FN Thomson Reuters Web of Science™ VR 1.0 PT B AU Pogribny, IP AF Pogribny, Igor P. BE Kovalchuk, I Kovalchuk, O TI LIFESTYLE FACTORS, EPIGENETIC ABNORMALITIES, AND GENOMIC INSTABILITY: IMPLICATIONS FOR CARCINOGENESIS SO GENOME INSTABILITY AND TRANSGENERATIONAL EFFECTS SE Genetics-Research and Issues LA English DT Article; Book Chapter ID ISLAND METHYLATOR PHENOTYPE; HISTONE LYSINE METHYLATION; CANCER MUTATIONAL HOTSPOTS; ABERRANT DNA METHYLATION; LUNG-CANCER; PROMOTER HYPERMETHYLATION; CYTOSINE METHYLATION; SKIN-CANCER; REPAIR GENE; MULTISTAGE CARCINOGENESIS C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 150 TC 0 Z9 0 U1 0 U2 0 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60876-831-8 J9 GEN-RES ISSUES PY 2010 BP 291 EP 307 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA BPA47 UT WOS:000278384100014 ER PT B AU Merati, N Chamberlin, C Moore, C Titov, V Vance, TC AF Merati, Nazila Chamberlin, Christopher Moore, Christopher Titov, Vasily Vance, Tiffany C. BE Showalter, PS Lu, Y TI Integration of Tsunami Analysis Tools into a GIS Workspace - Research, Modeling, and Hazard Mitigation efforts Within NOAA's Center for Tsunami Research SO GEOSPATIAL TECHNIQUES IN URBAN HAZARD AND DISASTER ANALYSIS SE Geotechnologies and the Environment LA English DT Article; Book Chapter DE Tsunami; GIS; Modeling; Inundation; Hazard assessment; Data management; Bathymetry; Mapping; Emergency management; Coastal processes AB The National Oceanic and Atmospheric Administration's (NOAA) Center for Tsunami Research (NCTR) uses geospatial data and GIS analysis techniques in support of building an accurate tsunami forecasting system for the US Tsunami Warning Centers. The resulting forecast products can be integrated into applications and visualizations to assess hazard risk and provide mitigation for US coastal communities ranging from small towns to large urban centers. NCTR also conducts basic research on the nature of tsunami propagation and inundation, which relies on accurate geospatial information. In this chapter, we discuss how we have used both open source and commercially available geospatial technologies to address issues in tsunami research and hazard mitigation - including model visualization, data delivery, and emergency management products. Additionally, we discuss the development and coupling of tsunami model results with coastal risk, vulnerability, and evacuation models, raising the issues of integration, visualization, proliferation of mapping applications, and the ease of use and intended audience of these products. C1 [Merati, Nazila; Chamberlin, Christopher] NOAA, Pacific Marine Environm Lab, NCTR, JISAO, Seattle, WA 98115 USA. [Vance, Tiffany C.] NOAA, Natl Marine Fisheries Serv, RACE, Seattle, WA 98115 USA. RP Merati, N (reprint author), NOAA, Pacific Marine Environm Lab, NCTR, JISAO, 7600 Sand Point Way Ne, Seattle, WA 98115 USA. EM nazila.merati@noaa.gov; Chris.Chamberlin@noaa.gov; Christopher.Moore@noaa.gov; vasily.titov@noaa.gov; tiffany.c.vance@noaa.gov NR 29 TC 2 Z9 2 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-90-481-2237-0 J9 GEOTECH ENVIRON PY 2010 VL 2 BP 273 EP 294 DI 10.1007/978-90-481-2238-7_14 D2 10.1007/978-90-481-2238-7 PG 22 WC Environmental Sciences; Geography; Geosciences, Multidisciplinary; Urban Studies SC Environmental Sciences & Ecology; Geography; Geology; Urban Studies GA BMM11 UT WOS:000272785600014 ER PT J AU Bongat, AFG Saksena, R Adamo, R Fujimoto, Y Shiokawa, Z Peterson, DC Fukase, K Vann, WF Kovac, P AF Bongat, Aileen F. G. Saksena, Rina Adamo, Roberto Fujimoto, Yukari Shiokawa, Zenyu Peterson, Dwight C. Fukase, Koichi Vann, Willie F. Kovac, Pavol TI Multimeric bivalent immunogens from recombinant tetanus toxin H-C fragment, synthetic hexasaccharides, and a glycopeptide adjuvant SO GLYCOCONJUGATE JOURNAL LA English DT Article DE Conjugate vaccine; Vibrio cholerae; Adjuvant; Squaric acid; Tetanus toxin C fragment ID VIBRIO-CHOLERAE O-1; SQUARIC ACID DIESTER; SEROTYPE OGAWA; PROTEIN CARRIER; ESCHERICHIA-COLI; C-13-NMR SPECTRA; DIETHYL SQUARATE; IMMUNE-RESPONSE; O-PS; GANGLIOSIDE AB Using recombinant tetanus toxin H-C fragment (rTT-H-C) as carrier, we prepared multimeric bivalent immunogens featuring the synthetic hexasaccharide fragment of O-PS of Vibrio cholerae O:1, serotype Ogawa, in combination with either the synthetic hexasaccharide fragment of O-PS of Vibrio cholerae O:1, serotype Inaba, or a synthetic disaccharide tetrapeptide peptidoglycan fragment as adjuvant. The conjugation reaction was effected by squaric acid chemistry and monitored in virtually real time by SELDI-TOF MS. In this way, we could prepare well-defined immunogens with predictable carbohydrate-carrier ratio, whose molecular mass and the amount of each saccharide attached could be independently determined. The ability to prepare such neoglycoconjugates opens unprecedented possibilities for preparation of conjugate vaccines for bacterial diseases from synthetic carbohydrates. C1 [Bongat, Aileen F. G.; Adamo, Roberto; Kovac, Pavol] NIDDK, LBC, NIH, Bethesda, MD 20892 USA. [Fujimoto, Yukari; Shiokawa, Zenyu; Fukase, Koichi] Osaka Univ, Dept Chem, Grad Sch Sci, Osaka 5600043, Japan. [Saksena, Rina; Peterson, Dwight C.; Vann, Willie F.] US FDA, OVRR, CBER, Lab Bacterial Toxins, Bethesda, MD 20892 USA. RP Kovac, P (reprint author), NIDDK, LBC, NIH, Bethesda, MD 20892 USA. EM kpn@helix.nih.gov RI Kovac, Pavol/B-8813-2008; Fujimoto, Yukari/M-7282-2014 OI Kovac, Pavol/0000-0001-5044-3449; Fujimoto, Yukari/0000-0001-5320-3192 FU NIH, NIDDK FX This research was supported by the Intramural Research Program of the NIH, NIDDK. NR 51 TC 10 Z9 10 U1 0 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0282-0080 J9 GLYCOCONJUGATE J JI Glycoconjugate J. PD JAN PY 2010 VL 27 IS 1 BP 69 EP 77 DI 10.1007/s10719-009-9259-4 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 549HC UT WOS:000274037100007 PM 19757026 ER PT B AU Goldstein, B Nelson, RM Nadel, S AF Goldstein, Brahm Nelson, Robert M. Nadel, Simon BE Rose, K VanDenAnker, JN TI Paediatric Critical Care SO GUIDE TO PAEDIATRIC DRUG DEVELOPMENT AND CLINICAL RESEARCH LA English DT Article; Book Chapter ID BACTERICIDAL/PERMEABILITY-INCREASING PROTEIN; SEVERE MENINGOCOCCAL SEPSIS; RANDOMIZED CONTROLLED-TRIAL; TRAUMATIC BRAIN-INJURY; CLINICAL-TRIALS; CHILD ASSENT; RESUSCITATION RESEARCH; PARENTAL PERMISSION; INFORMED-CONSENT; HYPOTHERMIA C1 [Goldstein, Brahm] Ikaria Inc, Translat Sci, Clinton, NJ 08801 USA. [Goldstein, Brahm] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. [Nelson, Robert M.] US FDA, Off Paediat Therapeut, Off Commissioner, Silver Spring, MD USA. [Nadel, Simon] Imperial Coll Healthcare NHS Trust, London W2 1NY, England. [Goldstein, Brahm] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Clinton, NJ 08801 USA. RP Goldstein, B (reprint author), Ikaria Inc, Translat Sci, Clinton, NJ 08801 USA. EM brahm.goldstein@ikaria.com; Robert.Nelson@fda.hhs.gov; s.nadel@imperial.ac.uk NR 42 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND BN 978-3-8055-9362-5 PY 2010 BP 144 EP 154 PG 11 WC Pediatrics; Pharmacology & Pharmacy SC Pediatrics; Pharmacology & Pharmacy GA BPH17 UT WOS:000278841300021 ER PT B AU Fleisher, D Sweet, BV Parekh, A Boullata, JI AF Fleisher, David Sweet, Burgunda V. Parekh, Ameeta Boullata, Joseph I. BE Boullata, JI Armenti, VT TI Drug Absorption with Food SO HANDBOOK OF DRUG-NUTRIENT INTERACTIONS, SECOND EDITION SE Nutrition and Health Series LA English DT Article; Book Chapter DE Absorption; bioavailability; dissolution; food; gastrointestinal; permeability ID DEPENDENT INTESTINAL-ABSORPTION; PROTEASE INHIBITOR SAQUINAVIR; RELEASE DOSAGE FORMS; P-GLYCOPROTEIN; GRAPEFRUIT JUICE; PHYSICOCHEMICAL PROPERTIES; CLINICAL PHARMACOKINETICS; GASTROINTESTINAL TRANSIT; SYSTEMIC AVAILABILITY; ORAL AVAILABILITY AB Objectives Describe the factors involved in oral drug absorption and the influences of meal-related variables on those factors. Discuss the role that the BCS or BDDCS may play in allowing prediction of meal effects on oral drug bioavailability. Describe practical issues in determining the influence of food on oral drug bioavailability within the current regulatory framework. C1 [Sweet, Burgunda V.] Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. [Sweet, Burgunda V.] Univ Michigan Hlth Syst, Dept Pharm Serv, Drug Informat & Invest Drug Serv, Ann Arbor, MI USA. [Parekh, Ameeta] US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Boullata, Joseph I.] Univ Penn, Sch Nursing, Biobehav Res Ctr, Philadelphia, PA 19104 USA. [Boullata, Joseph I.] Hosp Univ Penn, Clin Nutr Support Serv, Philadelphia, PA 19104 USA. NR 104 TC 2 Z9 2 U1 2 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-363-3 J9 NUTR HEALTH SER JI Nutr. Health Ser. PY 2010 BP 209 EP 241 DI 10.1007/978-1-60327-362-6_8 D2 10.1007/978-1-60327-362-6 PG 33 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BLZ61 UT WOS:000271589800008 ER PT B AU Slikker, W AF Slikker, William, Jr. BE Krieger, R TI Neurotoxicology of Pesticides SO HAYES' HANDBOOK OF PESTICIDE TOXICOLOGY, VOLS 1 AND 2, 3RD EDITION LA English DT Article; Book Chapter C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Slikker, W (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 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 978-0-08-092201-0 PY 2010 BP 791 EP 791 DI 10.1016/B978-0-12-374367-1.00029-X PG 1 WC Toxicology SC Toxicology GA BCS50 UT WOS:000311281800032 ER PT J AU Slikker, W AF Slikker, William, Jr. BE Krieger, R TI A Systems Biology Approach to Assess the Impact of Pesticides on the Nervous System SO HAYES' HANDBOOK OF PESTICIDE TOXICOLOGY, VOLS 1 AND 2, 3RD EDITION LA English DT Article; Book Chapter ID REPRODUCTIVE TOXICITY; FUNCTIONAL GENOMICS; SERUM PARAOXONASE; RISK-ASSESSMENT; NEONATAL-RATS; EXPOSURE; CHLORPYRIFOS; TOXICOLOGY; ADULTHOOD; METABOLISM C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Slikker, W (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 39 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 978-0-08-092201-0 PY 2010 BP 793 EP 797 DI 10.1016/B978-0-12-374367-1.00030-6 PG 5 WC Toxicology SC Toxicology GA BCS50 UT WOS:000311281800033 ER PT J AU Paule, MG AF Paule, Merle G. BE Krieger, R TI The Nonhuman Primate as a Translational Model for Pesticide Research SO HAYES' HANDBOOK OF PESTICIDE TOXICOLOGY, VOLS 1 AND 2, 3RD EDITION LA English DT Article; Book Chapter ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; NMDA RECEPTOR ANTAGONISTS; MARIJUANA SMOKE EXPOSURE; COMPLEX OPERANT-BEHAVIOR; FEMALE RHESUS-MONKEYS; TEST BATTERY; COGNITIVE FUNCTION; NEUROPSYCHOLOGICAL FUNCTION; PHOTOSENSITIVE EPILEPSY; DEVELOPMENTAL ASPECTS C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Paule, MG (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 103 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 978-0-08-092201-0 PY 2010 BP 847 EP 859 DI 10.1016/B978-0-12-374367-1.00034-3 PG 13 WC Toxicology SC Toxicology GA BCS50 UT WOS:000311281800037 ER PT J AU Seidman, SJ Brockman, R Lewis, BM Guag, J Shein, MJ Clement, WJ Kippola, J Digby, D Barber, C Huntwork, D AF Seidman, Seth J. Brockman, Randall Lewis, Brian Marc Guag, Joshua Shein, Mitchell J. Clement, Wesley J. Kippola, James Digby, Dennis Barber, Catherine Huntwork, Dan TI In vitro tests reveal sample radiofrequency identification readers inducing clinically significant electromagnetic interference to implantable pacemakers and implantable cardioverter-defibrillators SO HEART RHYTHM LA English DT Article DE Implantable pacemaker; Implantable cardioverter-defibrillator; ICD; Electromagnetic compatibility; EMC; Electromagnetic interference; EMI; Radiofrequency identification; RFID ID CARE AB BACKGROUND The use of radiofrequency identification (RFID) systems is expanding and highlights the need to address electromagnetic interference (EMI) to implantable pacemakers and implantable cardioverter-defibrillators (ICDs). OBJECTIVE This study sought to examine the electromagnetic compatibility (EMC) between RFID readers and implantable pacemakers or ICDs. METHODS During in vitro testing, 15 implantable pacemakers and 15 ICDs were exposed to 13 passive RFID readers in 3 frequency bands: 134 kHz (low frequency [LF]), 13.56 MHz (high frequency [HF]), and 915 MHz (ultra high frequency [UHF]). RESULTS While being exposed to LF RFID, a reaction was observed for 67% of all pacemaker tests (maximum distance 60 cm) and 47% of all ICD tests (maximum distance 40 cm). During HF RFID exposure, a reaction was observed for 6% of all pacemaker tests (maximum distance 22.5 cm) and 1% of all ICD tests (maximum distance 7.5 cm). For both pacemakers and ICDs, no reactions were observed during exposure to UHF RFID or continuous-wave RFID. Pacemakers and ICDs were most susceptible to modulated LF RFID readers. CONCLUSION Although there is in vitro testing evidence for concern for implantable pacemaker and ICD EMI at LF and HF, the FDA has not received any incident reports of pacemaker or ICD EMI caused by any RFID system. We do not believe the current situation reveals an urgent public health risk. C1 [Seidman, Seth J.; Brockman, Randall; Lewis, Brian Marc; Guag, Joshua; Shein, Mitchell J.] US FDA, Silver Spring, MD 20993 USA. [Clement, Wesley J.] Medtronic Inc, Minneapolis, MN USA. [Kippola, James] Boston Sci, St Paul, MN USA. [Digby, Dennis] Biotronik, Berlin, Germany. [Barber, Catherine] St Jude Med, St Paul, MN USA. [Huntwork, Dan] Sorin, Milan, Italy. RP Seidman, SJ (reprint author), US FDA, 10903 New Hampshire Ave,White Oak Bldg 62,Room 11, Silver Spring, MD 20993 USA. EM seth.seidman@fda.hhs.gov NR 10 TC 36 Z9 36 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD JAN PY 2010 VL 7 IS 1 BP 99 EP 107 DI 10.1016/j.hrthm.2009.09.071 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 576ZI UT WOS:000276188500017 PM 20129290 ER PT J AU Zhao, Y Navia, BA Marra, CM Singer, EJ Chang, L Berger, J Ellis, RJ Kolson, DL Simpson, D Miller, EN Lipton, SA Evans, SR Schifitto, G AF Zhao, Yu Navia, Bradford A. Marra, Christina M. Singer, Elyse J. Chang, Linda Berger, Joseph Ellis, Ronald J. Kolson, Dennis L. Simpson, David Miller, Eric N. Lipton, Stuart A. Evans, Scott R. Schifitto, Giovanni CA Adult AIDS Clinical Trial Grp ACTG TI Memantine for AIDS Dementia Complex: Open-Label Report of ACTG 301 SO HIV CLINICAL TRIALS LA English DT Article DE AIDS dementia; cognitive impairment; memantine; HIV ID ACTIVE ANTIRETROVIRAL THERAPY; COGNITIVE IMPAIRMENT; HIV; MODERATE; DISEASE; ERA AB To evaluate the long-term safety and efficacy of memantine use as treatment of HIV-associated cognitive impairment. Background: The results of a 20-week, randomized, double-blind, placebo-controlled trial of memantine in HIV-infected participants with cognitive impairment (ACTG 301) were previously reported. We report the results of the up-to-60-week open-label phase following the double-blind phase. Method: Participants received open-label memantine and were escalated to a 40 mg/day dose or their maximum tolerated dose in the double-blind phase. Adverse experiences were used to evaluate safety, and changes in the mean of eight neuropsychological test scores (NPZ-8) were used to evaluate efficacy. Results: Ninety-nine participants entered the initial 12-week open-label phase and 45 in the additional 48-week extension. Twenty-seven participants reported severe adverse experiences. During the initial 12-week open-label phase, participants randomized to memantine in the double-blind phase had a statistically significant higher improvement in NPZ-8 compared to those randomized to placebo in the double-blind phase. No statistically significant NPZ-8 changes were detected during the 48-week extension. Conclusion: Long-term use of memantine appears safe and tolerable. Future randomized studies with longer follow-up are necessary to establish efficacy of memantine for the treatment of HIV-associated cognitive impairment. C1 [Zhao, Yu] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Navia, Bradford A.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Marra, Christina M.] Univ Washington, Seattle, WA 98195 USA. [Singer, Elyse J.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. [Chang, Linda] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. [Berger, Joseph] Univ Kentucky, Med Ctr, Lexington, KY USA. [Ellis, Ronald J.] Univ Calif San Diego, San Diego, CA 92103 USA. [Kolson, Dennis L.] Univ Penn, Philadelphia, PA 19104 USA. [Simpson, David] Mt Sinai Sch Med, New York, NY USA. [Miller, Eric N.] Univ Calif Los Angeles, Semel Inst Neurosci, Los Angeles, CA USA. [Lipton, Stuart A.] Sanford Burnham Med Res Inst, La Jolla, CA USA. [Lipton, Stuart A.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Schifitto, Giovanni] Univ Rochester, Rochester, NY USA. RP Zhao, Y (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,WO66-2211, Silver Spring, MD 20993 USA. EM yu.zhao@fda.hhs.gov RI Ellis, Ronald/K-3543-2015 OI Ellis, Ronald/0000-0003-4931-752X FU National Institute of Allergy and Infectious Diseases [U01AI068636, AI38858] FX The project described was supported by Award Number U01AI068636 and AI38858 from the National Institute of Allergy and Infectious Diseases. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. ACTG 301 is registered at ClinicalTrials.gov (identifier NCT00000867) located at http://www.clinicaltrials.gov/ct/show/NCT00000867?order=1. NR 13 TC 24 Z9 25 U1 0 U2 6 PU THOMAS LAND PUBLISHERS, INC PI ST LOUIS PA 255 JEFFERSON RD, ST LOUIS, MO 63119 USA SN 1528-4336 J9 HIV CLIN TRIALS JI HIV Clin. Trials PD JAN-FEB PY 2010 VL 11 IS 1 BP 59 EP 67 DI 10.1310/hct1101-59 PG 9 WC Infectious Diseases; Pharmacology & Pharmacy SC Infectious Diseases; Pharmacology & Pharmacy GA 582HY UT WOS:000276588900007 PM 20400412 ER PT J AU Hoffman, SL Billingsley, PF James, E Richman, A Loyevsky, M Li, T Chakravarty, S Gunasekera, A Chattopadhyay, R Li, ML Stafford, R Ahumada, A Epstein, JE Sedegah, M Reyes, S Richie, TL Lyke, KE Edelman, R Laurens, MB Plowe, CV Sim, BKL AF Hoffman, Stephen L. Billingsley, Peter F. James, Eric Richman, Adam Loyevsky, Mark Li, Tao Chakravarty, Sumana Gunasekera, Anusha Chattopadhyay, Rana Li, Minglin Stafford, Richard Ahumada, Adriana Epstein, Judith E. Sedegah, Martha Reyes, Sharina Richie, Thomas L. Lyke, Kirsten E. Edelman, Robert Laurens, Matthew B. Plowe, Christopher V. Sim, B. Kim Lee TI Development of a metabolically active, non-replicating sporozoite vaccine to prevent Plasmodium falciparum malaria SO HUMAN VACCINES LA English DT Article DE Malaria; malaria vaccine; Plasmodium falciparum; sporozoite; malaria immunity; pre-erythrocytic ID HUMORAL IMMUNE-RESPONSES; T-LYMPHOCYTE RESPONSES; PROTECTIVE IMMUNITY; STERILE IMMUNITY; STAGE MALARIA; CIRCUMSPOROZOITE PROTEIN; ATTENUATED SPOROZOITES; IRRADIATED SPOROZOITES; SURFACE PROTEIN-2; HUMAN VOLUNTEERS AB Immunization of volunteers by the bite of mosquitoes carrying radiation-attenuated Plasmodium falciparum sporozoites protects greater than 90% of such volunteers against malaria, if adequate numbers of immunizing biting sessions and sporozoite-infected mosquitoes are used. Nonetheless, until recently it was considered impossible to develop, license and commercialize a live, whole parasite P. falciparum sporozoite (PfSPZ) vaccine. In 2003 Sanaria scientists reappraised the potential impact of a metabolically active, non-replicating PfSPZ vaccine, and outlined the challenges to producing such a vaccine. Six years later, significant progress has been made in overcoming these challenges. This progress has enabled the manufacture and release of multiple clinical lots of a 1(st) generation metabolically active, non-replicating PfSPZ vaccine, the Sanaria (TM) PfSPZ Vaccine, submission of a successful Investigational New Drug application to the US Food and Drug Administration, and initiation of safety, immunogenicity and protective efficacy studies in volunteers in MD, US. Efforts are now focused on how best to achieve submission of a successful Biologics License Application and introduce the vaccine to the primary target population of African children in the shortest possible period of time. This will require implementation of a systematic, efficient clinical development plan. Short term challenges include optimizing the (1) efficiency and scale up of the manufacturing process and quality control assays, (2) dosage regimen and method of administration, ( 3) potency of the vaccine, and (4) logistics of delivering the vaccine to those who need it most, and finalizing the methods for vaccine stabilization and attenuation. A medium term goal is to design and build a facility for manufacturing highly potent and stable vaccine for pivotal Phase 3 studies and commercial launch. C1 [Hoffman, Stephen L.; Billingsley, Peter F.; James, Eric; Richman, Adam; Loyevsky, Mark; Li, Tao; Chakravarty, Sumana; Gunasekera, Anusha; Chattopadhyay, Rana; Stafford, Richard; Ahumada, Adriana; Sim, B. Kim Lee] Sanaria Inc, Rockville, MD USA. [Li, Minglin; Stafford, Richard; Ahumada, Adriana; Sim, B. Kim Lee] Prot Potential LLC, Rockville, MD USA. [Epstein, Judith E.; Sedegah, Martha; Reyes, Sharina; Richie, Thomas L.] USN, Med Res Ctr, US Mil Malaria Vaccine Program, Silver Spring, MD USA. [Lyke, Kirsten E.; Edelman, Robert; Laurens, Matthew B.; Plowe, Christopher V.] Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. [Laurens, Matthew B.; Plowe, Christopher V.] Univ Maryland, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21201 USA. [Chattopadhyay, Rana] US FDA, Ctr Biol & Evaluat, Off Blood & Res Review, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20014 USA. RP Hoffman, SL (reprint author), Sanaria Inc, Rockville, MD USA. EM slhoffman@sanaria.com RI Laurens, Matthew/E-7293-2013; OI Laurens, Matthew/0000-0003-3874-581X; Richie, Thomas/0000-0002-2946-5456 FU National Institute of Allergy and Infectious Disease; Institute for One World Health, San Francisco, CA; United States Department of Defense; PATH-Malaria Vaccine Initiative, Seattle WA; Top Institut Pharma, Leiden, the Netherlands; Doris Duke Charitable Foundation; US Army Medical Research & Materiel Command FX Funding for Sanaria's development efforts has been provided by the National Institute of Allergy and Infectious Disease, Small Business Innovation Research grant program; The Institute for One World Health, San Francisco, CA; The United States Department of Defense; The PATH-Malaria Vaccine Initiative, Seattle WA; and Top Institut Pharma, Leiden, the Netherlands. We thank David Dolberg and Alexander Hoffman for review of the manuscript and Robert C. Thompson for support throughout.; Site assessment for African trials of Sanaria (TM) PfSPZ Vaccine has been supported by the Howard Hughes Medical Institute and the PATH Malaria Vaccine Initiative. K.E.L. and C.V.P. are supported by awards from the Doris Duke Charitable Foundation.; The work performed by J.E.E. and T.L.R. was supported by funds allocated to the Naval Medical Research Center by the US Army Medical Research & Materiel Command. The views expressed are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government. J.E.E. and T.L.R. are military service members and performed this work as part of official duties. Title 17 U.S.C.S 105 provides that 'Copyright protection under this title is not available for any work of the United States Government.' Title 17 U.S.C.S 101 defines a U.S. Government work as a work prepared by a military service member or employee of the U.S. Government as part of that person's official duties. Protocols for clinical studies were approved by the Naval Medical Research Center Institutional Review Board in compliance with all applicable Federal regulations governing the protection of human subjects. Animal experiments reported herein were conducted in compliance with the Animal Welfare Act and in accordance with the principles set forth in the "Guide for the Care and Use of Laboratory Animals," Institute of Laboratory Animals Resources, National Research Council, National Academy Press, 1996. NR 69 TC 126 Z9 127 U1 1 U2 28 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8600 J9 HUM VACCINES JI Hum. Vaccines PD JAN PY 2010 VL 6 IS 1 BP 97 EP 106 PG 10 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA 557DT UT WOS:000274650200013 PM 19946222 ER PT J AU Cooper-DeHoff, RM Wen, S Beitelshees, AL Zineh, I Gums, JG Turner, ST Gong, Y Hall, K Parekh, V Chapman, AB Boerwinkle, E Johnson, JA AF Cooper-DeHoff, Rhonda M. Wen, Sheron Beitelshees, Amber L. Zineh, Issam Gums, John G. Turner, Stephen T. Gong, Yan Hall, Karen Parekh, Vishal Chapman, Arlene B. Boerwinkle, Eric Johnson, Julie A. TI Impact of Abdominal Obesity on Incidence of Adverse Metabolic Effects Associated With Antihypertensive Medications SO HYPERTENSION LA English DT Article DE atenolol; hydrochlorothiazide; abdominal obesity; metabolic syndrome; new-onset diabetes mellitus; hypertension ID BODY-MASS INDEX; CARDIOVASCULAR-DISEASE; HYPERTENSION; GLUCOSE; RISK; THERAPY; ADULTS; HYDROCHLOROTHIAZIDE; METAANALYSIS; HYPOKALEMIA AB We assessed adverse metabolic effects of atenolol and hydrochlorothiazide among hypertensive patients with and without abdominal obesity using data from a randomized, open-label study of hypertensive patients without evidence of cardiovascular disease or diabetes mellitus. Intervention included randomization to 25 mg of hydrochlorothiazide or 100 mg of atenolol monotherapy followed by their combination. Fasting glucose, insulin, triglycerides, high-density lipoprotein cholesterol, and uric acid levels were measured at baseline and after monotherapy and combination therapy. Outcomes included new occurrence of and predictors for new cases of glucose >= 100 mg/dL (impaired fasting glucose), triglyceride >= 150 mg/dL, high-density lipoprotein <= 40 mg/dL for men or <= 50 mg/dL for women, or new-onset diabetes mellitus according to the presence or absence of abdominal obesity. Abdominal obesity was present in 167 (58%) of 395 patients. Regardless of strategy, in those with abdominal obesity, 20% had impaired fasting glucose at baseline compared with 40% at the end of study (P<0.0001). Proportion with triglycerides >= 150 mg/dL increased from 33% at baseline to 46% at the end of study (P<0.01). New-onset diabetes mellitus occurred in 13 patients (6%) with and in 4 patients (2%) without abdominal obesity. Baseline levels of glucose, triglyceride, and high-density lipoprotein predicted adverse outcomes, and predictors for new-onset diabetes mellitus after monotherapy in those with abdominal obesity included hydrochlorothiazide strategy (odds ratio: 46.91 [95% CI: 2.55 to 862.40]), female sex (odds ratio: 31.37 [95% CI: 2.10 to 468.99]), and uric acid (odds ratio: 3.19 [95% CI: 1.35 to 7.52]). Development of adverse metabolic effect, including new-onset diabetes mellitus associated with short-term exposure to hydrochlorothiazide and atenolol was more common in those with abdominal obesity. (Hypertension. 2010;55:61-68.) C1 [Cooper-DeHoff, Rhonda M.] Univ Florida, Coll Pharm, Dept Pharmacotherapy & Translat Res, Gainesville, FL 32610 USA. [Cooper-DeHoff, Rhonda M.; Gums, John G.; Hall, Karen; Johnson, Julie A.] Univ Florida, Coll Med, Gainesville, FL 32610 USA. [Cooper-DeHoff, Rhonda M.; Wen, Sheron; Gums, John G.; Gong, Yan; Johnson, Julie A.] Univ Florida, Ctr Pharmacogenom, Gainesville, FL 32610 USA. [Beitelshees, Amber L.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Zineh, Issam] US FDA, Silver Spring, MD USA. [Turner, Stephen T.] Mayo Clin, Coll Med, Rochester, MN USA. [Parekh, Vishal] Morehouse Sch Med, Atlanta, GA 30310 USA. [Chapman, Arlene B.] Emory Univ, Sch Med, Atlanta, GA USA. [Boerwinkle, Eric] Univ Texas Houston, Ctr Human Genet, Houston, TX USA. [Boerwinkle, Eric] Univ Texas Houston, Inst Mol Med, Houston, TX USA. RP Cooper-DeHoff, RM (reprint author), Univ Florida, Coll Pharm, Dept Pharmacotherapy & Translat Res, 1600 SW Archer Rd,Box 100486, Gainesville, FL 32610 USA. EM dehoff@cop.ufl.edu FU National Institutes of Health [U01 GM074492]; Pharmacogenetics Research Network; National Institutes of Health, National Center for Research Resources [M01 RR00082, UL1 RR025008, M01 RR00039, UL1 RR024150]; National Heart Lung and Blood Institute [K23HL08655, K23HL091120] FX This work is supported by a grant from the National Institutes of Health, grant U01 GM074492, funded as part of the Pharmacogenetics Research Network. In addition, this work is supported by the following grants from the National Institutes of Health, National Center for Research Resources: M01 RR00082 to the University of Florida, UL1 RR025008 and M01 RR00039 to Emory University, and UL1 RR024150 to Mayo Clinic, as well as the National Heart Lung and Blood Institute grants K23HL08655 (to R.M.C.-D.) and K23HL091120 (to A. L. B.). NR 33 TC 26 Z9 26 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JAN PY 2010 VL 55 IS 1 BP 61 EP 68 DI 10.1161/HYPERTENSIONAHA.109.139592 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 533GW UT WOS:000272812700012 PM 19917874 ER PT J AU He, X Gallas, BD Frey, EC AF He, Xin Gallas, Brandon D. Frey, Eric C. TI Three-Class ROC Analysis-Toward a General Decision Theoretic Solution SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Extended receiver operating characteristic (ROC) analysis; ROC analysis; three-class ROC analysis ID IDEAL OBSERVER DECISION; N-CLASS CLASSIFICATION; FORCED-CHOICE TASKS; SIGNAL DETECTABILITY; SURFACE; OPTIMIZATION; CLASSIFIERS; MULTICLASS; VARIABLES; VOLUME AB Multiclass receiver operating characteristic (ROC) analysis has remained an open theoretical problem since the introduction of binary ROC analysis in the 1950s. Previously, we have developed a paradigm for three-class ROC analysis that extends and unifies decision theoretic, linear discriminant analysis, and probabilistic foundations of binary ROC analysis in a three-class paradigm. One critical element in this paradigm is the equal error utility (EEU) assumption. This assumption allows us to reduce the intrinsic space of the three-class ROC analysis (5-D hypersurface in 6-D hyperspace) to a 2-D surface in the 3-D space of true positive fractions (sensitivity space). In this work, we show that this 2-D ROC surface fully and uniquely provides a complete descriptor for the optimal performance of a system for a three-class classification task, i.e., the triplet of likelihood ratio distributions, assuming such a triplet exists. To be specific, we consider two classifiers that utilize likelihood ratios, and we assumed each classifier has a continuous and differentiable 2-D sensitivity-space ROC surface. Under these conditions, we proved that the classifiers have the same triplet of likelihood ratio distributions if and only if they have the same 2-D sensitivity-space ROC surfaces. As a result, the 2-D sensitivity surface contains complete information on the optimal three-class task performance for the corresponding likelihood ratio classifier. C1 [He, Xin; Frey, Eric C.] Johns Hopkins Sch Med, Dept Radiol, Baltimore, MD 21287 USA. [Gallas, Brandon D.] US FDA, DIAM OSEL CDRH, Silver Spring, MD 20993 USA. RP He, X (reprint author), Johns Hopkins Sch Med, Dept Radiol, Baltimore, MD 21287 USA. EM xinhe@jhmi.edu; brandon.gallas@fda.hhs.gov; efrey@jhmi.edu OI Gallas, Brandon/0000-0001-7332-1620 FU National Institutes of Health (NIH) [K99 EB007620, R01 EB000288] FX This work was supported by the National Institutes of Health (NIH) under Grant K99 EB007620 and Grant R01 EB000288. The content of this work is solely the responsibility of the authors and does not necessarily represent the official view of the NIH or its various institutes. NR 36 TC 10 Z9 10 U1 0 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD JAN PY 2010 VL 29 IS 1 BP 206 EP 215 DI 10.1109/TMI.2009.2034516 PG 10 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 540LY UT WOS:000273334400019 PM 19884079 ER PT S AU Pine, PS AF Pine, P. Scott BE Oliver, C Jamur, MC TI Overview of Laser Microbeam Applications as Related to Antibody Targeting SO IMMUNOCYTOCHEMICAL METHODS AND PROTOCOLS, THIRD EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Laser; Microbeam; Antibody; Fluorescence; FRAP; FRET; Ablation; Photobleaching ID FLUORESCENCE ENERGY-TRANSFER; LATERAL DIFFUSION; PROTEIN FUNCTION; SINGLE CELLS; INACTIVATION; NEURONS; MANIPULATION; MEMBRANES AB This chapter reviews several techniques which combine the use of laser microbeams with antibodies to study molecular and cellular biology An overview of the basic properties of lasers and their integration with microscopes and computers is provided. Biophysical applications, such as fluorescence recovery after photobleaching to measure molecular mobility and fluorescence resonance energy transfer to measure molecular distances, as well as ablative applications for the selective inactivation of proteins or the selective killing of cells are described. Other techniques, Such as optical trapping, that do not rely on the interaction of the laser with the targeting antibody, arc also discussed. C1 US FDA, Div Appl Pharmacol & Res, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Pine, PS (reprint author), US FDA, Div Appl Pharmacol & Res, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 29 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-58829-463-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 588 BP 203 EP 217 DI 10.1007/978-1-59745-324-0_22 D2 10.1007/978-1-59745-324-0 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BND72 UT WOS:000274239800022 PM 20012833 ER PT J AU Sheng-Fowler, L Cai, F Fu, HQ Zhu, Y Orrison, B Foseh, G Blair, DG Hughes, SH Coffin, JM Lewis, AM Peden, K AF Sheng-Fowler, Li Cai, Fang Fu, Haiqing Zhu, Yong Orrison, Brian Foseh, Gideon Blair, Don G. Hughes, Stephen H. Coffin, John M. Lewis, Andrew M., Jr. Peden, Keith TI Tumors Induced in Mice by Direct Inoculation of Plasmid DNA Expressing Both Activated H-ras and c-myc SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE H-ras; c-myc; oncogenes ID TUMORIGENIC CONVERSION; CHROMOSOMAL INSERTION; EMBRYO FIBROBLASTS; CELLULAR DNA; FOREIGN DNA; MICRORNAS; ONCOGENES; CARCINOGENESIS; TRANSFORMATION; CANCER AB Vaccines contain residual DNA derived from the cells used to produce them. As part of our investigation to assess the risk of this cellular DNA, we are developing a quantitative in vivo assay to assess the oncogenicity of DNA. In an earlier study, we had generated expression plasmids for two oncogenes - human activated T24-H-ras and murine c-myc - and had shown that these two plasmids, pMSV-T24-H-ras and pMSV-c-myc, could act in concert to induce tumors in mice, although the efficiency was low. In this study, we took two approaches to increase the oncogenic efficiency: 1) both oncogene-expression cassettes were placed on the same plasmid; 2) transfection facilitators, which increase DNA uptake and expression in vitro, were tested. The dual-expression plasmid, pMSV-T24-H-ras/MSV-c-myc, is about 20-fold more efficient at tumor induction in newborn NIH Swiss mice than the separate expression plasmids, with tumors being induced with 1 mu g of the dual-expression plasmid DNA. However, none of the transfection facilitators tested increased the efficiency of tumor induction. Based on these data, the dual-expression plasmid pMSV-T24-H-ras/MSV-c-myc will be used as the positive control to develop a sensitive and quantitative animal assay that can be used to assess the oncogenic activity of DNA. C1 [Sheng-Fowler, Li; Cai, Fang; Fu, Haiqing; Zhu, Yong; Orrison, Brian; Foseh, Gideon; Lewis, Andrew M., Jr.; Peden, Keith] US FDA, Div Viral Prod, OVRR, CBER, Bethesda, MD 20892 USA. [Blair, Don G.; Hughes, Stephen H.; Coffin, John M.] NCI, Frederick Canc Res Facil, Frederick, MD 21702 USA. [Blair, Don G.] Tufts Univ, Boston, MA 02111 USA. RP Peden, K (reprint author), US FDA, Div Viral Prod, OVRR, CBER, Bldg 29A,Room 3D08,29 Lincoln Dr, Bethesda, MD 20892 USA. EM andrew.lewis@fda.hhs.gov; keith.peden@fda.hhs.gov FU Office of the Commissioner, FDA; National Vaccine Program Office; National Institute of Allergy and Infectious Diseases; NIAID; National Institutes of Health, National Cancer Institute, Center for Cancer Research; American Cancer Society; George Kirby Foundation FX This work was initiated following support from a grant from the Office of the Commissioner, FDA. Additional support came from a grant from the National Vaccine Program Office; current work is supported by a contract from the Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases through an Interagency Agreement with CBER/FDA. F. C., H. F. and Y.Z. were supported by the NIAID contract. This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research (to S. H. H). JMC was a research Professor of the American Cancer Society, with support from the George Kirby Foundation. We thank Hana Golding, Arifa Khan, Jerry Weir, Phil Krause, and Robin Levis for discussions and/or comments on the manuscript. NR 37 TC 5 Z9 6 U1 0 U2 2 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2010 VL 6 IS 2 BP 151 EP 162 PG 12 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 586AT UT WOS:000276873800004 PM 20376206 ER PT J AU Ellis, A AF Ellis, Amy TI Introduction to Division of Anti-Infectives and Ophthalmology Products SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the American-College-of-Toxicology CY NOV 01-04, 2009 CL Palm Springs, CA SP Amer Coll Toxicol DE FDA; Regulatory; Pharmacology/Toxicology C1 [Ellis, Amy] US FDA, CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD JAN PY 2010 VL 29 IS 1 BP 112 EP 112 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 552AF UT WOS:000274255600073 ER PT J AU Reid, L AF Reid, Lynnda TI Introduction to Division of Reproductive and Urologic Products SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the American-College-of-Toxicology CY NOV 01-04, 2009 CL Palm Springs, CA SP Amer Coll Toxicol DE FDA; regulatory; pharmacology/toxicology C1 [Reid, Lynnda] US FDA, CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD JAN PY 2010 VL 29 IS 1 BP 112 EP 112 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 552AF UT WOS:000274255600076 ER PT J AU Willard, JM AF Willard, James M. TI Slippery Slope: Experiences of the CDER Phospholipidosis Working Group SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the American-College-of-Toxicology CY NOV 01-04, 2009 CL Palm Springs, CA SP Amer Coll Toxicol DE phospholipidosis; QT prolongation; database C1 [Willard, James M.] US FDA, Div Cardiovasc & Renal Prod, CDER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD JAN PY 2010 VL 29 IS 1 BP 117 EP 118 PG 2 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 552AF UT WOS:000274255600092 ER PT J AU Murray, J AF Murray, Jeffrey TI Introduction, Mechanisms of Action, Historical Perspective, and Changes in Drug Development Paradigms SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the American-College-of-Toxicology CY NOV 01-04, 2009 CL Palm Springs, CA SP Amer Coll Toxicol DE HIV; Regulatory; Clinical C1 [Murray, Jeffrey] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD JAN PY 2010 VL 29 IS 1 BP 121 EP 121 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 552AF UT WOS:000274255600102 ER PT J AU Myers, LP AF Myers, L. Peyton TI Nonclinical Safety Assessment of Anti-HIV Therapeutics--A Regulatory Perspective SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the American-College-of-Toxicology CY NOV 01-04, 2009 CL Palm Springs, CA SP Amer Coll Toxicol DE HIV; Regulatory; Guidance C1 [Myers, L. Peyton] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD JAN PY 2010 VL 29 IS 1 BP 121 EP 121 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 552AF UT WOS:000274255600103 ER PT J AU Ricci, MS AF Ricci, M. Stacey TI CDER Perspective on Comparability of a Biologic Product SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the American-College-of-Toxicology CY NOV 01-04, 2009 CL Palm Springs, CA SP Amer Coll Toxicol C1 [Ricci, M. Stacey] US FDA, CDER, Off New Drugs, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD JAN PY 2010 VL 29 IS 1 BP 122 EP 122 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 552AF UT WOS:000274255600108 ER PT J AU Vatsan, R AF Vatsan, Ramjay TI CBER Perspective on Comparability SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the American-College-of-Toxicology CY NOV 01-04, 2009 CL Palm Springs, CA SP Amer Coll Toxicol C1 [Vatsan, Ramjay] US FDA, GTB, Div Cellular & Gene Therapies, OCTCT,CBER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD JAN PY 2010 VL 29 IS 1 BP 122 EP 122 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 552AF UT WOS:000274255600110 ER PT J AU Billingslea, FB AF Billingslea, Felicia B. TI Food Allergy Update SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the American-College-of-Toxicology CY NOV 01-04, 2009 CL Palm Springs, CA SP Amer Coll Toxicol C1 [Billingslea, Felicia B.] US FDA, DHHS, Ctr Food Safety & Appl Nutr, Off Nutr Labeling & Dietary Supplements, College Pk, MD 20740 USA. EM felicia.billingslea@hhs.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD JAN PY 2010 VL 29 IS 1 BP 128 EP 128 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 552AF UT WOS:000274255600127 ER PT J AU Powell, B AF Powell, Bob TI FDA-CDER Use of Modeling and Simulation with an Emphasis on Systems Biology and Safety SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the American-College-of-Toxicology CY NOV 01-04, 2009 CL Palm Springs, CA SP Amer Coll Toxicol C1 [Powell, Bob] Ctr Drug Evaluat & Res, Off Translat Sci, Fda White Oak, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD JAN PY 2010 VL 29 IS 1 BP 130 EP 130 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 552AF UT WOS:000274255600134 ER PT J AU Weaver, CM Trucksess, MW AF Weaver, Carol M. Trucksess, Mary W. TI Determination of Aflatoxins in Botanical Roots by a Modification of AOAC Official Method(SM) 991.31: Single-Laboratory Validation SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID IMMUNOAFFINITY COLUMN CLEANUP; OCHRATOXIN-A; MYCOTOXINS; GINSENG; PLANTS; HERBS AB AOAC Official Method(SM) 991.31 for the determination of aflatoxins (AFs; sum of aflatoxins B-1, B-2, G(1), and G(2)) in corn, raw peanuts, and peanut butter by using immunoaffinity column cleanup with LC has been modified and applied to the determination of AFs in botanical roots. The modifications were necessary to improve the performance of the method for matrixes beyond corn and peanuts. The extraction solvent was changed from a mixture of methanol and water to acetonitrile and water. The accuracy, repeatability, and reproducibility characteristics of this method were determined. Replicates of 10 test portions of each powdered root (black cohosh, echinacea, ginger, ginseng, kava kava, and valerian) at each spiking level (AFs at 0, 2, 4, 8, and 16 ng/g) were analyzed on 3 separate days. Test portions were extracted with acetonitrile-water (84 + 16, v/v), and the extracts were centrifuged, diluted with phosphate-buffered saline, filtered, and applied to an immunoaffinity column containing antibodies specific for AFs. After the column was washed with water, the toxins were eluted from the column with methanol and quantified by HPLC with fluorescence detection. All test materials except kava kava were found to contain AF at <0.1 ng/g. Kava kava was naturally contaminated with AFs at 0.5 ng/g. Average within-day and between-days recoveries of AFs from botanical roots ranged from 88 to 112 and from 86 to 118%, respectively. Total RSD values for within-day and between-days repeatability ranged from 1.4 to 15.9%. HorRat values were <0.4 for all of the matrixes examined. The modified AOAC Official Method 991.31 was found to be applicable to an analysis of the six botanical roots. C1 [Weaver, Carol M.; Trucksess, Mary W.] US FDA, College Pk, MD 20740 USA. RP Trucksess, MW (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM mary.trucksess@fda.hhs.gov FU Office of Dietary Supplements, National Institutes of Health, Bethesda, MD FX This work was supported in part by the Office of Dietary Supplements, National Institutes of Health, Bethesda, MD. NR 15 TC 17 Z9 17 U1 0 U2 7 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 2010 VL 93 IS 1 BP 184 EP 189 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 563AD UT WOS:000275096600023 PM 20334179 ER PT J AU Jablonski, JE Fu, TJ Jackson, LS Gendel, SM AF Jablonski, Joseph E. Fu, Tong-Jen Jackson, Lauren S. Gendel, Steven M. TI Determination of Protein Levels in Soy and Peanut Oils by Colorimetric Assay and ELISA SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID VEGETABLE-OILS; FOOD ALLERGY; ALLERGENICITY; IMMUNOASSAY; STABILITY AB Analytical methods are needed for measuring the levels of protein from allergenic food transferred into cooking oil. A simple method for determination of total protein in cooking oils was developed. Oil was extracted with phosphate-buffered saline with 0.05% Tween (PBST) and the extracts were partitioned with hexane to remove residual oil. Total protein in the PBST extracts was assayed with bicinchoninic acid (BCA), micro-BCA, reducing-agent compatible BCA and CB-X (TM) kits. These methods were used to measure recovery of protein from peanut butter spikes of soy and peanut oil in the range of 50-1000 ppm. Recoveries were generally above 70%. However, the BCA and micro-BCA assays were subject to interference and enhanced color formation which were probably due to co-extracted antioxidants present in oil. The reducing agent-compatible BCA and CB-X protein assays reduced interference and gave lower protein values in crude, cold-pressed, and refined peanut oils. Heating oil to 180 degrees C before extraction also reduced interference-induced color enhancement. A commercial ELISA test kit was also used to measure peanut protein in oil spiked with peanut buffer. Recovery of peanut residues measured by ELISA was significantly decreased when the peanut butter-spiked oil was heated to 180 degrees C compared to unheated oil. Recovery of spiked peanut butter protein measured by the buffer extraction-colorimetric method was not decreased in heated oil. The method developed here could be used to determine protein levels in crude and refined oil, and to assess the potential for allergen cross-contact from reused cooking oil. C1 [Jablonski, Joseph E.; Fu, Tong-Jen; Jackson, Lauren S.] US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. [Gendel, Steven M.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Jablonski, JE (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM joseph.jablonski@fda.hhs.gov NR 36 TC 2 Z9 2 U1 3 U2 49 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 2010 VL 93 IS 1 BP 213 EP 220 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 563AD UT WOS:000275096600027 PM 20334183 ER PT J AU McCleary, BV DeVries, JW Rader, JI Cohen, G Prosky, L Mugford, DC Champ, M Okuma, K AF McCleary, Barry V. DeVries, Jonathan W. Rader, Jeanne I. Cohen, Gerald Prosky, Leon Mugford, David C. Champ, Martine Okuma, Kazuhiro TI Determination of Total Dietary Fiber (CODEX Definition) by Enzymatic-Gravimetric Method and Liquid Chromatography: Collaborative Study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID RESISTANT STARCH; FOOD-PRODUCTS AB A method for the determination of total dietary fiber (TDF), as defined by the CODEX Alimentarius, was validated in foods. Based upon the principles of AOAC Official Methods(SM) 985.29, 991.43, 2001.03, and 2002.02, the method quantitates high- and low-molecular-weight dietary fiber (HMWDF and LMWDF, respectively). In 2007, McCleary described a method of extended enzymatic digestion at 37 degrees C to simulate human intestinal digestion followed by gravimetric isolation and quantitation of HMWDF and the use of LC to quantitate low-molecular-weight soluble dietary fiber (LMWSDF). The method thus quantitates the complete range of dietary fiber components from resistant starch (by utilizing the digestion conditions of AOAC Method 2002.02) to digestion resistant oligosaccharides (by incorporating the deionization and LC procedures of AOAC Method 2001.03). The method was evaluated through an AOAC collaborative study. Eighteen laboratories participated with 16 laboratories returning valid assay data for 16 test portions (eight blind duplicates) consisting of samples with a range of traditional dietary fiber, resistant starch, and nondigestible oligosaccharides. The dietary fiber content of the eight test pairs ranged from 11.57 to 47.83%. Digestion of samples under the conditions of AOAC Method 2002.02 followed by the isolation and gravimetric procedures of AOAC Methods 985.29 and 991.43 results in quantitation of HMWDF. The filtrate from the quantitation of HMWDF is concentrated, deionized, concentrated again, and analyzed by LC to determine the LMWSDF, i.e., all nondigestible oligosaccharides of degree of polymerization 3. TDIF is calculated as the sum of HMWDF and LMWSDF. Repeatability standard deviations (s(r)) ranged from 0.41 to 1.43, and reproducibility standard deviations (s(R)) ranged from 1.18 to 5.44. These results are comparable to other official dietary fiber methods, and the method is recommended for adoption as Official First Action. C1 [McCleary, Barry V.] Megazyme Int, Bray, Wicklow, Ireland. [DeVries, Jonathan W.] Medall Labs Gen Mills, Golden Valley, MN 55427 USA. [Rader, Jeanne I.] US FDA, College Pk, MD 20740 USA. [Cohen, Gerald] Kraft Foods, Tarrytown, NY USA. [Prosky, Leon] US FDA, Rockville, MD 20850 USA. [Mugford, David C.] BRI Res Pty Ltd, N Ryde, NSW 1670, Australia. [Champ, Martine] Univ Nantes, F-44093 Nantes 1, France. [Okuma, Kazuhiro] Matsutani Chem, Res Lab, Itami, Hyogo 6648508, Japan. RP McCleary, BV (reprint author), Megazyme Int, Bray Business Pk, Bray, Wicklow, Ireland. EM barry@megazyme.com NR 14 TC 48 Z9 49 U1 4 U2 37 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 2010 VL 93 IS 1 BP 221 EP 233 PG 13 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 563AD UT WOS:000275096600028 PM 20334184 ER PT J AU Mahmood, M Casciano, DA Mocan, T Iancu, C Xu, Y Mocan, L Iancu, DT Dervishi, E Li, ZR Abdalmuhsen, M Biris, AR Ali, N Howard, P Biris, AS AF Mahmood, Meena Casciano, Daniel A. Mocan, Teodora Iancu, Cornel Xu, Yang Mocan, Lucian Iancu, Dana Todea Dervishi, Enkeleda Li, Zhongrui Abdalmuhsen, Mustafa Biris, Alexandru R. Ali, Nawab Howard, Paul Biris, Alexandru S. TI Cytotoxicity and biological effects of functional nanomaterials delivered to various cell lines SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE nanoparticles; cytotoxicity; cancer cells; chemotherapeutic agents ID WALLED CARBON NANOTUBES; POLY(ADP-RIBOSE) POLYMERASE; SELECTIVE NANOPHOTOTHERMOLYSIS; ULTRAFINE PARTICLES; ICE/CED-3 PROTEASE; NANOPARTICLES; APOPTOSIS; ACTIVATION; THERAPY; TISSUE AB Functional nanomaterials that included gold, silver nanoparticles and single wall carbon nanotubes were delivered to two cell lines (MLO-Y4 osteocytic cells and HeLa cervical cancer cells) in various concentrations. The cells were found to uptake the nanomaterials in a relatively short time, a process that significantly affected the shape and the size of the cells. The percentage of cellular death, due to the delivery of these nanomaterials, was found to be the highest for carbon nanotubes and increased gradually with the concentration of these nanostructures. Moreover, when the nanomaterials were delivered to the cells combined with commonly used chemotherapeutic agents such as etoposide or dexamethasone, the number of the cells that died increased significantly (100-300%) as compared with the case when only the nanomaterials or the chemotherapeutic agents were delivered. The experimental results were confirmed by Caspase 3 studies, indicating a strong interaction between the nanomaterials used in this study and the protein structure of the cells, which allowed a more effective action of the apoptotic agents. These findings could be the foundation of a new class of cancer therapies that are composed of both chemotherapeutic agents and nanomaterials. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Mahmood, Meena; Casciano, Daniel A.; Xu, Yang; Dervishi, Enkeleda; Li, Zhongrui; Abdalmuhsen, Mustafa; Ali, Nawab; Biris, Alexandru S.] Univ Arkansas, Dept Appl Sci, Nonotechnol Ctr, Grad Inst Technol, Little Rock, AR 72204 USA. [Mocan, Teodora; Iancu, Cornel; Mocan, Lucian; Iancu, Dana Todea; Biris, Alexandru S.] Univ Med & Pharm Iuliu Hatieganu, Surg Clin 3, Cluj Napoca 3400, Romania. [Biris, Alexandru R.] Natl Inst Res & Dev Isotop & Mol Technol, R-400293 Cluj Napoca, Romania. [Howard, Paul] Natl Ctr Toxicol Res, Food & Drug Adm, Jefferson, AR 72079 USA. RP Biris, AS (reprint author), Univ Arkansas, Dept Appl Sci, Nonotechnol Ctr, Grad Inst Technol, Little Rock, AR 72204 USA. EM dacasciano@ualr.edu; asbiris@ualr.edu RI Biris, Alexandru/A-8507-2010; Dervishi, Enkeleda/B-2239-2010; Biris, Alexandru /C-4517-2011; Mocan, Lucian/C-4123-2011; Iancu, Cornel/C-4115-2011; Mocan, Teodora/C-4081-2011 NR 25 TC 59 Z9 63 U1 3 U2 20 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD JAN PY 2010 VL 30 IS 1 BP 74 EP 83 DI 10.1002/jat.1475 PG 10 WC Toxicology SC Toxicology GA 543PX UT WOS:000273591800011 PM 19760634 ER PT J AU Yoon, SS Dillon, CF Carroll, M Illoh, K Ostchega, Y AF Yoon, Sung Sug (Sarah) Dillon, Charles F. Carroll, Margaret Illoh, Kachi Ostchega, Yechiam TI Effects of Statins on Serum Inflammatory Markers: The U.S. National Health and Nutrition Examination Survey 1999-2004 SO JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS LA English DT Article DE Statins; Inflammation; White blood cell count (WBC); C-reactive protein (CRP); Ferritin ID C-REACTIVE PROTEIN; RANDOMIZED CONTROLLED-TRIALS; CARDIOVASCULAR RISK-FACTORS; ACUTE CORONARY SYNDROMES; MYOCARDIAL-INFARCTION; HEART-DISEASE; PRAVASTATIN; THERAPY; WOMEN; MEN AB Aim: To evaluate the effects of HMG-CoA reductase inhibitor (statin) treatment on serum inflammatory markers using data from the National Health and Nutrition Examination Survey (NHANES 1999-2004). Methods and Results: A total of 9,128 individuals aged 40 and older participated in the NHANES. The inflammatory markers studied were white blood cell counts (WBC), high sensitivity C-reactive protein (CRP) and ferritin. Other covariables were: age, gender, race/ethnicity, body mass index, prescription or nonprescription medication use within the previous 30 days (statins, anti-inflammatory drugs, antibiotics). Four analytic groups for drug use were defined: Statin users; AI/Antibiotic users (use of either anti-inflammatory or antibiotic drugs); Combination group (use of both Statins and anti-inflammatory or antibiotic drugs), and a Non-use group (taking none of the listed drugs). The mean CRP level was significantly lower in the Statin use group than the Non-use group (0.3 mg/dL, 95% CI: 0.3-0.3 and 0.4 mg/dL, 95% CI: 0.4-0.5). In multivariable regression modeling, the Statin use group had significantly lower predicted mean WBC (Beta Coeff: -0.2, p < 0.05) and CRP (Beta Coeff: -0.1, p < 0.01) values than the Non-use group. Conclusions: Treatment with statins was significantly associated with decreased WBC and CRP levels in this large population-based sample. C1 [Yoon, Sung Sug (Sarah); Dillon, Charles F.; Carroll, Margaret; Ostchega, Yechiam] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Hlth & Nutr Examinat Survey, Hyattsville, MD 20782 USA. [Illoh, Kachi] US FDA, Div Neurol Prod, Silver Spring, MD 20993 USA. RP Yoon, SS (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Hlth & Nutr Examinat Survey, 3311 Toledo Rd,Room 4331, Hyattsville, MD 20782 USA. EM syoon1@cdc.gov NR 33 TC 12 Z9 12 U1 0 U2 1 PU JAPAN ATHEROSCLEROSIS SOC PI TOKYO PA NICHINAI-KAIKAN B1, 3-28-8 HONGO BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 1340-3478 EI 1880-3873 J9 J ATHEROSCLER THROMB JI J. Atheroscler. Thromb. PY 2010 VL 17 IS 11 BP 1176 EP 1182 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 690OS UT WOS:000285014700008 PM 20805636 ER PT J AU Choudhuri, S AF Choudhuri, Supratim TI Small Noncoding RNAs: Biogenesis, Function, and Emerging Significance in Toxicology SO JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY LA English DT Article DE miRNA; siRNA; piRNA; rasiRNA ID DOUBLE-STRANDED-RNA; CAENORHABDITIS-ELEGANS; MESSENGER-RNA; MICRO-RNA; GENETIC INTERFERENCE; SILENCING PATHWAYS; DISTINCT ROLES; RAT-LIVER; EXPRESSION; DROSOPHILA AB In recent years, the discovery of small ncRNAs (noncoding RNAs) has unveiled a slew of powerful riboregulators of gene expression. So far, many different types of small ncRNAs have been described. Of these, miRNAs (microRNAs), siRNAs (small interfering RNAs), and piRNAs (Piwi-interacting RNAs) have been studied in more detail. A significant fraction of genes in most organisms and tissues is targets of these small ncRNAs. Because these tiny RNAs are turning out to be important regulators of gene and genome expression, their aberrant expression profiles are expected to be associated with cellular dysfunction and disease. In fact, an ever-increasing number of studies have implicated miRNAs and siRNAs in human health and disease ranging from metabolic disorders to diseases of various organ systems as well as various forms of cancer. Nevertheless, despite the flurry of research on these small ncRNAs, many aspects of their biology still remain to be understood. The following discussion focuses on some aspects of the biogenesis and function of small ncRNAs with major emphasis on miRNAs since these are the most widespread endogenous small ncRNAs that have been called "micromanagers" of gene expression. Their emerging significance in toxicology is also discussed. (C)2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:195-216,2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI10:1002/jbt.20325 C1 [Choudhuri, Supratim] US FDA, Ctr Food Safety & Appl Nutr, Div Biotechnol, College Pk, MD 20740 USA. [Choudhuri, Supratim] US FDA, GRAS Notice Review, College Pk, MD 20740 USA. RP Choudhuri, S (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Biotechnol, College Pk, MD 20740 USA. EM supratim.choudhuri@fda.hhs.gov RI Xie, Huangming/B-2260-2012 NR 103 TC 33 Z9 33 U1 1 U2 14 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1095-6670 J9 J BIOCHEM MOL TOXIC JI J. Biochem. Mol. Toxicol. PY 2010 VL 24 IS 3 BP 195 EP 216 DI 10.1002/jbt.20325 PG 22 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 615AD UT WOS:000279100300006 PM 20143452 ER PT J AU Lyle, DB Bushar, GS Langone, JJ AF Lyle, Daniel B. Bushar, Grace S. Langone, John J. TI Screening biomaterials for functional complement activation in serum SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE complement activation; alternative pathway; classical pathway; biomaterials; screening; medical devices ID AGAROSE; CARTILAGE; SURFACES AB Complement plays an important role in the immune attack against invading microorganisms. However, blood-contacting medical device biomaterials lacking specific complement inhibitors, with free hydroxyl and/or amino groups, or with absorbed antibodies, may inappropriately activate complement. Inappropriate activation by either the antibody-mediated classical or the antibody-independent alternative pathway may have well-known acute or poorly understood chronic effects on the host or device. This article describes methods for screening biomaterials for functional whole complement activation using normal human serum, or specifically for alternative pathway activation using C4-deficient guinea pig serum, or for classical pathway activation using both sera in combination. Detailed protocols are available as standard methodologies from the American Society for Testing and Materials (ASTM F1984, ASTM F2065, and ASTM F2567). Results obtained with these functional tests are confirmed by detection of classical and alternative pathway-specific markers C4d and Bb, respectively. These methods demonstrate dose and time-course activation of complement to beaded agarose, cellulose acetate, and purified alginate as examples of biomaterials. Significant difference in a functional endpoint denoting specific complement pathways is an appropriate screening method for complement activation by medical device biomaterials which might result in adverse events when the device is implanted or contacts human blood. (C) 2009 Wiley Periodicals, Inc.