction of Cyt c. The electron transfer of Cyt c is also disturbed by SWCNTs, as measured with electron spin resonance spectroscopy. In conclusion, the redox activity of Cyt (was affected by SWCNTs treatment due to attenuated electron transfer and conformational change of Cyt c, which consequently changed mitochondrial respiration of SWCNTs-treated cells. This work is significant to SWCNTs research because it provides a novel understanding of SWCNTs' disruption of mitochondria function and has important implications for biomedical applications of SWCNTs. C1 [Zhang, Li-Hua; Sun, Ji-Hong; Wu, Xia] Beijing Univ Technol, Coll Environm & Energy Engn, Dept Chem & Chem Engn, Beijing 100124, Peoples R China. [Ma, Xiaowei; Zhang, Li-Hua; Wang, Li-Rong; Xue, Xue; Wu, Yan; Zou, Guozhang; Wu, Xia; Zheng, Kaiyuan; Liang, Xing-Jie] Chinese Acad Sci, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China. [Wang, Paul C.] Howard Univ, Dept Radiol, Mol Imaging Lab, Washington, DC 20060 USA. [Wamer, Wayne G.; Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Sun, JH (reprint author), Beijing Univ Technol, Coll Environm & Energy Engn, Dept Chem & Chem Engn, Beijing 100124, Peoples R China. EM jhsun@bjut.edu.cn; liangxj@nanoctr.cn RI Yin, Jun Jie /E-5619-2014 FU Chinese Natural Science Foundation project [30970784, 81171455]; National Key Basic Research Program of China [2009CB930200]; Chinese Academy of Sciences (CAS) "Hundred Talents Program" [07165111ZX]; CAS Knowledge Innovation Program; NIH/NCRR [3 G12 RR003048]; NIH/NIMHD [8 G12 MD007597]; USAMRMC [W81XWH-10-1-0767]; FDA Nanotechnology CORES Program [FY11] FX This work was supported by grants from the Chinese Natural Science Foundation project (Nos. 30970784 and 81171455), National Key Basic Research Program of China (2009CB930200), Chinese Academy of Sciences (CAS) "Hundred Talents Program" (07165111ZX), and CAS Knowledge Innovation Program. This work was supported in part by NIH/NCRR 3 G12 RR003048, NIH/NIMHD 8 G12 MD007597, and USAMRMC W81XWH-10-1-0767 grants. This article is not an official U.S. Food and Drug Administration (FDA) guidance or policy statement. No official support or endorsement by the U.S. FDA is intended or should be inferred. This work was supported by a regulatory science grant under the FY11 FDA Nanotechnology CORES Program (J.J.Y. and W.G.W.). NR 45 TC 33 Z9 35 U1 3 U2 99 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 J9 ACS NANO JI ACS Nano PD DEC PY 2012 VL 6 IS 12 BP 10486 EP 10496 DI 10.1021/nn302457v PG 11 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 057LA UT WOS:000312563600008 PM 23171082 ER PT J AU Wang, HG Mattes, WB Richter, P Mendrick, DL AF Wang, Honggang Mattes, William B. Richter, Patricia Mendrick, Donna L. TI An omics strategy for discovering pulmonary biomarkers potentially relevant to the evaluation of tobacco products SO BIOMARKERS IN MEDICINE LA English DT Article DE biomarker; genomics; lung; metabolomics; proteomics; smoking ID SURFACTANT PROTEIN-D; CELL LUNG-CANCER; FAMILY SMOKING PREVENTION; EXHALED BREATH CONDENSATE; DNA METHYLATION MARKERS; GENOME-WIDE ASSOCIATION; SURROGATE END-POINTS; CIGARETTE-SMOKE; GENE-EXPRESSION; SYSTEMIC INFLAMMATION AB Smoking is known to cause serious lung diseases including chronic bronchitis, chronic obstructive lung disease, obstruction of small airways, emphysema and cancer. Tobacco smoke is a complex chemical aerosol containing at least 8000 chemical constituents, either tobacco derived or added by tobacco product manufacturers. Identification of all of the toxic agents in tobacco smoke is challenging, and efforts to understand the mechanisms by which tobacco use causes disease will be informed by new biomarkers of exposure and harm. In 2009, President Obama signed into law the Family Smoking Prevention and Tobacco Control Act granting the US FDA the authority to regulate tobacco products to protect public health. This perspective article presents the background, rationale and strategy for using omics technologies to develop new biomarkers, which may be of interest to the FDA when implementing the Family Smoking Prevention and Tobacco Control Act. C1 [Mendrick, Donna L.] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Mattes, William B.] PharmPoint Consulting, Poolesville, MD 20837 USA. [Richter, Patricia] US FDA, Off Sci, Ctr Tobacco Prod, Rockville, MD 20850 USA. RP Mendrick, DL (reprint author), US FDA, Div Syst Biol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM donna.mendrick@fda.hhs.gov NR 154 TC 5 Z9 5 U1 1 U2 29 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 EI 1752-0371 J9 BIOMARK MED JI Biomark. Med. PD DEC PY 2012 VL 6 IS 6 BP 849 EP 860 DI 10.2217/BMM.12.78 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 055LA UT WOS:000312416600025 PM 23227851 ER PT J AU Li, HP Bhaskara, A Megalis, C Tortorello, ML AF Li, Haiping Bhaskara, Anuhya Megalis, Christina Tortorello, Mary Lou TI Transcriptomic Analysis of Salmonella Desiccation Resistance SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID ENTERICA SEROVAR TYPHIMURIUM; ESCHERICHIA-COLI; WATER ACTIVITY; SURVIVAL; ENTERITIDIS; TREHALOSE; GROWTH; PERSISTENCE; ADAPTATION AB The survival of Salmonella in low moisture foods and processing environments remains a great challenge for the food industry and public health. To explore the mechanisms of Salmonella desiccation resistance, we studied the transcriptomic responses in Salmonella Tennessee (Tennessee), using Salmonella Typhimurium LT2 (LT2), a strain weakly resistant to desiccation, as a reference strain. In response to 2 h of air-drying at 11% equilibrated relative humidity, approximately one-fourth of the open reading frames (ORFs) in the Tennessee genome and one-fifth in LT2 were differentially expressed (>2-fold). Among all differentially expressed functional groups (>5-fold) in both strains, the expression fold change associated with fatty acid metabolism was the highest, and constituted 51% and 35% of the total expression fold change in Tennessee and LT2, respectively. Tennessee showed greater changes in expression of genes associated with stress response and envelope modification than LT2, while showing lesser changes in protein biosynthesis expression. Expression of flagella genes was significantly more inhibited in stationary phase cells of Tennessee than LT2 both before and after desiccation. The accumulation of the osmolyte trehalose was significantly induced by desiccation in Tennessee, but no increase was detectable in LT2, which is consistent with the expression patterns of the entire trehalose biosynthesis and degradation pathways in both strains. Results from this study present a global view of the dynamic desiccation responses in Salmonella, which will guide future research efforts to control Salmonella in low moisture environments. C1 [Li, Haiping; Megalis, Christina; Tortorello, Mary Lou] US FDA, Div Food Proc Sci & Technol, Bedford Pk, IL 60501 USA. [Bhaskara, Anuhya] Inst Food Safety & Hlth, Illinois Inst Technol, Bedford Pk, IL USA. RP Li, HP (reprint author), US FDA, Div Food Proc Sci & Technol, 6502 S Archer Rd, Bedford Pk, IL 60501 USA. EM haiping.li@fda.hhs.gov NR 28 TC 12 Z9 13 U1 4 U2 35 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1535-3141 J9 FOODBORNE PATHOG DIS JI Foodborne Pathog. Dis. PD DEC PY 2012 VL 9 IS 12 BP 1143 EP 1151 DI 10.1089/fpd.2012.1254 PG 9 WC Food Science & Technology SC Food Science & Technology GA 055WM UT WOS:000312448600014 PM 23237410 ER PT J AU Malik, M Stockbridge, N AF Malik, Marek Stockbridge, Norman TI Thorough QT Studies and Indirect Causes of QTc Changes SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Editorial Material DE Electrocardiogram; Long QT ID MYOCARDIAL-INFARCTION; INTERVAL; PROLONGATION; ECG C1 [Malik, Marek] St Pauls Cardiac Electrophysiol, London, England. [Malik, Marek] Univ London, London, England. [Stockbridge, Norman] US FDA, Div Cardiovasc & Renal Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Malik, M (reprint author), SPCE London, Verulam Ave, Purley CR8 3NQ, Surrey, England. EM marek.malik@btinternet.com NR 23 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD DEC PY 2012 VL 35 IS 12 BP 1411 EP 1412 DI 10.1111/pace.12008 PG 2 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 055VW UT WOS:000312446900010 PM 23035657 ER PT J AU Lanier, WA Johnson, EM Rolfs, RT Friedrichs, MD Grey, TC AF Lanier, William A. Johnson, Erin M. Rolfs, Robert T. Friedrichs, Michael D. Grey, Todd C. TI Risk Factors for Prescription Opioid-Related Death, Utah, 2008-2009 SO PAIN MEDICINE LA English DT Article DE Overdose; Analgesics; Opioid; Drug Prescriptions; Prevalence; Risk Factors ID CHRONIC NONMALIGNANT PAIN; DRUG OVERDOSE DEATHS; UNITED-STATES; CIGARETTE-SMOKING; MENTAL-ILLNESS; PREVALENCE; MANAGEMENT; ANALGESICS; ADULTS; PREDICTORS AB Objective Utah prescription opioid death rates increased nearly fivefold during 20002009. Inadequate understanding of risk factors hinders prevention. The goal of this study was to determine risk factors for prescription opioid death in Utah. Design Case-control study. Cases were 254 Utah decedents with =1 prescription opioid causing death during 20082009 with nonintentional manner of death (information obtained via next-of-kin interviews). Controls were 1,308 Utah 2008 Behavioral Risk Factor Surveillance System respondents who reported prescription opioid use during the previous year. Outcome Measures Exposure prevalence ratios (EPRs) for selected characteristics and confidence intervals (CIs) were calculated. Results Decedents were more likely than the comparison group to have used prescription pain medication more than prescribed (52.9% vs 3.2%; EPR, 16.5; 95% CI, 9.323.7), obtained prescription pain medication from nonprescription sources (39.6% vs 8.3%; EPR, 4.8; 95% CI, 3.66.0), smoked daily (54.5% vs 9.7%; EPR, 5.6; 95% CI, 4.46.9), not graduated high school (18.5% vs 6.2%; EPR, 3.0; 95% CI, 2.03.9), and been divorced or separated (34.6% vs 9.4%; EPR, 3.7; 95% CI, 3.04.4). Decedents were more likely to have had chronic pain than the comparison group (94.2% vs 31.6%; EPR, 3.0; 95% CI, 2.73.3). Conclusions Use of pain medication outside prescription bounds was a risk factor for death. However, decedents were more likely to have had chronic pain, and the majority of both groups had obtained pain medication by prescription. Other factors (e.g., smoking status) might also play important roles in prescription opioid-related death. Prescribers should screen chronic pain patients for risk factors. C1 [Grey, Todd C.] Utah Dept Hlth, Off Med Examiner, Salt Lake City, UT 84116 USA. [Lanier, William A.] Ctr Dis Control & Prevent, EIS Field Assignments Branch, Epidem Intelligence Serv, Atlanta, GA USA. [Lanier, William A.] US PHS, Rockville, MD USA. RP Lanier, WA (reprint author), US FDA, 4300 River Rd, College Pk, MD 20740 USA. EM william.lanier@fda.hhs.gov NR 45 TC 13 Z9 13 U1 3 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD DEC PY 2012 VL 13 IS 12 BP 1580 EP 1589 DI 10.1111/j.1526-4637.2012.01518.x PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 058QW UT WOS:000312649700008 PM 23137228 ER PT J AU Schoen, B Mossoba, MM Chizhikov, V Rashid, A Martinez-Diaz, K Al-Khaldi, SF AF Schoen, Brianna Mossoba, Magdi M. Chizhikov, Vladimir Rashid, Anis Martinez-Diaz, Karen Al-Khaldi, Sufian F. TI Enhanced Mid-Infrared Chemical Imaging (IRCI) Detection of DNA Microarrays SO APPLIED SPECTROSCOPY LA English DT Article DE Headings: Mid-infrared; Chemical imaging; DNA microarrays ID YERSINIA-ENTEROCOLITICA; IDENTIFICATION; HYBRIDIZATION AB We report on the optimization of a recently proposed mid-infrared chemical imaging (IRCI) detection method for the analysis of DNA microarrays. The improved protocol allowed for a ten-fold reduction in the time needed to generate a mosaic image of an entire microarray and the production of IR images with high contrast that would facilitate data analysis and interpretation. Advantages of using this protocol were evaluated by applying it to the analysis of four virulence genes in the genomes of 19 strains of the food bacterial pathogen Yersinia enterocolitica. C1 [Mossoba, Magdi M.; Martinez-Diaz, Karen] US FDA, Div Analyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Schoen, Brianna; Rashid, Anis; Al-Khaldi, Sufian F.] US FDA, Div Microbiol, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Chizhikov, Vladimir] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Mossoba, MM (reprint author), US FDA, Div Analyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM magdi.mossoba@fda.hhs.gov NR 11 TC 1 Z9 1 U1 0 U2 8 PU SOC APPLIED SPECTROSCOPY PI FREDERICK PA 5320 SPECTRUM DRIVE SUITE C, FREDERICK, MD 21703 USA SN 0003-7028 J9 APPL SPECTROSC JI Appl. Spectrosc. PD DEC PY 2012 VL 66 IS 12 BP 1480 EP 1486 DI 10.1366/12-06772 PG 7 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA 052YL UT WOS:000312236500016 PM 23231912 ER PT J AU Sprando, RL Reimschuessel, R Stine, CB Black, T Olejnik, N Scott, M Keltner, Z Bandele, O Ferguson, M Nemser, SM Tkachenko, A Evans, E Crosby, T Woodling, K Loukotkova, L da Costa, GG AF Sprando, Robert L. Reimschuessel, Renate Stine, Cynthia B. Black, Thomas Olejnik, Nicholas Scott, Michael Keltner, Zachary Bandele, Omari Ferguson, Martine Nemser, Sarah M. Tkachenko, Andriy Evans, Eric Crosby, Tina Woodling, Kellie Loukotkova, Lucie da Costa, Goncalo Gamboa TI Timing and route of exposure affects crystal formation in melamine and cyanuric exposed male and female rats: Gavage vs. feeding SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Melamine; Cyanuric acid; Gavage vs. feeding; Renal crystal formation; Kidney ID DOSE-RESPONSE ASSESSMENT; RENAL-FAILURE; F344 RATS; RISK-FACTOR; ACID; HYPERURICEMIA; COHORT; NEPHROTOXICITY; PIGS AB Effects of the dosing matrix and timing on the onset of renal crystal formation were evaluated in male and non-pregnant female rats (Fisher 344) exposed to both melamine (MEL) and cyanuric acid (CYA) for 28 days. Rats were fed ground feed containing 60 ppm MEL and 60 ppm CYA, (5 mg/kg bw/day equivalent), or exposed via oral gavage to carboxymethylcellulose containing 5 mg/kg bw MEL followed by 5 mg/kg bw CYA either consecutively (<1 min apart) or delayed 45 min after MEL Staggered gavage exposure to MEL/CYA caused extensive renal crystal formation as compared to when the two compounds were administered consecutively or in feed. Treatment related effects included reduced weight gain, feed consumption, and testicular weight and increased kidney weight, water consumption and urine output. Animals from the staggered MEL/CYA gavage exposure group became ill and were removed after 9 days of exposure. Approximately 1 week after the initiation of exposure microscopic urinalysis revealed MEL/CYA crystals in both groups of gavaged animals but not in the MEL/CYA feed treatment groups. Urinary crystals were smaller (10 mu m) in animals consecutively gavaged. In contrast the urinary crystals were larger (20-40 mu m) and frequently clumped in the animals in the staggered gavage group. Published by Elsevier Ltd. C1 [Sprando, Robert L.] US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div Toxicol, Laurel, MD 20708 USA. [Reimschuessel, Renate; Stine, Cynthia B.; Nemser, Sarah M.; Tkachenko, Andriy; Evans, Eric; Crosby, Tina] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [Woodling, Kellie; Loukotkova, Lucie; da Costa, Goncalo Gamboa] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Sprando, RL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div Toxicol, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM rsprando@cfsan.fda.gov FU FDA [FDA IAG:22407-0007, NIH Y1ES1027]; National Institute of Environmental Health Sciences [FDA IAG:22407-0007, NIH Y1ES1027] FX This study was supported in part through an interagency agreement between the FDA and the National Toxicology Program at the National Institute of Environmental Health Sciences (FDA IAG:22407-0007; NIH Y1ES1027). The opinions expressed in this paper do not necessarily represent those of the U.S. Food and Drug Administration or National Toxicology Program. NR 23 TC 11 Z9 11 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 EI 1873-6351 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD DEC PY 2012 VL 50 IS 12 BP 4389 EP 4397 DI 10.1016/j.fct.2012.07.051 PG 9 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 053QM UT WOS:000312288000020 PM 22963836 ER PT J AU Pollard, AJ Savulescu, J Oxford, J Hill, AVS Levine, MM Lewis, DJM Read, RC Graham, DY Sun, W Openshaw, P Gordon, SB AF Pollard, Andrew J. Savulescu, Julian Oxford, John Hill, Adrian V. S. Levine, Myron M. Lewis, David J. M. Read, Robert C. Graham, David Y. Sun, Wellington Openshaw, Peter Gordon, Stephen B. TI Human microbial challenge: the ultimate animal model SO LANCET INFECTIOUS DISEASES LA English DT Editorial Material ID MALARIA VACCINE; DISEASE; TRANSMISSION; VOLUNTEERS; PROTECTION; EFFICACY; TRIAL C1 [Pollard, Andrew J.] Univ Oxford, Oxford Vaccine Grp, Dept Paediat, Oxford OX3 9DU, England. [Pollard, Andrew J.] Childrens Hosp, NIHR Oxford Biomed Res Ctr, Oxford OX3 9DU, England. [Savulescu, Julian] Univ Oxford, Oxford Uehiro Ctr Pract Eth, Oxford OX3 9DU, England. [Hill, Adrian V. S.] Univ Oxford, Ctr Clin Vaccinol, Oxford OX3 9DU, England. [Hill, Adrian V. S.] Univ Oxford, Jenner Inst, Oxford OX3 9DU, England. [Oxford, John] Barts & London Queen Marys Sch Med & Dent, Blizard Inst Cell & Mol Sci, London, England. [Levine, Myron M.] Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. [Lewis, David J. M.] Univ Surrey, Clin Res Ctr, Inst Biosci & Med, Guildford GU2 5XH, Surrey, England. [Read, Robert C.] Univ Southampton, Dept Clin & Expt Sci, Southampton, Hants, England. [Graham, David Y.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Graham, David Y.] Baylor Coll Med, Houston, TX 77030 USA. [Sun, Wellington] Ctr Biol Evaluat & Res, Div Vaccines & Related Prod Applicat, Off Vaccines Res & Review, Rockville, MD USA. [Openshaw, Peter] Univ London Imperial Coll Sci Technol & Med, Ctr Resp Infect, London, England. [Gordon, Stephen B.] Univ Liverpool, Liverpool Sch Trop Med, Dept Clin Sci, Liverpool L3 5QA, Merseyside, England. RP Pollard, AJ (reprint author), Univ Oxford, Oxford Vaccine Grp, Dept Paediat, Oxford OX3 9DU, England. OI Lewis, David JM/0000-0003-3105-9075; Gordon, Stephen/0000-0001-6576-1116 FU Wellcome Trust [090532, 095540] NR 14 TC 20 Z9 20 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1473-3099 EI 1474-4457 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD DEC PY 2012 VL 12 IS 12 BP 903 EP 905 DI 10.1016/S1473-3099(12)70292-X PG 3 WC Infectious Diseases SC Infectious Diseases GA 052EH UT WOS:000312180000006 PM 23174372 ER PT J AU Bai, JPF Hausman, E Lionberger, R Zhang, XY AF Bai, Jane P. F. Hausman, Ethan Lionberger, Robert Zhang, Xinyuan TI Modeling and Simulation of the Effect of Proton Pump Inhibitors on Magnesium Homeostasis. 1. Oral Absorption of Magnesium SO MOLECULAR PHARMACEUTICS LA English DT Article DE proton pump inhibitors; hypomagnesemia; TRPM6/TRPM7; oral absorption; solubility; balance of input and output; adverse reactions ID MOLECULAR DETERMINANTS; SECONDARY HYPOCALCEMIA; INTESTINAL-ABSORPTION; HYPOMAGNESEMIA; TRPM6; CHANNEL; MG2+; OMEPRAZOLE; PERMEABILITY; SENSITIVITY AB Prolonged use of proton pump inhibitors has reportedly caused rare clinically symptomatic hypomagnesemia. A review of the literature suggests PPI drugs may impair intestinal magnesium absorption. With the goal of preventing PPI-induced hypomagnesemia, an oral absorption-centric model was developed by referencing literature data. Our modeling with human data reveals that magnesium absorption is substantial in the distal intestine. We then perform simulations by referring to the reported reduction in mid to distal intestinal pH caused by one week of oral esomeprazole, and to reported reduction of the divalent cation-sensitive current when the carboxyl side chains of glutamic and aspartic residues in the binding channels of TRPM6/TRPM7 were neutralized. Our simulations reveal that short-term PPI therapy may cause a very small reduction (5%) in the serum magnesium level, which is qualitatively consistent with the reported 1% reduction in magnesium absorption following 1 week of omeprazole in humans. Simulations provide insight into the benefit of frequent but small dose of magnesium supplementation in maintaining the serum magnesium level when magnesium deficiency occurs. C1 [Lionberger, Robert; Zhang, Xinyuan] US FDA, Off Gener Drugs, Off Pharmaceut Sci, Rockville, MD 20857 USA. [Hausman, Ethan] US FDA, Off Pharmacovigilance & Epidemiol, Off Surveillance & Epidemiol, Rockville, MD 20857 USA. [Bai, Jane P. F.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat, Rockville, MD 20857 USA. RP Bai, JPF (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, CDER, Silver Spring, MD 20993 USA. EM jane.bai@fda.hhs.gov NR 55 TC 22 Z9 23 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD DEC PY 2012 VL 9 IS 12 BP 3495 EP 3505 DI 10.1021/mp300323q PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 046OI UT WOS:000311773900009 PM 23051182 ER PT J AU Benedict, RHB Walton, MK AF Benedict, Ralph H. B. Walton, Marc K. TI Evaluating cognitive outcome measures for MS clinical trials: what is a clinically meaningful change? SO MULTIPLE SCLEROSIS JOURNAL LA English DT Review DE Multiple sclerosis; outcome measurement; cognitive tests; neuropsychology; processing speed; memory; vocational disability; cognitive impairment; study design; clinically meaningful change ID SCLEROSIS FUNCTIONAL COMPOSITE; TIMED INSTRUMENTAL ACTIVITIES; MULTIPLE-SCLEROSIS; NEUROPSYCHOLOGICAL PERFORMANCE; STATISTICAL-METHODS; MEMORY IMPAIRMENT; RELIABLE CHANGE; 25-FOOT WALK; QUESTIONNAIRE; ASSESSMENTS AB Brief cognitive assessments are increasingly emphasized in MS treatment studies and clinical care. While much is known about the reliability of several widely-used neuropsychological tests, interpretation of the changes in individual patients is inadequate. The FDA offers guidance on the issue, as related to patient-reported outcomes. Unfortunately, cognitive ability is only weakly correlated with the frequency and severity of self-reported cognitive problems. In this review, we critically examined the psychometrics of neuropsychological testing in MS, emphasizing statistical and anchor-based approaches to interpreting clinically meaningful change. We suggest that there are two paths forward that should be currently pursued. First, to employ co-primary outcomes, including a brief cognitive test and a clinician or observer's impression on a scale of change, where successful treatment would require showing significant improvement in both measures. Secondly, to work toward showing that when reliable brief cognitive tests are employed, increments of statistically-relevant change would correlate with changes in clinicallyrelevant anchors (such as vocational disability or clinical relapses with cognitive impairment). The latter goal will allow a more parsimonious and scientifically efficient approach of utilizing only the brief cognitive test as a primary outcome. While some progress has been made in this direction, more research is needed. We are of the opinion that data from both the statistical and clinically meaningful approaches will be necessary to develop valid definitions of meaningful change on cognitive outcome measures, and that it would be best to pursue research using tests that already have well-established reliability and validity. C1 [Benedict, Ralph H. B.] SUNY Buffalo, Dept Neurol, Buffalo, NY 14203 USA. [Walton, Marc K.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Benedict, RHB (reprint author), SUNY Buffalo, Dept Neurol, Buffalo Gen Hosp, Suite E2,100 High St, Buffalo, NY 14203 USA. EM benedict@buffalo.edu NR 46 TC 11 Z9 11 U1 0 U2 9 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER J JI Mult. Scler. J. PD DEC PY 2012 VL 18 IS 12 BP 1673 EP 1679 DI 10.1177/1352458512454774 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 052IX UT WOS:000312192300004 PM 22824644 ER PT J AU Fang, L Zhao, F Shen, XF Ouyang, WM Liu, XQ Xu, Y Yu, T Jin, BQ Chen, JY Luo, WJ AF Fang, Liang Zhao, Fang Shen, Xuefeng Ouyang, Weiming Liu, Xinqin Xu, Yan Yu, Tao Jin, Boquan Chen, Jingyuan Luo, Wenjing TI Pb exposure attenuates hypersensitivity in vivo by increasing regulatory T cells SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Pb; Hypersensitivity; Regulatory T cells ID DELAYED-TYPE HYPERSENSITIVITY; LEAD-EXPOSURE; OCCUPATIONAL LEAD; IMMUNOTOXICITY; TOLERANCE; RESPONSES; SUBSETS; WORKERS; MICE AB Pb is a common environmental pollutant affecting various organs. Exposure of the immune system to Pb leads to immunosuppression or immunodysregulation. Although previous studies showed that Pb exposure can modulate the function of helper T cells, Pb immunotoxicity remains incompletely understood. In this study, we investigated the effect of Pb exposure on T cell development, and the underlying mechanism of Pb-induced suppression of the delayed-type hypersensitivity (DTH) response in vivo. Sprague-Dawley rats were exposed to 300 ppm Pb-acetate solution via the drinking water for six weeks, and we found that Pb exposure significantly increased Pb concentrations in the blood by 4.2-fold (p<0.05) as compared to those in the control rats. In Pb-exposed rats, the amount of thymic CD4(+) CD8(-) and peripheral CD4(+) T cells was significantly reduced, whereas, CD8(+) population was not affected. In contrast to conventional CD4(+) T cells, Foxp3(+) regulatory T cells (Tregs) were increased in both the thymus and peripheral lymphoid organs of Pb-exposed rats. In line with the increase of Tregs, the DTH response of Pb-exposed rats was markedly suppressed. Depletion of Tregs reversed the suppression of DTH response by Pb-exposed CD4(+) T cells in an adoptive transfer model, suggesting a critical role of the increased Tregs in suppressing the DTH response. Collectively, this study revealed that Pb-exposure may upregulate Tregs, thereby leading to immunosuppression. (C) 2012 Elsevier Inc. All rights reserved. C1 [Zhao, Fang; Shen, Xuefeng; Liu, Xinqin; Xu, Yan; Yu, Tao; Chen, Jingyuan; Luo, Wenjing] Fourth Mil Med Univ, Sch Publ Hlth, Dept Occupat & Environm Hlth, Xian 710032, Peoples R China. [Zhao, Fang; Shen, Xuefeng; Liu, Xinqin; Xu, Yan; Yu, Tao; Chen, Jingyuan; Luo, Wenjing] Fourth Mil Med Univ, Sch Publ Hlth, Minist Educ, Key Lab Hazard Assessment & Control Special Opera, Xian 710032, Peoples R China. [Fang, Liang; Jin, Boquan] Fourth Mil Med Univ, Dept Immunol, Xian 710032, Peoples R China. [Ouyang, Weiming] US FDA, Cell Biol Lab, Div Monoclonal Antibodies, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Chen, JY (reprint author), Fourth Mil Med Univ, Sch Publ Hlth, Dept Occupat & Environm Hlth, Xian 710032, Peoples R China. EM jy_chen@fmmu.edu.cn; luowenj@fmmu.edu.cn FU Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT); National Natural Science Foundation of China [30830087, 81001233, 30901176]; National Basic Research Program of China [2012CB525004]; Program for New Century Excellent Talents in University (NCET); Science and Technology Innovation Projects of Shaanxi Province [2011KTCL03-19] FX This work was supported by Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT).; This work was supported by grants from the Key Program of National Natural Science Foundation of China (Grant No. 30830087); the National Basic Research Program of China (Grant No. 2012CB525004); Program for New Century Excellent Talents in University (NCET); National Natural Science Foundation of China (Grant No. 81001233 and 30901176); and Science and Technology Innovation Projects of Shaanxi Province (Grant No. 2011KTCL03-19). NR 31 TC 7 Z9 8 U1 0 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD DEC 1 PY 2012 VL 265 IS 2 BP 272 EP 278 DI 10.1016/j.taap.2012.10.001 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 052WK UT WOS:000312230500014 PM 23058909 ER PT J AU Simpson, NE Tryndyak, VP Pogribna, M Beland, FA Pogribny, IP AF Simpson, Natalie E. Tryndyak, Volodymyr P. Pogribna, Marta Beland, Frederick A. Pogribny, Igor P. TI Modifying metabolically sensitive histone marks by inhibiting glutamine metabolism affects gene expression and alters cancer cell phenotype SO EPIGENETICS LA English DT Article DE breast cancer; glutamine metabolism; histone modifications; gene expression ID DOWN-REGULATION; BREAST-CANCER; MEDIATED APOPTOSIS; TUMOR; PATHWAY; GROWTH; RETINOBLASTOMA; TUMORIGENESIS; DEMETHYLASES; TRASTUZUMAB AB The interplay of metabolism and epigenetic regulatory mechanisms has become a focal point for a better understanding of cancer development and progression. In this study, we have acquired data supporting previous observations that demonstrate glutamine metabolism affects histone modifications in human breast cancer cell lines. Treatment of non-invasive epithelial (T-47D and MDA-MB-361) and invasive mesenchymal (MDA-MB-231 and Hs-578T) breast cancer cell lines with the glutaminase inhibitor, compound 968, resulted in cytotoxicity in all cell lines, with the greatest effect being observed in MDA-MB-231 breast cancer cells. Compound 968 treatment induced significant downregulation of 20 critical cancer-related genes, the majority of which are anti-apoptotic and/or promote metastasis, including AKT, BCL2, BCL2L1, CCND1, CDKN3, ERBB2, ETS1, E2F1, JUN, KITLG, MYB and MYC. Histone H3K4me3, a mark of transcriptional activation, was reduced at the promoters of all but one of these critical cancer genes. The decrease in histone H3K4me3 at global and gene-specific levels correlated with reduced expression of SETD1 and ASH2L, genes encoding the histone H3K4 methyltransferase complex. Further, the expression of other epigenetic regulatory genes, known to be downregulated during apoptosis (e.g., DNMT1, DNMT3B, SETD1 and SIRT1), was also downregulated by compound 968. These changes in gene expression and histone modifications were accompanied by the activation of apoptosis, and decreased invasiveness and resistance of MDA-MB-231 cells to chemotherapeutic drug doxorubicin. The results of this study provide evidence to a link between cytotoxicity caused by inhibiting glutamine metabolism with alterations of the epigenome of breast cancer cells and suggest that modification of intracellular metabolism may enhance the efficiency of epigenetic therapy. C1 [Simpson, Natalie E.; Tryndyak, Volodymyr P.; Pogribna, Marta; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov NR 45 TC 14 Z9 15 U1 1 U2 9 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1559-2294 J9 EPIGENETICS-US JI Epigenetics PD DEC PY 2012 VL 7 IS 12 BP 1413 EP 1420 DI 10.4161/epi.22713 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 048UK UT WOS:000311938500008 PM 23117580 ER PT J AU Feng, PCH Keys, C Lacher, DW Beutin, L Bentancor, A Heuvelink, A Afset, JE Rumi, V Monday, S AF Feng, Peter C. H. Keys, Christine Lacher, David W. Beutin, Lothar Bentancor, Adriana Heuvelink, Annet Afset, Jan E. Rumi, Valeria Monday, Steven TI Clonal relations of atypical enteropathogenic Escherichia coli O157:H16 strains isolated from various sources from several countries SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE Escherichia coli; O157:H16; Atypical enteropathogenic Escherichia coli; clonality ID VIRULENCE PROFILES; CARRY EAE; GENE; EPEC; IDENTIFICATION; PREVALENCE; SEROTYPES; EVOLUTION; ADHERENCE; O157-H7 AB Atypical enteropathogenic Escherichia coli (aEPEC) is comprised of a large heterogeneous group of strains and serotypes that carry the intimin gene (eae) but no other EPEC virulence factors. In a previous study, we examined a few aEPEC strains of O157:H16 serotype from the U.S. and France and found these to be nearly homologous, and speculated that the same strain had been disseminated or perhaps they are part of a large clonal group that exists worldwide. To test that hypothesis, we examined additional 45 strains isolated from various sources from 4 other countries and determined that although there are a few eae-negative O157:H16 strains, most are aEPEC that carried eae and specifically, the e-eae allele. Analysis by pulsed field gel electrophoresis (PFGE) and multilocus sequence typing showed that as a whole, O157:H16 strains are phylogenetically diverse and have different sequence types and PFGE profiles. But the aEPEC strains within the O157:H16 serotype, regardless of the eae allele carried, are a highly conserved and homologous group of sequence type (ST)-171 strains that shared similar PFGE profiles. These aEPEC strains of O157:H16 serotype are not closely related to any of the major EPEC and enterohemorrhagic E. coli clonal lineages and appear to be part of a large clonal group that are prevalent worldwide. C1 [Feng, Peter C. H.; Keys, Christine; Monday, Steven] US FDA, Div Microbiol, College Pk, MD 20740 USA. [Lacher, David W.] US FDA, Div Mol Biol, Laurel, MD USA. [Beutin, Lothar] Fed Inst Risk Assessment, Natl Reference Lab Escherichia Coli, Berlin, Germany. [Bentancor, Adriana; Rumi, Valeria] Univ Buenos Aires, Fac Vet Sci, Buenos Aires, DF, Argentina. [Heuvelink, Annet] GD Anim Hlth Serv, Deventer, Netherlands. [Afset, Jan E.] St Olavs Univ Hosp, Dept Med Microbiol, Trondheim, Norway. [Afset, Jan E.] Norwegian Univ Sci & Technol, Fac Med, N-7034 Trondheim, Norway. RP Feng, PCH (reprint author), US FDA, Div Microbiol, HFS-711,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM peter.feng@fda.hhs.gov OI Afset, Jan Egil/0000-0003-2489-4179 NR 22 TC 4 Z9 4 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0378-1097 EI 1574-6968 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD DEC PY 2012 VL 337 IS 2 BP 126 EP 131 DI 10.1111/1574-6968.12017 PG 6 WC Microbiology SC Microbiology GA 050VE UT WOS:000312081600007 PM 23020830 ER PT J AU Goyvaerts, C De Groeve, K Dingemans, J Van Lint, S Robays, L Heirman, C Reiser, J Zhang, XY Thielemans, K De Baetselier, P Raes, G Breckpot, K AF Goyvaerts, C. De Groeve, K. Dingemans, J. Van Lint, S. Robays, L. Heirman, C. Reiser, J. Zhang, X-Y Thielemans, K. De Baetselier, P. Raes, G. Breckpot, K. TI Development of the Nanobody display technology to target lentiviral vectors to antigen-presenting cells SO GENE THERAPY LA English DT Article DE antigen-presenting cell; Nanobody; lentiviral vector; targeting ID VESICULAR STOMATITIS-VIRUS; DENDRITIC CELLS; IN-VIVO; CANCER-IMMUNOTHERAPY; GENETIC-MODIFICATION; T-CELLS; TRANSDUCTION; IMMUNIZATION; IMMUNITY; THERAPY AB Lentiviral vectors (LVs) provide unique opportunities for the development of immunotherapeutic strategies, as they transduce a variety of cells in situ, including antigen-presenting cells (APCs). Engineering LVs to specifically transduce APCs is required to promote their translation towards the clinic. We report on the Nanobody (Nb) display technology to target LVs to dendritic cells (DCs) and macrophages. This innovative approach exploits the budding mechanism of LVs to incorporate an APC-specific Nb and a binding-defective, fusion-competent form of VSV. G in the viral envelope. In addition to production of high titer LVs, we demonstrated selective, Nb-dependent transduction of mouse DCs and macrophages both in vitro and in situ. Moreover, this strategy was translated to a human model in which selective transduction of in vitro generated or lymph node (LN)-derived DCs and macrophages, was demonstrated. In conclusion, the Nb display technology is an attractive approach to generate LVs targeted to specific cell types. Gene Therapy (2012) 19, 1133-1140; doi: 10.1038/gt.2011.206; published online 12 January 2012 C1 [Goyvaerts, C.; Van Lint, S.; Robays, L.; Heirman, C.; Thielemans, K.; Breckpot, K.] Vrije Univ Brussel, Dept Immunol Physiol, Lab Mol & Cellular Therapy, B-1090 Brussels, Belgium. [De Groeve, K.; Dingemans, J.; De Baetselier, P.; Raes, G.] Vrije Univ Brussel, Lab Cellular & Mol Immunol, B-1090 Brussels, Belgium. [De Groeve, K.; Dingemans, J.; De Baetselier, P.; Raes, G.] VIB Dept Mol & Cellular Interact, Brussels, Belgium. [Reiser, J.