* J Biomed Mater Res 92A: 205-213, 2010 C1 [Lyle, Daniel B.; Bushar, Grace S.; Langone, John J.] US FDA, CDRH, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. RP Lyle, DB (reprint author), US FDA, Div Biol, CDRH, Off Sci Engn Labs, White Oak Life Sci Bldg 64-3036,10903 New Hampshi, Silver Spring, MD 20993 USA. EM dan.lyle@fda.hhs.gov NR 29 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1549-3296 EI 1552-4965 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD JAN PY 2010 VL 92A IS 1 BP 205 EP 213 DI 10.1002/jbm.a.32281 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 531BF UT WOS:000272637000022 PM 19172622 ER PT J AU Lim, N Ahn, H Moon, H Chen, JJ AF Lim, Noha Ahn, Hongshik Moon, Hojin Chen, James J. TI Classification of High-Dimensional Data with Ensemble of Logistic Regression Models SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Aggregation; Class prediction; Cross-validation; Decision threshold; Majority voting; Random partition AB A classification method is developed based on ensembles of logistic regression models, with each model fitted from a different set of predictors determined by a random partition of the feature space. The proposed method enables class prediction by an ensemble of logistic regression models for a high-dimensional data set, which is impossible by a single logistic regression model due to the restriction that the sample size needs to be larger than the number of predictors. The proposed classification method is applied to gene expression data on pediatric acute myeloid leukemia (AML) patients to predict each patient's risk for treatment failure or relapse at the time of diagnosis. Hence, specific prognostic biomarkers can be used to predict outcomes in pediatric AML and formulate individual risk-adjusted treatment. Our study shows that the proposed method is comparable to other widely used models in generalized accuracy and is significantly improved in balance between sensitivity and specificity. The proposed ensemble algorithm enables the standard classification model to be used for classification of high-dimensional data. C1 [Ahn, Hongshik] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. [Lim, Noha] Univ Calif San Francisco, Immune Tolerance Network, San Francisco, CA 94143 USA. [Moon, Hojin] Calif State Univ Long Beach, Dept Math & Stat, Long Beach, CA 90840 USA. [Chen, James J.] Natl Ctr Toxicol Res, Biometry Branch, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. RP Ahn, H (reprint author), SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. EM hahn@ams.sunysb.edu FU Oak Ridge Institute for Science and Education; U. S. Department of Energy; U.S. Food and Drug Administration; CSULB FX Hongshik Ahn's research 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 the U. S. Department of Energy and U.S. Food and Drug Administration. Hojin Moon's research was partially supported by the SCAC Award from CSULB. NR 10 TC 5 Z9 5 U1 2 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1054-3406 EI 1520-5711 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2010 VL 20 IS 1 BP 160 EP 171 AR PII 918539621 DI 10.1080/10543400903280639 PG 12 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 544DX UT WOS:000273633800012 PM 20077255 ER PT J AU Tsong, Y Zhang, JN AF Tsong, Yi Zhang, Joanne TI Further Discussion on the Design and Analysis of Thorough QTc Clinical Trials: Guest Editors' Notes SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Editorial Material ID STATISTICAL ASSESSMENT; CONFIDENCE-BOUNDS C1 [Tsong, Yi; Zhang, Joanne] US FDA, Div Biometr 6, Off Biostat, Off Translat Sci,Ctr Drug Evaluation & Res, Silver Spring, MD USA. RP Tsong, Y (reprint author), US FDA, Div Biometr 6, Off Biostat, Off Translat Sci,Ctr Drug Evaluation & Res, Silver Spring, MD USA. EM yi.tsong@fda.hhs.gov NR 10 TC 1 Z9 1 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2010 VL 20 IS 3 BP 493 EP 496 AR PII 921493322 DI 10.1080/10543400903581937 PG 4 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 595CG UT WOS:000277587700001 PM 20358431 ER PT J AU Yan, LHK Zhang, JN Ng, MJ Dang, QY AF Yan, Lihan K. Zhang, Joanne Ng, Moh Jee Dang, Qianyu TI Statistical Characteristics of Moxifloxacin-Induced QTc Effect SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Assay sensitivity; Moxifloxacin; Thorough QTc study ID THOROUGH QT AB Moxifloxacin has been the most commonly used positive control in othorougho QTc (TQT) studies. In a TQT study, the assay sensitivity is often considered to be established if the baseline corrected mean difference in QTc between moxifloxacin and placebo is greater than 5ms in common practice at one or more prespecified time points and the observed moxifloxacin induced QTc effect over time follows the proper pharmacokinetics profile. To better understand the statistical characteristics of moxifloxacin-induced QTc prolongation and to provide guidance for future studies, 20 TQT studies that involved moxifloxacin have been evaluated. We study the QTc profile of the baseline adjusted mean difference in QTc between moxifloxacin and placebo over time. Zhang (2008) proposed that the moxifloxacin induced QTc effect can be evaluated between 1 and 4h after a single dose (400mg) administration near the time (Tmax) of peak concentration instead of all time points (typically 9-12 time points) at which QT was measured for the study drug evaluation. After evaluating 20 TQT studies, we confirm that the maximum moxifloxacin effect occurs in the time window between 1 and 4h post dose. We also investigate the variability of the data as well as correlations between time points and between regimens. These findings and results can be used as a reference for future studies. C1 [Yan, Lihan K.; Zhang, Joanne; Ng, Moh Jee; Dang, Qianyu] US FDA, Div Biometr 6, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Zhang, JN (reprint author), US FDA, Div Biometr 6, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Room 4668,Bldg 21,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Joanne.Zhang@fda.hhs.gov NR 6 TC 30 Z9 31 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2010 VL 20 IS 3 BP 497 EP 507 AR PII 921493198 DI 10.1080/10543400903581945 PG 11 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 595CG UT WOS:000277587700002 PM 20358432 ER PT J AU Tsong, Y Zhong, JL AF Tsong, Yi Zhong, Jinglin TI Multiple Comparisons of Repeated Measured Response: Issues of Assessment of Prolongation of QT Interval in Thorough QT Trials SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Multiple comparisons; QT interval; Repeated measured responses ID STATISTICAL ISSUES; CONFIDENCE-BOUNDS; QT/QTC AB The primary objective of a thorough QT clinical trial is to demonstrate the lack of QT prolongation induced by the test treatment. The ICH E14 guidance defined drug-induced prolongation of QT interval as evidenced by an upper bound of the 95% one-sided confidence interval around the mean effect on QTc of 10ms. Furthermore, it defined a negative thorough QT/QTc study as one in which the upper bound of the 95% one-sided confidence interval for the largest time-matched mean effect of the drug on the QTc interval excludes 10ms. Conventionally, this objective is tested with the intersection-union test by testing the mean difference between the test treatment and placebo of QTc changes from baseline at each of the matched time points. The multiple-comparison nature of the test leads to higher false positive rate when comparisons are made repeatedly at multiple time points. Many approaches have been proposed in the last 5 years in order to improve the efficiency of the test. In this article, we survey and discuss some of the approaches. C1 [Tsong, Yi; Zhong, Jinglin] US FDA, DBVI, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Tsong, Y (reprint author), Room 4628,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM yi.tsong@fda.hhs.gov NR 12 TC 3 Z9 3 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2010 VL 20 IS 3 BP 613 EP 623 AR PII 921493432 DI 10.1080/10543400903582018 PG 11 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 595CG UT WOS:000277587700010 ER PT J AU Tsong, Y Yan, LHK Zhong, JL Nie, L Zhang, JN AF Tsong, Yi Yan, Lihan K. Zhong, Jinglin Nie, Lei Zhang, Joanne TI Multiple Comparisons of Repeatedly Measured Response: Issues of Validation Testing in Thorough QT/QTc Clinical Trials SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Assay sensitivity; Bonferroni adjustment; Controlling type I error rate; Hochberg adjustment; Holm method; Length theorem; Multiple comparisons ID BONFERRONI PROCEDURE; QT AB In order to validate the results of a thorough QT/QTc clinical trial, ICH E14 recommended that a concurrent positive control treatment be included in the trial. Zhang (2008) recommended that the study results are validated if the positive control establishes assay sensitivity, i.e., has an effect on the mean QT/QTc interval of 5ms or more. Zhang (2008) and Tsong et al. (2008) discussed the intersection-union test approach and an alternative global average test approach for testing assay sensitivity during the validation process. In this article, we further discuss the multiple comparison issues of the repeatedly measured QT difference between positive control treatment and placebo in the validation test. We describe and discuss several approaches for type I error rate adjustment that are applicable to the situation. C1 [Tsong, Yi] 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@fda.hhs.gov NR 15 TC 6 Z9 6 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2010 VL 20 IS 3 BP 654 EP 664 AR PII 921495679 DI 10.1080/10543400903582059 PG 11 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 595CG UT WOS:000277587700013 PM 20358443 ER PT J AU Tsong, Y Zhong, JL Chen, WJ AF Tsong, Yi Zhong, Jinglin Chen, Wen Jen TI Response to Letter to the Editor: Validation Testing in Thorough QT/QTc Clinical Trials by Yi Tsong et al. SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Letter C1 [Tsong, Yi; Zhong, Jinglin; Chen, Wen Jen] US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Tsong, Y (reprint author), US FDA, 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 1 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2010 VL 20 IS 3 BP 688 EP 688 AR PII 921497886 DI 10.1080/10543400903582075 PG 1 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 595CG UT WOS:000277587700016 ER PT J AU Wang, YN Garnett, C AF Wang, Yaning Garnett, Christine TI Letter to the Editor: Statistical Issues of QT Prolongation Assessment Based on Linear Concentration Modeling by Yi Tsong et al. SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Letter C1 [Wang, Yaning; Garnett, Christine] US FDA, Off Clin Pharmacol, Silver Spring, MD 20993 USA. RP Wang, YN (reprint author), US FDA, Off Clin Pharmacol, 10903 New Hampshire Ave,Bldg 51,Rm 1252, Silver Spring, MD 20993 USA. EM yaning.wang@fda.hhs.gov NR 10 TC 4 Z9 5 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2010 VL 20 IS 3 BP 689 EP 692 AR PII 921494297 DI 10.1080/10543400903094881 PG 4 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 595CG UT WOS:000277587700017 PM 20358447 ER PT J AU Tsong, Y Shen, MY Zhong, JL Zhang, JN AF Tsong, Yi Shen, Meiyu Zhong, Jinglin Zhang, Joanne TI Response to Letter to the Editor: Statistical Issues of QT Prolongation Assessment Based on Linear Concentration Modeling by Yi Tsong et al. SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Letter ID INEQUALITIES; HYPOTHESES; POWERFUL; TESTS C1 [Tsong, Yi; Shen, Meiyu; Zhong, Jinglin; Zhang, Joanne] US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Tsong, Y (reprint author), US FDA, 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 8 TC 0 Z9 0 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2010 VL 20 IS 3 BP 693 EP 697 AR PII 921496009 DI 10.1080/10543400903582083 PG 5 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 595CG UT WOS:000277587700018 ER PT J AU Zaslavsky, BG AF Zaslavsky, Boris G. TI Bayesian Adaptive Dose-Finding Studies with Delayed Responses SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Bayesian adaptive design; Dose-finding study; Integrated two-component prediction model; Prediction model; Utility function ID P-VALUES; FREQUENTIST EVIDENCE; TESTING PROBLEM; HYPOTHESIS; PARADOX AB In recent years, Bayesian response-adaptive designs have been used to improve the efficiency of learning in dose-finding studies. Many current methods for analyzing the data at the time of the interim analysis only use the data from patients who have completed the study. Therefore, data collected at intermediate time points are not used for decision making in these studies. However, in some disease areas such as diabetes and obesity, patients may need to be studied for several weeks or months for a drug effect to emerge. Additionally, slow enrollment rates can limit the number of patients who complete the study in a given period of time. Consequently, at the time of an interim analysis, there may be only a small proportion (e.g., 20%) of patients who have completed the study. In this paper, we propose a new Bayesian prediction model to incorporate all the data (from patients who have completed the study and those who have not completed) to make decisions about the study at the interim analysis. Examples of decisions made at the interim analysis include adaptive treatment allocation, dropping nonefficacious dose arms, stopping the study for positive efficacy, and stopping the study for futility. The model is able to handle incomplete longitudinal data including missing data considered missing at random (MAR). A utility-function-based decision rule is also discussed. The benefit of our new method is demonstrated through trial simulations. Three scenarios are examined, and the simulation results demonstrate that this new method outperforms traditional design with the same sample size in each of these scenarios. C1 US FDA, Rockville, MD 20852 USA. RP Zaslavsky, BG (reprint author), US FDA, 1401 Rockville Pike,HFM 219, Rockville, MD 20852 USA. EM Boris.Zaslavsky@FDA.HHS.gov FU FDA/CBER Critical Path initiative FX This research was partially supported by the FDA/CBER Critical Path initiative grant. NR 29 TC 6 Z9 6 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 EI 1520-5711 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2010 VL 20 IS 5 BP 985 EP 997 AR PII 925940084 DI 10.1080/10543401003619023 PG 13 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 640VN UT WOS:000281082200006 PM 20721786 ER PT J AU Wang, SJ AF Wang, Sue-Jane TI Editorial: Adaptive Designs: Appealing in Development of Therapeutics, and Where do Controversies Lie? SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Editorial Material ID PLAY-WINNER RULE; CLINICAL-TRIALS C1 US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Biostat, Silver Spring, MD 20993 USA. RP Wang, SJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Biostat, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM suejane.wang@fda.hhs.gov NR 24 TC 8 Z9 8 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 EI 1520-5711 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2010 VL 20 IS 6 SI SI BP 1083 EP 1087 AR PII 929073846 DI 10.1080/10543406.2010.514461 PG 5 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 676BU UT WOS:000283885900001 PM 21058102 ER PT J AU Wang, SJ AF Wang, Sue-Jane TI Perspectives on the Use of Adaptive Designs in Clinical Trials. Part I. Statistical Considerations and Issues SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Bias; Confirmatory adaptive trial design; Exploratory adaptive trial design; Familywise Type I error rate; Learn-and-confirm ID MODERN PROTOCOL DESIGN; SELECTION; INTERIM AB With greater and enthusiastic interests in pursuing adaptive design clinical trials, the pharmaceutical industry as a whole is in the midst of gaining better understanding of scientifically sound approaches. In light of the public's greater interests, the Basel Biometric Section (BBS) of the Austo-Swiss Region of the International Biometric Society held a spring conference on oPerspectives on the Use of Adaptive Designs in clinical trialso at Basel University, Basel, Switzerland (March 12, 2010). The conference opened with statistical considerations and issues of adaptive designs in clinical trials, followed by a panel discussion in which international representatives from industry, academia, and regulatory agencies participated. In addition, six presentations were given by individual research groups mainly focusing on adaptive design methodologies, some illustrated with examples. There are two parts in this special article capturing the morning session of the conference. Part I summarizes the highlights given at the statistical considerations and issues session and is presented here. Part II, capturing the panelists' perspectives given at the panel discussion session, can be found immediately following Part I. C1 US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Biostat, Silver Spring, MD 20993 USA. RP Wang, SJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Biostat, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM suejane.wang@fda.hhs.gov NR 30 TC 9 Z9 9 U1 2 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2010 VL 20 IS 6 SI SI BP 1090 EP 1097 AR PII 929111715 DI 10.1080/10543406.2010.514446 PG 8 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 676BU UT WOS:000283885900003 PM 21058104 ER PT J AU Benda, N Brannath, W Bretz, F Burger, HU Friede, T Maurer, W Wang, SJ AF Benda, Norbert Brannath, Werner Bretz, Frank Burger, Hans-Ulrich Friede, Tim Maurer, Willi Wang, Sue-Jane TI Perspectives on the Use of Adaptive Designs in Clinical Trials. Part II. Panel Discussion SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Clinical trial design; Confirmatory study; Drug development; Exploratory study ID DRUG DEVELOPMENT; SEQUENTIAL TRIALS; SELECTION AB In the midst of gaining more experience in pursuing scientifically sound approaches of adaptive designs in clinical trials, a panel discussion with international representatives from industry, academia, and regulatory agencies was held at the Basel Biometric Society Spring Conference, March 12, 2010. The goal was to develop some consensus among industry, government, and academic statisticians concerning requirements and methods for adaptive designs in clinical trials. In this paper, we summarize the panelists' perspectives given at that session. C1 [Bretz, Frank; Maurer, Willi] Novartis Pharma AG, Stat Methodol, CH-4002 Basel, Switzerland. [Brannath, Werner] Med Univ Vienna, Vienna, Austria. [Benda, Norbert] Fed Inst Drugs & Med Devices, Bonn, Germany. [Burger, Hans-Ulrich] Hoffmann La Roche AG, Basel, Switzerland. [Friede, Tim] Univ Med Ctr Gottingen, Gottingen, Germany. [Wang, Sue-Jane] US FDA, Silver Spring, MD USA. RP Bretz, F (reprint author), Novartis Pharma AG, Stat Methodol, CH-4002 Basel, Switzerland. EM frank.bretz@novartis.com RI Bretz, Frank/F-6927-2014 NR 32 TC 7 Z9 7 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2010 VL 20 IS 6 SI SI BP 1098 EP 1112 AR PII 929076459 DI 10.1080/10543406.2010.514447 PG 15 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 676BU UT WOS:000283885900004 PM 21058105 ER PT J AU Su, YA Yang, J Tao, L Nguyen, H He, P AF Su, Yan A. Yang, Jun Tao, Lian Hein Nguyen He, Ping TI Undetectable and Decreased Expression of KIAA1949 (Phostensin) Encoded on Chromosome 6p21.33 in Human Breast Cancers Revealed by Transcriptome Analysis SO JOURNAL OF CANCER LA English DT Article DE Breast cancer; MDA-MB-231; Microarray; Tumor suppressor gene; Phostensin; KIAA1949 AB Cytogenetic aberration and loss of heterozygosity (LOH) are documented on chromosome 6 in many cancers and the introduction of a neo-tagged chromosome 6 into breast cancer cell lines mediates suppression of tumorigenicity. In this study, we described the identification of KIAA1949 (phostensin) as a putative tumor suppressor gene. Our microarray analysis screened 25,985 cDNAs between a tumorigenic and metastatic breast cancer cell line MDA-MB-231 and the chromosome 6-mediated suppressed, non-tumorigenic and non-metastatic derivative cell line MDA/H6, resulting in the identification of 651 differentially expressed genes. Using customized microarrays containing these 651 cDNAs and 117 controls, we identified 200 frequently dysregulated genes in 10 breast cancer cell lines and 5 tumor tissues using MDA/H6 as reference. Our bioinformatics analysis revealed that chromosome 6 encodes 25 of these 200 genes, with 4 downregulation and 21 upergulation. Northern analysis validated microarray results and was used to detect the size and number of RNA species of 2 downregulated (KIAA1949, PTK7) and 2 upregulated (SFRS3, HMGN3) genes in the cell lines. Particularly, the KIAA1949 gene at 6p21.33, a band region with the frequent cytogenetic aberration and LOH encodes 4 poly(A)-RNA species (4.6-, 4-, 3- and 1.5-kb) in multiple normal and breast cancer samples. Microarray analysis revealed KIAA1949 downregulation in 86.7% (n=15) of breast cancer cell lines and tumor tissues. Northern analysis demonstrated undetectable and decreased expression of KIAA1949 in 100% (n=10) of breast cancer cell lines. Taken together, these results strongly suggest KIAA1949 is a novel candidate breast cancer suppressor gene. C1 [Su, Yan A.; Yang, Jun; Tao, Lian; Hein Nguyen] GenProMarkers Inc, Rockville, MD 20850 USA. [He, Ping] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. RP Su, YA (reprint author), GenProMarkers Inc, 9700 Great Seneca Highway,Suite 182, Rockville, MD 20850 USA. EM gpmyas@genpromarkers.com FU United States Army Medical Research and Materiel Command award [DAMD17-97-1-7236]; V Foundation FX The authors greatly appreciate Dr. Massimo Negrini for generously providing us with the MDA/H6 cell line. This work was supported in part by the United States Army Medical Research and Materiel Command award DAMD17-97-1-7236 and The V Foundation grant to YAS. NR 32 TC 13 Z9 13 U1 0 U2 2 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 2010 VL 1 BP 38 EP 50 PG 13 WC Oncology SC Oncology GA V28QL UT WOS:000208695200007 PM 20842223 ER PT J AU Khurana, S Norris, PJ Busch, MP Haynes, BF Park, S Sasono, P Mlisana, K Salim, AK Hecht, FM Mulenga, J Chomba, E Hunter, E Allen, S Nemo, G Rodriguez-Chavez, IR Margolick, JB Golding, H AF Khurana, Surender Norris, Philip J. Busch, Michael P. Haynes, Barton F. Park, Susan Sasono, Pretty Mlisana, Koleka Salim, Abdool Karim Hecht, Frederick M. Mulenga, Joseph Chomba, Elwyn Hunter, Eric Allen, Susan Nemo, George Rodriguez-Chavez, Isaac R. Margolick, Joseph B. Golding, Hana CA Women's Interagency HIV Study Coll MACS TI HIV-Selectest Enzyme Immunoassay and Rapid Test: Ability To Detect Seroconversion following HIV-1 Infection SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; VACCINE-GENERATED ANTIBODIES; DIFFERENTIAL-DIAGNOSIS; ANTIRETROVIRAL THERAPY; RNA LEVELS; PLASMA; RESPONSES; VIREMIA; FACE AB HIV-Selectest is a serodiagnostic enzyme immunoassay (EIA), containing p6 and gp41 peptides, designed to differentiate between vaccine-induced antibodies and true infections. A rapid test version of the HIV-Selectest was developed. Both assays detected HIV antibodies in men and women within 2 to 4 weeks of infection, with sensitivity similar to third-generation EIAs. C1 [Khurana, Surender; Park, Susan; Sasono, Pretty; Golding, Hana] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. [Norris, Philip J.; Busch, Michael P.] Blood Syst Res Inst, San Francisco, CA 94118 USA. [Norris, Philip J.; Busch, Michael P.; Hecht, Frederick M.] Univ Calif San Francisco, San Francisco, CA 94118 USA. [Haynes, Barton F.] Duke Human Vaccine Inst, Durham, NC 27710 USA. [Mlisana, Koleka; Salim, Abdool Karim] Univ KwaZulu Natal, Ctr AIDS Programme Res S Africa, ZA-4013 Durban, South Africa. [Mulenga, Joseph] ZEHRP, Lusaka, Zambia. [Mulenga, Joseph; Chomba, Elwyn] Zambia Blood Transfus Serv, Lusaka, Zambia. [Hunter, Eric] Emory Vaccine Res Ctr, Atlanta, GA 30329 USA. [Allen, Susan] Emory Univ, Sch Publ Hlth, Atlanta, GA 30322 USA. [Nemo, George] NHLBI, NIH, Bethesda, MD 20817 USA. [Rodriguez-Chavez, Isaac R.] Natl Inst Dent & Craniofacial Res, AIDS & Immunosuppress Program, NIH, Bethesda, MD 20892 USA. [Women's Interagency HIV Study Coll] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. [Margolick, Joseph B.; MACS] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. RP Golding, H (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Room 1A21,Bldg 29A,8800 Rockville Pike, Bethesda, MD 20892 USA. EM hana.golding@fda.hhs.gov RI Abdool Karim, Salim Safurdeen/N-5947-2013; OI Abdool Karim, Salim Safurdeen/0000-0002-4986-2133; Mlisana, Koleka/0000-0002-8436-3268; Cranston, Ross/0000-0002-2687-6217 FU NHLBI IAG; Center for HIV/AIDS Vaccine Immunology (CHAVI) [AI-067854]; NIAID [R37-AI51231, R01-AI64060]; NIH [AI51794]; South African National Research Foundation [67385]; IAVI; Office of Women's Health, FDA; NIH, National Institute of Allergy and Infectious Diseases [UO1-AI35042, 5-MO1-RR-00052, UO1-AI-35043, UO1-AI-35039, UO1-AI-35040, UO1-AI-35041, U01AI42532]; National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources (UCSF-CTSI) [UL1 RR024131] FX We do not have any conflicts of interest. This project was supported in part by NHLBI IAG (2005 to 2006), Center for HIV/AIDS Vaccine Immunology (CHAVI) grant AI-067854, by NIAID grants R37-AI51231 and R01-AI64060, by NIH grant AI51794, by the South African National Research Foundation (grant 67385), by IAVI, and by a grant from the Office of Women's Health, FDA (2006 to 2007). This study is partially funded by the FDA Office of Women's Health.; Vaccine samples were provided by Barney Graham, Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, NIH, Bethesda, MD.; The Multicenter AIDS Cohort Study (MACS) includes the following: in Baltimore, MD, at The Johns Hopkins University Bloomberg School of Public Health, Joseph B. Margolick (Principal Investigator), Barbara Crain, Adrian Dobs, Homayoon Farzadegan, Joel Gallant, Lisette Johnson-Hill, Shenghan Lai, Ned Sacktor, Ola Selnes, James Shepard, and Chloe Thio; in Chicago, IL, at Howard Brown Health Center, Feinberg School of Medicine, Northwestern University, and Cook County Bureau of Health Services, John P. Phair (Principal Investigator), Steven M. Wolinsky (Co-Principal Investigator), Sheila Badri, Bruce Cohen, Craig Conover, Maurice O'Gorman, David Ostrow, Frank Palella, and Daina Variakojis; in Los Angeles, CA, at University of California, UCLA Schools of Public Health and Medicine, Roger Detels (Principal Investigator), Otoniel Martinez-Maza (Co-Principal Investigator), Aaron Aronow, Robert Bolan, Elizabeth Breen, Anthony Butch, Rita Effros, John Fahey, Beth Jamieson, Eric N. Miller, John Oishi, Harry Vinters, Barbara R. Visscher, Dorothy Wiley, Mallory Witt, Otto Yang, Stephen Young, and Zuo Feng Zhang; in Pittsburgh, PA, at University of Pittsburgh, Graduate School of Public Health, Charles R. Rinaldo (Principal Investigator), Lawrence A. Kingsley (Co-Principal Investigator), James T. Becker, Ross D. Cranston, Jeremy J. Martinson, John W. Mellors, Anthony J. Silvestre, and Ronald D. Stall; at the Data Coordinating Center, The Johns Hopkins University Bloomberg School of Public Health, Lisa P. Jacobson (Principal Investigator), Alvaro Munoz (Co-Principal Investigator), Alison Abraham, Keri Althoff, Christopher Cox, Gypsyanber D'Souza, Stephen J. Gange, Elizabeth Golub, Janet Schollenberger, Eric C. Seaberg, and Sol Su; at the NIH, National Institute of Allergy and Infectious Diseases, Robin E. Huebner; and at the National Cancer Institute, Geraldina Dominguez. Funding includes grants UO1-AI35042, 5-MO1-RR-00052 (GCRC), UO1-AI-35043, UO1-AI-35039, UO1-AI-35040, UO1-AI-35041, and U01AI42532 (JM). The MACS website is located at http://www.statepi.jhsph.edu/macs/macs.html. Data in this article were collected by the Women's Interagency HIV Study (WIHS) Collaborative Study Group, with centers (Principal Investigators) at the New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff); Washington, DC, Metropolitan Consortium (Mary Young); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/ Southern California Consortium (Alexandra Levine); Chicago Consortium (Mardge Cohen); and Data Coordinating Center (Stephen Gange). The WIHS is funded by the National Institute of Allergy and Infectious Diseases (grants UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant UO1-HD-32632). The study is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI grant UL1 RR024131). NR 11 TC 4 Z9 5 U1 0 U2 1 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 JAN PY 2010 VL 48 IS 1 BP 281 EP 285 DI 10.1128/JCM.01573-09 PG 5 WC Microbiology SC Microbiology GA 576NL UT WOS:000276151500039 PM 19906903 ER PT J AU Rasmussen, MA Benahmed, FH AF Rasmussen, M. A. Benahmed, F. H. TI Development of a PCR assay for the detection of Zymomonas mobilis in distillers grains SO JOURNAL OF DAIRY SCIENCE LA English DT Meeting Abstract DE distillers grains; Zymomonas; bioethanol C1 [Rasmussen, M. A.; Benahmed, F. H.] US FDA, Ctr Vet Med, Res Off, Laurel, MD USA. RI Rasmussen, Mark/N-9509-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-0302 J9 J DAIRY SCI JI J. Dairy Sci. PY 2010 VL 93 SU 1 BP 163 EP 163 PG 1 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA 822NU UT WOS:000295056200487 ER PT J AU Nsofor, U Ustunol, Z AF Nsofor, U. Ustunol, Z. TI Sensory attributes of yogurt fortified with predigested, non-germinated or germinated whole soy powder SO JOURNAL OF DAIRY SCIENCE LA English DT Meeting Abstract DE yogurt; soy; sensory C1 [Nsofor, U.; Ustunol, Z.] Michigan State Univ, E Lansing, MI 48824 USA. [Nsofor, U.] US FDA, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-0302 J9 J DAIRY SCI JI J. Dairy Sci. PY 2010 VL 93 SU 1 BP 335 EP 335 PG 1 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA 822NU UT WOS:000295056201274 ER PT J AU Nsofor, U Ustunol, Z AF Nsofor, U. Ustunol, Z. TI Activity and viability of lactic acid bacteria in yogurts fortified with predigested non-germinated or germinated whole soy powder SO JOURNAL OF DAIRY SCIENCE LA English DT Meeting Abstract DE yogurt; soy; lactic acid bacteria C1 [Nsofor, U.; Ustunol, Z.] Michigan State Univ, E Lansing, MI 48824 USA. [Nsofor, U.] US FDA, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-0302 J9 J DAIRY SCI JI J. Dairy Sci. PY 2010 VL 93 SU 1 BP 335 EP 335 PG 1 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA 822NU UT WOS:000295056201273 ER PT J AU Lee, SH Lillehoj, H Park, MS Lee, KW Baldwin, C Tompkins, D Wagner, B Babu, U Del Cacho, E AF Lee, S. -H. Lillehoj, H. Park, M. -S. Lee, K. -W. Baldwin, C. Tompkins, D. Wagner, B. Babu, U. Del Cacho, E. TI Development and characterization of mouse monoclonal antibodies reactive with chicken CD80 SO JOURNAL OF DAIRY SCIENCE LA English DT Meeting Abstract DE chickens; CD80; monoclonal antibody C1 [Lee, S. -H.; Lillehoj, H.; Park, M. -S.; Lee, K. -W.] USDA ARS, Anim & Nat Resources Inst, Beltsville, MD USA. [Baldwin, C.; Tompkins, D.] Univ Massachusetts, Amherst, MA 01003 USA. [Wagner, B.] Cornell Univ, Ithaca, NY USA. [Babu, U.] US FDA, Laurel, MD USA. [Del Cacho, E.] Univ Zaragoza, Zaragoza, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-0302 J9 J DAIRY SCI JI J. Dairy Sci. PY 2010 VL 93 SU 1 BP 544 EP 544 PG 1 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA 822NU UT WOS:000295056202162 ER PT J AU Guo, L Mei, N Xia, QS Chen, T Chan, PC Fu, PP AF Guo, Lei Mei, Nan Xia, Qingsu Chen, Tao Chan, Po-Chuen Fu, Peter P. TI Gene Expression Profiling as an Initial Approach for Mechanistic Studies of Toxicity and Tumorigenicity of Herbal Plants and Herbal Dietary Supplements SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE herbal dietary supplements; DNA microarray; drug metabolizing enzyme; drug metabolizing gene; gene expression; toxicity; tumorigenicity ID COMFREY SYMPHYTUM-OFFICINALE; DRUG-METABOLIZING-ENZYMES; HUMAN CYTOCHROMES P450; ST-JOHNS-WORT; GINKGO-BILOBA; KAVA EXTRACT; F344 RATS; PYRROLIZIDINE ALKALOIDS; OXIDATIVE STRESS; RISK-ASSESSMENT AB Dietary supplements are consumed by more than 300 million people worldwide, and herbal dietary supplements represent the most rapidly growing portion of this industry. Even though adverse health effects of many herbal dietary supplements have been reported, safety assurances are not being addressed adequately. Toxicological data on the identification of genotoxic and tumorigenic ingredients in many raw herbs are also lacking. Currently, more than 30 herbal dietary supplements and active ingredients have been selected by the National Toxicology Program (NTP) for toxicity and tumorigenicity studies. Due to the complexity of the chemical components present in plant extracts, there are no established methodologies for determining the mechanisms of toxicity (particularly tumorigenicity) induced by herbs, such as Gingko biloba leaf extract (GBE) and other herbal plant extracts. Consequently, the understanding of toxicity of herbal dietary supplements remains limited. We have proposed that application of DNA microarrays could be a highly practical initial approach for revealing biological pathways and networks associated with toxicity induced by herbal dietary supplements and the generation of hypotheses to address likely mechanisms. The changes in expression of subsets of genes of interest, such as the modulation of drug metabolizing genes, can be analyzed after treatment with an herbal dietary supplement. Although levels of gene expression do not represent fully the levels of protein activities, we propose that subsequent biochemical and genomic experiments based on these initial observations will enable elucidation of the mechanisms leading to toxicity, including tumorigenicity. This review summarizes the current practices of microarray analysis of gene expressions in animals treated with herbal dietary supplements and discusses perspectives for the proposed strategy. C1 [Guo, Lei; Xia, Qingsu; Fu, Peter P.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Mei, Nan; Chen, Tao] US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Chan, Po-Chuen] NIEHS, Res Triangle Pk, NC 27709 USA. RP Guo, L (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM lei.guo@fda.hhs.gov RI Guo, Lei/E-9232-2011; mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 FU NIH, National Institute of Environmental Health Sciences FX We thank Drs. James C. Fuscoe, Qiang Shi, and Frederick A. Beland from NCTR and Richard D. Irwin and Michael L. Cunningham from NIEHS for their critical review of this manuscript. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 72 TC 9 Z9 9 U1 1 U2 23 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 CHESTNUT 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. PY 2010 VL 28 IS 1 BP 60 EP 87 AR PII 920001920 DI 10.1080/10590500903585416 PG 28 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 595CN UT WOS:000277588400004 PM 20390968 ER PT J AU Chen, T AF Chen, Tao TI The Role of MicroRNA in Chemical Carcinogenesis SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE microRNA; carcinogen; genotoxicity; carcinogenesis; biomarker ID TUMOR-SUPPRESSOR NETWORK; TARGET MESSENGER-RNAS; C-ELEGANS; CAENORHABDITIS-ELEGANS; EXPRESSION PROFILES; CIGARETTE-SMOKE; GENE-EXPRESSION; DOWN-REGULATION; NUCLEAR EXPORT; POSTTRANSCRIPTIONAL REGULATION AB MicroRNAs (miRNAs) are important regulators of gene expression. Alteration of miRNA expression caused by exposure of different carcinogens has been well reported. This review aims to present the miRNAs dysregulated by exposure of different types of carcinogens in different biological systems and to discuss their potential roles in different stages of chemical carcinogenesis, following an introduction of miRNA biogenesis, regulatory mechanisms, and target identification. Available information shows that expression of a large number of miRNAs is readily changed by exposure of carcinogens in tissue- and chemical-specific manners. Carcinogenic agents generally induce many more changes in miRNA expression than non-carcinogenic chemicals. There are many more changes in cancer-target tissues than in the non-target tissues after acute or chronic exposure to carcinogens. Many of the miRNAs deregulated by carcinogens are involved in regulation of genes that are important for every stage of chemical carcinogenesis, including xenobiotic metabolism, carcinogen-induced hypomethylation, DNA repair, apoptosis, cell proliferation, tumor suppression, cell transformation, oncogenesis, tumor angiogenesis, tumor progress, mangliant transformation, and other functions. Many miRNAs function as putative oncogenes and tumor suppressor genes. The carcinogenic functions of carcinogens may be dependent on the balance between tumor-suppressor miRNAs and oncogenic miRNAs. Thus, the miRNA profiles and miRNAs specific to carcinogen exposure have the potential to be used as biomarkers for identifying genotoxicity and carcinogenicity of chemicals and indicating exposure of carcinogens. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT 130, Jefferson, AR 72079 USA. RP Chen, T (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT 130, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM tao.chen@fda.hhs.gov NR 134 TC 39 Z9 44 U1 1 U2 9 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, 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. PY 2010 VL 28 IS 2 BP 89 EP 124 AR PII 923039493 DI 10.1080/10590501.2010.481477 PG 36 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 611AN UT WOS:000278782900001 PM 20552498 ER PT J AU Fang, JL Stingley, RL Beland, FA Harrouk, W Lumpkins, DL Howard, P AF Fang, Jia-Long Stingley, Robin L. Beland, Frederick A. Harrouk, Wafa Lumpkins, Debbie L. Howard, Paul TI Occurrence, Efficacy, Metabolism, and Toxicity of Triclosan SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE triclosan; metabolism; endocrine disruption effect; toxicity ID CARRIER PROTEIN REDUCTASE; PERSONAL CARE PRODUCTS; ETHER IRGASAN DP300; BREAST-CANCER CELLS; WASTE-WATER; 2,4,4'-TRICHLORO-2'-HYDROXYDIPHENYL ETHER; STAPHYLOCOCCUS-AUREUS; CHLORINATED DERIVATIVES; PERCUTANEOUS-ABSORPTION; PSEUDOMONAS-AERUGINOSA AB Triclosan has broad-spectrum anti-microbial activity against most gram-negative and gram-positive bacteria. It is widely used in personal care products, household items, medical devices, and clinical settings. Due to its extensive use, there is potential for humans in all age groups to receive life-time exposures to triclosan, and, indeed, triclosan has been detected in human tissues and the environment. Data gaps exist regarding the chronic dermal toxicity and carcinogenicity of triclosan, which is needed for the risk assessment of triclosan. The US Food and Drug Administration (FDA) nominated triclosan to the National Toxicology Program (NTP) for toxicological evaluations. Currently, the NTP is conducting several dermal toxicological studies to determine the carcinogenic potential of triclosan, evaluate its endocrine and developmental-reproductive effects, and investigate the potential UV-induced dermal formation of chlorinated phenols and dioxins of triclosan. This paper reviews data on the human exposure, environmental fate, efficacy of anti-microbial activity, absorption, distribution, metabolism and elimination, endocrine disrupting effects, and toxicity of triclosan. C1 [Fang, Jia-Long; Stingley, Robin L.; Beland, Frederick A.; Howard, Paul] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Harrouk, Wafa; Lumpkins, Debbie L.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Fang, JL (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM jia-long.fang@fda.hhs.gov FU National Center for Toxicological Research [224-07-0007]; US Food and Drug Administration; National Institute for Environmental Health Sciences/National Toxicology Program FX This research was supported by Interagency Agreement 224-07-0007 between the National Center for Toxicological Research, US Food and Drug Administration and the National Institute for Environmental Health Sciences/National Toxicology Program. NR 111 TC 47 Z9 49 U1 11 U2 128 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1059-0501 J9 J ENVIRON SCI HEAL C JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev. PY 2010 VL 28 IS 3 BP 147 EP 171 AR PII 927101215 DI 10.1080/10590501.2010.504978 PG 25 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 652RD UT WOS:000282026700001 PM 20859822 ER PT J AU Stine, CB Kane, AS Baya, AM AF Stine, C. B. Kane, A. S. Baya, A. M. TI Mycobacteria isolated from Chesapeake Bay fish SO JOURNAL OF FISH DISEASES LA English DT Article DE Atlantic menhaden; Chesapeake Bay; mycobacteria; striped bass; white perch ID BASS MORONE-SAXATILIS; STRIPED BASS; SP-NOV. AB Mycobacteriosis in fish can result in ulcers, emaciation, and in some cases death. Mycobacteria have been previously isolated from a variety of Chesapeake Bay fish species, and the current study was designed to identify potential host specificity and location fidelity of mycobacterial isolates. Mycobacteria were isolated from wild fish of the Chesapeake Bay collected from the Upper Bay, the Choptank River, Herring Bay, the Chicamacomico River, the Pocomoke River and the Potomac River in 2003-2006. Mycobacterial isolates were recovered from striped bass, Morone saxatilis, Atlantic menhaden, Brevoortia tyrannus, white perch, Morone americana, summer flounder, Paralichthys dentatus, spot, Leiostomus xanthurus, largemouth bass, Micropterus salmoides, channel catfish, Ictalurus punctatus, common carp, Cyprinus carpio carpio, spotted seatrout, Cynoscion nebulosus, killifish, Fundulus sp., blueback herring, Alosa aestivalis, American gizzard shad, Dorosoma cepedianum and American silver perch, Bairdiella chrysoura. Twenty-nine well-defined mycobacterial groups resulted from gas chromatography dendrogram clustering of isolates. The majority of groups included more than one host species and more than one site of collection. However, four groups contained only striped bass isolates, three of which were similar to M. shottsii. Therefore, multiple Chesapeake Bay fish species are colonized with multiple mycobacterial isolates, of which few appear to be host or location specific. C1 [Kane, A. S.] Univ Florida, Aquat Pathobiol Lab, Emerging Pathogens Inst, Gainesville, FL 32611 USA. [Stine, C. B.] US FDA, Ctr Vet Med, Laurel, MD USA. [Kane, A. S.] Univ Florida, Coll Publ Hlth & Hlth Profess, Dept Environm & Global Hlth, Gainesville, FL 32611 USA. [Baya, A. M.] Univ Maryland, Dept Vet Med, College Pk, MD 20742 USA. [Baya, A. M.] Maryland Dept Agr, College Pk, MD USA. RP Kane, AS (reprint author), Univ Florida, Aquat Pathobiol Lab, Emerging Pathogens Inst, POB 100009, Gainesville, FL 32611 USA. EM kane@ufl.edu RI Stine, Cynthia/F-1040-2011 FU Chesapeake Bay Office of the National Oceanic and Atmospheric Administration [NA03NMF4570377]; Centers for Disease Control and Prevention [U50/CCU323376]; Maryland Agriculture Experiment Station; Maryland Sea Grant FX For their support of this study, the authors thank Mark Matsche, Larry Pieper, Kevin Rosemary and Cindy Driscoll, Maryland DNR/Sarbanes Cooperative Oxford Laboratory; John Jacobs, NOAA/Sarbanes Cooperative Oxford Laboratory; John Abel, Maryland Department of Agriculture; and Renate Reimchuessel, US FDA Center for Veterinary Medicine. We also thank Maddy Sigrist, James Salierno, Jaime Fernando Gonzalez, Mohammed Ally, Jessica Yen, Eddy Johnson, Andrea Ferrero-Perez and Ruby Paramadhas for their invaluable assistance in field collections and isolate processing. This project was supported by the Chesapeake Bay Office of the National Oceanic and Atmospheric Administration (NA03NMF4570377), the Centers for Disease Control and Prevention (U50/CCU323376), and the Maryland Agriculture Experiment Station. Support for CS was also provided through Program Development Funds from Maryland Sea Grant. NR 21 TC 4 Z9 4 U1 0 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0140-7775 J9 J FISH DIS JI J. Fish Dis. PD JAN PY 2010 VL 33 IS 1 BP 39 EP 46 DI 10.1111/j.1365-2761.2009.01087.x PG 8 WC Fisheries; Marine & Freshwater Biology; Veterinary Sciences SC Fisheries; Marine & Freshwater Biology; Veterinary Sciences GA 531IH UT WOS:000272657700004 PM 19909394 ER PT J AU Contreras, CA Ochoa, TJ Lacher, DW DebRoy, C Navarro, A Talledo, M Donnenberg, MS Ecker, L Gil, AI Lanata, CF Cleary, TG AF Contreras, C. A. Ochoa, T. J. Lacher, D. W. DebRoy, C. Navarro, A. Talledo, M. Donnenberg, M. S. Ecker, L. Gil, A. I. Lanata, C. F. Cleary, T. G. TI Allelic variability of critical virulence genes (eae, bfpA and perA) in typical and atypical enteropathogenic Escherichia coli in Peruvian children SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID INFANTILE DIARRHEA; INTIMIN SUBTYPES; UNITED-KINGDOM; TISSUE TROPISM; STRAINS; EPEC; IDENTIFICATION; ASSOCIATION; MICROARRAY; SEROTYPES AB Enteropathogenic Escherichia coli (EPEC) is a leading cause of infantile diarrhoea in developing countries. The aim of this study was to describe the allelic diversity of critical EPEC virulence genes and their association with clinical characteristics. One hundred and twenty EPEC strains isolated from a cohort diarrhoea study in Peruvian children were characterized for the allele type of eae (intimin), bfpA (bundlin pilin protein of bundle-forming pilus) and perA (plasmid encoded regulator) genes by PCR-RFLP. Atypical EPEC strains (eae+, bfp-) were the most common pathotype in diarrhoea (54/74, 73%) and control samples from children without diarrhoea (40/46, 87%). Overall, there were 13 eae alleles; the most common were beta (34/120, 28%), theta (24/120, 20%), kappa (114/120, 12%) and mu (8/120, 7%). There were five bfpA alleles; the most common were beta 1/7 (10/26), alpha3 (7/26) and beta5 (3/26). There were three perA alleles: beta (8/16), alpha (7/16) and gamma (1/16). The strains belonged to 36 distinct serogroups; 055 was the most frequent. The gamma-intimin allele was more frequently found in diarrhoea episodes of longer duration (> 7 days) than those of shorter duration (3/26, 12% vs 0/48, 0%, P < 0.05). The kappa-intimin allele had the highest clinical severity score in comparison with other alleles (P < 0.05). In Peruvian children, the virulence genes of EPEC strains are highly variable. Further studies are needed to evaluate additional virulence markers to determine whether relationships exist between specific variants and clinical features of disease. C1 [Contreras, C. A.; Ochoa, T. J.; Talledo, M.] Univ Peruana Cayetano Heredia, Inst Med Trop Alexander von Humboldt, Lima, Peru. [Ochoa, T. J.; Cleary, T. G.] Univ Texas Sch Publ Hlth, Houston, TX USA. [Lacher, D. W.] US FDA, Laurel, MD USA. [DebRoy, C.] Penn State Univ, Dept Vet & Biomed Sci, E Coli Reference Ctr, University Pk, PA 16802 USA. [Navarro, A.] Univ Nacl Autonoma Mexico, Fac Med, Dept Salud Publ, Mexico City 04510, DF, Mexico. [Talledo, M.] Univ Antwerp, Dept Med Genet, B-2020 Antwerp, Belgium. [Donnenberg, M. S.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Ecker, L.; Gil, A. I.; Lanata, C. F.] Inst Invest Nutr, Lima, Peru. [Lanata, C. F.] Univ Peruana Ciencias Aplicadas, Lima, Peru. RP Ochoa, TJ (reprint author), Univ Peruana Cayetano Heredia, Inst Med Trop Alexander von Humboldt, Lima, Peru. EM Theresa.J.Ochoa@uth.tmc.edu FU National Institutes of Health [1K01TW007405, R01-HD051716, R01 AI-37606]; C.F.L.'s Institutional Research Funds FX This work was funded by Public Health Service awards 1K01TW007405 (T.J.O.), R01-HD051716 (T.G.C.) and R01 AI-37606 (M.S.D.) from the National Institutes of Health; it was partially funded by C.F.L.'s Institutional Research Funds. The views expressed in this article are those of the author and do not necessarily reflect the official policy or position of the US Government, nor the National Institutes of Health or other funding institutions. There is no conflict of interest for any of the authors. NR 33 TC 16 Z9 16 U1 0 U2 3 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-2615 EI 1473-5644 J9 J MED MICROBIOL JI J. Med. Microbiol. PD JAN PY 2010 VL 59 IS 1 BP 25 EP 31 DI 10.1099/jmm.0.013706-0 PG 7 WC Microbiology SC Microbiology GA 544ME UT WOS:000273660200004 PM 19797469 ER PT J AU Stingley, RL Zou, W Heinze, TM Chen, HZ Cerniglia, CE AF Stingley, Robin L. Zou, Wen Heinze, Thomas M. Chen, Huizhong Cerniglia, Carl E. TI Metabolism of azo dyes by human skin microbiota SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID FMN-DEPENDENT AZOREDUCTASE; ENTEROCOCCUS-FAECALIS; STAPHYLOCOCCUS; REDUCTION; CARCINOGENESIS; MICROCOCCUS; GENERATION; COLORANTS; BACTERIA; ANION AB Reduction of Methyl Red (MR) and Orange II (Or II) by 26 human skin bacterial species was monitored by a rapid spectrophotometric assay. The analysis indicated that skin bacteria, representing the genera Staphylococcus, Corynebacterium, Micrococcus, Dermacoccus and Kocuria, were able to reduce MR by 74-100% in 24 h, with only three species unable to reduce completely the dye in that time. Among the species tested, only Corynebacterium xerosis was unable to reduce Or II to any degree by 24 h, and only Staphylococcus delphini, Staphylococcus sciuri subsp. sciuri and Pseudomonas aeruginosa were able to reduce completely this dye within 24 In. MR reduction started with early-exponential growth in Staphylococcus aureus and Staphylococcus epidermidis, and around late-exponential/early-stationary growth in P. aeruginosa. Reduction of Or II, Ponceau S and Ponceau BS started during late-exponential/early-stationary growth for all three species. Using liquid chromatography/electrospray ionization mass spectrometry analyses, MR metabolites produced by Staph. aureus, Staph. epidermidis and P. aeruginosa were identified as N,N-dimethyl-p-phenylenediamine and 2-aminobenzoic acid. Searches of available genomic and proteomic data revealed that at least four of the staphylococci in this study, Staphylococcus haemolyticus, Staph. epidermidis, Staphylococcus cohnii and Staphylococcus saprophyticus, have hypothetical genes with 77, 76, 75 and 74% sequence identity to azol encoding an azoreductase from Staph. aureus and hypothetical proteins with 82, 80, 72 and 74% identity to Azo1, respectively. In addition, Staphylococcus capitis has a protein with 79% identity to Azo1. Western analysis detected proteins similar to Azo1 in all the staphylococci tested, except Staph, delphini, Staph. sciuri subsp. sciuri and Staphylococcus auricularis. The data presented in this report will be useful in the risk assessment process for evaluation of public exposure to products containing these dyes. C1 [Heinze, Thomas M.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Zou, Wen; Chen, Huizhong; Cerniglia, Carl E.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Stingley, Robin L.] US FDA, Natl Ctr Toxicol Res, Off Sci Coordinat, Jefferson, AR 72079 USA. RP Chen, HZ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM huizhong.chen@fda.hhs.gov FU Office of Women's Health; National Center for Toxicological Research, United States Food and Drug Administration; Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the US Food and Drug Administration FX We thank Drs Mohamed S. Nawaz and Jinhui Feng for critical review of the manuscript, and Dr Mark Hart for strains NTH 125 and NTH 118 and helpful discussions. This study was funded by the Office of Women's Health and the National Center for Toxicological Research, United States Food and Drug Administration, and was supported in part by appointments (R. L. S. and W. Z.) to the Postgraduate Research Program at the National Center for Toxicological Research, administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the US Food and Drug Administration. The views presented in this article do not necessarily reflect those of the US Food and Drug Administration. NR 24 TC 25 Z9 26 U1 3 U2 15 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-2615 J9 J MED MICROBIOL JI J. Med. Microbiol. PD JAN PY 2010 VL 59 IS 1 BP 108 EP 114 DI 10.1099/jmm.0.012617-0 PG 7 WC Microbiology SC Microbiology GA 544ME UT WOS:000273660200016 PM 19729456 ER PT J AU Thompson, K AF Thompson, Karol TI Toxicogenomics and Studies of Genomic Effects of Dietary Components SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Article ID GENE-EXPRESSION PROFILES; RNA REFERENCE SAMPLES; RAT-LIVER; TISSUE; TRANSCRIPTOME; PERFORMANCE; COMPENDIUM; TOXICOLOGY; PLATFORMS; REVEALS C1 [Thompson, Karol] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Thompson, K (reprint author), 10903 New Hampshire Ave,WO64-2036, Silver Spring, MD 20993 USA. EM karol.thompson@fda.hhs.gov NR 26 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2010 VL 3 IS 4-6 BP 251 EP 258 DI 10.1159/000324361 PG 8 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 751LA UT WOS:000289617900012 PM 21474956 ER PT J AU Starlard-Davenport, A Tryndyak, V Kosyk, O Ross, SR Rusyn, I Beland, FA Pogribny, IP AF Starlard-Davenport, Athena Tryndyak, Volodymyr Kosyk, Oksana Ross, Sharon R. Rusyn, Ivan Beland, Frederick A. Pogribny, Igor P. TI Dietary Methyl Deficiency, microRNA Expression and Susceptibility to Liver Carcinogenesis SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Article ID HUMAN HEPATOCELLULAR-CARCINOMA; TUMOR-SUPPRESSOR; CYCLOOXYGENASE-2 EXPRESSION; GENE-EXPRESSION; BREAST-CANCER; IN-VIVO; APOPTOSIS; CELLS; DISEASE; ACTIVATION C1 [Starlard-Davenport, Athena; Tryndyak, Volodymyr; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Kosyk, Oksana; Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC USA. [Ross, Sharon R.] NCI, Canc Prevent Div, Bethesda, MD 20892 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 [P30 ES010126] NR 48 TC 5 Z9 5 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2010 VL 3 IS 4-6 BP 259 EP 266 DI 10.1159/000324362 PG 8 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 751LA UT WOS:000289617900013 PM 21474957 ER PT J AU Yang, YS Shah, RB Faustino, PJ Raw, A Yu, LX Khan, MA AF Yang, Yongsheng Shah, Rakhi B. Faustino, Patrick J. Raw, Andre Yu, Lawrence X. Khan, Mansoor A. TI Thermodynamic Stability Assessment of a Colloidal Iron Drug Product: Sodium Ferric Gluconate SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE colloid; molecular weight determination; stability; thermodynamics; chromatography ID BIOCHEMISTRY AB A high performance gel permeation chromatography (HP-GPC) method was developed, validated and used to determine the molecular weight (1 m of sodium ferric gluconate following various stress conditions. The intra-day accuracy (90-103%), intra-day precision (1.5-2.7%), inter-day accuracy (91-105%), inter-day precision (1.3-3.2%) were within acceptable range stated in FDA guidance. The MW of sodium ferric gluconate remained unchanged after: (1) autoclaving (121 degrees C), (2) moderate thermal stress (30 days at 50 degrees C or 7 days at 70 and 90 degrees C), (3) excipient dilution, (4) basic buffer dilution (pH of 8 and 9), (5) ultracentrifugation, (6) dialysis, and (7) electrolyte dilution. However sodium ferric gluconate showed signs of instability at higher temperatures (>90 degrees C) after 30 days and at pH of 10-11. Sodium ferric gluconate was found to be a lypophilic colloidal solution with an average particle size of 10 nm and a zeta potential of -13 mV. The colloid osmotic pressure was 3.5 mmHg and remained unchanged after moderate thermal stress. Additionally, in-house drug products with similar MW to sodium ferric gluconate were produced by three different synthetic procedures, suggesting that this colloidal iron drug product might be thermodynamically stable. (C) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:142-153, 2010 C1 [Yang, Yongsheng; Shah, Rakhi B.; Faustino, Patrick J.; Khan, Mansoor A.] US FDA, Div Prod Qual Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Raw, Andre; Yu, Lawrence X.] US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Rockville, MD 20855 USA. RP Khan, MA (reprint author), US FDA, Div Prod Qual Res, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM mansoor.khan@fda.hhs.gov NR 16 TC 1 Z9 2 U1 0 U2 9 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD JAN PY 2010 VL 99 IS 1 BP 142 EP 153 DI 10.1002/jps.21806 PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 537YV UT WOS:000273151500010 PM 19492341 ER PT J AU Gao, ZM Thies, A Doub, W AF Gao, Zongming Thies, Andrea Doub, William TI Vibration Effects of Lab Equipment on Dissolution Testing With USP Paddle Method SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE dissolution testing; vibration; accelerometers ID VARIABILITY; APPARATUS AB Environmental vibration induced by laboratory equipment, building construction, or even by the analysts themselves is one of the more complicated factors affecting dissolution testing. It is difficult to control and/or calibrate by mechanical means or performance-based methods. In this study, dissolution apparatus vibration levels were measured in the frequency range from 10 to 270 Hz along all three axes using commercially available, single-axis accelerometers. The vibration distribution on the dissolution vessel plate was mapped, and acceleration was subsequently measured during dissolution runs involving NCDA#2 (10 mg prednisone) tablets using the paddle method. Several types of laboratory equipment were used to induce vibration during dissolution testing and vibration levels along the X-, Y-, and Z-axes of the vessel plate were measured in an attempt to establish possible correlation with dissolution results. In the frequency range studied, root mean square (RMS) acceleration values above 0.01 g, in either vertical or horizontal direction, typically affected dissolution results. (C) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:403-412, 2010 C1 [Gao, Zongming; Thies, Andrea; Doub, William] US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Gao, ZM (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, St Louis, MO 63101 USA. EM zongming.gao@fda.hhs.gov NR 18 TC 2 Z9 2 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD JAN PY 2010 VL 99 IS 1 BP 403 EP 412 DI 10.1002/jps.21847 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 537YV UT WOS:000273151500034 PM 19544371 ER PT J AU Braddy, AC Jackson, AJ AF Braddy, April C. Jackson, Andre J. TI Role of Metabolites for Drugs That Undergo Nonlinear First-Pass Effect: Impact on Bioequivalency Assessment Using Single-Dose Simulations SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE absorption; bioequivalence; first-pass metabolism; nonlinear pharmacokinetics; simulations ID HIGHLY VARIABLE DRUGS; LINEAR PHARMACOKINETICS; STEADY-STATE AB We investigated the effects of dose and intrasubject variability (ISV) on bioequivalence (BE) of a parent drug with a single metabolite formed by nonlinear first-pass. A BE simulation was done using a four-compartment model at doses of 17.5, 35.0, and 70.0 mg. ISV was set at either 10% or 20% for clearance and either 20% or 50% for the absorption rate constant, K(a). The ratio of K(atest)/K(areference) was fixed at 1.00 while fraction available ratios, F(test)/F(reference), were varied from 1.00 to 1.25. Results showed the probability of passing the 90% confidence interval (CI) BE requirement for AUC(I), area-under-the-concentration curve to time infinity, and C(max), concentration maximum, were greater for the metabolite than the parent at all F(test)/F(reference) ratios. For the parent, the probability of meeting BE criteria for AUC(I) and C(max) declined from 100% to 60% at the 70 mg dose as the ISV for K(a) increased from 20% to 50% with an increased Ftest/Freference ratio. For the metabolite, the probability of meeting BE criteria was above 80% for all doses and ISV values and F(test)/F(reference) ratios less than 1.15. Results show that the parent, reflected absorption, is more informative for determining BE than the metabolite. Clinical data gave a similar result. (C) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:515-523, 2010 C1 [Jackson, Andre J.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Braddy, April C.] US FDA, Div Bioequivalence, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Jackson, AJ (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM andre.jackson@fda.hhs.gov NR 16 TC 7 Z9 7 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD JAN PY 2010 VL 99 IS 1 BP 515 EP 523 DI 10.1002/jps.21838 PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 537YV UT WOS:000273151500043 PM 19670465 ER PT J AU Nell, DM Myers, MR AF Nell, Diane M. Myers, Matthew R. TI Thermal effects generated by high-intensity focused ultrasound beams at normal incidence to a bone surface SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID TRANSIENT TEMPERATURE RISE; BONE/SOFT-TISSUE INTERFACE; DIAGNOSTIC ULTRASOUND; MAMMALIAN-TISSUES; COMPILATION; ABSORPTION; METASTASES; ELEVATION; THERAPY; MODELS AB Experiments and computations were performed to study factors affecting thermal safety when high-intensity focused ultrasound (HIFU) beams are normally incident (i.e., beam axis normal to the interface) upon a bone/soft-tissue interface. In particular, the temperature rise and thermal dose were determined as a function of separation between the beam focus and the interface. Under conditions representative of clinical HIFU procedures, it was found that the thermal dose at the bone surface can exceed the threshold for necrosis even when the beam focus is more than 4 cm from the bone. Experiments showed that reflection of the HIFU beam from the bone back into the transducer introduced temperature fluctuations of as much as +/- 15% and may be an important consideration for safety analyses at sufficiently high acoustic power. The applicability of linear propagation models in predicting thermal dose near the interface was also addressed. Linear models, while underpredicting thermal dose at the focus, provided a conservative (slight overprediction) estimate of thermal dose at the bone surface. Finally, temperature rise due to absorption of shear waves generated by the HIFU beam in the bone was computed. Modeling shear-wave propagation in the thermal analysis showed that the predicted temperature rise off axis was as much as 30% higher when absorption of shear waves is included, indicating that enhanced heating due to shear-wave absorption is potentially important, even for normally incident HIFU beams. [DOI: 10.1121/1.3257547] C1 [Nell, Diane M.; Myers, Matthew R.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Nell, DM (reprint author), US FDA, Ctr Devices & Radiol Hlth, Bldg 62,10902 New Hampshire Ave, Silver Spring, MD 20993 USA. NR 38 TC 19 Z9 21 U1 0 U2 10 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JAN PY 2010 VL 127 IS 1 BP 549 EP 559 DI 10.1121/1.3257547 PG 11 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 540UF UT WOS:000273364700061 PM 20059000 ER PT J AU Mei, N Guo, L Fu, PP Fuscoe, JC Luan, Y Chen, T AF Mei, Nan Guo, Lei Fu, Peter P. Fuscoe, James C. Luan, Yang Chen, Tao TI Metabolism, Genotoxicity, annd Carcinogenicity of Comfrey SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART B-CRITICAL REVIEWS LA English DT Review ID DNA ADDUCT FORMATION; HEPATOTOXIC PYRROLIZIDINE ALKALOIDS; VENO-OCCLUSIVE DISEASE; BIG BLUE RATS; SYMPHYTUM-OFFICINALE; DIETARY-SUPPLEMENTS; N-OXIDES; VENOOCCLUSIVE DISEASE; MASS-SPECTROMETRY; HERB TEA AB Comfrey has been consumed by humans as a vegetable and a tea and used as an herbal medicine for more than 2000 years. Comfrey, however, produces hepatotoxicity in livestock and humans and carcinogenicity in experimental animals. Comfrey contains as many as 14 pyrrolizidine alkaloids (PA), including 7-acetylintermedine, 7-acetyllycopsamine, echimidine, intermedine, lasiocarpine, lycopsamine, myoscorpine, symlandine, symphytine, and symviridine. The mechanisms underlying comfrey-induced genotoxicity and carcinogenicity are still not fully understood. The available evidence suggests that the active metabolites of PA in comfrey interact with DNA in liver endothelial cells and hepatocytes, resulting in DNA damage, mutation induction, and cancer development. Genotoxicities attributed to comfrey and riddelliine (a representative genotoxic PA and a proven rodent mutagen and carcinogen) are discussed in this review. Both of these compounds induced similar profiles of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts and similar mutation spectra. Further, the two agents share common mechanisms of drug metabolism and carcinogenesis. Overall, comfrey is mutagenic in liver, and PA contained in comfrey appear to be responsible for comfrey-induced toxicity and tumor induction. C1 [Mei, Nan; Chen, Tao] US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Guo, Lei; Fu, Peter P.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Fuscoe, James C.] US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Luan, Yang] Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, Shanghai, Peoples R China. RP Mei, N (reprint author), US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM nan.mei@fda.hhs.gov RI Guo, Lei/E-9232-2011; mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 NR 88 TC 17 Z9 18 U1 1 U2 29 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1093-7404 J9 J TOXICOL ENV HEAL B JI J. Toxicol. Env. Health-Pt b-Crit. Rev. PY 2010 VL 13 IS 7-8 BP 509 EP 526 AR PII 931351813 DI 10.1080/10937404.2010.509013 PG 18 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 696AK UT WOS:000285414100001 PM 21170807 ER PT J AU Mohammed, HP Ramos, MM Rivera, A Johansson, M Munoz-Jordan, JL Sun, W Tomashek, KM AF Mohammed, Hamish P. Ramos, Mary M. Rivera, Aidsa Johansson, Michael Munoz-Jordan, Jorge L. Sun, Wellington Tomashek, Kay M. TI Travel-Associated Dengue Infections in the United States, 1996 to 2005 SO JOURNAL OF TRAVEL MEDICINE LA English DT Article ID VIRUS IMMUNOGLOBULIN-M; TEXAS-MEXICO BORDER; HEMORRHAGIC-FEVER; RISK-FACTORS; CLINICAL-FEATURES; EPIDEMIC DENGUE; PUBLIC-HEALTH; PUERTO-RICO; SURVEILLANCE; ANTIBODIES AB Methods. Data from the US Centers for Disease Control and Prevention's laboratory-based Passive Dengue Surveillance System (PDSS) were used to describe trends in travel-associated dengue reported from January 1, 1996 to December 31, 2005. The PDSS relies on provider-initiated requests for diagnostic testing of serum samples via state health departments. A case of travel-associated dengue was defined as a laboratory-positive dengue infection in a resident of the 50 US states and the District of Columbia who had been in a dengue-endemic area within 14 days before symptom onset. Dengue infection was confirmed by serologic and virologic techniques. Results. One thousand one hundred and ninety-six suspected travel-associated dengue cases were reported-334 (28%) were laboratory-positive, 597 (50%) were laboratory-negative, and 265 (22%) were laboratory-indeterminate. The incidence of laboratory-positive cases varied from 1996 to 2005, but had an overall increase with no significant trend (53.5 to 121.3 per 108 US travelers, p = 0.36). The most commonly visited regions were the Caribbean, Mexico and Central America, and Asia. The median age of laboratory-positive cases was 37 years (range: < 1 to 75 y) and 166 (50%) were male. Of the 334 laboratory-positive cases, 41 (12%) were hospitalized, and 2 (1%) died. Conclusions. Residents of the US traveling to dengue-endemic regions are at risk of dengue infection and need to be instructed on appropriate prevention measures prior to travel. Especially in light of the potential transmissibility of dengue virus via blood transfusion, consistent reporting of travel-associated dengue infections is essential. C1 [Mohammed, Hamish P.] Ross Univ Sch Vet Med, Dept Pathobiol, Basseterre, St Kitts, W Ind Assoc St. [Mohammed, Hamish P.] Ross Univ Sch Vet Med, Dept Pathobiol, Nevis, W Ind Assoc St. [Mohammed, Hamish P.; Rivera, Aidsa; Johansson, Michael; Munoz-Jordan, Jorge L.; Tomashek, Kay M.] Ctr Dis Control & Prevent, Dengue Branch, Div Vector Borne Infect Dis, San Juan, PR USA. [Ramos, Mary M.] Univ New Mexico, Dept Pediat, Albuquerque, NM 87131 USA. [Sun, Wellington] US FDA, Div Vaccine & Related Prod Applicat, Kensington, MD USA. RP Mohammed, HP (reprint author), Ross Univ Sch Vet Med, Dept Pathobiol, POB 334, Basseterre, St Kitts, W Ind Assoc St. EM hamohammed@rossvet.edu.kn NR 39 TC 32 Z9 36 U1 0 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1195-1982 J9 J TRAVEL MED JI J. Travel Med. PD JAN-FEB PY 2010 VL 17 IS 1 BP 8 EP 14 DI 10.1111/j.1708-8305.2009.00374.x PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 540EV UT WOS:000273314900002 PM 20074096 ER PT J AU Yang, MH Sun, S Kostov, Y Rasooly, A AF Yang, Minghui Sun, Steven Kostov, Yordan Rasooly, Avraham TI Lab-on-a-chip for carbon nanotubes based immunoassay detection of Staphylococcal Enterotoxin B (SEB) SO LAB ON A CHIP LA English DT Article ID FIELD-EFFECT TRANSISTORS; ENHANCED CHEMILUMINESCENCE IMMUNOASSAY; ASSAY KIT TECRA; ELECTROCHEMICAL IMMUNOSENSOR; FOOD; DEVICES; TOXIN; ADSORPTION; NETWORKS; RICIN AB We describe a new eight channel Lab-On-a-Chip (LOC) for a Carbon Nanotube (CNT) based immunoassay with optical detection of Staphylococcal Enterotoxin B (SEB) for food safety applications. In this work, we combined four biosensing elements: (1) CNT technology for primary antibody immobilization, (2) Enhanced Chemiluminescence (ECL) for light signal generation, (3) a cooled charge-coupled device (CCD) for detection and (4) polymer lamination technology for developing a point of care immunological assay for SEB detection. Our concept for developing versatile LOCs, which can be used for many different applications, is to use a modular design with interchangeable recognition elements (e. g. various antibodies) to determine the specificity. Polymer lamination technology was used for the fabrication of a six layer, syringe operated LOC capable of analyzing eight samples simultaneously. An anti-SEB antibody-nanotube mixture was immobilized onto a polycarbonate strip, to serve as an interchangeable ligand surface that was then bonded onto the LOC. SEB samples are loaded into the device and detected by an ELISA assay using Horse Radish Peroxidase (HRP) conjugated anti-SEB IgG as a secondary antibody and ECL, with detection by a previously described portable cooled CCD detector. Eight samples of SEB in buffer or soy milk were assayed simultaneously with a limit of detection of 0.1 ng mL(-1). CNT immobilization of the antibody increased the sensitivity of detection six fold. Use of a simple interchangeable immunological surface allows this LOC to be adapted to any immunoassay by simply replacing the ligand surface. A syringe was used to move fluids for this assay so no power is needed to operate the device. Our versatile portable point-of-care CCD detector combined with the LOC immunoassay method described here can be used to reduce the exposure of users to toxins and other biohazards when working outside the lab, as well as to simplify and increase sensitivity for many other types of immunological diagnostics and detection assays. C1 [Sun, Steven; Rasooly, Avraham] US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. [Yang, Minghui; Sun, Steven; Kostov, Yordan] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Rasooly, Avraham] NCI, Bethesda, MD 20892 USA. [Yang, Minghui] Univ Jinan, Sch Chem & Chem Engn, Jinan 250022, Peoples R China. RP Rasooly, A (reprint author), US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. EM rasoolya@mail.nih.gov RI Zhou, Feng/E-9510-2011; OI zaraat, javad/0000-0001-5341-7481 NR 50 TC 42 Z9 43 U1 4 U2 30 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2010 VL 10 IS 8 BP 1011 EP 1017 DI 10.1039/b923996k PG 7 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 577JL UT WOS:000276218900007 PM 20358108 ER PT J AU Sun, S Yang, MH Kostov, Y Rasooly, A AF Sun, Steven Yang, Minghui Kostov, Yordan Rasooly, Avraham TI ELISA-LOC: lab-on-a-chip for enzyme-linked immunodetection SO LAB ON A CHIP LA English DT Article ID STAPHYLOCOCCAL-ENTEROTOXIN-B; ENHANCED CHEMILUMINESCENCE IMMUNOASSAY; CARBON NANOTUBES; ARRAY BIOSENSOR; MICROFLUIDIC DEVICE; FOODS; ANTIBODIES; ASSAY; FLOW; IMMUNOSENSOR AB A miniature 96 sample ELISA-lab-on-a-chip (ELISA-LOC) was designed, fabricated, and tested for immunological detection of Staphylococcal Enterotoxin B (SEB). The chip integrates a simple microfluidics system into a miniature ninety-six sample plate, allowing the user to carry out an immunological assay without a laboratory. Assay reagents are delivered into the assay plate without the need for separate devices commonly used in immunoassays. The ELISA-LOC was constructed using Laminated Object Manufacturing (LOM) technology to assemble six layers with an acrylic (poly(methyl methacrylate) (PMMA)) core and five polycarbonate layers micromachined by a CO(2) laser. The ELISA-LOC has three main functional elements: reagent loading fluidics, assay and detection wells, and reagent removal fluidics, a simple "surface tension'' valve used to control the flow. To enhance assay sensitivity and to perform the assay without a lab, ELISA-LOC detection combines several biosensing elements: (1) carbon nanotube (CNT) technology to enhance primary antibody immobilization, (2) sensitive ECL (electrochemiluminescence) detection, and (3) a charge-coupled device (CCD) detector for measuring the light signal generated by ECL. Using a sandwich ELISA assay, the system detected SEB at concentrations as low as 0.1 ng n ml(-1), which is similar to the reported sensitivity of conventional ELISA. The fluidics system can be operated by a syringe and does not require power for operation. This simple point-of-care (POC) system is useful for carrying out various immunological assays and other complex medical assays without a laboratory. C1 [Sun, Steven; Rasooly, Avraham] US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. [Sun, Steven; Yang, Minghui; Kostov, Yordan] Univ Maryland Baltimore Cty, Baltimore, MD 21250 USA. [Rasooly, Avraham] NCI, Bethesda, MD 20892 USA. [Yang, Minghui] Univ Jinan, Sch Chem & Chem Engn, Jinan 250022, Peoples R China. RP Rasooly, A (reprint author), US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. EM rasoolya@mail.nih.gov OI zaraat, javad/0000-0001-5341-7481 NR 45 TC 56 Z9 56 U1 4 U2 85 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2010 VL 10 IS 16 BP 2093 EP 2100 DI 10.1039/c003994b PG 8 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 632BK UT WOS:000280394800011 PM 20544092 ER PT J AU Yang, MH Sun, S Bruck, HA Kostov, Y Rasooly, A AF Yang, Minghui Sun, Steven Bruck, Hugh Alan Kostov, Yordan Rasooly, Avraham TI Lab-on-a-chip for label free biological semiconductor analysis of Staphylococcal Enterotoxin B SO LAB ON A CHIP LA English DT Article ID ATOPIC-DERMATITIS; CARBON NANOTUBES; ELECTRICAL PERCOLATION; RHEUMATOID-ARTHRITIS; REAL-TIME; FOOD; SEB; SUPERANTIGENS; MICROFLUIDICS; PREVALENCE AB We describe a new lab-on-a-chip (LOC) which utilizes a biological semiconductor (BSC) transducer for label free analysis of Staphylococcal Enterotoxin B (SEB) (or other biological interactions) directly and electronically. BSCs are new transducers based on electrical percolation through a multi-layer carbon nanotube-antibody network. In BSCs the passage of current through the conductive network is dependent upon the continuity of the network. Molecular interactions within the network, such as binding of antigens to the antibodies, disrupt the network continuity causing increased resistance of the network. For the fabrication of a BSC based detector, we combined several elements: (1) BSC transducers for direct detection, (2) LOC for flow through continuous measurements, (3) a digital multimeter with computer connection for data logging, (4) pumps and valves for fluid delivery, and (5) a computer for fluid delivery control and data analysis. Polymer lamination technology was used for the fabrication of a four layer LOC for BSC detection, the BSC on the chip is fabricated by immobilizing pre-functionalized single-walled carbon nanotubes (SWNTs)-antibody complex directly on the PMMA surface of the LOC. SEB samples were loaded into the device using a peristaltic pump and the change in resistance resulting from antibody-antigen interactions was continuously monitored and recorded. Binding of SEB rapidly increases the BSC electrical resistance. SEB in buffer was assayed with limit of detection (LOD) of 5 ng mL(-1) at a signal to baseline (S/B) ratio of 2. A secondary antibody was used to verify the presence of the SEB captured on the surface of the BSC and for signal amplification. The new LOC system permits rapid detection and semi-automated operation of BSCs. Such an approach may enable the development of multiple biological elements "Biological Central Processing Units (CPUs)'' for parallel processing and sorting out automatically information on multiple analytes simultaneously. Such an approach has potential use for point-of-care medical and environmental testing. C1 [Sun, Steven; Rasooly, Avraham] US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. [Yang, Minghui; Sun, Steven; Kostov, Yordan] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Bruck, Hugh Alan] UMCP, College Pk, MD 20742 USA. [Rasooly, Avraham] NCI, Bethesda, MD 20892 USA. [Yang, Minghui] Univ Jinan, Sch Chem & Chem Engn, Jinan 250022, Peoples R China. [Rasooly, Avraham] NCI, NIH, Rockville, MD 20852 USA. RP Rasooly, A (reprint author), US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. EM rasoolya@mail.nih.gov OI zaraat, javad/0000-0001-5341-7481 NR 31 TC 10 Z9 10 U1 2 U2 13 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2010 VL 10 IS 19 BP 2534 EP 2540 DI 10.1039/c005141a PG 7 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 647JN UT WOS:000281614900007 PM 20668726 ER PT S AU Anders, J Moges, H Wu, XJ Ilev, I Waynant, R Longo, L AF Anders, Juanita Moges, Helina Wu, Xingjia Ilev, Ilko Waynant, Ronald Longo, Leonardo BE Longo, L TI The Combination of Light and Stem Cell Therapies: A Novel Approach in Regenerative Medicine SO LASER FLORENCE 2009: A GALLERY THROUGH THE LASER MEDICINE WORLD SE AIP Conference Proceedings LA English DT Proceedings Paper CT 23rd International Congress on Laser Medicine/IALMS Courses/3rd Biennial Congress of the International-Photo-Therapy-Association CY NOV 06-07, 2009 CL Florence, ITALY SP Int Photo Therapy Assoc, Int Acad Laser Med & Surg, Int Soc Laser Surg & Med (ISLSM), World Federation Laser Surg & Med Soc, Inst Laser Med Florence, World Federat Laser Dent (WFLD), Soc Italian Laser Odontostomatol, New European Surg Acad (NESA), President Italian Republ, Univ Res Italian Office, Florence Med Assoc, Tuscany Region DE Adult Stem Cells; Embryonic Stem Cells; Light Therapy; Progenitors; Proliferation; Differentiation; Transplantation ID INTENSITY LASER IRRADIATION; IN-VITRO; PROLIFERATION; PROMOTES; DIFFERENTIATION; SURVIVAL; CULTURE; LEVEL; ATP AB Light therapy commonly referred to as low level laser therapy can alter cellular functions and clinical conditions. Some of the commonly reported in vitro and in vivo effects of light therapy include cellular proliferation, alterations in the inflammatory response to injury, and increases in mitochondrial respiration and adenosine triphosphate synthesis. Based on the known effects of light on cells and tissues in general and on reports in the last 5 years on the interaction of light with stem cells, evidence is mounting indicating that light therapy could greatly benefit stem cell regenerative medicine. Experiments on a variety of harvested adult stem cells demonstrate that light therapy enhances differentiation and proliferation of the cells and alters the expression of growth factors in a number of different types of adult stem cells and progenitors in vitro. It also has the potential to attenuate cytotoxic effects of drugs used to purge harvested autologous stem cells and to increase survival of transplanted cells. C1 [Anders, Juanita; Moges, Helina; Wu, Xingjia] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. [Ilev, Ilko; Waynant, Ronald] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Longo, Leonardo] Univ Siegen, Inst Laser Med, San Marino, CA 47890 USA. RP Anders, J (reprint author), Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. NR 30 TC 3 Z9 3 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0770-1 J9 AIP CONF PROC PY 2010 VL 1226 BP 3 EP + DI 10.1063/1.3453785 PG 3 WC Optics; Physics, Applied SC Optics; Physics GA BRL14 UT WOS:000283001000001 ER PT J AU Tata, D Abliz, E Waynant, R Collins, J Friedberg, J Kumar, A Bell, H AF Tata, Darrell Abliz, Erkinay Waynant, Ronald Collins, Joshua Friedberg, Joseph Kumar, Ajith Bell, Howard TI NOVEL APPLICATION OF RARE-EARTH PARTICLES IN ACTIVATING PHOTOFRIN II THROUGH X-RAY INDUCED VISIBLE LUMINESCENCE: AN IN VITRO STUDY SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 29th Annual Conference of the American-Society-for-Laser-Medicine and Surgery CY APR 16-18, 2010 CL Phoenix, AZ SP Amer Soc Laser Med & Surg C1 George Washington Univ, Washington, DC USA. US FDA, Silver Spring, MD USA. Univ Penn, Philadelphia, PA 19104 USA. Sunstone Biosci Inc, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2010 SU 22 BP 4 EP 4 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 578LL UT WOS:000276295000011 ER PT S AU Chen, WJ Gallas, BD AF Chen, Weijie Gallas, Brandon D. BE Karssemeijer, N Summers, RM TI Training variability in the evaluation of automated classifiers SO MEDICAL IMAGING 2010: COMPUTER - AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging 2010 - Computer-Aided Diagnosis CY FEB 16-18, 2010 CL San Diego, CA SP SPIE, Medtronic, Inc, Aeroflex, Inc, Tungsten Heavy Powder, Inc DE training variability; classification; AUC; bootstrap; resampling ID STATISTICAL PATTERN-RECOGNITION; NONPARAMETRIC APPROACH; ROC ANALYSIS; BOOTSTRAP; VARIANCE; AREA AB The evaluation of automated classifiers in computer-aided diagnosis of medical images often involves a training dataset for classifier design and a test dataset for performance estimation in terms of, e.g., area under the receiver operating characteristic (ROC) curve, or AUC. The traditional approach to assess the uncertainty of the estimated AUC only considers the finite testing set as the source of variability. However, a finite training set is also a random sample and the AUC varies with varying training sets. We categorize the assessement of classifiers into three levels and provide analytical expressions for the variance of the estimated AUC at each level: (1) training treated as a fixed effect, the estimated performance generalizable only to the population of testing sets; (2) training treated as a random effect, the estimated performance generalizable to both the population of training sets and the population of testing sets; (3) training treated as a random effect, performance averaged over training sets generalizable to both the population of training sets and the population of testing sets. The two multi-reader multi-case (MRMC) ROC paradigm in reader studies. We show the one-to-one analogy between the automated classifiers and human readers at these three levels as well as the practical difference in estimating their performance, especially regarding variance. C1 [Chen, Weijie; Gallas, Brandon D.] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, CDRH, Silver Spring, MD 20993 USA. RP Chen, WJ (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, CDRH, Silver Spring, MD 20993 USA. EM weijie.chen@fda.hhs.gov NR 20 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 978-0-8194-8025-5 J9 PROC SPIE PY 2010 VL 7624 AR 762404 DI 10.1117/12.844605 PG 9 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSK55 UT WOS:000284752400002 ER PT S AU Gavrielides, MA Kinnard, LM Myers, KJ Zeng, RP Petrick, N AF Gavrielides, Marios A. Kinnard, Lisa M. Myers, Kyle J. Zeng, Rongping Petrick, Nicholas BE Karssemeijer, N Summers, RM TI FDA phantom CT database: a resource for the assessment of lung nodule size estimation methodologies and software development SO MEDICAL IMAGING 2010: COMPUTER - AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging 2010 - Computer-Aided Diagnosis CY FEB 16-18, 2010 CL San Diego, CA SP SPIE, Medtronic, Inc, Aeroflex, Inc, Tungsten Heavy Powder, Inc DE computed tomography; phantom studies; lung nodules; database; public resource; measurement error; volumetric CT; CT scans ID SOLID TUMORS AB As part of a more general effort to probe the interrelated factors impacting the accuracy and precision of lung nodule size estimation, we have been conducting phantom CT studies with an anthropomorphic thoracic phantom containing a vasculature insert on which synthetic nodules were inserted or attached. The utilization of synthetic nodules with known truth regarding size and location allows for bias and variance analysis, enabled by the acquisition of repeat CT scans. Using a factorial approach to probe imaging parameters (acquisition and reconstruction) and nodule characteristics (size, density, shape, location), ten repeat scans have been collected for each protocol and nodule layout. The resulting database of CT scans is incrementally becoming available to the public via the National Biomedical Imaging Archive to facilitate the assessment of lung nodule size estimation methodologies and the development of image analysis software among other possible applications. This manuscript describes the phantom CT scan database and associated information including image acquisition and reconstruction protocols, nodule layouts and nodule truth. C1 [Gavrielides, Marios A.; Kinnard, Lisa M.; Myers, Kyle J.; Zeng, Rongping; Petrick, Nicholas] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Gavrielides, MA (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. EM marios.gavrielides@fda.hhs.gov NR 8 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8025-5 J9 PROC SPIE PY 2010 VL 7624 AR 762417 DI 10.1117/12.844329 PG 8 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSK55 UT WOS:000284752400040 ER PT S AU Zeng, RP Petrick, N Gavrielides, MA Myers, KJ AF Zeng, Rongping Petrick, Nicholas Gavrielides, Marios A. Myers, Kyle J. BE Karssemeijer, N Summers, RM TI Approximations of noise structures in helical multi-detector CT scans: application to lung nodule volume estimation SO MEDICAL IMAGING 2010: COMPUTER - AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging 2010 - Computer-Aided Diagnosis CY FEB 16-18, 2010 CL San Diego, CA SP SPIE, Medtronic, Inc, Aeroflex, Inc, Tungsten Heavy Powder, Inc DE Multi-detector CT; noise covariance; noise power spectrum; nodule volume; prewhitening matched filter; estimation ID MODERN DIAGNOSTIC MDCT; COMPUTED-TOMOGRAPHY; POWER SPECTRUM AB We have previously presented a match filtered (MF) approach for estimating lung nodule size from helical multi-detector CT (MDCT) images [1], in which we minimized the sum of squared differences between the simulated CT templates and the actual nodule CT images. A previous study showed the potential of this approach for reducing the bias and variance in nodule size estimation. However, minimizing SSD is not statistically optimal because the noise in 3D helical CT images is correlated. The goal of this work is to investigate the noise properties and explore several approximate descriptions of the three-dimensional (3D) noise covariance for more accurate estimates. The approximations include: variance only, noise power spectrum (NPS), axial correlation, two-dimensional (2D) in-plane correlation and fully 3D correlation. We examine the effectiveness of these second-order noise approximations by applying them to our volume estimation approach with a simulation study. Our simulations show that: the variance-based pre-whitening and axial pre-whitening perform very similar to the non-prewhitening case, with accuracy (measured in RMSE) differences within 1%; the NPS based pre-whitening performs slightly better, with a 4% decrease in RMSE; the in-plane pre-whitening and 3D fully pre-whitening perform best, with about a 10% decrease in RMSE over the non-prewhitening case. The simulation results suggest that the NPS, 2D in-plane and fully 3D prewhitening can be beneficial for lung nodule size estimation, albeit with greater computational costs in determining these noise characterizations. C1 [Zeng, Rongping; Petrick, Nicholas; Gavrielides, Marios A.; Myers, Kyle J.] US FDA, Ctr Devices & Radiol Heath, Off Sci & Engn Labs, Div Imaging & Appl Math, Silver Spring, MD 20993 USA. RP Zeng, RP (reprint author), US FDA, Ctr Devices & Radiol Heath, Off Sci & Engn Labs, Div Imaging & Appl Math, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8025-5 J9 PROC SPIE PY 2010 VL 7624 AR 762415 DI 10.1117/12.844216 PG 10 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSK55 UT WOS:000284752400038 ER PT S AU Cheng, WC Badano, A AF Cheng, Wei-Chung Badano, Aldo BE Manning, DJ Abbey, CK TI A Gaze-contingent High-dynamic Range Display for Medical Imaging Applications SO MEDICAL IMAGING 2010: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND TECHNOLOGY ASSESSMENT SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Image Perception, Observer Performance, and Technology Assessment CY FEB 17-18, 2010 CL San Diego, CA SP SPIE, Medtronic Inc, Aeroflex Inc, OpenXi, Tungsten Heavy Powder Inc DE High-dynamic range display; Gaze-contingent display; Eye movement AB The grayscale resolution of current liquid crystal display technology limits its applications in medical imaging with wide dynamic range and dense grayscales are required. We propose an approach that dynamically processes the display image such that the luminance and contrast of the gazed area is optimized. A gaze-contingent interactive display system based on an 8-bit LCD and an eye-tracker was implemented to emulate the proposed concept for a high-dynamic range display. C1 [Cheng, Wei-Chung; Badano, Aldo] US FDA, Ctr Device & Radiol Hlth, Silver Spring, MD USA. RP Cheng, WC (reprint author), US FDA, Ctr Device & Radiol Hlth, Silver Spring, MD USA. OI badano, aldo/0000-0003-3712-6670 NR 8 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 978-0-8194-8028-6 J9 PROC SPIE PY 2010 VL 7627 AR 76270A DI 10.1117/12.845782 PG 6 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSO00 UT WOS:000285046700009 ER PT S AU Abboud, S Badal, A Stern, SH Kyprianou, IS AF Abboud, Samir Badal, Andreu Stern, Stanley H. Kyprianou, Iacovos S. BE Samei, E Pelc, NJ TI Designing a phantom for dose evaluation in multi-slice CT SO MEDICAL IMAGING 2010: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE-The International Society for Optical Engineering LA English DT Proceedings Paper CT Conference on Medical Imaging - Physics of Medical Imaging CY FEB 15-18, 2010 CL San Diego, CA SP SPIE ID MONTE-CARLO; DOSIMETRY; CTDI100 AB Accurately representing radiation dose delivered in MSCT is becoming a concern as the maximum beam width of some modern CT scanners tends to become wider than the 100 mm charge-collection length of the pencil ionization chamber generally used in CT dosimetry. We investigate two alternative methods of dose evaluation in CT scanners. We investigate two alternative approaches for better characterization of CT dose than conventional evaluation of CTDI(100). First, we simulate dose profiles and energy deposition in phantoms longer than the typically used 14-15 cm length right-circular cylinders. Second we explore the accuracy and practicality of applying mathematical convolution to a scatter kernel in order to generate dose profiles. A basic requirement for any newly designed phantom is that it be able to capture approximately the same dose as would an infinitely long cylinder, but yet be of a size and weight that a person could easily carry and position. Using the PENELOPE Monte Carlo package, we simulated dose profiles in cylindrical polymethyl methacrylate (PMMA) phantoms of 10, 16, 20, 24 and 32 cm diameter and 15, 30 and 300 cm length. Beam widths were varied from 1 cm to 60 cm. Lengths necessary to include within the dose integrals values associated with the scatter tails as well as with the primary radiation of the profile were then calculated as the full width at five percent of maximum dose. The resulting lengths suggest that to accommodate wide beam widths, phantoms longer than those currently used are necessary. The results also suggest that using a longer phantom is a relatively more accurate approach, while using mathematical convolution is simpler and more practical to implement than using the long phantoms designed according to direct Monte Carlo simulations. C1 [Abboud, Samir; Badal, Andreu; Stern, Stanley H.; Kyprianou, Iacovos S.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Abboud, S (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,W062-3109, Silver Spring, MD 20993 USA. EM samir.abboud@fda.hhs.gov NR 14 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8023-1 J9 P SOC PHOTO-OPT INS PY 2010 VL 7622 AR 762232 DI 10.1117/12.844355 PG 9 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSO01 UT WOS:000285047200105 ER PT S AU Badal, A Kyprianou, I Sharma, D Badano, A AF Badal, Andreu Kyprianou, Iacovos Sharma, Diksha Badano, Aldo BE Samei, E Pelc, NJ TI Fast cardiac CT simulation using a Graphics Processing Unit-accelerated Monte Carlo code SO MEDICAL IMAGING 2010: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE-The International Society for Optical Engineering LA English DT Proceedings Paper CT Conference on Medical Imaging - Physics of Medical Imaging CY FEB 15-18, 2010 CL San Diego, CA SP SPIE DE CT simulation; Monte Carlo; PENELOPE; GPU; CUDA ID PHOTON TRANSPORT; ALGORITHM; PENELOPE AB The simulation of imaging systems using Monte Carlo x-ray transport codes is a computationally intensive task. Typically, many days of computation are required to simulate a radiographic projection image and, as a consequence, the simulation of the hundreds of projections needed to perform a tomographic reconstruction may require an unaffordable amount of computing time. To speed up x-ray transport simulations, a MC code that can be executed in a graphics processing unit (GPU) was developed using the CUDA (TM) programming model, an extension to the C language for the execution of general-purpose computations on NVIDIA's GPUs. The code implements the accurate photon interaction models from PENELOPE and takes full advantage of the GPU massively parallel architecture by simulating hundreds of particle tracks simultaneously. In this work we describe a new version of this code adapted to the simulation of computed tomography (CT) scans, and allowing the execution in parallel in multiple GPUs. An example simulation of a cardiac CT using a detailed voxelized anthropomorphic phantom is presented. A comparison of the simulation computational performance in one or multiple GPUs and in a CPU (Central Processing Unit), and a benchmark with a standard PENELOPE code, are provided. This study shows that low-cost GPU clusters are a good alternative to CPU clusters for Monte Carlo simulation of x-ray transport. C1 [Badal, Andreu; Kyprianou, Iacovos; Sharma, Diksha; Badano, Aldo] US FDA, Div Imaging & Appl Math, OSEL, CDRH, Silver Spring, MD USA. RP Badal, A (reprint author), US FDA, Div Imaging & Appl Math, OSEL, CDRH, Silver Spring, MD USA. EM Andreu.Badal-Soler@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 NR 14 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 978-0-8194-8023-1 J9 P SOC PHOTO-OPT INS PY 2010 VL 7622 AR 762231 DI 10.1117/12.845562 PG 9 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSO01 UT WOS:000285047200104 ER PT S AU Liu, HM Badano, A Benevides, L Chakrabarti, K Kaczmarek, RV Kyprianou, IS AF Liu, Haimo Badano, Aldo Benevides, Luis Chakrabarti, Kish Kaczmarek, Richard V. Kyprianou, Iacovos S. BE Samei, E Pelc, NJ TI Task specific evaluation of clinical Full Field Digital Mammography systems using the Fourier definition of the Hotelling observer SNR SO MEDICAL IMAGING 2010: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Physics of Medical Imaging CY FEB 15-18, 2010 CL San Diego, CA SP SPIE DE Full Filed Digital Mammography; pixel SNR; Hotelling observer SNR; BRTES phantom; image processing ID RADIOGRAPHIC IMAGING-SYSTEMS; MICROANGIOGRAPHIC SYSTEM; PERFORMANCE; EFFICIENCY; EXPOSURE; DETECTOR; QUALITY; SCATTER AB Pixel Signal to Noise Ratio (SNR) is a commonly used clinical metric for evaluating mammography. However, we showed in this paper, the pixel SNR can produce misleading system detectability when image processing is utilized. We developed a simple, reliable and clinically applicable methodology to evaluate mammographic imaging systems using a task SNR that accounts for the imaging system performance in the presence of the patient. We used the Hotelling observer method in spatial frequency domain to calculate the task SNR of small disk test objects embedded in the breast tissue-equivalent series (BRTES) phantom for GE Senographe DS Full Field Digital Mammography (FFDM) system. The results were compared to the calculation of pixel SNR. We calculated the Hotelling observer SNR by estimating the generalized modulation transfer function (GMTF), generalized normalized noise power spectrum (GNNPS) and generalized noise equivalent quanta (GNEQ) in the presence of the breast phantom. The task SNR we calculated increased with the square root of the exposure as expected. Furthermore, we showed that the method is stable under image processing. The task SNR is a more reliable method for evaluating the performance of imaging systems especially under realistic clinical conditions where patient equivalent phantoms or image processing is used. C1 [Liu, Haimo] US FDA, Silver Spring, MD 20903 USA. RP Liu, HM (reprint author), US FDA, 10903 New Hampshire Ave W062-3145, Silver Spring, MD 20903 USA. EM haimo.liu@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 NR 35 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 978-0-8194-8023-1 J9 PROC SPIE PY 2010 VL 7622 AR 762212 DI 10.1117/12.845509 PG 10 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSO01 UT WOS:000285047200036 ER PT S AU Park, S Zeng, RP Myers, KJ AF Park, Subok Zeng, Rongping Myers, Kyle J. BE Samei, E Pelc, NJ TI Singular system analysis of breast tomosynthesis systems for choosing projection angles SO MEDICAL IMAGING 2010: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE-The International Society for Optical Engineering LA English DT Proceedings Paper CT Conference on Medical Imaging - Physics of Medical Imaging CY FEB 15-18, 2010 CL San Diego, CA SP SPIE DE tomosynthesis; singular value decomposition; singular system analysis; measurable component; null component; null space; breast tomosynthesis; optimization AB Optimization of digital breast tomosynthesis (DBT) has been investigated in the medical imaging field for the last several years as DBT has the potential for improved detection of breast cancer. However, a systematic method for choosing the angular range and number of projections of DBT has yet to be developed. Singular system analysis of a linear imaging system(1) gives knowledge of how much information about the object being imaged is transferred through the given system, or equivalently how much information about the object is lost through the system. These components of the object to be imaged, which are fully transferrable and non-transferrable through the imaging system in the absence of noise, are respectively called measurable and null components of the object. 1 In this work, given a projection angle, a ray tracing algorithm(2) is used to linearly approximate the nonlinear x-ray imaging process in the 3D object and hence producing a matrix representing for the imaging process. For a DBT system using a combination of different projection angles, the imaging matrices corresponding to the projection angles are combined to form a DBT system matrix, to which the singular system analysis is applied in order to produce singular vectors of the given DBT design. The singular vectors of the DBT system are then used to estimate the null and measurable components of the object and to identify the angular projections of the DBT system that transfer maximum information regarding the object to be imaged. This method facilitates the ability to choose effective projection angles and maximizing information tranfer regarding the object by the system. C1 [Park, Subok; Zeng, Rongping; Myers, Kyle J.] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Park, S (reprint author), 10903 New Hampshire Ave,Bldg 62,Rm 3111, Silver Spring, MD 20993 USA. EM subok.park@fda.hhs.gov NR 3 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 978-0-8194-8023-1 J9 P SOC PHOTO-OPT INS PY 2010 VL 7622 AR 762243 DI 10.1117/12.844237 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSO01 UT WOS:000285047200140 ER PT S AU Rao, N Freed, M Badano, A AF Rao, Nahush Freed, Melanie Badano, Aldo BE Samei, E Pelc, NJ TI Comparing experimental measurements of x-ray detector responses with Monte Carlo predictions: figures of merit and model improvements SO MEDICAL IMAGING 2010: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE-The International Society for Optical Engineering LA English DT Proceedings Paper CT Conference on Medical Imaging - Physics of Medical Imaging CY FEB 15-18, 2010 CL San Diego, CA SP SPIE ID POINT-SPREAD FUNCTION; PENETRATION; COLLIMATORS AB Thalium-activated Cesium Iodide (CsI:Tl) scintillator screens coupled with optical readout arrays are currently the most commonly implemented detection method for digital x-ray imaging. The development of Monte Carlo code to provide detailed simulations of detectors has created the need to quantitatively compare Monte Carlo simulated versus experimentally measured point-response functions (PRFs) for validation. MANTIS is a Monte Carlo code developed for the detailed simulation of columnar CsI scintillator screens. In previous work we have validated the ability of MANTIS to reliably predict experimental PRFs and formulated an analytical model of CsI detector response that generates a PRF comparable to that of MANTIS in less than one millionth of the computation time. At the same time, these results demonstrated the need for optimization of MANTIS input parameters and the method for quantitatively comparing Monte Carlo generated PRFs with experimental data. In this study, we explore the figure-of-merit (FOM) used to compare MANTIS and experimental PRFs and the parameter space of the MANTIS inputs. We used high-resolution PRFs experimentally measured using a 30-mu m pinhole arrangement. Multiple sets of simulated PRFs based on partial knowledge of the experimental setup and CsI: Tl screen structures have been produced to compare with the experimental measurements pertaining to a screen with a thickness of 170 mu m, an x-ray energy spectrum of 40 kVp, and two x-ray beam incidence angles of 0 and 45 degrees. Input parameters of the Monte Carlo code that were not fixed by the experimental setup or previous validation results were varied to produce the different simulated PRFs. We introduced different FOMs to compare simulated and experimental PRFs and used these FOMs to fine-tune MANTIS models to best represent a particular screen design. C1 [Rao, Nahush; Freed, Melanie; Badano, Aldo] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Rao, N (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. OI badano, aldo/0000-0003-3712-6670 NR 8 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 978-0-8194-8023-1 J9 P SOC PHOTO-OPT INS PY 2010 VL 7622 AR 762252 DI 10.1117/12.845192 PG 9 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSO01 UT WOS:000285047200173 ER PT J AU Saha, A Kelley, EF Badano, A AF Saha, Anindita Kelley, Edward F. Badano, Aldo TI Accurate color measurement methods for medical displays SO MEDICAL PHYSICS LA English DT Article DE medical display; color measurements; luminance measurements ID LIQUID-CRYSTAL DISPLAYS; VIEWING-ANGLE; PERFORMANCE AB Purpose: The necessity for standard instrumentation and measurements of color that are repeatable and reproducible is the major motivation behind this work. Currently, different instrumentation and methods can yield very different results when measuring the same feature such as color uniformity or color difference. As color increasingly comes into play in medical imaging diagnostics, display color will have to be quantified in order to assess whether the display should be used for imaging purposes. The authors report on the characterization of three novel probes for measuring display color with minimal contamination from screen areas outside the measurement spot or from off-normal emissions. They compare three probe designs: A modified small-spot luminance probe and two conic probe designs based on black frusta. Methods: To compare the three color probe designs, spectral and luminance measurements were taken with specialized instrumentation to determine the luminance changes and color separation abilities of the probes. The probes were characterized with a scanning slit method, veiling glare, and a moving laser and LED arrangement. The scanning slit measurement was done using a black slit plate over a white line on an LCD monitor. The luminance was measured in 1 mm increments from the center of the slit to +/-15 mm above and below the slit at different distances between the probe and the slit. The veiling glare setup consisted of measurements of the luminance of a black spot pattern with a white disk of radius of 100 mm as the black spot increases in 1 mm radius increments. The moving LED and laser method consisted of a red and green light orthogonal to the probe tip for the light to directly shine into the probe. The green light source was moved away from the red source in 1 cm increments to measure color stray-light contamination at different probe distances. Results: The results of the color testing using the LED and laser methods suggest a better performance of one of the frusta probes at shorter distances between the light sources, which translates to less contamination. The tails of the scans indicate the magnitude of the spread in signal due to light from areas outside the intended measurement spot. The measurements indicate a corresponding glare factor for a large spot of 140, 500, and 2000 for probe A, B1, and B2, respectively. The dual-laser setup suggests that color purity can be maintained up to a few tens of millimeters outside the measurement spot. Conclusions: The comparison shows that there are significant differences in the performance of each probe design, and that those differences have an effect on the measured quantity used to quantify display color. Different probe designs show different measurements of the level of light contamination that affects the quantitative color determination. [DOI: 10.1118/1.3265879] C1 [Saha, Anindita; Kelley, Edward F.; Badano, Aldo] US Food & Drug, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Badano, A (reprint author), US Food & Drug, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,WO 62-3116, Silver Spring, MD 20993 USA. EM aldo.badano@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 NR 12 TC 2 Z9 2 U1 0 U2 1 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 2010 VL 37 IS 1 BP 74 EP 81 DI 10.1118/1.3265879 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 538GI UT WOS:000273172100010 PM 20175468 ER PT J AU Elkins, KL Colombini, SM Meierovics, AI Chu, MC Chou, AY Cowley, SC AF Elkins, Karen L. Colombini, Susan M. Meierovics, Anda I. Chu, May C. Chou, Alicia Y. Cowley, Siobhan C. TI Survival of secondary lethal systemic Francisella LVS challenge depends largely on interferon gamma SO MICROBES AND INFECTION LA English DT Article DE Francisella; Interferon gamma; T lymphocytes; Vaccination; Macrophages; Mice ID LIVE-VACCINE-STRAIN; CD4(+) T-CELLS; VIRULENT TYPE-A; PROTECTIVE IMMUNITY; TULARENSIS LVS; INTRANASAL VACCINATION; AEROSOL CHALLENGE; INFECTION; MICE; TUBERCULOSIS AB Although survival of primary infection with the live vaccine strain (LVS) of Francisella tularensis depends on interferon gamma (IFN-gamma), the relative importance of IFN-gamma to secondary protective immunity in vivo has not been clearly established. Here we examine the role of IFN-gamma in T cell priming and expression of vaccine-induced protection against lethal intraperitoneal challenge of mice. Large amounts of IFN-gamma were detected between days 3 and 7 in the sera of LVS-immunized mice, while relatively small amounts were found transiently after secondary LVS challenge. Consistent with the production of this cytokine, mice lacking IFN-gamma (gamma interferon knockout, GKO, mice) could not be successfully vaccinated with LVS or an attenuated mglA mutant of F. novicida to withstand secondary Francisella LVS challenge. Further, splenocytes from such primed mice did not adoptively transfer protection to naive GKO recipient mice in vivo, nor control the intramacrophage growth of LVS in vitro. Finally, LVS-immune WT mice depleted of IFN-gamma prior to intraperitoneal challenge survived only the lowest doses of challenge. Thus successful priming of protective LVS-immune T cells, as well as complete expression of protection against Francisella during secondary challenge, depends heavily on IFN-gamma. Published by Elsevier Masson SAS. C1 [Elkins, Karen L.; Colombini, Susan M.; Meierovics, Anda I.; Chou, Alicia Y.; Cowley, Siobhan C.] CBER FDA, Lab Mycobacterial Dis & Cellular Immunol, Div Bacterial Parasit & Allergen Prod, Rockville, MD 20852 USA. [Chu, May C.] Ctr Dis Control, Div Vector Born Dis, Ft Collins, CO USA. RP Elkins, KL (reprint author), CBER FDA, Lab Mycobacterial Dis & Cellular Immunol, Div Bacterial Parasit & Allergen Prod, 1401 Rockville Pike,HFM 431, Rockville, MD 20852 USA. EM karen.elkins@fda.hhs.gov NR 31 TC 12 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD JAN PY 2010 VL 12 IS 1 BP 28 EP 36 DI 10.1016/j.micinf.2009.09.012 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 547DG UT WOS:000273865200005 PM 19781659 ER PT J AU Romero-Weaver, AL Wang, HW Steen, HC Scarzello, AJ Hall, VL Sheikh, F Donnelly, RP Gamero, AM AF Romero-Weaver, Ana L. Wang, Hsiang-Wen Steen, Hakan C. Scarzello, Anthony J. Hall, Veronica L. Sheikh, Faruk Donnelly, Raymond P. Gamero, Ana M. TI Resistance to IFN-alpha-Induced Apoptosis Is Linked to a Loss of STAT2 SO MOLECULAR CANCER RESEARCH LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; INTERFERON-ALPHA; MELANOMA-CELLS; SIGNALING PATHWAY; TYROSINE PHOSPHORYLATION; MAMMALIAN TARGET; CLASS-I; ACTIVATION; EXPRESSION; INDUCTION AB Type I IFNs (IFN-alpha/beta) are pleitropic cytokines widely used in the treatment of certain malignancies, hepatitis B and C, and multiple sclerosis. IFN resistance is a challenging clinical problem to overcome. Hence, understanding the molecular mechanism by which IFN immunotherapy ceases to be effective is of translational importance. In this study, we report that continuous IFN-alpha stimulation of the human Jurkat variant H123 led to resistance to type I IFN-induced apoptosis due to a loss of signal transducers and activators of transcription 2 (STAT2) expression. The apoptotic effects of IFN-alpha were hampered as STAT2-deficient cells were defective in activating the mitochondrial-dependent death pathway and ISGF3-mediated gene activation. Reconstitution of STAT2 restored the apoptotic effects of IFN-alpha as measured by the loss of mitochondrial membrane potential, cytochrome c release from mitochondria, caspase activation, and ultimately cell death. Nuclear localization of STAT2 was a critical event as retention of tyrosine-phosphorylated STAT2 in the cytosol was not sufficient to activate apoptosis. Furthermore, silencing STAT2 gene expression in Saos2 and A375S.2 tumor cell lines significantly reduced the apoptotic capacity of IFN-alpha. Altogether, we show that STAT2 is a critical mediator in the activation of type I IFN-induced apoptosis. More importantly, defects in the expression or nuclear localization of STAT2 could lessen the efficacy of type I IFN immunotherapy. Mol Cancer Res; 8(1); 80-92. (C) 2010 AACR. C1 [Romero-Weaver, Ana L.; Wang, Hsiang-Wen; Scarzello, Anthony J.; Hall, Veronica L.; Gamero, Ana M.] NCI, Expt Immunol Lab, Canc & Inflammat Program, NIH, Frederick, MD 21701 USA. [Steen, Hakan C.; Gamero, Ana M.] Temple Univ, Sch Med, Dept Biochem, Philadelphia, PA 19122 USA. [Sheikh, Faruk; Donnelly, Raymond P.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Gamero, AM (reprint author), 3440 N Broad St,Kresge Hall,Room 622, Philadelphia, PA 19041 USA. EM gameroa@temple.edu FU National Cancer Institute, NIH [N01-CO-12400]; National Cancer Institute [K22CA095326]; NIH, National Cancer Institute, Center for Cancer Research FX Whole or in part with Federal funds from the National Cancer Institute, NIH under contract no. N01-CO-12400 (A. M. Gamero, A. L. Romero-Weaver, H-W. Wang). This project described was also supported by award no. K22CA095326 from the National Cancer Institute (A. M. Gamero). This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 45 TC 17 Z9 17 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD JAN PY 2010 VL 8 IS 1 BP 80 EP 92 DI 10.1158/1541-7786.MCR-08-0344 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 606EK UT WOS:000278404700008 PM 20068068 ER PT B AU Warren, BR Lampel, KA Schneider, KR AF Warren, Benjamin R. Lampel, Keith A. Schneider, Keith R. BE Liu, D TI Shigella SO MOLECULAR DETECTION OF FOODBORNE PATHOGENS LA English DT Article; Book Chapter ID ACTIN-BASED MOTILITY; ENTEROINVASIVE ESCHERICHIA-COLI; SHIGA TOXIN; FLEXNERI 2A; UNIPOLAR LOCALIZATION; ANTIMICROBIAL-RESISTANCE; BACILLARY DYSENTERY; AEROBACTIN GENES; RAPID DETECTION; MOLECULAR-BASIS C1 [Warren, Benjamin R.] ConAgra Foods Inc, Res Qual & Innovat, Omaha, NE 68102 USA. [Lampel, Keith A.] US FDA, Div Microbiol, College Pk, MD USA. [Schneider, Keith R.] Univ Florida, Food Sci & Human Nutr Dept, Gainesville, FL USA. RP Warren, BR (reprint author), ConAgra Foods Inc, Res Qual & Innovat, Omaha, NE 68102 USA. NR 109 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 978-1-4200-7644-8; 978-1-4200-7643-1 PY 2010 BP 471 EP 484 PG 14 WC Food Science & Technology; Virology SC Food Science & Technology; Virology GA BC7OS UT WOS:000355127100035 ER PT B AU Rahman, A Kalush, F AF Rahman, Atiqur Kalush, Francis BE Jorgensen, JT Winther, H TI SAFETY AND EFFECTIVE BIOMAKERS IN ONCOLOGY - A REGULATORY DRUG AND DEVICE PERSPECTIVE SO MOLECULAR DIAGNOSTICS: THE KEY DRIVER IN PERSONALIZED CANCER MEDICINE LA English DT Article; Book Chapter ID METASTATIC COLORECTAL-CANCER; THIOPURINE METHYLTRANSFERASE; ADJUVANT TAMOXIFEN; PHARMACOGENETICS; IRINOTECAN; METABOLISM; INDUSTRY C1 [Rahman, Atiqur; Kalush, Francis] US FDA, Ctr Drug Evaluat & Res, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Rahman, A (reprint author), US FDA, Ctr Drug Evaluat & Res, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM namatiqur.rahman@fda.hhs.gov NR 29 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 978-9-81424-145-8 PY 2010 BP 275 EP 296 PG 22 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BTV86 UT WOS:000288202600014 ER PT J AU Kishnani, PS Goldenberg, PC DeArmey, SL Heller, J Benjamin, D Young, S Bali, D Smith, SA Li, JS Mandel, H Koeberl, D Rosenberg, A Chen, YT AF Kishnani, Priya S. Goldenberg, Paula C. DeArmey, Stephanie L. Heller, James Benjamin, Danny Young, Sarah Bali, Deeksha Smith, Sue Ann Li, Jennifer S. Mandel, Hanna Koeberl, Dwight Rosenberg, Amy Chen, Y. -T TI Cross-reactive immunologic material status affects treatment outcomes in Pompe disease infants SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Pompe disease; Glycogen storage disease; Enzyme replacement therapy; Lysosomal storage disease; Acid alpha glucosidase; GAA; Cross-reactive immunologic material; CRIM; Antibody ID ACID ALPHA-GLUCOSIDASE; ENZYME-REPLACEMENT THERAPY; IMMUNE TOLERANCE; FABRY-DISEASE; MUCOPOLYSACCHARIDOSIS I; GAUCHER-DISEASE; CLINICAL-TRIAL; MOUSE MODEL; FACTOR-VIII; RECOMBINANT AB Deficiency of acid alpha glucosidase (GAA) causes Pompe disease, which is usually fatal if onset occurs in infancy. Patients synthesize a non-functional form of GAA or are unable to form native enzyme. Enzyme replacement therapy with recombinant human GAA (rhGAA) prolongs survival in infantile Pompe patients but may be less effective in cross-reactive immunologic material (CRIM)-negative patients. We retrospectively analyzed the influence of CRIM status on outcome in 21 CRIM-positive and 11 CRIM-negative infantile Pompe patients receiving rhGAA. Patients were from the clinical setting and from clinical trials of rhGAA, were <= 6 months of age, were not invasively ventilated, and were treated with IV rhGAA at a cumulative or total dose of 20 or 40 mg/kg/2 weeks. Outcome measures included survival, invasive ventilator-free survival, cardiac status, gross motor development, development of antibodies to rhGAA, and levels of urinary Glc(4). Following 52 weeks of treatment, 6/11 (54.5%) CRIM-negative and 1/21 (4.8%) CRIM-positive patients were deceased or invasively ventilated (p < 0.0001). By age 27.1 months, all CRIM-negative patients and 4/21 (19.0%) CRIM-positive patients were deceased or invasively ventilated. Cardiac function and gross motor development improved significantly more in the CRIM-positive group. IgG antibodies to rhGAA developed earlier and serotiters were higher and more sustained in the CRIM-negative group. CRIM-negative status predicted reduced overall survival and invasive ventilator-free survival and poorer clinical outcomes in infants with Pompe disease treated with rhGAA. The effect of CRIM status on outcome appears to be mediated by antibody responses to the exogenous protein. (C) 2009 Elsevier Inc. All rights reserved. C1 [Kishnani, Priya S.; Goldenberg, Paula C.; DeArmey, Stephanie L.; Young, Sarah; Bali, Deeksha; Koeberl, Dwight; Chen, Y. -T] Duke Univ, Med Ctr, Div Med Genet, Dept Pediat, Durham, NC 27710 USA. [Heller, James] Duke Univ, Med Ctr, Dept Surg, Div Speech & Hearing, Durham, NC 27710 USA. [Benjamin, Danny] Duke Univ, Dept Med, Durham, NC 27710 USA. [Benjamin, Danny] Duke Univ, Duke Clin Res Inst, Durham, NC 27710 USA. [Smith, Sue Ann] Oregon Hlth & Sci Univ, Dept Pediat, Div Neonatol, Portland, OR 97201 USA. [Li, Jennifer S.] Duke Univ, Med Ctr, Div Cardiol, Dept Pediat, Durham, NC 27710 USA. [Mandel, Hanna] Rambam Med Ctr, Dept Pediat & Med Genet, Haifa, Israel. [Rosenberg, Amy] US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Off Biotechnol Prod, Rockville, MD 20857 USA. [Chen, Y. -T] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan. RP Kishnani, PS (reprint author), Duke Univ, Med Ctr, Div Med Genet, Dept Pediat, Box 103856 DUMC,4th Floor GSRBI,595 LaSalle St, Durham, NC 27710 USA. EM kishn001@mc.duke.edu FU Duke Clinical Research Unit Program [1UL1RR024128]; National Center for Research Resources; National Institutes of Health; Synpac, Inc.; Genzyme Corporation FX The authors would like to thank the patients, their families, and the health care providers who participated in the clinical studies of rhGAA whose outcomes are summarized here. We would like to thank the GCRC staff at Duke University for the excellent care provided to patients at the Duke site. The clinical trials were supported by Genzyme Corporation and Grant 1UL1RR024128 from the Duke Clinical Research Unit Program, National Center for Research Resources, and the National Institutes of Health. Dr. Deya Corzo of Genzyme Corporation provided input and critical review of the paper. Katherine Lewis of Genzyme Corporation provided editorial assistance. The original clinical studies from which patients were culled for this analysis were sponsored by Synpac, Inc. (Durham, NC, USA) and Genzyme Corporation (Cambridge, MA, USA). We thank Susan Richards and her clinical science laboratory at Genzyme Corporation for providing antibody analyses. All data included in this paper were verified and analyzed independently by the authors. P.S. Kishnani had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 42 TC 154 Z9 156 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JAN PY 2010 VL 99 IS 1 BP 26 EP 33 DI 10.1016/j.ymgme.2009.08.003 PG 8 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 545SV UT WOS:000273758000005 PM 19775921 ER PT S AU Huque, M Rohmel, J AF Huque, Mohammad Roehmel, Joachim BE Dmitrienko, A Tamhane, AC Bretz, F TI Multiplicity Problems in Clinical Trials: A Regulatory Perspective SO MULTIPLE TESTING PROBLEMS IN PHARMACEUTICAL STATISTICS SE Chapman & Hall-CRC Biostatistics Series LA English DT Article; Book Chapter C1 [Huque, Mohammad] US FDA, Div Biometr IV OB OTS CDER, Silver Spring, MD 20993 USA. [Roehmel, Joachim] Bremen Inst Prevent Res & Social Med, Bremen, Germany. RP Huque, M (reprint author), US FDA, Div Biometr IV OB OTS CDER, Silver Spring, MD 20993 USA. NR 0 TC 3 Z9 3 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 978-1-58488-985-4; 978-1-58488-984-7 J9 CH CRC BIOSTAT SER JI Chapman & Hall-CRC Biostat. Ser. PY 2010 VL 33 BP 1 EP 33 PG 33 WC Mathematical & Computational Biology; Pharmacology & Pharmacy SC Mathematical & Computational Biology; Pharmacology & Pharmacy GA BD7JF UT WOS:000363208600002 ER PT B AU Burgess, SJ Narayanan, S Borrego, F Coligan, JE AF Burgess, Steven J. Narayanan, Sriram Borrego, Francisco Coligan, John E. BE St Georgiev, V Zoon, KC TI Role of the NKG2D Receptor in Health and Disease SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID MHC CLASS-I; NATURAL-KILLER-CELLS; CD8(+) T-CELLS; CYTOMEGALOVIRUS GLYCOPROTEIN UL16; NK CELLS; DOWN-REGULATION; CUTTING EDGE; TUMOR-CELLS; MEDIATED CYTOTOXICITY; IMMUNE-RESPONSE C1 [Burgess, Steven J.] Pfizer Global Res & Dev, Sandwich CT13 9NJ, Kent, England. [Borrego, Francisco] CDER FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, Bethesda, MD USA. NIAID, Receptor Cell Biol Sect, Immunogenet Lab, Div Intramural Res,NIH, Rockville, MD USA. RP Burgess, SJ (reprint author), Pfizer Global Res & Dev, Sandwich CT13 9NJ, Kent, England. NR 150 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 261 EP 273 DI 10.1007/978-1-60761-512-5_28 D2 10.1007/978-1-60761-512-5 PG 13 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800028 ER PT J AU Cote, T Kelkar, A Xu, K Braun, MM Phillips, MI AF Cote, Timothy Kelkar, Aditya Xu, Kui Braun, M. Miles Phillips, M. Ian TI Orphan products: an emerging trend in drug approvals SO NATURE REVIEWS DRUG DISCOVERY LA English DT Letter C1 [Cote, Timothy; Kelkar, Aditya; Xu, Kui; Braun, M. Miles] US FDA, Off Orphan Prod Dev, Rockville, MD 20857 USA. [Kelkar, Aditya; Phillips, M. Ian] Keck Grad Inst, Claremont, CA 91711 USA. RP Cote, T (reprint author), US FDA, Off Orphan Prod Dev, Rockville, MD 20857 USA. EM timothy.cote@fda.hhs.gov NR 7 TC 20 Z9 21 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD JAN PY 2010 VL 9 IS 1 BP 84 EP U11 DI 10.1038/nrd2546-c1 PG 2 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 566GD UT WOS:000275357200029 PM 20043031 ER PT S AU Virmani, A Ali, SF Binienda, ZK AF Virmani, Ashraf Ali, Syed F. Binienda, Zbigniew K. BE Andrews, RJ Slikker, W Trembly, B Patterson, TA TI Neuroprotective strategies in drug abuse-evoked encephalopathy SO NEUROPROTECTIVE AGENTS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 9th International Conference on Neuroprotective Agents CY SEP 07-11, 2008 CL Marine Biol Lab, Woods Hole, MA HO Marine Biol Lab DE leucoencephalopathy; nutrition; neurotoxicity; drug-abuse; cocaine; methamphetamine; alcohol; amphetamines ID METHAMPHETAMINE-INDUCED NEUROTOXICITY; INDUCED DOPAMINERGIC NEUROTOXICITY; ACETYL-L-CARNITINE; TOXIC LEUKOENCEPHALOPATHY; METABOLIC SYNDROME; OXIDATIVE STRESS; NEURONAL APOPTOSIS; COCAINE TOXICITY; GENE-EXPRESSION; MOUSE-BRAIN AB Encephalopathy is evidenced as an altered mental state with various neurological symptoms, such as memory and cognitive problems. The type of a substance-evoked encephalopathy will depend on the drug, substance, or combination being abused. The categories into which we could place the various abused substances could be tentatively divided into stimulants, amphetamines, hallucinogens, narcotics, inhalants, anesthetics, anabolic steroids, and antipsychotics/antidepressants. Other factors that may underlie encephalopathy, such as infectious agents, environmental, and other factors have also to be taken into account. Drugs of abuse can be highly toxic to the CNS following acute, but more so in chronic exposure, and can produce significant damage to other organs, such as the heart, lungs, liver, and kidneys. The damage to these organs may be at least partially reversible when drug abuse is stopped but CNS damage from repeated or prolonged abuse is often irreversible. The major pathways for the organ and CNS toxicity could be related to ischemic events as well as increased cell damage due to metabolic or mitochondrial dysfunction resulting in increased excitotoxicity, reduced energy production, and lowered antioxidant potential. These susceptibilities could be strengthened by the use of antioxidants to combat free radicals (e.g., vitamin E, lipoic acid); trying to improve energy generation by using mitochondriotropic/metabolic compounds (e.g., thiamine, coenzyme Q10, carnitine, riboflavin); by reducing excitotoxicity (e.g., glutamate antagonists) and other possible strategies, such as robust gene response, need to be investigated further. The drug-abuse-evoked encephalopathy still needs to be studied further to enable better preventative and protective strategies. C1 [Virmani, Ashraf] Sigma Tau Pharmaceut Co, Sci & Med Affairs, I-00040 Pomezia, Italy. [Virmani, Ashraf] EMMA, London, England. [Virmani, Ashraf] EMMA, Rome, Italy. [Ali, Syed F.] US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Jefferson, AR 72079 USA. [Binienda, Zbigniew K.] US FDA, Natl Ctr Toxicol Res, Neurophysiol Lab, Jefferson, AR 72079 USA. RP Virmani, A (reprint author), Sigma Tau Pharmaceut Co, Via Pontina Km 30,400, I-00040 Rome, Italy. EM ashraf.virmani@sigma-tau.it NR 113 TC 12 Z9 12 U1 2 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-777-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2010 VL 1199 BP 52 EP 68 DI 10.1111/j.1749-6632.2009.05171.x PG 17 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BRJ59 UT WOS:000282838900006 PM 20633109 ER PT J AU Tasset, I Perez-De La Cruz, V Elinos-Calderon, D Carrillo-Mora, P Gonzalez-Herrera, IG Luna-Lopez, A Konigsberg, M Pedraza-Chaverri, J Maldonado, PD Ali, SF Tunez, I Santamaria, A AF Tasset, Inmaculada Perez-De La Cruz, Veronica Elinos-Calderon, Diana Carrillo-Mora, Paul Gabriela Gonzalez-Herrera, Irma Luna-Lopez, Armando Konigsberg, Mina Pedraza-Chaverri, Jose Maldonado, Perla D. Ali, Syed F. Tunez, Isaac Santamaria, Abel TI Protective Effect of Tert-Butylhydroquinone on the Quinolinic-Acid-Induced Toxicity in Rat Striatal Slices: Role of the Nrf2-Antioxidant Response Element Pathway SO NEUROSIGNALS LA English DT Article DE Oxidative damage; Quinolinate; Tert-butylhydroquinone; Nrf2; Antioxidant defense; Glutathione-S-transferase; Redox signaling ID OXIDATIVE STRESS; ANTIOXIDANT RESPONSE; INDUCED NEUROTOXICITY; HUNTINGTONS-DISEASE; LIPID-PEROXIDATION; S-ALLYLCYSTEINE; IN-VIVO; NRF2; BRAIN; DAMAGE AB Tert-butylhydroquinone (tBHQ) is a xenobiotic with reported antioxidant properties. tBHQ has been shown to induce nuclear translocation of the transcription factor NF-E2-related factor 2 (Nrf2) to further activate the antioxidant response element (ARE). In turn, the Nrf2/ARE pathway is responsible for the induction of phase 2 antioxidant enzymes that detoxify oxidant promoters from different toxic insults. In this work, the antioxidant and protective actions of tBHQ were explored for the first time on different biomarkers of the neurotoxic model produced by the excitotoxic and pro-oxidant molecule quinolinic acid (QUIN) in rat striatal slices. For comparison purposes, 3-nitropropionic acid was used as reference model. Our results show that tBHQ (25 mu M) prevented the QUIN-induced lipid peroxidation and mitochondrial dysfunction. In addition, tBHQ enhanced glutathione-S-transferase activity, partially recovering its depletion induced by QUIN treatment. Our results also demonstrated that tBHQ was able to induce nuclear accumulation of Nrf2 and further antioxidant protection: while QUIN alone decreased the nuclear Nrf2, a treatment with tBHQ preserved the nuclear levels Nrf2 in the presence of QUIN. Therefore, the tBHQ-mediated Nrf2/ARE induction constitutes a signaling-mediated antioxidant strategy and therapeutic tool to be tested in different neurotoxic models. Copyright (C) 2009 S. Karger AG, Basel C1 [Perez-De La Cruz, Veronica; Elinos-Calderon, Diana; Carrillo-Mora, Paul; Gabriela Gonzalez-Herrera, Irma; Santamaria, Abel] Inst Nacl Neurol & Neurocirugia Manuel Velasco S, Lab Aminoacidos Excitadores, Mexico City 14269, DF, Mexico. [Maldonado, Perla D.] Inst Nacl Neurol & Neurocirugia Manuel Velasco S, Lab Patol Vasc Cerebral, Mexico City 14269, DF, Mexico. [Tasset, Inmaculada; Tunez, Isaac] Univ Cordoba, Fac Med, Dept Bioquim & Biol Mol, Cordoba, Spain. [Luna-Lopez, Armando; Konigsberg, Mina] Univ Autonoma Metropolitana Iztapalapa, Dept Ciencias Salud, Div Ciencias Biol & Salud, Mexico City 09340, DF, Mexico. [Pedraza-Chaverri, Jose] Univ Nacl Autonoma Mexico, Fac Quim, Dept Biol, Mexico City 04510, DF, Mexico. [Ali, Syed F.; Santamaria, Abel] US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Tunez, Isaac] IMIBIC, Cordoba, Spain. RP Santamaria, A (reprint author), Inst Nacl Neurol & Neurocirugia Manuel Velasco S, Lab Aminoacidos Excitadores, Insurgentes 3877, Mexico City 14269, DF, Mexico. EM absada@yahoo.com FU CONACyT-Mexico [48370-Q]; DGAPA PAPIIT [IN 207007] FX This work was supported by CONACyT-Mexico Grant 48370-Q (A. S.) and DGAPA PAPIIT (IN 207007) (J.P.). NR 40 TC 19 Z9 20 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-862X EI 1424-8638 J9 NEUROSIGNALS JI Neurosignals PY 2010 VL 18 IS 1 BP 24 EP 31 DI 10.1159/000243650 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology; Neurosciences SC Biochemistry & Molecular Biology; Biophysics; Cell Biology; Neurosciences & Neurology GA 648BB UT WOS:000281664300003 PM 19797933 ER PT J AU Boctor, SY Ferguson, SA AF Boctor, Sherin Y. Ferguson, Sherry A. TI Altered adult locomotor activity in rats from phencyclidine treatment on postnatal days 7, 9 and 11, but not repeated ketamine treatment on postnatal day 7 SO NEUROTOXICOLOGY LA English DT Article DE Ketamine; Phencyclidine; Open field; Running wheel; Spatial alternation; Motor coordination ID SPRAGUE-DAWLEY RATS; NMDA RECEPTOR ANTAGONISTS; SEX-DEPENDENT DIFFERENCES; D-ASPARTATE RECEPTOR; PERINATAL PHENCYCLIDINE; BEHAVIORAL-DEVELOPMENT; INDUCED HYPERACTIVITY; PREPULSE INHIBITION; SPATIAL ALTERNATION; CIRCADIAN SYSTEM AB Neonatal ketamine (KET) or phencyclidine (PCP) treatment can trigger apoptotic neurodegeneration in rodents. Previously, we described KET- and PCP-induced altered body weight and home cage, slant board and forelimb hang behaviors in preweaning rats (Boctor et al., 2008). In that study, L-carnitine (LC) attenuated the KET-induced behavioral alterations and body weight decrements. The four subcutaneous (sc) treatment groups were: (1) saline; (2) 10 mg/kg PCP on PNDs 7, 9 and 11; (3) 20 mg/kg KET (6 injections; one every 2 h on PND 7); or (4) a regimen of KET and 250 mg/kg LC (KLC) both administered on PND 7, with additional 250 mg/kg doses of LC on PNDs 8-11. A portion of each treatment group was evaluated for postweaning behaviors which included grip strength and motor coordination (postnatal days (PNDs) 22 or 71), locomotor sensitization (PND 42), spatial alternation (PNDs 22-70) and residential running wheel activity (PNDs 72-77). On PND 42 or 78, whole and regional brain weights were measured. Grip strength and motor coordination were unaffected at either age by neonatal treatment. On PND 42, neonatally treated KET- or KLC-treated rats responded to a challenge of 5 mg/kg KET with activity similar to controls that received the same challenge. Neonatal PCP treatment, however, induced significant sensitization to a challenge of 3 mg/kg PCP on PND 42 relative to controls that received the same challenge, causing increased activity which was especially profound in females. Performance on a continuous spatial alternation task requiring a "win-shift, lose-stay" strategy appeared unaffected by neonatal KET or KLC treatment. PCP treatment, however, caused significantly increased random responding and shorter choice latencies. In addition, neonatal PCP treatment elevated light and dark period running wheel activity and reduced PND 42 and 78 body and whole brain weights. These findings provide further evidence that PCP treatment on PNDs 7,9, and 11 causes subtle cognitive deficits and long-term alterations in activity that are unrelated to deficits in grip strength OF motor coordination. Further, repeated KET treatment on PND 7 does not appear to result in severe behavioral modifications. Published by Elsevier Inc. C1 [Boctor, Sherin Y.; Ferguson, Sherry A.