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Zhang, X-Y] Univ Miami, Leonard M Miller Sch Med, Miami, FL USA. RP Breckpot, K (reprint author), Vrije Univ Brussel, Dept Immunol Physiol, Lab Mol & Cellular Therapy, Laarbeeklaan 103, B-1090 Brussels, Belgium. EM kbreckpo@vub.ac.be RI Raes, Geert/H-5185-2013; De Baetselier, Patrick/D-3866-2014; Breckpot, Karine/A-4298-2008 OI Raes, Geert/0000-0002-9065-1549; Breckpot, Karine/0000-0003-4331-3480 FU Research foundation Flanders (FWO-V); Agency of Innovation by Science and Technology (IWT-SBO); Interuniversity Attraction Poles Program (IUAP); Belgian State-Belgian Science Policy; research committee of the VUB; IWT-SBO; FWO-V FX We thank Elsy Vaeremans, Petra Roman, Xavier Debaere and Dr Aude Bonehill (VUB) for their help in purifying plasmid DNA and the generation of single cell suspensions from human LNs, respectively. We furthermore thank Profs Axel Bossuyt and Tony Lahoutte for the use of the imaging facilities. This research was performed with the financial support of the Research foundation Flanders (FWO-V), the Agency of Innovation by Science and Technology (IWT-SBO), the Interuniversity Attraction Poles Program (IUAP), the Belgian State-Belgian Science Policy and the research committee of the VUB (OZR). CG, LR and KB are funded by the research committee of the VUB (OZR), the IWT-SBO and the FWO-V, respectively. NR 44 TC 21 Z9 21 U1 0 U2 28 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD DEC PY 2012 VL 19 IS 12 BP 1133 EP 1140 DI 10.1038/gt.2011.206 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 049QF UT WOS:000311997800002 PM 22241177 ER PT J AU Obuchowski, NA Gallas, BD Hillis, SL AF Obuchowski, Nancy A. Gallas, Brandon D. Hillis, Stephen L. TI Multi-reader ROC Studies with Split-plot Designs: A Comparison of Statistical Methods SO ACADEMIC RADIOLOGY LA English DT Article DE Multireader imaging study; MRMC study; ROC analysis; split-plot design ID OPERATING CHARACTERISTIC ANALYSIS; OF-VARIANCE MODELS; MRMC METHOD; MULTIREADER; COMPONENTS; BOOTSTRAP; SYSTEMS; CURVES AB Rationale and Objectives: Multireader imaging trials often use a factorial design, in which study patients undergo testing with all imaging modalities and readers interpret the results of all tests for all patients. A drawback of this design is the large number of interpretations required of each reader. Split-plot designs have been proposed as an alternative, in which one or a subset of readers interprets all images of a sample of patients, while other readers interpret the images of other samples of patients. In this paper, the authors compare three methods of analysis for the split-plot design. Materials and Methods: Three statistical methods are presented: the Obuchowski-Rockette method modified for the split-plot design, a newly proposed marginal-mean analysis-of-variance approach, and an extension of the three-sample U-statistic method. A simulation study using the Roe-Metz model was performed to compare the type I error rate, power, and confidence interval coverage of the three test statistics. Results: The type I error rates for all three methods are close to the nominal level but tend to be slightly conservative. The statistical power is nearly identical for the three methods. The coverage of 95% confidence intervals falls close to the nominal coverage for small and large sample sizes. Conclusions: The split-plot multireader, multicase study design can be statistically efficient compared to the factorial design, reducing the number of interpretations required per reader. Three methods of analysis, shown to have nominal type I error rates, similar power, and nominal confidence interval coverage, are available for this study design. C1 [Obuchowski, Nancy A.] Cleveland Clin Fdn, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA. [Gallas, Brandon D.] US FDA, Div Imaging & Appl Math, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Hillis, Stephen L.] Univ Iowa, Dept Radiol, Comprehens Access & Delivery Res & Evaluat Ctr, Iowa City VA Hlth Care Syst, Iowa City, IA 52242 USA. [Hillis, Stephen L.] Univ Iowa, Dept Biostat, Comprehens Access & Delivery Res & Evaluat Ctr, Iowa City VA Hlth Care Syst, Iowa City, IA 52242 USA. RP Obuchowski, NA (reprint author), Cleveland Clin Fdn, Dept Quantitat Hlth Sci, JJN-3,9500 Euclid Ave, Cleveland, OH 44195 USA. EM obuchon@ccf.org OI Hillis, Stephen/0000-0002-4886-8584 FU National Institute of Biomedical Imaging and Bioengineering (Bethesda, MD) [R01EB000863, R01EB013667] FX Dr Hillis is supported by grants R01EB000863 and R01EB013667 from the National Institute of Biomedical Imaging and Bioengineering (Bethesda, MD). NR 29 TC 8 Z9 8 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD DEC PY 2012 VL 19 IS 12 BP 1508 EP 1517 DI 10.1016/j.acra.2012.09.012 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 044WB UT WOS:000311654800010 PM 23122570 ER PT J AU Taylor, CL Meyers, LD AF Taylor, Christine L. Meyers, Linda D. TI Perspectives and Progress on Upper Levels of Intake in the United States SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT 8th Workshop on the Assessment of Adequate and Safe Intake of Dietary Amino Acids CY NOV 10-11, 2011 CL undefined, WA ID DOSE-RESPONSE AB In the US, recognition of the appropriateness of including an upper level of intake estimate among reference values for nutrient substances was made in 1994 when the Food and Nutrition Board of the Institute of Medicine (IOM) specified the inclusion of an "upper safe" level among its proposed reference points for intake of nutrients and food components. By 1998, a group convened by the IOM had established a risk assessment model for establishing upper intake levels for nutrients, eventually termed the tolerable upper intake levels (UL). A risk assessment framework (i.e., a scientific undertaking intended to characterize the nature and likelihood of harm resulting from human exposure to agents in the environment), as developed in other fields of study, was a logical fit for application to nutrients. But importantly, whereas risk assessment requires that information be organized in specific ways, it does not require specific scientific evaluation methods. Rather, it makes transparent and documents the decision-making that occurs given the available data and the related uncertainties. During the 1990s and beyond, the various CM committees charged with developing UL for a range of nutrients utilized the risk assessment framework, making modifications and adjustments as dictated by the data. This experience informed the general organizational process for establishing UL but also underscored the dearth of data. For many reasons, undertaking scientific research and obtaining data about the effects of excessive intake have been challenging. It is time to consider creative and focused strategies for modeling, simulating, and otherwise studying the effects of excessive intake of nutrient substances. J. Nutr. 142: 2207S-2211S, 2012. C1 [Taylor, Christine L.] US FDA, College Pk, MD USA. [Meyers, Linda D.] Food & Nutr Board, Inst Med, Washington, DC USA. RP Taylor, CL (reprint author), US FDA, College Pk, MD USA. EM ctaylor3450@gmail.com FU International Council on Amino Acid Science (ICAAS); International Life Sciences Institute (ILSI) Research Foundation; Office of Dietary Supplements, Office of the Director, NIH FX Published in a supplement to The Journal of Nutrition. Presented at the 8th Workshop on the Assessment of Adequate and Safe Intake of Dietary Amino Acids, held in Washington, DC, November 10-11, 2011. The conference was sponsored by the International Council on Amino Acid Science (ICAAS) and the International Life Sciences Institute (ILSI) Research Foundation. The Organizing Committee for the workshop included Sidney M. Morris, Jr, Dennis M. Bier, Luc A. Cynober, Motoni Kadowaki, and Andrew G. Renwick. The views expressed in these papers are not necessarily those of the Supplement Coordinator or Guest Editors. The Supplement Coordinator for this supplement was D'Ann Finley, University California, Davis. Supplement Coordinator disclosures: D'Ann Finley received travel support and compensation from ICAAS for editorial services provided for this supplement publication. The supplement is the responsibility of the Guest Editor to whom the Editor of The Journal of Nutrition has delegated supervision of both technical conformity to the published regulations of The Journal of Nutrition and general oversight of the scientific merit of each article. The Guest Editor for this supplement was Harry Dawson. Guest Editor disclosure: Harry Dawson had no conflicts to disclose. Publication costs for this supplement were defrayed in part by the payment of page charges. This publication must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact. The opinions expressed in this publication are those of the authors and are not attributable to the sponsors or the Publisher, Editor, or Editorial Board of The Journal of Nutrition.; Supported in part by the Office of Dietary Supplements, Office of the Director, NIH. The responsibility for the content of this article rests with the authors and does not necessarily represent the views of the Institute of Medicine or its committees. NR 13 TC 2 Z9 2 U1 0 U2 3 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 EI 1541-6100 J9 J NUTR JI J. Nutr. PD DEC PY 2012 VL 142 IS 12 BP 2207S EP 2211S DI 10.3945/jn.112.159087 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 044XK UT WOS:000311658300020 PM 23077188 ER PT J AU Zhang, H Schaubel, DE Kalbfleisch, JD Robinson, BM Pisoni, RL Port, FK Saran, R AF Zhang, Hui Schaubel, Douglas E. Kalbfleisch, John D. Robinson, Bruce M. Pisoni, Ronald L. Port, Friedrich K. Saran, Rajiv TI Choice of reference in the evaluation of the day-of-week effect on mortality on hemodialysis SO KIDNEY INTERNATIONAL LA English DT Letter ID DIALYSIS C1 [Schaubel, Douglas E.; Kalbfleisch, John D.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Zhang, Hui] US FDA, Silver Spring, MD USA. [Schaubel, Douglas E.; Kalbfleisch, John D.; Saran, Rajiv] Univ Michigan, Kidney Epidemiol & Cost Ctr, Ann Arbor, MI 48109 USA. [Robinson, Bruce M.; Pisoni, Ronald L.; Port, Friedrich K.] Arbor Res Collaborat Hlth, Ann Arbor, MI USA. RP Schaubel, DE (reprint author), Univ Michigan, Dept Biostat, 1415 Washington Hts, Ann Arbor, MI 48109 USA. EM deschau@umich.edu NR 2 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 2012 VL 82 IS 12 BP 1339 EP 1340 DI 10.1038/ki.2012.342 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 048EI UT WOS:000311892600016 PM 23203024 ER PT J AU Christian, JB Finkle, JK Ky, B Douglas, PS Gutstein, DE Hockings, PD Lainee, P Lenihan, DJ Mason, JW Sager, PT Todaro, TG Hicks, KA Kane, RC Ko, HS Lindenfeld, J Michelson, EL Milligan, J Munley, JY Raichlen, JS Shahlaee, A Strnadova, C Ye, B Turner, JR AF Christian, Jennifer B. Finkle, John K. Ky, Bonnie Douglas, Pamela S. Gutstein, David E. Hockings, Paul D. Lainee, Pierre Lenihan, Daniel J. Mason, Jay W. Sager, Philip T. Todaro, Thomas G. Hicks, Karen A. Kane, Robert C. Ko, Hon-Sum Lindenfeld, JoAnn Michelson, Eric L. Milligan, James Munley, Jiefen Y. Raichlen, Joel S. Shahlaee, Amir Strnadova, Colette Ye, Brenda Turner, J. Rick TI Cardiac imaging approaches to evaluate drug-induced myocardial dysfunction SO AMERICAN HEART JOURNAL LA English DT Article ID CARDIOVASCULAR MAGNETIC-RESONANCE; EARLY ANTHRACYCLINE CARDIOTOXICITY; OF-ECHOCARDIOGRAPHYS GUIDELINES; VENTRICULAR EJECTION FRACTION; TERM-FOLLOW-UP; HEART-FAILURE; 3-DIMENSIONAL ECHOCARDIOGRAPHY; DOXORUBICIN CARDIOTOXICITY; ENDOMYOCARDIAL BIOPSY; RADIONUCLIDE ANGIOGRAPHY AB The ability to make informed benefit-risk assessments for potentially cardiotoxic new compounds is of considerable interest and importance at the public health, drug development, and individual patient levels. Cardiac imaging approaches in the evaluation of drug-induced myocardial dysfunction will likely play an increasing role. However, the optimal choice of myocardial imaging modality and the recommended frequency of monitoring are undefined. These decisions are complicated by the array of imaging techniques, which have varying sensitivities, specificities, availabilities, local expertise, safety, and costs, and by the variable time-course of tissue damage, functional myocardial depression, or recovery of function. This White Paper summarizes scientific discussions of members of the Cardiac Safety Research Consortium on the main factors to consider when selecting nonclinical and clinical cardiac function imaging techniques in drug development. We focus on 3 commonly used imaging modalities in the evaluation of cardiac function: echocardiography, magnetic resonance imaging, and radionuclide (nuclear) imaging and highlight areas for future research. (Am Heart J 2012;164:846-55.) C1 [Christian, Jennifer B.] GlaxoSmithKline, Clin Effectiveness & Safety, Durham, NC 27709 USA. [Finkle, John K.] GlaxoSmithKline, Upper Providence, PA USA. [Ky, Bonnie] Univ Penn, Sch Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA. [Douglas, Pamela S.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Gutstein, David E.] Merck Sharp & Dohme Corp, Rahway, NJ USA. [Hockings, Paul D.] AstraZeneca AB, Molndal, Sweden. [Lenihan, Daniel J.] Vanderbilt Univ, Div Cardiovasc Med, Nashville, TN USA. [Mason, Jay W.] Univ Utah, Salt Lake City, UT USA. [Sager, Philip T.] Sager Consulting Partners, San Francisco, CA USA. [Todaro, Thomas G.] Medpace, Cincinnati, OH USA. [Hicks, Karen A.] US FDA, Div Cardiovasc & Renal Prod, Off Drug Evaluat 1, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Kane, Robert C.] US FDA, Div Hematol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Ko, Hon-Sum] US FDA, Div Dermatol & Dent Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Lindenfeld, JoAnn] Univ Colorado, Dept Med, Aurora, CO USA. [Michelson, Eric L.; Munley, Jiefen Y.; Raichlen, Joel S.] AstraZeneca LP, Wilmington, DE USA. [Shahlaee, Amir] US FDA, Off Hematol & Oncol Prod, Silver Spring, MD USA. [Strnadova, Colette] Hlth Canada, Ottawa, ON K1A 0L2, Canada. [Ye, Brenda] US FDA, Div Med Imaging Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Turner, J. Rick] Quintiles, Durham, NC USA. RP Christian, JB (reprint author), GlaxoSmithKline, Clin Effectiveness & Safety, 5 Moore Dr,B 3116, Durham, NC 27709 USA. EM Jennifer.B.Christian@gsk.com RI Hockings, Paul/C-1629-2010 OI Hockings, Paul/0000-0002-7154-9047 FU NHLBI NIH HHS [K23 HL095661] NR 79 TC 9 Z9 9 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD DEC PY 2012 VL 164 IS 6 BP 846 EP 855 DI 10.1016/j.ahj.2012.09.001 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 044PU UT WOS:000311634500011 PM 23194484 ER PT J AU Al-Saleem, FH Ancharski, DM Joshi, SG Elias, M Singh, A Nasser, Z Simpson, LL AF Al-Saleem, Fetweh H. Ancharski, Denise M. Joshi, Suresh G. Elias, M. Singh, Ajay Nasser, Zidoon Simpson, Lance L. TI Analysis of the Mechanisms That Underlie Absorption of Botulinum Toxin by the Inhalation Route SO INFECTION AND IMMUNITY LA English DT Article ID INTESTINAL EPITHELIAL-CELLS; CLOSTRIDIUM-BOTULINUM; WOUND BOTULISM; PROGENITOR TOXIN; UNITED-STATES; HA PROTEINS; DRUG-USERS; NEUROTOXIN; BINDING; TRANSCYTOSIS AB Botulinum toxin is a highly potent oral and inhalation poison, which means that the toxin must have an efficient mechanism for penetration of epithelial barriers. To date, three models for toxin passage across epithelial barriers have been proposed: (i) the toxin itself undergoes binding and transcytosis; (ii) an auxiliary protein, HA35, transports toxin from the apical to the basal side of epithelial cells; and (iii) an auxiliary protein, HA35, acts on the basal side of epithelial cells to disrupt tight junctions, and this permits paracellular flux of toxin. These models were evaluated by studying toxin absorption following inhalation exposure in mice. Three types of experiments were conducted. In the first, the potency of pure neurotoxin was compared with that of progenitor toxin complex, which contains HA35. The results showed that the rate and extent of toxin absorption, as well as the potency of absorbed toxin, did not depend upon, nor were they enhanced by, the presence of HA35. In the second type of experiment, the potencies of pure neurotoxin and progenitor toxin complex were compared in the absence or presence of antibodies on the apical side of epithelial cells. Antibodies directed against the neurotoxin protected against challenge, but antibodies against HA35 did not. In the final type of experiment, the potency of pure neurotoxin and toxin complex was compared in animals pretreated to deliver antibodies to the basal side of epithelial cells. Once again, antibodies directed against the neurotoxin provided resistance to challenge, but antibodies directed against HA35 did not. Taken collectively, the data indicate that the toxin by itself is capable of crossing epithelial barriers. The data do not support any hypothesis in which HA35 is essential for toxin penetration of epithelial barriers. C1 [Al-Saleem, Fetweh H.; Ancharski, Denise M.; Elias, M.; Simpson, Lance L.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Philadelphia, PA 19107 USA. [Simpson, Lance L.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Biochem & Mol Biol, Philadelphia, PA 19107 USA. [Joshi, Suresh G.; Elias, M.] Drexel Coll Med, Dept Surg, Philadelphia, PA USA. [Singh, Ajay] Ctr Food Safety & Appl Nutr, Off Regulatory Sci, Div Microbiol, College Pk, MD USA. [Nasser, Zidoon] Tufts Univ, Sch Med, St Elizabeths Med Ctr, Dept Surg, Boston, MA 02111 USA. RP Simpson, LL (reprint author), Inventox Inc, Lankenau Inst Med Res, Wynnewood, PA USA. EM Lance.Simpson@jefferson.edu FU NIH [NO1-AI30028, GM57345]; DTRA [1-07-0032] FX This work was supported in part by NIH grants NO1-AI30028 and GM57345 and by DTRA contract 1-07-0032. NR 36 TC 8 Z9 8 U1 0 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2012 VL 80 IS 12 BP 4133 EP 4142 DI 10.1128/IAI.00669-12 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 036MQ UT WOS:000311030800009 PM 22966044 ER PT J AU Ju, WT Cao, GJ Rump, L Strain, E Luo, Y Timme, R Allard, M Zhao, SH Brown, E Meng, JH AF Ju, Wenting Cao, Guojie Rump, Lydia Strain, Errol Luo, Yan Timme, Ruth Allard, Marc Zhao, Shaohua Brown, Eric Meng, Jianghong TI Phylogenetic Analysis of Non-O157 Shiga Toxin-Producing Escherichia coli Strains by Whole-Genome Sequencing SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID UNITED-STATES; EVOLUTION; INFECTIONS; PATHOGENS; VIRULENCE; ALIGNMENT; REVEALS; O157-H7; VERSION; MODEL AB Non-O157 Shiga toxin-producing Escherichia coli (STEC) strains are emerging food-borne pathogens causing life-threatening diseases and food-borne outbreaks. A better understanding of their evolution provides a framework for developing tools to control food safety. We obtained 15 genomes of non-O157 STEC strains, including O26, O111, and O103 strains. Phylogenetic trees revealed a close relationship between O26:H11 and O111:H11 and a scattered distribution of O111. We hypothesize that STEC serotypes with the same H antigens might share common ancestors. C1 [Ju, Wenting; Cao, Guojie; Rump, Lydia; Meng, Jianghong] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Ju, Wenting; Cao, Guojie; Rump, Lydia; Meng, Jianghong] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. [Strain, Errol; Luo, Yan] US FDA, Biostat Branch, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Timme, Ruth; Allard, Marc; Brown, Eric] US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Zhao, Shaohua] US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, College Pk, MD USA. RP Meng, JH (reprint author), Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. EM jmeng@umd.edu FU Joint Institute for Food Safety and Applied Nutrition (JIFSAN), University of Maryland, College Park, MD FX The study was supported in part by the Joint Institute for Food Safety and Applied Nutrition (JIFSAN), University of Maryland, College Park, MD. NR 22 TC 16 Z9 16 U1 0 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 2012 VL 50 IS 12 BP 4123 EP 4127 DI 10.1128/JCM.02262-12 PG 5 WC Microbiology SC Microbiology GA 038ZE UT WOS:000311211800054 PM 23052305 ER PT J AU Parshikov, IA Sutherland, JB AF Parshikov, Igor A. Sutherland, John B. TI Microbial transformations of antimicrobial quinolones and related drugs SO JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY LA English DT Review DE Biotransformation; Ciprofloxacin; Enrofloxacin; Fluoroquinolones; Pradofloxacin ID FUNGUS MUCOR-RAMANNIANUS; URINARY-TRACT INFECTIONS; WATER TREATMENT-PLANT; IN-VITRO ACTIVITIES; FLUOROQUINOLONE ENROFLOXACIN; ANTIBACTERIAL ACTIVITY; ROT FUNGUS; PLASMODIUM-FALCIPARUM; GLOEOPHYLLUM-STRIATUM; BACTERIAL-INFECTIONS AB The quinolones are an important group of synthetic antimicrobial drugs used for treating bacterial diseases of humans and animals. Microorganisms transform antimicrobial quinolones (including fluoroquinolones) and the pharmacologically related naphthyridones, pyranoacridones, and cinnolones to a variety of metabolites. The biotransformation processes involve hydroxylation of methyl groups; hydroxylation of aliphatic and aromatic rings; oxidation of alcohols and amines; reduction of carboxyl groups; removal of methyl, carboxyl, fluoro, and cyano groups; addition of formyl, acetyl, nitrosyl, and cyclopentenone groups; and cleavage of aliphatic and aromatic rings. Most of these reactions greatly reduce or eliminate the antimicrobial activity of the quinolones. C1 [Sutherland, John B.