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Boctor, Sherin Y.; Ferguson, Sherry A.] Univ Arkansas Med Sci, Dept Interdisciplinary Biomed Sci, Little Rock, AR 72205 USA. RP Ferguson, SA (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM Sherry.Ferguson@fda.hhs.gov FU Oak Ridge Institute for Science and Education (ORISE); NCTR/FDA and the NIEHS/NTP [224-93-0001] FX The authors thank Lee McVay (The Bionetics Corporation) and Joseph (Ruda) Pollard for their superb technical help. In addition, we gratefully acknowledge the hardware expertise provided by Richard Rasmussen (The Bionetics Corporation), the software proficiency of Tim Wingfield (Z-Tech Corporation), and the statistical analyses of Paul Felton (Division of Personalized Nutrition and Medicine, NCTR). SYB was supported by an Oak Ridge Institute for Science and Education (ORISE) predoctoral fellowship. Supported by Interagency Agreement #224-93-0001 between the NCTR/FDA and the NIEHS/NTP. NR 53 TC 19 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD JAN PY 2010 VL 31 IS 1 BP 42 EP 54 DI 10.1016/j.neuro.2009.10.007 PG 13 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 556SE UT WOS:000274611000005 PM 19853622 ER PT S AU Humbles, AA Reed, JL Parker, J Kiener, PA Molfino, NA Kolbeck, R Coyle, AJ AF Humbles, Alison A. Reed, Jennifer L. Parker, Joseph Kiener, Peter A. Molfino, Nestor A. Kolbeck, Roland Coyle, Anthony J. BA Barnes, PJ BF Barnes, PJ BE Hansel, TT TI Monoclonal antibody therapy directed against interleuliin-9: MEDI-528 SO NEW DRUGS AND TARGETS FOR ASTHMA AND COPD SE Progress in Respiratory Research LA English DT Article; Book Chapter ID MAST-CELLS; AIRWAY INFLAMMATION; TRANSGENIC MICE; PULMONARY INFLAMMATION; ATOPIC ASTHMATICS; RI EXPRESSION; SMOOTH-MUSCLE; INTERLEUKIN 9; TGF-BETA; IL-9 AB With the identification of T helper 2 (Th2)-derived cytokines, including interleukin (IL)-9, as orchestrators of allergic asthma, the profound impact of IL-9 on both immune cells and structural cells of the lung has received great attention. Both IL-9 and IL-9 receptor expression are upregulated in human asthmatics, and genetic linkage studies have associated 1L-9 with the susceptibility to develop airway hyperresponsiveness. Moreover, preclinical studies highlighting the mast cell-enhancing activity of 1L-9, which is unique among the Th2 cytokines, indicate that 1L-9 blockade could provide a novel approach to the treatment of both noneosinophilic asthma, which is resistant to inhaled corticosteroid therapy, as well as of eosinophilic asthma. MEDI-528 is a humanized immunoglobulin GI antibody that inhibits the activity of IL-9 and is currently in clinical development, undergoing evaluation in phase 11a studies in mild to moderate asthmatics. MEDI-528 is currently the only program in clinical development directly targeting the IL-9-dependent pathway and may have important therapeutic possibilities in allergic and nonallergic inflammatory diseases where mast cell contributions are prominent. C1 [Humbles, Alison A.; Reed, Jennifer L.; Parker, Joseph; Kolbeck, Roland; Coyle, Anthony J.] Medimmune Inc, Gaithersburg, MD 20878 USA. [Reed, Jennifer L.] Food & Drug Adm, Rockville, MD USA. [Kiener, Peter A.] Zyngenia Inc, Gaithersburg, MD USA. RP Humbles, AA (reprint author), Medimmune Inc, 1 MedImmune Way, Gaithersburg, MD 20878 USA. EM humblesa@medimmune.com NR 56 TC 1 Z9 1 U1 1 U2 4 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1422-2140 BN 978-3-8055-9566-7 J9 PROG RESPIR RES JI Prog. Respir. Res. PY 2010 VL 39 BP 137 EP 140 PG 4 WC Allergy; Pharmacology & Pharmacy; Respiratory System SC Allergy; Pharmacology & Pharmacy; Respiratory System GA BQW48 UT WOS:000282013600019 ER PT J AU Grajkowski, A Cieslak, J Gapeev, A Beaucage, SL AF Grajkowski, Andrzej Cieslak, Jacek Gapeev, Alexei Beaucage, Serge L. TI Hydroxyalkylated phosphoramidate, phosphoramidothioate and phosphorodiamidothioate derivatives as thiophosphate protecting groups in the development of thermolytic DNA prodrugs SO NEW JOURNAL OF CHEMISTRY LA English DT Article ID SOLID-PHASE SYNTHESIS; CONTROLLED-PORE GLASS; BACTERIAL-DNA; OLIGODEOXYRIBONUCLEOTIDES; PHOSPHOROTHIOATES; OLIGONUCLEOTIDES; REVERSIBILITY; DEPROTECTION; 1,1-DIOXIDE; CLEAVAGE AB The hydroxyalkylated phosphoramidate 4a, phosphoramidothioates 4b, 4e-j, and phosphorodiamidothioates 4c and 4d have been identified as a new class of heat-sensitive thiophosphate protecting groups in the development of thermolytic immunomodulatory DNA prodrugs. These alcohols are converted to their deoxyribonucleoside phosphoramidite derivatives 6a-j, which are then used in the preparation of the thermosensitive dinucleoside phosphorothioates 7a-j. The negatively charged thiophosphate protecting groups of 7a-b and 7e-j presumably undergo thermolytic cyclodeesterification at elevated temperature under essentially neutral conditions. The thiophosphate protecting groups of 7e and 7f show relatively rapid deprotection kinetics at 37 degrees C (t(1/2) = 20 and 42 h, respectively) and are therefore suitable for the protection of phosphodiester functions flanking the CpG motifs of immunomodulatory DNA sequences, whereas the thiophosphate protecting groups of 7g-j with thermolytic deprotection half-lives in the range of 94-265 h at 37 degrees C are more appropriate for the thiophosphate protection of CpG motifs. Furthermore, the thermostability of the group protecting the thiophosphate function of 7a (t(1/2) = 82 min at 90 degrees C) should offer adequate protection of the 5'- and/or 3'-terminal phosphodiester functions of DNA prodrugs against ubiquitous extracellular and intracellular exonucleases. C1 [Grajkowski, Andrzej; Cieslak, Jacek; Beaucage, Serge L.] US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20014 USA. [Gapeev, Alexei] Univ Maryland, Dept Chem & Biochem, Baltimore, MD 21201 USA. RP Beaucage, SL (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20014 USA. EM serge.beaucage@fda.hhs.gov NR 26 TC 5 Z9 5 U1 1 U2 4 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1144-0546 J9 NEW J CHEM JI New J. Chem. PY 2010 VL 34 IS 5 BP 880 EP 887 DI 10.1039/b9nj00692c PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 592SD UT WOS:000277399200012 ER PT J AU Trumbo, PR AF Trumbo, Paula R. TI Perchlorate consumption, iodine status, and thyroid function SO NUTRITION REVIEWS LA English DT Review DE iodide; iodine; perchlorate; reference dose; safety; thyroid ID LOW-DOSE PERCHLORATE; DRINKING-WATER; UNITED-STATES; BREAST-MILK; LONG-TERM; EXPOSURE; PREGNANCY; NEWBORNS; CHILDREN; HEALTH AB Perchlorate inhibits the uptake of iodide into the thyroid gland, thereby possibly affecting the synthesis of thyroid hormones. Pregnant women and their fetuses and newborns have the greatest potential for risk of adverse health effects following exposure to perchlorate. Perchlorate is present in some foods and in drinking water in certain areas of the United States. Based on the available information, the United States Food and Drug Administration (FDA) is not recommending that consumers of any age alter their diet or eating habits due to perchlorate exposure. If one eats a healthy diet that is consistent with the Dietary Guidelines for Americans, taking iodine supplements is not necessary for protection against health effects associated with perchlorate at the levels present in water and foods. C1 [Trumbo, Paula R.] US FDA, Div Nutr Programs & Labeling, College Pk, MD USA. RP Trumbo, PR (reprint author), HFS 830,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM paula.trumbo@FDA.HHS.gov NR 36 TC 10 Z9 13 U1 1 U2 9 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD JAN PY 2010 VL 68 IS 1 BP 62 EP 66 DI 10.1111/j.1753-4887.2009.00260.x PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 535XV UT WOS:000273006200004 PM 20042000 ER PT J AU Mckee, AE Farrell, AT Pazdur, R Woodcock, J AF McKee, Amy E. Farrell, Ann T. Pazdur, Richard Woodcock, Janet TI The Role of the US Food and Drug Administration Review Process: Clinical Trial Endpoints in Oncology SO ONCOLOGIST LA English DT Article DE Effectiveness; Endpoint; Approval ID APPROVAL AB The U.S. Food and Drug Administration grants marketing approval for drug products based on a comprehensive review of safety and efficacy data. The clinical trial endpoints that have been used to support approval in the oncology setting have evolved over the last 30 years commensurate with an improved understanding of the natural history of cancers and the mechanisms of action of drugs. Overall survival is the gold standard for a registration trial designed to gain marketing approval; however, additional endpoints have been used in the approval of oncology drugs. Advantages of specific endpoints are discussed, including the accuracy of an endpoint's measurement and its relation to clinical benefit. Surrogate endpoints may be acceptable for "accelerated" approval, with a sponsor commitment to provide evidence of clinical benefit in a subsequent trial. The Oncologist 2010;15(suppl1):13-18 C1 [McKee, Amy E.; Farrell, Ann T.; Pazdur, Richard] US FDA, Off Oncol Drug Prod, Silver Spring, MD 20993 USA. [Woodcock, Janet] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Mckee, AE (reprint author), US FDA, Off Oncol Drug Prod, 10903 New Hampshire Ave,Bldg 22,Room 5232, Silver Spring, MD 20993 USA. EM amy.mckee@fda.hhs.gov NR 7 TC 32 Z9 32 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2010 VL 15 SU 1 BP 13 EP 18 DI 10.1634/theoncologist.2010-S1-13 PG 6 WC Oncology SC Oncology GA 570XQ UT WOS:000275712300004 PM 20237212 ER PT J AU Summers, J Cohen, MH Keegan, P Pazdur, R AF Summers, Jeff Cohen, Martin H. Keegan, Patricia Pazdur, Richard TI FDA Drug Approval Summary: Bevacizumab plus Interferon for Advanced Renal Cell Carcinoma SO ONCOLOGIST LA English DT Article ID FACTOR-TARGETED THERAPY; PHASE-III TRIAL; PROGNOSTIC-FACTORS; INTERLEUKIN-2; CANCER; ALPHA; COMBINATION; SURVIVAL AB On July 31, 2009, the U. S. Food and Drug Administration granted approval for the use of bevacizumab (Avastin(R); Genentech, Inc., South San Francisco, CA) in combination with interferon (IFN)-alpha 2a for the treatment of patients with metastatic renal cell carcinoma. The approval was primarily based on results from a randomized, double-blind, placebo-controlled clinical trial. The primary efficacy endpoint, progression-free survival (PFS), was assessed by investigators and by an independent review committee (IRC) blinded to treatment assignment. In total, 649 patients (bevacizumab plus IFN, 327; placebo plus IFN, 322) were enrolled. The median PFS times, by investigator determination, were 10.2 months for the bevacizumab plus IFN arm and 5.4 months for the placebo plus IFN arm (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.49-0.72; p < .0001). The IRC analysis of 569 patients with available radiographs yielded similar results (median PFS time, 10.4 months versus 5.5 months; HR, 0.57; 95% CI, 0.45-0.72; p < .0001). There was no survival advantage (HR, 0.86; 95% CI, 0.72-1.04; p = .13). Support for the above results was provided by summarized results of a North American cooperative group study of bevacizumab plus IFN-alpha 2b versus IFN-alpha 2b alone. The median PFS times were 8.4 months versus 4.9 months in favor of the bevacizumab combination. There was no survival advantage. In the reviewed trial, serious adverse events and National Cancer Institute Common Terminology Criteria for Adverse Events grade >= 3 adverse events were reported more frequently in bevacizumab-treated patients (31% versus 19% and 63% versus 47%, respectively). The most common bevacizumab-related toxicities were bleeding/hemorrhage, hypertension, proteinuria, and venous or arterial thromboembolic events. The Oncologist 2010; 15: 104-111 C1 [Summers, Jeff; Cohen, Martin H.; Keegan, Patricia; Pazdur, Richard] US FDA, Div Biol Oncol Prod, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Cohen, MH (reprint author), US FDA, Div Biol Oncol Prod, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, White Oak Campus,10903 New Hampshire Ave,Bldg 22, Silver Spring, MD 20993 USA. EM martin.cohen@fda.hhs.gov NR 27 TC 31 Z9 32 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2010 VL 15 IS 1 BP 104 EP 111 DI 10.1634/theoncologist.2009-0250 PG 8 WC Oncology SC Oncology GA 550SF UT WOS:000274149000012 PM 20061402 ER PT J AU Cohen, MH Cortazar, P Justice, R Pazdur, R AF Cohen, Martin H. Cortazar, Patricia Justice, Robert Pazdur, Richard TI Approval Summary: Imatinib Mesylate in the Adjuvant Treatment of Malignant Gastrointestinal Stromal Tumors SO ONCOLOGIST LA English DT Article DE Imatinib; Gleevec; Kit; CD117; Gastrointestinal stromal tumors ID OF-FUNCTION MUTATIONS; TERM-FOLLOW-UP; PDGFRA MUTATIONS; KIT AB On December 19, 2008, the U. S. Food and Drug Administration approved imatinib mesylate tablets for oral use (Gleevec (R); Novartis Pharmaceuticals Corporation, East Hanover, NJ) for the adjuvant treatment of adult patients following complete gross resection of Kit(+) (CD117(+)) gastrointestinal stromal tumor (GIST). A randomized, double-blind, placebo-controlled study enrolling 713 patients was submitted. The primary objective of the clinical trial was to compare the recurrence-free survival (RFS) intervals of the two groups. Overall survival (OS) was a secondary end-point. Eligible patients were >= 18 years of age with a histological diagnosis of GIST (Kit(+)), resected tumor size >= 3 cm, and a complete gross resection within 14-70 days prior to registration. Imatinib, 400 mg orally, was administered once daily for 1 year. The study was terminated after completion of the third protocol-specified interim analysis. At that time, 100 RFS events were confirmed by a blinded central independent review. With a median follow-up of 14 months, 30 RFS events were observed in the imatinib group and 70 were observed in the placebo group (hazard ratio, 0.398; 95% confidence interval, 0.259-0.610; two-sided p-value < .0001). OS results are immature. Most patients in both groups experienced at least one adverse reaction, and 31% of the imatinib group and 18% of the placebo group experienced grade >= 3 adverse reactions. The most frequently reported adverse reactions (>= 20%) were diarrhea, fatigue, nausea, edema, decreased hemoglobin, rash, vomiting, and abdominal pain. Drug was discontinued for adverse reactions in 17% and 3% of the imatinib and placebo-treated patients, respectively. The Oncologist 2010; 15: 300-307 C1 [Cohen, Martin H.; Cortazar, Patricia; Justice, Robert; Pazdur, Richard] US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Cohen, MH (reprint author), US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, White Oak Campus,10903 New Hampshire Ave,Bldg 22,, Silver Spring, MD 20993 USA. EM martin.cohen@fda.hhs.gov NR 19 TC 22 Z9 26 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2010 VL 15 IS 3 BP 300 EP 307 DI 10.1634/theoncologist.2009-0120 PG 8 WC Oncology SC Oncology GA 574OA UT WOS:000275998400009 PM 20200041 ER PT J AU Kwitkowski, VE Prowell, TM Ibrahim, A Farrell, AT Justice, R Mitchell, SS Sridhara, R Pazdur, R AF Kwitkowski, Virginia E. Prowell, Tatiana M. Ibrahim, Amna Farrell, Ann T. Justice, Robert Mitchell, Shan Sun Sridhara, Rajeshwari Pazdur, Richard TI FDA Approval Summary: Temsirolimus as Treatment for Advanced Renal Cell Carcinoma SO ONCOLOGIST LA English DT Article DE Temsirolimus; Renal cell carcinoma; Mammalian target of rapamycin; mTOR ID INTERFERON-ALPHA; SUNITINIB; TRIAL; SORAFENIB; SURVIVAL; CANCER AB This report summarizes the U. S. Food and Drug Administration (FDA)'s approval of temsirolimus (Torisel(R)), on May 30, 2007, for the treatment of advanced renal cell carcinoma (RCC). Information provided includes regulatory history, study design, study results, and literature review. A multicenter, three-arm, randomized, open-label study was conducted in previously untreated patients with poor-prognosis, advanced RCC. The study objectives were to compare overall survival (OS), progression-free survival (PFS), objective response rate, and safety in patients receiving interferon (IFN)-alpha versus those receiving temsirolimus alone or in combination with IFN-alpha. In the second planned interim analysis of the intent-to-treat population (n = 626), there was a statistically significant longer OS time in the temsirolimus (25 mg) arm than in the IFN-alpha arm (median, 10.9 months versus 7.3 months; hazard ratio [HR], 0.73; p = .0078). The combination of temsirolimus (15 mg) and IFN-alpha did not lead to a significant difference in OS compared with IFN-alpha alone. There was also a statistically significant longer PFS time for the temsirolimus (25 mg) arm than for the IFN-alpha arm (median, 5.5 months versus 3.1 months; HR, 0.66, p = .0001). Common adverse reactions reported in patients receiving temsirolimus were rash, asthenia, and mucositis. Common laboratory abnormalities were anemia, hyperglycemia, hyperlipidemia, and hypertriglyceridemia. Serious but rare cases of interstitial lung disease, bowel perforation, and acute renal failure were observed. Temsirolimus has demonstrated superiority in terms of OS and PFS over IFN-alpha and provides an additional treatment option for patients with advanced RCC. The Oncologist 2010; 15: 428-435 C1 [Kwitkowski, Virginia E.; Prowell, Tatiana M.; Ibrahim, Amna; Farrell, Ann T.; Justice, Robert; Sridhara, Rajeshwari; Pazdur, Richard] US FDA, Div Drug Oncol Prod, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Mitchell, Shan Sun] Univ Texas Arlington, Dept Math, Arlington, TX 76019 USA. RP Kwitkowski, VE (reprint author), US FDA, Div Drug Oncol Prod, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Mailstop 2105, Silver Spring, MD 20993 USA. EM Virginia.Kwitkowski@fda.hhs.gov NR 12 TC 74 Z9 74 U1 0 U2 4 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2010 VL 15 IS 4 BP 428 EP 435 DI 10.1634/theoncologist.2009-0178 PG 8 WC Oncology SC Oncology GA 587AD UT WOS:000276957400012 PM 20332142 ER PT J AU Brave, M Farrell, A Lin, SC Ocheltree, T Miksinski, SP Lee, SL Saber, H Fourie, J Tornoe, C Booth, B Yuan, WS He, K Justice, R Pazdur, R AF Brave, Michael Farrell, Ann Lin, Sue Ching Ocheltree, Terrance Miksinski, Sarah Pope Lee, Shwu-Luan Saber, Haleh Fourie, Jeanne Tornoe, Christoffer Booth, Brian Yuan, Weishi He, Kun Justice, Robert Pazdur, Richard TI FDA Review Summary: Mozobil in Combination with Granulocyte Colony-Stimulating Factor to Mobilize Hematopoietic Stem Cells to the Peripheral Blood for Collection and Subsequent Autologous Transplantation SO ONCOLOGY LA English DT Review DE Granulocyte colony-stimulating factor; Hematopoietic stem cells; Plerixafor ID PROGENITOR CELLS; LYMPHOMA PATIENTS; BONE-MARROW; POOR MOBILIZATION; ENGRAFTMENT; APHERESIS; MYELOMA; DONORS AB Purpose: On December 15, 2008, the US Food and Drug Administration approved plerixafor (Mozobil (R); Genzyme Corp.), a new small-molecule inhibitor of the CXCR4 chemokine receptor, for use in combination with granulocyte colony-stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSC) to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). This summary reviews the database supporting this approval. Experimental Design: The safety and efficacy of plerixafor were demonstrated by 2 multicenter, randomized, placebo-controlled studies in patients with NHL and MM who were eligible for autologous HSC transplantation. The primary efficacy end points were the collection of >= 5 x 10(6) CD34+ cells/kg from the peripheral blood in 4 or fewer apheresis sessions in patients with NHL or >= 6 x 10(6) CD34+ cells/kg from the peripheral blood in 2 or fewer apheresis sessions in patients with MM. Results: The 2 randomized studies combined enrolled 600 patients (298 with NHL and 302 with MM). Fifty-nine percent of patients with NHL who were mobilized with G-CSF and plerixafor had peripheral blood HSC collections of >= 5 x 10(6) CD34+ cells/kg in 4 or fewer apheresis sessions, compared with 20% of patients with NHL who were mobilized with G-CSF and placebo (p < 0.001). Seventy-two percent of patients with MM who were mobilized with Mozobil and G-CSF had peripheral blood HSC collections of >= 6 x 10(6) CD34+ cells/kg in 2 or fewer apheresis sessions, compared with 34% of patients with MM who were mobilized with placebo and G-CSF (p < 0.001). Common adverse reactions included diarrhea, nausea, vomiting, flatulence, injection site reactions, fatigue, arthralgia, headache, dizziness, and insomnia. Conclusions: This report describes the Food and Drug Administration review supporting the approval of plerixafor. Copyright (C) 2010 S. Karger AG, Basel C1 [Brave, Michael; Farrell, Ann; Lee, Shwu-Luan; Saber, Haleh; Justice, Robert; Pazdur, Richard] US FDA, Off Oncol Drug Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. [Lin, Sue Ching; Ocheltree, Terrance; Miksinski, Sarah Pope] US FDA, Off New Drug Qual Assessment, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. [Fourie, Jeanne; Tornoe, Christoffer; Booth, Brian] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. [Yuan, Weishi; He, Kun] US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. RP Brave, M (reprint author), US FDA, Off Oncol Drug Prod, Off New Drugs, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Room 2137, Silver Spring, MD 20903 USA. EM michael.brave@fda.hhs.gov NR 18 TC 52 Z9 52 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY-BASEL JI Oncology PY 2010 VL 78 IS 3-4 BP 282 EP 288 DI 10.1159/000315736 PG 7 WC Oncology SC Oncology GA 618CZ UT WOS:000279330300017 PM 20530974 ER PT B AU Lemery, S Keegan, P Pazdur, R AF Lemery, Steven Keegan, Patricia Pazdur, Richard BE Kelly, WK Halabi, S TI The Drug Evaluation Process in Oncology: FDA Perspective SO ONCOLOGY CLINICAL TRIALS LA English DT Article; Book Chapter ID APPROVAL C1 [Lemery, Steven] US FDA, OODP, CDER, Silver Spring, MD USA. [Keegan, Patricia] US FDA, Div Biol Oncol Prod, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Lemery, S (reprint author), US FDA, OODP, CDER, Silver Spring, MD USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-38-9 PY 2010 BP 307 EP 314 PG 8 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy GA BMU36 UT WOS:000273577900032 ER PT S AU Kim, DH Klein, KF Ilev, IK AF Kim, Do-Hyun Klein, Karl-Friedrich Ilev, Ilko K. BE Gannot, I TI Suppression of Modal Noise in a Multimode Fiber-Optic Delivery Output from an Ultra-Broadband Supercontinuum Light Source SO OPTICAL FIBERS AND SENSORS FOR MEDICAL DIAGNOSTICS AND TREATMENT APPLICATIONS X SE Proceedings of SPIE-The International Society for Optical Engineering LA English DT Proceedings Paper CT Conference on Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications X CY JAN 23-24, 2010 CL San Francisco, CA SP SPIE DE supercontinuum generation; photonic crystal fiber; modal noise ID OPTICAL-FIBER; GENERATION; SYSTEMS AB We have tested various methods to suppress the modal noise in multi-mode fiber (MMF) output from an ultra-broadband supercontinuum light which is generated in a nonlinear photonic-crystal fiber (PCF) pumped with a 1.06-mu m-wavelength, sub-nanosecond-pulse-width, 8-kHz-rep-rate Nd:YAG laser source. Significant amount of modal noise including spectral fluctuations was observed when the output from the photonic crystal single-mode fiber (SMF) was directly coupled into MMF. Standard mode-exciting and -mixing techniques such as mode scrambling and fiber stretching showed minimal effect on noise suppression. We observed significant suppression of modal noise by expanding the output beam from the PCF and tightly focus back into MMF using multiple lenses. The resulting spectra of the different MMFs are compared with the output from different SMFs coupled to the supercontinuum source, which are necessary to cover the broadband range of the supercontinuum source over more than two octaves, from 450 nm up to 2100 nm wavelength. C1 [Kim, Do-Hyun; Ilev, Ilko K.] US FDA, Div Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Kim, DH (reprint author), US FDA, Div Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. NR 16 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 978-0-8194-7955-6 J9 P SOC PHOTO-OPT INS PY 2010 VL 7559 AR 75590U DI 10.1117/12.846973 PG 6 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSL73 UT WOS:000284872400022 ER PT S AU Kim, DH Ilev, IK AF Kim, Do-Hyun Ilev, Ilko K. BE Gannot, I TI Analysis of Some Substantial Collimating Lens Functions in Fiber-Optic Confocal Microscopy SO OPTICAL FIBERS AND SENSORS FOR MEDICAL DIAGNOSTICS AND TREATMENT APPLICATIONS X SE Proceedings of SPIE-The International Society for Optical Engineering LA English DT Proceedings Paper CT Conference on Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications X CY JAN 23-24, 2010 CL San Francisco, CA SP SPIE DE confocal microscopy; high numerical aperture fiber ID SCANNING MICROSCOPE; AXIAL RESOLUTION AB Some substantial functions of collimating lens in two-lens confocal microscope configuration were studied using ray-tracing software and experiments. Also, basic advantages of using a high-numerical-aperture optical fiber for a confocal microscope configuration were investigated. It provides higher confocality without reducing the coupling efficiency between light signal and fiber. We performed comparative experiments using two optical fibers with different numerical apertures and the results from axial confocal response tests agreed with the theoretical prediction. C1 [Kim, Do-Hyun; Ilev, Ilko K.] US FDA, Div Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Kim, DH (reprint author), US FDA, Div Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. NR 10 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 978-0-8194-7955-6 J9 P SOC PHOTO-OPT INS PY 2010 VL 7559 AR 75590E DI 10.1117/12.843689 PG 6 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSL73 UT WOS:000284872400012 ER PT S AU Sapsford, KE AF Sapsford, Kim E. BE Zourob, M Lakhtakia, A TI Total-Internal-Reflection Platforms for Chemical and Biological Sensing Applications SO OPTICAL GUIDED-WAVE CHEMICAL AND BIOSENSOS I SE Springer Series on Chemical Sensors and Biosensors LA English DT Article; Book Chapter DE Total internal reflection; Fluorescence; Biosensor; Chemical sensor; Multiplex detection; Array ID PLANAR WAVE-GUIDES; PHOTONIC CRYSTAL-SURFACE; FLUORESCENCE-BASED MICROARRAYS; SELF-ASSEMBLED MONOLAYERS; ARRAY BIOSENSOR; ENHANCED FLUORESCENCE; PROTEIN MICROARRAYS; ORIENTED IMMOBILIZATION; ANTIMICROBIAL PEPTIDES; HYBRIDIZATION ASSAYS AB Sensing platforms based on the principle of total internal reflection (TIR) represent a fairly mature yet still expanding and exciting field of research. Sensor development has mainly been driven by the need for rapid, stand-alone, automated devices for application in the fields of clinical diagnosis and screening, food and water safety, environmental monitoring, and chemical and biological warfare agent detection. The technologies highlighted in this chapter are continually evolving, taking advantage of emerging advances in microfabrication, lab-on-a-chip, excitation, and detection techniques. This chapter describes many of the underlying principles of TIR-based sensing platforms and additionally focusses on planar TIR fluorescence (TIRF)-based chemical and biological sensors. C1 US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. RP Sapsford, KE (reprint author), US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. EM kim.sapsford@fda.hhs.gov NR 121 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1612-7617 BN 978-3-540-88241-1 J9 SPRINGER SER CHEM SE PY 2010 VL 7 BP 3 EP 20 DI 10.1007/978-3-540-88242-8_1 PG 18 WC Chemistry, Analytical; Optics SC Chemistry; Optics GA BOY77 UT WOS:000278072100001 ER PT B AU Lampel, KA AF Lampel, Keith A. BE Juneja, VK Sofos, JN TI Shigella SO PATHOGENS AND TOXINS IN FOODS: CHALLENGES AND INTERVENTIONS LA English DT Article; Book Chapter ID ENTEROINVASIVE-ESCHERICHIA-COLI; HEMOLYTIC-UREMIC SYNDROME; UNITED-STATES; WATERBORNE OUTBREAKS; TOMATO SURFACES; GLOBAL BURDEN; FLEXNERI 2A; DAY-CARE; SONNEI; SURVIVAL C1 US FDA, College Pk, MD 20740 USA. RP Lampel, KA (reprint author), US FDA, HFS 710,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 93 TC 0 Z9 0 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-459-5 PY 2010 BP 131 EP 145 PG 15 WC Food Science & Technology SC Food Science & Technology GA BLX01 UT WOS:000271246200009 ER PT B AU Hall, S AF Hall, Sherwood BE Juneja, VK Sofos, JN TI Seafood Toxins SO PATHOGENS AND TOXINS IN FOODS: CHALLENGES AND INTERVENTIONS LA English DT Article; Book Chapter ID PARALYTIC SHELLFISH TOXINS; PERFORMANCE LIQUID-CHROMATOGRAPHY; DINOFLAGELLATE GYMNODINIUM-CATENATUM; PHOSPHATASE INHIBITION ASSAY; RECEPTOR-BINDING ASSAY; PRINCE-EDWARD-ISLAND; PACIFIC RED TIDES; DOMOIC ACID; OKADAIC ACID; MASS-SPECTROMETRY C1 US FDA, Chem Contaminants Branch HFS 716, Div Bioanalyt Chem, Off Regulatory Sci,Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Hall, S (reprint author), US FDA, Chem Contaminants Branch HFS 716, Div Bioanalyt Chem, Off Regulatory Sci,Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 180 TC 1 Z9 1 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-459-5 PY 2010 BP 233 EP 247 PG 15 WC Food Science & Technology SC Food Science & Technology GA BLX01 UT WOS:000271246200015 ER PT B AU Diaz-Amigo, C Yeung, JM AF Diaz-Amigo, Carmen Yeung, Jupiter M. BE Juneja, VK Sofos, JN TI Critical Evaluation of Uncertainties of Gluten Testing: Issues and Solutions for Food Allergen Detection SO PATHOGENS AND TOXINS IN FOODS: CHALLENGES AND INTERVENTIONS LA English DT Article; Book Chapter ID FLIGHT MASS-SPECTROMETRY; CELIAC-DISEASE; WHEAT-GLUTEN; MONOCLONAL-ANTIBODY; COMPETITIVE ELISA; GLIADIN CONTENT; FLOUR PROTEINS; FREE DIET; HEAT; BARLEY C1 [Diaz-Amigo, Carmen] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Yeung, Jupiter M.] Grocery Manufacturers Assoc, Washington, DC 20005 USA. RP Diaz-Amigo, C (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. NR 66 TC 5 Z9 5 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-459-5 PY 2010 BP 286 EP 300 PG 15 WC Food Science & Technology SC Food Science & Technology GA BLX01 UT WOS:000271246200018 ER PT B AU Momcilovic, D AF Momcilovic, Dragan BE Juneja, VK Sofos, JN TI Prions and Prion Diseases SO PATHOGENS AND TOXINS IN FOODS: CHALLENGES AND INTERVENTIONS LA English DT Article; Book Chapter ID BOVINE SPONGIFORM ENCEPHALOPATHY; CHRONIC WASTING DISEASE; CREUTZFELDT-JAKOB-DISEASE; DEER ODOCOILEUS-HEMIONUS; CAPTIVE MULE DEER; TRANSGENIC MICE; NERVOUS-SYSTEM; GREAT-BRITAIN; SCRAPIE AGENT; PROTEINASE-K C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Momcilovic, D (reprint author), US FDA, Ctr Vet Med, Rockville, MD 20855 USA. NR 115 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-459-5 PY 2010 BP 343 EP 356 PG 14 WC Food Science & Technology SC Food Science & Technology GA BLX01 UT WOS:000271246200022 ER PT J AU Bocchini, JA Bradley, JS Brady, MT Bernstein, HH Byington, CL Fisher, MC Glode, MP Jackson, MA Keyserling, HL Kimberlin, DW Orenstein, WA Schutze, GE Willoughby, RE Bell, BP Bortolussi, R Clover, RD Fischer, MA Gorman, RL Lee, L Pratt, RD Read, JS Gellin, BG Starke, JR Swanson, J Meissner, HC Rubin, LG Pickering, LK Baker, CJ Long, SS Frantz, J AF Bocchini, Joseph A., Jr. Bradley, John S. Brady, Michael T. Bernstein, Henry H. Byington, Carrie L. Fisher, Margaret C. Glode, Mary P. Jackson, Mary Anne Keyserling, Harry L. Kimberlin, David W. Orenstein, Walter A. Schutze, Gordon E. Willoughby, Rodney E., Jr. Bell, Beth P. Bortolussi, Robert Clover, Richard D. Fischer, Marc A. Gorman, Richard L. Lee, Lucia Pratt, R. Douglas Read, Jennifer S. Gellin, Bruce G. Starke, Jeffrey R. Swanson, Jack Meissner, H. Cody Rubin, Lorry G. Pickering, Larry K. Baker, Carol J. Long, Sarah S. Frantz, Jennifer CA Comm Infect Dis TI Policy Statement-Recommended Childhood and Adolescent Immunization Schedules-United States, 2010 SO PEDIATRICS LA English DT Article C1 [Bell, Beth P.; Fischer, Marc A.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Bortolussi, Robert] Canadian Paediat Soc, Ottawa, ON, Canada. [Clover, Richard D.] Amer Acad Family Phys, Leawood, KS USA. [Gorman, Richard L.] NIH, Bethesda, MD USA. [Lee, Lucia; Pratt, R. Douglas] US FDA, Rockville, MD 20857 USA. [Read, Jennifer S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. OI Byington, Carrie/0000-0002-7350-9495 NR 3 TC 10 Z9 11 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2010 VL 125 IS 1 BP 195 EP 196 DI 10.1542/peds.2009-3194 PG 2 WC Pediatrics SC Pediatrics GA 540PR UT WOS:000273348000027 ER PT J AU McKibben, LJ Boone, DJ Marchibroda, J Issa, AM AF McKibben, Linda J. Boone, D. Joe Marchibroda, Janet Issa, Amalia M. TI A novel Transformation Model (c) for personalized medicine laboratory systems SO PERSONALIZED MEDICINE LA English DT Article DE diffusion of innovations; genomic diagnostics; laboratory health systems; laboratory medicine; pharmacogenetics; pharmacogenomics; Transformation Model (c) ID HEALTH-CARE; PREVENTION AB The role of health system laboratories is critical to the appropriate clinical integration of personalized medicine. We conducted semistructured interviews with experts and opinion leaders representing laboratory medicine, health policy and the diagnostics industry, to examine what is known about the real-world effectiveness of health laboratories as organizations. We describe and encourage the wider use of an evidence-based, novel Transformation Model (c) to prepare for the future and set goals for a better health system. A collaborative approach appropriately integrates the efficiency and high-quality expertise of the health laboratory system with the transformative vision of the personalized medicine community. C1 [Issa, Amalia M.] Univ Houston, Program Personalized Med & Targeted Therapeut, Dept Pharmacol & Pharmaceut Sci, Dept Clin Sci & Adm,Coll Pharm, Houston, TX 77030 USA. [McKibben, Linda J.] US FDA, Rockville, MD 20857 USA. [Boone, D. Joe] Battelle Inc, Columbus, OH USA. [Marchibroda, Janet] IBM Healthcare, Bethesda, MD USA. RP Issa, AM (reprint author), Univ Houston, Program Personalized Med & Targeted Therapeut, Dept Pharmacol & Pharmaceut Sci, Dept Clin Sci & Adm,Coll Pharm, 1441 Moursund St, Houston, TX 77030 USA. EM aissa@uh.edu NR 21 TC 1 Z9 1 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 J9 PERS MED JI Pers. Med. PD JAN PY 2010 VL 7 IS 1 BP 87 EP 94 DI 10.2217/PME.09.66 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 543MS UT WOS:000273582900013 ER PT S AU Thompson, K AF Thompson, Karol BE Simopoulous, AP Milner, JA TI Toxicogenomics and Studies of Genomic Effects of Dietary Components SO PERSONALIZED NUTRITION: TRANSLATING NUTRIGENETIC/NUTRIGENOMIC RESEARCH INTO DIETARY GUIDELINES SE World Review of Nutrition and Dietetics LA English DT Article; Book Chapter ID GENE-EXPRESSION PROFILES; RNA REFERENCE SAMPLES; RAT-LIVER; TISSUE; TRANSCRIPTOME; LABORATORIES; PERFORMANCE; COMPENDIUM; TOXICOLOGY; PLATFORMS C1 [Thompson, Karol] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Thompson, K (reprint author), 10903 New Hampshire Ave,WO64-2036, Silver Spring, MD 20993 USA. EM karol.thompson@fda.hhs.gov NR 26 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0084-2230 BN 978-3-8055-9427-1 J9 WORLD REV NUTR DIET JI World Rev.Nutr.Diet. PY 2010 VL 101 BP 115 EP 122 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BOY58 UT WOS:000278067400012 PM 20436258 ER PT S AU Starlard-Davenport, A Tryndyak, V Kosyk, O Ross, SR Rusyn, I Beland, FA Pogribny, IP AF Starlard-Davenport, Athena Tryndyak, Volodymyr Kosyk, Oksana Ross, Sharon R. Rusyn, Ivan Beland, Frederick A. Pogribny, Igor P. BE Simopoulous, AP Milner, JA TI Dietary Methyl Deficiency, microRNA Expression and Susceptibility to Liver Carcinogenesis SO PERSONALIZED NUTRITION: TRANSLATING NUTRIGENETIC/NUTRIGENOMIC RESEARCH INTO DIETARY GUIDELINES SE World Review of Nutrition and Dietetics LA English DT Article; Book Chapter ID HUMAN HEPATOCELLULAR-CARCINOMA; TUMOR-SUPPRESSOR; CYCLOOXYGENASE-2 EXPRESSION; GENE-EXPRESSION; BREAST-CANCER; IN-VIVO; APOPTOSIS; CELLS; ACTIVATION; MIR-122 C1 [Starlard-Davenport, Athena; Tryndyak, Volodymyr; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Kosyk, Oksana; Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. [Ross, Sharon R.] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 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 ES015241] NR 48 TC 4 Z9 6 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0084-2230 BN 978-3-8055-9427-1 J9 WORLD REV NUTR DIET JI World Rev.Nutr.Diet. PY 2010 VL 101 BP 123 EP 130 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BOY58 UT WOS:000278067400013 PM 20436259 ER PT B AU Buehler, G Huynh-Ba, K AF Buehler, Gary Huynh-Ba, Kim BE HuynhBa, K TI Regulatory Perspectives on Product Stability SO PHARMACEUTICAL STABILITY TESTING TO SUPPORT GLOBAL MARKETS SE Biotechnology Pharmaceutical Aspects LA English DT Proceedings Paper CT Workshop on Pharmaceutical Stability Testing to Support Global Markets CY SEP 10-12, 2007 CL Bethesda, MD SP Amer Assoc Pharmaceut Scientists AB Recently, FDA has adopted the principles of Quality-by-Design and promotes the use of pharmaceutical development information in original applications. Stability studies occur in three phases in the life-cycle of a pharmaceutical product. They are: Stability studies during product development, stability studies that support a marketing application and stability studies that support post-approval changes. Quality-by-Design determines the stability studies conducted during product development. At the time of submission of an application, a package of stability data on the to-be-marketed product is combined with the knowledge gained during product development to establish a shelf-life for the drug product. After approval, routine stability data is collected to monitor product quality. When changes to the product formulation or its manufacturing occur, it may be recommended to the sponsor to obtain stability data to verify whether the change does not adversely affect the stability of the drug product. C1 [Buehler, Gary] US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Rockville, VA USA. RP Buehler, G (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Rockville, VA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ARLINGTON PA 2107 WILSON BLVD, STE 700, ARLINGTON, VA 22201 USA BN 978-1-4419-0888-9 J9 BIOTECH PHARM ASPECT PY 2010 VL 12 BP 9 EP 13 DI 10.1007/978-1-4419-0889-6_2 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BQY09 UT WOS:000282088400001 ER PT B AU Molzon, JA AF Molzon, Justina A. BE HuynhBa, K TI Current International Harmonization Efforts SO PHARMACEUTICAL STABILITY TESTING TO SUPPORT GLOBAL MARKETS SE Biotechnology Pharmaceutical Aspects LA English DT Proceedings Paper CT Workshop on Pharmaceutical Stability Testing to Support Global Markets CY SEP 10-12, 2007 CL Bethesda, MD SP Amer Assoc Pharmaceut Scientists AB Efforts towards international cooperation or harmonization can occur at varying levels at the level of technical and scientific requirements, of dossier format and content, or of assessment and review practices. Three contrasting models for regional cooperation in drug regulation harmonization, the corporate, populist, and cooperative, are described and compared. Utilizing a specific case, drug stability testing requirements in Climatic Zone IV, the author explores each organizational model in action, reviews recent history of a key stability debate among harmonization initiatives from different climatic zones, discusses benefits and disadvantages seen in organizational models, and proposes the best practices approach to global harmonization efforts for the future. C1 US FDA, Ctr Drug Evaluat & Res, Int Programs, Rockville, VA USA. RP Molzon, JA (reprint author), US FDA, Ctr Drug Evaluat & Res, Int Programs, Rockville, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ARLINGTON PA 2107 WILSON BLVD, STE 700, ARLINGTON, VA 22201 USA BN 978-1-4419-0888-9 J9 BIOTECH PHARM ASPECT PY 2010 VL 12 BP 15 EP 22 DI 10.1007/978-1-4419-0889-6_3 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BQY09 UT WOS:000282088400002 ER PT B AU Buehler, G Huynh-Ba, K AF Buehler, Gary Huynh-Ba, Kim BE HuynhBa, K TI Regulatory Requirements for Stability Testing of Generics SO PHARMACEUTICAL STABILITY TESTING TO SUPPORT GLOBAL MARKETS SE Biotechnology Pharmaceutical Aspects LA English DT Proceedings Paper CT Workshop on Pharmaceutical Stability Testing to Support Global Markets CY SEP 10-12, 2007 CL Bethesda, MD SP Amer Assoc Pharmaceut Scientists AB The Office of Generic Drugs (OGD) of the Food and Drug Administration (FDA) believes that stability of drug products is best ensured through quality-by-design. Quality-by-Design (QbD) in the context of stability means that a sponsor identifies potential mechanisms for instability and designs the formulation, container-closure system and manufacturing processes to mitigate the potential for instability. Under OGD's new question-based review system, quality-by-design is documented in the pharmaceutical development report. However, the stability of generic drug products must still be demonstrated with data. On June 1, 2006, the FDA withdrew the 1998 draft stability guidance leaving the ICH QI documents as the only advice to sponsors. The scope of the ICH Stability Guidance is limited to new molecular entities and associated products. However, many sections of the ICH Q1 documents could apply to the new Abbreviated New Drug Applications (ANDAs). For example the storage temperature and relative humidity that are specified in ICH Ql for accelerated, long term, and other conditions could be used for ANDAs. This talk will attempt to cover those recommendations which differ from ICH Q1 (e.g., initial submissions for new ANDAs), those for which no guidance is provided in the ICH document (e.g., post-approval changes), and those for which additional information is provided (e.g., data to support in-use conditions). C1 [Buehler, Gary] US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Rockville, VA USA. RP Buehler, G (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Rockville, VA USA. NR 0 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 BN 978-1-4419-0888-9 J9 BIOTECH PHARM ASPECT PY 2010 VL 12 BP 61 EP 66 DI 10.1007/978-1-4419-0889-6_9 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BQY09 UT WOS:000282088400008 ER PT B AU Khan, MA AF Khan, Mansoor A. BE HuynhBa, K TI Stability of Repackaged Products SO PHARMACEUTICAL STABILITY TESTING TO SUPPORT GLOBAL MARKETS SE Biotechnology Pharmaceutical Aspects LA English DT Proceedings Paper CT Workshop on Pharmaceutical Stability Testing to Support Global Markets CY SEP 10-12, 2007 CL Bethesda, MD SP Amer Assoc Pharmaceut Scientists ID VALIDATED HPLC METHOD; UNIT-DOSE CONTAINERS; DRUG PRODUCTS; GABAPENTIN; SYRUP AB For better patient compliance and easier distribution, some drug products are frequently repackaged from their original containers into unit-dose packages by pharmacists or commercial repackagers. The USP indicates that for non-sterile solid dosage forms packaged in unit-dose containers, the beyond-use date shall be 1 year from the date the drug is packaged into the unit-dose container or the expiration date on the manufacturer's container, whichever is earlier, unless stability data or the manufacturer's labeling indicates otherwise. Due to differences in moisture permeation, thermal susceptibility or surface chemistry of the new packaging material when compared to the original, the stability of a repackaged drug product can differ from that obtained from original container. This concern prompted us to study the stability issues associated with certain repackaged products. This chapter will highlight some of the findings in our research laboratory. C1 US FDA, Div Prod Qual Res, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Khan, MA (reprint author), US FDA, Div Prod Qual Res, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 11 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ARLINGTON PA 2107 WILSON BLVD, STE 700, ARLINGTON, VA 22201 USA BN 978-1-4419-0888-9 J9 BIOTECH PHARM ASPECT PY 2010 VL 12 BP 123 EP 133 DI 10.1007/978-1-4419-0889-6_17 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BQY09 UT WOS:000282088400016 ER PT B AU Sayeed, VA Gupta, A Khan, MA AF Sayeed, Vilayat A. Gupta, Abhay Khan, Mansoor A. BE HuynhBa, K TI Stability of Split Tablets SO PHARMACEUTICAL STABILITY TESTING TO SUPPORT GLOBAL MARKETS SE Biotechnology Pharmaceutical Aspects LA English DT Proceedings Paper CT Workshop on Pharmaceutical Stability Testing to Support Global Markets CY SEP 10-12, 2007 CL Bethesda, MD SP Amer Assoc Pharmaceut Scientists ID RELEASE THEOPHYLLINE TABLETS; DISSOLUTION; WHOLE; CHOLESTEROL; INVITRO AB The current pharmacy practice of splitting tablets has grown exponentially in the last few years to contain the ever growing cost of health care. At present, there is no scientific evidence in the public domain to demonstrate that the random splitting of tablets would not pose any safety concerns by compromising the quality of the product. The presentation would addresses the quality risk associated with the tablet splitting and the need for generating adequate scientific data before recommending a tablet splitting. C1 [Sayeed, Vilayat A.] US FDA, Div Chem 3, Rockville, MD 20857 USA. RP Sayeed, VA (reprint author), US FDA, Div Chem 3, Rockville, MD 20857 USA. NR 10 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 BN 978-1-4419-0888-9 J9 BIOTECH PHARM ASPECT PY 2010 VL 12 BP 153 EP 160 DI 10.1007/978-1-4419-0889-6_20 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BQY09 UT WOS:000282088400019 ER PT J AU Alosh, M AF Alosh, Mohamed TI Modeling longitudinal count data with dropouts SO PHARMACEUTICAL STATISTICS LA English DT Article DE covariate-dependent dropouts; generalized Poisson autoregressive model; generalized mixed effects model; GEE; weighted GEE ID MISSING DATA AB This paper explores the utility of different approaches for modeling longitudinal count data with dropouts arising from a clinical study for the treatment of actinic keratosis lesions on the face and balding scalp. A feature of these data is that as the disease for subjects on the active arm improves their data show larger dispersion compared with those on the vehicle, exhibiting an over-dispersion relative to the Poisson distribution. After fitting the marginal (or population averaged) model using the generalized estimating equation (GEE), we note that inferences from such a model might be biased as dropouts are treatment related. Then, we consider using a weighted GEE (WGEE) where each subject's contribution to the analysis is weighted inversely by the subject's probability of dropout. Based on the model findings, we argue that the WGEE might not address the concerns about the impact of dropouts on the efficacy findings when dropouts are treatment related. As an alternative, we consider likelihood-based inference where random effects are added to the model to allow for heterogeneity across subjects. Finally, we consider a transition model where, unlike the previous approaches that model the log-link function of the mean response, we model the subject's actual lesion counts. This model is an extension of the Poisson autoregressive model of order 1, where the autoregressive parameter is taken to he a function of treatment as well as other covariates to induce different dispersions and correlations for the two treatment arms. We conclude with a discussion about model selection. Published in 2009 by John Wiley & Sons, Ltd. C1 US FDA, Div Biometr 3, OB, OTS,CDER, Silver Spring, MD USA. RP Alosh, M (reprint author), US FDA, Div Biometr 3, OB, OTS,CDER, Silver Spring, MD USA. FU CDER/FDA [RSR 07-59] FX This research was supported by CDER/FDA grant. RSR # 07-59. I would like to express my thanks to two anonymous referees and the Editor, Dr Scott Patterson, for their comments that improved the presentation of the materials. I would also like to thank my colleagues Drs A A. Alzaid and Kathleen Fritsch for their comments on the draft of this paper. NR 16 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1539-1604 J9 PHARM STAT JI Pharm. Stat. PD JAN-MAR PY 2010 VL 9 IS 1 BP 35 EP 45 DI 10.1002/pst.366 PG 11 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 580CS UT WOS:000276425100005 PM 19191272 ER PT B AU Gupta, A Sayeed, VA Khan, MA AF Gupta, Abhay Sayeed, Vilayat A. Khan, Mansoor A. BE Kulshreshtha, AK Singh, ON Wall, GM TI The Science and Regulatory Perspectives of Pharmaceutical Suspensions SO PHARMACEUTICAL SUSPENSIONS: FROM FORMULATION DEVELOPMENT TO MANUFACTURING LA English DT Article; Book Chapter AB This chapter details the requirements of the U.S. Food and Drug Administration pertaining to suspension drug products. Extensive information is provided on nomenclature, regulatory filing requirements for new drug applications and abbreviated new drug applications, as well as postapproval changes and supplements. The global move to the common technical document format is also discussed. Finally, the authors present an overview of how quality by design principles can be effectively applied to suspension drug product technology. The views expressed are authors own and do not necessarily reflect the policies of the FDA. C1 [Gupta, Abhay; Khan, Mansoor A.] US FDA, Div Prod Qual Res, Off Testing & Res, CDER, Silver Spring, MD 20993 USA. [Sayeed, Vilayat A.] US FDA, Div Chem, OGD, CDER, Rockville, MD 20857 USA. RP Khan, MA (reprint author), US FDA, Div Prod Qual Res, Off Testing & Res, CDER, Silver Spring, MD 20993 USA. EM mansoor.khan@fda.hhs.gov NR 17 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-1086-8 PY 2010 BP 265 EP 283 DI 10.1007/978-1-4419-1087-5_9 D2 10.1007/978-1-4419-1087-5 PG 19 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BMJ16 UT WOS:000272542500009 ER PT J AU Devine, S West, S Andrews, E Tennis, P Hammad, TA Eaton, S Thorp, J Olshan, A AF Devine, Scott West, Suzanne Andrews, Elizabeth Tennis, Pat Hammad, Tarek A. Eaton, Susan Thorp, John Olshan, Andrew TI The identification of pregnancies within the general practice research database SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE pregnancy; medication; GPRD ID INFORMATION; CONCEPTION AB Background The United States is moving toward active drug safety surveillance using sources such as administrative claims and electronic medical records, but use of these data for studying teratogenicity has been challenging, as they typically do not allow for the easy identification of pregnancies. Our goal was to develop and validate an algorithm for the identification of pregnancies in the general practice research database (GPRD) that could be used to study pregnancy outcomes. Methods The algorithm identified pregnancies in women 15-45-year-old that were pregnant between 1 January 1987 and 31 December 2006. We identified live births, stillbirths, and spontaneous and elective terminations within a woman's record. We validated the algorithm using the additional clinical details maternity (ACDM) file and de-identified free-text records. Results We analyzed 16 035 394 records from 3 093 927 individuals and identified 383 184 women who had a total of 580 356 pregnancies. There were 415 221 full-term live births, 3080 pre- or post-term births, 1834 multi-fetus deliveries, 86 408 spontaneous abortions or miscarriages, 72 164 elective terminations, and 1649 stillbirths or fetal deaths. A marker of pregnancy care was identifiable for 86.3% of the 580356 pregnancies. The internal validation steps indicated that the algorithm produced consistent results with the ACDM file. Conclusions We were successful in identifying a large number of pregnancies in the GPRD. Our use of a hierarchical approach to identify pregnancy outcomes builds upon the methods suggested in previous work, while implementing additional steps to minimize potential misclassification of pregnancy outcomes. Copyright (c) 2009 John Wiley & Sons, Ltd. C1 [Devine, Scott; West, Suzanne; Thorp, John; Olshan, Andrew] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. [Andrews, Elizabeth; Tennis, Pat] RTI Hlth Solut, Res Triangle Pk, NC USA. [Hammad, Tarek A.] US FDA, Silver Spring, MD USA. [Eaton, Susan] GPRD, London, England. RP Devine, S (reprint author), 9648 Olive Blvd 218, St Louis, MO 63132 USA. EM sdevine@unc.edu RI Research Datalink, Clinical Practice/H-2477-2013; Research Datalink RT, Clinical Practice/I-7852-2013; CPRD, CPRD/B-9594-2017; OI Devine, Scott/0000-0003-2691-0507 FU NICHD NIH HHS [R24 HD050924] NR 16 TC 22 Z9 22 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JAN PY 2010 VL 19 IS 1 BP 45 EP 50 DI 10.1002/pds.1862 PG 6 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 544WR UT WOS:000273691100007 PM 19823973 ER PT B AU Shure, D AF Shure, Deborah BE Legato, MJ TI Gender-Specific Considerations in Pulmonary Hypertension SO PRINCIPLES OF GENDER-SPECIFIC MEDICINE, 2ND EDITION LA English DT Article; Book Chapter ID ARTERIAL-HYPERTENSION; SYSTEMIC-SCLEROSIS; ANTIRETROVIRAL THERAPY; CLINICAL-IMPLICATIONS; GERMLINE MUTATIONS; PLEXIFORM LESIONS; UNITED-STATES; DISEASE; SCLERODERMA; RECEPTOR C1 Ctr Devices & Radiol Hlth, Miami, FL USA. RP Shure, D (reprint author), Ctr Devices & Radiol Hlth, Miami, FL USA. NR 49 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-08-092150-1 PY 2010 BP 270 EP 276 DI 10.1016/B978-0-12-374271-1.00024-1 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA BEO92 UT WOS:000317610700030 ER PT B AU Hartong, M Goel, R Wijesekera, D AF Hartong, Mark Goel, Rajni Wijesekera, Duminda GP ASME TI POSITIVE TRAIN CONTROL AND THE RAIL SAFETY IMPROVEMENT ACT OF 2008 SO PROCEEDINGS OF THE ASME JOINT RAIL CONFERENCE, VOL 1: RAILROAD INFRASTRUCTURE ENGINEERING SAFETY, SECURITY AND ENVIRONMENT LA English DT Proceedings Paper CT ASME 2010 Joint Rail Conference CY APR 27-29, 2010 CL Univ Illinois Urbana Champaign, Urbana, IL SP ASME, Transportat Div HO Univ Illinois Urbana Champaign DE Railroad Safety; Regulations AB A series of high profile rail accidents, culminating in a head on collision on September 12, 2008 between a Union Pacific freight train and a METROLINK passenger train in Chatsworth, California, provided the impetus for the passage of the Rail Safety Improvement Act (RSIA) of 2008 (Public Law 110-432). The RSIA mandated the installation of Positive Train Control Systems across the US rail system by December 31, 2015. These new statutory requirements represent one of the most significant changes in US signal and train control systems since the introduction of track circuits and Centralized Traffic Control in the 1920's. This paper discusses the background which led to the passage of the RSIA, the new PTC requirements imposed by the law, and highlights the significant changes from existing federal safety regulations associated with voluntary PTC implementations that are being adopted by the to meet the law's requirement C1 [Hartong, Mark] US FDA, Off Safety, Washington, DC 20590 USA. RP Hartong, M (reprint author), US FDA, Off Safety, Washington, DC 20590 USA. EM mark.hartong@dot.gov; rgoel@howard.edu; dwijesek@gmu.edu NR 15 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 978-0-7918-4906-4 PY 2010 BP 407 EP 414 PG 8 WC Engineering, Civil; Engineering, Mechanical; Transportation Science & Technology SC Engineering; Transportation GA BUU81 UT WOS:000290415700048 ER PT J AU Li, JX Shefcheck, K Callahan, J Fenselau, C AF Li, Jinxi Shefcheck, Kevin Callahan, John Fenselau, Catherine TI Primary sequence and site-selective hydroxylation of prolines in isoforms of a major peanut allergen protein Ara h 2 SO PROTEIN SCIENCE LA English DT Article DE peanut antigen; de novo sequencing; tandem mass spectrometry; post-translational modifications ID MASS-SPECTROMETRY; ARA-H-2 AB The Ara h 2 proteins are major determinants of peanut allergens. These proteins have not been fully studied at the molecular level. It has been previously proposed that there are two isoforms of Ara h 2, based on primary structures that were deduced from two reported cDNA sequences. In this report, four isoforms have been purified and characterized individually. Mass spectrometric methods have been used to determine the protein sequences and to define post-translational modifications for all four isoforms. Two pairs of isoforms have been identified, corresponding to a long-chain form and a form that is shorter by 12 amino acids. Each pair is further differentiated by the presence or absence of a two amino acid sequence at the carboxyl terminus of the protein. Modifications that were characterized include site-specific hydroxylation of proline residues, but no glycosylation was found, in contrast to previous reports. C1 [Li, Jinxi; Fenselau, Catherine] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. [Shefcheck, Kevin; Callahan, John] CFSAN Food & Drug Adm, College Pk, MD 20740 USA. RP Fenselau, C (reprint author), Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. EM fenselau@umd.edu NR 11 TC 21 Z9 23 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD JAN PY 2010 VL 19 IS 1 BP 174 EP 182 DI 10.1002/pro.295 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 544FM UT WOS:000273638700020 PM 19937656 ER PT S AU Mei, N Fuscoe, JC Lobenhofer, EK Guo, L AF Mei, Nan Fuscoe, James C. Lobenhofer, Edward K. Guo, Lei BE Anegon, I TI Application of Microarray-Based Analysis of Gene Expression in the Field of Toxicogenomics SO RAT GENOMICS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Gene expression; Microarray; Mutagens; Toxicogenomics; Pathway analysis; Rat ID COMFREY SYMPHYTUM-OFFICINALE; TOXICOLOGICAL-RESEARCH; PRIMARY HEPATOCYTES; PROFILES; TOXICITY; AGONISTS; LIVER; RATS AB The field of toxicogenomics, which is becoming ail important sub-discipline of toxicology, resulted from the natural convergence of the field of conventional toxicological research and the emergent field of functional genomics. One technology that has played a significant role in the field of toxicogenomics (in addition to many others) is the gene expression microarray. In this chapter, the authors provide ail example of the application of gene expression microarrays to the field of toxicogenomics by detailing the strategy that was used for obtaining, analyzing, and interpreting gene expression data generated from RNA isolated from the liver of toxicant-exposed rats. C1 [Mei, Nan] Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Fuscoe, James C.; Guo, Lei] Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. [Lobenhofer, Edward K.] Cogenics, Sci Affairs, Morrisville, NC USA. RP Mei, N (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. OI MEI, NAN/0000-0002-3501-9014 NR 15 TC 4 Z9 4 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-388-6 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 597 BP 227 EP 241 DI 10.1007/978-1-60327-389-3_16 D2 10.1007/978-1-60327-389-3 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Physiology SC Biochemistry & Molecular Biology; Physiology GA BND76 UT WOS:000274240400016 PM 20013237 ER PT B AU Herold, KE Rasooly, A AF Herold, Keith E. Rasooly, A. BE Zourob, M TI Oligonucleotides as Recognition and Catalytic Elements SO RECOGNITION RECEPTORS IN BIOSENSORS LA English DT Article; Book Chapter DE Oligonucleotides; Recognition; Catalytic; RNA; DNA; Aptamers ID NEAREST-NEIGHBOR THERMODYNAMICS; PEPTIDE NUCLEIC-ACIDS; SMALL INTERFERING RNA; WHOLE-GENOME AMPLIFICATION; SURFACE-PLASMON RESONANCE; DOUBLE-STRANDED-RNA; DOT-T MISMATCHES; POLYMERASE CHAIN-REACTION; RATIONAL SIRNA DESIGN; SHORT HAIRPIN RNAS AB Oligonucleotides function as recognition elements for both nucleic acids and proteins in many ways. starting front their basic function as genetic material recognizing the complementary sequences of RNA or DNA, through their role as genetic regulatory elements in the form of antisense DNA/RNA, interfering RNA (RNAi) as well as enzymatic activities such as trails-cleaving ribozymes. Oligonucleotides call also serve as recognition elements for proteins ill the form of aptamers. All of these functions are derived from the basic primary, secondary, and tertiary structures along with their combinatorial nature, which allows vast variability within even short sequences. For biotechnology, the utility of oligonucleotides goes far beyond their basic function as a carrier of genetic information. Oligonucleotides are widely used as recognition elements for a large number of DNA and protein manipulation technologies. Including numerous Methods for DNA amplification. manipulation (e.g., mutation insertion or repair), and DNA Sequence recognition and analysis They are used for manipulation of gene expression including the use of ribozymes to catalyze RNA digestion, and siRNA and anti-sense RNA/DNA used for gene silencing ill both ill vitro and in vivo lit addition, they serve as ail alternative to antibodies as ligands for protein detection. The term oligonucleotide (or oligo) refers to a short segment of DNA or RNA commonly synthesized today by polymerizing nucleotide precursors using automated synthesizers Although most oligos used in molecular biology arc short ill the range of 20-30 bases (or mer), the term Is used here also to refer to longer sequences (e.g., similar to 200 bases) and to ribozymes, which arc traditionally clot viewed as oligos. In this manuscript. we describe the basic Structure of oligonucleotides relevant to general utility tit molecular biology and biotechnology This utility Includes function as recognition elements, basic utility for DNA amplification, recognition and manipulation, application for the regulation of gene expression and function and utility as protein recognition elements. C1 [Herold, Keith E.] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. [Rasooly, A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20903 USA. [Rasooly, A.] NCI, NIH, Rockville, MD 20852 USA. RP Herold, KE (reprint author), Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. EM herold@umd.edu; rasoolya@mail.nih.gov NR 205 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-0918-3 PY 2010 BP 631 EP 674 DI 10.1007/978-1-4419-0919-0_16 D2 10.1007/978-1-4419-0919-0 PG 44 WC Engineering, Biomedical SC Engineering GA BNU87 UT WOS:000275618200016 ER PT S AU Gammell, PM Maruvada, S Liu, YB Harris, GR AF Gammell, Paul M. Maruvada, Subha Liu, Yunbo Harris, Gerald R. BE Thompson, DO Chimenti, DE TI A PRE-EMPHASIS TECHNIQUE TO BROADEN THE USABLE FREQUENCY RANGE IN SWEPT-FREQUENCY SYSTEMS SO REVIEW OF PROGRESS IN QUANTITATIVE NONDESTRUCTIVE EVALUATION, VOLS 29A AND 29B SE AIP Conference Proceedings LA English DT Proceedings Paper CT 36th Annual Review of Progress in Quantitative Nondestructive Evaluation CY JUL 26-31, 2009 CL Univ Rhode Isl, Kingston, RI HO Univ Rhode Isl DE Acoustic Signal Processing; Time Delay Spectrometry; Attenuation Measurement; Hydrophone Calibration; Transducer Calibration ID TIME-DELAY SPECTROMETRY; MHZ AB The usable frequency range of an ultrasonic swept-frequency system can be compromised because of transducer bandwidth limitations or sample frequency response and corresponding signal-to-noise (S/N) considerations. By adding a variable gain amplifier together with an arbitrary waveform generator that is synchronized with the frequency sweep, the dynamic range of the receiver can be accommodated over a wider frequency range. This pre-emphasis approach has been demonstrated for two applications: substitution calibration of hydrophones and attenuation measurements. C1 [Gammell, Paul M.] LLC, Gammell Appl Technol, Exmore, VA 23350 USA. [Maruvada, Subha; Liu, Yunbo; Harris, Gerald R.] US FDA, Ctr Devices & Radiolog Hlth, Ultrason Lab, Silver Spring 20993, MD USA. RP Gammell, PM (reprint author), LLC, Gammell Appl Technol, Exmore, VA 23350 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0748-0 J9 AIP CONF PROC PY 2010 VL 1211 BP 670 EP + DI 10.1063/1.3362459 PG 2 WC Engineering, Aerospace; Physics, Applied SC Engineering; Physics GA BQW91 UT WOS:000282038500081 ER PT J AU Riordan, W Brorson, K Lute, S Etzel, M AF Riordan, William Brorson, Kurt Lute, Scott Etzel, Mark TI Examination of the Adsorption of Large Biological Molecules to Anion Exchange Surfaces Using Surface Plasmon Resonance SO SEPARATION SCIENCE AND TECHNOLOGY LA English DT Article DE adsorption kinetics; anion exchange chromatography; bioseparations; mass transfer limitations; surface plasmon resonance; viral clearance ID MEMBRANE CHROMATOGRAPHY; MASS-TRANSPORT; ANTIBODY PURIFICATION; OPTICAL BIOSENSOR; RATE CONSTANTS; BINDING; PROTEIN; VIRUS; BIACORE; PERFORMANCE AB Separation of viruses and other contaminants from protein therapeutics using anion exchange membrane adsorbers is a successful new approach to viral clearance; however, the fundamental phenomena that control performance are not well understood. For example, the kinetics of adsorption to the anion exchange surface may limit clearance, but has yet to be characterized experimentally and mathematically. In the present study, surface plasmon resonance was used to determine the adsorption kinetics for five large biological molecules: phage PP7, phage phi X174, phage PR772, thyroglobulin, and DNA. Rate constants were incorporated into a kinetic model of chromatography to illustrate the impact on performance. C1 [Riordan, William; Etzel, Mark] Univ Wisconsin, Dept Chem & Biol Engn, Madison, WI 53706 USA. [Brorson, Kurt; Lute, Scott] CDER FDA, Div Monoclonal Antibodies, Silver Spring, MD USA. RP Riordan, W (reprint author), Univ Wisconsin, Dept Chem & Biol Engn, 1605 Linden Dr, Madison, WI 53706 USA. EM wtriordan@gmail.com NR 37 TC 1 Z9 1 U1 1 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0149-6395 J9 SEPAR SCI TECHNOL JI Sep. Sci. Technol. PY 2010 VL 45 IS 1 BP 1 EP 10 AR PII 918410324 DI 10.1080/01496390903401770 PG 10 WC Chemistry, Multidisciplinary; Engineering, Chemical SC Chemistry; Engineering GA 553EE UT WOS:000274348000001 ER PT B AU Marszal, E AF Marszal, Ewa BE Georgiev, B Markovski, S TI THE STRUCTURE OF alpha(1)-PROTEINASE INHIBITOR POLYMER: FACTS AND HYPOTHESES SO SERPINS AND PROTEIN KINASE INHIBITORS: NOVEL FUNCTIONS, STRUCTURAL FEATURES AND MOLECULAR MECHANISMS SE Protein Biochemistry Synthesis Structure and Cellular Functions LA English DT Article; Book Chapter ID SERPIN POLYMERIZATION; CRYSTAL-STRUCTURE; ALPHA-1-PROTEINASE INHIBITOR; CONFORMATIONAL DISEASE; SHEET POLYMERIZATION; MASS-SPECTROMETRY; BETA-SHEET; IN-VIVO; ALPHA(1)-ANTITRYPSIN; LOOP AB The metastable structure of a serpin alpha(1)-proteinase inhibitor (alpha(1)-PI) makes it prone to conformational changes as a result of certain mutations and under mild denaturing conditions. Polymers of several variants of alpha(1)-PI, e.g., the most clinically relevant Z variant, accumulate in the liver and are believed to be the underlying cause of the liver disease associated with alpha(1)-PI deficiency: Such polymers have also been found in the circulation and in the lung. The structure of these polymers, which is important for structure-based drug design, remains unknown. The historically first and generally accepted model of the alpha(1)-PI polymers, the loop-A sheet model, which assumes insertion of the reactive center loop (RCL) of one alpha(1)-PI molecule between the central strands of the A beta-sheet of another molecule, has never been proven. In addition, this model is inconsistent with resonance energy transfer data obtained for heteropolymers formed from the Z and S variants. It is also difficult to envision how this model or even the more compact loop-A sheet model, deduced from fluorescence data obtained for the Z and S variant heteropolymers, can be compatible with electron microscopy (EM) images, which show apparently flexible polymer chains. Two other polymer models were deduced from the interactions seen between molecules in the crystals of two other serpins, antithrombin (AT) and plasminogen activator inhibitor-1 (PAI-1), which demonstrated the ability of the reactive center loop (RCL) to assume the beta-strand conformation and to extend the C or A beta-sheet in a neighboring molecule by formation of an additional edge strand. This became the ground for the loop-C sheet and strand s7A models of the polymer, although the interactions seen in crystals appear not to be stable in solution and, thus, appear not to reflect interactions existing in alpha(1)-PI polymers, which actually are stable. The focus of this paper is to review the observations used to support the proposed models and to revisit the wealth of literature data in search for unexplained observations and possible new interpretations. I also put forward the hypothesis that a fusion of beta-sheets, rather than insertion of the reactive center loop into a beta-sheet, may underlie the polymerization process of alpha(1)-PI. This hypothesis is an expansion of the recent head-to-head model proposed based on the polymerization of the alpha(1)-PI disulfide-linked dimer. C1 US FDA, Div Hematol, Off Blood Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Marszal, E (reprint author), US FDA, Div Hematol, Off Blood Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 44 TC 0 Z9 0 U1 1 U2 1 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60741-187-1 J9 PROTEIN BIOCHEM SYNT PY 2010 BP 199 EP 209 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BTD59 UT WOS:000286566700011 ER PT B AU Abramowicz, JS Fowlkes, JB Stratmeyer, ME Ziskin, M AF Abramowicz, Jacques S. Fowlkes, J. Brian Stratmeyer, Melvin E. Ziskin, Marvin BE Sheiner, E TI Bioeffects and Safety of Fetal Ultrasound Exposure: Why do we Need Epidemiology? SO TEXTBOOK OF PERINATAL EPIDEMIOLOGY LA English DT Article; Book Chapter ID RANDOMIZED CONTROLLED-TRIAL; ROUTINE ULTRASONOGRAPHY INUTERO; MACAQUE MACACA-FASCICULARIS; NEURAL-TUBE DEFECTS; DIAGNOSTIC ULTRASOUND; PRENATAL ULTRASOUND; IN-UTERO; FOLLOW-UP; NEUROLOGICAL DEVELOPMENT; CHILDHOOD MALIGNANCIES C1 [Fowlkes, J. Brian] Univ Michigan, Ann Arbor, MI 48109 USA. [Stratmeyer, Melvin E.] US FDA, Ctr Devices & Radiol Hlth, OSEL, Div Biol, Silver Spring, MD USA. [Ziskin, Marvin] Temple Univ, Sch Med, Ctr Biomed Phys, Philadelphia, PA 19140 USA. RP Abramowicz, JS (reprint author), Rush Univ, Med Ctr, Rush Fetal & Neonatal Med Program, Chicago, IL 60612 USA. EM Jacques_Abramowicz@rush.edu; fowlkes@umich.edu; melvin.stratmeyer@fda.hhs.gov; ziskin@temple.edu NR 100 TC 3 Z9 3 U1 0 U2 0 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60741-648-7 PY 2010 BP 251 EP 264 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BSD80 UT WOS:000284237200015 ER PT S AU Mattamal, GJ AF Mattamal, George J. BE Chandra, T Wanderka, N Reimers, W Ionescu, M TI Recent US FDA Reclassification on the Regulation of Tissue Adhesives for Skin Approximation in Clinical Applications SO THERMEC 2009, PTS 1-4 SE Materials Science Forum LA English DT Proceedings Paper CT 6th International Conference on Processing and Manufacturing of Advanced Materials CY AUG 25-29, 2009 CL Berlin, GERMANY SP Minerals, Met & Mat Soc DE Tissue Adhesives; Topical; Polymeric; Transitional Devices; Cyanoacrylate; Skin; Class I, II, III; 510 (k); IDE; PMA; Regulation; Dental Cement; Orthodontic; Neurologic; Embolization; Special Control; Guidance; Final Rule; FDA; CDRH AB Since the Medical Device Amendments of 1976 were enacted, the FDA considers Tissue Adhesives as "Transitional Devices" that are classified as Class III medical devices and are marketed in the United States subsequent to the approval of a Pre-market Approval Application (PMA). On February 9, 2006, Regulatory & Clinical Research Institute, Inc. submitted a petition to FDA to reclassify tissue adhesive transitional medical devices for skin approximation from Class III to Class 11 (special controls). FDA consulted with the General and Plastic Surgery Devices Advisory Panel, and on August 25, 2006, in a public meeting, the panel unanimously recommended that the tissue adhesive transitional medical devices for topical approximation of skin be classified from class III into Class II. Consequently, since June 30, 2008, following the effective date of the FDA Final Rule [I] that reclassified tissue adhesive transitional medical devices for skin approximation, any firm submitting a Premarket Notification [510(k)] for a tissue adhesive for the topical approximation of skin will need to address the issues covered in the published "Class II Special Control Guidance Document: Tissue Adhesive for the Topical Approximation of Skin, dated May 30, 2008" [2]. Accordingly, the firm needs to show that its device meets the recommendations of the published Class II guidance document or in some other way provides equivalent assurances of safety and effectiveness. Also, the author provides a short regulatory description of US FDA, under what laws its operates, how FDA evaluates new medical devices for marketing as Class I, Class 11, and Class III [3] C1 US FDA, Div Surg Orthoped & Restorat Devices, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Mattamal, GJ (reprint author), US FDA, Div Surg Orthoped & Restorat Devices, Off Device Evaluat, Ctr Devices & Radiol Hlth, 9200 Corp Blvd, Rockville, MD 20850 USA. NR 2 TC 1 Z9 1 U1 0 U2 1 PU TRANS TECH PUBLICATIONS LTD PI STAFA-ZURICH PA LAUBLSRUTISTR 24, CH-8717 STAFA-ZURICH, SWITZERLAND SN 0255-5476 J9 MATER SCI FORUM PY 2010 VL 638-642 BP 624 EP 628 DI 10.4028/www.scientific.net/MSF.638-642.624 PN 1-4 PG 5 WC Materials Science, Multidisciplinary; Materials Science, Biomaterials; Materials Science, Coatings & Films; Materials Science, Composites SC Materials Science GA BQH93 UT WOS:000281043800103 ER PT J AU Wang, C Zhang, XA Liu, F Paule, MG Slikker, W AF Wang, Cheng Zhang, Xuan Liu, Fang Paule, Merle G. Slikker, William, Jr. TI Anesthetic-Induced Oxidative Stress and Potential Protection SO THESCIENTIFICWORLDJOURNAL LA English DT Article DE N-methyl-D-aspartate (NMDA) receptors; reactive oxygen species (ROS); neurodegeneration; protective agents ID INDUCED DOPAMINERGIC NEUROTOXICITY; DEVELOPING RAT-BRAIN; INDUCED APOPTOTIC NEURODEGENERATION; CYANIDE-INDUCED APOPTOSIS; FACTOR-KAPPA-B; NITRIC-OXIDE; L-CARNITINE; CORTICAL-NEURONS; UP-REGULATION; ASPARTATE RECEPTORS AB Prolonged exposure of developing mammals to general anesthetics affects the N-methyl-D- aspartate (NMDA)-type glutamate or gamma-aminobutyric acid (GABA) receptor systems and enhances neuronal toxicity. Stimulation of immature neurons by NMDA antagonists or GABA agonists is thought to increase overall nervous system excitability and may contribute to abnormal neuronal cell death during development. Although the precise mechanisms by which NMDA antagonists or GABA agonists cause neuronal cell death are still not completely understood, up-regulation of the NMDA receptor subunit NR1 may be an initiative factor in neuronal cell death. It is increasingly apparent that mitochondria lie at the center of the cell death regulation process. Evidence for the role of oxidative stress in anesthetic-induced neurotoxicity has been generated in studies that apply oxidative stress blockers. Prevention of neuronal death by catalase and superoxide dismutase in vitro, or by M40403 (superoxide dismutase mimetic) in vivo, supports the contention that the involvement of reactive oxygen species (ROS) and the nature of neuronal cell death in rodents is mainly apoptotic. However, more evidence is necessary to in order verify the role of the NMDA receptor subunit NR1 and ROS in anesthetic-induced neurodegeneration. C1 [Wang, Cheng; Zhang, Xuan; Liu, Fang; Paule, Merle G.; Slikker, William, Jr.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Wang, C (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM cheng.wang@fda.hhs.gov NR 45 TC 15 Z9 16 U1 0 U2 4 PU THESCIENTIFICWORLD LTD PI NEWBURY PA 29-34, VENTURE WEST, NEW GREENHAM PARK, NEWBURY, BERKSHIRE RG19 6HX, ENGLAND SN 1537-744X J9 THESCIENTIFICWORLDJO JI TheScientificWorldJOURNAL PY 2010 VL 10 BP 1473 EP 1482 DI 10.1100/tsw.2010.118 PG 10 WC Environmental Sciences; Multidisciplinary Sciences SC Environmental Sciences & Ecology; Science & Technology - Other Topics GA 630LF UT WOS:000280273900020 PM 20661539 ER PT J AU Long, GG Morton, D Peters, T Short, B Skydsgaard, M AF Long, Gerald G. Morton, Daniel Peters, Terry Short, Brian Skydsgaard, Mikala TI Alternative Mouse Models for Carcinogenicity Assessment: Industry Use and Issues with Pathology Interpretation SO TOXICOLOGIC PATHOLOGY LA English DT Article DE alternative models; carcinogenesis; sarcoma; mouse ID GENETICALLY-ENGINEERED MICE; HISTORICAL CONTROL DATA; METHYL-N-NITROSOUREA; TRANSGENIC MICE; NONRESPONDER PHENOTYPE; POSITIVE CONTROL; P53(+/-) MOUSE; OVARIAN-TUMORS; AVAILABLE DATA; UTILITY AB The Carcinogenicity Alternative Mouse Models (CAMM) working Group of the Society of Toxicologic Pathology (STP) surveyed the membership to define current practices and Opinions in industry regarding the use of alternative mouse models for carcinogenicity testing The results of the survey indicated that CAMM are used most often to fulfill a regulatory requirement (e.g., to replace the two-year mouse bioassay) and arc being accepted by regulatory agencies. Alternative models are also sometimes Used For internal decision making or to address a mechanistic question. The CAMM most commonly used are the p53+/- and rasH2. The rasH2 appears to be the currently accepted model for general carcinogenicity testing. problems with study interpretation included lack of historic background data, unexpected tumor finding, and tumor identification/characterization of early lesions. problems with implementation or conduct of the study included extent of the pathology evaluation, number of animals. survival, and study duration. Recommendations were developed for, frequency and type of positive control testing. extent of histopathologic examination of test article-treated and positive control animals, current use and future development of diagnostic criteria: increased availability and use of historic data, and use of other genetically modified mice in carcinogenicity testing. C1 [Long, Gerald G.] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46225 USA. [Morton, Daniel] Pfizer Inc, Groton, CT 06340 USA. [Peters, Terry] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Short, Brian] Allergan Pharmaceut Inc, Irvine, CA USA. [Skydsgaard, Mikala] LAB Res Scantox, Lille Skensved, Denmark. RP Long, GG (reprint author), Eli Lilly & Co, Lilly Res Labs, 355 E Merrill St, Indianapolis, IN 46225 USA. EM Long_gerald_g@lilly.com NR 34 TC 19 Z9 19 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2010 VL 38 IS 1 BP 43 EP 50 DI 10.1177/0192623309354107 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA 559EL UT WOS:000274804800003 PM 19915137 ER PT J AU French, JE Leblanc, B Long, GG Morton, D Storer, R Leighton, J Swenberg, J Tsuda, H AF French, John E. Leblanc, Bernard Long, Gerald G. Morton, Daniel Storer, Richard Leighton, John Swenberg, James Tsuda, Hiroyuki TI Panel Discussion: Alternative Mouse Models for Carcinogenicity Assessment SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material DE carcinogenesis; animal models; genetically engineered mice; preclinical safety; assessment/risk management AB This article summarizes key points from Dr. Bernard Leblane's presentation European Perpectives on Alternative Mouse Carcinogenicity Models and a distillation of questions and answers from a panel discussion following plesentations on Alternative Mouse Models for Carcinogenicity Assessment at the Society of Toxicologic Pathology's annual symposium on June 23. 2009. in Washington. DC. C1 [French, John E.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Leblanc, Bernard] Pfizer, Amboise, France. [Long, Gerald G.] Eli Lilly & Co, Greenfield, IN USA. [Morton, Daniel] Pfizer Inc, Groton, CT 06340 USA. [Storer, Richard] Merck Res Labs, West Point, PA USA. [Leighton, John] US FDA, Silver Spring, MD USA. [Swenberg, James] Univ N Carolina, Chapel Hill, NC USA. [Tsuda, Hiroyuki] Nagoya City Univ, Sch Med, Nagoya, Aichi 467, Japan. RP Morton, D (reprint author), Pfizer Inc, MS-8274-1345,Eastern Point Rd, Groton, CT 06340 USA. EM dan.g.morton@pfizer.com NR 3 TC 2 Z9 2 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2010 VL 38 IS 1 BP 72 EP 75 DI 10.1177/0192623309352091 PG 4 WC Pathology; Toxicology SC Pathology; Toxicology GA 559EL UT WOS:000274804800006 PM 19884653 ER PT J AU Senior, JR AF Senior, John R. TI Unintended Hepatic Adverse Events Associated with Cancer Chemotherapy SO TOXICOLOGIC PATHOLOGY LA English DT Article DE chemotherapy; hepatoxicity; liver adaptation; benefit-risk balance ID ALANINE AMINOTRANSFERASE LEVELS; INDUCED LIVER-INJURY; TRANSAMINASE-ACTIVITY; DIAGNOSTIC-TESTS; HEALTHY RANGES; HEPATOTOXICITY; ACCURACY; TOXICITY; ONCOLOGY AB Chemotherapy is meant to be toxic, but it is particularly aimed at the tumor cells. Collateral damage may occur to normal cells and tissues, especially if they are fairly rapidly regenerating, as is the case for bone marrow cells, intestinal epithelial cells. and liver cells after hepatic injury. The liver has a great capacity to resist injury, overcome it. and to regenerate, even after quite massive injury (resection of 50%-65%, for example). This capacity may make it susceptible to chemotherapeutic toxicity, and a struggle between injury and adaptation. leading to recovery and tolerance of, to failure and death. If the chemotherapy is aimed just at delaying progression of the cancer for a few weeks or months, it may not be worth the risk of irreversible liver injury developing in that time. Close clinical observation and sound clinical judgment are required. C1 US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. RP Senior, JR (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Bldg 22 3482,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM john.senior@fda.hhs.gov NR 29 TC 8 Z9 9 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2010 VL 38 IS 1 BP 142 EP 147 DI 10.1177/0192623309351719 PG 6 WC Pathology; Toxicology SC Pathology; Toxicology GA 559EL UT WOS:000274804800013 PM 19858501 ER PT J AU Jacobson-Kram, D AF Jacobson-Kram, David TI Cancer Risk Assessment Approaches at the FDA/CDER: Is the Era of the 2-Year Bioassay Drawing to a Close? SO TOXICOLOGIC PATHOLOGY LA English DT Article DE cancer risk assessment; toxicogenomics; chronic bioassay AB Determining the carcinogenic potential of materials to which humans have significant exposures is an important, complex, and imperfect exercise. Not only are the methods for such determinations protracted and expensive and use large numbers of animals, extrapolation of data from such Studies to human risk is imprecise. With improved understanding of oncogene activation and tumor suppressor gene inactivation, a Bomber of animal models have been developed to dramatically reduce latency for chemically induced cancers and has led to the development and use of shorter carcinogenicity assays. Recent studies by a number of investigators suggest that specific gene signature patterns seen after short-term exposure of rats to test chemicals can predict long-term outcomes in cancer bioassays with relatively high accuracy. In addition, a recent survey performed by PhRMA member companies examined two hundred drug years to determine whether histological biomarkers seen at the end of a six- or twelve-month toxicology study in rats can predict the outcome of a two-year carcinogenicity Study, With only a handful of exceptions, chronic Studies appear capable of predicting effects at the end of two years with good accuracy. It is hoped that the combination of results from transgenic mouse assays and six-month rat studies will soon supplant the need for most two-year bioassays. C1 US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Silver Spring, MD 20993 USA. RP Jacobson-Kram, D (reprint author), US FDA, Ctr Drug Evaluat & Res, Off New Drugs, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM david.jacobsonkram@fda.hhs.gov NR 5 TC 17 Z9 17 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2010 VL 38 IS 1 BP 169 EP 170 DI 10.1177/0192623309351892 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 559EL UT WOS:000274804800016 PM 19887650 ER PT J AU Hines, RN Sargent, D Autrup, H Birnbaum, LS Brent, RL Doerrer, NG Hubal, EAC Juberg, DR Laurent, C Luebke, R Olejniczak, K Portier, CJ Slikker, W AF Hines, Ronald N. Sargent, Dana Autrup, Herman Birnbaum, Linda S. Brent, Robert L. Doerrer, Nancy G. Hubal, Elaine A. Cohen Juberg, Daland R. Laurent, Christian Luebke, Robert Olejniczak, Klaus Portier, Christopher J. Slikker, William TI Approaches for Assessing Risks to Sensitive Populations: Lessons Learned from Evaluating Risks in the Pediatric Population SO TOXICOLOGICAL SCIENCES LA English DT Review DE sensitive populations; pharmacokinetics; pharmacodynamics; genetic variability; pediatric population; risk assessment; exposure assessment ID NMDA RECEPTOR ANTAGONISTS; HUMAN PARAOXONASE PON1; HUMAN-FETAL LIVER; EXPOSURE ASSESSMENT; CHILDRENS HEALTH; ENVIRONMENTAL TOXICANTS; DEVELOPMENTAL-STAGE; IONIZING-RADIATION; NATIONAL CHILDRENS; POLYCHLORINATED-BIPHENYLS AB Assessing the risk profiles of potentially sensitive populations requires a "tool chest" of methodological approaches to adequately characterize and evaluate these populations. At present, there is an extensive body of literature on methodologies that apply to the evaluation of the pediatric population. The Health and Environmental Sciences Institute Subcommittee on Risk Assessment of Sensitive Populations evaluated key references in the area of pediatric risk to identify a spectrum of methodological approaches. These approaches are considered in this article for their potential to be extrapolated for the identification and assessment of other sensitive populations. Recommendations as to future research needs and/or alternate methodological considerations are also made. C1 [Doerrer, Nancy G.] Hlth & Environm Sci Inst, Int Life Sci Inst, Washington, DC 20005 USA. [Hines, Ronald N.] Childrens Hosp & Hlth Syst, Childrens Res Inst, Dept Pediat, Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Sargent, Dana] Bayer CropSci, Res Triangle Pk, NC 27709 USA. [Autrup, Herman] Univ Aarhus, Dept Environm & Occupat Med, DK-8000 Aarhus C, Denmark. [Birnbaum, Linda S.; Portier, Christopher J.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Brent, Robert L.] Alfred I duPont Hosp Children, Wilmington, DE 19899 USA. [Hubal, Elaine A. Cohen; Luebke, Robert] US EPA, Res Triangle Pk, NC 27709 USA. [Juberg, Daland R.] Dow AgroSci, Indianapolis, IN 46268 USA. [Laurent, Christian] European Food Safety Author, I-43100 Parma, Italy. [Olejniczak, Klaus] BfArM, Fed Inst Drugs & Med Devices, D-53175 Bonn, Germany. [Slikker, William] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Doerrer, NG (reprint author), Hlth & Environm Sci Inst, Int Life Sci Inst, 1156 15th St NW,2nd Floor, Washington, DC 20005 USA. EM ndoerrer@hesiglobal.org RI Portier, Christopher/A-3160-2010; OI Portier, Christopher/0000-0002-0954-0279; Hines, Ronald/0000-0002-3094-4200 FU NIGMS NIH HHS [R01 GM081344] NR 143 TC 13 Z9 15 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JAN PY 2010 VL 113 IS 1 BP 4 EP 26 DI 10.1093/toxsci/kfp217 PG 23 WC Toxicology SC Toxicology GA 534ZH UT WOS:000272935700002 PM 19770482 ER PT J AU Sharma, SK Basavanna, U Shukla, HD AF Sharma, Shashi K. Basavanna, Uma Shukla, Hem D. TI Protein Domain Analysis of C. botulinum Type A Neurotoxin and Its Relationship with Other Botulinum Serotypes SO TOXINS LA English DT Article DE protein domain; neurotoxin; BoNT serotypes; coiled-coil domain; phylogenetic AB Botulinum neurotoxins (BoNTs) are highly potent poisons produced by seven serotypes of Clostridium botulinum. The mechanism of neurotoxin action is a multistep process which leads to the cleavage of one of three different SNARE proteins essential for synaptic vesicle fusion and transmission of the nerve signals to muscles: synaptobrevin, syntaxin, or SNAP-25. In order to understand the precise mechanism of neurotoxin in a host, the domain structure of the neurotoxin was analyzed among different serotypes of C. botulinum. The results indicate that neurotoxins type A, C, D, E and F contain a coiled-coil domain while types B and type G neurotoxin do not. Interestingly, phylogenetic analysis based on neurotoxin sequences has further confirmed that serotypes B and G are closely related. These results suggest that neurotoxin has multi-domain structure, and coiled-coil domain plays an important role in oligomerisation of the neurotoxin. Domain analysis may help to identify effective antibodies to treat Botulinum toxin intoxication. C1 [Sharma, Shashi K.; Basavanna, Uma] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Shukla, Hem D.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. RP Sharma, SK (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM shashi.sharma@fda.hhs.gov; uma.basavanna@fda.hhs.gov; hshukla2@jhu.edu NR 26 TC 2 Z9 2 U1 0 U2 3 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6651 J9 TOXINS JI Toxins PD JAN PY 2010 VL 2 IS 1 BP 1 EP 9 DI 10.3390/toxins2010001 PG 9 WC Toxicology SC Toxicology GA V24UE UT WOS:000208434500001 PM 22069543 ER PT J AU Mohan, KVK Rao, SS Atreya, CD AF Mohan, Ketha V. K. Rao, Shilpakala Sainath Atreya, Chintamani D. TI Evaluation of antimicrobial peptides as novel bactericidal agents for room temperature-stored platelets SO TRANSFUSION LA English DT Article ID BLOOD COMPONENTS; PATHOGEN-REDUCTION; WHOLE-BLOOD; TRANSFUSION; CONTAMINATION; MECHANISMS; SYSTEMS AB BACKGROUND: A single cost-effective pathogen inactivation approach would help to improve the safety of our nation's blood supply. Several methods and technologies are currently being studied to help reduce bacterial contamination of blood components. There is clearly need for simple and easy-to-use pathogen inactivation techniques specific to plasma, platelets (PLTs), and red blood cells. STUDY DESIGN AND METHODS: In this report, we introduce a novel proof of concept: using known therapeutic antimicrobial peptides (AMPs) as bactericidal agents for room temperature-stored PLT concentrates (PCs). Nine synthetic AMPs, four from PLT microbicidal protein-derived peptides (PD1-4) and five Arg-Trp (RW) repeat peptides containing one to five repeats, were tested for bactericidal activity in plasma and PC samples spiked with Staphylococcus aureus, S. epidermidis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Bacillus cereus. A 3-log reduction of viable bacteria was considered as the bactericidal activity of a given peptide. RESULTS: In both plasma alone and PCs, RW3 peptide demonstrated bactericidal activity against S. aureus, S. epidermidis, E. coli, P. aeruginosa, and K. pneumoniae; PD4 and RW2 against P. aeruginosa; and RW4 against K. pneumoniae. The activity of each of these four peptides against the remaining bacterial species in the test panel resulted in less than a 3-log reduction in the number of viable bacteria and hence considered ineffective. CONCLUSIONS: These findings suggest a new approach to improving the safety of blood components, demonstrating the potential usefulness of screening therapeutic AMPs against selected bacteria to identify suitable bactericidal agents for stored plasma, PCs, and other blood products. C1 [Mohan, Ketha V. K.; Rao, Shilpakala Sainath; Atreya, Chintamani D.] US FDA, Ctr Biol Evaluat & Res, Sect Cell Biol, Lab Cellular Hematol, Bethesda, MD 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); Oak Ridge Institute for Science and Education (ORISE) 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 intraagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. The authors thank M. Kannan and S. Kulkarni, DH, OBRR, CBER, for review of the scientific content of the manuscript and Mitchell Berger, OBRR, CBER, for editorial review. NR 27 TC 10 Z9 10 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JAN PY 2010 VL 50 IS 1 BP 166 EP 173 DI 10.1111/j.1537-2995.2009.02376.x PG 8 WC Hematology SC Hematology GA 538FX UT WOS:000273171000025 PM 19761549 ER PT J AU Williams, DK Khan, AS AF Williams, Dhanya K. Khan, Arifa S. TI Role of neutralizing antibodies in controlling simian foamy virus transmission and infection SO TRANSFUSION LA English DT Article ID HTLV-I; IMMUNOGLOBULIN PROPHYLAXIS; RETROVIRAL TRANSMISSION; PASSIVE-IMMUNIZATION; HUMANS; BLOOD; HIV-1; TRANSFUSION; MACAQUES; REPLICATION AB BACKGROUND: Human infections with simian foamy viruses (SFVs) have been reported after occupational and nonoccupational exposure to infected animals and their tissues, blood, and body fluids, although there is no evidence for human-to-human transmission. We previously demonstrated SFV transmission in monkeys by blood transfusion with whole blood from one donor animal that had a low neutralizing antibody (NAb) endpoint titer, whereas blood transfusion from a second donor monkey that had a high NAb titer failed to transmit virus. These results suggested a role for NAbs in SFV transmission and establishment of infection. STUDY DESIGN AND METHODS: Whole blood and antibody-reduced blood were transfused into SFV-negative rhesus macaques. SFV infection in recipient animals was monitored by detection of virus sequences using polymerase chain reaction assays with nucleotide sequence confirmation, by analysis for antibody development in Western blots, and by virus isolation in coculture assays. NAb titer was evaluated by endpoint dilution assays. RESULTS: SFV transmission by whole blood transfusion from a donor monkey with high NAb endpoint titer failed to establish infection in SFV-negative monkeys, whereas virus transmission was successful with transfer of antibody-reduced blood cells. CONCLUSIONS: Passive transfer of high-titer NAbs blocked SFV cell-associated transmission, indicating that NAbs may play a role in virus transmission to individuals exposed to SFV-infected blood and tissues. C1 [Williams, Dhanya K.; Khan, Arifa S.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Khan, AS (reprint author), 8800 Rockville Pike,HFM-454,Bldg 29B,Room 4NN10, Bethesda, MD 20892 USA. EM arifa.khan@fda.hhs.gov NR 41 TC 8 Z9 8 U1 1 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JAN PY 2010 VL 50 IS 1 BP 200 EP 207 DI 10.1111/j.1537-2995.2009.02372.x PG 8 WC Hematology SC Hematology GA 538FX UT WOS:000273171000030 PM 19719470 ER PT B AU Hernandez, TD Levisohn, PM Buytaert-Hoefen, K Naritoku, DK AF Hernandez, Theresa D. Levisohn, Paul M. Buytaert-Hoefen, Kimberley Naritoku, Dean K. BE Ashley, MJ TI Posttraumatic Epilepsy and Neurorehabilitation SO TRAUMATIC BRAIN INJURY: REHABILITATION, TREATMENT, AND CASE MANAGEMENT, 3RD EDITION LA English DT Article; Book Chapter ID TRAUMATIC BRAIN-INJURY; AMYGDALA-KINDLED RATS; QUALITY STANDARDS SUBCOMMITTEE; EXCITOTOXIC CELL-DEATH; TONIC CLONIC SEIZURES; ACADEMY-OF-NEUROLOGY; DORSAL RAPHE NEURONS; ANTIEPILEPTIC DRUGS; FUNCTIONAL RECOVERY; HEAD-INJURY C1 [Hernandez, Theresa D.] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA. [Levisohn, Paul M.] Univ Colorado Denver, Sch Med, Neurosci Program, Aurora, CO USA. [Levisohn, Paul M.] Univ Colorado Denver, Childrens Hosp, Aurora, CO USA. [Buytaert-Hoefen, Kimberley] US FDA, Dept Hlth & Human Serv, Denver, CO USA. [Naritoku, Dean K.] Southern Illinois Univ, Sch Med, Dept Neurol, Springfield, IL USA. [Naritoku, Dean K.] Southern Illinois Univ, Sch Med, Dept Pharmacol, Springfield, IL USA. RP Hernandez, TD (reprint author), Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA. NR 194 TC 0 Z9 0 U1 1 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 978-1-4398-4982-8; 978-1-4200-7194-8 PY 2010 BP 29 EP 61 DI 10.1201/9781439849828-c2 D2 10.1201/9781439849828 PG 33 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA BF7QW UT WOS:000384329900003 ER PT B AU Binn, LN Lemon, SM AF Binn, Leonard N. Lemon, Stanley M. BE Artenstein, AW TI Hepatitis A SO VACCINES: A BIOGRAPHY LA English DT Article; Book Chapter ID CELL-CULTURE; VIRUS-VACCINE; EXPERIMENTAL-INFECTION; NEUTRALIZING ANTIBODY; AOTUS-TRIVIRGATUS; VIRAL-HEPATITIS; SERIAL PASSAGE; MRC-5 CELLS; LIVE; CHIMPANZEES C1 [Binn, Leonard N.] Walter Reed Army Inst Res, Div Viral Dis, Silver Spring, MD 20910 USA. [Lemon, Stanley M.] Univ Texas Med Branch, Inst Human Infect & Immun, Ctr Hepatitis Res, Dept Microbiol & Immunol, Galveston, TX 77555 USA. [Lemon, Stanley M.] US FDA, Advisory Comm Vaccines & Related Biol, Rockville, MD 20857 USA. RP Binn, LN (reprint author), Walter Reed Army Inst Res, Div Viral Dis, Silver Spring, MD 20910 USA. EM leonard.binn@us.army.mil; smlemon@utmb.edu NR 52 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1107-0 PY 2010 BP 335 EP 346 DI 10.1007/978-1-4419-1108-7_19 D2 10.1007/978-1-4419-1108-7 PG 12 WC History & Philosophy Of Science; Immunology; Microbiology SC History & Philosophy of Science; Immunology; Microbiology GA BNC81 UT WOS:000274169300019 ER PT B AU Calvo, MS Whiting, SJ AF Calvo, Mona S. Whiting, Susan J. BE Holick, MF TI Determinants of Vitamin D Intake SO VITAMIN D: PHYSIOLOGY, MOLECULAR BIOLOGY, AND CLINICAL APPLICATIONS, SECOND EDITION SE Nutrition and Health Series LA English DT Article; Book Chapter DE Cholecalciferol (vitamin D-3); ergocalciferol (vitamin D-2); 25-hydroxyvitamin D (25(OH)D); dietary guidelines; dietary supplements; food fortification ID RANDOMIZED CONTROLLED-TRIAL; SERUM 25-HYDROXYVITAMIN-D CONCENTRATION; AFRICAN-AMERICAN WOMEN; D DEFICIENCY; D SUPPLEMENTATION; UNITED-STATES; HEALTH CONSEQUENCES; D-3-FORTIFIED MILK; HYPOVITAMINOSIS-D; D FORTIFICATION AB The objective of our chapter is to provide convincing evidence of how changes in food consumption patterns, judicious fortification of food staples, and targeted supplementation of at-risk groups could be effective public health strategies to help increase vitamin D intake, maintain bone health. and potentially prevent chronic disease. We demonstrate the limitations of the Canadian and American food supply to provide sufficient vitamin D to Meet increased dietary needs when cutaneous synthesis of vitamin D is compromised. Vitamin D deficiency as measured by low circulating 25-hydroxyvitamin D [25(OH)D] and its link to increased risk of chronic disease is a significant global reality and threat to general public health, yet dietary intakes of vitamin D remain lower than the recommended dietary guidelines for the majority of individuals experiencing the lowest levels of 25(OH)D. C1 [Calvo, Mona S.] US FDA, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD USA. [Whiting, Susan J.] Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK, Canada. RP Calvo, MS (reprint author), US FDA, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD USA. NR 84 TC 3 Z9 3 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-300-8 J9 NUTR HEALTH SER JI Nutr. Health Ser. PY 2010 BP 361 EP 382 DI 10.1007/978-1-60327-303-9_18 D2 10.1007/978-1-60327-303-9 PG 22 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BOR11 UT WOS:000277365800018 ER PT S AU Arzhantsev, S Ruzicka, CM Kauffman, JF AF Arzhantsev, Sergey Ruzicka, Connie M. Kauffman, John F. BE Champion, PM Ziegler, LD TI Comparative Studies of Therapeutic Protein Secondary Structure Using Deep UV Resonance Raman Spectroscopy SO XXII INTERNATIONAL CONFERENCE ON RAMAN SPECTROSCOPY SE AIP Conference Proceedings LA English DT Proceedings Paper CT 22nd International Conference on Raman Spectroscopy CY AUG 08-13, 2010 CL Boston, MA SP NE Univ, Boston Univ & Photon Ctr, Horiba Sci, Thermo Sci, Bruker Opt ID SPECTROMETER; NM C1 [Arzhantsev, Sergey; Ruzicka, Connie M.; Kauffman, John F.] US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Arzhantsev, S (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, 1114 Market St,Room 1002, St Louis, MO 63101 USA. NR 10 TC 1 Z9 1 U1 1 U2 3 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0818-0 J9 AIP CONF PROC PY 2010 VL 1267 BP 176 EP 177 DI 10.1063/1.3482450 PG 2 WC Physics, Applied SC Physics GA BQK65 UT WOS:000281210900096 ER PT J AU Binet, R Maurelli, AT AF Binet, Rachel Maurelli, Anthony T. TI The chlamydial functional homolog of KsgA confers kasugamycin sensitivity to Chlamydia trachomatis and impacts bacterial fitness SO BMC MICROBIOLOGY LA English DT Article ID 16S RIBOSOMAL-RNA; MITOCHONDRIAL TRANSCRIPTION FACTOR; OBLIGATE INTRACELLULAR BACTERIA; ESCHERICHIA-COLI; ADENINE DIMETHYLTRANSFERASE; PHYLOGENETIC ANALYSIS; THERMUS-THERMOPHILUS; DEVELOPMENTAL CYCLE; PSITTACI 6BC; GENE AB Background: rRNA adenine dimethyltransferases, represented by the Escherichia coli KsgA protein, are highly conserved phylogenetically and are generally not essential for growth. They are responsible for the post-transcriptional transfer of two methyl groups to two universally conserved adenosines located near the 3'end of the small subunit rRNA and participate in ribosome maturation. All sequenced genomes of Chlamydia reveal a ksgA homolog in each species, including C. trachomatis. Yet absence of a S-adenosyl-methionine synthetase in Chlamydia, the conserved enzyme involved in the synthesis of the methyl donor S-adenosyl-L-methionine, raises a doubt concerning the activity of the KsgA homolog in these organisms. Results: Lack of the dimethylated adenosines following ksgA inactivation confers resistance to kasugamycin (KSM) in E. coli. Expression of the C. trachomatis L2 KsgA ortholog restored KSM sensitivity to the E. coli ksgA mutant, suggesting that the chlamydial KsgA homolog has specific rRNA dimethylase activity. C. trachomatis growth was sensitive to KSM and we were able to isolate a KSM resistant mutant of C. trachomatis containing a frameshift mutation in ksgA, which led to the formation of a shorter protein with no activity. Growth of the C. trachomatis ksgA mutant was negatively affected in cell culture highlighting the importance of the methylase in the development of these obligate intracellular and as yet genetically intractable pathogens. Conclusion: The presence of a functional rRNA dimethylase enzyme belonging to the KsgA family in Chlamydia presents an excellent chemotherapeutic target with real potential. It also confirms the existence of S-adenosyl-methionine-dependent methylation reactions in Chlamydia raising the question of how these organisms acquire this cofactor. C1 [Binet, Rachel; Maurelli, Anthony T.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. RP Binet, R (reprint author), US FDA, Off Regulatory Sci, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM rbinet@usuhs.mil; amaurelli@usuhs.mil FU National Institute of Allergy and Infectious Diseases [AI44033] FX This work was supported by grant AI44033 from the National Institute of Allergy and Infectious Diseases. NR 57 TC 12 Z9 12 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2180 J9 BMC MICROBIOL JI BMC Microbiol. PD DEC 31 PY 2009 VL 9 AR 279 DI 10.1186/1471-2180-9-279 PG 12 WC Microbiology SC Microbiology GA 547TK UT WOS:000273911900001 PM 20043826 ER PT J AU Lampel, KA Chen, Y AF Lampel, K. A. Chen, Y. TI Method for the isolation and detection of Enterobacter sakazakii (Cronobacter) from powdered infant formula SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article; Proceedings Paper CT 1st International Conference on Cronobacter CY JAN 22-23, 2009 CL Univ Coll Dublin, Belfield, IRELAND SP UCD Ctr Food Safety, FAO, WHO, DAFF, Food Safety Author Ireland, safefood, Soc Gen Microbiol, Teagase, Sci Fdn Ireland HO Univ Coll Dublin DE Enterobacter sakazakii; Detection; Isolation; Cronobacter ID TURICENSIS SP-NOV; MILK AB In the United States, there are approximately 76 million foodborne cases annually. Although the number of food-related infections caused by Enterobacter sakazakii is relatively low, the United States Food and Drug Administration in 2002 became concerned about the incidence of E. sakazakii infections related to powdered infant formula (PIF). At that time, a method to isolate this pathogen from PIF was developed and implemented in several cases. This protocol requires multiple steps and up to 7 days to complete. Recently, a new method was developed that incorporates a real-time PCR-based assay and chromogenic agars to improve isolating and detecting this pathogen in PIF. The updated protocol has undergone and successfully concluded an AOAC precollaborative study and is in the process of further validation for the inclusion into the FDA's Bacteriological Analytical Manual. This manuscript describes the performance evaluation of the new method. Published by Elsevier B.V. C1 [Lampel, K. A.; Chen, Y.] US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Lampel, KA (reprint author), US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM Keith.lampel@fda.hhs.gov NR 10 TC 31 Z9 33 U1 0 U2 18 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 DEC 31 PY 2009 VL 136 IS 2 BP 179 EP 184 DI 10.1016/j.ijfoodmicro.2009.08.016 PG 6 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 530DS UT WOS:000272569800006 PM 19733413 ER PT J AU Baylor, NW Wharton, M AF Baylor, Norman W. Wharton, Melinda TI Efficacy Data and HPV Vaccination Studies SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Baylor, Norman W.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Wharton, Melinda] US Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA. RP Baylor, NW (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM norman.baylor@fda.hhs.gov NR 4 TC 2 Z9 2 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 23 PY 2009 VL 302 IS 24 BP 2658 EP 2659 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 535JU UT WOS:000272965300012 PM 20040548 ER PT J AU Zhong, L Haynes, L Struble, EB Tamin, A Virata-Theimer, ML Zhang, P AF Zhong, Lilin Haynes, Lia Struble, Evi Budo Tamin, Azaibi Virata-Theimer, Maria Luisa Zhang, Pei TI Antibody-mediated synergy and interference in the neutralization of SARS-CoV at an epitope cluster on the spike protein SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE SARS-CoV; Monoclonal antibody; Neutralization; Epitope ID ACUTE RESPIRATORY SYNDROME; HEPATITIS-C VIRUS; SYNDROME CORONAVIRUS; ANIMAL VIRUSES; DC-SIGN; RECEPTOR; BINDING; GLYCOPROTEIN; CHIMPANZEES; INFECTION AB Incomplete neutralization of virus, especially when it occurs in the presence of excess neutralizing antibody, represents a biological phenomenon that impacts greatly on antibody-mediated immune prophylaxis of viral infection and on successful vaccine design. To understand the mechanism by which a virus escapes from antibody-mediated neutralization, we have investigated the interactions of non-neutralizing and neutralizing antibodies at an epitope cluster on the spike protein of severe acute respiratory syndrome coronavirus (SARS-CoV). The epitope cluster was mapped at the C-terminus of the spike protein; it consists of structurally intertwined epitopes recognized by two neutralizing monoclonal antibodies (mAbs), 341 C and 540C, and a non-neutralizing mAb, 240C. While mAb 341 C binds to a mostly linear epitope composed of residues (507)PAT(509) and V(349), MAb 240C binds to an epitope that partially overlaps the former by at least two residues (p(507) and A(508)). The epitope corresponding to mAb 540C is a conformational one, involving residues L(504) and N(505). In neutralization assays, non-neutralizing 240C disrupted virus neutralization by mAb 341C and/or mAb 540C, whereas a combination of mAbs 341C and 540C blocked virus infectivity synergistically. These findings indicate that the epitope cluster on the spike protein may serve as an evolutionarily conserved platform at which a dynamic interplay between neutralizing and non-neutralizing antibodies occurs, thereby determining the outcome of SARS-CoV infection. Published by Elsevier Inc. C1 [Zhong, Lilin; Struble, Evi Budo; Virata-Theimer, Maria Luisa; Zhang, Pei] US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Haynes, Lia; Tamin, Azaibi] Ctr Dis Control & Prevent, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. RP Zhang, P (reprint author), US FDA, Div Hematol, Ctr Biol Evaluat & Res, 29 Lincoln Dr, Bethesda, MD 20892 USA. EM lilin.zhong@fda.hhs.gov; loh5@cdc.gov; evi.struble@fda.hhs.gov; atamin@cdc.gov; marialuisa.virata@fda.hhs.gov; pei.zhang@fda.hhs.gov FU Center for Biologics Evaluation and Research, Food and Drug Administration FX We thank Drs. John Finlayson and Mahmood Farshid for comments on the manuscript: Dr. Basil Golding for interest and support; and the Core Laboratory of the Center for Biologics Evaluation and Research for peptide synthesis and DNA sequencing. This study was supported by the Center for Biologics Evaluation and Research, Food and Drug Administration. NR 32 TC 7 Z9 7 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 18 PY 2009 VL 390 IS 3 BP 1056 EP 1060 DI 10.1016/j.bbrc.2009.10.115 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 529KY UT WOS:000272516700128 PM 19861118 ER PT J AU Zhao, S Blickenstaff, K Glenn, A Ayers, SL Friedman, SL Abbott, JW McDermott, PF AF Zhao, S. Blickenstaff, K. Glenn, A. Ayers, S. L. Friedman, S. L. Abbott, J. W. McDermott, P. F. TI beta-Lactam Resistance in Salmonella Strains Isolated from Retail Meats in the United States by the National Antimicrobial Resistance Monitoring System between 2002 and 2006 SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID DECREASED SUSCEPTIBILITY; ESCHERICHIA-COLI; FOOD ANIMALS; ENTERICA; TYPHIMURIUM; INFECTIONS; EMERGENCE; HUMANS; AMPC; IDENTIFICATION AB Ampicillin-resistant (Amp(r)) Salmonella enterica isolates (n = 344) representing 32 serotypes isolated from retail meats from 2002 to 2006 were tested for susceptibility to 21 other antimicrobial agents and screened for the presence of five beta-lactamase gene families (bla(CMY), bla(TEM), bla(SHV), bla(OXA), and bla(CTX-M)) and class 1 integrons. Among the Amp(r) isolates, 66.9% were resistant to five or more antimicrobials and 4.9% were resistant to 10 or more antimicrobials. Coresistance to other beta-lactams was noted for amoxicillin-clavulanic acid (55.5%), ceftiofur (50%), cefoxitin (50%), and ceftazidime (24.7%), whereas less than 5% of isolates were resistant to piperacillin-tazobactam (4.9%), cefotaxime (3.5%), ceftriaxone (2%), and aztreonam (1.2%). All isolates were susceptible to cefepime, imipenem, and cefquinome. No Salmonella producing extended-spectrum beta-lactamases was found in this study. Approximately 7% of the isolates displayed a typical multidrug-resistant (MDR)-AmpC phenotype, with resistance to ampicillin, chloramphenicol, streptomycin, sulfonamide, tetracycline, plus resistance to amoxicillin-clavulanic acid, cefoxitin, and ceftiofur and with decreased susceptibility to ceftriaxone (MIC >= 4 mu g/ml). Pulsed-field gel electrophoresis results showed that several MDR clones were geographically dispersed in different types of meats throughout the five sampling years. Additionally, 50% of the isolates contained bla(CMY), 47% carried bla(TEM-1), and 2.6% carried both genes. Only 15% of the isolates harbored class I integrons carrying various combinations of aadA, aadB, and dfrA gene cassettes. The bla(CMY), bla(TEM), and class 1 integrons were transferable through conjugation and/or transformation. Our findings indicate that a varied spectrum of coresistance traits is present in Amp(r) Salmonella strains in the meat supply of the United States, with a continued predominance of bla(CMY) and bla(TEM) genes in beta-lactam-resistant isolates. C1 [Zhao, S.; Blickenstaff, K.; Glenn, A.; Ayers, S. L.; Friedman, S. L.; Abbott, J. W.; McDermott, P. F.] US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. RP Zhao, S (reprint author), US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM shaohua.zhao@fda.hhs.gov NR 36 TC 37 Z9 40 U1 0 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD DEC 15 PY 2009 VL 75 IS 24 BP 7624 EP 7630 DI 10.1128/AEM.01158-09 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 528FZ UT WOS:000272429100007 PM 19854922 ER PT J AU Bassen, HI Mendoza, GG AF Bassen, Howard I. Mendoza, Gonzalo G. TI In-vitro mapping of E-fields induced near pacemaker leads by simulated MR gradient fields SO BIOMEDICAL ENGINEERING ONLINE LA English DT Article ID MAGNETIC-FIELDS; SYSTEMS; EXPOSURE; SAFETY AB Background: Magnetic resonance imaging (MRI) of patients with implanted cardiac pacemakers is generally contraindicated but some clinicians condone scanning certain patients. We assessed the risk of inducing unintended cardiac stimulation by measuring electric fields (E) induced near lead tips by a simulated MRI gradient system. The objectives of this study are to map magnetically induced E near distal tips of leads in a saline tank to determine the spatial distribution and magnitude of E and compare them with E induced by a pacemaker pulse generator (PG). Methods: We mapped magnetically induced E with 0.1 mm resolution as close as 1 mm from lead tips. We used probes with two straight electrodes (e.g. wire diameter of 0.2 mm separated by 0.9 mm). We generated magnetic flux density (B) with a Helmholtz coil throughout 0.6% saline in a 24 cm diameter tank with (dB/dt) of 1 T/sec (1 kHz sinusoidal waveform). Separately, we measured E near the tip of leads when connected to a PG set to a unipolar mode. Measurements were non-invasive (not altering the leads or PG under study). Results: When scaled to 30 T/s (a clinically relevant value), magnetically-induced E exceeded the E produced by a PG. The magnetically-induced E only occurred when B was coincident with or within 15 msec of implantable pacemaker's pulse. Conclusions: Potentially hazardous situations are possible during an MR scan due to gradient fields. Unintended stimulation can be induced via abandoned leads and leads connected to a pulse generator with loss of hermetic seal at the connector. Also, pacemaker-dependent patients can receive drastically altered pacing pulses. C1 [Bassen, Howard I.] FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Phys, Silver Spring, MD 20993 USA. [Mendoza, Gonzalo G.] Catholic Univ Amer, Sch Engn, Washington, DC 20064 USA. RP Bassen, HI (reprint author), FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Phys, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM howard.bassen@fda.hhs.gov; gonzalo.mendoza@fda.hhs.gov FU Biophan Technologies Inc. through a Cooperative Research and Development Agreement with the U.S. FDA FX Bandar Hakim PhD, participated in the development and testing of the original E-field probe. Partial support for this project was provided by Biophan Technologies Inc. through a Cooperative Research and Development Agreement with the U.S. FDA. NR 13 TC 8 Z9 8 U1 0 U2 3 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 DEC 15 PY 2009 VL 8 AR 39 DI 10.1186/1475-925X-8-39 PG 18 WC Engineering, Biomedical SC Engineering GA 539WP UT WOS:000273290200001 PM 20003479 ER PT J AU Priya, R Biukovic, G Gayen, S Vivekanandan, S Gruber, G AF Priya, Ragunathan Biukovic, Goran Gayen, Shovanlal Vivekanandan, Subramanian Grueber, Gerhard TI Solution Structure, Determined by Nuclear Magnetic Resonance, of the b30-82 Domain of Subunit b of Escherichia coli F1Fo ATP Synthase SO JOURNAL OF BACTERIOLOGY LA English DT Article ID DIMERIZATION DOMAIN; PERIPHERAL STALK; F0F1-ATP SYNTHASE; ROTARY MOTOR; STATOR; DYNAMICS AB Subunit b, the peripheral stalk of bacterial F1Fo ATP synthases, is composed of a membrane-spanning and a soluble part. The soluble part is divided into tether, dimerization, and delta-binding domains. The first solution structure of b30-82, including the tether region and part of the dimerization domain, has been solved by nuclear magnetic resonance, revealing an alpha-helix between residues 39 and 72. In the solution structure, b30-82 has a length of 48.07 angstrom. The surface charge distribution of b30-82 shows one side with a hydrophobic surface pattern, formed by alanine residues. Alanine residues 61, 68, 70, and 72 were replaced by single cysteines in the soluble part of subunit b, b22-156. The cysteines at positions 61, 68, and 72 showed disulfide formation. In contrast, no cross-link could be formed for the A70C mutant. The patterns of disulfide bonding, together with the circular dichroism spectroscopy data, are indicative of an adjacent arrangement of residues 61, 68, and 72 in both alpha-helices in b22-156. C1 [Priya, Ragunathan; Biukovic, Goran; Gayen, Shovanlal; Vivekanandan, Subramanian; Grueber, Gerhard] Nanyang Technol Univ, Sch Biol Sci, Singapore 637551, Singapore. [Vivekanandan, Subramanian] CBER FDA, Struct Biol NMR Spect, Bethesda, MD 20892 USA. RP Gruber, G (reprint author), Nanyang Technol Univ, Sch Biol Sci, 60 Nanyang Dr, Singapore 637551, Singapore. EM ggrueber@ntu.edu.sg RI S, Vivekanandan/E-5197-2011; Subramanian, Vivekanandan/F-5865-2012 FU Ministry of Education, Singapore [ARC 6/06, RG144/06]; Nanyang Technological University, Singapore FX This research and the fellowships for R. Priya were supported by a grant from the Ministry of Education, Singapore (ARC 6/06 and RG144/06). S. Gayen is a recipient of the Graduate Research Scholarship, Nanyang Technological University, Singapore. NR 36 TC 12 Z9 12 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD DEC 15 PY 2009 VL 191 IS 24 BP 7538 EP 7544 DI 10.1128/JB.00540-09 PG 7 WC Microbiology SC Microbiology GA 522WI UT WOS:000272030400017 PM 19820091 ER PT J AU Lyle, DB Shallcross, JC Langone, JJ AF Lyle, Daniel B. Shallcross, Jonathan C. Langone, John J. TI Sensitivity of insulin production from encapsulated islets to endotoxin-stimulated macrophage inflammatory mediators SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE alginate; encapsulation; nitric oxide inflammation; macrophage; islets ID PANCREATIC BETA-CELLS; NITRIC-OXIDE SYNTHASE; ENZYME GENE-EXPRESSION; LINE RAW 264.7; IN-VITRO; ALGINATE MICROCAPSULES; NO PRODUCTION; RELEASE; TRANSPLANTATION; DYSFUNCTION AB Chronic inflammation may compromise function of implanted encapsulated islets. Increased purity of alginate used for encapsulation prolongs encapsulated graft function, correlating with decreased presence of impurities like bacterial endotoxin. Limits for endotoxin contamination in biomaterials based on indirect inhibition of function of embedded cells have yet to be established. In a coculture system with RAW 264.7 inonocyte/macrophage cells in the presence of 50 ng/mL murine recombinant gamma-interferon (mrIFN-gamma), the insulin response to glucose challenge of both rat and pig unencapsulated islets was prevented by endotoxin (LPS) in the medium down to 0.3 EU/mL (LOEL), but not 0.06 EU/mL (NOEL). Evaluation of nitrite concentrations in supernatants revealed that pig islets were more resistant to LPS-stimulated macrophage mediators than rat islets. Encapsulation in highly purified alginate produced little change in observed inhibitory effects of macrophage-generated nitric oxide (NO) toward islet function. Chemically released NO was much less effective in inhibiting insulin responsiveness to glucose challenge than was coculture of islets with LPS and mrIFN-gamma-stimulated RAW 264.7. These results taken together with other data Suggest that an upper limit of 0.3 EU/mL LPS within the encapsulating alginate will not impair the function of implanted encapsulated islets by toxic concentrations of macrophage-mediated inflammatory agents. (C) 2009 Wiley Periodicals, Inc.(star) J Biomed Mater Res 91 A: 1221-1238, 2009 C1 [Lyle, Daniel B.] US FDA, Div Biol, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Lyle, DB (reprint author), US FDA, Div Biol, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, White Oak Life Sci Bldg 64-3036,10903 New Hampshi, Silver Spring, MD 20993 USA. EM dan.lyle@fda.hhs.gov NR 68 TC 3 Z9 3 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1549-3296 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD DEC 15 PY 2009 VL 91A IS 4 BP 1221 EP 1238 DI 10.1002/jbm.a.32351 PG 18 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 525EN UT WOS:000272196900028 PM 19165788 ER PT J AU Mielke, LA Elkins, KL Wei, L Starr, R Tsichlis, PN O'Shea, JJ Watford, WT AF Mielke, Lisa A. Elkins, Karen L. Wei, Lai Starr, Robyn Tsichlis, Philip N. O'Shea, John J. Watford, Wendy T. TI Tumor Progression Locus 2 (Map3k8) Is Critical for Host Defense against Listeria monocytogenes and IL-1 beta Production SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TNF-ALPHA PRODUCTION; NF-KAPPA-B; INNATE IMMUNE-RESPONSES; C-TYPE LECTIN; TPL2 KINASE; MURINE LISTERIOSIS; ERK ACTIVATION; BETA-GLUCANS; MICE LACKING; I RECEPTOR AB Tumor progression locus 2 (Tpl2, also known as Map3k8 and Cot) is a serine-threonine kinase critical in innate immunity, linking toll-like receptors (TLRs) to TNF production through its activation of ERK. Tpl2(-/-) macrophages have abrogated TNF production but overproduce IL-12 in response to TLR ligands. Despite enhanced IL-12 production, Tpl2(-/-) T cells have impaired IFN-gamma production. Therefore, the role of Tpl2 in a bona fide bacterial infection where all of these cytokines are important in host defense is unclear. To address this issue,we infected Tpl2(-/-) mice with the model pathogen Listeria monocytogenes. We found that Tpl2(-/-) mice infected i.v. with L. monocytogenes had increased pathogen burdens compared with wild-type mice and rapidly succumbed to infection. Enhanced susceptibility correlated with impaired signaling through TLR2 and nucleotide-binding oligomerization domain 2, two receptors previously shown. to mediate Listeria recognition. Surprisingly, TNF production in response to infection was not significantly impaired, even though Tpl2 has been implicated in the regulation of TNF. We found that the role of Tpl2 has cell-type specific effects in regulating TNF and transduces signals from some, but not all, pattern recognition receptors (PRR). In contrast to the cell-type- and receptor-specific regulation of TNF, we found that Tpl2 is essential for IL-1 beta production from both macrophages and dendritic cells. These studies implicate Tpl2 as an important mediator for collaboration of pattern recognition receptors with danger-associated molecular patterns to induce TNF and IL-1 beta production and optimal host defense. The Journal of Immunology, 2009, 183: 7984-7993. C1 [Mielke, Lisa A.; Wei, Lai; O'Shea, John J.; Watford, Wendy T.] Natl Inst Arthrit Musculoskeletal & Skin Dis, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. [Mielke, Lisa A.] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Mol Med, Parkville, Vic 3050, Australia. [Mielke, Lisa A.] Univ Melbourne, Dept Med Biol, Parkville, Vic 3052, Australia. [Elkins, Karen L.] US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Div Bacterial Parasit & Allergen Prod, Rockville, MD 20852 USA. [Starr, Robyn] St Vincents Inst Med Res, Signal Transduct Lab, Fitzroy, Vic 3065, Australia. [Tsichlis, Philip N.] Tufts Univ New England Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. RP Watford, WT (reprint author), Univ Georgia, Coll Vet Med, Dept Infect Dis, Athens, GA 30602 USA. EM watfordw@uga.edu RI Wei, Lai/D-1088-2014 FU National Institutes of Health [R01 CA095431, 1 K22 AR53953-01] FX P.N.T. is supported by National Institutes of Health Grant R01 CA095431. W.T.W. is supported by National Institutes of Health Grant 1 K22 AR53953-01. NR 60 TC 43 Z9 44 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2009 VL 183 IS 12 BP 7984 EP 7993 DI 10.4049/jimmunol.0901336 PG 10 WC Immunology SC Immunology GA 533YE UT WOS:000272861300043 PM 19933865 ER PT J AU Xie, H Liu, TM Lu, XH Wu, ZQ Belser, JA Katz, JM Tumpey, TM Ye, ZP AF Xie, Hang Liu, Teresa M. Lu, Xiuhua Wu, Zhengqi Belser, Jessica A. Katz, Jacqueline M. Tumpey, Terrence M. Ye, Zhiping TI A Live Attenuated H1N1 M1 Mutant Provides Broad Cross-Protection against Influenza A Viruses, Including Highly Pathogenic A/Vietnam/1203/2004, in Mice SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MATRIX PROTEIN; T-CELLS; HETEROSUBTYPIC VIRUS; INFECTION; VACCINES; IMMUNITY; NUCLEOPROTEIN; RESTRICTION; RESISTANCE; FERRETS AB The emergence of novel influenza A H1N1 and highly pathogenic avian influenza (HPAI) H5N1 viruses underscores the urgency of developing efficient vaccines against an imminent pandemic. M(NLS-88R) (H1N1), an A/WSN/33 mutant with modifications in the multibasic motif 101RKLKR105 of the matrix (M1) protein and its adjacent region, was generated by reverse genetics. The M(NLS-88R) mutant had in vitro growth characteristics similar to those of wild-type A/WSN/33 (wt-WSN), but it was attenuated in mice. Vaccination with M(NLS-88R) not only fully protected mice from lethal homologous challenges but also prevented mortality caused by antigenically distinct H3N2 and H5N1 viruses. M(NLS-88R)-induced homologous protection was mainly antibody dependent, but cellular immunity was also beneficial in protecting against sublethal wt-WSN infection. Adoptive transfer studies indicated that both humoral and cellular immune responses were crucial for M(NLS-88R)-induced heterologous protection. Our study suggests an alternative approach to attenuate wt influenza viruses for the development of a pandemic vaccine with broad cross-protection. C1 [Xie, Hang; Liu, Teresa M.; Wu, Zhengqi; Ye, Zhiping] US FDA, Lab Resp Viral Dis, Div Viral Prod, Off Vaccine Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Lu, Xiuhua; Belser, Jessica A.; Katz, Jacqueline M.; Tumpey, Terrence M.] US Ctr Dis Control & Prevent, Influenza Div, Atlanta, GA USA. RP Xie, H (reprint author), 29A Lincoln Dr,Room 1B11, Bethesda, MD 20892 USA. EM Hang.Xie@fda.hhs.gov; Zhiping.Ye@fda.hhs.gov FU National Vaccine Program FX Financial support: National Vaccine Program (to Z.Y.). NR 30 TC 12 Z9 14 U1 0 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2009 VL 200 IS 12 BP 1874 EP 1883 DI 10.1086/648405 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 520UH UT WOS:000271874000010 PM 19909080 ER PT J AU Lucas, AD Gordon, EA Stratmeyer, ME AF Lucas, Anne D. Gordon, Edward A. Stratmeyer, Melvin E. TI Analysis of polyhexamethylene biguanide in multipurpose contact lens solutions SO TALANTA LA English DT Article DE Contact lens; Polyhexamethylene biguanide; Liquid chromatography ID HYDROCHLORIDE AB The objective of this study was to establish a reasonably simple and reliable method to measure very low concentrations of polyhexamethylene biguanicle (PHMB) in multipurpose contact lens solutions (MPSs). By using a weak cation exchange solid phase extraction cartridge to extract the PHMB from MPS, followed by HPLC analysis using an evaporative light scattering detector, low levels (0.1 ppm) of PHMB were detected. Application of this method to a series of off-the-shelf MPS with PHMB as the active ingredient demonstrated these solutions contain I ppm. The contact lens solution with hydrogen peroxide as the active ingredient gave no peak where the PHMB peak eluted. The Polyquad (R) contact lens solution generated a peak close to the retention time of PHMB. Recovery of PHMB from fortified hydrogen peroxide contact lens solution was good at 0.25 ppm and above; 105% with a RSD of 17% or less. The repeatability of the HPLC system ranged from 4 to 11% RSD: the reproducibility of the entire method was less than 17.5% RSD. Storage and stability studies indicated that storage of MPS with PHMB for chemical analysis are not temperature dependent, but are affected by the composition of the container in which the contact lens solution is stored. Published by Elsevier B.V. C1 [Lucas, Anne D.; Gordon, Edward A.; Stratmeyer, Melvin E.] US FDA, Ctr Devices & Radiol Hlth, OSEL DB, Silver Spring, MD 20993 USA. RP Lucas, AD (reprint author), US FDA, Ctr Devices & Radiol Hlth, OSEL DB, 10903 New Hampshire Ave,Bldg 64 Room 4011, Silver Spring, MD 20993 USA. EM anne.lucas@fda.hhs.gov NR 15 TC 12 Z9 14 U1 2 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0039-9140 J9 TALANTA JI Talanta PD DEC 15 PY 2009 VL 80 IS 2 BP 1016 EP 1019 DI 10.1016/j.talanta.2009.07.031 PG 4 WC Chemistry, Analytical SC Chemistry GA 518OI UT WOS:000271701900093 PM 19836589 ER PT J AU Valerio, LG AF Valerio, Luis G., Jr. TI In silico toxicology for the pharmaceutical sciences SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Review DE In silico; Pharmaceutical; Computational; Predictive; Safety; Drug ID TOXICITY HAZARD IDENTIFICATION; DETECTING STRUCTURAL ALERTS; PREDICTING DRUG-METABOLISM; E-STATE INDEXES; RODENT CARCINOGENICITY; DEVELOPMENTAL TOXICITY; QSAR MODELS; QUANTITATIVE STRUCTURE; GENETIC TOXICITY; MDL-QSAR AB The applied use of in silico technologies (a.k.a. computational toxicology, in silico toxicology, computer-assisted tox, e-tox, i-drug discovery, predictive ADME, etc.) for predicting preclinical toxicological endpoints, clinical adverse effects, and metabolism of pharmaceutical substances has become of high interest to the scientific community and the public. The increased accessibility of these technologies for scientists and recent regulations permitting their use for chemical risk assessment supports this notion. The scientific community is interested in the appropriate use of such technologies as a tool to enhance product development and safety of pharmaceuticals and other xenobiotics, while ensuring the reliability and accuracy of in silica approaches for the toxicological and pharmacological sciences. For pharmaceutical substances, this means active and impurity chemicals in the drug product may be screened using specialized software and databases designed to cover these substances through a chemical structure-based screening process and algorithm specific to a given software program. A major goal for use of these software programs is to enable industry scientists not only to enhance the discovery process but also to ensure the judicious use of in silico tools to support risk assessments of drug-induced toxicities and in safety evaluations. However, a great amount of applied research is still needed, and there are many limitations with these approaches which are described in this review. Currently, there is a wide range of endpoints available from predictive quantitative structure-activity relationship models driven by many different computational software programs and data sources, and this is only expected to grow. For example, there are models based on nonproprietary and/or proprietary information specific to assessing potential rodent carcinogenicity, in silica screens for ICH genetic toxicity assays, reproductive and developmental toxicity, theoretical prediction of human drug metabolism, mechanisms of action for pharmaceuticals, and newer models for predicting human adverse effects. How accurate are these. approaches is both a statistical issue and challenge in toxicology. In this review, fundamental concepts and the current capabilities and limitations of this technology will be critically addressed. Published by Elsevier Inc. C1 US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Valerio, LG (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, White Oak 51 Room 4128,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Luis.Valerio@fda.hhs.gov NR 136 TC 106 Z9 109 U1 2 U2 37 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD DEC 15 PY 2009 VL 241 IS 3 BP 356 EP 370 DI 10.1016/j.taap.2009.08.022 PG 15 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 520JX UT WOS:000271841400013 PM 19716836 ER PT J AU Kolibab, K Parra, M Yang, AL Perera, LP Derrick, SC Morris, SL AF Kolibab, Kristopher Parra, Marcela Yang, Amy L. Perera, Liyanage P. Derrick, Steven C. Morris, Sheldon L. TI A practical in vitro growth inhibition assay for the evaluation of TB vaccines SO VACCINE LA English DT Article DE Tuberculosis; In vitro assay; Vaccine; Mouse; Cytokines ID MYCOBACTERIUM-TUBERCULOSIS INFECTION; INTRACELLULAR GROWTH; INTERFERON-GAMMA; IMMUNE-RESPONSES; IFN-GAMMA; CELLS; CD4(+); MICE; BCG; IMMUNOGENICITY AB New vaccines and novel immunization strategies are needed to improve the control of the global tuberculosis epidemic. To facilitate vaccine development, we have been creating in vitro mycobacterial intra-macrophage growth inhibition assays. Here we describe the development of an in vitro assay designed for BSL-2 laboratories which measures the capacity of vaccine-induced immune splenocytes to control the growth of isoniazid-resistant Mycobacterium bovis BCG (INH(r) BCG). The use of the INH(r) BCG as the infecting organism allows the discrimination of BCG bacilli used in murine vaccinations from BCG used in the in vitro assay. In this study, we showed that protective immune responses evoked by four different types of Mycobacterium tuberculosis vaccines [BCG, an ESAT6/Antigen 85B fusion protein formulated in DDA/MPL adjuvant, a DNA vaccine expressing the same fusion protein, and a TB Modified Vaccinia Ankara construct expressing four TB antigens (MVA-4TB)] were detected. Importantly, the levels of vaccine-induced protective immunity seen in the in vitro assay correlated with the results from in vivo protection studies in the mouse model of pulmonary tuberculosis. Furthermore, the growth inhibition data for the INH(r) BCG assay was similar to the previously reported results for a M. tuberculosis infection assay. The cytokine expression profiles at day 7 of the INHr BCG growth inhibition studies were also similar but not identical to the cytokine patterns detected in earlier M. tuberculosis co-culture assays. Overall, we have shown that a BSL-2 compatible in vitro growth inhibition assay using INHr BCG as the intra-macrophage target organism should be useful in developing and evaluating new TB immunization strategies. Published by Elsevier Ltd. C1 [Morris, Sheldon L.] US FDA, Lab Mycobacterial Dis & Cellular Immunol, CBER, Bethesda, MD 20892 USA. [Perera, Liyanage P.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Morris, SL (reprint author), US FDA, Lab Mycobacterial Dis & Cellular Immunol, CBER, Bldg 29 Room 502,29 Lincol Dr, Bethesda, MD 20892 USA. EM sheldon.morris@fda.hhs.gov FU National Institute of Allergy and Infectious Diseases; National Institutes of Health; Department of Health and Human Services [IAA 227-06-1322] FX This project was funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under IAA 227-06-1322. NR 26 TC 12 Z9 12 U1 2 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD DEC 11 PY 2009 VL 28 IS 2 BP 317 EP 322 DI 10.1016/j.vaccine.2009.10.047 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 559YS UT WOS:000274869300005 PM 19879231 ER PT J AU Edwards, GB Benjamin, SP AF Edwards, G. B. Benjamin, Suresh P. TI A first look at the phylogeny of the Myrmarachninae, with rediscovery and redescription of the type species of Myrmarachne (Araneae: Salticidae) SO ZOOTAXA LA English DT Article DE Myrmarachninae; new combination; new name; new synonym; phylogeny; species groups; Belippo; Bocus; Damoetas; Judalana; Ligonipes; Panachraesta; Rhombonotus ID JUMPING SPIDERS; ANT; MIMICRY; INFERENCE; REVISION; AMERICA; MRBAYES; MODELS AB Myrmarachne melanocephala MacLeay, 1839, type species of the genus Myrmarachne MacLeay, 1839, is rediscovered and redescribed, and a neotype is here designated. Five new synonyms of M. melanocephala are proposed: M. contracta (Karsch, 1880) [lectotype here designated], M. providens (Peckham & Peckham, 1892), M. ramosa Badcock, 1918, M. albicrurata Badcock, 1918, and M. lateralis Badcock, 1918. Myrmarachne melanocephala is shown to be a widespread species in southern Asia that mimics the ant Tetraponera rufonigra (Jerdon). Myrmarachne christae (Proszynski, 2001) and Myrmarachne galianoae (Proszynski, 2001) are transferred from Damoetas, new combinations. The latter results in a homonym with Myrmarachne galianoae Cutler, 1981: we rename the species Myrmarachne mariaelenae Edwards & Benjamin, replacement name. Further characterization of the species groups of Myrmarachne is presented, related genera are discussed, and a preliminary phylogeny of the Myrmarachninae is given. C1 [Edwards, G. B.] Florida State Collect Arthropods, FDACS Div Plant Ind, Gainesville, FL 32614 USA. [Benjamin, Suresh P.] Inst Fundamental Studies, Kandy, Sri Lanka. [Benjamin, Suresh P.] Smithsonian Inst, Dept Entomol, Natl Museum Nat Hist, MRC 105, Washington, DC 20013 USA. RP Edwards, GB (reprint author), Florida State Collect Arthropods, FDACS Div Plant Ind, POB 147100, Gainesville, FL 32614 USA. EM edwardg@doacs.state.fl.us; suresh.benjamin@gmail.com FU Smithsonian Institution; Institute of Fundamental Studies FX We are grateful to the following curators and museums: Gonzalo Giribet and Laura Leibensperger, Museum of Comparative Zoology, Cambridge, Massachusetts; Jason A. Dunlop, Museum fur Naturkunde, Berlin; and Janet Beccaloni, British Natural History Museum for the loan of type specimens; Jonathan Coddington and Dana De Roche, U. S. National Museum of Natural History, Smithsonian Institution, Washington, D. C.; Peter Schwendinger, Museum d'Histoire Naturelle, Geneve, Switzerland; and Charles Griswold and Darrell Ubick, California Academy of Sciences, San Francisco, for providing us with additional material from Sri Lanka and India. Thanks also to Mr. A. H. Sumanasena (Department of Wild Life Conservation, Colombo) for providing a research permit to collect in Sri Lanka. SPB would like to express his gratitude to his brother Donald Benjamin and his students Ziyard Jaleel (Open University of Sri Lanka) and Sudath V. Nanayakkara for accompanying him during fieldwork in Sri Lanka. A Smithsonian Institution postdoctoral fellowship and the Institute of Fundamental Studies provided financial support for this project to SPB. Gita Bodner and Junxia Zhang co-observed various types of salticid mimicry with GBE in Costa Rica and Panama, respectively. Thanks also to Paul Selden and Norman Platnick for discussion on the type locality of M. melanocephala, to Marek Zabka for information about other Asian and Australian genera related to Myrmarachne, to Junxia Zhang who assisted with the phylogenetic analysis, and to Lloyd Davis who identified the ant. Thanks also to the following for searching for or other information about the type specimen of M. melanocephala: Beth Mantle and Barry Richardson, CSIRO; Graham Milledge and Helen Smith, Australian Museum; Elizabeth Jefferys, Macleay Museum. Jerzy Proszynski kindly contributed his versions of Wanless' species groups, suggested new groups, and provided Figure 7. The Willi Hennig Society is acknowledged for making TNT available free to users. We also appreciate Paul Skelley's thorough review, as well as those of Christoph Muster and two anonymous reviewers. This is FDACS, DPI, Bureau of Entomology, Nematology, and Plant Pathology, Entomology Section Contribution # 1141. NR 65 TC 9 Z9 12 U1 5 U2 6 PU MAGNOLIA PRESS PI AUCKLAND PA PO BOX 41383, AUCKLAND, ST LUKES 1030, NEW ZEALAND SN 1175-5326 EI 1175-5334 J9 ZOOTAXA JI Zootaxa PD DEC 11 PY 2009 IS 2309 BP 1 EP 29 PG 29 WC Zoology SC Zoology GA 530VA UT WOS:000272619200001 ER PT J AU Dworkin, RH Turk, DC McDermott, MP Peirce-Sandner, S Burke, LB Cowan, P Farrar, JT Hertz, S Raja, SN Rappaport, BA Rauschkolb, C Sampaio, C AF Dworkin, Robert H. Turk, Dennis C. McDermott, Michael P. Peirce-Sandner, Sarah Burke, Laurie B. Cowan, Penney Farrar, John T. Hertz, Sharon Raja, Srinivasa N. Rappaport, Bob A. Rauschkolb, Christine Sampaio, Cristina TI Interpreting the clinical importance of group differences in chronic pain clinical trials: IMMPACT recommendations SO PAIN LA English DT Review DE Chronic pain; Randomized clinical trials; Group differences; Clinical importance; Clinical meaningfulness; Effect size ID QUALITY-OF-LIFE; DIABETIC PERIPHERAL NEUROPATHY; PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; DOUBLE-BLIND; OUTCOME MEASURES; KNEE OSTEOARTHRITIS; PREGABALIN; MANAGEMENT; DULOXETINE AB An essential component of the interpretation of results of randomized clinical trials of treatments for chronic pain involves the determination of their clinical importance or meaningfulness. This involves two distinct processes-interpreting the clinical importance of individual patient improvements and the clinical importance of group differences-which are frequently misunderstood. In this article, we first describe the essential differences between the interpretation of the clinical importance of patient improvements and of group differences. We then discuss the factors to consider when evaluating the clinical importance of group differences, which include the results of responder analyses of the primary outcome measure, the treatment effect size compared to available therapies, analyses of secondary efficacy endpoints, the safety and tolerability of treatment, the rapidity of onset and durability of the treatment benefit, convenience, cost, limitations of existing treatments, and other factors. The clinical importance of individual patient improvements can be determined by assessing what patients themselves consider meaningful improvement using well-described methods. In contrast, the clinical meaningfulness of group differences must be determined by a multi-factorial evaluation of the benefits and risks of the treatment and of other available treatments for the condition in light of the primary goals of therapy. Such determinations must be conducted on a case-by-case basis, and are ideally informed by patients and their significant others, clinicians, researchers, statisticians, and representatives of society at large. (C) 2009 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Dworkin, Robert H.; Peirce-Sandner, Sarah] Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY 14642 USA. [Dworkin, Robert H.] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA. [Turk, Dennis C.] Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. [McDermott, Michael P.] Univ Rochester, Sch Med & Dent, Dept Biostat, Rochester, NY 14642 USA. [McDermott, Michael P.] Univ Rochester, Sch Med & Dent, Dept Computat Biol & Neurol, Rochester, NY 14642 USA. [Burke, Laurie B.; Hertz, Sharon; Rappaport, Bob A.] US FDA, Bethesda, MD 20014 USA. [Cowan, Penney] Amer Chron Pain Assoc, Rocklin, CA USA. [Farrar, John T.] Univ Penn, Dept Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Raja, Srinivasa N.] Johns Hopkins Univ, Dept Anesthesiol & Crit Care Med, Baltimore, MD USA. [Rauschkolb, Christine] Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ USA. [Sampaio, Cristina] Fac Med Lisbon, Lisbon, Portugal. 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 RI Farrar, John/A-1037-2007; OI Farrar, John/0000-0001-8656-5157; Yang, Shuman/0000-0002-9638-0890 NR 39 TC 199 Z9 201 U1 2 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD DEC 5 PY 2009 VL 146 IS 3 BP 238 EP 244 DI 10.1016/j.pain.2009.08.019 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 525OX UT WOS:000272226900007 PM 19836888 ER PT J AU Tsai, HT Caporaso, NE Kyle, RA Katzmann, JA Dispenzieri, A Hayes, RB Marti, GE Albitar, M Ghia, P Rajkumar, SV Landgren, O AF Tsai, Huei-Ting Caporaso, Neil E. Kyle, Robert A. Katzmann, Jerry A. Dispenzieri, Angela Hayes, Richard B. Marti, Gerald E. Albitar, Maher Ghia, Paolo Rajkumar, S. Vincent Landgren, Ola TI Evidence of serum immunoglobulin abnormalities up to 9.8 years before diagnosis of chronic lymphocytic leukemia: a prospective study SO BLOOD LA English DT Article ID UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; MULTIPLE-MYELOMA; CIRCULATING CD20; LIGHT; SURVIVAL; MARKER; PROTEINS; DISEASE; RISK AB Immune-related deficiencies are well-known complications of chronic lymphocytic leukemia (CLL). Although recent data indicate that almost all CLL patients are preceded by a monoclonal B-cell lymphocytosis precursor state, patterns of immune defects preceding CLL diagnosis are unclear. We identified 109 persons who developed CLL from the prospective and nationwide Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial with 77 469 participants, with serially collected prediagnostic serum samples. We assayed monoclonal (M)-proteins, kappa/lambda free light chains (FLCs) in prediagnostic obtained up to 9.8 years before CLL diagnosis. The prevalence of an abnormal FLC ratio, M-protein, and hypogammaglobulinemia before CLL diagnosis was 38% (95% confidence interval, 29%-47%), 13% (7%-21%), and 3% (1%-8%), respectively. M-proteins and abnormal FLC ratios were detected up to 9.8 years before CLL diagnosis in a total of 48 persons (44%). Hypogammaglobulinemia was not present until 3 years before the diagnosis of CLL. Among 37 patients with information on tumor cell immunophenotype, an association between immunophenotype and involved FLC (P = .024, Fisher exact test) was observed. Among 61 persons with a normal FLC ratio and without an M-protein, 17 had elevated kappa and/or lambda FLC levels, indicating polyclonal B-cell activation in 17 of 109 (16%) patients. These findings support a role for chronic immune stimulation in CLL genesis. (Blood. 