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Parshikov, Igor A.] First Moscow State Med Univ IM Sechenov, Moscow, Russia. RP Sutherland, JB (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM john.sutherland@fda.hhs.gov OI Parshikov, Igor/0000-0003-1466-1128 NR 96 TC 4 Z9 5 U1 3 U2 63 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1367-5435 J9 J IND MICROBIOL BIOT JI J. Ind. Microbiol. Biotechnol. PD DEC PY 2012 VL 39 IS 12 BP 1731 EP 1740 DI 10.1007/s10295-012-1194-x PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 038WW UT WOS:000311205800001 PM 23007957 ER PT J AU Goehe, RW Di, X Sharma, K Bristol, ML Henderson, SC Valerie, K Rodier, F Davalos, AR Gewirtz, DA AF Goehe, Rachel W. Di, Xu Sharma, Khushboo Bristol, Molly L. Henderson, Scott C. Valerie, Kristoffer Rodier, Francis Davalos, Albert R. Gewirtz, David A. TI The Autophagy-Senescence Connection in Chemotherapy: Must Tumor Cells (Self) Eat Before They Sleep? SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DNA-DAMAGE RESPONSE; INDUCED PREMATURE SENESCENCE; ONCOGENE-INDUCED SENESCENCE; HUMAN BREAST-CANCER; CELLULAR SENESCENCE; REACTIVE OXYGEN; SIGNALING PATHWAY; INDUCED APOPTOSIS; ACCELERATED SENESCENCE; BETA-GALACTOSIDASE AB Exposure of MCF-7 breast tumor cells or HCT-116 colon carcinoma cells to clinically relevant concentrations of doxorubicin (Adriamycin; Farmitalia Research Laboratories, Milan, Italy) or camptothecin results in both autophagy and senescence. To determine whether autophagy is required for chemotherapy-induced senescence, reactive oxygen generation induced by Adriamycin was suppressed by N-acetyl cysteine and glutathione, and the induction of ataxia telangiectasia mutated, p53, and p21 was modulated pharmacologically and/or genetically. In all cases, autophagy and senescence were collaterally suppressed. The close association between autophagy and senescence indicated by these experiments reflects their collateral regulation via common signaling pathways. The potential relationship between autophagy and senescence was further examined through pharmacologic inhibition of autophagy with chloroquine and 3-methyl-adenine and genetic ablation of the autophagy-related genes ATG5 and ATG7. However, inhibition of autophagy by pharmacological and genetic approaches could not entirely abrogate the senescence response, which was only reduced and/or delayed. Taken together, our findings suggest that autophagy and senescence tend to occur in parallel, and furthermore that autophagy accelerates the development of the senescent phenotype. However, these responses are not inexorably linked or interdependent, as senescence can occur when autophagy is abrogated. C1 [Gewirtz, David A.] Virginia Commonwealth Univ, Massey Canc Ctr, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. [Goehe, Rachel W.; Valerie, Kristoffer] Virginia Commonwealth Univ, Dept Radiat Oncol, Richmond, VA 23298 USA. [Bristol, Molly L.] Virginia Commonwealth Univ, Dept Pathol, Richmond, VA 23298 USA. [Henderson, Scott C.] Virginia Commonwealth Univ, Dept Anat & Neurobiol, Richmond, VA 23298 USA. [Di, Xu] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Rodier, Francis] Univ Montreal, Dept Radiol, Montreal, PQ, Canada. [Rodier, Francis] Ctr Hosp Univ Montreal, Montreal, PQ, Canada. [Rodier, Francis] Inst Canc Montreal, Montreal, PQ, Canada. [Davalos, Albert R.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA. RP Gewirtz, DA (reprint author), Virginia Commonwealth Univ, Massey Canc Ctr, Dept Pharmacol & Toxicol, 401 Coll St, Richmond, VA 23298 USA. EM gewirtz@vcu.edu OI Henderson, Scott/0000-0002-1076-3867 FU National Institutes of Health National Cancer Institute [P30CA16059, T32 CA113277-04]; National Institutes of Health [R01-NS064593, R21-CA156995]; National Institutes of Health, National Institute of Neurological Disorders and Stroke [5P30NS047463] FX The Virginia Commonwealth University Flow Cytometry and Imaging Shared Resource Facility is supported in part by the National Institutes of Health National Cancer Institute [Grant P30CA16059]. R.W.G. was supported by the National Institutes of Health National Cancer Institute [Grant T32 CA113277-04]. KV was supported in part by the National Institutes of Health [Grants R01-NS064593, R21-CA156995].; Electron microscopy was performed at the Virginia Commonwealth University Department of Anatomy and Neurobiology Microscopy Facility, which is supported, in part, by the National Institutes of Health, National Institute of Neurological Disorders and Stroke [Grant 5P30NS047463]. Quantification of beta-galactosidase and acridine orange staining were conducted at the Virginia Commonwealth University Flow Cytometry and Imaging Shared Resource Facility. The RFP-LC3 vector was generously provided by Dr. Keith Miskimins (University of South Dakota, Vermillion, SD) and was originally developed at the laboratory of Dr. A. M. Tolkovsky (University of Cambridge, Cambridge, UK). The MCF7/ATG7-/- cells were a generous gift from the laboratory of Dr. Ameeta Kelekar (University of Minnesota, Minneapolis, MN). We thank Sarah Golding and Amy Hawkins (Department of Radiation Oncology. Virginia Commonwealth University) for guidance with the studies relating to ATM signaling and silencing. NR 62 TC 42 Z9 43 U1 0 U2 7 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 2012 VL 343 IS 3 BP 763 EP 778 DI 10.1124/jpet.112.197590 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 037JH UT WOS:000311099300023 PM 22927544 ER PT J AU Azizian, H Kramer, JKG Mossoba, MM AF Azizian, Hormoz Kramer, John K. G. Mossoba, Magdi M. TI Evaluating the Transferability of FT-NIR Calibration Models for Fatty Acid Determination of Edible Fats and Oils Among Five Same-make Spectrometers Using Transmission or Transflection Modes with Different Pathlengths SO JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY LA English DT Article DE FT-NIR; Rapid fatty acid determination; Transferability; Calibration models; trans Fatty acids; Saturated fatty acids ID NEAR-INFRARED SPECTROSCOPY; ION LIQUID-CHROMATOGRAPHY; GAS-CHROMATOGRAPHY; EMPHASIS; ISOMERS AB Fourier transform near-infrared (FT-NIR) spectroscopy in conjunction with partial least squares 1 (PLS1) calibration models was previously reported to be an alternative method to GC for the rapid determination of the fatty acid (FA) composition of fats and oils. These calibration models had been developed based on accurate GC data (primary reference method) and observed FT-NIR spectra. In the present three-laboratory limited collaborative study, the transferability of these pre-developed calibration models to four other FT-NIR spectrometers from the same manufacturer was evaluated. Six samples were selected that provided a wide range of FA contents. Our results indicate that these models were successfully transferable to spectrometers operating in the transflection mode with 2- or 4-mm pathlength fiber optic probes or in the transmission mode using 5-mm, but not 8-mm, outer diameter tubes. The predicted FA composition fell within the statistically accepted limits of agreement between FT-NIR and GC. The FT-NIR precision data were consistent with those reported in a published GC collaborative study. The application of FT-NIR to the determination of the total content of SFA, trans FA, MUFA, and PUFA is cost-effective and potentially suitable for the rapid screening of commercial products for compliance verification with labeling regulations. C1 [Azizian, Hormoz; Kramer, John K. G.] NIR Technol Inc, Oakville, ON L6M 2M2, Canada. [Mossoba, Magdi M.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD USA. RP Azizian, H (reprint author), NIR Technol Inc, 1312 Fairmeadow Trail, Oakville, ON L6M 2M2, Canada. EM hazizian@nirtechnologies.com NR 24 TC 8 Z9 8 U1 3 U2 30 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0003-021X J9 J AM OIL CHEM SOC JI J. Am. Oil Chem. Soc. PD DEC PY 2012 VL 89 IS 12 BP 2143 EP 2154 DI 10.1007/s11746-012-2116-9 PG 12 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 041KJ UT WOS:000311400400004 ER PT J AU Wang, YMC Fang, LY Zhou, L Wang, J Ahn, HY AF Wang, Yow-Ming C. Fang, Lanyan Zhou, Lin Wang, Jie Ahn, Hae-Young TI A Survey of Applications of Biological Products for Drug Interference of Immunogenicity Assays SO PHARMACEUTICAL RESEARCH LA English DT Article DE biologics; drug interference; drug tolerance; immunogenicity assay; immunogenicity rate ID INFLAMMATORY-BOWEL-DISEASE; RED-CELL APLASIA; BIOTECHNOLOGY PRODUCTS; THERAPEUTIC PROTEINS; RHEUMATOID-ARTHRITIS; IMMUNE TOLERANCE; HOST ANTIBODIES; INFLIXIMAB; RECOMMENDATIONS; IMMUNOASSAYS AB Biological drugs in circulation can interfere with anti-drug antibody (ADA) assays and cause false ADA negatives. We surveyed the applications of biological products approved by FDA during 2005-2011 for prevalence of drug interferences and proposed approaches to address this issue scientifically. The immunogenicity assay drug tolerance, steady-state drug concentrations, and immunogenicity rates were reviewed for 26 BLA/NDA and 2 sBLA. Many FDA approved biologics had higher steady-state drug concentrations than the drug tolerance of ADA assays, by 1.2- to 800-fold. Reported immunogenicity rates may be negatively impacted. Some sponsors triaged immunogenicity samples according to the drug tolerance, leaving some samples un-assayed or reporting them as inconclusive ADA; but these samples were interpreted as ADA- for calculating immunogenicity rates. Implementation of ADA assays that can tolerate therapeutic drug concentrations is imperative. Given drug interferences, we propose in this paper the following practices: (i) to measure drug concentrations in ADA samples, (ii) to explicitly list all ADA status, including inconclusive ADA and un-assayed samples, (iii) to calculate population immunogenicity rates based on only subjects with confirmed ADA+ and ADA-, and (iv) to make available ADA assay specifics relevant to the use of ADA data in disease management. C1 [Wang, Yow-Ming C.; Fang, Lanyan; Zhou, Lin; Wang, Jie; Ahn, Hae-Young] US FDA, Div Clin Pharmacol 3, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat Res, Silver Spring, MD 20993 USA. RP Wang, YMC (reprint author), US FDA, Div Clin Pharmacol 3, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM yowming.wang@fda.hhs.gov NR 41 TC 15 Z9 15 U1 1 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORDR JI Pharm. Res. PD DEC PY 2012 VL 29 IS 12 BP 3384 EP 3392 DI 10.1007/s11095-012-0833-2 PG 9 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 040CZ UT WOS:000311299300014 PM 22903525 ER PT J AU Chen, MJ Zhang, M Borlak, J Tong, WD AF Chen, Minjun Zhang, Min Borlak, Juergen Tong, Weida TI A Decade of Toxicogenomic Research and Its Contribution to Toxicological Science SO TOXICOLOGICAL SCIENCES LA English DT Review DE bioinformatics; toxicogenomics; liver; systems toxicology ID INDUCED LIVER-INJURY; COMPLEMENTARY-DNA MICROARRAY; DRUG-INDUCED HEPATOTOXICITY; GENE-EXPRESSION PATTERNS; IN-VIVO; UNDERSTAND MECHANISMS; TOXICITY; PREDICTION; DATABASE; DISCOVERY AB Toxicogenomics enjoyed considerable attention as a ground-breaking addition to conventional toxicology assays at its inception. However, the pace at which toxicogenomics was expected to perform has been tempered in recent years. Next to cost, the lack of advanced knowledge discovery and data mining tools significantly hampered progress in this new field of toxicological sciences. Recently, two of the largest toxicogenomics databases were made freely available to the public. These comprehensive studies are expected to stimulate knowledge discovery and development of novel data mining tools, which are essential to advance this field. In this review, we provide a concise summary of each of these two databases with a brief discussion on the commonalities and differences between them. We place our emphasis on some key questions in toxicogenomics and how these questions can be appropriately addressed with the two databases. Finally, we provide a perspective on the future direction of toxicogenomics and how new technologies such as RNA-Seq may impact this field. C1 [Chen, Minjun; Zhang, Min; Tong, Weida] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Borlak, Juergen] Hannover Med Sch, Ctr Pharmacol & Toxicol, D-30625 Hannover, Germany. RP Tong, WD (reprint author), US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM weida.tong@fda.hhs.gov FU German Federal Ministry for Education and Research, Virtual Liver Network initiative [031 6154]; ORISE Stipend of the FDA FX German Federal Ministry for Education and Research as part of the Virtual Liver Network initiative (Grant number 031 6154to J.B.). J.B. is also the recipient of an ORISE Stipend of the FDA, which is gratefully acknowledged. NR 55 TC 44 Z9 45 U1 1 U2 42 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 EI 1096-0929 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2012 VL 130 IS 2 BP 217 EP 228 DI 10.1093/toxsci/kfs223 PG 12 WC Toxicology SC Toxicology GA 040FN UT WOS:000311307600002 PM 22790972 ER PT J AU Pierce, SE Bell, RL Hellberg, RS Cheng, CM Chen, KS Williams-Hill, DM Martin, WB Allard, MW AF Pierce, Sarah E. Bell, Rebecca L. Hellberg, Rosalee S. Cheng, Chorng-Ming Chen, Kai-Shun Williams-Hill, Donna M. Martin, William B. Allard, Marc W. TI Detection and Identification of Salmonella enterica, Escherichia coli, and Shigella spp. via PCR-Electrospray Ionization Mass Spectrometry: Isolate Testing and Analysis of Food Samples SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID REAL-TIME PCR; MULTIPLEX PCR; LISTERIA-MONOCYTOGENES; UNIVERSAL BIOSENSOR; VIRULENCE GENES; RAPID DETECTION; SUBSP ENTERICA; BACTERIA; ASSAY; STRAINS AB An assay to identify the common food-borne pathogens Salmonella, Escherichia coli, Shigella, and Listeria monocytogenes was developed in collaboration with Ibis Biosciences (a division of Abbott Molecular) for the Plex-ID biosensor system, a platform that uses electrospray ionization mass spectroscopy (ESI-MS) to detect the base composition of short PCR amplicons. The new food-borne pathogen (FBP) plate has been experimentally designed using four gene segments for a total of eight amplicon targets. Initial work built a DNA base count database that contains more than 140 Salmonella enterica, 139 E. coli, 11 Shigella, and 36 Listeria patterns and 18 other Enterobacteriaceae organisms. This assay was tested to determine the scope of the assay's ability to detect and differentiate the enteric pathogens and to improve the reference database associated with the assay. More than 800 bacterial isolates of S. enterica, E. coli, and Shigella species were analyzed. Overall, 100% of S. enterica, 99% of E. coli, and 73% of Shigella spp. were detected using this assay. The assay was also able to identify 30% of the S. enterica serovars to the serovar level. To further characterize the assay, spiked food matrices and food samples collected during regulatory field work were also studied. While analysis of preenrichment media was inconsistent, identification of S. enterica from selective enrichment media resulted in serovar-level identifications for 8 of 10 regulatory samples. The results of this study suggest that this high-throughput method may be useful in clinical and regulatory laboratories testing for these pathogens. C1 [Pierce, Sarah E.; Hellberg, Rosalee S.; Cheng, Chorng-Ming; Chen, Kai-Shun; Williams-Hill, Donna M.; Martin, William B.] US FDA, Pacific Reg Lab SW, Irvine, CA USA. [Bell, Rebecca L.; Allard, Marc W.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD USA. RP Pierce, SE (reprint author), US FDA, Pacific Reg Lab SW, Irvine, CA USA. EM sarah.pierce@fda.hhs.gov FU FDA/CFSAN; FDA Commissioner's Fellowship Program FX Funding was provided by FDA/CFSAN and the FDA Commissioner's Fellowship Program. NR 37 TC 13 Z9 13 U1 2 U2 33 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD DEC PY 2012 VL 78 IS 23 BP 8403 EP 8411 DI 10.1128/AEM.02272-12 PG 9 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 035AY UT WOS:000310915300027 PM 23001674 ER PT J AU Iarikov, D Demian, H Rubin, D Alexander, J Nambiar, S AF Iarikov, D. Demian, H. Rubin, D. Alexander, J. Nambiar, S. TI Choice and Doses of Antibacterial Agents for Cement Spacers in Treatment of Prosthetic Joint Infections: Review of Published Studies SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID TOTAL KNEE ARTHROPLASTY; TOTAL HIP-ARTHROPLASTY; ACUTE-RENAL-FAILURE; IMPREGNATED BONE-CEMENT; 2-STAGE REVISION; ARTICULATING SPACER; ELUTION CHARACTERISTICS; ANTIBIOTIC-THERAPY; SYSTEMIC SAFETY; REPLACEMENT AB Background. Addition of antibacterial drugs to interim antibacterial cement spacers (ACSs) is considered to be standard of care for surgical revision in prosthetic joint infections (PJIs). We reviewed published studies evaluating the choice and doses of antibacterials in spacers. Methods. We conducted a PubMed search of all clinical study reports evaluating the use of ACSS in a 2-stage hip or knee arthroplasty for treatment of PJI (1988 through August 2011). The trial design, antibacterials used, and end points studied were analyzed. Results. No randomized trials were found comparing either ACSs with different concentrations of antibacterials or ACSs with or without antibacterials. Most of the studies were uncontrolled and used various time points to evaluate the outcome. Twenty publications that reported doses of antibacterials in spacers and had a follow-up of >= 24 months after the second stage were selected for review. Most ACSs included vancomycin and aminoglycosides. The doses of aminoglycosides and vancomycin ranged from 0.25 to 4.8 g and from 1 to 4 g, respectively, per 40 g of cement. No association between reported eradication of the infection and antibacterial load was found. Conclusions. Published data do not allow evaluation of whether antibacterials in temporary cement spacers provide additional benefits in the treatment of PJI, compared with systemic antibacterials, and are not sufficient to support recommendations on dosages. Complications of ACSs have not been consistently analyzed. Prospective randomized trials comparing spacers with and without antibacterials or spacers with different loads of antibacterials are needed to evaluate the safety and efficacy of ACSs. C1 [Iarikov, D.; Alexander, J.; Nambiar, S.] US FDA, Div Antiinfect Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Demian, H.] US FDA, Off Device Evaluat, Div Surg Orthoped & Restorat Devices, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Rubin, D.] US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Biostat, Silver Spring, MD USA. RP Iarikov, D (reprint author), US FDA, Div Antiinfect Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM dmitri.iarikov@fda.hhs.gov NR 48 TC 16 Z9 16 U1 1 