2009; 114: 4928-4932) C1 [Landgren, Ola] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Tsai, Huei-Ting; Caporaso, Neil E.; Landgren, Ola] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Kyle, Robert A.; Katzmann, Jerry A.; Dispenzieri, Angela; Rajkumar, S. Vincent] Mayo Clin, Div Hematol & Internal Med, Rochester, MN USA. [Kyle, Robert A.; Katzmann, Jerry A.; Dispenzieri, Angela] Mayo Clin, Div Clin Biochem & Immunol, Rochester, MN USA. [Kyle, Robert A.; Katzmann, Jerry A.; Dispenzieri, Angela] Mayo Clin, Div Lab Med & Pathol, Rochester, MN USA. [Hayes, Richard B.] NYU, Inst Canc, Langone Med Ctr, Dept Environm Med,Div Epidemiol, New York, NY 10003 USA. [Marti, Gerald E.] NIH, Ctr Biol Evaluat & Res, US FDA, Bethesda, MD 20892 USA. [Albitar, Maher] Quest Diagnost, Nichols Inst, San Juan Capistrano, CA USA. [Ghia, Paolo] Univ Vita Salute San Raffaele, Lab Cell Neoplasia B, Div Mol Oncol, Milan, Italy. [Ghia, Paolo] Univ Vita Salute San Raffaele, Dept Oncol, Unit Lymphoid Malignancies, Milan, Italy. [Ghia, Paolo] Ist Sci San Raffaele, Milan, Italy. RP Landgren, O (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10 Rm 13N240F, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov RI Ghia, Paolo/K-7138-2016; OI Ghia, Paolo/0000-0003-3750-7342; Rajkumar, S. Vincent/0000-0002-5862-1833; Hayes, Richard/0000-0002-0918-661X; Dispenzieri, Angela/0000-0001-8780-9512 FU National Cancer Institute and the Intramural Research Program of the National Institutes of Health [CA62242, CA 107476] FX This work was supported in part by Research Grants CA62242 and CA 107476 from the National Cancer Institute and the Intramural Research Program of the National Institutes of Health. NR 31 TC 34 Z9 34 U1 0 U2 2 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 3 PY 2009 VL 114 IS 24 BP 4928 EP 4932 DI 10.1182/blood-2009-08-237651 PG 5 WC Hematology SC Hematology GA 527WX UT WOS:000272403000006 PM 19828698 ER PT J AU Jacobs, JM Rhodes, MR Baya, A Reimschuessel, R Townsend, H Harrell, RM AF Jacobs, John M. Rhodes, Matt R. Baya, Ana Reimschuessel, Renate Townsend, Howard Harrell, Reginal M. TI Influence of nutritional state on the progression and severity of mycobacteriosis in striped bass Morone saxatilis SO DISEASES OF AQUATIC ORGANISMS LA English DT Article DE Mycobacteriosis; Nutrition; Disease; Stress; Striped bass ID INFECTIOUS PANCREATIC NECROSIS; ONCORHYNCHUS-MYKISS WALBAUM; CHESAPEAKE-BAY; RAINBOW-TROUT; FISH; TUBERCULOSIS; MARINUM; SURVIVAL; VIRULENCE; PSEUDOSHOTTSII AB Challenge studies with Mycobacterium maximum clearly demonstrate that a poor diet. affects the progression and severity of mycobacteriosis in striped bass Morone saxatilis. Fish (n = 512 total, wt = 65 +/- 15 g) were inoculated intraperitoneally with 10(4) colony-forming units (CFU) g(-1) body weigth (BW) or a physiological saline solution (controls) and evaluated for 8 mo, Inoculated fish fed a low-ration diet (0.15%, BW d(-1)) developed a severe, systemic infection characterized by a high bacterial load (>10(8) CFU g(-1) spleen) and poor granuloma formation, which commonly progressed to mortality by 6 wk. In contrast, inoculated fish fed an adequate ration diet (1 % BW d(-1)) developed classic granulomatous inflammation of reduced severity and total body energy similar to that found in uninoculated controls (p > 0.05). After 4 wk, fish fed adequate rations maintained an equilibrium state throughout the study period, even though 10(6) CFU g(-1) spleen mycobacteria were consistently cultured. In a second study, reactivation of an acute inflammatory state was demonstrated by placing previously infected fish on reducing diets (0.073 %, BW d(-1)). In both Studies, the energetic demand of this disease was only appreciable when associated with active, severe, inflammatory states. To our knowledge, this study is the first to demonstrate the interaction of diet and mycobacteriosis in fish. C1 [Jacobs, John M.; Rhodes, Matt R.] NOAA Natl Ocean Serv, CCEHBR, Cooperat Oxford Lab, Oxford, MD 21654 USA. [Baya, Ana] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA. [Reimschuessel, Renate] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [Townsend, Howard] NOAA Natl Marine Fisheries Serv, Chesapeake Bay Off, Oxford, MD 21654 USA. [Harrell, Reginal M.] Univ Maryland, Dept Environm Sci & Technol, College Pk, MD 20742 USA. RP Jacobs, JM (reprint author), NOAA Natl Ocean Serv, CCEHBR, Cooperat Oxford Lab, Oxford, MD 21654 USA. EM john.jacobs@noaa.gov FU Maryland Agricultural Experiment Station; NOAA/NCCOS Cooperative Oxford Lab FX This work benefited greatly from the technical assistance of B. Bingaman, C. S. Stine, and A. Ferrero-Perez. Funding for this project was provided by the Maryland Agricultural Experiment Station and the NOAA/NCCOS Cooperative Oxford Lab, The research in this article does not signify that the contents necessarily reflect the views and policies of the agencies involved nor do trade names or commercial products constitute endorsement oi recommendation for use. NR 69 TC 13 Z9 14 U1 3 U2 8 PU INTER-RESEARCH PI OLDENDORF LUHE PA NORDBUNTE 23, D-21385 OLDENDORF LUHE, GERMANY SN 0177-5103 J9 DIS AQUAT ORGAN JI Dis. Aquat. Org. PD DEC 3 PY 2009 VL 87 IS 3 BP 183 EP 197 DI 10.3354/dao02114 PG 15 WC Fisheries; Veterinary Sciences SC Fisheries; Veterinary Sciences GA 537KR UT WOS:000273112300004 PM 20099412 ER PT J AU Birnkrant, D Cox, E AF Birnkrant, Debra Cox, Edward TI The Emergency Use Authorization of Peramivir for Treatment of 2009 H1N1 Influenza SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Birnkrant, Debra; Cox, Edward] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Birnkrant, D (reprint author), US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 2 TC 121 Z9 125 U1 2 U2 10 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 3 PY 2009 VL 361 IS 23 BP 2204 EP 2207 DI 10.1056/NEJMp0910479 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 525ZM UT WOS:000272257100002 PM 19884645 ER PT J AU Gao, ZM AF Gao, Zongming TI In Vitro Dissolution Testing with Flow-Through Method: A Technical Note SO AAPS PHARMSCITECH LA English DT Article DE dissolution; IVIVC; USP4 apparatus ID COLLABORATIVE INVITRO DISSOLUTION; CALIBRATOR TABLETS; ABSORPTION; SYSTEM; PH C1 US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Gao, ZM (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, 1114 Market St,Room 1002, St Louis, MO 63101 USA. EM zongming.gao@fda.hhs.gov NR 15 TC 7 Z9 8 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 2009 VL 10 IS 4 BP 1401 EP 1405 DI 10.1208/s12249-009-9339-6 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 538HD UT WOS:000273174300040 PM 19937283 ER PT J AU Carman, RJ Genheimer, CW Rafii, F Park, M Hiltonsmith, MF Lyerly, DM AF Carman, Robert J. Genheimer, Christopher W. Rafii, Fatemeh Park, Miseon Hiltonsmith, Megan F. Lyerly, David M. TI Diversity of moxifloxacin resistance during a nosocomial outbreak of a predominantly ribotype ARU 027 Clostridium difficile diarrhea SO ANAEROBE LA English DT Article; Proceedings Paper CT 9th Biennial Congress of the Anaerobe-Society-of-the-Americas CY JUN 24-27, 2008 CL Long Beach, CA SP Anaerobe Soc Amer DE Clostridium difficile; Quinolone; Moxifloxacin; Resistance; gyrA; gyrB; QRDR; PCR; SNP; MAMA ID BINARY TOXIN GENES; ADP-RIBOSYLTRANSFERASE; STRAIN; MUTATIONS; GYRA; DISEASE; EUROPE; PCR AB To characterize the extent and diversity of moxifloxacin resistance among Clostridium difficile isolates recovered during a predominantly Anaerobe Reference Unit (ARU) ribotype 027-associated nosocomial outbreak of antibiotic associated diarrhea we measured the susceptibility of 34 field isolates and 6 laboratory strains of C. difficile to moxifloxacin. We ribotyped the isolates as well as assaying them by PCR for the metabolic gene, gdh, and the virulence genes, tcdA, tcdB, tcdC, cdtA and cdtB. All the laboratory isolates, including the historical ARU 027 isolate Cd196, were susceptible to moxifloxacin (<= 2 mu g/mL). 13 field isolates were susceptible to <= 2 4g/mL. Five were resistant to from 4 to 12 mu g/mL (moderate resistance); 16 were resistant to >= 16 mu g/mL (high resistance). We sequenced the quinolone resistance determining regions of gyrA (position 71-460) and gyrB (position 1059-1448) from two susceptible laboratory strains, all five isolates with moderate resistance and two highly resistant isolates. Two highly resistant isolates (Pitt 40, ribotype ARU 027 and Pitt 33, ribotype ARU 001) had the same C245T (Thr(82)Delta Ile) mutation. No other changes were seen. Amplification with primer pairs specific for the C245T mutant gyrA and for the wild type gene respectively confirmed all 16 highly resistant ARU 027 isolates, as well as the highly resistant isolates from other ribotypes, had the C245T mutation and that the mutation was absent from all other isolates. Among the five isolates with moderate resistance we found combinations of mutations within gyrA (T128A, Val(43)Delta Asp and G349T, Ala(117)Delta Ser) and gyrB (G1276A, Arg(426)Delta Asn). The G1396A (Glu(466)Delta Lys) mutation was not associated with increased resistance. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Carman, Robert J.; Genheimer, Christopher W.; Hiltonsmith, Megan F.; Lyerly, David M.] TechLab Inc, Blacksburg, VA 24060 USA. [Rafii, Fatemeh; Park, Miseon] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Carman, RJ (reprint author), TechLab Inc, 2001 Kraft Dr, Blacksburg, VA 24060 USA. EM rjcarman@techlab.com NR 28 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1075-9964 EI 1095-8274 J9 ANAEROBE JI Anaerobe PD DEC PY 2009 VL 15 IS 6 SI SI BP 244 EP 248 DI 10.1016/j.anaerobe.2009.09.009 PG 5 WC Microbiology SC Microbiology GA 547XH UT WOS:000273922700007 PM 19818865 ER PT J AU Rafii, F Park, M da Costa, GG Camacho, L AF Rafii, Fatemeh Park, Miseon da Costa, Goncalo Gamboa Camacho, Luisa TI Comparison of the metabolic activities of four wild-type Clostridium perfringens strains with their gatifloxacin-selected resistant mutants SO ARCHIVES OF MICROBIOLOGY LA English DT Article DE Clostridium perfringens; Fluoroquinolone; Resistance; Azoreductase; Nitroreductase; Gatifloxacin ID ANTIBIOTIC-ASSOCIATED DIARRHEA; INTESTINAL MICROFLORA; ESCHERICHIA-COLI; TOPOISOMERASE-IV; DIFFICILE; NITROREDUCTASE; TOXIN; GENE; CIPROFLOXACIN; AZOREDUCTASE AB The production of short-chain fatty acids, reductive enzymes, and hydrolytic enzymes by four gatifloxacin-selected, fluoroquinolone-resistant, mutant strains of C. perfringens, with stable mutations either in DNA gyrase or in both DNA gyrase and topoisomerase IV, was compared with that produced by the wild-type parent strains to investigate the effect of mutations associated with the selection of gatifloxacin resistance on bacterial metabolic activities. The mutants differed from their respective wild-type parent strains in the enzymatic activities of azoreductase, nitroreductase, and beta-glucosidase and in the ratio of butyric acid to acetic acid production. Microarray analysis of one wild type and the corresponding mutant revealed different levels of mRNA expression for the enzymes involved in short-chain fatty acid (SCFA) synthesis and for beta-glucosidase and oxidoreductases. In addition to mutations in the target genes, selection of resistance to gatifloxacin resulted in strain-specific physiological changes in the resistant mutants of C. perfringens that affected their metabolic activities. C1 [Rafii, Fatemeh; Park, Miseon] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [da Costa, Goncalo Gamboa; Camacho, Luisa] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Rafii, F (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM fatemeh.rafii@fda.hhs.gov RI Camacho, Luisa/D-1088-2012 NR 40 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0302-8933 J9 ARCH MICROBIOL JI Arch. Microbiol. PD DEC PY 2009 VL 191 IS 12 BP 895 EP 902 DI 10.1007/s00203-009-0518-3 PG 8 WC Microbiology SC Microbiology GA 519JB UT WOS:000271761200004 PM 19855959 ER PT J AU Benjamin, DK Smith, PB Sun, MJM Murphy, MD Avant, D Mathis, L Rodriguez, W Califf, RM Li, JS AF Benjamin, Daniel K., Jr. Smith, P. Brian Sun, M. Jessica M. Murphy, M. Dianne Avant, Debbie Mathis, Lisa Rodriguez, William Califf, Robert M. Li, Jennifer S. TI Safety and Transparency of Pediatric Drug Trials SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID PARTIAL SEIZURES; CHILDREN; EXCLUSIVITY; PUBLICATION; EFFICACY; INFANTS AB Objectives: To quantify the frequency and type of new safety information arising from studies performed under the auspices of the Pediatric Exclusivity Program, to describe the dissemination of these findings in the peer-reviewed literature and compare this with the US Food and Drug Administration (FDA) review, and to describe their effect on pediatric labeling. Design: Cohort study of the 365 trials performed for 153 drugs. Setting: The Pediatric Exclusivity incentive from December 1997 through September 2007. Participants: Food and Drug Administration publicly available records and peer-reviewed literature retrievable by MEDLINE search. Main Exposures: New safety findings obtained from the trials completed for exclusivity. Outcome Measures: Concordance of the information highlighted in the peer-reviewed article abstracts with the information in the FDA labeling and drug reviews. Results: There were 137 labeling changes; we evaluated 129 of these (the 8 selective serotonin reuptake inhibitors were excluded from review). Thirty-three products (26%) had pediatric safety information added to the labeling. Of these, 12 products had neuropsychiatric safety findings and 21 had other important safety findings. Only 16 of 33 of these trials (48%) were reported in the peer-reviewed literature; however, 7 of 16 focused on findings substantively different from those highlighted in the FDA reviews and labeling changes. Conclusions: Medication adverse events in children often differ from those in adults, particularly those that are neuropsychiatric in nature. Labeling changes for pediatric use demonstrate that pediatric drug studies provide valuable and unique safety data that can guide the use of these drugs in children. Unfortunately, most of these articles are not published, and almost half of the published articles focus their attention away from the crucial safety data. C1 [Benjamin, Daniel K., Jr.; Smith, P. Brian; Califf, Robert M.; Li, Jennifer S.] Duke Univ, Duke Clin Res Inst, Durham, NC 27705 USA. [Benjamin, Daniel K., Jr.; Smith, P. Brian; Sun, M. Jessica M.; Li, Jennifer S.] Duke Univ, Dept Pediat, Durham, NC 27705 USA. [Smith, P. Brian; Murphy, M. Dianne; Avant, Debbie; Rodriguez, William; Li, Jennifer S.] US FDA, Off Pediat Therapeut, Off Commissioner, Rockville, MD 20857 USA. [Mathis, Lisa] US FDA, Pediat & Maternal Hlth Staff Off, New Drugs Immediate Off, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Benjamin, DK (reprint author), Duke Univ, Duke Clin Res Inst, POB 17969, Durham, NC 27705 USA. EM danny.benjamin@duke.edu RI Smith, Phillip/I-5565-2014 FU National Institute of Child Health and Human Development [1U10-HD45962-04, 1UL 1RR024128-02]; US Government [1R01HD057956-02, 1R01FD003519-01, 1U10-HD45962-06, 1K24HD05873501, HHSN267200700051C] FX This study was supported by grants 1U10-HD45962-04 and 1UL 1RR024128-02 (Drs Benjamin, Smith, and Li), and 1UL 1RR024128-02 (Dr Califf) from the National Institute of Child Health and Human Development. Dr Benjamin has received support from the US Government for his work in pediatric and neonatal clinical pharmacology (1R01HD057956-02, 1R01FD003519-01, 1U10-HD45962-06, 1K24HD05873501, and Government Contract HHSN267200700051C), the nonprofit organization Thrasher Research Foundation for his work in neonatal candidiasis (http://www.thrasherresearch.org), and from industry for neonatal and pediatric drug development (http://www.dcri.duke.edu/research/coi.jsp). NR 19 TC 27 Z9 28 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD DEC PY 2009 VL 163 IS 12 BP 1080 EP 1086 PG 7 WC Pediatrics SC Pediatrics GA 529DF UT WOS:000272495300001 PM 19996043 ER PT J AU Woodcock, J AF Woodcock, Janet TI Progress on the FDA's Critical Path Initiative SO BIOMARKERS IN MEDICINE LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. RP Woodcock, J (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51 Suite 6100, Silver Spring, MD 20903 USA. EM janet.woodcock@fda.hhs.gov NR 2 TC 1 Z9 1 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 J9 BIOMARK MED JI Biomark. Med. PD DEC PY 2009 VL 3 IS 6 BP 671 EP 673 DI 10.2217/BMM.09.72 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 541IS UT WOS:000273409100003 PM 20477704 ER PT J AU Parsons, BL Meng, FX AF Parsons, Barbara L. Meng, Fanxue TI K-RAS mutation in the screening, prognosis and treatment of cancer SO BIOMARKERS IN MEDICINE LA English DT Review DE biomarker; carcinogenesis; mutation detection; oncogene; personalized medicine ID METASTATIC COLORECTAL-CANCER; CELL LUNG-CANCER; FRAGMENT-LENGTH-POLYMORPHISM; POLYMERASE-CHAIN-REACTION; MELTING CURVE ANALYSIS; PEPTIDE NUCLEIC-ACID; KRAS2 GENE-MUTATIONS; FECAL OCCULT BLOOD; PANCREATIC-CANCER; PLASMA DNA AB The potential use of K-RAS mutation as a cancer screening biomarker has been investigated for many years. Numerous associations between K-RAS mutation and various cancers have been established, but these associations have not been translated into effective, cost-efficient cancer screening strategies. This lack of progress may be due to the existence of K-RAS mutation in nontumor tissues and/or using detection, rather than quantitation, of K-RAS mutation as the endpoint for cancer risk categorization. K-RAS mutation appears to be a useful prognostic biomarker for colon cancer. Recent progress toward sensitive and quantitative mutation characterization and the successful use of K-RAS mutation in a personalized medicine approach to targeted biological therapy selection are likely to re-direct and expand the use of K-RAS mutation as a cancer biomarker in the near future. C1 [Parsons, Barbara L.; Meng, Fanxue] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Parsons, BL (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM barbara.parsons@fda.hhs.gov NR 104 TC 26 Z9 28 U1 0 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 J9 BIOMARK MED JI Biomark. Med. PD DEC PY 2009 VL 3 IS 6 BP 757 EP 769 DI 10.2217/BMM.09.95 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 541IS UT WOS:000273409100018 PM 20477713 ER PT J AU Hussong, D Brorson, K McVey, J Faustino, P Lute, S AF Hussong, David Brorson, Kurt McVey, James Faustino, Patrick Lute, Scott TI Untitled reply SO BIOPHARM INTERNATIONAL LA English DT Letter C1 [Hussong, David] US FDA, Off Biotechnol Prod, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Off Testing & Res, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Hussong, D (reprint author), US FDA, Off Biotechnol Prod, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ADVANSTAR COMMUNICATIONS INC PI WOODLAND HILLS PA 6200 CANOGA AVE, 2ND FLR, WOODLAND HILLS, CA 91367 USA SN 1542-166X J9 BIOPHARM INT JI Biopharm. Int. PD DEC PY 2009 VL 22 IS 12 BP 12 EP + PG 2 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 533GN UT WOS:000272811800003 ER PT J AU Wise, LD Buschmann, J Feuston, MH Fisher, JE Hew, KW Hoberman, AM Lerman, SA Ooshima, Y Stump, DG AF Wise, L. David Buschmann, Jochen Feuston, Maureen H. Fisher, J. Edward Hew, Kok Wah Hoberman, Alan M. Lerman, Steven A. Ooshima, Yojiro Stump, Donald G. TI Embryo-Fetal Developmental Toxicity Study Design for Pharmaceuticals SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Review DE developmental toxicity; embryo-fetal development; safety assessment; hazard assessment; teratogenicity ID 5-ALPHA-REDUCTASE INHIBITOR; SKELETAL DEVELOPMENT; EXTERNAL GENITALIA; RATS; ABNORMALITIES; TERMINOLOGY; RABBITS; CLASSIFICATION; HARMONIZATION; HEMATOLOGY AB Assessment of potential developmental and reproductive toxicity of human pharmaceuticals is currently guided by the International Conference on Harmonization (ICH) S5(R2) document (available at http://www.ich.org). The studies that assess developmental hazard are generally conducted in rodents and rabbits. Based on the authors' collective experience, adequate designs (including range-finding studies) and the presentation of data for these studies are described in detail. In addition, the suggested initiation and then total duration of these studies in relation to clinical studies that enroll women of childbearing potential are described. Optional parameters that may be included in the studies are discussed, as are study designs that combine assessments of fertility and developmental toxicity. New methods that may replace or enhance current procedures are outlined. The details described herein will assist all laboratories performing these studies, individuals who need to plan for the studies, and regulatory agencies that ultimately review these studies. Birth Defects Res (Part B) 86:418-4.28, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Wise, L. David] Merck Res Labs, West Point, PA 19486 USA. [Buschmann, Jochen] Fraunhofer Inst Toxicol & Expt Med, Hannover, Germany. [Feuston, Maureen H.] Sanofi Aventis US Inc, Malvern, PA USA. [Fisher, J. Edward] US FDA, CDER, Silver Spring, MD USA. [Hew, Kok Wah] Takeda Global Res & Dev Ctr Inc, Lake Forest, IL USA. [Lerman, Steven A.] GlaxoSmith Kline R&D, King Of Prussia, PA USA. [Ooshima, Yojiro] Shin Nippon Biomed Labs, Kagoshima, Japan. [Stump, Donald G.] WIL Res Labs LLC, Ashland, OH USA. RP Wise, LD (reprint author), Merck Res Labs, WP 45-115, West Point, PA 19486 USA. EM ld_wise@merck.com NR 49 TC 20 Z9 20 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD DEC PY 2009 VL 86 IS 6 BP 418 EP 428 DI 10.1002/bdrb.20214 PG 11 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 539RM UT WOS:000273275500002 PM 20025038 ER PT J AU Bailey, GP Wise, LD Buschmann, J Hurtt, M Fisher, JE AF Bailey, Graham P. Wise, L. David Buschmann, Jochen Hurtt, Mark Fisher, J. Edward TI Pre- and Postnatal Developmental Toxicity Study Design for Pharmaceuticals SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Review DE prenatal; postnatal developmental toxicity; neonatal development; safety assessment; hazard assessment ID NEURODEVELOPMENTAL END-POINTS; EXPERT WORKING GROUP; MALE-RAT; TOXICOLOGY AB Assessment of potential developmental and reproductive toxicity of human pharmaceuticals is currently guided by the ICH S5(R2) document. The studies that assess the hazard of both pre- and postnatal exposure are predominantly conducted in rodents (rat and mouse). Utilizing the collective experience of the authors, acceptable designs for both the range-finding and definitive studies are presented with detailed descriptions for the presentation of data. In addition, the suggested initiation and then total duration of these studies in relation to clinical studies are described. Optional parameters that may be included in the studies, as well as possible combination with other study designs are discussed. The details described herein will assist all laboratories performing these studies, individuals who need to plan for the studies, and regulatory agencies that ultimately review these studies. Birth Defects Res (Part B) 86:437-445, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Bailey, Graham P.] Johnson & Johnson Pharmaceut Res & Dev, B-2340 Beerse, Belgium. [Wise, L. David] Merck Res Labs, West Point, PA USA. [Buschmann, Jochen] Fraunhofer Inst Toxicol & Expt Med, Hannover, Germany. [Hurtt, Mark] Pfizer Drug Safety Res & Dev, Groton, CT USA. [Fisher, J. Edward] US FDA, CDER, Silver Spring, MD USA. RP Bailey, GP (reprint author), Johnson & Johnson Pharmaceut Res & Dev, Turnhoutseweg 30, B-2340 Beerse, Belgium. EM gbailey1@its.jnj.com NR 24 TC 24 Z9 24 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD DEC PY 2009 VL 86 IS 6 BP 437 EP 445 DI 10.1002/bdrb.20217 PG 9 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 539RM UT WOS:000273275500004 PM 20025040 ER PT J AU Cappon, GD Bailey, GP Buschmann, J Feuston, MH Fisher, JE Hew, KW Hoberman, AM Ooshima, Y Stump, DG Hurtt, ME AF Cappon, Gregg D. Bailey, Graharn P. Buschmann, Jochen Feuston, Maureen H. Fisher, J. Edward Hew, Kok Wah Hoberman, Alan M. Ooshima, Yojiro Stump, Donald G. Hurtt, Mark E. TI Juvenile Animal Toxicity Study Designs to Support Pediatric Drug Development SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Review DE pharmaceuticals; regulatory; safety assessment; juvenile toxicity ID REPRODUCTIVE-SYSTEM; FEMALE RATS; AGE; NEUROTOXICITY; MATURATION; PARATHION; EXPOSURE; GROWTH AB The objective of juvenile animal toxicity studies of pharmaceuticals is to obtain safety data, including information on the potential for adverse effects on postnatal growth and development. Studies in juvenile animals may assist in identifying postnatal developmental toxicities or other adverse effects that are not adequately assessed in the routine toxicity evaluations and that cannot be safely or adequately measured in pediatric clinical trials. Unlike the traditional reproductive and developmental toxicology studies that have been discussed in the accompanying reports, the design requirements for toxicity studies in juvenile animals are not explicitly defined in regulatory guidance. However, studies in juvenile animals can be useful in providing safety information necessary to enable pediatric clinical trials in pediatric patients or when there are special concerns for toxicities that cannot be safely or adequately measured in clinical trials. These juvenile animal toxicity studies are designed on a case-by-case basis. General design considerations and examples of study designs for assessment of juvenile animal toxicity are discussed. Birth Defects Res (Part B) 86:463-469, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Cappon, Gregg D.; Hurtt, Mark E.] Groton Labs, Pfizer Global Res & Dev, Groton, CT 06340 USA. [Bailey, Graharn P.] Janssen Pharmaceut, Johnson & Johnson PRD, B-2340 Beerse, Belgium. [Buschmann, Jochen] Fraunhofer Inst Toxicol & Expt Med, Hannover, Germany. [Feuston, Maureen H.] Sanofi Aventis US Inc, Malvern, PA USA. [Fisher, J. Edward] US FDA, CDER, Silver Spring, MD USA. [Hew, Kok Wah] Takeda Global Res & Dev Ctr Inc, Lake Forest, IL USA. [Ooshima, Yojiro] Shin Nippon Biomed Labs, Kagoshima, Japan. [Stump, Donald G.] WIL Res Labs LLC, Ashland, OH USA. RP Cappon, GD (reprint author), Groton Labs, Pfizer Global Res & Dev, Eastern Point Rd,MS 8274-1260, Groton, CT 06340 USA. EM Gregg.d.cappon@pfizer.com NR 32 TC 36 Z9 40 U1 1 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD DEC PY 2009 VL 86 IS 6 BP 463 EP 469 DI 10.1002/bdrb.20220 PG 7 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 539RM UT WOS:000273275500006 PM 20025047 ER PT J AU Tang, YC Thoman, M Linton, PJ Deisseroth, A AF Tang, Yu Cheng Thoman, Marilyn Linton, Phyllis-Jean Deisseroth, Albert TI Use of CD40L immunoconjugates to overcome the defective immune response to vaccines for infections and cancer in the aged SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Vaccines; Immunoconjugates; MUC-1; CD40L ID T-CELL RESPONSES; INFLUENZA VACCINATION; DENDRITIC CELLS; ELDERLY-PEOPLE; OLD-AGE; LIGAND; MICE; POPULATION; MUC1; IMMUNOGENICITY AB Multiple investigators have reported the presence of defects in the immune response of the elderly [Castle In: Clin Infect Dis 31:578, 2000; Ortqvist et al. In: Eur Respir J 30:414-422, 2007; Saurwein-Teissl et al. In: J Immunol 168:5893, 2002; Haynes et al. In: Proc Natl Acad Sci USA 100:15053-15058, 2003]. These defects reduce the magnitude of the immune response to infection and to vaccination. In individuals greater than 55 years of age, the probability of developing a fully protective neutralizing antibody response to the yearly multivalent particle inactivated influenza vaccine is less than 20% [Jefferson et al. In: Lancet 264:1165-1174, 2005; Goodwin et al. In: Vaccine 24:1159-1169, 2006; Jackson et al. In: Lancet 372:398-405, 2008; Simonsen and Taylor In: Lancet 7:658-666, 2007]. The defects in the aged immune system that are responsible for this limited response to vaccination in the older age groups include functional defects of the antigen presenting cells, functional defects in CD4 helper CD4 T cells and monocytes, and an altered microenvironment [Eaton et al. In: J Exp Med 200:1613-1622, 2004; Dong et al. In: J Gen Virol 84:1623-1628, 2003; Deng et al. In: Immunology 172:3437-3446, 2004; Cella et al. In: J Exp Med 184:747-752, 1996]. Starting at puberty, the involution of the thymus and the consequent reduction of the export of na < ve T cells specific to neo-antigens leads to the reduction of the ratio of antigen na < ve to memory cells as chronological age advances [Prelog In: Autoimmun Rev 5:136-139, 2006; McElhaney et al. In: J Immunology 176:6333-6339, 2006]. Changes in glycosylation of T cells and target antigens acquired during the aging process and the antibodies to these new glycopeptides and glycoproteins may also contribute to a reduction in the functioning of the adaptive immune response [Ishii et al. In: J Clin Neurosci 14:110-115, 2007; Shirai et al. In: Clin Exp Immunol 12:455-464, 1972; Adkins and Riley In: Mech Ageing Dev 103:147-164, 1998; Ben-Yehuda and Weksler In: Cancer Investigation 10:525-531, 1992]. One of the more interesting examples of the functional defects in the cells of the adaptive immune response is a reduced level of expression in the surface cytoadhesion and activation receptor molecules on CD4 helper T cells undergoing activation during vaccination. Upon infection or vaccination, CD40L is typically increased on the surface of CD4 helper T cells during activation, and this increased expression is absolutely essential to the CD40L promotion of expansion of antigen-specific B cells and CD 8 effector T cells in response to infection or vaccination [Singh et al. In: Protein Sci 7:1124-1135, 1998; Grewal and Flavell In: Immunol Res 16: 59-70, 1997; Kornbluth In: J Hematother Stem Cell Res 11:787-801, 2002; Garcia de Vinuesa et al. In: Eur J Immunol 29:3216-3224, 1999]. In aged human beings and mice, the reduced levels of expression of CD40 ligand (CD40L) in activated CD4 helper T cells is dramatically reduced [Eaton et al. In: J Exp Med 200:1613-1622, 2004; Dong et al. In: J Gen Virol 84:1623-1628, 2003]. To circumvent the reduction in CD40L expression and the subsequent reduction in immune response in the elderly, we have developed a chimeric vaccine comprised of the CD40L linked to the target antigen, in a replication incompetent adenoviral vector and in booster protein. This review will discuss the implementation the potential use of this approach for the vaccination of the older populations for cancer and infection. C1 [Tang, Yu Cheng; Thoman, Marilyn; Linton, Phyllis-Jean; Deisseroth, Albert] Sidney Kimmel Canc Ctr, San Diego, CA 92121 USA. RP Deisseroth, A (reprint author), US FDA, Off Oncol Drug Prod, 10903 New Hampshire Ave,Bldg 22,Room 6378, Silver Spring, MD 20993 USA. EM albert.deisseroth@yahoo.com NR 39 TC 12 Z9 12 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD DEC PY 2009 VL 58 IS 12 BP 1949 EP 1957 DI 10.1007/s00262-009-0718-3 PG 9 WC Oncology; Immunology SC Oncology; Immunology GA 498UE UT WOS:000270168800006 PM 19444444 ER PT J AU Kandzari, DE Farb, A Boam, AB AF Kandzari, David E. Farb, Andrew Boam, Ashley B. TI Percutaneous Coronary Intervention in Perspective Drug-Eluting Stents as a Model for Regulatory Review SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Review DE delivery of health care; public policy; government regulation; stents ID BARE-METAL STENTS; RANDOMIZED CLINICAL-TRIALS; LONG-TERM OUTCOMES; OFF-LABEL; ANTIPLATELET THERAPY; FOLLOW-UP; THROMBOSIS; IMPLANTATION; PREDICTORS; SAFETY C1 [Kandzari, David E.] Scripps Clin, Div Cardiovasc Dis, La Jolla, CA 92037 USA. [Farb, Andrew; Boam, Ashley B.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Kandzari, DE (reprint author), Scripps Green Clin, Div Cardiovasc Dis, Maildrop S1056,10666 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM kandzari.david@scrippshealth.org FU Cordis Corporation and Medtronic Vascular FX Dr Kandzari serves as a consultant to the FDA Circulatory System Devices Panel under special government employee status. Dr Kandzari receives research/grant support from Cordis Corporation and Medtronic Vascular and is a former employee of Cordis Corporation/Johnson & Johnson but has no equity conflict. Dr Farb and Ashley Boam are US government employees of the FDA. NR 39 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7640 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD DEC PY 2009 VL 2 IS 6 BP 574 EP 579 DI 10.1161/CIRCINTERVENTIONS.109.871996 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 575LS UT WOS:000276069100013 PM 20031776 ER PT J AU Menzies, SL Kadwad, V Pawloski, LC Lin, TL Baughman, AL Martin, M Tondella, MLC Meade, BD AF Menzies, Sandra L. Kadwad, Vijay Pawloski, Lucia C. Lin, Tsai-Lien Baughman, Andrew L. Martin, Monte Tondella, Maria Lucia C. Meade, Bruce D. CA Pertussis Assay Working Grp TI Development and Analytical Validation of an Immunoassay for Quantifying Serum Anti-Pertussis Toxin Antibodies Resulting from Bordetella pertussis Infection SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID LINKED IMMUNOSORBENT ASSAYS; EUROPEAN-SEROEPIDEMIOLOGY-NETWORK; IMMUNOGLOBULIN-G ANTIBODIES; UNITED-STATES; DIAGNOSIS; EPIDEMIOLOGY; ADULTS; STANDARDIZATION; ADOLESCENTS; VACCINE AB Adequately sensitive and specific methods to diagnose pertussis in adolescents and adults are not widely available. Currently, no Food and Drug Administration-approved diagnostic assays are available for the serodiagnosis of Bordetella pertussis. Since concentrations of B. pertussis-specific antibodies tend to be high during the later phases of disease, a simple, rapid, easily transferable serodiagnostic test was developed. This article describes test development, initial evaluation of a prototype kit enzyme-linked immunosorbent assay ( ELISA) in an interlaboratory collaborative study, and analytical validation. The data presented here demonstrate that the kit met all prespecified criteria for precision, linearity, and accuracy for samples with anti-pertussis toxin ( PT) immunoglobulin G (IgG) antibody concentrations in the range of 50 to 150 ELISA units (EU)/ml, the range believed to be most relevant for serodiagnosis. The assay met the precision and linearity criteria for a wider range, namely, from 50 to 200 EU/ml; however, the accuracy criterion was not met at 200 EU/ml. When the newly adopted World Health Organization International Standard for pertussis antiserum ( human) reference reagent was used to evaluate accuracy, the accuracy criteria were met from 50 to 200 international units/ml. In conclusion, the IgG anti-PT ELISA met all assay validation parameters within the range considered most relevant for serodiagnosis. This ELISA was developed and analytically validated as a user-friendly kit that can be used in both qualitative and quantitative formats. The technology for producing the kit is transferable to public health laboratories. C1 [Menzies, Sandra L.] US FDA, CBER, DBPAP, OVRR, Rockville, MD 20850 USA. [Pawloski, Lucia C.; Baughman, Andrew L.; Martin, Monte; Tondella, Maria Lucia C.] Ctr Dis Control & Prevent, Div Bacterial Dis, Atlanta, GA USA. [Lin, Tsai-Lien] US FDA, Ctr Biol Evaluat & Res, Div Biostat, Rockville, MD 20850 USA. [Kadwad, Vijay] BRIT, Immunoassay Dept, Bombay, Maharashtra, India. [Meade, Bruce D.] Meade Biol LLC, Hillsborough, NC USA. RP Menzies, SL (reprint author), US FDA, CBER, DBPAP, OVRR, 1401 Rockville Pike,HFM 422, Rockville, MD 20850 USA. EM Sandra.Menzies@fda.hhs.gov FU CDC; FDA/CBER FX This project was funded in part by an interagency agreement between the CDC and the FDA/CBER. NR 38 TC 20 Z9 21 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD DEC PY 2009 VL 16 IS 12 BP 1781 EP 1788 DI 10.1128/CVI.00248-09 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 524QG UT WOS:000272157200009 PM 19864485 ER PT J AU Wagner, JA Wright, EC Ennis, MM Prince, M Kochan, J Nunez, DJR Schneider, B Wang, MD Chen, Y Ghosh, S Musser, BJ Vassileva, MT AF Wagner, J. A. Wright, E. C. Ennis, M. M. Prince, M. Kochan, J. Nunez, D. J. R. Schneider, B. Wang, M-D Chen, Y. Ghosh, S. Musser, B. J. Vassileva, M. T. TI Utility of Adiponectin as a Biomarker Predictive of Glycemic Efficacy Is Demonstrated by Collaborative Pooling of Data From Clinical Trials Conducted by Multiple Sponsors SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID NONDIABETIC PATIENTS; PLASMA ADIPONECTIN; DIABETIC-PATIENTS; DRUG DISCOVERY; GAMMA-AGONISTS; ROSIGLITAZONE; PIOGLITAZONE; ADIPOKINES; RECEPTORS; INDUCTION AB This study, conducted under the metabolic Disorders steering Committee of the Biomarkers Consortium (a public-private partnership managed by the Foundation for the national institutes of health (FNIH)), analyzed blinded data on 2,688 type 2 diabetes (T2D) patients from randomized clinical trials conducted by four pharmaceutical companies. an increase in the levels of adiponectin was observed after peroxisome proliferator-activated receptor (PPAR)-agonist treatment (P < 0.0001), but not after treatment with non-PPAR drugs. This increase correlated with decreases in levels of glucose, hemoglobin A(1c) (Hb(A1c)), hematocrit, and triglycerides, and increases in levels of blood urea nitrogen, creatinine, and high-density lipoprotein cholesterol (HDL-C). early (6-8 weeks) increases in levels of adiponectin after treatment with PPAR agonists showed a negative correlation (r = -0.21, P < 0.0001) with subsequent changes in levels of Hb(A1c). Changes in adiponectin level did not appear to be associated with baseline level of Hb(A1c). logistic regression demonstrated that an increase in the level of adiponectin predicts a decrease in the level of Hb(A1c). These analyses confirm previously demonstrated relationships between adiponectin levels and metabolic parameters and support the robust predictive utility of adiponectin across the spectrum of glucose tolerance. Cross-company precompetitive collaboration is a feasible and powerful approach to biomarker qualification. C1 [Vassileva, M. T.] Fdn Natl Inst Hlth, Biomarkers Consortium, Bethesda, MD USA. [Wagner, J. A.] Merck Res Labs, Dept Clin Pharmacol, Rahway, NJ USA. [Wright, E. C.] NIDDKD, NIH, Bethesda, MD 20892 USA. [Ennis, M. M.] Quintiles, Biostat, Austin, TX USA. [Prince, M.] Eli Lilly & Co, Diabet Endocrine Med, Indianapolis, IN 46285 USA. [Kochan, J.] Roche, Metab Dis, Nutley, NJ USA. [Nunez, D. J. R.] GlaxoSmithKline Inc, Metab Pathways Ctr Excellence Drug Discovery, Res Triangle Pk, NC USA. [Schneider, B.] US FDA, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Wang, M-D] Eli Lilly & Co, Lilly Corp Ctr, Global Stat Sci, Indianapolis, IN 46285 USA. [Chen, Y.; Musser, B. J.] Merck Res Labs, Late Dev Stat, Rahway, NJ USA. [Ghosh, S.] P5 Med, Cary, NC USA. RP Vassileva, MT (reprint author), Fdn Natl Inst Hlth, Biomarkers Consortium, Bethesda, MD USA. EM mvassileva@fnih.org OI GHOSH, SUJOY/0000-0002-7601-165X NR 22 TC 25 Z9 26 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 DEC PY 2009 VL 86 IS 6 BP 619 EP 625 DI 10.1038/clpt.2009.88 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 523IY UT WOS:000272067700013 PM 19553931 ER PT J AU Jefferson, WN Doerge, D Padilla-Banks, E Woodling, KA Kissling, GE Newbold, R AF Jefferson, Wendy N. Doerge, Daniel Padilla-Banks, Elizabeth Woodling, Kellie A. Kissling, Grace E. Newbold, Retha TI Oral Exposure to Genistin, the Glycosylated Form of Genistein, during Neonatal Life Adversely Affects the Female Reproductive System SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE development; diethylstilbestrol; endocrine disruptors; environmental estrogen; isoflavone; ovary ID SPRAGUE-DAWLEY RATS; SOY ISOFLAVONE GENISTEIN; OOCYTE NEST BREAKDOWN; EXPERT PANEL REPORT; PHYTOESTROGEN GENISTEIN; DEVELOPMENTAL TOXICITY; POSTNATAL-DEVELOPMENT; INFANT FORMULAS; ESTROUS-CYCLE; MOUSE OVARY AB BACKGROUND: Developmental exposure to environmental estrogens is associated with adverse consequences later in life. Exposure to genistin (GIN), the glycosylated form of the phytoestrogen genistein (GEN) found in soy products, is of concern because approximately 20% of U.S. infants are fed soy formula. High circulating levels of GEN have been measured in the serum of these infants, indicating that GIN is readily absorbed, hydrolyzed, and circulated. OBJECTIVES: We investigated whether orally administered GIN is estrogenic in neonatal mice and whether it causes adverse effects on the developing female reproductive tract. METHODS: Female CD-I mice were treated on postnatal days 1-5 with oral GIN (6.25, 12.5, 25, or 37.5 mg/kg/day; GEN-equivalent doses), oral GEN (25, 37.5, or 75 mg/kg/day), or subcutaneous GEN (12.5, 20, or 25 mg/kg/day). Estrogenic activity was measured on day 5 by determining uterine wet weight gain and induction of the estrogen-responsive gene lactoferrin. Vaginal opening, estrous cyclicity, fertility, and morphologic alterations in the ovary/reproductive tract were examined. RESULTS: Oral GIN elicited an estrogenic response in the neonatal uterus, whereas the response to oral GEN was much weaker. Oral GIN altered ovarian differentiation (i.e., multioocyte follicles), delayed vaginal opening, caused abnormal estrous cycles, decreased fertility, and delayed parturition. CONCLUSIONS: Our results support the idea that the dose of the physiologically active compound reaching the target tissue, rather than the administered dose or route, is most important in modeling chemical exposures. This is particularly true with young animals in which phase II metabolism capacity is underdeveloped relative to adults. C1 [Jefferson, Wendy N.; Padilla-Banks, Elizabeth] NIEHS, Reprod & Dev Toxicol Lab, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. [Jefferson, Wendy N.; Padilla-Banks, Elizabeth; Newbold, Retha] NIEHS, Mol Toxicol Lab, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. [Doerge, Daniel; Woodling, Kellie A.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Kissling, Grace E.] NIEHS, Biostat Branch, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. [Newbold, Retha] NIEHS, Natl Toxicol Program, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Jefferson, WN (reprint author), NIEHS, Reprod & Dev Toxicol Lab, NIH, US Dept HHS, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM jeffers1@niehs.nih.gov FU National Institute of Environmental Health Sciences/National Institutes of Health; Oak Ridge Institute for Science and Education; U.S. Department of Energy and Food and Drug Administration FX This research was supported by the Intramural Research Program of National Institute of Environmental Health Sciences/National Institutes of Health. K.A.W. acknowledges support from Oak Ridge Institute for Science and Education administered through an interagency agreement between the U.S. Department of Energy and Food and Drug Administration. NR 51 TC 44 Z9 46 U1 5 U2 19 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 2009 VL 117 IS 12 BP 1883 EP 1889 DI 10.1289/ehp.0900923 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 528VH UT WOS:000272474600030 PM 20049207 ER PT J AU Pogribny, IP AF Pogribny, Igor P. TI MicroRNA dysregulation during chemical carcinogenesis SO EPIGENOMICS LA English DT Review DE apoptosis; cancer; cell proliferation; chemical carcinogenesis; microRNA ID TUMOR-SUPPRESSOR GENE; INDUCED RAT HEPATOCARCINOGENESIS; TERM TAMOXIFEN EXPOSURE; ALTERED DNA METHYLATION; PRONE B6C3F1 MICE; HUMAN LUNG-CANCER; HEPATOCELLULAR-CARCINOMA; CIGARETTE-SMOKE; DOWN-REGULATION; BREAST-CANCER AB MicroRNAs, potent negative modulators of gene expression, are involved in the regulation of fundamental cellular processes, including cell differentiation, metabolic regulation, signal transduction, cell proliferation and apoptosis. Aberrant levels of miRNAs have been documented in all major human cancers, leading to the suggestion that deregulation of miRNA expression might be significant in tumorigenesis. This review presents the current evidence that demonstrates the involvement of miRNA deregulation in the early stages of lung, liver and breast carcinogenesis induced by chemical carcinogens, suggesting their major role as contributors to the pathogenesis of cancer. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov NR 128 TC 12 Z9 12 U1 0 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-1911 J9 EPIGENOMICS-UK JI Epigenomics PD DEC PY 2009 VL 1 IS 2 BP 281 EP 290 DI 10.2217/EPI.09.17 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 604SN UT WOS:000278298900010 PM 22122703 ER PT J AU Kingsley, DH Calci, K Holliman, S Dancho, B Flick, G AF Kingsley, David H. Calci, Kevin Holliman, Sheila Dancho, Brooke Flick, George TI High Pressure Inactivation of HAV Within Oysters: Comparison of Shucked Oysters with Whole-In-Shell Meats SO FOOD AND ENVIRONMENTAL VIROLOGY LA English DT Article DE HAV; High pressure; Shell oysters ID HEPATITIS-A VIRUS; HIGH HYDROSTATIC-PRESSURE; TEMPERATURE; NOROVIRUS; CALICIVIRUS; PERSISTENCE; ROTAVIRUS AB High pressure inactivation of hepatitis A virus (HAV) within oysters bioaccumulated under simulated natural conditions to levels >10(5) PFU/oyster has been evaluated. Five minute treatments at 20 degrees C were administered at 350, 375, and 400 MegaPascals (MPa). Shucked and whole-in-shell oysters were directly compared to determine if there were any differences in inactivation levels. For whole-in-shell oysters and shucked oysters, average values obtained were 2.56 and 2.96 log(10) inactivation of HAV, respectively, after a 400-MPa treatment. Results indicate that there is no significant inactivation difference (P = 0.05) between inactivation for whole-in-shell oysters as compared to shucked oysters observed for all pressure treatments. This study indicates that commercial high pressure processing applied to whole-in-shell oysters will be capable of inactivating HAV pathogens. C1 [Kingsley, David H.; Dancho, Brooke] Delaware State Univ, USDA, ARS, Microbial Food Safety Res Unit,James WW Baker Ctr, Dover, DE 19901 USA. [Calci, Kevin] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. [Holliman, Sheila; Flick, George] Virginia Polytech Inst & State Univ, Dept Food Sci & Technol, Blacksburg, VA 24061 USA. RP Kingsley, DH (reprint author), Delaware State Univ, USDA, ARS, Microbial Food Safety Res Unit,James WW Baker Ctr, Dover, DE 19901 USA. EM david.kingsley@ars.usda.gov NR 15 TC 9 Z9 10 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1867-0334 J9 FOOD ENVIRON VIROL JI Food Environ. Virol. PD DEC PY 2009 VL 1 IS 3-4 BP 137 EP 140 DI 10.1007/s12560-009-9018-5 PG 4 WC Environmental Sciences; Microbiology; Virology SC Environmental Sciences & Ecology; Microbiology; Virology GA 618JY UT WOS:000279350200004 ER PT J AU Day, JB Nguyen, H Sharma, SK Al-Khaldi, SE Hao, YYD AF Day, J. B. Nguyen, H. Sharma, S. K. Al-Khaldi, S. E. Hao, Y-Y D. TI Effect of dehydrated storage on the survival of Francisella tularensis in infant formula SO FOOD MICROBIOLOGY LA English DT Article DE Francisella tularensis; Infant formula; Survival; Dehydration ID ENTEROBACTER-SAKAZAKII; TULAREMIA; BIOTERRORISM; OUTBREAK; BACTERIA; TURKEY; TIME AB Francisella tularensis is a Gram-negative bacterium that can cause gastrointestinal or oropharyngeal tularemia in humans from ingestion of contaminated food or water. Despite the potential for accidental or intentional contamination of foods with F tularensis, there are few studies on the long-term survivability of this organism in food matrices. Infant formula has previously been implicated as a vehicle for the transmission of a variety of bacteria[ pathogens in infants. In this study, we investigated the survival of F. tularensis in dehydrated infant formula under various storage conditions. F tularensis was stored for up to 12 weeks in dehydrated infant formula in an ambient air, dry or nitrogen atmosphere. Viable counts of fresh F tularensis at 12 weeks in infant formula revealed a 4.15, 3.37 and 3.72-log decrease in ambient air, dry and nitrogen atmosphere, respectively. D-values were calculated (in weeks) as 3.99, 4.68 and 4.47 in air, dry and nitrogen atmosphere, respectively. Published by Elsevier Ltd. C1 [Day, J. B.; Sharma, S. K.; Al-Khaldi, S. E.; Hao, Y-Y D.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Nguyen, H.] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Day, JB (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-712,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM james.day@fda.hhs.gov NR 41 TC 4 Z9 4 U1 0 U2 10 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD DEC PY 2009 VL 26 IS 8 BP 932 EP 935 DI 10.1016/j.fm.2009.06.005 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 520DD UT WOS:000271819300026 PM 19835784 ER PT J AU Teisl, MF Fein, SB Levy, AS AF Teisl, Mario F. Fein, Sara B. Levy, Alan S. TI Information effects on consumer attitudes toward three food technologies: Organic production, biotechnology, and irradiation SO FOOD QUALITY AND PREFERENCE LA English DT Article DE Food safety; Environmental safety; Nutrition; Knowledge ID KNOWLEDGE; EDUCATION; MODELS; PREFERENCES; ACCEPTANCE; CONJOINT; PURCHASE; SCIENCE; DISEASE; DEFICIT AB It is important to understand how information supplied to consumers affects their attitudes about food technologies because these attitudes can impact market behavior. As technologies are actively promoted and cross-promoted, the relation between one's knowledge of, and attitude toward, a technology may well depend on the source of one's information. We examine the relation between knowledge and attitudes toward food technologies and find that greater self-rated knowledge of each technology is associated with positive attitudes about that technology. We also find strong negative cross-informational effects; increased knowledge of one technology leads to more negative attitudes of other technologies. This effect may be due to negative information being provided by opponents of specific technologies. (c) 2009 Elsevier Ltd. All rights reserved. C1 [Teisl, Mario F.] Univ Maine, Sch Econ, Orono, ME 04469 USA. [Fein, Sara B.; Levy, Alan S.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Teisl, MF (reprint author), Univ Maine, Sch Econ, 5782 Winslow Hall, Orono, ME 04469 USA. EM teisl@maine.edu OI teisl, mario/0000-0002-2021-9208 NR 61 TC 16 Z9 16 U1 2 U2 21 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0950-3293 J9 FOOD QUAL PREFER JI Food. Qual. Prefer. PD DEC PY 2009 VL 20 IS 8 SI SI BP 586 EP 596 DI 10.1016/j.foodqual.2009.07.001 PG 11 WC Food Science & Technology SC Food Science & Technology GA 506KR UT WOS:000270774200009 ER PT J AU Badal, A Kyprianou, I Banh, DP Badano, A Sempau, J AF Badal, Andreu Kyprianou, Iacovos Banh, Diem Phuc Badano, Aldo Sempau, Josep TI penMesh-Monte Carlo Radiation Transport Simulation in a Triangle Mesh Geometry SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Computer-aided design; Monte Carlo; NCAT; PENELOPE; penMesh; triangle mesh ID PENELOPE; TOOLKIT; PACKAGE; SPECT; CODE AB We have developed a general-purpose Monte Carlo simulation code, called penMesh, that combines the accuracy of the radiation transport physics subroutines from PENELOPE and the flexibility of a geometry based on triangle meshes. While the geometric models implemented in most general-purpose codes-such as PENELOPE's quadric geometry-impose some limitations in the shape of the objects that can be simulated, triangle meshes can be used to describe any free-form (arbitrary) object. Triangle meshes are extensively used in computer-aided design and computer graphics. We took advantage of the sophisticated tools already developed in these fields, such as an octree structure and an efficient ray-triangle intersection algorithm, to significantly accelerate the triangle mesh ray-tracing. A detailed description of the new simulation code and its ray-tracing algorithm is provided in this paper. Furthermore, we show how it can be readily used in medical imaging applications thanks to the detailed anatomical phantoms already available. In particular, we present a whole body radiography simulation using a triangulated version of the anthropomorphic NCAT phantom. An example simulation of scatter fraction measurements using a standardized abdomen and lumbar spine phantom, and a benchmark of the triangle mesh and quadric geometries in the ray-tracing of a mathematical breast model, are also presented to show some of the capabilities of penMesh. C1 [Badal, Andreu; Sempau, Josep] Univ Politecn Cataluna, Inst Tech Energet, E-08028 Barcelona, Spain. [Badal, Andreu; Kyprianou, Iacovos; Banh, Diem Phuc; Badano, Aldo] US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Silver Spring, MD 20993 USA. [Sempau, Josep] Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Barcelona 08028, Spain. RP Badal, A (reprint author), Univ Politecn Cataluna, Inst Tech Energet, E-08028 Barcelona, Spain. EM andreu.badal-soler@fda.hhs.gov; iacovos.kyprianou@fda.hhs.gov RI Sempau, Josep/J-7834-2013; OI Sempau, Josep/0000-0002-2754-7685; badano, aldo/0000-0003-3712-6670 FU U.S. Food and Drug Administration (FDA) Office of Womens' Health; NIH-NIBIB; U.S. Department of Energy; FDA; Spanish Ministerio de Educacion V Ciencia [FIS2006-07016] FX This work was supported in part by the U.S. Food and Drug Administration (FDA) Office of Womens' Health, in part by the NIH-NIBIB, and in part by an appointment to the Research Participation Program at the Center for Devices and Radiological Health administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the FDA. The work of J. Sempau was supported by the Spanish Ministerio de Educacion V Ciencia under Project FIS2006-07016. NR 33 TC 22 Z9 22 U1 1 U2 10 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD DEC PY 2009 VL 28 IS 12 BP 1894 EP 1901 DI 10.1109/TMI.2009.2021615 PG 8 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 525UO UT WOS:000272242100004 PM 19435677 ER PT J AU Schwartzkopff, F Grimm, TA Lankford, CSR Fields, K Wang, J Brandt, E Clouse, KA AF Schwartzkopff, Franziska Grimm, Tobias A. Lankford, Carla S. R. Fields, Karen Wang, Jiun Brandt, Ernst Clouse, Kathleen A. TI Platelet factor 4 (CXCL4) facilitates human macrophage infection with HIV-1 and potentiates virus replication SO INNATE IMMUNITY LA English DT Article DE CXCL4; cytokines; HIV-1; macrophages; M-CSF ID HUMAN-IMMUNODEFICIENCY-VIRUS; MONOCYTE-DERIVED MACROPHAGES; PLATELET FACTOR-IV; CORECEPTOR USAGE; CHEMOTACTIC PROTEIN-1; BIOLOGICAL PHENOTYPE; TYPE-1 REPLICATION; T-CELLS; IN-VIVO; CHEMOKINES AB Platelet factor 4 (CXCL4), a member of the CXC chemokine subfamily released in high amounts by activated platelets, has been identified as a monocyte survival factor that induces monocyte differentiation into macrophages. Although CXCL4 has been shown to have biological effects unique to chemokines, nothing is known about the role of CXCL4-derived human macrophages or CXCL4 in human immunodeficiency virus (HIV) disease. In this study, CXCL4-derived macrophages are compared with macrophage-colony stimulating factor (M-CSF)-derived macrophages for their ability to support HIV-1 replication. We show that CXCL4-derived macrophages can be infected with macrophage-tropic HIV-1 that uses either CC-chemokine receptor 5 (CCR5) or CXC-chemokine receptor 4 (CXCR4) as a co-receptor for viral entry. We also find that M-CSF and the chemokines, monocyte chemoattractant protein 1 (MCP-1; CCL2) and macrophage-inflammatory-protein-1-alpha (MIP-1 alpha; CCL3) are produced upon R5- and X4-tropic HIV-1 replication in both M-CSF- and CXCL4-derived human macrophages. In addition, CXCL4 added to M-CSF-derived macrophages after virus adsorption and maintained throughout the infection enhances HIV-1 replication. We thus propose a novel role for CXCL4 in HIV disease. C1 [Grimm, Tobias A.; Lankford, Carla S. R.; Fields, Karen; Wang, Jiun; Clouse, Kathleen A.] US FDA, CDER, OBP, DMA, Rockville, MD 20857 USA. [Schwartzkopff, Franziska; Brandt, Ernst] Res Ctr Borstel, Dept Immunol & Cell Biol, Borstel, Germany. RP Clouse, KA (reprint author), US FDA, CDER, OBP, DMA, Bldg 29B Room 3NN16 HFD-123,5600 Fishers Lane, Rockville, MD 20857 USA. EM kathleen.clouse@fda.hhs.gov FU Research Fellowship Program at the Center for Drug Evaluation and Research FX This project was supported, in part, by an appointment to the Research Fellowship Program at the Center for Drug Evaluation and Research administered by the Oak Ridge Associated Universities through a contract with the US Food and Drug Administration. NR 53 TC 10 Z9 10 U1 1 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1753-4259 J9 INNATE IMMUN JI Innate Immun. PD DEC PY 2009 VL 15 IS 6 BP 368 EP 379 DI 10.1177/1753425909106171 PG 12 WC Biochemistry & Molecular Biology; Immunology; Medicine, Research & Experimental; Microbiology SC Biochemistry & Molecular Biology; Immunology; Research & Experimental Medicine; Microbiology GA 530WR UT WOS:000272623500005 PM 19773294 ER PT J AU Cole, SR Chu, HT Nie, L Schisterman, EF AF Cole, Stephen R. Chu, Haitao Nie, Lei Schisterman, Enrique F. TI Estimating the odds ratio when exposure has a limit of detection SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Biomarkers; epidemiologic methods; limit of detection; statistical method ID ANTIRETROVIRAL THERAPY; VIRAL LOAD; REGRESSION; MODELS; INFERENCE; MARKERS; ZERO; MASS AB Methods We calculate the odds of anti-HIV therapy naivete in 45 HIV-infected men as a function of measured log(10) plasma HIV RNA viral load using five approaches including ad hoc methods as well as a maximum likelihood estimate (MLE). We also generated simulations of a binary outcome with 10% incidence and a 1.5-fold increased odds per log increase in a log-normally distributed exposure with 25, 50 and 75% of exposure data below LOD. Simulated data were analysed using the same five methods, as well as the full data. Results In the example, the estimated odds ratio (OR) varied by 1.22-fold across methods, from 1.45 to 1.77 per log(10) copies of viral load and the standard error for the log OR varied by 1.52-fold across methods, from 0.31 to 0.47. In the simulations, use of full data or the MLE was unbiased with appropriate confidence interval (CI) coverage. However, as the proportion of exposure below LOD increased, substituting LOD, LOD/root 2 or LOD/2 was increasingly biased with increasingly inappropriate CI coverage. Finally, exclusion of values below LOD was unbiased but imprecise. Conclusions In this example and the settings explored by simulation, and among methods readily available to investigators (i.e. sans full data), the MLE provided an unbiased and appropriately precise estimate of the exposure-outcome OR. C1 [Cole, Stephen R.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Cole, Stephen R.] Univ N Carolina, Ctr AIDS Res, Chapel Hill, NC USA. [Chu, Haitao] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Chu, Haitao] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Nie, Lei] Fed Drug Adm, DB4 OB OTS CDER, Silver Spring, MD USA. [Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, NIH, Bethesda, MD USA. RP Cole, SR (reprint author), McGavran Greenberg Hall,Campus Box 7435, Chapel Hill, NC 27599 USA. EM cole@unc.edu RI Chu, Haitao /J-7576-2012; OI Chu, Haitao/0000-0003-0932-598X; Schisterman, Enrique/0000-0003-3757-641X FU American Chemical Council; Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH [R03-AI-071763, R01-AA-017594, P30-AI-50410]; National Cancer Institute [CA16086]; American Chemistry Council FX American Chemical Council and the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH grants R03-AI-071763, R01-AA-017594 and P30-AI-50410 (to S. R. C.); Lineberger Cancer Center Core Grant CA16086 from the National Cancer Institute and P30-AI-50410 from the National Institutes of Health (to H. C.); Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health and the American Chemistry Council (to E. F. S.). NR 23 TC 35 Z9 36 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD DEC PY 2009 VL 38 IS 6 BP 1674 EP 1680 DI 10.1093/ije/dyp269 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 528RP UT WOS:000272464700031 PM 19667054 ER PT J AU Tabasi, SH Moolchandani, V Fahmy, R Hoag, SW AF Tabasi, Simin Hassannejad Moolchandani, Vikas Fahmy, Raafat Hoag, Stephen W. TI Sustained release dosage forms dissolution behavior prediction: A study of matrix tablets using NIR spectroscopy SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE NIR spectroscopy; Dissolution prediction; Drug release prediction; Matrix formulation; Multivariate calibration; Chemometrics ID NEAR-INFRARED SPECTROSCOPY; DIFFUSE-REFLECTANCE SPECTROSCOPY; NONDESTRUCTIVE METHOD; DRUG DISSOLUTION; COATING PROCESS; DELIVERY; QUALITY; DESIGN AB The objective of this study was to predict dissolution behavior of sustained release theophylline matrix tablets using near infrared (NIR) diffuse reflectance spectroscopy and multivariate calibration models. Eudragit NE 30D was used as a granulation binder to prepare theophylline sustained release tablets. A total of 117 tablets from 5 batches containing different proportions of Eudragit NE 30D were scanned using a NIR spectrometer. The release characteristics of the tablets were investigated in the acetate buffer for 4 h. The percentage release at 1, 2, 3 and 4 h was used to build the PLS calibration models. The Mahalanobis distance in principal component space and the 2nd derivative transformation were used for sample selection prior to building a four 4-factor partial least square (PLS) calibration models for predicting 1, 2,3 and 4 h release rates. For PLS(1 h), the standard error of calibration (SEC), and standard error of prediction (SEP) were 2.8 and 3.4%. For PLS(2 h), the SEC and SEP were 2.7 and 3.5%. For PLS(3 h), the SEC and SEP were 2.6 and 3.5% and for PLS(4 h), the SEC and SEP were 3.0 and 3.5%, respectively. For the first time, NIR spectroscopy was successfully applied to predict drug release in the matrix tablets by correlating dissolution profile of each batch to its corresponding Eudragit NE 30D variation in tablet composition. (C) 2009 Elsevier B.V. All rights reserved. C1 [Tabasi, Simin Hassannejad; Moolchandani, Vikas; Hoag, Stephen W.] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. [Fahmy, Raafat] FDA, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. [Tabasi, Simin Hassannejad] Perrigo Co, Res & Dev, Allegan, MI 49010 USA. RP Hoag, SW (reprint author), Univ Maryland, Sch Pharm, 20 N Pine St, Baltimore, MD 21201 USA. EM shoag@rx.umaryland.edu NR 14 TC 28 Z9 29 U1 3 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARMACEUT JI Int. J. Pharm. PD DEC 1 PY 2009 VL 382 IS 1-2 BP 1 EP 6 DI 10.1016/j.ijpharm.2009.07.029 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 524PY UT WOS:000272156400001 PM 19660535 ER PT J AU Mora, A Blanco, M Yamamoto, D Dahbi, G Blanco, JE Lopez, C Alonso, MP Vieira, MAM Hernandes, RT Abe, CM Piazza, RMF Lacher, DW Elias, WP Gomes, TAT Blanco, J AF Mora, Azucena Blanco, Miguel Yamamoto, Denise Dahbi, Ghizlane Blanco, Jesus E. Lopez, Cecilia Alonso, Maria P. Vieira, Monica A. M. Hernandes, Rodrigo T. Abe, Cecilia M. Piazza, Roxane M. F. Lacher, David W. Elias, Waldir P. Gomes, Tania A. T. Blanco, Jorge TI HeLa-cell adherence patterns and actin aggregation of enteropathogenic Escherichia coli (EPEC) and Shiga-toxin-producing E. coli (STEC) strains carrying different eae and tir alleles SO INTERNATIONAL MICROBIOLOGY LA English DT Article DE enteropathogenic E. coli; Shiga-toxin-producing E. coli; HeLa-cell adherence; intimin ID BUNDLE-FORMING PILUS; INTIMIN TYPES; VIRULENCE FACTORS; LOCALIZED ADHERENCE; O-SEROGROUPS; BFPA GENES; SEROTYPES; IDENTIFICATION; DIARRHEA; CATTLE AB A collection of 69 eae-positive strains expressing 29 different intimin types and eight fir alleles was characterized with respect to their adherence patterns to HeLa cells, ability to promote actin accumulation in vitro, the presence of bfpA alleles in positive strains, and bundle-forming pilus (BFP) expression. All of the nine typical enteropathogenic Escherichia coli (tEPEC) studied harbored the enteropathogenic E. coli adherence factor (EAF) plasmid, as shown by PCR and/or EAF probe results. In addition, they were positive for bfpA, as shown by PCR, and BFP expression, as confirmed by immunofluorescence (IFL) and/or immunoblotting (IBL) assays. Localized adherence (LA) was exclusively displayed by those nine tEPEC, while localized-adherence-like (LAL) was the most frequent pattern among atypical EPEC (aEPEC) and Shiga-toxin-producing E. coli (STEC). All LA and LAL strains were able to cause attaching and effacing (AE) lesions, as established by means of the FAS test. There was a significant association between the presence of tir allele alpha 1 and bfpA-positive strains, and consequently, with the LA pattern. However, intimin type or bfpA was not associated with the adherence pattern displayed in HeLa cells. Among the eight bfpA alleles detected, a new type (beta 10; accession number FN391178) was identified in a strain of serotype O157:H45, and a truncated variant (beta 3.2-t; accession number FN 39118 1) in four strains belonging to different pathotypes. [Int Microbiol 2009; 12(4):243-251] C1 [Mora, Azucena; Blanco, Miguel; Dahbi, Ghizlane; Blanco, Jesus E.; Lopez, Cecilia; Blanco, Jorge] Univ Santiago de Compostela, Fac Vet Sci, Dept Microbiol & Parasitol, Lugo 27002, Spain. [Yamamoto, Denise; Vieira, Monica A. M.; Hernandes, Rodrigo T.; Gomes, Tania A. T.] Univ Fed Sao Paulo, Sao Paulo Sch Med, Dept Microbiol Immunol & Parasitol, Sao Paulo, Brazil. [Abe, Cecilia M.; Piazza, Roxane M. F.; Elias, Waldir P.] Butantan Inst, Bacteriol Lab, Sao Paulo, Brazil. [Alonso, Maria P.] Calde Xeral Hosp, Microbiol Unit, Lugo, Spain. [Lacher, David W.] US FDA, Div Mol Biol, Ctr Food Safety & Appl Nutr, Laurel, MD USA. RP Blanco, J (reprint author), Univ Santiago de Compostela, Fac Vet, Dept Microbiol & Parasitol, Lugo 27002, Spain. EM jorge.blanco@usc.es RI Tavanelli Hernandes, Rodrigo/H-2728-2012; Elias, Waldir/B-9890-2013; Blanco, Jorge/C-7161-2013; Abe, Cecilia/F-1518-2013; Gomes, Tania/H-3950-2012; Mora Gutierrez, Azucena/F-4612-2016; Piazza, Roxane Maria/K-9807-2016; OI Abe, Cecilia/0000-0003-0218-9372; Gomes, Tania/0000-0002-4525-8705; Mora Gutierrez, Azucena/0000-0002-0785-5795; BLANCO, JESUS EULOGIO/0000-0002-5071-4760; Elias, Waldir/0000-0003-3470-5706; Blanco, Jorge/0000-0003-0264-4136 FU European Commission [FAIR6-CT-4093, FOOD-CT-2006-36256]; Ministerio de Sanidad y Consumo de Espana [FIS G03-025-COLIRED-O157, PI052023, PI051481, REIPI RD06/0008/1018-1016]; Ministerio de Educacion y Ciencia de Espana [AGL-2008-02129]; Xunta de Galicia [PGIDIT 05BTF26101P, PGIDIT065TAL26101P, 07MRU036261PR, 08TAL0172 61PR, 2007/000044-0]; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [08/53812-4] FX We thank Monserrat Lamela for skilful technical assistance. This work was supported by grants from the European Commission (FAIR6-CT-4093; PEN project FOOD-CT-2006-36256), the Fondo de Investigacion Sanitaria from the Ministerio de Sanidad y Consumo de Espana (grants FIS G03-025-COLIRED-O157, PI052023, PI051481 and REIPI RD06/0008/1018-1016), the Ministerio de Educacion y Ciencia de Espana (AGL-2008-02129), Xunta de Galicia (grants PGIDIT 05BTF26101P, PGIDIT065TAL26101P, 07MRU036261PR, 08TAL0172 61PR, 2007/000044-0), and Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (grant 08/53812-4 to TATG). A. Mora acknowledges Ramon y Cajal program from the Ministerio de Educacion y Ciencia de Espana and R.M.F. Piazza acknowledges Fundacion Carolina. NR 52 TC 21 Z9 22 U1 1 U2 8 PU VIGUERA EDITORES, S L PI BARCELONA PA PLAZA TETUAN, 7, BARCELONA, E-08010, SPAIN SN 1139-6709 EI 1618-1905 J9 INT MICROBIOL JI Int. Microbiol. PD DEC PY 2009 VL 12 IS 4 BP 243 EP 251 DI 10.2436/20.1501.01.104 PG 9 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 548ZW UT WOS:000274010800006 PM 20112229 ER PT J AU Jeske, DR Xu, HK Blessinger, T Jensen, P Trumble, J AF Jeske, Daniel R. Xu, Huaying Karen Blessinger, Todd Jensen, Peter Trumble, John TI Testing for the Equality of EC50 Values in the Presence of Unequal Slopes With Application to Toxicity of Selenium Types SO JOURNAL OF AGRICULTURAL BIOLOGICAL AND ENVIRONMENTAL STATISTICS LA English DT Article DE Equality of EC50 values; Natural response parameter; Probit regression AB The likelihood ratio test (LRT) for the equality of EC50 values using a probit model that has parallel slopes is implemented in a variety of software packages. A preliminary LRT can be used to ascertain the plausibility of parallel slopes. Testing for equal EC50 values is not as straightforward if the preliminary test rejects that the slopes are equal or, equivalently, if a practitioner would rather not deal with the implications on the size of the test in the presence of the preliminary test. An LRT for testing equal EC50 values is not available in software packages for the case of arbitrary slopes. In this article, we describe a simple and effective algorithm for implementing the LRT procedure in this case. We also derive a quadratic form test procedure for the same hypothesis and compare the two tests (size and power) in the context of our application that deals with comparing the toxicity of four different types of selenium. The R-code is available as supplemental material online. C1 [Jeske, Daniel R.; Xu, Huaying Karen] Univ Calif Riverside, Dept Stat, Riverside, CA 92521 USA. [Blessinger, Todd] Fed Drug Adm, Rockville, MD 20855 USA. [Jensen, Peter] Univ Maryland, Dept Entomol, College Pk, MD 20742 USA. RP Jeske, DR (reprint author), Univ Calif Riverside, Dept Stat, Riverside, CA 92521 USA. EM daniel.jeske@ucr.edu; karen.xu@ucr.edu; todd.blessinger@fda.hhs.gov; pjensen@umd.edu; john.trumble@ucr.edu NR 13 TC 3 Z9 3 U1 1 U2 6 PU AMER STATISTICAL ASSOC & INT BIOMETRIC SOC PI WASHINGTON PA 1444 I ST NW, STE 700, WASHINGTON, DC 20005 USA SN 1085-7117 J9 J AGR BIOL ENVIR ST JI J. Agric. Biol. Environ. Stat. PD DEC PY 2009 VL 14 IS 4 BP 469 EP 483 DI 10.1198/jabes.2009.07088 PG 15 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 531AF UT WOS:000272634200007 ER PT J AU Ezzeldin, HH Acosta, EP Mattison, LK Fourie, J Modak, A Diasio, RB AF Ezzeldin, Hany H. Acosta, Edward P. Mattison, Lori K. Fourie, Jeanne Modak, Anil Diasio, Robert B. TI C-13-5-FU breath test current status and future directions: a comprehensive review SO JOURNAL OF BREATH RESEARCH LA English DT Review ID DIHYDROPYRIMIDINE DEHYDROGENASE-DEFICIENCY; SEVERE 5-FLUOROURACIL TOXICITY; ALTERED URACIL CATABOLISM; BETA-UREIDOPROPIONASE; ADJUVANT CHEMOTHERAPY; GENETIC-REGULATION; AFRICAN-AMERICANS; CANCER-PATIENTS; DPD DEFICIENCY; COLON-CANCER AB Breath tests (BTs) represent a safe non-invasive alternative strategy that could provide valuable diagnostic information in conditions like fat malabsorption, carbohydrate ( lactose and fructose) malabsorption, liver dysfunction, impaired gastric emptying, abnormal small bowel transit time, small intestinal bacterial overgrowth and Helicobacter pylori infection. To date, despite the availability of a number of breath tests, only three have gained approval by the FDA for application in a clinical setting (C-13-urea breath test for the detection of H. pylori; NO breath test for monitoring asthma and alkane breath test for heart transplant rejection). Unfortunately, none of these tests investigate cancer patients or response to cancer chemotherapy. Several years ago it was realized that the presence of a reliable non-invasive approach could assist in the detection of patients at risk of developing severe life-threatening toxicities prior to the administration of fluoropyrimidines ( e. g. 5-FU) or related cancer chemotherapy. 