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 1 PY 2012 VL 55 IS 11 BP 1474 EP 1480 DI 10.1093/cid/cis735 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 035RR UT WOS:000310966200011 PM 22918993 ER PT J AU Ding, X Andraca-Carrera, E Cooper, C Miele, P Kornegay, C Soukup, M Marcus, KA AF Ding, Xiao Andraca-Carrera, Eugenio Cooper, Charles Miele, Peter Kornegay, Cynthia Soukup, Mat Marcus, Kendall A. TI No Association of Abacavir Use With Myocardial Infarction: Findings of an FDA Meta-Analysis SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 18th Conference on Retroviruses and Opportunistic Infections (CROI) CY FEB 27-MAR 02, 2011 CL Boston, MA DE abacavir; myocardial infarction; antiretroviral therapy; meta-analysis ID REVERSE-TRANSCRIPTASE INHIBITORS; HIV-INFECTED PATIENTS; IMMUNODEFICIENCY-VIRUS-INFECTION; RANDOMIZED-TRIAL; ANTIRETROVIRAL THERAPY; PROTEASE INHIBITORS; INCREASED RISK; LIPID PROFILE; SUBSTITUTION; LIPOATROPHY AB Background: Several studies have reported an association between abacavir (ABC) exposure and increased risk of myocardial infarction (MI) among HIV-infected individuals. Randomized controlled trials (RCTs) and a pooled analysis by GlaxoSmithKline, however, do not support this association. To better estimate the effect of ABC use on risk of MI, the US Food and Drug Administration (FDA) conducted a trial-level meta-analysis of RCTs in which ABC use was randomized as part of a combined antiretroviral regimen. Methods: From a literature search conducted among 4 databases, 26 RCTs were selected that met the following criteria: conducted in adults, sample size more than 50 subjects, status completed, not a pharmacokinetic trial, and not conducted in Africa. The Mantel-Haenszel method, with risk difference and 95% confidence interval, was used for the primary analysis, along with additional alternative analyses, based on FDA-requested adverse event reports of MI provided by each investigator. Results: The 26 RCTs were conducted from 1996 to 2010, and included 9868 subjects (5028 ABC and 4840 non-ABC). Mean follow-up was 1.43 person-years in the ABC group and 1.49 person-years in the non-ABC group. Forty-six (0.47%) MI events were reported [24 (0.48%) ABC and 22 (0.46%) non-ABC], with no significant difference noted between the 2 groups (risk difference of 0.008% with 95% confidence interval: -0.26% to 0.27%). Conclusions: To the best of our knowledge, our study represents the largest trial-level meta-analysis to date of clinical trials in which ABC use was randomized. Our analysis found no association between ABC use and MI risk. C1 [Miele, Peter; Marcus, Kendall A.] US FDA, Off Antiinfect Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Ding, Xiao; Andraca-Carrera, Eugenio; Soukup, Mat] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Cooper, Charles] US FDA, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Kornegay, Cynthia] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Marcus, KA (reprint author), US FDA, Off Antiinfect Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD USA. EM kendall.marcus@fda.hhs.gov NR 31 TC 76 Z9 76 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 1 PY 2012 VL 61 IS 4 BP 441 EP 447 DI 10.1097/QAI.0b013e31826f993c PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 037DU UT WOS:000311083200009 PM 22932321 ER PT J AU Ingwersen, SH Khurana, M Madabushi, R Watson, E Jonker, DM Tu, DLT Jacobsen, LV Tornoe, CW AF Ingwersen, Steen H. Khurana, Manoj Madabushi, Rajanikanth Watson, Estelle Jonker, Daniel M. Tu Duyen Le Thi Jacobsen, Lisbeth V. Tornoe, Christoffer W. TI Dosing Rationale for Liraglutide in Type 2 Diabetes Mellitus: A Pharmacometric Assessment SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE Pharmacometrics; GLP-1; HbA(1c); calcitonin; regulatory approval ID GLUCAGON-LIKE PEPTIDE-1; HUMAN GLP-1 ANALOG; SAFETY; PHARMACOKINETICS; COMBINATION; METFORMIN; EFFICACY; PLACEBO; NN2211 AB The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide was approved in 2010 by the US Food and Drug Administration (FDA) as an adjunct treatment to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. This article provides insights into the use of pharmacometric analyses for regulatory review with a focus on the dosing recommendations. The assessment was based on the totality of exploratory and confirmatory analysis of dose-finding and pivotal clinical data and was structured around a set of key questions in accordance with current FDA review practice. For the pharmacometric review of liraglutide, the key questions focused on exposure-response relationships for effects on fasting plasma glucose, hemoglobin A(1c), and calcitonin and on variability in exposure across demographic subgroups of patients. The importance of conducting exploratory exposure-response analysis and population pharmacokinetic studies in clinical drug development to support dosing recommendations is highlighted. C1 [Khurana, Manoj; Madabushi, Rajanikanth] US FDA, Off Clin Pharmacol, Silver Spring, MD USA. RP Ingwersen, SH (reprint author), Novo Nordisk AS, Quantitat Clin Pharmacol, Vandtarnsvej 108-110, DK-2860 Soborg, Denmark. EM si@novonordisk.com FU Novo Nordisk A/S, Bagsvaerd, Denmark FX This work was supported by Novo Nordisk A/S, Bagsvaerd, Denmark. NR 20 TC 13 Z9 13 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD DEC PY 2012 VL 52 IS 12 BP 1815 EP 1823 DI 10.1177/0091270011430504 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 031ZJ UT WOS:000310681200003 PM 22174428 ER PT J AU Mehrotra, S Florian, J Gobburu, J AF Mehrotra, Shailly Florian, Jeffry, Jr. Gobburu, Jogarao TI Don't Get Boxed In: Commentary on the Visual Inspection Practices to Assess Exposure-Response Relationships From Binary Clinical Variables SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE Exposure-response; box plots; quantile plot; dose selection; binary outcomes ID DRUG CONCENTRATIONS; PLASMA C1 [Florian, Jeffry, Jr.] US FDA, Div Pharmacometr, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Gobburu, Jogarao] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. [Gobburu, Jogarao] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Gobburu, J (reprint author), 20 Penn St HSF 2, Baltimore, MD 21201 USA. EM JGobburu@rx.umaryland.edu NR 10 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 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD DEC PY 2012 VL 52 IS 12 BP 1912 EP 1917 DI 10.1177/0091270011429568 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 031ZJ UT WOS:000310681200013 PM 22174427 ER PT J AU Peer, CJ Younis, IR Leonard, SS Gannett, PM Minarchick, VC Kenyon, AJ Rojanasakul, Y Callery, PS AF Peer, Cody J. Younis, Islam R. Leonard, Stephen S. Gannett, Peter M. Minarchick, Valerie C. Kenyon, Allison J. Rojanasakul, Yon Callery, Patrick S. TI Glutathione conjugation of busulfan produces a hydroxyl radical-trapping dehydroalanine metabolite SO XENOBIOTICA LA English DT Article DE Dehydroalanine; busulfan; metabolite; glutathione; hydroxyl radical; carbon-centered radical; EPR ID N-ACYL DEHYDROALANINES; KAPPA-B ACTIVATION; LIPID-PEROXIDATION; MASS-SPECTROMETRY; THERAPEUTIC ACTIVITY; AMINO-ACIDS; IDENTIFICATION; REBAMIPIDE; RESONANCE; PROTEINS AB 1. The Phase 2 drug metabolism of busulfan yields a glutathione conjugate that undergoes a beta-elimination reaction. The elimination product is an electrophilic metabolite that is a dehydroalanine-containing tripeptide, gamma-glutamyldehydroalanylglycine (EdAG). In the process, glutathione lacks thiol-related redox properties and gains a radical scavenging dehydroalanine group. 2. EdAG scavenged hydroxyl radical generated in the Fenton reaction in a concentration-dependent manner was monitored by electron paramagnetic resonance (EPR) spectroscopy. The apparent rate of hydroxyl radical scavenging was in the same range as published values for known antioxidants, including N-acyl dehydroalanines. 3. A captodatively stabilized carbon-centered radical intermediate was spin trapped in the reaction of EdAG with hydroxyl radical. The proposed structure of a stable product in the Fenton reaction with EdAG was consistent with that of a gamma-glutamylserylglycyl dimer. 4. Observation of the hydroxyl trapping properties of EdAG suggests that the busulfan metabolite EdAG may contribute to or mitigate redox-related cytotoxicity associated with the therapeutic use of busulfan, and reaffirms indicators that support a role in free radical biology for dehydroalanine-containing peptides and proteins. C1 [Callery, Patrick S.] W Virginia Univ, Sch Pharm, Dept Basic Pharmaceut Sci, Morgantown, WV 26506 USA. [Peer, Cody J.; Younis, Islam R.; Gannett, Peter M.; Rojanasakul, Yon; Callery, Patrick S.] W Virginia Univ, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA. [Younis, Islam R.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Leonard, Stephen S.; Minarchick, Valerie C.; Kenyon, Allison J.] NIOSH, Pathol & Physiol Res Branch, Hlth Effects Lab Div, Morgantown, WV USA. RP Callery, PS (reprint author), W Virginia Univ, Sch Pharm, Dept Basic Pharmaceut Sci, 1 Med Ctr Dr, Morgantown, WV 26506 USA. EM pcallery@hsc.wvu.edu RI Gannett, Peter/J-3347-2015; OI Gannett, Peter/0000-0002-7859-5468; Rojanasakul, Yon/0000-0002-8839-6462 FU WVU PSCoR FX The authors thank Heather Glover for accurate mass measurements at the WVU Mass Spectrometry Center. CP current address, Clinical Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Some authors are affiliated with the US Food and Drug Administration, Silver Spring, Maryland or the National Cancer Institute. However, their contributions to the article were made in their private capacity. No official support or endorsement by the Food and Drug Administration or the National Institutes of Health is intended or should be inferred. Funding from WVU PSCoR is gratefully acknowledged. NR 49 TC 2 Z9 3 U1 0 U2 8 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD DEC PY 2012 VL 42 IS 12 BP 1170 EP 1177 DI 10.3109/00498254.2012.696740 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 033PS UT WOS:000310810900002 PM 22725664 ER PT J AU Karnaukhova, E Krupnikova, SS Rajabi, M Alayash, AI AF Karnaukhova, Elena Krupnikova, Sonia Silinsky Rajabi, Mohsen Alayash, Abdu I. TI Heme binding to human alpha-1 proteinase inhibitor SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE Alpha-1 proteinase inhibitor; Heme; Protoporphyrin; Bilirubin; Circular dichroism; Surface plasmon resonance ID HUMAN-SERUM-ALBUMIN; HIGH-RESOLUTION; SECONDARY STRUCTURE; ALPHA(1)-ANTITRYPSIN; BILIRUBIN; VARIABILITY; RESONANCE; KINETICS; ISOFORMS; DISEASE AB Background: Heme is a unique prosthetic group of various hemoproteins that perform diverse biological functions: however, in its free form heme is intrinsically toxic in vivo. Due to its potential toxicity, heme binding to plasma proteins is an important safety issue in regard to protein therapeutics derived from human blood. While heme binding by hemopexin, albumin and alpha(1)-microglobulin has been extensively studied, the role of other plasma proteins remains largely unknown. Methods: We examined two acute-phase plasma proteins, haptoglobin (Hp) and alpha-1 proteinase inhibitor (alpha(1)-PI) for possible interactions with heme and bilirubin (BR), the final product of heme degradation, using various techniques: UV/Vis spectroscopy, fluorescence, circular dichroism (CD), and surface plasmon resonance (SPR). Results: According to our data, Hp exhibits a very weak association with both heme and BR; alpha(1)-PI's affinity to BR is also very low. However, alpha(1)-PI's affinity to heme (K-D 2.0 x 10(-8) M) is of the same order of magnitude as that of albumin (1.26x10(-8) M). The data for alpha(1)-PI binding with protoporphyrin IX (PPIX) suggest that the elimination of the iron atom from the porphyrin structure results in almost 350-fold lower affinity (K-D 6.93 x 10(-6) M), thus indicating that iron is essential for the heme coordination with the alpha(1)-PI. Conclusions: This work demonstrates for the first time that human alpha(1)-PI is a heme binding protein with an affinity to heme comparable to that of albumin. General significance: Our data may have important implications for safety and efficacy of plasma protein therapeutics. Published by Elsevier B.V. C1 [Karnaukhova, Elena; Krupnikova, Sonia Silinsky; Rajabi, Mohsen; Alayash, Abdu I.] US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Karnaukhova, E (reprint author), US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, 8800 Rockville Pike,NIH Bldg 29,Room 300, Bethesda, MD 20892 USA. EM elena.karnaukhova@fda.hhs.gov FU Oak Ridge Institute for Science and Education (ORISE) FX The authors are thankful to Drs. Todd Mollan and Christine Harman (Center for Biologics Evaluation and Research, FDA) for critical reading of the manuscript and helpful comments. MR and SSK are grateful to the Oak Ridge Institute for Science and Education (ORISE) for fellowship. NR 46 TC 5 Z9 5 U1 3 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD DEC PY 2012 VL 1820 IS 12 BP 2020 EP 2029 DI 10.1016/j.bbagen.2012.09.012 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 036CM UT WOS:000311004000020 PM 23000493 ER PT J AU Zhao, L Shang, EY Sahajwalla, CG AF Zhao, Liang Shang, Elizabeth Y. Sahajwalla, Chandrahas G. TI Application of pharmacokinetics-pharmacodynamics/clinical response modeling and simulation for biologics drug development SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE ADME; pharmacokinetics; pharmacodynamics; pharmacokinetic; pharmacodynamic models; physiological model ID NON-HODGKINS-LYMPHOMA; NEONATAL FC-RECEPTOR; BLOOD-CONCENTRATION DIFFERENCE; MONOCLONAL-ANTIBODIES; RHEUMATOID-ARTHRITIS; IMMUNOGLOBULIN-G; ENTEROHEPATIC CIRCULATION; RECIRCULATORY MODEL; CLINICAL-RESPONSE; RESIDENCE TIME AB Biologics, specifically monoclonal antibody (mAb) drugs, have unique pharmacokinetic (PK) and pharmacodynamic (PD) characteristics as opposed to small molecules. Under the paradigm of model-based drug development, PKPD/clinical response models offer critical insight in guiding biologics development at various stages. On the basis of the molecular structure and corresponding properties of biologics, typical mechanism-based [target-mediated drug disposition (TMDD)], physiologically based PK, PKPD, and doseresponse meta-analysis models are summarized. Examples of using TMDD, PKPD, and meta-analysis in helping starting dose determination in first-in-human studies and dosing regimen optimization in phase II/III trials are discussed. Instead of covering the entirety of model-based biologics development, this review focuses on the guiding principles and the core mathematical descriptions underlying the PK or PKPD models most used. (c) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:43674382, 2012 C1 [Zhao, Liang; Shang, Elizabeth Y.; Sahajwalla, Chandrahas G.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Zhao, L (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM liang.zhao@fda.hhs.gov NR 80 TC 12 Z9 14 U1 1 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD DEC PY 2012 VL 101 IS 12 BP 4367 EP 4382 DI 10.1002/jps.23330 PG 16 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 029DH UT WOS:000310474500001 PM 23018763 ER PT J AU Ji, P Wang, YN Li, ZH Doddapaneni, S Hertz, S Furness, S Sahajwalla, CG AF Ji, Ping Wang, Yaning Li, Zhihong Doddapaneni, Suresh Hertz, Sharon Furness, Scott Sahajwalla, Chandrahas G. TI Regulatory review of acetaminophen clinical pharmacology in young pediatric patients SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Review DE ADME; clinical pharmacokinetics; disposition; metabolism; pediatric; pharamcokinetics; pharmacodynamics; pharmacokinetics; pharmacodynamics ID FEBRILE CHILDREN; ANTIPYRETIC EFFICACY; UDP-GLUCURONOSYLTRANSFERASES; CEREBROSPINAL-FLUID; FASTED VOLUNTEERS; CONTROLLED-TRIAL; PARACETAMOL; IBUPROFEN; PHARMACOKINETICS; FEVER AB The acetaminophen dosage schedule in pediatric patients below 12 years of age for the over-the-counter (OTC) monograph is one of the many issues being evaluated and discussed in the development of the Proposed Rule for Internal Analgesic, Antipyretic, and Anti-rheumatic drug products. The dosage regimen based on age and weight, with instructions that weight-based dosage should be used if a child's weight is known, is currently being assessed by the agency. This review summarizes the available pharmacokinetic and pharmacodynamic (fever reduction) data of oral acetaminophen in pediatric patients of 6 months to 12 years of age. Acetaminophen is metabolized in the liver mainly through glucuronidation, sulfation, and to a lesser extent oxidation. Because of the difference in the ontogeny of various metabolizing pathways, the relative contribution of each pathway to the overall acetaminophen metabolism in children changes with age. The sulfation pathway plays a more important role in metabolizing acetaminophen than the glucuronidation pathway in younger children as compared with older children and adults. The pharmacokinetic exposure of acetaminophen in pediatric patients of 6 months to 12 years of age given oral administration of 1015 mg/kg is within the adult exposure range given the OTC monograph dose. The antipyretic effect of acetaminophen is dose dependent and appears to be better than placebo at the dose range of 1015 mg/kg in pediatric patients of 6 months to 12 years of age. (c) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:43834389, 2012 C1 [Ji, Ping; Li, Zhihong; Doddapaneni, Suresh; Sahajwalla, Chandrahas G.] US FDA, Div Clin Pharmacol 2, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Wang, Yaning] US FDA, Div Pharmacometr, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Hertz, Sharon] US FDA, Div Anesthesia Analgesia & Addict Prod, Off Drug Evaluat 2, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Furness, Scott] US FDA, Div Nonprescript Regulat Dev, Off Drug Evaluat 4, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Sahajwalla, CG (reprint author), US FDA, Div Clin Pharmacol 2, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM Chandrahas.Sahajwalla@fda.hhs.gov NR 53 TC 9 Z9 9 U1 4 U2 34 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD DEC PY 2012 VL 101 IS 12 BP 4383 EP 4389 DI 10.1002/jps.23331 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 029DH UT WOS:000310474500002 PM 23073837 ER PT J AU Yu, D Evans, ER Hasbrouck, N Reimschuessel, R Shaikh, B AF Yu, D. Evans, E. R. Hasbrouck, N. Reimschuessel, R. Shaikh, B. TI Residue depletion of albendazole and its metabolites in aquacultured yellow perch (Perca flavescens) SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID CHANNEL CATFISH; RAINBOW-TROUT; MUSCLE-TISSUE; BIOTRANSFORMATION; KINETICS; TILAPIA AB Yu, D., Evans, E. R., Hasbrouck, N., Reimschuessel, R., Shaikh, B. Residue depletion of albendazole and its metabolites in aquacultured yellow perch (Perca flavescens). J. vet. Pharmacol. Therap. 