5-FU toxicity results mainly from deficient uracil catabolism. This review discusses the development of a BT that utilizes an orally administered pyrimidine ([2-C-13]-uracil) which is metabolized via the same catabolic pathway as 5-FU. This ([2-C-13]-uracil) breath test could provide a valuable addition to the patients' standard of care. C1 [Ezzeldin, Hany H.; Diasio, Robert B.] Mayo Clin, Rochester, MN 55905 USA. [Acosta, Edward P.] Univ Alabama, Birmingham, AL 35294 USA. [Mattison, Lori K.] US Patent & Trademark Off, Alexandria, VA 22313 USA. [Fourie, Jeanne] US FDA, Silver Spring, MD 20993 USA. [Modak, Anil] Cambridge Isotope Labs Inc, Andover, MA 01810 USA. RP Ezzeldin, HH (reprint author), Mayo Clin, Rochester, MN 55905 USA. EM Diasio.robert@mayo.edu NR 39 TC 8 Z9 8 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1752-7155 J9 J BREATH RES JI J. Breath Res. PD DEC PY 2009 VL 3 IS 4 AR 047002 DI 10.1088/1752-7155/3/4/047002 PG 12 WC Biochemical Research Methods; Respiratory System SC Biochemistry & Molecular Biology; Respiratory System GA 666OY UT WOS:000283126600007 PM 21386199 ER PT J AU Scherr, D Sharma, K Dalal, D Spragg, D Chilukuri, K Cheng, A Dong, J Henrikson, CA Nazarian, S Berger, RD Calkins, H Marine, JE AF Scherr, Daniel Sharma, Kavita Dalal, Darshan Spragg, David Chilukuri, Karuna Cheng, Alan Dong, Jun Henrikson, Charles A. Nazarian, Saman Berger, Ronald D. Calkins, Hugh Marine, Joseph E. TI Incidence and Predictors of Periprocedural Cerebrovascular Accident in Patients Undergoing Catheter Ablation of Atrial Fibrillation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE ablation; atrial fibrillation; complication; embolism; cerebrovascular accident; warfarin ID PULMONARY VEIN ISOLATION; LONG-TERM; INTRACARDIAC ECHOCARDIOGRAPHY; RADIOFREQUENCY ABLATION; ANTICOAGULATION; RISK; EFFICACY; SAFETY; STROKE; RECOMMENDATIONS AB Background: Cerebrovascular accident (CVA) is a serious complication of catheter ablation of atrial fibrillation (AF). The incidence and clinical predictors of periprocedural CVA in patients undergoing AF ablation are not fully understood. Methods: This study included 721 cases (age 57 +/- 11 years; 23% female; 345 persistent AF) in 579 consecutive patients referred for AF ablation. Periprocedural CVA was defined as onset of a new neurologic deficit that occurred anytime between the start of the procedure and 30 days after the AF ablation, and was confirmed by a neurologist. Cranial imaging with CT and/or MRI was performed in each case. Patients were anticoagulated with warfarin for at least 4 weeks pre- and immediately postprocedure and were bridged with enoxaparin. Transesophageal echocardiography was performed within 24 hours prior to ablation in all cases. Results: Periprocedural CVA occurred in 10 of 721 cases (1.4%). The risk of periprocedural CVA did not vary significantly during the course of the study. Among these 10 patients (age 62 +/- 11 years; 1 female; 5 persistent AF), 6 manifested neurological deficits within 24 hours, 3 after 24-48 hours, and 1 patient had a CVA 6 days following AF ablation despite a therapeutic INR level. All CVAs were ischemic. Five patients had residual deficits after 30 days. Four of 43 patients (9.3%) with a prior history of CVA had periprocedural CVA. Periprocedural CVA occurred in 0.3%, 1.0%, and 4.7% of patients with CHADS(2) scores of 0, 1, and >= 2 (P < 0.001). In 2 separate multivariate analyses, a CHADS(2) score >= 2 (OR 7.1, P = 0.02) and history of CVA (OR 9.5, P < 0.01) remained independent predictors of periprocedural CVA. Conclusions: Despite periprocedural anticoagulation and transesophageal echocardiography, we found a 1.4% incidence of periprocedural CVA in AF ablation patients. A CHADS(2) score >= 2 and a history of CVA are independent predictors of CVA after AF ablation. The CVA risk is low in patients with CHADS(2) score of 0. (J Cardiovasc Electrophysiol, Vol. 20, pp. 1357-1363, December 2009). C1 [Scherr, Daniel; Sharma, Kavita; Dalal, Darshan; Spragg, David; Chilukuri, Karuna; Cheng, Alan; Dong, Jun; Henrikson, Charles A.; Nazarian, Saman; Berger, Ronald D.; Calkins, Hugh; Marine, Joseph E.] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Scherr, Daniel] Med Univ Graz, Dept Med, Div Cardiol, Graz, Austria. [Dong, Jun] US FDA, Ctr Devices & Radiol Hlth, Div Cardiovasc Devices, Rockville, MD 20857 USA. RP Marine, JE (reprint author), Johns Hopkins Med Inst, 4940 Eastern Ave,A-1 E, Baltimore, MD 21224 USA. EM jmarine2@jhmi.edu FU Erwin Schroedinger Research Grant [J2559]; FWF Austrian Science Fund; Norbert and Louise Grunwald Cardiac Arrhythmia Research Fund FX Dr. Scherrwas supported by the Erwin Schroedinger Research Grant (J2559) of the FWF Austrian Science Fund. Dr. Chilukuri is supported by the Norbert and Louise Grunwald Cardiac Arrhythmia Research Fund. NR 31 TC 64 Z9 66 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD DEC PY 2009 VL 20 IS 12 BP 1357 EP 1363 DI 10.1111/j.1540-8167.2009.01540.x PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 524FQ UT WOS:000272129600009 PM 19572951 ER PT J AU O'Callaghan, KM AF O'Callaghan, Kathryn M. TI Solutions for Disparities for Women with Heart Disease SO JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH LA English DT Article DE Cardiovascular Disease; Sex Differences; Gender Disparities; Estrogen; Sex Hormones; Biomarkers; FDA ID ARTERY-BYPASS-SURGERY; PERCUTANEOUS CORONARY INTERVENTION; SYNDROME EVALUATION WISE; GENDER-BASED OUTCOMES; CARDIOVASCULAR-DISEASE; SEX-DIFFERENCES; MYOCARDIAL-INFARCTION; DIABETES-MELLITUS; TASK-FORCE; RISK AB Cardiovascular disease (CVD) mortality and morbidity is a major burden on the US and global population. Observed differences in prevalence, incidence, outcomes, and risk factors suggest a possible sex difference in etiology and pathophysiology of CVD. Disparate rates of referral and diagnosis may be attributable to differences in symptoms, presentation, and diagnostic accuracy. Many common procedural, pharmaceutical, and medical device therapies have been associated with worse outcomes in women compared to men. Awareness campaigns and efforts to improve female inclusion in clinical trials are contributing to improvements in CVD healthcare delivery for women, but much remains unknown about the biological basis for the differences described above, such as the role of estrogen, life-cycle changes (puberty, menstrual cycle, pregnancy, menopause), and possible chromosomal or genetic mechanisms. This is where translational research is uniquely poised to make immense contributions to resolving disparities in the quality of care and outcomes for women with CVD. C1 US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP O'Callaghan, KM (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 66,Rm 1546, Silver Spring, MD 20993 USA. EM kathryn.ocallaghan@fda.hhs.gov NR 59 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1937-5387 J9 J CARDIOVASC TRANSL JI J. Cardiovasc. Transl. Res. PD DEC PY 2009 VL 2 IS 4 SI SI BP 518 EP 525 DI 10.1007/s12265-009-9125-6 PG 8 WC Cardiac & Cardiovascular Systems; Medicine, Research & Experimental SC Cardiovascular System & Cardiology; Research & Experimental Medicine GA 686IW UT WOS:000284691000020 PM 20560011 ER PT J AU Brandt, M Moss, J Ferguson, M AF Brandt, Mary Moss, Julie Ferguson, Martine TI The 2006-2007 Food Label and Package Survey (FLAPS): Nutrition labeling, trans fat labeling SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS LA English DT Article; Proceedings Paper CT 32nd National Nutrient Database Conference CY MAY 14-14, 2008 CL Ottawa, CANADA DE Nutrition labeling; Trans fat; Food Label and Package Survey; Nutrition labeling databases; Food data management; Data compilation; Food composition ID CLAIMS AB Since the 1970s, the Center for Food Safety and Applied Nutrition at the United States (US) Food and Drug Administration (FDA) has studied product labels from the US food supply through the Food Label and Package Survey (FLAPS). The sampling frame for the latest survey, FLAPS 2006-2007, was the ACNielsen Strategic Planner food sales database. As the newest addition to the Nutrition Facts label, this latest FLAPS included trans fat and was utilized to characterize the prevalence of foods reporting trans fat information. For this Survey, FDA used a new probability-based sample design to draw a list of food products. Products were purchased from retail stores across the US, and label information was recorded to create the FLAPS 2006-2007 database. Results of initial data analyses show that an estimated 96.3% of FDA-regulated processed, packaged foods have nutrition labeling, with an additional 3.7% exempt from mandatory nutrition labeling requirements. FLAPS data show that 12% of products provide a nutrient content claim about the amount of trans fat on the principal display panel, with over 75% displaying "0 g trans fat." FDA will continue to analyze FLAPS data as a tracking mechanism to monitor the market response to food label regulations and to support policy, regulatory, economic, and food safety decisions. Published by Elsevier Inc. C1 [Brandt, Mary; Moss, Julie; Ferguson, Martine] US FDA, Off Nutr Labeling & Dietary Supplements HFS 830, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Brandt, M (reprint author), US FDA, Off Nutr Labeling & Dietary Supplements HFS 830, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM mary.brandt@fda.hhs.gov NR 5 TC 14 Z9 14 U1 1 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1575 J9 J FOOD COMPOS ANAL JI J. Food Compos. Anal. PD DEC PY 2009 VL 22 BP S74 EP S77 DI 10.1016/j.jfca.2009.01.004 PG 4 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 540ZB UT WOS:000273379000014 ER PT J AU McCabe-Sellers, BJ Chenard, CA Lovera, D Champagne, CM Bogle, ML Kaput, J AF McCabe-Sellers, Beverly J. Chenard, Catherine Ann Lovera, Dalia Champagne, Catherine M. Bogle, Margaret L. Kaput, Jim TI Readiness of food composition databases and food component analysis systems for nutrigenomics SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS LA English DT Article; Proceedings Paper CT 32nd National Nutrient Database Conference CY MAY 14-14, 2008 CL Ottawa, CANADA DE Nutrigenomics; Dietetics; Nutrition assessment; Nutrition surveys; Food composition; Food composition databases; Diet ID NUTRITIONAL GENOMICS; NUTRIENT DATABASE; HEALTH; ENDB; DIET; EPIDEMIOLOGY; PREVENTION; MEDICINE; PROJECT; CANCER AB The two-fold purpose of this paper is to examine the adequacy of food composition databases and dietary assessment techniques to meet the needs of nutritional genomic research and to explore the challenges and opportunities presented by the emerging field of nutrigenomics to future development of food composition databases and food composition analysis systems. A review Of published literature and the Internet for organizations and their ongoing dialogues were used to explore how current food composition databases and nutritional assessment methodology could be made more useful in nutrigenomics research. An outline of current projects and potential approaches to develop more reliable and cost-effective methods for the study of nutrigenomics in diverse populations is presented. Many issues related to these dietary and database methodologies need to be addressed and overcome if nutrigenomics is to reach its potential for promoting optimal health through better individualization of diet and physical activity recommendations. To meet the complex research and clinical challenges of individualizing nutrition and health care, a network of diverse health care professionals and scientists is needed to move the world toward optimal health practices. (C) 2009 Published by Elsevier Inc. C1 [McCabe-Sellers, Beverly J.; Lovera, Dalia; Bogle, Margaret L.] ARS, USDA, Delta Obes Prevent Res Unit, Little Rock, AR 72211 USA. [Chenard, Catherine Ann] Univ Iowa, Inst Clin & Translat Sci, Iowa City, IA 52242 USA. [Champagne, Catherine M.] Pennington Biol Res Ctr, Baton Rouge, LA 70808 USA. [Kaput, Jim] US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. RP McCabe-Sellers, BJ (reprint author), ARS, USDA, Delta Obes Prevent Res Unit, 900 S Shackleford Rd,Suite 509, Little Rock, AR 72211 USA. EM bev.mccabe-sellers@ars.usda.gov NR 70 TC 5 Z9 6 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1575 J9 J FOOD COMPOS ANAL JI J. Food Compos. Anal. PD DEC PY 2009 VL 22 BP S57 EP S62 DI 10.1016/j.jfca.2009.02.004 PG 6 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 540ZB UT WOS:000273379000011 ER PT J AU Shimakawa, T Weingaertner, DW Schmit, DM Brandt, MM AF Shimakawa, Tomoko Weingaertner, David W. Schmit, Diane M. Brandt, Mary M. TI Development of downloadable and printable posters for nutrition information of raw fruits, vegetables, and fish SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS LA English DT Article; Proceedings Paper CT 32nd National Nutrient Database Conference CY MAY 14-14, 2008 CL Ottawa, CANADA DE US Food and Drug Administration; Food data; Information dissemination; Nutrition education; Nutrition labeling; Fruits; Vegetables; Fish; Food composition AB In the United States, nutrition labeling for raw fruits, vegetables, and fish is currently voluntary. In order to encourage retail stores that sell these foods to participate in the voluntary nutrition labeling program and to be compliant with the guidelines, the United States Food and Drug Administration (FDA) has developed downloadable and printable posters containing nutrition information for the 20 most frequently consumed raw fruits, vegetables, and fish in the United States. The FDA has made the posters available on its website (http://www.cfsan.fda.gov/nutinfo.html), and has urged retail stores to download and print the posters and to display them in their stores for consumers to use in making purchase decisions. In developing these posters, FDA followed the agency's guidelines for voluntary nutrition labeling. The names and nutrition labeling values for the raw fruits, vegetables and fish are based on the updated nutrition labeling regulation published in the Federal Register oil August 17, 2006, which corrected the July 25, 2006 final rule. FDA issued a Constituent Update (electronic newsletter) and contacted trade associations representing retail food stores to inform them about the posters. Published by Elsevier Inc. C1 [Shimakawa, Tomoko; Brandt, Mary M.] US FDA, Off Nutr Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Weingaertner, David W.] US FDA, Off Commissioner, Rockville, MD 20857 USA. [Schmit, Diane M.] Comp Technol Serv Inc, Rockville, MD USA. RP Shimakawa, T (reprint author), US FDA, Off Nutr Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 830, College Pk, MD 20740 USA. EM Tomoko.Shimakawa@fda.hhs.gov NR 22 TC 1 Z9 1 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1575 J9 J FOOD COMPOS ANAL JI J. Food Compos. Anal. PD DEC PY 2009 VL 22 BP S93 EP S98 DI 10.1016/j.jfca.2009.02.002 PG 6 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 540ZB UT WOS:000273379000018 ER PT J AU Trumbo, P Shimakawa, T AF Trumbo, Paula Shimakawa, Tomoko TI US Food and Drug Administration on modernization of the Nutrition and Supplements Facts labels SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS LA English DT Article; Proceedings Paper CT 32nd National Nutrient Database Conference CY MAY 14-14, 2008 CL Ottawa, CANADA DE Daily Value; Nutrition Facts label; Supplements Facts label; Food labeling; United States food legislation; Food data management; Food composition AB The U.S. Food and Drug Administration (FDA) issued an Advance Notice of Proposed Rulemaking (ANPRM) for obtaining public comments on modernizing the Nutrition and Supplements Facts label. Public comments to specific questions asked in the ANPRM will be considered by FDA for future rulemaking. There are numerous issues that FDA will consider during the rulemaking process, such as determining (I) which Dietary Reference Intakes (DRIs) to use for setting the Daily Values (DVs), (2) the approach for setting a single nutrient DV for adults and children over the age of 4 years, (3) which vitamins and minerals are of public health concern in the United States and therefore required to be declared in the Nutrition Facts label, (4) the definition of certain nutrients, such as total carbohydrate and fiber, (5) the labeling of trans fat, and (6) the use of International Units (IUs) for providing the amount of a vitamin. After reviewing the public comments, as well as any other new relevant information, FDA will publish a proposed rule in the Federal Register that provides the agency's proposed decisions for modernizing the Nutrition and Supplements Facts label. Publication of a final rule, along with the Code of Federal Regulations, will set forth the new regulatory requirements for the Nutrition and Supplements Facts labels. Published by Elsevier Inc. C1 [Trumbo, Paula; Shimakawa, Tomoko] US FDA, College Pk, MD 20740 USA. RP Trumbo, P (reprint author), US FDA, 5100 Paint Branch Pkwy,HFS 830, College Pk, MD 20740 USA. EM Paula.Trumbo@FDA.HHS.gov NR 23 TC 0 Z9 0 U1 2 U2 10 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 2009 VL 22 BP S13 EP S18 DI 10.1016/j.jfca.2009.01.002 PG 6 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 540ZB UT WOS:000273379000003 ER PT J AU Chen, HZ Xu, HY Heinze, TM Cerniglia, CE AF Chen, Huizhong Xu, Haiyan Heinze, Thomas M. Cerniglia, Carl E. TI Decolorization of water and oil-soluble azo dyes by Lactobacillus acidophilus and Lactobacillus fermentum SO JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY LA English DT Article DE Azo dyes; Sudan dyes; Lactobacillus species; Aromatic amines; Biodegradation ID HUMAN INTESTINAL MICROFLORA; OXIDATIVE DNA-DAMAGE; SUDAN-I; LIQUID-CHROMATOGRAPHY; ORTHO-TOLUIDINE; CARCINOGENICITY; REDUCTION; ACID; FAT; AZOREDUCTASE AB The capability of Lactobacillus acidophilus and Lactobacillus fermentum to degrade azo dyes was investigated. The bacteria were incubated under anaerobic conditions in the presence of 6 A mu g/ml Methyl Red, Ponceau BS, Orange G, Amaranth, Orange II, and Direct Blue 15; 5 A mu g/ml Sudan I and II; or 1.5 A mu g/ml Sudan III and IV in deMann-Rogosa-Sharpe broth at 37A degrees C for 36 h, and reduction of the dyes was monitored. Both bacteria were capable of degrading all of the water-soluble azo dyes to some extent. They were also able to completely reduce the oil-soluble diazo dyes Sudan III and IV but were unable to reduce the oil-soluble monoazo dyes Sudan I and II to any significant degree in the concentrations studied. Growth of the bacteria was not significantly affected by the presence of the Sudan azo dyes. Metabolites of the bacterial degradation of Sudan III and IV were isolated and identified by liquid chromatography electrospray ionization tandem mass spectrometry analyses and compared with authentic standards. Aniline and o-toluidine (2-methylaniline), both potentially carcinogenic aromatic amines, were metabolites of Sudan III and IV, respectively. C1 [Chen, Huizhong; Xu, Haiyan; Cerniglia, Carl E.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Heinze, Thomas M.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Chen, HZ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM huizhong.chen@fda.hhs.gov FU Office of Women's Health; National Center for Toxicological Research; US Food and Drug Administration; Oak Ridge Institute for Science and Education FX We thank Drs. Robin L. Stingley, Bruce D. Erickson, and Jinhui Feng for their critical review of the manuscript. This study was funded by the Office of Women's Health and the National Center for Toxicological Research, US Food and Drug Administration, and supported in part by an appointment (HX) to the Postgraduate Research Fellowship Program by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the US Food and Drug Administration. The views presented in this article do not necessarily reflect those of the Food and Drug Administration. NR 35 TC 20 Z9 21 U1 1 U2 16 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 2009 VL 36 IS 12 BP 1459 EP 1466 DI 10.1007/s10295-009-0633-9 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 518ZO UT WOS:000271735000004 PM 19727875 ER PT J AU Woodcock, SA Jones, RC Edmondson, RD Malliri, A AF Woodcock, Simon A. Jones, Richard C. Edmondson, Ricky D. Malliri, Angeliki TI A Modified Tandem Affinity Purification Technique Identifies That 14-3-3 Proteins Interact with Tiam1, an Interaction Which Controls Tiam1 Stability SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE Tiam1; 14-3-3; Rac; stability; phosphorylation; TAP; cross-linking ID EXCHANGE FACTOR TIAM1; RAC ACTIVATOR TIAM1; 14-3-3-PROTEINS; INVASION; REQUIRES AB The Rac-specific GEF (guanine-nucleotide exchange factor) Tiam1 has important functions in multiple cellular processes including proliferation, apoptosis and adherens junction maintenance. Here we describe a modified tandem affinity purification (TAP) technique that we have applied to specifically enrich Tiam1-containing protein complexes from mammalian cells. Using this technique in conjunction with LC-MS/MS mass spectrometry, we have identified additional Tiam1-interacting proteins not seen with the standard technique, and have identified multiple 14-3-3 family members as Tiam1 interactors. We confirm the Tiam1/14-3-3 protein interaction by GST-pulldown and coimmunoprecipitation experiments, show that it is phosphorylation-dependent, and that they colocalize in cells. The interaction is largely dependent on the N-terminal region of Tiam1; within this region, there are four putative phospho-serine-containing 14-3-3 binding motifs, and we confirm that two of them (Ser172 and Ser231) are phosphorylated in cells using mass spectrometry. Moreover, we show that phosphorylation at three of these motifs (containing Ser60, Ser172 and Ser231) is required for the binding of 14-3-3 proteins to this region of Tiam1. We show that phosphorylation of these sites does not affect Tiam1 activity; significantly however, we demonstrate that phosphorylation of the Ser60-containing motif is required for the degradation of Tiam1. Thus, we have established and proven methodology that allows the identification of additional protein-protein interactions in mammalian cells, resulting in the discovery of a novel mechanism of regulating Tiam1 stability. C1 [Woodcock, Simon A.; Malliri, Angeliki] Univ Manchester, Cell Signalling Grp, Canc Res UK Paterson Inst Canc Res, Manchester M20 4BX, Lancs, England. [Jones, Richard C.; Edmondson, Ricky D.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Woodcock, SA (reprint author), Univ Manchester, Cell Signalling Grp, Canc Res UK Paterson Inst Canc Res, Manchester M20 4BX, Lancs, England. EM swoodcock@picr.man.ac.uk; amalliri@picr.man.ac.uk FU Cancer Research UK [C147/A6058] FX We thank J. G. Collard, F. Barr, and H. Clevers for reagents, members of the Cell Signalling Group for helpful discussions, A. Gambus and K. Labib for advice on the TAP strategies, and Y. Connolly and D. Smith for critical reading of the manuscript and very helpful discussions, advice and assistance in setting Lip the modified TAP strategy, and mass spectrometry work at the PICR. We are also grateful to Steve Bagley for his help with microscopy. This work was supported by Cancer Research UK [CR-UK] grant number C147/A6058 to A.M. NR 21 TC 18 Z9 19 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD DEC PY 2009 VL 8 IS 12 BP 5629 EP 5641 DI 10.1021/pr900716e PG 13 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 527AV UT WOS:000272339100022 PM 19899799 ER PT J AU Wu, ZY Lin, ZC Mackill, P Wei, C Noonan, J Cherniack, J Gillis-Landrum, D AF Wu, Zhongyu Lin, Zhichao Mackill, Pamela Wei, Cong Noonan, John Cherniack, James Gillis-Landrum, Deborah TI Evaluation of food emergency response laboratories' capability for Po-210 analysis using proficiency test material with verifiable traceability SO JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY LA English DT Article; Proceedings Paper CT 8th International Conference on Methods and Applications of Radioanalytical Chemistry CY APR 05-10, 2009 CL Kona, HI SP Amer Nucl Soc DE Po-210; Proficiency test; Food Emergency Response Network; Traceability ID PERFORMANCE EVALUATION; NETWORK AB Measurement capability and data comparability are essential for emergency response when analytical data from cooperative laboratories are used for risk assessment and post incident decision making. In this study, the current capability of food emergency response laboratories for the analysis of Po-210 in water was evaluated using a proficiency test scheme in compliance with ISO-43 and ILAC G13 guidelines, which comprises a test sample preparation and verification protocol and an insightful statistical data evaluation. The results of performance evaluations on relative bias, value trueness, precision, false positive detection, minimum detection limit, and limit of quantification, are presented. C1 [Wu, Zhongyu; Lin, Zhichao; Mackill, Pamela; Wei, Cong; Noonan, John; Cherniack, James; Gillis-Landrum, Deborah] US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. RP Wu, ZY (reprint author), US FDA, Winchester Engn & Analyt Ctr, 109 Holton St, Winchester, MA 01890 USA. EM zhongyu.wu@fda.hhs.gov NR 16 TC 1 Z9 2 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0236-5731 J9 J RADIOANAL NUCL CH JI J. Radioanal. Nucl. Chem. PD DEC PY 2009 VL 282 IS 3 BP 971 EP 977 DI 10.1007/s10967-009-0286-1 PG 7 WC Chemistry, Analytical; Chemistry, Inorganic & Nuclear; Nuclear Science & Technology SC Chemistry; Nuclear Science & Technology GA 526PK UT WOS:000272303100054 ER PT J AU Wear, KA AF Wear, Keith A. TI Frequency dependence of average phase shift from human calcaneus in vitro SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article DE bioacoustics; biomechanics; bone; ultrasonic dispersion ID BOVINE CANCELLOUS BONE; ULTRASONIC WAVE-PROPAGATION; HUMAN TRABECULAR BONE; QUANTITATIVE ULTRASOUND; VELOCITY DISPERSION; NEGATIVE DISPERSION; STRATIFIED MODEL; MECHANICAL-PROPERTIES; ACOUSTIC-WAVES; BIOTS THEORY AB If dispersion in a medium is weak and approximately linear with frequency (over the experimental band of frequencies), then it can be shown that the constant term in a polynomial representation of phase shift as a function of frequency can produce errors in measurements of phase-velocity differences in through-transmission, substitution experiments. A method for suppressing the effects of the constant phase shift in the context of the single-wave-model was tested on measurements from 30 cancellous human calcaneus samples in vitro. Without adjustment for constant phase shifts, the estimated phase velocity at 500 kHz was 1516 +/- 6 m/s (mean +/- standard error), and the estimated dispersion was -24 +/- 4 m/s MHz (mean +/- standard error). With adjustment for constant phase shifts, the estimated mean velocity decreased by 4-9 m/s, and the estimated magnitude of mean dispersion decreased by 50%-100%. The average correlation coefficient between the measured attenuation coefficient and frequency was 0.997 +/- 0.0026 (mean +/- standard deviation), suggesting that the signal for each sample was dominated by one wave. A single-wave, linearly dispersive model conformed to measured complex transfer functions from the 30 cancellous-bone samples with an average root-mean-square error of 1.9%+/- 1.0%. C1 US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM keith.wear@fda.hhs.gov FU U.S. Food and Drug Administration Office of Women's Health FX The author is grateful to the U.S. Food and Drug Administration Office of Women's Health for funding, the Heather Pierce of Computerized Imaging Reference Systems, Norfolk, VA, for assistance in phantom design and construction, and Reviewer 1 of this manuscript for excellent suggestions. NR 53 TC 5 Z9 5 U1 1 U2 2 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD DEC PY 2009 VL 126 IS 6 BP 3291 EP 3300 DI 10.1121/1.3257550 PG 10 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 533QH UT WOS:000272838800054 PM 20000943 ER PT J AU Kumar, A Brooks, SS Cavanaugh, K Zuckerman, B AF Kumar, Allison Brooks, Steven S. Cavanaugh, Kenneth Zuckerman, Bram TI FDA perspective on objective performance goals and clinical trial design for evaluating catheter-based treatment of critical limb ischemia SO JOURNAL OF VASCULAR SURGERY LA English DT Article AB The article by Conte et al.(1) on behalf of the Society for Vascular Surgery (SVS) in this issue of the journal of Vascular Surgery provides guidelines for improving the consistency and interpretability of clinical trials intended to evaluate treatment options for patients with critical limb ischemia (CLI). This article identifies a number of key challenges with conducting and comparing CLI trials, including the wide spectrum of clinical presentations that CLI encompasses, the use of disparate eligibility criteria and endpoint measurements, and logistical and economic considerations that can limit study initiation and completion. The authors propose definitions for a number of performance goals derived from historical surgical literature as a means of reducing the negative impact of these factors. The current editorial reviews aspects of this proposal from the perspective of the authors in terms of their understanding of the statutory obligations of the U.S. Food and Drug Administration (FDA) to regulate the marketing of cardiovascular devices based on valid scientific evidence. (J Vase Surg 2009;50:1474-6.) C1 [Kumar, Allison; Brooks, Steven S.; Cavanaugh, Kenneth; Zuckerman, Bram] US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Cardiovasc Devices, Silver Spring, MD 20993 USA. RP Kumar, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Cardiovasc Devices, 10903 New Hampshire Ave,WO66-1270, Silver Spring, MD 20993 USA. EM allison.kumar@fda.hhs.gov NR 3 TC 15 Z9 15 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD DEC PY 2009 VL 50 IS 6 BP 1474 EP 1476 DI 10.1016/j.jvs.2009.09.045 PG 3 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 533YA UT WOS:000272860900029 PM 19897334 ER PT J AU Murata, H Teferedegne, B Lewis, AM Peden, K AF Murata, Haruhiko Teferedegne, Belete Lewis, Andrew M., Jr. Peden, Keith TI A quantitative PCR assay for SV40 neutralization adaptable for high-throughput applications SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE SV40; Polyomavirus; Neutralization; Antibody; Quantitative PCR; SYBR Green ID CAPSID PROTEIN; REAL-TIME; BK VIRUS; HEMAGGLUTINATION INHIBITION; PARVOVIRUS B19; HUMAN SERA; POLYOMAVIRUS; IDENTIFICATION; ANTIBODIES; REACTIVITY AB A neutralization assay incorporating a quantitative SYBR Green PCR endpoint has been developed for SV40. The present study demonstrates that crude virus samples can serve as suitable amplification templates for quantitative PCR without the need for nucleic acid extraction. The denaturation temperature of thermocycling appears to be sufficient to release the encapsidated viral genome and allow its availability as a PCR template. Issues arising from inhibitors of PCR present in crude virus samples can be circumvented easily by a 100-fold dilution step. Using a streamlined procedure that eliminates sample nucleic acid extraction (a hitherto rate-limiting step that diminishes throughput substantially), quantitative PCR was applied in order to assess: (1) the replication kinetics of SV40 and (2) the inhibition of SV40 productive infection by neutralizing antibodies. A similar high-throughput approach might be feasible for related polyomaviruses (e.g., BKV and JCV) as well as for other families of viruses. Published by Elsevier B.V. C1 [Murata, Haruhiko; Teferedegne, Belete; Lewis, Andrew M., Jr.] US FDA, Ctr Biol Evaluat & Res, Lab DNA Viruses, Div Viral Prod, Bethesda, MD 20892 USA. [Peden, Keith] US FDA, Ctr Biol Evaluat & Res, Lab Retrovirus Res, Div Viral Prod, Bethesda, MD 20892 USA. RP Murata, H (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab DNA Viruses, Div Viral Prod, Bldg 29A,Room 1A01,29 Lincoln Dr, Bethesda, MD 20892 USA. EM haruhiko.murata@fda.hhs.gov FU National Vaccine Program Office FX We thank Steve Feinstone, Judy Beeler, and Carol Weiss for comments on the manuscript. This study was funded in part by a grant from the National Vaccine Program Office. NR 34 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD DEC PY 2009 VL 162 IS 1-2 BP 236 EP 244 DI 10.1016/j.jviromet.2009.08.012 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 517BA UT WOS:000271586500036 PM 19729038 ER PT J AU Black, S Eskola, J Siegrist, CA Halsey, N MacDonald, N Law, B Miller, E Andrews, N Stowe, J Salmon, D Vannice, K Izurieta, HS Akhtar, A Gold, M Oselka, G Zuber, P Pfeifer, D Vellozzi, C AF Black, Steven Eskola, Juhani Siegrist, Claire-Anne Halsey, Neal MacDonald, Noni Law, Barbara Miller, Elizabeth Andrews, Nick Stowe, Julia Salmon, Daniel Vannice, Kirsten Izurieta, Hector S. Akhtar, Aysha Gold, Mike Oselka, Gabriel Zuber, Patrick Pfeifer, Dina Vellozzi, Claudia TI Importance of background rates of disease in assessment of vaccine safety during mass immunisation with pandemic H1N1 influenza vaccines SO LANCET LA English DT Article ID GUILLAIN-BARRE-SYNDROME; EVENT REPORTING SYSTEM; SPONTANEOUS-ABORTION; MULTIPLE-SCLEROSIS; OPTIC NEURITIS; YOUNG-ADULTS; SUDDEN-DEATH; RISK; POPULATION; EPIDEMIOLOGY AB Because of the advent of a new influenza A H1N1. strain, many countries have begun mass immunisation programmes. Awareness of the background rates of possible adverse events will be a crucial part of assessment of possible vaccine safety concerns and will help to separate legitimate safety concerns from events that are temporally associated with but not caused by vaccination. We identified background rates of selected medical events for several countries. Rates of disease events varied by age, sex, method of ascertainment, and geography. Highly visible health conditions, such as Guillain-Barre syndrome, spontaneous abortion, or even death, will occur in coincident temporal association with novel influenza vaccination. On the basis of the reviewed data, if a cohort of 10 million individuals was vaccinated in the UK, 21.5 cases of Guillain-Barre syndrome and 5.75 cases of sudden death would be expected to occur within 6 weeks of vaccination as coincident background cases. In female vaccinees in the USA, 86.3 cases of optic neuritis per 10 million population would be expected within 6 weeks of vaccination. 397 per 1 million vaccinated pregnant women would be predicted to have a spontaneous abortion within 1 day of vaccination. C1 [Black, Steven] Cincinnati Childrens Hosp, Ctr Global Hlth, Cincinnati, OH 45229 USA. [Black, Steven] Cincinnati Childrens Hosp, Div Infect Dis, Cincinnati, OH 45229 USA. [Eskola, Juhani] Natl Inst Hlth & Welf, Helsinki, Finland. [Siegrist, Claire-Anne] Univ Geneva, Ctr Vaccinol & Neonatal Immunol, Dept Pediat, Geneva, Switzerland. [Halsey, Neal] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Inst Vaccine Safety, Baltimore, MD USA. [MacDonald, Noni] Dalhousie Univ, Dept Pediat, Div Infect Dis, Halifax, NS, Canada. [Law, Barbara] Publ Hlth Agcy Canada, Vaccine Safety Sect, Ctr Immunizat & Resp Infect Dis, Ottawa, ON, Canada. [Miller, Elizabeth; Andrews, Nick; Stowe, Julia] Hlth Protect Agcy, Ctr Infect, London, England. [Salmon, Daniel; Vannice, Kirsten] Dept Hlth & Human Serv, Natl Vaccine Program Off, Washington, DC USA. [Izurieta, Hector S.; Akhtar, Aysha] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Gold, Mike] Univ Adelaide, Discipline Paediat, Sch Paediat & Reprod Hlth, Adelaide, SA 5005, Australia. [Oselka, Gabriel] Univ Sao Paulo, Dept Pediat, Fac Med, Sao Paulo, Brazil. [Zuber, Patrick; Pfeifer, Dina] WHO, Qual Safety & Stand Team, CH-1211 Geneva, Switzerland. [Vellozzi, Claudia] Ctr Dis Control & Prevent, Immunizat Safety Off, Atlanta, GA USA. RP Black, S (reprint author), Cincinnati Childrens Hosp, Ctr Global Hlth, 3333 Burnet Ave,MLC 2048, Cincinnati, OH 45229 USA. EM Steven.Black1@cchmc.org FU Centers for Disease Control and Prevention; Department of Health and Human Services; WHO; US Food and Drug Administration; UK Health Protection Agency FX The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention, the Department of Health and Human Services, WHO, the US Food and Drug Administration, or the UK Health Protection Agency. NR 44 TC 115 Z9 117 U1 0 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD DEC-JAN PY 2009 VL 374 IS 9707 BP 2115 EP 2122 DI 10.1016/S0140-6736(09)61877-8 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 537OO UT WOS:000273122900035 PM 19880172 ER PT J AU Brown, JS Moore, KM Braun, MM Ziyadeh, N Chan, KA Lee, GM Kulldorff, M Walker, AM Platt, R AF Brown, Jeffrey S. Moore, Kristen M. Braun, M. Miles Ziyadeh, Najat Chan, K. Arnold Lee, Grace M. Kulldorff, Martin Walker, Alexander M. Platt, Richard TI Active Influenza Vaccine Safety Surveillance Potential Within a Healthcare Claims Environment SO MEDICAL CARE LA English DT Article; Proceedings Paper CT 24th International Confernece on Pharmacoepidemiology and Therapeutic Risk Management CY AUG, 2008 CL Copenhagen, DENMARK DE active vaccine safety surveillance; pandemic influenza; vaccine adverse events; sequential analysis; maxSPRT ID GUILLAIN-BARRE-SYNDROME; IMMUNIZATION PRACTICES ACIP; EVENT REPORTING SYSTEM; ADVERSE EVENTS; ADVISORY-COMMITTEE; POPULATION; CHILDREN; RECOMMENDATIONS AB Background: Rapid safety assessment of novel vaccines, especially those targeted against pandemic influenza, is a public health priority. Objectives: Assess the feasibility of using healthcare claims data to rapidly detect influenza vaccine adverse events using sequential analytic methods. Research Design: Retrospective pilot study simulating prospective surveillance using 6 cumulative monthly administrative claims data extracts. The first included encounters occurring in October; each subsequent extract included an additional month of encounters. Ten adverse events were evaluated, comparing postvaccination rates during the 2006-2007 influenza season to those expected based on rates observed in the prior season. Subjects: Members of a large, multistate health insurer who had a claim for influenza vaccination during the 2005-2006 or 2006-2007 influenza seasons. Measures: The completeness of monthly claims extracts. Results: Most vaccinations and outcomes were identified early in the 2006-2007 season; about 50% of vaccinations and short latency events were identified in the second monthly data extract, which would typically become available by mid-December, and 80% of vaccinations and events were identified in the third extract. With respect to overall claims lag, approximately 90% of vaccinations and events were identified within I to 2 months after vaccination, regardless of vaccination month. Conclusions: This study suggests that administrative claims data might contribute to same season influenza vaccine safety surveillance in large, defined populations, especially during a threat of pandemic influenza. Based on our previous work, we believe this method could be applied to multiple health plans' data to monitor a large portion of the US population. C1 [Brown, Jeffrey S.; Moore, Kristen M.; Lee, Grace M.; Kulldorff, Martin; Platt, Richard] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA 02215 USA. [Brown, Jeffrey S.; Moore, Kristen M.; Lee, Grace M.; Kulldorff, Martin; Platt, Richard] Harvard Pilgrim Hlth Care, Boston, MA 02215 USA. [Brown, Jeffrey S.; Moore, Kristen M.; Platt, Richard] HMO Res Network Ctr Educ & Res Therapeut, Boston, MA USA. [Braun, M. Miles] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Ziyadeh, Najat; Chan, K. Arnold] i3 Drug Safety, Waltham, MA USA. [Chan, K. Arnold; Walker, Alexander M.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Lee, Grace M.] Childrens Hosp Boston, Dept Med, Boston, MA USA. [Lee, Grace M.] Childrens Hosp Boston, Dept Lab Med, Boston, MA USA. [Walker, Alexander M.] World Hlth Informat Sci Consultants LLC, Wellesley, MA USA. RP Brown, JS (reprint author), Harvard Univ, Sch Med, Dept Populat Med, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA. EM jeff_brown@harvardpilgrim.org RI Kulldorff, Martin/H-4282-2011; OI Chan, Kinwei/0000-0001-8161-1986; Kulldorff, Martin/0000-0002-5284-2993 FU PHS HHS [200-2002-00732] NR 33 TC 13 Z9 13 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD DEC PY 2009 VL 47 IS 12 BP 1251 EP 1257 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 529AM UT WOS:000272488100009 PM 19786905 ER PT J AU Wang, SJ Yao, JH Liu, JM Petrick, N Van Uitert, RL Periaswamy, S Summers, RM AF Wang, Shijun Yao, Jianhua Liu, Jiamin Petrick, Nicholas Van Uitert, Robert L. Periaswamy, Senthil Summers, Ronald M. TI Registration of prone and supine CT colonography scans using correlation optimized warping and canonical correlation analysis SO MEDICAL PHYSICS LA English DT Article DE colon registration; correlation optimized warping; dynamic time warping; canonical correlation analysis; virtual colonoscopy ID FALSE POSITIVES; COLONIC POLYPS; VIRTUAL COLONOSCOPY; REDUCTION; CAD AB Purpose: In computed tomographic colonography (CTC), a patient will be scanned twice-Once supine and once prone-to improve the sensitivity for polyp detection. To assist radiologists in CTC reading, in this paper we propose an automated method for colon registration from supine and prone CTC scans. Methods: We propose a new colon centerline registration method for prone and supine CTC scans using correlation optimized warping (COW) and canonical correlation analysis (CCA) based on the anatomical structure of the colon. Four anatomical salient points on the colon are first automatically distinguished. Then correlation optimized warping is applied to the segments defined by the anatomical landmarks to improve the global registration based on local correlation of segments. The COW method was modified by embedding canonical correlation analysis to allow multiple features along the colon centerline to be used in our implementation. Results: We tested the COW algorithm on a CTC data set of 39 patients with 39 polyps (19 training and 20 test cases) to verify the effectiveness of the proposed COW registration method. Experimental results on the test set show that the COW method significantly reduces the average estimation error in a polyp location between supine and prone scans by 67.6%, from 46.27 +/- 52.97 to 14.98 mm +/- 11.41 mm, compared to the normalized distance along the colon centerline algorithm (p < 0.01). Conclusions: The proposed COW algorithm is more accurate for the colon centerline registration compared to the normalized distance along the colon centerline method and the dynamic time warping method. Comparison results showed that the feature combination of z-coordinate and curvature achieved lowest registration error compared to the other feature combinations used by COW. The proposed method is tolerant to centerline errors because anatomical landmarks help prevent the propagation of errors across the entire colon centerline. [DOI: 10.1118/1.3259727] C1 [Wang, Shijun; Yao, Jianhua; Liu, Jiamin; Summers, Ronald M.] NIH, Ctr Clin, Imaging Biomarkers & Comp Aided Diag Lab, Bethesda, MD 20892 USA. [Petrick, Nicholas] US FDA, NIBIB, CDRH, Lab Assessment Med Imaging Syst, Silver Spring, MD 20993 USA. [Van Uitert, Robert L.; Periaswamy, Senthil] iCAD Inc, Nashua, NH 03062 USA. RP Summers, RM (reprint author), NIH, Ctr Clin, Imaging Biomarkers & Comp Aided Diag Lab, Bldg 10,Room 1C368X,MSC 1182, Bethesda, MD 20892 USA. EM wangshi@cc.nih.gov; rms@nih.gov RI Wang, Shijun/E-5005-2010 FU NIH U.S. Food and Drug Administration FX This research was supported by the Intramural Research Programs of the NIH Clinical Center and the U.S. Food and Drug Administration (NP). We thank Dr. Perry Pickhardt, Dr. J. Richard Choi, and Dr. William Schindler for providing CT colonography data. NR 21 TC 20 Z9 21 U1 0 U2 2 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 EI 2473-4209 J9 MED PHYS JI Med. Phys. PD DEC PY 2009 VL 36 IS 12 BP 5595 EP 5603 DI 10.1118/1.3259727 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 524QJ UT WOS:000272157500024 PM 20095272 ER PT J AU Sassi, A Brichacek, B Hieny, S Yarovinsky, F Golding, H Grivel, JC Sher, A Margolis, L AF Sassi, Atfa Brichacek, Beda Hieny, Sara Yarovinsky, Felix Golding, Hana Grivel, Jean-Charles Sher, Alan Margolis, Leonid TI Toxoplasma gondii inhibits R5 HIV-1 replication in human lymphoid tissues ex vivo SO MICROBES AND INFECTION LA English DT Article DE HIV; Toxoplasma gondii; Cyclophilin; Ex vivo; Human lymphoid tissue ID GB-VIRUS-C; CXCR4-TROPIC HIV-1; INFECTION; SUPPRESSION; AIDS; COINFECTION; MACROPHAGES; MIP-1-ALPHA; CYTOKINES; MEASLES AB Critical events of HIV-1 pathogenesis occur in lymphoid tissues where HIV-1 is typically accompanied by infections with other pathogens (HIV co-pathogens). Co-pathogens greatly affect the clinical course of the disease and the transmission of HIV. The apicomplexan parasite Toxoplasma gondii is a common HIV co-pathogen associated with AIDS development. Here, we examined the interaction of T. gondii and HIV in coinfected human lymphoid tissue ex vivo. Both pathogens readily replicate in ex vivo infected blocks of human tonsillar tissue. Surprisingly, we found that live T. gondii preferentially inhibits R5 HIV-1 replication in coinfected tissues. This effect is reproduced by treatment of the tissue blocks with recombinant C-18, a T. gondii-encoded cyclophilin that binds to CCR5. These ex vivo findings raise the possibility that, in addition to being a co-factor in HIV disease, T. gondii may influence the outcome of viral infection by preferentially suppressing R5 variants. Published by Elsevier Masson SAS. C1 [Grivel, Jean-Charles] NICHHD, NIH, Sect Intercellular Interact, Program Phys Biol, Bethesda, MD 20892 USA. [Hieny, Sara; Sher, Alan] NIAID, Immunol Sect, Parasit Dis Lab, Bethesda, MD 20892 USA. [Yarovinsky, Felix] Univ Texas SW Med Ctr Dallas, Dept Immunol, Dallas, TX 75390 USA. [Golding, Hana] Fed Food & Drug Adm, Lab Retrovirus Res, Bethesda, MD 20892 USA. RP Grivel, JC (reprint author), NICHHD, NIH, Sect Intercellular Interact, Program Phys Biol, 10 Ctr Dr,Room 9D58,Bldg 10, Bethesda, MD 20892 USA. EM grivelj@mail.nih.gov FU NIH, National Institute of Child Health; National Institute of Allergy and Infectious Diseases and Human Development FX We thank Dr. M. Santi and the entire staff of the Department of Pathology of Children's National Medical Center for their generous assistance in obtaining human tonsillar tissues. We also thank Dr. D. Kabat of the Department of Biochemistry and Molecular Biology and Proteomics Shared Resource, Oregon Health and Science University, Portland, OR, for providing JR-CSF. This research was supported, in part, by the Intramural Research Program of the NIH, National Institute of Child Health, the National Institute of Allergy and Infectious Diseases and Human Development and by the Intramural AIDS Targeted Anti-viral Program (IATAP) of the NIH. NR 30 TC 2 Z9 2 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD DEC PY 2009 VL 11 IS 14-15 BP 1106 EP 1113 DI 10.1016/j.micinf.2009.08.004 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 539FL UT WOS:000273238900003 PM 19671446 ER PT J AU Slade, BA Leidel, L Vellozzi, C Woo, EJ Hua, W Sutherland, A Izurieta, HS Ball, R Miller, N Braun, MM Markowitz, LE Iskander, J AF Slade, Barbara A. Leidel, Laura Vellozzi, Claudia Woo, Emily Jane Hua, Wei Sutherland, Andrea Izurieta, Hector S. Ball, Robert Miller, Nancy Braun, M. Miles Markowitz, Lauri E. Iskander, John TI Postlicensure Safety Surveillance for Quadrivalent Human Papillomavirus Recombinant Vaccine EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material C1 [Slade, Barbara A.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. US FDA, Washington, DC 20204 USA. RP Slade, BA (reprint author), Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD DEC PY 2009 VL 64 IS 12 BP 796 EP 798 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 529SM UT WOS:000272537500014 ER PT J AU Bocchini, JA Bernstein, HH Bradley, JS Brady, MT Byington, CL Fisher, MC Glode, MP Jackson, MA Keyserling, HL Kimberlin, DW Orenstein, WA Schutze, GE Willoughby, RE Dennehy, PH Frenck, RW Bell, B Bortolussi, R Clover, RD Fischer, MA Gellin, B Gorman, RL Pratt, RD Lee, L Read, JS Starke, JR Swanson, J Baker, CJ Long, SS Pickering, LK Ledbetter, EO Meissner, HC Rubin, LG Hall, C Frantz, J AF Bocchini, Joseph A., Jr. Bernstein, Henry H. Bradley, John S. Brady, Michael T. Byington, Carrie L. Fisher, Margaret C. Glode, Mary P. Jackson, Mary Anne Keyserling, Harry L. Kimberlin, David W. Orenstein, Walter A. Schutze, Gordon E. Willoughby, Rodney E. Dennehy, Penelope H. Frenck, Robert W., Jr. Bell, Beth Bortolussi, Robert Clover, Richard D. Fischer, Marc A. Gellin, Bruce Gorman, Richard L. Pratt, R. Douglas Lee, Lucia Read, Jennifer S. Starke, Jeffrey R. Swanson, Jack Baker, Carol J. Long, Sarah S. Pickering, Larry K. Ledbetter, Edgar O. Meissner, H. Cody Rubin, Lorry G. Hall, Caroline Frantz, Jennifer TI Policy Statement-Modified Recommendations for Use of Palivizumab for Prevention of Respiratory Syncytial Virus Infections SO PEDIATRICS LA English DT Article DE RSV bronchiolitis; palivizumab; immunoprophylaxis ID PREMATURE-INFANTS BORN; INVESTIGATORS COLLABORATIVE NETWORK; CONGENITAL HEART-DISEASE; 35 COMPLETED WEEKS; HIGH-RISK INFANTS; REQUIRING HOSPITALIZATION; REDUCES HOSPITALIZATION; MONOCLONAL-ANTIBODY; COST-EFFECTIVENESS; GESTATIONAL-AGE AB Palivizumab was licensed in June 1998 by the US Food and Drug Administration for prevention of serious lower respiratory tract disease caused by respiratory syncytial virus (RSV) in pediatric patients who are at increased risk of severe disease. Safety and efficacy have been established for infants born at or before 35 weeks' gestation with or without chronic lung disease of prematurity and for infants and children with hemodynamically significant heart disease. The American Academy of Pediatrics (AAP) published a policy statement on the use of palivizumab in November 1998 (American Academy of Pediatrics, Committee on Infectious Diseases and Committee on Fetus and Newborn. Pediatrics. 1998; 102[5]: 1211-1216) and revised it in December 2003 (American Academy of Pediatrics, Committee on Infectious Diseases and Committee on Fetus and Newborn. Pediatrics. 2003; 112[6 pt 1]: 1442-1446), and an AAP technical report on palivizumab was published in 2003 (Meissner HC, Long SS; American Academy of Pediatrics, Committee on Infectious Diseases and Committee on Fetus and Newborn. Pediatrics. 2003; 112[6 pt 1]: 1447-1452). On the basis of the availability of additional data regarding seasonality of RSV disease as well as the limitations in available data on risk factors for identifying children who are at increased risk of serious RSV lower respiratory tract disease, AAP recommendations for immunoprophylaxis have been updated in an effort to ensure optimal balance of benefit and cost from this expensive intervention. This statement updates and replaces the 2003 AAP statement and the 2006 Red Book and is consistent with the 2009 Red Book recommendations. Pediatrics 2009; 124: 1694-1701 C1 [Bell, Beth; Fischer, Marc A.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Bortolussi, Robert] Canadian Paediat Soc, Ottawa, ON, Canada. [Clover, Richard D.] Amer Acad Family Phys, Leakwood, KS 66211 USA. [Gorman, Richard L.; Read, Jennifer S.] Natl Inst Hlth, Bethesda, MD 20892 USA. [Pratt, R. Douglas; Lee, Lucia] US FDA, Rockville, MD 20857 USA. OI Dennehy, Penelope/0000-0002-2259-5370; Byington, Carrie/0000-0002-7350-9495 NR 32 TC 143 Z9 149 U1 1 U2 5 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 2009 VL 124 IS 6 BP 1694 EP 1701 DI 10.1542/peds.2009-2345 PG 8 WC Pediatrics SC Pediatrics GA 524SE UT WOS:000272162400026 ER PT J AU Bellier, A Chen, CS Kao, CY Cinar, HN Aroian, RV AF Bellier, Audrey Chen, Chang-Shi Kao, Cheng-Yuan Cinar, Hediye N. Aroian, Raffi V. TI Hypoxia and the Hypoxic Response Pathway Protect against Pore-Forming Toxins in C. elegans SO PLOS PATHOGENS LA English DT Article ID CAENORHABDITIS-ELEGANS; BACILLUS-THURINGIENSIS; INDUCIBLE FACTOR; PSEUDOMONAS-AERUGINOSA; STAPHYLOCOCCUS-AUREUS; ENDOPLASMIC-RETICULUM; LIFE-SPAN; GENE; RESISTANCE; NEMATODES AB Pore-forming toxins (PFTs) are by far the most abundant bacterial protein toxins and are important for the virulence of many important pathogens. As such, cellular responses to PFTs critically modulate host-pathogen interactions. Although many cellular responses to PFTs have been recorded, little is understood about their relevance to pathological or defensive outcomes. To shed light on this important question, we have turned to the only genetic system for studying PFT-host interactions-Caenorhabditis elegans intoxication by Crystal (Cry) protein PFTs. We mutagenized and screened for C. elegans mutants resistant to a Cry PFT and recovered one mutant. Complementation, sequencing, transgenic rescue, and RNA interference data demonstrate that this mutant eliminates a gene normally involved in repression of the hypoxia ( low oxygen response) pathway. We find that up-regulation of the C. elegans hypoxia pathway via the inactivation of three different genes that normally repress the pathway results in animals resistant to Cry PFTs. Conversely, mutation in the central activator of the hypoxia response, HIF-1, suppresses this resistance and can result in animals defective in PFT defenses. These results extend to a PFT that attacks mammals since up-regulation of the hypoxia pathway confers resistance to Vibrio cholerae cytolysin (VCC), whereas down-regulation confers hypersusceptibility. The hypoxia PFT defense pathway acts cell autonomously to protect the cells directly under attack and is different from other hypoxia pathway stress responses. Two of the downstream effectors of this pathway include the nuclear receptor nhr-57 and the unfolded protein response. In addition, the hypoxia pathway itself is induced by PFT, and low oxygen is protective against PFT intoxication. These results demonstrate that hypoxia and induction of the hypoxia response protect cells against PFTs, and that the cellular environment can be modulated via the hypoxia pathway to protect against the most prevalent class of weapons used by pathogenic bacteria. C1 [Bellier, Audrey; Chen, Chang-Shi; Kao, Cheng-Yuan; Aroian, Raffi V.] Univ Calif San Diego, Sect Cell & Dev Biol, La Jolla, CA 92093 USA. [Cinar, Hediye N.] US FDA, Ctr Food Safety & Appl Nutr, Div Virulence Assessment, Laurel, MD USA. RP Bellier, A (reprint author), Univ Calif San Diego, Sect Cell & Dev Biol, La Jolla, CA 92093 USA. EM raroian@ucsd.edu RI KAO, CHENG-YUAN/A-7531-2010; Chen, Chang-Shi/B-9251-2009; bellier, audrey/D-7649-2015 OI KAO, CHENG-YUAN/0000-0003-0946-9270; bellier, audrey/0000-0002-3106-4547 FU NIH [AI056189, GM071603]; NSF MCB [0517718] FX This work was supported by grants to RVA: NIH AI056189 (AB, CSC), NSF MCB 0517718 (CSC), and NIH GM071603 (CYK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 60 TC 52 Z9 58 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD DEC PY 2009 VL 5 IS 12 AR e1000689 DI 10.1371/journal.ppat.1000689 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 551RP UT WOS:000274227000013 PM 20011506 ER PT J AU Clegg, LX Hankey, BF Tiwari, R Feuer, EJ Edwards, BK AF Clegg, Limin X. Hankey, Benjamin F. Tiwari, Ram Feuer, Eric J. Edwards, Brenda K. TI Estimating average annual per cent change in trend analysis SO STATISTICS IN MEDICINE LA English DT Article DE confidence interval for trends; geometric means; trend comparisons ID CANCER; NATION; RATES AB Trends in incidence or mortality rates over a specified time interval are usually described by the conventional annual per cent change (cAPC), under the assumption of a constant rate of change. When this assumption does not hold over the entire time interval, the trend may be characterized using the annual per cent changes from segmented analysis (sAPCs). This approach assumes that the change in rates is constant over each time partition defined by the transition points, but varies among different time partitions. Different groups (e.g. racial subgroups), however, may have different transition points and thus different time partitions over which they have constant rates of change, making comparison of sAPCs; problematic across groups over a common time interval of interest (e.g. the past 10 years). We propose a new measure, the average annual per cent change (AAPC), which uses sAPCs to summarize and compare trends for a specific time period. The advantage of the proposed AAPC is that it takes into account the trend transitions, whereas cAPC does not and can lead to erroneous conclusions. In addition, when the trend is constant over the entire time interval of interest, the AAPC has the advantage of reducing to both cAPC and sAPC. Moreover, because the estimated AAPC is based on the segmented analysis over the entire data series, any selected subinterval within a single time partition will yield the same AAPC estimate-that is it will be equal to the estimated sAPC for that time partition. The cAPC, however, is re-estimated using data only from that selected subinterval; thus, its estimate may be sensitive to the subinterval selected. The AAPC estimation has been incorporated into the segmented regression (free) software Joinpoint, which is used by many registries throughout the world for characterizing trends in cancer rates. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Clegg, Limin X.] US Dept Vet Affairs, Off Inspector Gen, Washington, DC USA. [Hankey, Benjamin F.] Informat Management Serv Inc, Silver Spring, MD USA. [Tiwari, Ram] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Feuer, Eric J.; Edwards, Brenda K.] NCI, Surveillance Res Program, Bethesda, MD 20892 USA. RP Clegg, LX (reprint author), US Dept Vet Affairs, Off Inspector Gen, 801 1 St NW,Room 1018, Washington, DC USA. EM lin_clegg@nih.gov NR 16 TC 118 Z9 123 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD DEC PY 2009 VL 28 IS 29 BP 3670 EP 3682 DI 10.1002/sim.3733 PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 533EU UT WOS:000272807300007 PM 19856324 ER PT J AU Lenas, P Moos, M Luyten, FP AF Lenas, Petros Moos, Malcolm, Jr. Luyten, Frank P. TI Developmental Engineering: A New Paradigm for the Design and Manufacturing of Cell-Based Products. Part I: From Three-Dimensional Cell Growth to Biomimetics of In Vivo Development SO TISSUE ENGINEERING PART B-REVIEWS LA English DT Article ID ENDOCHONDRAL BONE-FORMATION; HORMONE-RELATED PEPTIDE; EMBRYONIC STEM-CELLS; MAGNETITE NANOPARTICLES; ARTICULAR-CARTILAGE; CHONDROCYTE DIFFERENTIATION; EXTRACELLULAR-MATRIX; SKELETAL DEVELOPMENT; ALGINATE HYDROGELS; INDIAN-HEDGEHOG AB Recent advances in developmental biology, systems biology, and network science are converging to poise the heretofore largely empirical field of tissue engineering on the brink of a metamorphosis into a rigorous discipline based on universally accepted engineering principles of quality by design. Failure of more simplistic approaches to the manufacture of cell-based therapies has led to increasing appreciation of the need to imitate, at least to some degree, natural mechanisms that control cell fate and differentiation. The identification of many of these mechanisms, which in general are based on cell signaling pathways, is an important step in this direction. Some well-accepted empirical concepts of developmental biology, such as path-dependence, robustness, modularity, and semiautonomy of intermediate tissue forms, that appear sequentially during tissue development are starting to be incorporated in process design. C1 [Lenas, Petros] Univ Complutense Madrid, Fac Vet, Dept Biochem & Mol Biol 4, Madrid, Spain. [Lenas, Petros] CIBER BBN, Aragon Inst Hlth Sci, Networking Ctr Bioengn Biomat & Nanomed, Zaragoza, Spain. [Moos, Malcolm, Jr.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Luyten, Frank P.] Katholieke Univ Leuven, Dept Musculoskeletal Sci, Leuven, Belgium. [Luyten, Frank P.] KU Leuven Res & Dev, Div Prometheus Skeletal Tissue Engn, Leuven, Belgium. RP Luyten, FP (reprint author), Katholieke Univ Leuven Hosp, Dept Rheumatol, Herestr 49, B-3000 Louvain, Belgium. EM frank.luyten@uzleuven.be RI Moos, Malcolm/F-3673-2011 OI Moos, Malcolm/0000-0002-9575-9938 NR 76 TC 74 Z9 75 U1 0 U2 25 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3368 J9 TISSUE ENG PART B-RE JI Tissue Eng. Part B-Rev. PD DEC PY 2009 VL 15 IS 4 BP 381 EP 394 DI 10.1089/ten.teb.2008.0575 PG 14 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 528QY UT WOS:000272462900001 PM 19505199 ER PT J AU Lenas, P Moos, M Luyten, FP AF Lenas, Petros Moos, Malcolm, Jr. Luyten, Frank P. TI Developmental Engineering: A New Paradigm for the Design and Manufacturing of Cell-Based Products. Part II. From Genes to Networks: Tissue Engineering from the Viewpoint of Systems Biology and Network Science SO TISSUE ENGINEERING PART B-REVIEWS LA English DT Review ID EMBRYONIC STEM-CELLS; HORMONE-RELATED PEPTIDE; ENDOCHONDRAL BONE-FORMATION; GROWTH-PLATE CHONDROCYTES; SEGMENT POLARITY NETWORK; PARATHYROID-HORMONE; DROSOPHILA-MELANOGASTER; DEFINITIVE ENDODERM; SYNTHETIC BIOLOGY; INDIAN HEDGEHOG AB The field of tissue engineering is moving toward a new concept of "in vitro biomimetics of in vivo tissue development.'' In Part I of this series, we proposed a theoretical framework integrating the concepts of developmental biology with those of process design to provide the rules for the design of biomimetic processes. We named this methodology "developmental engineering'' to emphasize that it is not the tissue but the process of in vitro tissue development that has to be engineered. To formulate the process design rules in a rigorous way that will allow a computational design, we should refer to mathematical methods to model the biological process taking place in vitro. Tissue functions cannot be attributed to individual molecules but rather to complex interactions between the numerous components of a cell and interactions between cells in a tissue that form a network. For tissue engineering to advance to the level of a technologically driven discipline amenable to well-established principles of process engineering, a scientifically rigorous formulation is needed of the general design rules so that the behavior of networks of genes, proteins, or cells that govern the unfolding of developmental processes could be related to the design parameters. Now that sufficient experimental data exist to construct plausible mathematical models of many biological control circuits, explicit hypotheses can be evaluated using computational approaches to facilitate process design. Recent progress in systems biology has shown that the empirical concepts of developmental biology that we used in Part I to extract the rules of biomimetic process design can be expressed in rigorous mathematical terms. This allows the accurate characterization of manufacturing processes in tissue engineering as well as the properties of the artificial tissues themselves. In addition, network science has recently shown that the behavior of biological networks strongly depends on their topology and has developed the necessary concepts and methods to describe it, allowing therefore a deeper understanding of the behavior of networks during biomimetic processes. These advances thus open the door to a transition for tissue engineering from a substantially empirical endeavor to a technology-based discipline comparable to other branches of engineering. C1 [Luyten, Frank P.] Katholieke Univ Leuven, KU Leuven Res & Dev, Div Prometheus Skeletal Tissue Engn, Dept Musculoskeletal Sci, B-3000 Louvain, Belgium. [Lenas, Petros] Univ Complutense Madrid, Fac Vet, Dept Biochem & Mol Biol 4, Madrid, Spain. [Lenas, Petros] CIBER BBN, Networking Ctr Bioengn Biomat & Nanomed, Aragon Inst Hlth Sci, Zaragoza, Spain. [Moos, Malcolm, Jr.