35, 560562. Metabolism and residue depletion studies are conducted to determine the marker residue (MR) of a drug in a target tissue of food animals. The MR is used to monitor potential unauthorized use of drugs. The current work is a continuation of our efforts to study metabolism and depletion profiles of albendazole in multiple finfish species to determine a common MR. The results of this study suggest that albendazole sulfone metabolite could potentially serve as MR for albendazole in yellow perch muscle, similar to channel catfish and hybrid striped bass as reported previously by us. C1 [Yu, D.; Evans, E. R.; Hasbrouck, N.; Reimschuessel, R.; Shaikh, B.] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP Shaikh, B (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM badaruddin.shaikh@fda.hhs.gov NR 17 TC 0 Z9 0 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD DEC PY 2012 VL 35 IS 6 BP 560 EP 562 DI 10.1111/j.1365-2885.2011.01354.x PG 3 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 033LO UT WOS:000310798100006 PM 22150530 ER PT J AU Kohli, A Zhang, X Yang, J Russell, RS Donnelly, RP Sheikh, F Sherman, A Young, H Imamichi, T Lempicki, RA Masur, H Kottilil, S AF Kohli, A. Zhang, X. Yang, J. Russell, R. S. Donnelly, R. P. Sheikh, F. Sherman, A. Young, H. Imamichi, T. Lempicki, R. A. Masur, H. Kottilil, S. TI Distinct and overlapping genomic profiles and antiviral effects of Interferon-lambda and -alpha on HCV-infected and noninfected hepatoma cells SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE hepatitis C; Huh7.5 cells; IFN-alpha; IL28B; JFH-1 ID HEPATITIS-C VIRUS; NONSTRUCTURAL 5A PROTEIN; SIGNAL-TRANSDUCTION; GENETIC-VARIATION; PLUS RIBAVIRIN; IL28B; REPLICATION; CLEARANCE; CULTURE AB Recently, several SNPs in the region of the IL28B (IFN-lambda) gene have been associated with spontaneous clearance of hepatitis C virus (HCV) and enhanced cure rates for IFN-alfa-based therapies, suggesting a potential correlation between IFN-lambda and the ability to clear HCV. To understand the mechanism of IFN-lambda s as compared to IFN-alpha s antiviral activity, we performed a comprehensive analysis of their anti-HCV effects, whole genome transcriptome profiling with validation, and signalling of IFN-alpha and IFN-lambda using J6/JFH-1 and Huh7.5 cells in vitro. IFN-lambda and IFN-alpha exhibited comparable anti-HCV activity and gene expression profiles in Huh7.5 cells. While the majority of genes induced by IFN-alpha and IFN-lambda were similar, IFN-lambda exhibits profound, but delayed kinetics of IFN-stimulated genes (ISG) induction, while IFN-alpha induced more rapid induction of ISGs. Furthermore, the increased induction of ISG expression by IFN-lambda correlated with up-regulation of IFN-lambda receptor (IL-28RA) expression and more prolonged activation of the Jak-STAT signalling pathway. The findings from our comparative analysis of IFN-alpha and IFN-lambda in HCV-infected and noninfected cells support the clinical use of IFN-lambda as a potential alternative to IFN-alpha in the treatment of chronic hepatitis C. C1 [Kohli, A.; Zhang, X.; Sherman, A.; Kottilil, S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Yang, J.; Imamichi, T.; Lempicki, R. A.] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. [Russell, R. S.] Mem Univ Newfoundland, Fac Med, St John, NF, Canada. [Donnelly, R. P.; Sheikh, F.] US FDA, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. [Young, H.] NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21701 USA. [Masur, H.] NIH, CCMD, CC, Bethesda, MD 20892 USA. RP Kohli, A (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10 Magnuson Clin Ctr,Room 11N204,10 Ctr Dr, Bethesda, MD 20892 USA. EM kohlia@niaid.nih.gov RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X FU NIH [National Institute of Allergy and Infectious Diseases]; NIH [National Cancer Institute]; U.S. Food and Drug Administration FX This research was supported in whole by the Intramural Research Program of the NIH, [National Institute of Allergy and Infectious Diseases and National Cancer Institute and the U.S. Food and Drug Administration]. The content of this publication does not necessarily reflect the views or policies of the U. S. Department of Health and Human Services, or does mention of any trade names, commercial products or organizations imply endorsement by the U. S. Government. Some of the data in this manuscript were presented in an oral presentation at the American Association for Liver Disease Meeting, Oct 2010, Boston, MA. The authors do not have commercial ownership or other association that might pose a conflict of interest. NR 23 TC 20 Z9 22 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD DEC PY 2012 VL 19 IS 12 BP 843 EP 853 DI 10.1111/j.1365-2893.2012.01610.x PG 11 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 030WE UT WOS:000310600000003 PM 23121362 ER PT J AU Duan, HY Kachko, A Zhong, LL Struble, E Pandey, S Yan, HL Harman, C Virata-Theimer, ML Deng, L Zhao, Z Major, M Feinstone, S Zhang, P AF Duan, Hongying Kachko, Alla Zhong, Lilin Struble, Evi Pandey, Shivani Yan, Hailing Harman, Christine Virata-Theimer, Maria Luisa Deng, Lu Zhao, Zhong Major, Marian Feinstone, Stephen Zhang, Pei TI Amino Acid Residue-Specific Neutralization and Nonneutralization of Hepatitis C Virus by Monoclonal Antibodies to the E2 Protein SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNE-RESPONSES; INFECTION; CHIMPANZEES; BINDING; HCV; REINFECTION; PRESSURE; PLASMA; CD81 AB Antibodies to epitopes in the E2 protein of hepatitis C virus (HCV) reduce the viral infectivity in vivo and in vitro. However, the virus can persist in patients in the presence of neutralizing antibodies. In this study, we generated a panel of monoclonal antibodies that bound specifically to the region between residues 427 and 446 of the E2 protein of HCV genotype 1a, and we examined their capacity to neutralize HCV in a cell culture system. Of the four monoclonal antibodies described here, two were able to neutralize the virus in a genotype 1a-specific manner. The other two failed to neutralize the virus. Moreover, one of the nonneutralizing antibodies could interfere with the neutralizing activity of a chimpanzee polyclonal antibody at E2 residues 412 to 426, as it did with an HCV-specific immune globulin preparation, which was derived from the pooled plasma of chronic hepatitis C patients. Mapping the epitope-paratope contact interfaces revealed that these functionally distinct antibodies shared binding specificity for key amino acid residues, includingW(437), L-438, L-441, and F-442, within the same epitope of the E2 protein. These data suggest that the effectiveness of antibody-mediated neutralization of HCV could be deduced from the interplay between an antibody and a specific set of amino acid residues. Further understanding of the molecular mechanisms of antibody-mediated neutralization and nonneutralization should provide insights for designing a vaccine to control HCV infection in vivo. C1 [Zhong, Lilin; Struble, Evi; Yan, Hailing; Harman, Christine; Virata-Theimer, Maria Luisa; Deng, Lu; Zhao, Zhong; Zhang, Pei] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. [Duan, Hongying; Kachko, Alla; Pandey, Shivani; Major, Marian; Feinstone, Stephen] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. RP Zhang, P (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. EM stephen.feinstone@fda.hhs.gov; pei.zhang@fda.hhs.gov FU Modernizing Science Funds of the Food and Drug Administration FX This study was supported by the Modernizing Science Funds of the Food and Drug Administration. NR 32 TC 13 Z9 13 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 DEC PY 2012 VL 86 IS 23 BP 12686 EP 12694 DI 10.1128/JVI.00994-12 PG 9 WC Virology SC Virology GA 030QN UT WOS:000310585300021 PM 22973024 ER PT J AU Austin, CA Umbreit, TH Brown, KM Barber, DS Dair, BJ Francke-Carroll, S Feswick, A Saint-Louis, MA Hikawa, H Siebein, KN Goering, PL AF Austin, Carlye A. Umbreit, Thomas H. Brown, Ken M. Barber, David S. Dair, Benita J. Francke-Carroll, Sabine Feswick, April Saint-Louis, Melissa A. Hikawa, Hiroyuki Siebein, Kerry N. Goering, Peter L. TI Distribution of silver nanoparticles in pregnant mice and developing embryos SO NANOTOXICOLOGY LA English DT Article DE Silver; nanoparticles; embryos; mice; in vivo; distribution ID SPRAGUE-DAWLEY RATS; IN-VITRO; YOLK-SAC; INHALATION TOXICITY; PLACENTA; MOUSE; PARTICLES; EXPOSURE; VIVO; INCREASES AB The objective of this study was to evaluate the distribution of silver nanoparticles (NPs) in pregnant mice and their developing embryos. Silver NPs (average diameter 50 nm) were intravenously injected into pregnant CD-1 mice on gestation days (GDs) 7, 8, and 9 at dose levels of 0, 35, or 66 mu g Ag/mouse. Mice were euthanised on GD10, and tissue samples were collected and analysed for silver content. Compared with control animals injected with citrate buffer vehicle, silver content was significantly increased (p < 0.05) in nearly all tissues from silver NP-treated mice. Silver accumulation was significantly higher in liver, spleen, lung, tail (injection site), visceral yolk sac, and endometrium compared with other organs from silver NP-treated mice. Furthermore, silver NPs were identified in vesicles in endodermal cells of the visceral yolk sac. In summary, the results demonstrated that silver NPs distributed to most maternal organs, extra-embryonic tissues, and embryos, but did not accumulate significantly in embryos. C1 [Goering, Peter L.] US FDA, Ctr Devices & Radiol Hlth, White Oak Life Sci Lab, Silver Spring, MD 20993 USA. [Austin, Carlye A.; Brown, Ken M.] George Washington Univ, Dept Biol Sci, Washington, DC 20052 USA. [Barber, David S.; Feswick, April] Univ Florida, Ctr Environm & Human Toxicol, Gainesville, FL USA. [Francke-Carroll, Sabine] US FDA, Ctr Food Safety & Nutr, College Pk, MD USA. [Saint-Louis, Melissa A.] George Washington Univ, Reprod Endocrinol & Fertil Dept, Med Fac Associates, Washington, DC USA. [Hikawa, Hiroyuki] George Washington Univ, Dept Stat, Washington, DC 20052 USA. [Siebein, Kerry N.] Univ Florida, Dept Mat Sci & Engn, Gainesville, FL 32611 USA. RP Goering, PL (reprint author), US FDA, Ctr Devices & Radiol Hlth, White Oak Life Sci Lab, WO64-4064,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM peter.goering@fda.hhs.gov NR 51 TC 27 Z9 27 U1 2 U2 23 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1743-5390 J9 NANOTOXICOLOGY JI Nanotoxicology PD DEC PY 2012 VL 6 IS 8 BP 912 EP 922 DI 10.3109/17435390.2011.626539 PG 11 WC Nanoscience & Nanotechnology; Toxicology SC Science & Technology - Other Topics; Toxicology GA 032VY UT WOS:000310748400010 PM 22023110 ER PT J AU Comer, SD Zacny, JP Dworkin, RH Turk, DC Bigelow, GE Foltin, RW Jasinski, DR Sellers, EM Adams, EH Balster, R Burke, LB Cerny, I Colucci, RD Cone, E Cowan, P Farrar, JT Haddox, JD Haythornthwaite, JA Hertz, S Jay, GW Johanson, CE Junor, R Katz, NP Klein, M Kopecky, EA Leiderman, DB McDermott, MP O'Brien, C O'Connor, AB Palmer, PP Raja, SN Rappaport, BA Rauschkolb, C Rowbotham, MC Sampaio, C Setnik, B Sokolowska, M Stauffer, JW Walsh, SL AF Comer, Sandra D. Zacny, James P. Dworkin, Robert H. Turk, Dennis C. Bigelow, George E. Foltin, Richard W. Jasinski, Donald R. Sellers, Edward M. Adams, Edgar H. Balster, Robert Burke, Laurie B. Cerny, Igor Colucci, Robert D. Cone, Edward Cowan, Penney Farrar, John T. Haddox, J. David Haythornthwaite, Jennifer A. Hertz, Sharon Jay, Gary W. Johanson, Chris-Ellyn Junor, Roderick Katz, Nathaniel P. Klein, Michael Kopecky, Ernest A. Leiderman, Deborah B. McDermott, Michael P. O'Brien, Charles O'Connor, Alec B. Palmer, Pamela P. Raja, Srinivasa N. Rappaport, Bob A. Rauschkolb, Christine Rowbotham, Michael C. Sampaio, Cristina Setnik, Beatrice Sokolowska, Marta Stauffer, Joseph W. Walsh, Sharon L. TI Core outcome measures for opioid abuse liability laboratory assessment studies in humans: IMMPACT recommendations SO PAIN LA English DT Review DE Opioids; Opioid analgesics; Abuse; Abuse liability; Abuse potential ID RESEARCH-CENTER INVENTORY; PAIN CLINICAL-TRIALS; AGONIST-ANTAGONIST OPIOIDS; ORAL OXYCODONE; PRESCRIPTION OPIOIDS; SHORT-TERM; MORPHINE; ADDICTION; HYDROMORPHONE; POSTADDICTS AB A critical component in development of opioid analgesics is assessment of their abuse liability (AL). Standardization of approaches and measures used in assessing AL have the potential to facilitate comparisons across studies, research laboratories, and drugs. The goal of this report is to provide consensus recommendations regarding core outcome measures for assessing the abuse potential of opioid medications in humans in a controlled laboratory setting. Although many of the recommended measures are appropriate for assessing the AL of medications from other drug classes, the focus here is on opioid medications because they present unique risks from both physiological (e.g., respiratory depression, physical dependence) and public health (e.g., individuals in pain) perspectives. A brief historical perspective on AL testing is provided, and those measures that can be considered primary and secondary outcomes and possible additional outcomes in AL assessment are then discussed. These outcome measures include the following: subjective effects (some of which comprise the primary outcome measures, including drug liking; physiological responses; drug self-administration behavior; and cognitive and psychomotor performance. Before presenting recommendations for standardized approaches and measures to be used in AL assessments, the appropriateness of using these measures in clinical trials with patients in pain is discussed. Published by Elsevier B.V. on behalf of International Association for the Study of Pain. C1 [Comer, Sandra D.; Foltin, Richard W.] Columbia Univ, New York State Psychiat Inst, Coll Phys & Surg, Div Subst Abuse, New York, NY 10032 USA. [Zacny, James P.] Univ Chicago, Dept Anesthesia & Crit Care, Chicago, IL 60637 USA. [Dworkin, Robert H.] Univ Rochester, Dept Anesthesiol, Rochester, NY USA. [Turk, Dennis C.] Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. [Bigelow, George E.; Cone, Edward; Haythornthwaite, Jennifer A.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Jasinski, Donald R.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Sellers, Edward M.] Kendle Early Phase Toronto, Toronto, ON, Canada. [Adams, Edgar H.] Covance, Princeton, NJ USA. [Balster, Robert] Virginia Commonwealth Univ, Inst Drug & Alcohol Studies, Richmond, VA USA. [Burke, Laurie B.; Cerny, Igor; Hertz, Sharon; Klein, Michael; Rappaport, Bob A.] US FDA, Silver Spring, MD USA. [Colucci, Robert D.] Colucci & Associates LLC, Newtown, CT USA. [Cowan, Penney] Amer Chron Pain Assoc, Rocklin, CA USA. [Farrar, John T.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Haddox, J. David] Purdue Pharma LP, Stamford, CT USA. [Jay, Gary W.] Pfizer Inc, New London, CT USA. [Johanson, Chris-Ellyn] Wayne State Univ, Detroit, MI USA. [Junor, Roderick] Eisai & Co Ltd, Woodcliff Lake, NJ USA. [Katz, Nathaniel P.] Analges Res, Needham, MA USA. [Katz, Nathaniel P.] Tufts Univ, Dept Anesthesiol, Boston, MA 02111 USA. [Kopecky, Ernest A.] Endo Pharmaceut Inc, Chadds Ford, PA USA. [Leiderman, Deborah B.] CNS Drug Consulting LLC, Mclean, VA USA. [McDermott, Michael P.] Univ Rochester, Dept Biostat, Rochester, NY USA. [McDermott, Michael P.] Univ Rochester, Dept Neurol, Rochester, NY USA. [O'Brien, Charles] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [O'Connor, Alec B.] Univ Rochester, Dept Med, Rochester, NY USA. [Palmer, Pamela P.] AcelRx Pharmaceut Inc, Redwood City, CA USA. [Raja, Srinivasa N.] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA. [Rauschkolb, Christine] Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ USA. [Rowbotham, Michael C.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Sampaio, Cristina] Fac Med Lisbon, Clin Pharmacol & Therapeut Lab, Lisbon, Portugal. [Setnik, Beatrice] King Pharmaceut Inc, Cary, NC USA. [Sokolowska, Marta] Grunenthal USA Inc, Bedminster, NJ USA. [Stauffer, Joseph W.] Durect Corp, Cupertino, CA USA. [Walsh, Sharon L.] Univ Kentucky, Ctr Drug & Alcohol Res, Dept Behav Sci, Lexington, KY 40506 USA. RP Comer, SD (reprint author), Columbia Univ, New York State Psychiat Inst, Coll Phys & Surg, Div Subst Abuse, 1051 Riverside Dr,Unit 120, New York, NY 10032 USA. EM sdc10@columbia.edu RI Sellers, Edward/A-2281-2013; OI Yang, Shuman/0000-0002-9638-0890 FU US Department of Veterans Affairs; US Food and Drug Administration; US National Institutes of Health FX The views expressed in this article are those of the authors, none of whom have financial conflicts of interest related to the issues discussed in this manuscript. No official endorsement by the US Department of Veterans Affairs, US Food and Drug Administration, US National Institutes of Health, or the pharmaceutical companies that provided unrestricted grants to the University of Rochester Office of Continuing Professional Education should be inferred. NR 71 TC 14 Z9 14 U1 2 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD DEC PY 2012 VL 153 IS 12 BP 2315 EP 2324 DI 10.1016/j.pain.2012.07.035 PG 10 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 033DB UT WOS:000310772600006 PM 22998781 ER PT J AU Smith, SM Chang, RD Pereira, A Shah, N Gilron, I Katz, NP Lin, AH McDermott, MP Rappaport, BA Rowbotham, MC Sampaio, C Turk, DC Dworkin, RH AF Smith, Shannon M. Chang, R. Daniel Pereira, Anthony Shah, Nirupa Gilron, Ian Katz, Nathaniel P. Lin, Allison H. McDermott, Michael P. Rappaport, Bob A. Rowbotham, Michael C. Sampaio, Cristina Turk, Dennis C. Dworkin, Robert H. TI Adherence to CONSORT harms-reporting recommendations in publications of recent analgesic clinical trials: An ACTTION systematic review SO PAIN LA English DT Article DE CONSORT; Clinical trials; Analgesic medications; Harms; Adverse events; Systematic review ID RANDOMIZED CONTROLLED-TRIALS; CHRONIC PAIN; IMMPACT RECOMMENDATIONS; ADVERSE EVENTS; CONSOLIDATED STANDARDS; MEDICAL JOURNALS; QUALITY; STATEMENT; CHECKLIST; ARTICLES AB Recommendations for harms (ie, adverse events) reporting in randomized clinical trial publications were presented in a 2004 extension of the Consolidated Standards of Reporting Trials (CONSORT) statement. Our objectives were to assess harms reporting in 3 major pain journals (European Journal of Pain, Journal of Pain, and PAIN (R)) to determine whether harms reporting improved following publication of the 2004 CONSORT recommendations, and to examine study factors associated with adequacy of harms reporting. A total of 101 randomized, double-blind, noninvasive pharmacologic trials were identified in the 2000-2003 (epoch 1) and 2008-2011 (epoch 2) issues of these journals. Out of 10 reporting recommendations, the mean number fulfilled was 6.08 (SD 2.65). Although more harms recommendations were fulfilled in epoch 2 (m(2) = 6.49, SD 2.66) than in epoch 1 (m(1) = 5.39, SD 2.52; P = 0.04), only the recommendation to report harms per arm was satisfied by > 90% of trials in epoch 2, whereas < 60% reported withdrawals due to harms. Several trial characteristics ( study design, participant type, pain type, frequency of treatment administration, treatment administration method, sponsor, and number of randomized participants) were significantly associated with harms reporting. However, when trial characteristics and epoch were entered into a multiple regression analysis, only trials studying pain patients, those using oral treatments, and industry-sponsored trials were associated with better harms reporting. Despite some improvement in harms reporting, greater improvement is needed to provide informative, consistent reporting of adverse events and safety in analgesic clinical trials. (c) 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Smith, Shannon M.; Chang, R. Daniel; Pereira, Anthony; Dworkin, Robert H.] Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY 14627 USA. [Shah, Nirupa; Turk, Dennis C.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [Gilron, Ian] Queens Univ, Kingston, ON, Canada. [Katz, Nathaniel P.] Analges Solut, Natick, MA USA. [Katz, Nathaniel P.] Tufts Univ, Boston, MA 02111 USA. [Lin, Allison H.; Rappaport, Bob A.] US FDA, Bethesda, MA USA. [McDermott, Michael P.] Univ Rochester, Sch Med & Dent, Dept Biostat & Computat Biol, Rochester, NY USA. [McDermott, Michael P.; Dworkin, Robert H.] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA. [Rowbotham, Michael C.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Sampaio, Cristina] CHDI, New York, NY USA. [Dworkin, Robert H.] Univ Rochester, Sch Med & Dent, Ctr Human Expt Therapeut, Rochester, NY 14642 USA. RP Smith, SM (reprint author), Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY 14627 USA. EM shannon1_smith@urmc.rochester.edu FU ACTTION; U.S. Food and Drug Administration FX No official endorsement by the US Food and Drug Administration or the pharmaceutical companies that provided unrestricted grants to support the activities of ACTTION should be inferred. Financial support for this study was provided by ACTTION, which has received research contracts, grants, or other revenue from the U.S. Food and Drug Administration, various pharmaceutical companies, and other sources. The authors thank Donna Berryman, MLIS, and Michele Shipley, MLS, for their invaluable assistance. NR 33 TC 19 Z9 19 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD DEC PY 2012 VL 153 IS 12 BP 2415 EP 2421 DI 10.1016/j.pain.2012.08.009 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 033DB UT WOS:000310772600017 PM 22985899 ER PT J AU He, YQ Toldo, L Burns, G Tao, C Abernethy, DR AF He, Yongqun Toldo, Luca Burns, Gully Tao, Cui Abernethy, Darrell R. TI A 2012 Workshop: Vaccine and Drug Ontology in the Study of Mechanism and Effect (VDOSME 2012) SO JOURNAL OF BIOMEDICAL SEMANTICS LA English DT Editorial Material AB Vaccines and drugs have contributed to dramatic improvements in public health worldwide. Over the last decade, there have been efforts in developing biomedical ontologies that represent various areas associated with vaccines and drugs. These ontologies combined with existing health and clinical terminology systems (e.g., SNOMED, RxNorm, NDF-RT, MedDRA, VO, OAE, and AERO) could play significant roles on clinical and translational research. The first "Vaccine and Drug Ontology in the Study of Mechanism and Effect" workshop (VDOSME 2012) provided a platform for discussing problems and solutions in the development and application of biomedical ontologies in representing and analyzing vaccines/drugs, vaccine/drug administrations, vaccine/drug-induced immune responses (including positive host responses and adverse events), and similar topics. The workshop covered two main areas: (i) ontologies of vaccines, of drugs, and of studies thereof; and (ii) analysis of administration, mechanism and effect in terms of representations based on such ontologies. Six full-length papers included in this thematic issue focus on ontology representation and time analysis of vaccine/drug administration and host responses (including positive immune responses and adverse events), vaccine and drug adverse event text mining, and ontology-based Semantic Web applications. The workshop, together with the follow-up activities and personal meetings, provided a wonderful platform for the researchers and scientists in the vaccine and drug communities to demonstrate research progresses, share ideas, address questions, and promote collaborations for better representation and analysis of vaccine and drug-related terminologies and clinical and research data. C1 [He, Yongqun] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Unit Lab Anim Med, Ann Arbor, MI 48109 USA. [He, Yongqun] Univ Michigan, Sch Med, Ctr Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. [Toldo, Luca] Merck KGaA, D-64293 Darmstadt, Germany. [Burns, Gully] Univ So Calif, Inst Informat Sci, Marina Del Rey, CA 90292 USA. [Tao, Cui] Mayo Clin, Div Biomed Stat & Informat, Dept Hlth Sci Res, Rochester, MN USA. [Abernethy, Darrell R.] US FDA, Johns Hopkins Sch Med, Baltimore, MD USA. RP He, YQ (reprint author), Univ Michigan, Sch Med, Dept Microbiol & Immunol, Unit Lab Anim Med, Ann Arbor, MI 48109 USA. EM yongqunh@med.umich.edu RI Toldo, Luca/A-3784-2013; OI Toldo, Luca/0000-0003-2027-5717; He, Yongqun/0000-0001-9189-9661 NR 8 TC 3 Z9 3 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 2041-1480 J9 J BIOMED SEMANT JI J. Biomed. Semant. PD DEC PY 2012 VL 3 AR 12 DI 10.1186/2041-1480-3-12 PG 5 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA V34UC UT WOS:000209110000005 PM 23249650 ER PT J AU Nair, AK Anand, O Chun, N Conner, DP Mehta, MU Nhu, DT Polli, JE Yu, LX Davit, BM AF Nair, Anil K. Anand, Om Chun, Nam Conner, Dale P. Mehta, Mehul U. Nhu, Duong T. Polli, James E. Yu, Lawrence X. Davit, Barbara M. TI Statistics on BCS Classification of Generic Drug Products Approved Between 2000 and 2011 in the USA SO AAPS JOURNAL LA English DT Article DE ANDA; BCS biowaiver; bioequivalence; Biopharmaceutics Classification System; generic drug product ID SYSTEM AB The Biopharmaceutics Classification system (BCS) classifies drug substances based on aqueous solubility and intestinal permeability. The objective of this study was to use the World Health Organization Model List of Essential Medicines to determine the distribution of BCS Class 1, 2, 3, and 4 drugs in Abbreviated New drug Applications (ANDA) submissions. To categorize solubility and intestinal permeability properties of generic drugs under development, we used a list of 61 drugs which were classified as BCS 1, 2, 3, and 4 drugs with certainty in the World Health Organization Model List of Essential Medicines. Applying this list to evaluation of 263 ANDA approvals of BCS drugs during the period of 2000 to 2011 indicated 110 approvals (41.8%) for Class 1 drugs (based on both biowaiver and in vivo bioequivalence studies), 55 (20.9%) approvals for Class 2 drugs, 98 (37.3%) approvals for Class 3 drugs, and no (0%) approvals for Class 4 drugs. The present data indicated a trend of more ANDA approvals of BCS Class 1 drugs than Class 3 or Class 2 drugs. Antiallergic drugs in Class 1, drugs for pain relief in Class 2 and antidiabetic drugs in Class 3 have received the largest number of approvals during this period. C1 [Nair, Anil K.; Anand, Om; Chun, Nam; Conner, Dale P.; Nhu, Duong T.; Yu, Lawrence X.; Davit, Barbara M.] US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20855 USA. [Mehta, Mehul U.] US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Silver Spring, MD 20993 USA. [Polli, James E.] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. RP Nair, AK (reprint author), US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, 7520 Standish Pl, Rockville, MD 20855 USA. EM Anil.Nair@fda.hhs.gov RI Yu, Lawrence/L-6280-2016 NR 7 TC 6 Z9 6 U1 1 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD DEC PY 2012 VL 14 IS 4 BP 664 EP 666 DI 10.1208/s12248-012-9384-z PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 027QC UT WOS:000310367100002 PM 22718306 ER PT J AU Shur, J Lee, S Adams, W Lionberger, R Tibbatts, J Price, R AF Shur, Jagdeep Lee, Sau Adams, Wallace Lionberger, Robert Tibbatts, James Price, Robert TI Effect of Device Design on the In Vitro Performance and Comparability for Capsule-Based Dry Powder Inhalers SO AAPS JOURNAL LA English DT Article DE computational fluid dynamics; device design; dry powder inhaler; in vitro comparability; in vitro performance ID COMPUTATIONAL FLUID-DYNAMICS; NUMERICAL-SIMULATION; PARTICLE DEPOSITION; DELIVERY; MODEL; FLOW AB This study investigated the effect of modifying the design of the Cyclohaler on its aerosolization performance and comparability to the HandiHaler at multiple flow rates. The Cyclohaler and HandiHaler were designated as model test and reference unit-dose, capsule-based dry powder inhalers (DPIs), respectively. The flow field, pressure drop, and carrier particle trajectories within the Cyclohaler and HandiHaler were modeled via computational fluid dynamics (CFD). With the goal of achieving in vitro comparability to the HandiHaler, the CFD results were used to identify key device attributes and to design two modifications of the Cyclohaler (Mod 1 and Mod 2), which matched the specific resistance of the HandiHaler but exhibited different cyclonic flow conditions in the device. Aerosolization performance of the four DPI devices was evaluated by using the reference product's capsule and formulation (Spiriva capsule) and a multistage cascade impactor. The in vitro data showed that Mod 2 provided a closer match to the HandiHaler than the Cyclohaler and Mod 1 at 20, 39, and 55 l/min. The in vitro and CFD results together suggest that matching the resistance of test and reference DPI devices is not sufficient to attain comparable aerosolization performance, and the improved in vitro comparability of Mod 2 to the HandiHaler may be related to the greater degree of similarities of the flow rate of air through the pierced capsule (Q(c)) and the maximum impact velocity of representative carrier particles (V-n) in the Cyclohaler-based device. This investigation illustrates the importance of enhanced product understanding, in this case through the CFD modeling and in vitro characterization of aerosolization performance, to enable identification and modification of key design features of a test DPI device for achieving comparable aerosolization performance to the reference DPI device. C1 [Lee, Sau; Adams, Wallace; Lionberger, Robert] US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20855 USA. [Shur, Jagdeep; Tibbatts, James; Price, Robert] Univ Bath, Pharmaceut Surface Sci Res Grp, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England. RP Lee, S (reprint author), US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, 7519 Standish Pl, Rockville, MD 20855 USA. EM sau.lee@fda.hhs.gov NR 30 TC 28 Z9 30 U1 0 U2 23 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD DEC PY 2012 VL 14 IS 4 BP 667 EP 676 DI 10.1208/s12248-012-9379-9 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 027QC UT WOS:000310367100003 PM 22723022 ER PT J AU Davit, BM Chen, ML Conner, DP Haidar, SH Kim, S Lee, CH Lionberger, RA Makhlouf, FT Nwakama, PE Patel, DT Schuirmann, DJ Yu, LX AF Davit, Barbara M. Chen, Mei-Ling Conner, Dale P. Haidar, Sam H. Kim, Stephanie Lee, Christina H. Lionberger, Robert A. Makhlouf, Fairouz T. Nwakama, Patrick E. Patel, Devvrat T. Schuirmann, Donald J. Yu, Lawrence X. TI Implementation of a Reference-Scaled Average Bioequivalence Approach for Highly Variable Generic Drug Products by the US Food and Drug Administration SO AAPS JOURNAL LA English DT Review DE bioequivalence; generic drugs; highly variable drugs; reference-scaled average bioequivalence; US Food and Drug Administration ID SIDED TESTS PROCEDURE; BIOAVAILABILITY; POWER AB Highly variable (HV) drugs are defined as those for which within-subject variability (%CV) in bioequivalence (BE) measures is 30% or greater. Because of this high variability, studies designed to show whether generic HV drugs are bioequivalent to their corresponding HV reference drugs may need to enroll large numbers of subjects even when the products have no significant mean differences. To avoid unnecessary human testing, the US Food and Drug Administration's Office of Generic Drugs developed a reference-scaled average bioequivalence (RSABE) approach, whereby the BE acceptance limits are scaled to the variability of the reference product. For an acceptable RSABE study, an HV generic drug product must meet the scaled BE limit and a point estimate constraint. The approach has been implemented successfully. To date, the RSABE approach has supported four full approvals and one tentative approval of HV generic drug products. C1 [Davit, Barbara M.; Conner, Dale P.; Kim, Stephanie; Lee, Christina H.; Lionberger, Robert A.; Nwakama, Patrick E.; Patel, Devvrat T.; Yu, Lawrence X.] US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20855 USA. [Chen, Mei-Ling] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. [Haidar, Sam H.] US FDA, Off Compliance, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. [Makhlouf, Fairouz T.] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Rockville, MD 20855 USA. [Schuirmann, Donald J.] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. RP Davit, BM (reprint author), US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, 7520 Standish Pl,Metro Pk N 1, Rockville, MD 20855 USA. EM barbara.davit@fda.hhs.gov RI Yu, Lawrence/L-6280-2016 NR 53 TC 22 Z9 31 U1 3 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD DEC PY 2012 VL 14 IS 4 BP 915 EP 924 DI 10.1208/s12248-012-9406-x PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 027QC UT WOS:000310367100028 PM 22972221 ER PT J AU Stier, EM Davit, BM Chandaroy, P Chen, ML Fourie-Zirkelbach, J Jackson, A Kim, S Lionberger, R Mehta, M Uppoor, RS Wang, YN Yu, L Conner, DP AF Stier, Ethan M. Davit, Barbara M. Chandaroy, Parthapratim Chen, Mei-Ling Fourie-Zirkelbach, Jeanne Jackson, Andre Kim, Stephanie Lionberger, Robert Mehta, Mehul Uppoor, Ramana S. Wang, Yaning Yu, Lawrence Conner, Dale P. TI Use of Partial Area under the Curve Metrics to Assess Bioequivalence of Methylphenidate Multiphasic Modified Release Formulations SO AAPS JOURNAL LA English DT Article DE attention deficit hyperactivity disorder; bioequivalence; generic drugs; methylphenidate; pAUC ID CHILDREN C1 [Stier, Ethan M.; Davit, Barbara M.; Chandaroy, Parthapratim; Conner, Dale P.] US FDA, Div Bioequivalence, Off Gener Drugs, Rockville, MD 20855 USA. [Chen, Mei-Ling] US FDA, Off Pharmaceut Sci, Silver Spring, MD USA. [Fourie-Zirkelbach, Jeanne; Jackson, Andre; Mehta, Mehul; Uppoor, Ramana S.; Wang, Yaning] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Conner, DP (reprint author), US FDA, Div Bioequivalence, Off Gener Drugs, 7520 Standish Pl MPNI, Rockville, MD 20855 USA. EM Dale.Conner@fda.hhs.gov RI Yu, Lawrence/L-6280-2016 NR 7 TC 5 Z9 5 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD DEC PY 2012 VL 14 IS 4 BP 925 EP 926 DI 10.1208/s12248-012-9397-7 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 027QC UT WOS:000310367100029 PM 22976173 ER PT J AU Taylor-Edwards, CC Burrin, DG Kristensen, NB Holst, JJ McLeod, KR Harmon, DL AF Taylor-Edwards, C. C. Burrin, D. G. Kristensen, N. B. Holst, J. J. McLeod, K. R. Harmon, D. L. TI Glucagon-like peptide-2 (GLP-2) increases net amino acid utilization by the portal-drained viscera of ruminating calves SO ANIMAL LA English DT Article DE blood flow; glucose; amino acid; flux; ruminant ID INTESTINAL BLOOD-FLOW; FED NEONATAL PIGLETS; METABOLISM; GROWTH; GLUTAMINE; GLUCOSE; HUMANS; LIVER; GUT; ABSORPTION AB Glucagon-like peptide-2 (GLP-2) increases small intestinal mass and blood flow in ruminant calves, but its impact on nutrient metabolism across the portal-drained viscera (PDV) and liver is unknown. Eight Holstein calves with catheters in the carotid artery, mesenteric vein, portal vein and hepatic vein were paired by age and randomly assigned to control (0.5% bovine serum albumin in saline; n = 4) or GLP-2 (100 mu g/kg BW per day bovine GLP-2 in bovine serum albumin; n = 4). Treatments were administered subcutaneously every 12 h for 10 days. Blood flow was measured on days 0 and 10 and included 3 periods: baseline (saline infusion), treatment (infusion of bovine serum albumin or 3.76 mu g/kg BW per h GLP-2) and recovery (saline infusion). Arterial concentrations and net PDV, hepatic and total splanchnic fluxes of glucose, lactate, glutamate, glutamine, beta-hydroxybutyrate and urea-N were measured on days 0 and 10. Arterial concentrations and net fluxes of all amino acids and glucose metabolism using continuous intravenous infusion of [U-13-C]glucose were measured on day 10 only. A 1-h infusion of GLP-2 increased blood flow in the portal and hepatic veins when administered to calves not previously exposed to exogenous GLP-2, but after a 10-day administration of GLP-2 the blood flow response to the 1-h GLP-2 infusion was substantially attenuated. The 1-h GLP-2 infusion also did not appreciably alter nutrient fluxes on either day 0 or 10. In contrast, long-term GLP-2 administration reduced arterial concentrations and net PDV flux of many essential and non-essential amino acids. Despite the significant alterations in amino acid metabolism, glucose irreversible loss and utilization by PDV and non-PDV tissues were not affected by GLP-2. Fluxes of amino acids across the PDV were generally reduced by GLP-2, potentially by increased small intestinal epithelial growth and thus energy and amino acid requirements of this tissue. Increased PDV extraction of glutamine and alterations in PDV metabolism of arginine, ornithine and citrulline support the concept that GLP-2 influences intestine-specific amino acid metabolism. Alterations in amino acid metabolism but unchanged glucose metabolism suggests that the growth effects induced by GLP-2 in ruminants increase reliance on amino acids preferentially over glucose. Thus, GLP-2 increases PDV utilization of amino acids, but not glucose, C1 [Taylor-Edwards, C. C.; McLeod, K. R.; Harmon, D. L.] Univ Kentucky, Dept Anim & Food Sci, Lexington, KY 40546 USA. [Burrin, D. G.] USDA ARS, Childrens Nutr Res Ctr, Baylor Coll Med, Houston, TX 77030 USA. [Kristensen, N. B.] Aarhus Univ, Dept Anim Hlth & Biosci, DK-8830 Tjele, Denmark. [Holst, J. J.] Univ Copenhagen, Panum Inst, Dept Biomed Sci, DK-2200 Copenhagen, Denmark. RP Taylor-Edwards, CC (reprint author), US FDA, Ctr Vet Med, Rockville, MD 20857 USA. EM dharmon@uky.edu OI Kristensen, Niels Bastian/0000-0003-0214-2929; Holst, Jens Juul/0000-0001-6853-3805 FU U.S. Department of Agriculture, Agricultural Research Service [58-6250-6-001]; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine; Texas Children's Hospital; Texas Medical Center Digestive Diseases Center (NIH Grant) [P30 DK-56338] FX The authors express gratitude to Julie Cannon, Melissa Hudson, Samer El-Kadi, Alma True, Jimmy Klotz, Anne Koontz and Anne Ballou for assistance with sample collection, to Xioayan Chang and Leiwei Cui for assistance with immunohistochemistry and morphology measurements, and to Winston Lin for plasma analysis assistance. Support for this research was provided by the Kentucky Agricultural Experiment Station and is Publication No. 11-07-061. This work was supported in part by federal funds from the U.S. Department of Agriculture, Agricultural Research Service under Cooperative Agreement Number 58-6250-6-001 between USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital and by Texas Medical Center Digestive Diseases Center (NIH Grant P30 DK-56338). This manuscript was written by C. C. Taylor-Edwards in her private capacity. No official support or endorsement by the FDA is intended or should be inferred. NR 32 TC 2 Z9 2 U1 0 U2 7 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 1751-7311 J9 ANIMAL JI Animal PD DEC PY 2012 VL 6 IS 12 BP 1985 EP 1997 DI 10.1017/S175173111200095X PG 13 WC Agriculture, Dairy & Animal Science; Veterinary Sciences SC Agriculture; Veterinary Sciences GA 026WS UT WOS:000310314400011 PM 23031436 ER PT J AU Yang, BC Papoian, T AF Yang, Baichun Papoian, Thomas TI Tyrosine kinase inhibitor (TKI)-induced cardiotoxicity: approaches to narrow the gaps between preclinical safety evaluation and clinical outcome SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE tyrosine kinase inhibitor; cardiac toxicity; myocyte; isolated perfused heart; echocardiography; therapeutic index ID CELL-DERIVED CARDIOMYOCYTES; EXPERIMENTAL PULMONARY-HYPERTENSION; ACTIVATED PROTEIN-KINASE; CARDIOVASCULAR TOXICITY; MOLECULAR-MECHANISMS; CANCER THERAPEUTICS; SUNITINIB; IMATINIB; SORAFENIB; RISK AB Although therapies targeted to inhibit the activity of certain tyrosine kinases (TK) have helped advance cancer therapy in recent years, reports of cardiac toxicity following treatment with tyrosine kinase inhibitors (TKIs) were unexpected and not well predicted by preclinical studies. Such clinical findings exposed gaps in current preclinical drug testing for predicting the development of cardiac toxicities in humans. These gaps included a lack of a comprehensive TKI mechanism of action determination and appropriate cardiac functional evaluation. New preclinical approaches are suggested to address these issues. In addition to tyrosine kinase inhibition, other factors that may play a role in drug-induced cardiac effects should be assessed, such as unintended secondary targets of TKIs, toxic drug metabolites and drug accumulation in the heart. Both on-target and off-target toxic effects of TKIs on cultured cardiac myocytes have now been shown to be detectable, providing a rationale for using cardiomyocytes as a screening tool to study potential TKI-mediated cardiotoxicity. Incorporating isolated perfused heart methodology to chronic/subchronic rodent studies or including echocardiography in chronic large animal toxicity studies may improve the detection of changes in cardiac function over current methods, and they may eventually become a routine tool for screening drugs with suspected cardiotoxic potential. Further, assessing drug toxicity and efficacy together in an animal model of disease is highly informative for candidate drug selection, and should be encouraged to assess specific safety endpoints, such as cardiovascular function. Together, these approaches will help better close the gaps between preclinical testing and clinical outcomes. Published 2012. This article is a U.S. Government work and is in the public domain in the USA. C1 [Yang, Baichun] US FDA, Div Cardiovasc & Renal Prod, Off New Drugs 1, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Yang, BC (reprint author), US FDA, Div Cardiovasc & Renal Prod, Off New Drugs 1, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM baichun.yang@fda.hhs.gov NR 51 TC 13 Z9 13 U1 1 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0260-437X EI 1099-1263 J9 J APPL TOXICOL JI J. Appl. Toxicol. PD DEC PY 2012 VL 32 IS 12 BP 945 EP 951 DI 10.1002/jat.2813 PG 7 WC Toxicology SC Toxicology GA 029HJ UT WOS:000310485100001 PM 22961481 ER PT J AU Sun, JC Bhattacharyya, S Schnackenberg, LK Pence, L Ando, Y Zhang, J Stewart, S Rosenzweig, B Rouse, R Portilla, D Beger, RD AF Sun, Jinchun Bhattacharyya, Sudeepa Schnackenberg, Laura K. Pence, Lisa Ando, Yosuke Zhang, Jun Stewart, Sharon Rosenzweig, Barry Rouse, Rodney Portilla, Didier Beger, Richard D. TI Discovery of early urinary biomarkers in preclinical study of gentamicin-induced kidney injury and recovery in rats SO METABOLOMICS LA English DT Article DE Nephrotoxicity; Gentamicin; Biomarker; Efficacy; Dopamine; Metabolomics ID DRUG-INDUCED NEPHROTOXICITY; ACUTE-RENAL-FAILURE; H-1-NMR SPECTROSCOPY; GUT MICROBIOME; VALPROIC ACID; HPLC-TOF/MS; DOPAMINE; METABOLISM; QUALIFICATION; METABONOMICS AB LC/MS- and NMR-based global metabolomics analyses were utilized to study the changes in rat urine in response to gentamicin treatment. Sprague-Dawley rats were dosed with gentamicin sulfate at 0, 75, 150 or 300 mg/kg/day for one, two or three consecutive days. Four animals from each group were sacrificed to harvest kidney tissue and to collect urine on days 1, 2, 3, 7, 10, 15, 18, 22, 29, 36 and 44 for a total of 11 different time points. Both uni- and multivariate statistical analyses were employed to identify the significantly changed metabolites in urine at the different dose levels and time points. Increases and decreases in amino acids including tyrosine, valine and hydroxyproline reflected histopathology changes of kidney injury development and/or kidney injury recovery. Glucosuria was noted much earlier than changes in the classic kidney function biomarkers, blood urea nitrogen and serum creatinine. Dopamine-related compounds, homovanillic acid sulfate (HVA-SO4) and homoveratric acid sulfate (HVrA-SO4) were significantly increased at early time points and could be early indicators of a renal adaptive response to gentamicin-induced renal injury. Furthermore, the drug efficacy of gentamicin was evaluated through the detection of changes in gut microflora-related compounds (e.g. indole-containing metabolites). Metabolomics was successful in identifying valine, hydroxyproline, HVA-SO4 and HVrA-SO4 that might serve as potential early injury biomarkers or adaptive markers of gentamicin-induced renal injury, and in assessing gentamicin efficacy through changes in compounds reported to be related to gut microflora. However, caution should be taken in direct translation of the biomarkers reported in clinical settings because a much higher dose of gentamicin than the normal therapeutic dose (similar to 1-2 mg/kg) was used to cause kidney damaged. C1 [Sun, Jinchun; Schnackenberg, Laura K.; Pence, Lisa; Beger, Richard D.] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Bhattacharyya, Sudeepa] Arkansas Childrens Hosp, Little Rock, AR 72202 USA. [Ando, Yosuke] Daiichi Sankyo Co Ltd, Med Safety Res Labs, Tokyo, Japan. [Zhang, Jun; Stewart, Sharon; Rosenzweig, Barry; Rouse, Rodney] US FDA, Div Drug Safety Res, Off Testing & Res, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Portilla, Didier] Univ Arkansas Med Sci, Dept Internal Med, Div Nephrol, Little Rock, AR 72205 USA. [Portilla, Didier] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. RP Beger, RD (reprint author), US FDA, Div Syst Biol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Richard.Beger@fda.hhs.gov NR 42 TC 4 Z9 7 U1 3 U2 43 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1573-3882 J9 METABOLOMICS JI Metabolomics PD DEC PY 2012 VL 8 IS 6 BP 1181 EP 1193 DI 10.1007/s11306-012-0423-7 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 027ZW UT WOS:000310393600016 ER PT J AU Ju, WT Shen, JL Li, Y Toro, MA Zhao, SH Ayers, S Najjar, MB Meng, JH AF Ju, Wenting Shen, Jinling Li, Yi Toro, Magaly A. Zhao, Shaohua Ayers, Sherry Najjar, Mohamed Badaoui Meng, Jianghong TI Non-O157 Shiga toxin-producing Escherichia coli in retail ground beef and pork in the Washington DC area SO FOOD MICROBIOLOGY LA English DT Article DE Non-O157 STEC; Prevalence; Ground beef; Ground pork; Virulence ID HEMOLYTIC-UREMIC SYNDROME; ANTIMICROBIAL RESISTANCE; ENRICHMENT BROTHS; VIRULENCE GENES; UNITED-STATES; INTIMIN TYPES; FOOD; IDENTIFICATION; PREVALENCE; STRAINS AB The prevalence and characteristics of non-O157 Shiga toxin-producing Escherichia coli (STEC) in retail ground meat from the Washington D.C. area were investigated in this study. STEC from 480 ground beef and pork samples were identified using PCR screening followed by colony hybridization. The STEC isolates were serogrouped and examined for the presence of virulence genes (stx1, stx2, eae and hlyA), and antimicrobial susceptibility. PFGE was used to identify the clonal relationships of STEC isolates, and PCR-RFLP was employed to determine six subtypes. In addition, the cytotoxicity of STEC isolates was determined using a Vero cell assay. STEC were identified in 12(5.2%) of 231 ground pork and 13(5.2%) of 249 ground beef samples. Among 32 STEC isolates recovered from the 25 samples, 12 (37.5%) carried stx2dact and 7 (21.9%) carried hlyA, but none carried eae. Nine isolates were identified as 091, and 17 (53.1%) isolates were resistant to two or more antimicrobials. Verotoxicity was detected in 26 (81.3%) of the STEC isolates. Thus, the retail ground meat was contaminated with a heterogeneous population of non-O157 STEC, some of which were potential human pathogens. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Ju, Wenting; Shen, Jinling; Li, Yi; Toro, Magaly A.; Najjar, Mohamed Badaoui; Meng, Jianghong] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Meng, Jianghong] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Zhao, Shaohua; Ayers, Sherry] US FDA, Div Anim & Food Microbiol, Off Res, Ctr Vet Med, Laurel, MD 20708 USA. [Shen, Jinling] NW A&F Univ, Coll Food Sci & Engn, Yangling 712100, Shaanxi Provinc, Peoples R China. RP Meng, JH (reprint author), Univ Maryland, Dept Nutr & Food Sci, 0112 Skinner Bldg, College Pk, MD 20742 USA. EM jmeng@umd.edu RI Toro, Magaly/F-6525-2011 OI Toro, Magaly/0000-0002-6280-2215 NR 53 TC 27 Z9 27 U1 1 U2 19 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 EI 1095-9998 J9 FOOD MICROBIOL JI Food Microbiol. PD DEC PY 2012 VL 32 IS 2 BP 371 EP 377 DI 10.1016/j.fm.2012.07.017 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 021PG UT WOS:000309897200020 PM 22986203 ER PT J AU Kase, JA Maounounen-Laasri, A Son, I Deer, DM Borenstein, S Prezioso, S Hammack, TS AF Kase, Julie A. Maounounen-Laasri, Anna Son, Insook Deer, Deanne M. Borenstein, Stacey Prezioso, Samantha Hammack, Thomas S. TI Comparison of different sample preparation procedures for the detection and isolation of Escherichia coli O157:H7 and Non-O157 STECs from leafy greens and cilantro SO FOOD MICROBIOLOGY LA English DT Article DE Methodology; STEC; Raw produce ID PREENRICHMENT; SALMONELLA AB The FDA Bacteriological Analytical Manual (BAM) method for the detection/isolation of Shiga toxin-producing Escherichia coli (STEC) involves enrichment of produce rinses, blended homogenates or stomached homogenates. However, the effectiveness of rinsing produce to remove attached bacteria is largely unknown. Moreover, PCR inhibitors can be released under physical treatment. The study objective was to determine the relative effectiveness of recovery methods for STEC contaminated produce. Spinach, lettuce, and cilantro were contaminated with E. coli 0157:H7 or a non-O157 STEC, subjected to both the BIM method and a soak method, and tested by real-time PCR and cultural methods. For 0157:H7 and non-O157:H7 STECs, the soak method was significantly more productive than leafy green rinses. Of 320 test portions, PCR of recovered colonies confirmed 148 were positive by rinsing and 271 were positive by soaking (an 83% increase in sensitivity). For recovery of 0157:H7 from cilantro, of 60 test portions, positives were 38 by soaking, 41 by stomaching, and 28 by blending. Soaking and stomaching were significantly more productive than blending, although soaking was only arithmetically superior to stomaching. Based upon these results, it is recommended that a soak method replace the current BAM procedures. Published by Elsevier Ltd. C1 [Kase, Julie A.; Son, Insook; Deer, Deanne M.; Hammack, Thomas S.] US FDA, Div Microbiol, Microbial Methods Dev Branch, Off Regulatory Sci,Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Maounounen-Laasri, Anna; Borenstein, Stacey; Prezioso, Samantha] Oak Ridge Res Inst Sci & Educ, Oak Ridge, TN 37830 USA. RP Kase, JA (reprint author), US FDA, Div Microbiol, Microbial Methods Dev Branch, Off Regulatory Sci,Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,Rm 3E-023,HES 711, College Pk, MD 20740 USA. EM julie.kase@fda.hhs.gov; Anna.Laasri@fda.hhs.gov; Insook.Son@fda.hhs.gov; Deanne.Deer@fda.hhs.gov; staceyborenstein@gmail.com; uwr5@cdc.gov; Thomas.Hammack@fda.hhs.gov NR 8 TC 4 Z9 4 U1 1 U2 26 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 EI 1095-9998 J9 FOOD MICROBIOL JI Food Microbiol. PD DEC PY 2012 VL 32 IS 2 BP 423 EP 426 DI 10.1016/j.fm.2012.08.006 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 021PG UT WOS:000309897200026 PM 22986209 ER PT J AU Dunn, JD Gryniewicz-Ruzicka, CM Mans, DJ Mecker-Pogue, LC Kauffman, JF Westenberger, BJ Buhse, LF AF Dunn, Jamie D. Gryniewicz-Ruzicka, Connie M. Mans, Daniel J. Mecker-Pogue, Laura C. Kauffman, John F. Westenberger, Benjamin J. Buhse, Lucinda F. TI Qualitative screening for adulterants in weight-loss supplements by ion mobility spectrometry SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Ion mobility spectrometry; Portable; Hand-held; Weight-loss drugs; Herbal dietary supplements ID DIETARY-SUPPLEMENTS; SYNTHETIC ADULTERANTS; LIQUID-CHROMATOGRAPHY; ESI-MS; SIBUTRAMINE; ANALOGS; IDENTIFICATION AB Ion mobility spectrometry (IMS) served as a rapid, qualitative screening tool for the analysis of adulterated weight-loss products. We have previously shown that sibutramine extracted into methanol from dietary supplements can be detected at low levels (2 ng) using a portable IMS spectrometer, and have adapted a similar method for the analysis of additional weight-loss product adulterants. An FDA collaborative study helped to define the limits for fluoxetine with a limit of detection of 2 ng. We also evaluated more readily available, less toxic extraction solvents and found isopropanol and water were comparable to methanol. Isopropanol was favored over water for two reasons: (1) water increases the analysis time and (2) aqueous solutions were more susceptible to pH change, which affected the detection of sibutramine. In addition to sibutamine and fluoxetine, we surveyed 11 weight-loss adulterants; bumetanide, fenfluramine, furosemide, orlistat, phenolphthalein, phentermine, phenytoin, rimonabant, sertraline and two sibutramine analogs, desmethylsibutramine and didesmethylsibutramine, using portable and benchtop ion mobility spectrometers. Out of these 13 active pharmaceutical ingredients (APIs), portable and benchtop ion mobility spectrometers were capable of screening products for 10 of these APIs. The developed procedure was applied to two weight-loss dietary supplements using both portable and benchtop instruments. One product contained didesmethylsibutramine while the other contained didesmethylsibutramine and phenolphthalein. Published by Elsevier B.V. C1 [Dunn, Jamie D.; Gryniewicz-Ruzicka, Connie M.; Mans, Daniel J.; Mecker-Pogue, Laura C.; Kauffman, John F.; Westenberger, Benjamin J.; Buhse, Lucinda F.] US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Dunn, JD (reprint author), US FDA, Div Pharmaceut Anal, 1114 Market St, St Louis, MO 63101 USA. EM Jamie.Dunn@fda.hhs.gov FU U.S. FDA Center for Drug Evaluation and Research FX We would like to thank the U.S. FDA ORA scientists, Amy Irwin, Lauren Bounker, Mark Henry, Temar Williams and Valentino Fiorella and Oak Ridge Institute for Science and Education fellow Brendon Lyons for participating in the study. Funding was provided by the U.S. FDA Center for Drug Evaluation and Research Critical Path program. NR 21 TC 14 Z9 16 U1 1 U2 32 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD DEC PY 2012 VL 71 BP 18 EP 26 DI 10.1016/j.jpba.2012.07.020 PG 9 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 020BI UT WOS:000309783200003 PM 22902504 ER PT J AU Sepehr, E Lebl-Rinnova, M Mann, MK Pisani, SL Churchwell, MI Korol, DL Katzenellenbogen, JA Doerge, DR AF Sepehr, Estatira Lebl-Rinnova, Marketa Mann, Meagan K. Pisani, Samantha L. Churchwell, Mona I. Korol, Donna L. Katzenellenbogen, John A. Doerge, Daniel R. TI Pharmacokinetics of the estrogen receptor subtype-selective ligands, PPT and DPN: Quantification using UPLC-ES/MS/MS SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Estrogen receptor subtypes; Pharmacokinetics; Mass spectrometry; Synthetic deuterium labeling; Isotope dilution quantification ID ER-ALPHA; BETA; AGONISTS AB Estrogen receptor (ER) subtype specific agonists, diarylpropionitrile (DPN) for ER beta and propylpyrazoletriol (PPT) for ER alpha, are pharmacological probes used frequently to define mechanisms for estrogen actions in vitro and in vivo. Quantitative analytical methodology was developed and validated for DPN and PPT, based on synthetic stable labeled analogs (DPN-d(4) and PPT-d(5)) using isotope dilution liquid chromatographic tandem electrospray mass spectrometric detection. The validated method produced high sensitivity, with detection limits of 0.04-0.07 ng/ml serum. Serum pharmacokinetics were evaluated in Long-Evans rats following a single subcutaneous injection (2 mg/kg bw) of both compounds. The role of Phase IT metabolism was evaluated using beta-glucuronidase and arylsulfatase hydrolysis to measure total DPN and PPT in addition to the parent compounds. The pharmacokinetic properties of DPN and PPT reported could facilitate experimental designs requiring specified levels of receptor occupancy for quantitative comparisons of ER subtype specificities for natural and synthetic estrogens in vivo. Published by Elsevier B.V. C1 [Sepehr, Estatira; Churchwell, Mona I.; Doerge, Daniel R.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Lebl-Rinnova, Marketa; Mann, Meagan K.; Katzenellenbogen, John A.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA. [Pisani, Samantha L.; Korol, Donna L.] Univ Illinois, Neurosci Program, Urbana, IL 61801 USA. [Korol, Donna L.] Univ Illinois, Dept Psychol, Champaign, IL 61820 USA. RP Doerge, DR (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM Daniel.Doerge@fda.hhs.gov FU NIH [P50AT006268]; NIA; NCCAM; ODS; NCI [R37DK015556]; NSF [IOB 0520876, IOS 1118414] FX The authors acknowledge funding from Grant Number P50AT006268 to J.A.K. and D.R.D. from NIH, NIA, NCCAM, ODS, and NCI, as well as R37DK015556 to J.A.K. and NSF IOB 0520876 and IOS 1118414 to D.L.K. ES acknowledges support of a fellowship from the Oak Ridge Institute for Science and Education, administered through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. The authors have no conflicts of interest to report. The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration. NR 12 TC 3 Z9 3 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD DEC PY 2012 VL 71 BP 119 EP 126 DI 10.1016/j.jpba.2012.08.022 PG 8 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 020BI UT WOS:000309783200015 PM 22981216 ER EF