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Luyten, FP (reprint author), Katholieke Univ Leuven, KU Leuven Res & Dev, Div Prometheus Skeletal Tissue Engn, Dept Musculoskeletal Sci, B-3000 Louvain, Belgium. EM frank.luyten@uzleuven.be RI Moos, Malcolm/F-3673-2011 OI Moos, Malcolm/0000-0002-9575-9938 FU European project [LSHM-CT-2007-037862] FX Partial support from the European project LSHM-CT-2007-037862 is gratefully acknowledged. We would like to thank Eleni Nicodemou-Lena, Jan Schrooten, and Jeroen Eyckmans for numerous critical discussions on the biological aspects of the article; Andreina Elena Lanzara for the preparation of the figures and meaningful discussions for the final design of the figures; and Steve Bauer, Caitilin Hamill, Deborah Hursh, and Terrig Thomas for critical review of the manuscripts. NR 110 TC 34 Z9 35 U1 0 U2 9 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3368 J9 TISSUE ENG PART B-RE JI Tissue Eng. Part B-Rev. PD DEC PY 2009 VL 15 IS 4 BP 395 EP 422 DI 10.1089/ten.teb.2009.0461 PG 28 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 528QY UT WOS:000272462900002 PM 19589040 ER PT J AU Zhao, BZ Yin, JJ Bilski, PJ Chignell, CF Roberts, JE He, YY AF Zhao, Baozhong Yin, Jun-Jie Bilski, Piotr J. Chignell, Colin F. Roberts, Joan E. He, Yu-Ying TI Enhanced photodynamic efficacy towards melanoma cells by encapsulation of Pc4 in silica nanoparticles SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Photodynamic therapy; Nanoparticles; Melanoma; Phthalocyanine; Singlet oxygen; Apoptosis ID PHTHALOCYANINE PHOTOSENSITIZER PC-4; THERAPY-MEDIATED APOPTOSIS; SINGLET OXYGEN; CANCER-THERAPY; RADIOPROTECTIVE AGENT; PLASMA-MEMBRANE; CYTOCHROME-C; IN-VITRO; DELIVERY; DAMAGE AB Nanoparticles have been explored recently as an efficient means of delivering photosensitizers for cancer diagnosis and photodynamic therapy (PDT). Silicon phthalocyanine 4 (Pc4) is Currently being clinically tested as a photosensitizer for PDT. Unfortunately, Pc4 aggregates in aqueous solutions, which dramatically reduces its PDT efficacy and therefore limits its clinical application. We have encapsulated Pc4 using silica nanoparticles (Pc4SNP), which not only improved the aqueous solubility, stability, and delivery of the photodynamic drug but also increased its photodynamic efficacy compared to free Pc4 molecules. Pc4SNP generated photo-induced singlet oxygen more efficiently than free Pc4 as measured by chemical probe and EPR trapping techniques. Transmission electron microscopy and dynamic light scattering measurements showed that the size of the particles is in the range of 25-30 nm. Cell viability measurements demonstrated that Pc4SNP was more phototoxic to A375 or B16-F10 melanoma cells than free Pc4. Pc4SNP photodamaged melanoma cells primarily through apoptosis. Irradiation of A375 cells in the presence of Pc4SNP resulted in a significant increase in intracellular protein-derived peroxides, suggesting a Type II (singlet oxygen) mechanism for phototoxicity. More Pc4SNP than free Pc4 was localized in the mitochondria and lysosomes. Our results show that these stable, monodispersed silica nanoparticles may be an effective new formulation for Pc4 in its preclinical and clinical studies. We expect that modifying the surface of silicon nanoparticles encapsulating the photosensitizers with antibodies specific to melanoma cells will lead to even better early diagnosis and targeted treatment of melanoma in the future. (C) 2009 Elsevier Inc. All rights reserved. C1 [He, Yu-Ying] Univ Chicago, Dept Med, Dermatol Sect, Chicago, IL 60637 USA. [Zhao, Baozhong; Bilski, Piotr J.; Chignell, Colin F.] NIEHS, Pharmacol Lab, Res Triangle Pk, NC 27709 USA. [Yin, Jun-Jie] Food & Drug Adm, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Roberts, Joan E.] Fordham Univ, Dept Nat Sci, Bronx, NY 10458 USA. RP He, YY (reprint author), Univ Chicago, Dept Med, Dermatol Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM yyhe@medicine.bsd.uchicago.edu RI Zhao, Baozhong/B-5865-2011; Yin, Jun Jie /E-5619-2014 FU NIH, National institute of Environmental Health Sciences; Department of Medicine and the Section of Dermatology at the University of Chicago; University of Chicago Cancer Research Center; CTSA FX This research was supported by the Intramural Research Program of the NIH, National institute of Environmental Health Sciences, the Department of Medicine and the Section of Dermatology at the University of Chicago, the University of Chicago Cancer Research Center, and the CTSA. The authors are indebted to Dr. Ann Motten, NIEHS, for critical reading of the manuscript and Dr. Carl Bortner and Maria Sifre for their assistance with flow cytometry. NR 54 TC 98 Z9 99 U1 3 U2 42 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 2009 VL 241 IS 2 BP 163 EP 172 DI 10.1016/j.taap.2009.08.010 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 518SD UT WOS:000271712600005 PM 19695274 ER PT J AU Scheri, RC Lee, J Barofsky, DF Curtis, LR AF Scheri, Richard C. Lee, Junga Barofsky, Douglas F. Curtis, Lawrence R. TI Chlordecone increased subcellular distribution of scavenger receptor class B type II to murine hepatic microsomes without altering cytosolic cholesterol binding proteins SO TOXICOLOGY LETTERS LA English DT Article DE Chlordecone; Scavenger receptor class B type II; Cholesterol ID HIGH-DENSITY-LIPOPROTEIN; SR-BII; PLASMA-CHOLESTEROL; STEROL TRANSPORT; C57BL/6 MICE; TARGETS; CELLS; HYDROCARBONS; TRAFFICKING; DISPOSITION AB Pretreatment of male C57BL/6 mice with low doses of the persistent organochlorine pesticide, chlordecone (CD), stimulated biliary excretion of exogenous cholesterol (CH) up to 3-fold. Increased biliary excretion occurred without changes in hepatic ATP-binding cassette transporter G8 (ABCG8) of the bile canaliculus or scavenger receptor class B type I (SR-BI) of the sinusoidal surface. A variety of tissues express scavenger receptor class B type II (SR-BII) and this protein was identified as a splice variant from the SR-BI gene. Although the function of SR-BII has not been elucidated it may play a role in CH homeostasis and trafficking distinctly different than SR-BI. Western blotting demonstrated that a single dose of CD promoted subcellular distribution of SR-BII to murine hepatic microsomes about 2.2-fold when compared to controls without effect on liver crude membrane SR-BII content. This was consistent with increased vesicular CH trafficking. Relative quantification of hepatic cytosolic proteins in a fraction that sequestered [C-14]CH by mass spectrometry (MS) indicated no role for cytosolic CH binding proteins in CID altered CH homeostasis. Western blotting verified no effect of CD on liver fatty acid-binding protein (L-FABP) in cytosol. MS detected a statistically significant increase in myosin-9, which was also consistent with increased vesicular trafficking. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Curtis, Lawrence R.] Oregon State Univ, Dept Environm & Mol Toxicol, Corvallis, OR 97333 USA. [Barofsky, Douglas F.] Oregon State Univ, Dept Chem, Corvallis, OR 97333 USA. [Scheri, Richard C.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Lee, Junga] Sungkyunkwan Univ, Dept Civil & Environm Engn, Suwon 440746, Gyeonggi, South Korea. RP Curtis, LR (reprint author), Oregon State Univ, Dept Environm & Mol Toxicol, Corvallis, OR 97333 USA. EM larry.curtis@oregonstate.edu FU NIEHS NIH HHS [T32 ES007060] NR 42 TC 1 Z9 1 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 EI 1879-3169 J9 TOXICOL LETT JI Toxicol. Lett. PD DEC 1 PY 2009 VL 191 IS 1 BP 20 EP 25 DI 10.1016/j.toxlet.2009.07.029 PG 6 WC Toxicology SC Toxicology GA 526GW UT WOS:000272276700004 PM 19666090 ER PT J AU Masilamani, M Peruzzi, G Borrego, F Coligan, JE AF Masilamani, Madhan Peruzzi, Giovanna Borrego, Francisco Coligan, John E. TI Endocytosis and Intracellular Trafficking of Human Natural Killer Cell Receptors SO TRAFFIC LA English DT Review DE NK cell receptors; endocytosis; intra-cellular trafficking ID HUMAN NK CELLS; CLATHRIN-INDEPENDENT ENDOCYTOSIS; PROTEIN-KINASE-C; CD8(+) T-CELLS; CD94/NKG2A INHIBITORY RECEPTOR; IFN-GAMMA PRODUCTION; TGF-BETA RECEPTOR; IG-LIKE RECEPTORS; FC-EPSILON-RI; DENDRITIC CELLS AB Natural killer (NK) cells play a vital role in the defense against viral infections and tumor development. NK cell function is primarily regulated by the sum of signals from a broad array of activation and inhibitory receptors. Key to generating the input level of either activating or inhibitory signals is the maintenance of receptor expression levels on the cell surface. Although the mechanisms of endocytosis and trafficking for some cell surface receptors, such as transferrin receptor and certain immune receptors, are very well known, that is not the situation for receptors expressed by NK cells. Recent studies have uncovered that endocytosis and trafficking routes characteristic for specific activation and inhibitory receptors can regulate the functional responses of NK cells. In this review, we summarize the current knowledge of receptor endocytosis and trafficking, and integrate this with our current understanding of NK cell receptor trafficking. C1 [Peruzzi, Giovanna; Coligan, John E.] NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Masilamani, Madhan] Mt Sinai Sch Med, Dept Pediat, Jaffe Food Allergy Inst, New York, NY 10029 USA. [Borrego, Francisco] US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Coligan, JE (reprint author), NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Twinbrook 2,Room 205,12441 Parklawn Dr, Rockville, MD 20852 USA. EM jcoligan@niaid.nih.gov OI Masilamani, Madhan/0000-0001-8181-8848; Peruzzi, Giovanna/0000-0002-6517-9107 FU Division of Intramural Research, NIAID/NIH; Jaffe Food Allergy Institute, Mount Sinai School of Medicine FX This work is supported by funds from the Division of Intramural Research, NIAID/NIH to J. E. C., Intramural program, FDA to F. B. and by the Jaffe Food Allergy Institute, Mount Sinai School of Medicine to M. M. We would like to thank Dr Konrad Krzewski for his critical reading of the review. NR 173 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-9219 J9 TRAFFIC JI Traffic PD DEC PY 2009 VL 10 IS 12 BP 1735 EP 1744 DI 10.1111/j.1600-0854.2009.00973.x PG 10 WC Cell Biology SC Cell Biology GA 518ST UT WOS:000271714300002 PM 19719476 ER PT J AU Gubernot, DM Nakhasi, HL Mied, PA Asher, DM Epstein, JS Kumar, S AF Gubernot, Diane M. Nakhasi, Hira L. Mied, Paul A. Asher, David M. Epstein, Jay S. Kumar, Sanjai TI Transfusion-transmitted babesiosis in the United States: summary of a workshop SO TRANSFUSION LA English DT Editorial Material ID APHERESIS PLATELETS; PATHOGEN REDUCTION; ULTRAVIOLET-LIGHT; BLOOD-TRANSFUSION; SEROLOGIC TEST; MICROTI; DIAGNOSIS; PARASITEMIA; HUMANS; IDENTIFICATION AB Infections of humans with intraerythrocytic parasites of the genus Babesia can be locally prevalent in diverse regions of the United States. Transfusion of blood and blood products collected from donors infected with Babesia may result in a serious illness that can be fatal. In September 2008, the Food and Drug Administration organized a public workshop to discuss the various aspects of transfusion-transmitted babesiosis in the United States including the possible strategies to identify and defer blood donors who may have been infected with Babesia. Discussions were also held on the biology, pathogenesis, and epidemiology of Babesia species. In this article, we summarize the scientific presentations and panel discussions that took place during the workshop. C1 [Gubernot, Diane M.; Nakhasi, Hira L.; Mied, Paul A.; Asher, David M.; Epstein, Jay S.; Kumar, Sanjai] US FDA, OBRR, CBER, Rockville, MD 20852 USA. RP Kumar, S (reprint author), US FDA, OBRR, CBER, 1401 Rockville Pike, Rockville, MD 20852 USA. EM sanjai.kumar@fda.hhs.gov NR 30 TC 36 Z9 38 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD DEC PY 2009 VL 49 IS 12 BP 2759 EP 2771 DI 10.1111/j.1537-2995.2009.02429.x PG 13 WC Hematology SC Hematology GA 527CT UT WOS:000272344900027 PM 19821952 ER PT J AU Meyer, CR Armato, SG Fenimore, CP McLennan, G Bidaut, LM Barboriak, DP Gavrielides, MA Jackson, EF McNitt-Gray, MF Kinahan, PE Petrick, N Zhao, BS AF Meyer, Charles R. Armato, Samuel G., III Fenimore, Charles P. McLennan, Geoffrey Bidaut, Luc M. Barboriak, Daniel P. Gavrielides, Marios A. Jackson, Edward F. McNitt-Gray, Michael F. Kinahan, Paul E. Petrick, Nicholas Zhao, Binsheng TI Quantitative Imaging to Assess Tumor Response to Therapy: Common Themes of Measurement, Truth Data, and Error Sources SO TRANSLATIONAL ONCOLOGY LA English DT Article ID HIGH-RESOLUTION MEASUREMENT; FUNCTIONAL DIFFUSION MAP; TRACER BOLUS PASSAGES; SOLID TUMORS; BLOOD-FLOW; END-POINTS; RESPIRATORY MOTION; PULMONARY NODULES; RECIST CRITERIA; CONSORTIUM LIDC AB RATIONALE: Early detection of tumor response to therapy is a key goal. Finding measurement algorithms capable of early detection of tumor response could individualize therapy treatment as well as reduce the cost of bringing new drugs to market. On an individual basis, the urgency arises from the desire to prevent continued treatment of the patient with a high-cost and/or high-risk regimen with no demonstrated individual benefit and rapidly switch the patient to an alternative efficacious therapy for that patient. In the context of bringing new drugs to market, such algorithms could demonstrate efficacy in much smaller populations, which would allow phase 3 trials to achieve statistically significant decisions with fewer subjects in shorter trials. MATERIALS AND METHODS: This consensus-based article describes multiple, image modality-independent means to assess the relative performance of algorithms for measuring tumor change in response to therapy. In this setting, we describe specifically the example of measurement of tumor volume change from anatomic imaging as well as provide an overview of other promising generic analytic methods that can be used to assess change in heterogeneous tumors. To support assessment of the relative performance of algorithms for measuring small tumor change, data sources of truth are required. RESULTS: Very short interval clinical imaging examinations and phantom scans provide known truth for comparative evaluation of algorithms. CONCLUSIONS: For a given category of measurement methods, the algorithm that has the smallest measurement noise and least bias on average will perform best in early detection of true tumor change. C1 [Meyer, Charles R.] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Armato, Samuel G., III] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Fenimore, Charles P.] Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. [McLennan, Geoffrey] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. [Bidaut, Luc M.; Jackson, Edward F.] UT MD Anderson Canc Ctr, Dept Imaging Phys, Houston, TX USA. [Barboriak, Daniel P.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. [Gavrielides, Marios A.; Petrick, Nicholas] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [McNitt-Gray, Michael F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol, Los Angeles, CA 90095 USA. [Kinahan, Paul E.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Zhao, Binsheng] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. RP Meyer, CR (reprint author), A522 Biomed Sci Res Bldg,109 Zina Pitcher Pl, Ann Arbor, MI 48109 USA. EM cmeyer@umich.edu OI Kinahan, Paul/0000-0001-6461-3306; Bidaut, Luc/0000-0001-8253-2606; Jackson, Edward/0000-0002-5958-0076; McNItt-Gray, Michael/0000-0003-3004-4613 FU National Cancer Institute, National Institutes of Health [N01-CO-12400] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. NR 66 TC 35 Z9 35 U1 0 U2 6 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1936-5233 J9 TRANSL ONCOL JI Transl. Oncol. PD DEC PY 2009 VL 2 IS 4 BP 198 EP 210 DI 10.1593/tlo.09208 PG 13 WC Oncology SC Oncology GA 529XD UT WOS:000272551800002 PM 19956379 ER PT J AU McNitt-Gray, MF Bidaut, LM Armato, SG Meyer, CR Gavrielides, MA Fenimore, C McLennan, G Petrick, N Zhao, BS Reeves, AP Beichel, R Kim, HJ Kinnard, L AF McNitt-Gray, Michael F. Bidaut, Luc M. Armato, Samuel G., III Meyer, Charles R. Gavrielides, Marios A. Fenimore, Charles McLennan, Geoffrey Petrick, Nicholas Zhao, Binsheng Reeves, Anthony P. Beichel, Reinhard Kim, Hyun-Jung (Grace) Kinnard, Lisa TI Computed Tomography Assessment of Response to Therapy: Tumor Volume Change Measurement, Truth Data, and Error SO TRANSLATIONAL ONCOLOGY LA English DT Article ID SMALL PULMONARY NODULES; CELL LUNG-CANCER; IMAGE-DATABASE; CONSORTIUM LIDC; SOLID TUMORS; CT SCANS; THORACIC CT; VARIABILITY; RESOURCE; SEGMENTATION AB RATIONALE AND OBJECTIVES: This article describes issues and methods that are specific to the measurement of change in tumor volume as measured from computed tomographic (CT) images and how these would relate to the establishment of CT tumor volumetrics as a biomarker of patient response to therapy. The primary focus is on the measurement of lung tumors, but the approach should be generalizable to other anatomic regions. MATERIALS AND METHODS: The first issues addressed are the various sources of bias and variance in the measurement of tumor volumes, which are discussed in the context of measurement variation and its impact on the early detection of response to therapy. RESULTS AND RESOURCES: Research that seeks to identify the magnitude of some of these sources of error is ongoing, and several of these efforts are described herein. In addition, several resources for these investigations are being made available through the National Institutes of Health-funded Reference Image Database to Evaluate Response to therapy in cancer project, and these are described as well. Other measures derived from CT image data that might be predictive of patient response are described briefly, as well as the additional issues that each of these metrics may encounter in real-life applications. CONCLUSIONS: The article concludes with a brief discussion of moving from the assessment of measurement variation to the steps necessary to establish the efficacy of a metric as a biomarker for response. C1 [McNitt-Gray, Michael F.; Kim, Hyun-Jung (Grace)] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol, Los Angeles, CA 90095 USA. [Bidaut, Luc M.] UT MD Anderson Canc Ctr, Dept Imaging Phys, Div Diagnost Imaging, Houston, TX USA. [Armato, Samuel G., III] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Meyer, Charles R.; Petrick, Nicholas; Kinnard, Lisa] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Gavrielides, Marios A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Fenimore, Charles] Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. [McLennan, Geoffrey] Univ Iowa, Sch Med, Dept Internal Med, Iowa City, IA 52242 USA. [Zhao, Binsheng] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. [Reeves, Anthony P.] Cornell Univ, Sch EECS, Ithaca, NY USA. [Beichel, Reinhard] Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA. RP McNitt-Gray, MF (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Suite 650,924 Westwood Blvd, Los Angeles, CA 90095 USA. EM mmcnittgray@mednet.ucla.edu OI Bidaut, Luc/0000-0001-8253-2606; McNItt-Gray, Michael/0000-0003-3004-4613 FU National Cancer Institute, National Institutes of Health [N01-CO-12400, HHSN261200800001E] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contracts N01-CO-12400 and HHSN261200800001E. NR 26 TC 31 Z9 32 U1 0 U2 3 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1936-5233 J9 TRANSL ONCOL JI Transl. Oncol. PD DEC PY 2009 VL 2 IS 4 BP 216 EP 222 DI 10.1593/tlo.09226 PG 7 WC Oncology SC Oncology GA 529XD UT WOS:000272551800004 PM 19956381 ER PT J AU Rupprecht, CE Briggs, D Brown, CM Franka, R Katz, SL Kerr, HD Lett, S Levis, R Meltzer, MI Schaffner, W Cieslak, PR AF Rupprecht, Charles E. Briggs, Deborah Brown, Catherine M. Franka, Richard Katz, Samuel L. Kerr, Harry D. Lett, Susan Levis, Robin Meltzer, Martin I. Schaffner, William Cieslak, Paul R. TI Evidence for a 4-dose vaccine schedule for human rabies post-exposure prophylaxis in previously non-vaccinated individuals SO VACCINE LA English DT Article DE Rabies; Reduced vaccination schedules; Post-exposure prophylaxis ID POST-EXPOSURE PROPHYLAXIS; NEUTRALIZING ANTIBODY; IMMUNE GLOBULIN; UNITED-STATES; IMMUNOGENICITY; VIRUS; PATHOGENESIS; PROTECTION; SERUM; PREEXPOSURE AB After exposure, human rabies is preventable by prompt application of post-exposure prophylaxis. Historically, the total number of rabies vaccine doses administered during human prophylaxis has decreased, as modern biologics have improved and scientific knowledge has grown. A review of the literature on rabies virus pathogenesis, experimental animal studies, clinical trials, epidemiological surveillance, and economic analyses was conducted to determine the potential utility of reducing the current 5-dose intramuscular series of human rabies vaccine administered in the United States. Based upon the available evidence, a reduced schedule of cell-culture rabies vaccine, administered on days 0, 3, 7, and 14, given in conjunction with rabies immune globulin, was supported and recommended by the United States Advisory Committee on Immunization Practices. Published by Elsevier Ltd. C1 [Rupprecht, Charles E.; Franka, Richard] Natl Ctr Zoonot Vector Borne & Enter Dis, Atlanta, GA 30333 USA. [Briggs, Deborah] Kansas State Univ, Manhattan, KS 66506 USA. [Brown, Catherine M.; Lett, Susan] Massachusetts Dept Publ Hlth, Jamaica Plain, MA USA. [Katz, Samuel L.] Duke Univ, Med Ctr, Durham, NC USA. [Kerr, Harry D.] Amer Coll Emergency Phys, Dallas, TX USA. [Levis, Robin] US FDA, Washington, DC 20204 USA. [Meltzer, Martin I.] CDC, Natl Ctr Preparedness Detect & Control Infect Dis, Atlanta, GA 30333 USA. [Schaffner, William] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Cieslak, Paul R.] Oregon Dept Publ Hlth, Corvallis, OR USA. RP Rupprecht, CE (reprint author), Natl Ctr Zoonot Vector Borne & Enter Dis, 1600 Clifton Rd NE,MS G33, Atlanta, GA 30333 USA. EM cyr5@cdc.gov NR 70 TC 35 Z9 37 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD NOV 27 PY 2009 VL 27 IS 51 BP 7141 EP 7148 DI 10.1016/j.vaccine.2009.09.029 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 532FL UT WOS:000272731100002 PM 19925944 ER PT J AU Woodcock, J AF Woodcock, Janet TI A Difficult Balance - Pain Management, Drug Safety, and the FDA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Woodcock, J (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 4 TC 73 Z9 74 U1 2 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 26 PY 2009 VL 361 IS 22 BP 2105 EP 2107 DI 10.1056/NEJMp0908913 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 524BC UT WOS:000272117800001 PM 19940297 ER PT J AU Mathis, LL Pica-Branco, D Tassinari, MS AF Mathis, Lisa L. Pica-Branco, Denise Tassinari, Melissa S. TI Improving Access to FDA Reviews and Documents SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Mathis, Lisa L.; Pica-Branco, Denise; Tassinari, Melissa S.] US FDA, Silver Spring, MD USA. RP Mathis, LL (reprint author), US FDA, Silver Spring, MD USA. EM lisa.mathis@fda.hhs.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 25 PY 2009 VL 302 IS 20 BP 2204 EP 2205 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 523NI UT WOS:000272080500022 PM 19934419 ER PT J AU Lugovtsev, VY Smith, DF Weir, JP AF Lugovtsev, Vladimir Y. Smith, David F. Weir, Jerry P. TI Changes of the receptor-binding properties of influenza B virus B/Victoria/504/2000 during adaptation in chicken eggs SO VIROLOGY LA English DT Article DE Influenza B virus; Receptor binding; Egg adaptation, Glycan array ID SIALO-SUGAR CHAINS; HOST-CELL; GLYCOSYLATION SITE; AMINO-ACID; SPECIFICITY; HEMAGGLUTININ; GANGLIOSIDES; RECOGNITION; GROWTH; SIALYLOLIGOSACCHARIDES AB Selection of high-growth virus variants of strain B/Victoria/504/2000 by serial passage in eggs resulted in three amino acid substitutions, G141E, R162M, and D196Y, in the vicinity of the receptor-binding pocket of viral hemagglutinin. Virus variants containing the identified amino acid substitutions, individually or in various combinations, were constructed using reverse genetics and analyzed for their receptor-binding properties using glycan microarray platform. Three different patterns of virus binding were revealed. A low-growth virus variant, corresponding to the original egg-derived virus B/Victoria/504/2000 prior to acquisition of amino acid changes G141E, R162M, and D196Y, had a clear preference for the oligosaccharide chains terminated with alpha 2-6-linked sialic acid with very weak binding of the glycans terminated with alpha 2-3-linked sialic acid. Amino acid substitutions R162M and D196Y had similar effects, resulting in viruses that bound with high efficiency almost all terminally sialylated glycans represented on the array regardless of the type of glycosidic linkage. In contrast, substitution of G141E alone, or in combinations with the other two amino acid substitutions, significantly restricted virus glycan-binding capabilities. All virus variants possessing this substitution lost the ability to bind glycans with alpha 2-6 glycosidic linkage as well as most of the glycans with alpha 2-3 glycosidic linkage. Linear penta- and heptasaccharide chains represented at the non-reducing end by alpha 2-3 sialylated Type-II motif (LacNAc) were the only structures bound with high affinity by the virus variants with G141E substitution. In all cases when the effects on virus binding of individual amino acid substitutions differed, the effect of R162M was subordinate to the effect of either G141E or D196Y. Published by Elsevier Inc. C1 [Lugovtsev, Vladimir Y.; Weir, Jerry P.] US FDA, Lab Resp Viruses, Div Viral Prod, Off Vaccines Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Smith, David F.] Emory Univ, Sch Med, Dept Biochem, O Wayne Rollins Res Ctr, Atlanta, GA 30322 USA. [Smith, David F.] Consortium Funct Glyc Core H, Atlanta, GA 30322 USA. RP Lugovtsev, VY (reprint author), US FDA, Lab Resp Viruses, Div Viral Prod, Off Vaccines Res & Review,Ctr Biol Evaluat & Res, 8800 Rockville Pike,Bldg 29A,Room 2B17, Bethesda, MD 20892 USA. EM vladimir.lugovtsev@fda.hhs.gov NR 47 TC 15 Z9 15 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 25 PY 2009 VL 394 IS 2 BP 218 EP 226 DI 10.1016/j.virol.2009.08.014 PG 9 WC Virology SC Virology GA 521MC UT WOS:000271924500006 PM 19766280 ER PT J AU Pfefer, TJ Mehrabi, A James, R Landry, R Weininger, S Chang, I Kaufman, D Miller, S AF Pfefer, T. Joshua Mehrabi, Ali James, Robert Landry, Robert Weininger, Sandy Chang, Isaac Kaufman, Diana Miller, Sharon TI Optical-thermal characterization of cutaneous transilluminators SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID NEONATAL INTENSIVE-CARE; TRANS-ILLUMINATION; COLD LIGHT; BURNS; SAFETY; SKIN; VENIPUNCTURE; RADIATION; INFANTS; INJURY AB In recent years, there has been an increase in the popularity of light-emitting diode (LED)-based, battery-powered transilluminators (BPTs) for facilitating transdermal vascular access in adults and neonates. BPTs are believed to have lower potential for inducing skin burns than prior devices based on high-power broadband lamps; however, the optical and thermal outputs of BPTs are not well documented and safety limits for these devices are not well established. In this study, we characterize and assess the optical and thermal outputs of six BPTs that incorporate red, orange and white LEDs. Optical measurements included spectral irradiance and peak local irradiance. Thermal measurements included transient temperature readings for an exposure time of 4 min in ambient air and ex vivo tissue pre-heated to physiological temperatures. The greatest mean temperature rise produced in tissue by a non-white-light diode BPT was 2.5 degrees C, whereas a mean temperature rise of 9.1 degrees C was measured in a BPT that incorporated white-light diodes with relatively high irradiance levels. The dominant cause of temperature rise was most likely heat generation within the devices. Thermal damage analyses based on temperature limits and the Arrhenius equation indicate that although some of the devices studied approach the threshold for damage, none appear to exceed it under normal operating conditions. The results demonstrated that ambient air measurements may be suitable for identifying worst-case BPT temperatures. This study highlights the potential risk of LED-based medical devices as well as the need for additional research on related issues such as neonatal thermal injury thresholds. C1 [Pfefer, T. Joshua; Mehrabi, Ali; James, Robert; Landry, Robert; Weininger, Sandy; Chang, Isaac; Kaufman, Diana; Miller, Sharon] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Pfefer, TJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM joshua.pfefer@fda.hhs.gov RI Pfefer, Josh/I-9055-2012 NR 35 TC 4 Z9 4 U1 0 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD NOV 21 PY 2009 VL 54 IS 22 BP 6867 EP 6880 DI 10.1088/0031-9155/54/22/008 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 515EB UT WOS:000271448600008 PM 19864700 ER PT J AU Khan, M Cockrell, E Espinola, R Bartholomew, JR McCrae, KR AF Khan, Mohammad Cockrell, Erin Espinola, Ricardo Bartholomew, John R. McCrae, Keith R. TI Elevated Levels of Tissue Factor Bearing Microparticles in Patients with Antiphospholipid Antibodies: Analysis of Fresh, Unfrozen Samples SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Khan, Mohammad; McCrae, Keith R.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Cockrell, Erin] Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. [Espinola, Ricardo] US FDA, CBER, Div Hematol, Rockville, MD 20857 USA. [Bartholomew, John R.] Cleveland Clin, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 20 PY 2009 VL 114 IS 22 BP 68 EP 68 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725800149 ER PT J AU Goldin, LR Lanasa, MC Slager, SL Strom, SS Camp, NJ Cerhan, JR Spector, LG Leis, JF Morrison, VA Rassenti, LZ Rabe, K Fontaine, L Allgood, SD Abbasi, F Kay, NE Call, TG Hanson, CA Weinberg, B Marti, GE Caporaso, NE AF Goldin, Lynn R. Lanasa, Mark C. Slager, Susan L. Strom, Sara S. Camp, Nicola J. Cerhan, James R. Spector, Logan G. Leis, Jose F. Morrison, Vicki A. Rassenti, Laura Z. Rabe, Kari Fontaine, Laura Allgood, Sallie D. Abbasi, Fatima Kay, Neil E. Call, Timothy G. Hanson, Curtis A. Weinberg, Brice Marti, Gerald E. Caporaso, Neil E. TI Monoclonal B-Cell Lymphocytosis is Commonly Observed Among Unaffected Members of High Risk CLL Families SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Goldin, Lynn R.] NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. [Lanasa, Mark C.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Slager, Susan L.; Cerhan, James R.] Mayo Clin, Coll Med, Rochester, MN USA. [Strom, Sara S.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Camp, Nicola J.] Univ Utah, Salt Lake City, UT USA. [Spector, Logan G.] Univ Minnesota, Minneapolis, MN USA. [Leis, Jose F.] Mayo Clin Arizona, Phoenix, AZ USA. [Morrison, Vicki A.] VA Med Ctr, Minneapolis, MN USA. [Rassenti, Laura Z.] Moores UCSD Canc Ctr, CLL Res Consortium, La Jolla, CA USA. [Fontaine, Laura] Westat Corp, Rockville, MD USA. [Abbasi, Fatima] Food & Drug Adm, Cellular & Tissue Therapy Branch, Rockville, MD USA. [Weinberg, Brice] Duke Med Ctr, Durham, NC USA. [Weinberg, Brice] VA Med Ctr, Durham, NC USA. [Marti, Gerald E.] US FDA, CBER, Cellular & Tissue Therapy Branch, Rockville, MD 20857 USA. [Caporaso, Neil E.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 20 PY 2009 VL 114 IS 22 BP 508 EP 508 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725801412 ER PT J AU Ketha, KMV Rao, SS Atreya, CD AF Ketha, Krishna Mohan V. Rao, Shilpakala Sainath Atreya, Chintamani D. TI Activated Platelet-Derived Antimicrobial Peptides Exhibit Virucidal Properties against Vaccinia Virus in Plasma SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Ketha, Krishna Mohan V.; Rao, Shilpakala Sainath; Atreya, Chintamani D.] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 20 PY 2009 VL 114 IS 22 BP 835 EP 835 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725802486 ER PT J AU Kannan, M Kulkarni, S Atreya, CD AF Kannan, Meganathan Kulkarni, Sandhya Atreya, Chintamani D. TI Apoptotic Microrna Profiling of Packed Red Blood Cells During Storage SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Kannan, Meganathan; Kulkarni, Sandhya; Atreya, Chintamani D.] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 20 PY 2009 VL 114 IS 22 BP 1222 EP 1222 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725803700 ER PT J AU Sainath, S Ketha, KMV Atreya, CD AF Sainath, Shilpakala Ketha, Krishna Mohan V. Atreya, Chintamani D. TI Phage-Displayed Peptide-Q Dot Nanocrystal Combo for High-Sensitivity Bacterial Detection in Plasma SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Sainath, Shilpakala; Ketha, Krishna Mohan V.; Atreya, Chintamani D.] US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 20 PY 2009 VL 114 IS 22 BP 1224 EP 1224 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725803708 ER PT J AU Konduru, K Nakamura, SM Kaplan, GG AF Konduru, Krishnamurthy Nakamura, Siham M. Kaplan, Gerardo G. TI Hepatitis A virus (HAV) packaging size limit SO VIROLOGY JOURNAL LA English DT Article ID RIBOSOME ENTRY SITE; MONKEY KIDNEY-CELLS; CAPSID PROTEIN VP1; INTERNAL INITIATION; IMMUNE GLOBULIN; RNA TRANSCRIPTS; HIV GP41; IN-VITRO; TRANSLATION; POLYPROTEIN AB Background: Hepatitis A virus (HAV), an atypical Picornaviridae that causes acute hepatitis in humans, grows poorly in cell culture and in general does not cause cytopathic effect. Foreign sequences have been inserted into different parts of the HAV genome. However, the packaging size limit of HAV has not been determined. The purpose of the present study is to investigate the maximum size of additional sequences that the HAV genome can tolerate without loosing infectivity. Results: In vitro T7 polymerase transcripts of HAV constructs containing a 456-nt fragment coding for a blasticidin (Bsd) resistance gene, a 1,098-nt fragment coding for the same gene fused to GFP (GFP-Bsd), or a 1,032-nt fragment containing a hygromycin (Hyg) resistance gene cloned into the 2A-2B junction of the HAV genome were transfected into fetal Rhesus monkey kidney (FRhK4) cells. After antibiotic selection, cells transfected with the HAV construct containing the resistance gene for Bsd but not the GFP-Bsd or Hyg survived and formed colonies. To determine whether this size limitation was due to the position of the insertion, a 606 bp fragment coding for the Encephalomyocarditis virus (EMCV) internal ribosome entry site (IRES) sequence was cloned into the 5' nontranslated (NTR) region of HAV. The resulting HAV-IRES retained the EMCV IRES insertion for 1-2 passages. HAV constructs containing both the EMCV IRES at the 5' NTR and the Bsd-resistance gene at the 2A-2B junction could not be rescued in the presence of Bsd but, in the absence of antibiotic, the rescued viruses contained deletions in both inserted sequences. Conclusion: HAV constructs containing insertions of approximately 500-600 nt but not 1,000 nt produced viable viruses, which indicated that the HAV particles can successfully package approximately 600 nt of additional sequences and maintain infectivity. C1 [Konduru, Krishnamurthy; Nakamura, Siham M.; Kaplan, Gerardo G.] US FDA, Lab Hepatitis & Related Emerging Agents, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Kaplan, GG (reprint author), US FDA, Lab Hepatitis & Related Emerging Agents, Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM Krishnamurthy.konduru@fda.hhs.gov; Siham.naakamura@fda.hhs.gov; gk@helix.nih.gov FU FDA; Oak Ridge Institute for Science and Education; U. S. Department of Energy; U. S. Food and Drug Administration FX We thank Susan Zullo for critical review of the manuscript. The work was supported by FDA intramural funding to GGK. This project was supported in part by the appointment of SMN 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. All authors read and approved the final manuscript. NR 35 TC 1 Z9 1 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD NOV 18 PY 2009 VL 6 AR 204 DI 10.1186/1743-422X-6-204 PG 8 WC Virology SC Virology GA 526OK UT WOS:000272300300003 PM 19922643 ER PT J AU Nie, L AF Nie, Lei TI Re: "Methods of Covariate Selection: Directed Acyclic Graphs and the Change-in-Estimate Procedure" SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 US FDA, Div Biometr 4, Off Biometr, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Nie, L (reprint author), US FDA, Div Biometr 4, Off Biometr, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM lei.nie@fda.hhs.gov FU PHS HHS [RSR-09-14] 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 15 PY 2009 VL 170 IS 10 BP 1320 EP 1320 DI 10.1093/aje/kwp267 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 514FN UT WOS:000271379800016 PM 19720864 ER PT J AU Fujisawa, T Joshi, B Nakajima, A Puri, RK AF Fujisawa, Toshio Joshi, Bharat Nakajima, Atsushi Puri, Raj K. TI A Novel Role of Interleukin-13 Receptor alpha 2 in Pancreatic Cancer Invasion and Metastasis SO CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE PATHWAYS; PSEUDOMONAS EXOTOXIN; MATRIX METALLOPROTEINASES; SIGNAL-TRANSDUCTION; IN-VIVO; CELLS; CHAIN; EXPRESSION; FIBROSIS; TARGET AB Whereas interleukin-13 receptor alpha 2 chain (IL-13R alpha 2) is over-expressed in a variety of human solid cancers including pancreatic cancer, we investigated its significance in cancer invasion and metastasis. We used two pancreatic cancer cell lines, IL-13R alpha 2-negative HPAF-H and IL-13R alpha 2-positive HS766T, and generated IL-13Ra2 stably transfected HPAF-II as well as IL-13Ra2 RNA interference knocked-down HS766T cells. Ability of invasion and signal transduction was compared between IL-13R alpha 2-negative and IL-13R alpha 2-positive cells and tumor metastasis was assessed in murine model for human pancreatic cancer with orthotopic implantation of tumors. IL-13 treatment enhanced cell invasion in IL13R alpha 2-positive cancer cell lines but not in IL-13R alpha 2-negative cell lines. Furthermore, gene transfer of IL-13R alpha 2 in negative cell lines enhanced invasion, whereas its silencing downmodulated invasion of pancreatic cell lines in a Matrigel invasion assay. In vivo study revealed that II-13R alpha 2-positive cancer metastasized to lymph nodes, liver, and peritoneum at. a significantly higher rate compared with IL-13R alpha 2-negative tumors. The expression of IL-13R alpha 2 in metastatic lesions was found to be increased compared with primary tumors, and mice with IL-13R alpha 2-positive cancer displayed cachexia and poor prognosis. Invasion and metastasis also correlated with increased matrix metalloproteinase protease activity in these cells. Mechanistically, IL-13 activated extracellular signal-regulated kinase 1/2 and activator protein-1 nuclear factors in IL-13R alpha 2-positive pancreatic cancer cell lines but not in IL-13R alpha 2-negative cell lines. Taken together, our results show for the first time that IL-13 can signal through IL-13R alpha 2 in pancreatic cancer cells and IL-13Ra2 may serve as a prognostic biomarker of invasion and metastasis in pancreatic cancer. [Cancer Res 2009;69(22):8678-85] C1 [Fujisawa, Toshio; Joshi, Bharat; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Nakajima, Atsushi] Yokohama City Univ, Sch Med, Div Gastroenterol, Yokohama, Kanagawa 232, Japan. RP Puri, RK (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN20 HFM 735,29 Lincoln Dr, Bethesda, MD 20892 USA. EM raj.puri@fda.hhs.gov NR 35 TC 47 Z9 53 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2009 VL 69 IS 22 BP 8678 EP 8685 DI 10.1158/0008-5472.CAN-09-2100 PG 8 WC Oncology SC Oncology GA 520JC UT WOS:000271839200020 PM 19887609 ER PT J AU Shaikh, B Rummel, N Gieseker, C Cheely, CS Reimschuessel, R AF Shaikh, Badar Rummel, Nathan Gieseker, Charles Cheely, Christie-Sue Reimschuessel, Renate TI Residue depletion of albendazole and its metabolites in the muscle tissue of large mouth and hybrid striped bass after oral administration SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Aquaculture; Hybrid striped bass; Large mouth bass; HPLC; Residue depletion; Metabolism ID GROWTH AB The residue depletion profiles of albendazole (ABZ) and its major metabolites: albendazole sulfoxide (ABZ-SO), albendazole sulfone (ABZ-SO(2)) and albendazole aminosulfone (ABZ-2-NH(2)SO(2)) were studied in the muscle tissues of large mouth (LMB) and hybrid striped bass (HSB). A single oral dose of 10 mg/kg albendazole was given to the two fish species via infra-gastric tube. The muscle tissues with adhering skin were collected at 8, 16, 24, 48, 72, 96 and 120 h post dose from both species. The samples were homogenized in dry ice and subjected to extraction and cleanup procedures. The final sample extracts were analyzed by high performance liquid chromatography. The results indicate that both ABZ and its pharmacologically active metabolite ABZ-SO were retained longer in LMB than in HSB after oral treatment. Albendazole was detectable until 8 h or 6.7 degree days (degrees D) and 48h (40 degrees D) in HSB and LMB, respectively. However, ABZ-SO was detectable up to 48 h (40 degrees D) and 96 h (80 degrees D) in HSB and LMB, respectively. Among the inactive metabolites, ABZ-SO(2) was present in both fish species; however. ABZ-2-NH(2)SO(2) was detected only in LMB. Published by Elsevier B.V. C1 [Shaikh, Badar; Rummel, Nathan; Gieseker, Charles; Cheely, Christie-Sue; Reimschuessel, Renate] 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 13 TC 2 Z9 4 U1 0 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD NOV 13 PY 2009 VL 1216 IS 46 BP 8173 EP 8176 DI 10.1016/j.chroma.2009.04.009 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 517AT UT WOS:000271585800021 PM 19406409 ER PT J AU Smith, S Gieseker, C Reimschuessel, R Decker, CS Carson, MC AF Smith, Shani Gieseker, Charles Reimschuessel, Renate Decker, Christie-Sue Carson, Mary C. TI Simultaneous screening and confirmation of multiple classes of drug residues in fish by liquid chromatography-ion trap mass spectrometry SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Salmon; Trout; Catfish; Tilapia; Drug residues; Confirmation; Ion trap mass spectrometry ID VETERINARY DRUGS; LC-MS/MS; MULTICLASS; MILK AB LC-ion trap mass spectrometry was used to screen and confirm 38 compounds from a variety of drug classes in four species of fish: trout, salmon, catfish, and tilapia. Samples were extracted with acetonitrile and hexane. The acetonitrile phase was evaporated, redissolved in water and acetonitrile, and analyzed by gradient chromatography on a phenyl column. MS(2) or MS(3) spectra were monitored for each compound. Qualitative method performance was evaluated by the analysis over several days of replicate samples of control fish, fish fortified with a drug mixture at 1 ppm, 0.1 ppm and 0.01 ppm, and fish dosed with a representative from each drug class. Half of the 38 drugs were confirmed at 0.01 ppm, the lowest fortification level. This included all of the quinolones and fluoroquinolones, the macrolides, malachite green, and most of the imidazoles. Florfenicol amine, metronidazole, sulfonamides, tetracyclines, and most of the betalactams were confirmed at 0.1 ppm. Ivermectin and penicillin G were only detectable in the 1 ppm fortified samples. With the exception of amoxicillin, emamectin, metronidazole, and tylosin, residue presence was confirmed in all the dosed fish. Published by Elsevier B.V. C1 [Smith, Shani; Gieseker, Charles; Reimschuessel, Renate; Decker, Christie-Sue; Carson, Mary C.] US FDA, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. RP Carson, MC (reprint author), US FDA, Res Off, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM mary.carson@fda.hhs.gov NR 15 TC 32 Z9 35 U1 2 U2 23 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD NOV 13 PY 2009 VL 1216 IS 46 BP 8224 EP 8232 DI 10.1016/j.chroma.2009.06.077 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 517AT UT WOS:000271585800028 PM 19616215 ER PT J AU Niu, M Ball, R AF Niu, Manette Ball, Robert TI Adverse events after anthrax vaccination reported to the Vaccine Adverse Event Reporting System (VAERS), 1990-2007 [Vaccine 2009;27:290-297] SO VACCINE LA English DT Letter C1 [Niu, Manette] US FDA, Vaccine Safety Branch, Div Epidemiol, Off Biostat & Epidemiol,Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Niu, M (reprint author), US FDA, Vaccine Safety Branch, Div Epidemiol, Off Biostat & Epidemiol,Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-222, Rockville, MD 20852 USA. EM manette.niu@fda.hhs.gov NR 0 TC 1 Z9 1 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 NOV 12 PY 2009 VL 27 IS 48 BP 6654 EP 6655 DI 10.1016/j.vaccine.2009.08.027 PG 2 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 523QF UT WOS:000272088700003 PM 19716457 ER PT J AU Budnitz, DS Lewis, LL Shehab, N Birnkrant, D AF Budnitz, Daniel S. Lewis, Linda L. Shehab, Nadine Birnkrant, Debra TI Risk of Confusion in Dosing Tamiflu Oral Suspension in Children SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Budnitz, Daniel S.; Shehab, Nadine] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Lewis, Linda L.; Birnkrant, Debra] US FDA, Rockville, MD 20857 USA. RP Budnitz, DS (reprint author), Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. EM dbudnitz@cdc.gov NR 5 TC 1 Z9 2 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 5 PY 2009 VL 361 IS 19 BP 1913 EP 1914 DI 10.1056/NEJMc0909190 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 514OZ UT WOS:000271405800031 PM 19797275 ER PT J AU Price, GE Soboleski, MR Lo, CY Misplon, JA Pappas, C Houser, KV Tumpey, TM Epstein, SL AF Price, Graeme E. Soboleski, Mark R. Lo, Chia-Yun Misplon, Julia A. Pappas, Claudia Houser, Katherine V. Tumpey, Terrence M. Epstein, Suzanne L. TI Vaccination focusing immunity on conserved antigens protects mice and ferrets against virulent H1N1 and H5N1 influenza A viruses SO VACCINE LA English DT Article DE Influenza; Immunization; Heterosubtypic immunity; DNA vaccine; Prime-boost; Recombinant adenovirus; Cold-adapted; H5N1; Pandemic; Vaccine; Ferret; Mice; Intranasal; Systemic; Intramuscular ID CD8(+) T-CELLS; MATRIX PROTEIN-2; IN-VIVO; HETEROSUBTYPIC IMMUNITY; SELECTIVE EXPRESSION; MONOCLONAL-ANTIBODY; DNA VACCINES; M2 PROTEIN; MEMORY; RESPONSES AB Immunization against conserved virus components induces broad, heterosubtypic protection against diverse influenza A viruses, providing a strategy for controlling unexpected outbreaks or pandemics until strain-matched vaccines become available. This study characterized immunization to nucleoprotein (NP) and matrix 2 (M2) by DNA priming followed by parenteral or mucosal boosting in mice and ferrets. DNA vaccination followed by boosting with antigen-matched recombinant adenovirus (rAd) or cold-adapted (ca) influenza virus provided robust protection against virulent H1N1 and H5N1 challenges. Compared to other boosts, mucosal rAd induced stronger IgA responses, more virus-specific activated T-cells in the lung, and better protection against morbidity following challenge even eight months post-boost. In ferrets, both mucosal and parenteral rAd boosting protected from lethal H5N1 challenge. These findings demonstrate potent protection by vaccination highly focused on conserved antigens and identify immune response measures in mice that differed among vaccinations and correlated with outcome. Published by Elsevier Ltd. C1 [Price, Graeme E.; Soboleski, Mark R.; Lo, Chia-Yun; Misplon, Julia A.; Epstein, Suzanne L.] US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Rockville, MD 20852 USA. [Pappas, Claudia; Houser, Katherine V.; Tumpey, Terrence M.] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. RP Epstein, SL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Rockville, MD 20852 USA. EM suzanne.epstein@fda.hhs.gov FU FDA; National Vaccine Program Office; Office of Public Health Emergency Medical Countermeasures; CBER Pandemic Influenza Initiative FX This work is funded by FDA, the National Vaccine Program Office, the Office of Public Health Emergency Medical Countermeasures, and the CBER Pandemic Influenza Initiative. NR 48 TC 79 Z9 82 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 NOV 5 PY 2009 VL 27 IS 47 BP 6512 EP 6521 DI 10.1016/j.vaccine.2009.08.053 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 523FA UT WOS:000272056300004 PM 19729082 ER PT J AU Lemtouni, S DeFelice, A Uhl, K Willard, J AF Lemtouni, Selma DeFelice, Albert Uhl, Kathleen Willard, James TI Enrollment of Women and Ethnic Minorities and Their Drop-out Profiles: More Than a Quarter of a Century Experience (1973-2001) in Antihypertensive Drug Trials SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Lemtouni, Selma; DeFelice, Albert; Uhl, Kathleen; Willard, James] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S498 EP S499 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501008 ER PT J AU Muniyappa, R Chen, H Muzumdar, RH Einstein, FH Yan, X Yue, LQ Barzilai, N Quon, MJ AF Muniyappa, Ranganath Chen, Hui Muzumdar, Radhika H. Einstein, Francine H. Yan, Xu Yue, Lilly Q. Barzilai, Nir Quon, Michael J. TI Comparison between surrogate indexes of insulin sensitivity/resistance and hyperinsulinemic euglycemic clamp estimates in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE glucose clamp; calibration model; quantitative insulin-sensitivity check index ID HOMEOSTASIS MODEL ASSESSMENT; TYPE-2 DIABETIC-PATIENTS; FASTING PLASMA-GLUCOSE; BETA-CELL FUNCTION; CHECK INDEX; CARDIOVASCULAR-DISEASE; RECIPROCAL INDEX; VISCERAL FAT; RESISTANCE; MICE AB Muniyappa R, Chen H, Muzumdar RH, Einstein FH, Yan X, Yue LQ, Barzilai N, Quon MJ. Comparison between surrogate indexes of insulin sensitivity/resistance and hyperinsulinemic euglycemic clamp estimates in rats. Am J Physiol Endocrinol Metab 297: E1023-E1029, 2009. First published August 25, 2009; doi: 10.1152/ajpendo.00397.2009.-Assessing insulin resistance in rodent models gives insight into mechanisms that cause type 2 diabetes and the metabolic syndrome. The hyperinsulinemic euglycemic glucose clamp, the reference standard for measuring insulin sensitivity in humans and animals, is labor intensive and technically demanding. A number of simple surrogate indexes of insulin sensitivity/resistance have been developed and validated primarily for use in large human studies. These same surrogates are also frequently used in rodent studies. However, in general, these indexes have not been rigorously evaluated in animals. In a recent validation study in mice, we demonstrated that surrogates have a weaker correlation with glucose clamp estimates of insulin sensitivity/resistance than in humans. This may be due to increased technical difficulties in mice and/or intrinsic differences between human and rodent physiology. To help distinguish among these possibilities, in the present study, using data from rats substantially larger than mice, we compared the clamp glucose infusion rate (GIR) with surrogate indexes, including QUICKI, HOMA, 1/HOMA, log (HOMA), and 1/fasting insulin. All surrogates were modestly correlated with GIR (r = 0.34-0.40). Calibration analyses of surrogates adjusted for body weight demonstrated similar predictive accuracy for GIR among all surrogates. We conclude that linear correlations of surrogate indexes with clamp estimates and predictive accuracy of surrogate indexes in rats are similar to those in mice (but not as substantial as in humans). This additional rat study (taken with the previous mouse study) suggests that application of surrogate insulin sensitivity indexes developed for humans may not be appropriate for determining primary outcomes in rodent studies due to intrinsic differences in metabolic physiology. However, use of surrogates may be appropriate in rodents, where feasibility of clamps is an obstacle and measurement of insulin sensitivity is a secondary outcome. C1 [Muniyappa, Ranganath; Chen, Hui; Quon, Michael J.] NIH, Diabet Unit, NCCAM, Bethesda, MD 20892 USA. [Yan, Xu; Yue, Lilly Q.] US FDA, Div Biostat, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Muzumdar, Radhika H.; Einstein, Francine H.; Barzilai, Nir] Albert Einstein Coll Med, Inst Aging Res, Bronx, NY 10467 USA. [Muzumdar, Radhika H.; Einstein, Francine H.; Barzilai, Nir] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. RP Quon, MJ (reprint author), NIH, Diabet Unit, NCCAM, 9 Mem Dr,Bldg 9,Rm 1N-105 MSC 0920, Bethesda, MD 20892 USA. EM quonm@nih.gov RI Muzumdar, Radhika/D-9860-2014; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 FU Intramural Research Program; National Center for Complementary and Alternative Medicine; National Institutes of Health [K08-AG-027462, P60-DK-20541, R01-AG-18381, T32-AG-23475, P01-AG-021654]; Albert Einstein Diabetes Research and Training Center [P60-DK-20541] FX This work was supported by the Intramural Research Program, the National Center for Complementary and Alternative Medicine, and grants from the National Institutes of Health (K08-AG-027462 and P60-DK-20541 to R. H. Muzumdar; R01-AG-18381, T32-AG-23475, and P01-AG-021654 to N. Barzilai) and the Core Laboratories of the Albert Einstein Diabetes Research and Training Center (P60-DK-20541). NR 30 TC 25 Z9 26 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD NOV PY 2009 VL 297 IS 5 BP E1023 EP E1029 DI 10.1152/ajpendo.00397.2009 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 509CL UT WOS:000270990500007 PM 19706785 ER PT J AU Arguello, DF Gonzalez-Zeno, G Irizarry-Perez, EB Ramos, M Quinones, L Rivera, A Luxemburger, C Jusot, V Munoz, J Hunsperger, E Sun, W Tomashek, KM AF Argueello, D. Fermin Gonzalez-Zeno, Gladys Irizarry-Perez, E. Brian Ramos, Mary Quinones, Luz Rivera, Aidsa Luxemburger, Christine Jusot, Viviane Munoz, Jorge Hunsperger, Elizabeth Sun, Wellington Tomashek, Kay M. TI WHAT IS ENHANCED SURVEILLANCE? DESCRIPTION OF AN ENHANCE DENGUE SURVEILLANCE SYSTEM MODEL - THE PATILLAS ENHANCED DENGUE SURVEILLANCE SYSTEM (PEDSS), PATILLAS PUERTO RICO SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Argueello, D. Fermin; Gonzalez-Zeno, Gladys; Irizarry-Perez, E. Brian; Quinones, Luz; Rivera, Aidsa; Munoz, Jorge; Hunsperger, Elizabeth; Tomashek, Kay M.] Ctr Dis Control & Prevent, San Juan, PR USA. [Ramos, Mary] Univ New Mexico, Dept Pediat, Albuquerque, NM 87131 USA. [Luxemburger, Christine; Jusot, Viviane] Sanofi Pasteur, Lyon, France. [Sun, Wellington] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 354 BP 101 EP 101 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700354 ER PT J AU Ostera, GR Lukat-Rodgers, G Tokumasu, F Kumar, S Rodgers, K AF Ostera, Graciela R. Lukat-Rodgers, Gudrun Tokumasu, Fuyuki Kumar, Sanjai Rodgers, Kenton TI ASSOCIATION OF NITRIC OXIDE WITH HEME IN PLASMODIUM FALCIPARUM FOOD VACUOLES SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Ostera, Graciela R.; Tokumasu, Fuyuki] NIH, Rockville, MD USA. [Lukat-Rodgers, Gudrun; Rodgers, Kenton] N Dakota State Univ, Fargo, ND 58105 USA. [Kumar, Sanjai] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 844 BP 243 EP 243 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701259 ER PT J AU Whitaker, TB Trucksess, MW Weaver, CM Slate, A AF Whitaker, Thomas B. Trucksess, Mary W. Weaver, Carol M. Slate, Andrew TI Sampling and analytical variability associated with the determination of aflatoxins and ochratoxin A in bulk lots of powdered ginger marketed in 1-lb bags SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE Aflatoxin; Ochratoxin A; Ginger; Sampling and analytical variability; Sampling; Foods/beverages; Quality assurance/control ID PART I; VARIANCE-COMPONENTS; GINSENG; HERBS; UK AB Ginger has been used as a food, dietary supplement, and condiment for centuries. Mycotoxins such as the aflatoxins (AF) and ochratoxin A (OTA) have been reported in ginger roots in several studies. It is important to design effective sampling methods that will accurately and precisely predict the true mycotoxin level in a bulk lot. The objective of this study was to measure the sampling and analytical variability associated with the test procedure used to measure AF and OTA in a bulk lot of powdered ginger using a 5-g laboratory sample and HPLC analytical methods. Twelve 5-g laboratory samples were taken from each of two lots. Duplicate aliquots were removed from each 5-g laboratory sample/solvent blend, and each aliquot was simultaneously analyzed for AF and OTA by HPLC analytical methods. Using a balanced nested design, the total variance associated with the above AF and OTA test procedures was partitioned into sampling and analytical variance components for each lot. Averaged across both lots, the sampling and analytical variances accounted for 87% and 13% of the total variance, respectively, for AF and 97% and 3%, respectively, for OTA. The sampling and analytical coefficients of variation were 9.5% and 3.6%, respectively, for AF, and 16.6% and 2.9%, respectively, for OTA when using a single 5-g laboratory sample and HPLC analytical methods. Equations are derived to show the effect of increasing laboratory sample size and/or number of aliquots on reducing the variability of the test procedures used to estimate OTA and AF in powdered ginger. C1 [Whitaker, Thomas B.] N Carolina State Univ, USDA, ARS, Raleigh, NC 27695 USA. [Trucksess, Mary W.; Weaver, Carol M.] US FDA, College Pk, MD 20740 USA. RP Whitaker, TB (reprint author), N Carolina State Univ, USDA, ARS, POB 7625, Raleigh, NC 27695 USA. EM Tom_Whitaker@ncsu.edu FU Office of Dietary Supplements, National Institute of Health, Bethesda, MD, USA FX This work was supported in part by the Office of Dietary Supplements, National Institute of Health, Bethesda, MD, USA. NR 19 TC 13 Z9 13 U1 2 U2 7 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 EI 1618-2650 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD NOV PY 2009 VL 395 IS 5 BP 1291 EP 1299 DI 10.1007/s00216-009-2880-z PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 507ZY UT WOS:000270897000011 PM 19529924 ER PT J AU Silverman, TA Weiskopf, RB AF Silverman, Toby A. Weiskopf, Richard B. CA Planning Comm Speakers TI Hemoglobin-based Oxygen Carriers Current Status and Future Directions SO ANESTHESIOLOGY LA English DT Article ID CROSS-LINKED HEMOGLOBIN; HUMAN POLYMERIZED HEMOGLOBIN; RECOMBINANT HUMAN HEMOGLOBIN; CELL-FREE HEMOGLOBIN; INTRAOPERATIVE AUTOLOGOUS DONATION; REDUCE TRANSFUSION REQUIREMENTS; TRAUMATIC HEMORRHAGIC-SHOCK; ABDOMINAL AORTIC-ANEURYSM; ACUTE ISCHEMIC-STROKE; BYPASS GRAFT-SURGERY C1 [Silverman, Toby A.] US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Weiskopf, Richard B.] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. RP Silverman, TA (reprint author), US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, 1401 Rockville Pike,Suite 400N, Rockville, MD 20852 USA. EM toby.silverman@fda.hhs.gov NR 91 TC 48 Z9 54 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 2009 VL 111 IS 5 BP 946 EP 963 PG 18 WC Anesthesiology SC Anesthesiology GA 511NN UT WOS:000271172500006 PM 19858869 ER PT J AU Shord, SS Bressler, LR Villano, JL AF Shord, Stacy S. Bressler, Linda R. Villano, J. Lee TI Comment: Evaluation of the Modified Diet in Renal Disease Equation for Calculation of Carboplatin Dose Reply SO ANNALS OF PHARMACOTHERAPY LA English DT Letter C1 [Shord, Stacy S.] Univ Illinois, Coll Pharm MC 886, Chicago, IL 60607 USA. [Bressler, Linda R.] Univ Illinois, Coll Pharm, Chicago, IL USA. [Villano, J. Lee] Univ Illinois, Coll Med, Chicago, IL USA. RP Shord, SS (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Div Clin Pharmacol 5, Silver Spring, MD USA. EM stacy.shord@fda.hhs.gov NR 2 TC 0 Z9 0 U1 0 U2 0 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD NOV PY 2009 VL 43 IS 11 BP 1915 EP 1915 DI 10.1345/aph.IL446b PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 515QE UT WOS:000271486500029 ER PT J AU Willey, JZ Xu, Q Boden-Albala, B Paik, MC Moon, YP Sacco, RL Elkind, MSV AF Willey, Joshua Z. Xu, Qiang Boden-Albala, Bernadette Paik, Myunghee C. Moon, Yeseon Park Sacco, Ralph L. Elkind, Mitchell S. V. TI Lipid Profile Components and Risk of Ischemic Stroke The Northern Manhattan Study (NOMAS) SO ARCHIVES OF NEUROLOGY LA English DT Article ID DENSITY-LIPOPROTEIN-CHOLESTEROL; TREATMENT PANEL-III; CAROTID ATHEROSCLEROSIS; HEART-DISEASE; NONFASTING TRIGLYCERIDES; MYOCARDIAL-INFARCTION; CEREBROVASCULAR-DISEASE; SERUM-CHOLESTEROL; STATIN THERAPY; LOW HDL AB Objective: To explore the relationship between lipid profile components and incident ischemic stroke in a stroke-free prospective cohort. Design: Population-based prospective cohort study. Setting: Northern Manhattan, New York. Patients: Stroke-free community residents. Intervention: As part of the Northern Manhattan Study, baseline fasting blood samples were collected on stroke-free community residents followed up for a mean of 7.5 years. Main Outcome Measures: Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals for lipid profile components and ischemic stroke after adjusting for demographic and risk factors. In secondary analyses, we used repeated lipid measures over 5 years from a 10% sample of the population to calculate the change per year of each of the lipid parameters and to impute time-dependent lipid parameters for the full cohort. Results: After excluding those with a history of myocardial infarction, 2940 participants were available for analysis. Baseline high-density lipoprotein cholesterol, triglyceride, and total cholesterol levels were not associated with risk of ischemic stroke. Low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol levels were associated with a paradoxical reduction in risk of stroke. There was an interaction with use of cholesterol-lowering medication on follow-up, such that LDL-C level was only associated with a reduction in stroke risk among those taking medications. An LDL-C level greater than 130 mg/dL as a time-dependent covariate showed an increased risk of ischemic stroke (adjusted hazard ratio, 3.81; 95% confidence interval, 1.53-9.51). Conclusions: Baseline lipid panel components were not associated with an increased stroke risk in this cohort. Treatment with cholesterol-lowering medications and changes in LDL-C level over time may have attenuated the risk in this population, and lipid measurements at several points may be a better marker of stroke risk. C1 [Willey, Joshua Z.; Boden-Albala, Bernadette; Moon, Yeseon Park; Elkind, Mitchell S. V.] Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. [Boden-Albala, Bernadette] Columbia Univ, Joseph P Mailman Sch Publ Hlth, Dept Sociomed Sci, New York, NY USA. [Paik, Myunghee C.] Columbia Univ, Joseph P Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA. [Willey, Joshua Z.; Boden-Albala, Bernadette; Moon, Yeseon Park; Elkind, Mitchell S. V.] Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY USA. [Xu, Qiang] US FDA, Rockville, MD 20857 USA. [Sacco, Ralph L.] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. RP Elkind, MSV (reprint author), Neurol Inst, 710 W 168th St, New York, NY 10032 USA. EM mse13@columbia.edu RI Boden Albala, Bernadette/J-5703-2013 OI Boden Albala, Bernadette/0000-0001-5664-2342 FU National Institutes of Health/National Institute of Neurological Disorders and Stroke [R37 NS 29993]; National Institute of Neurological Disorders and Stroke [T32 NS 07153] FX Funding for this project was provided by National Institutes of Health/National Institute of Neurological Disorders and Stroke grant R37 NS 29993. Dr Willey was funded by National Institute of Neurological Disorders and Stroke grant T32 NS 07153. NR 41 TC 32 Z9 34 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD NOV PY 2009 VL 66 IS 11 BP 1400 EP 1406 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 517AF UT WOS:000271584400015 PM 19901173 ER PT J AU Rider, LG Lachenbruch, PA Monroe, JB Ravelli, A Cabalar, I Feldman, BM Villalba, ML Myones, BL Pachman, LM Rennebohm, RM Reed, AM Miller, FW AF Rider, Lisa G. Lachenbruch, Peter A. Monroe, Jason B. Ravelli, Angelo Cabalar, Imelda Feldman, Brian M. Villalba, Maria L. Myones, Barry L. Pachman, Lauren M. Rennebohm, Robert M. Reed, Ann M. Miller, Frederick W. CA IMACS Grp TI Damage Extent and Predictors in Adult and Juvenile Dermatomyositis and Polymyositis as Determined With the Myrositis Damage Index SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; IDIOPATHIC INFLAMMATORY MYOPATHIES; COLLABORATING-CLINICS/AMERICAN-COLLEGE; 3 ETHNIC-GROUPS; MULTICENTER COHORT; INITIAL VALIDATION; DISEASE-ACTIVITY; CHILDHOOD-ONSET; RISK-FACTORS; ASSOCIATION AB Objective. We undertook this study to validate the Myositis Damage Index (MDI) in juvenile and adult myositis, to describe the degree and types of damage and to develop predictors of damage. Methods. Retrospective MDI evaluations and prospective assessment of disease activity and illness features were conducted. Patients with juvenile-onset disease (n = 143) were evaluated a median of 18 months after diagnosis; 135 patients were assessed 7-9 months later, and 121 were last assessed a median of 82 months after diagnosis. Ninety-six patients with adult-onset dermatomyositis or polymyositis had a baseline assessment a median of 30 months after diagnosis; 77 patients had a 6-month followup evaluation, and 55 had a final assessment a median of 60 months after diagnosis. Results. Damage was present in 79% of juvenile patients and in 97% of adult patients. In juveniles, scarring, contractures, persistent weakness, muscle dysfunction, and calcinosis were most frequent (23-30%) at the last evaluation. In adults, muscle atrophy, muscle dysfunction, and muscle weakness were most frequent (74-84%). MDI severity correlated with physician-assessed global damage, serum creatinine, and muscle atrophy on magnetic resonance imaging, and in juveniles also with functional disability and weakness. MDI damage scores and frequency were highest in patients with a chronic illness course and in adult patients who died. Predictors of damage included functional disability, duration of active disease, disease severity at diagnosis, physician-assessed global disease activity, and illness features, including ulcerations in children and pericarditis in adults. Conclusion. Damage is common in myositis after a median duration of 5 years in patients with adult-onset disease and 6.8 years in patients with juvenile-onset disease. The MDI has good content, construct, and predictive validity in juvenile and adult myositis. C1 [Rider, Lisa G.] Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, NIH, Bethesda, MD 20892 USA. [Lachenbruch, Peter A.] Oregon State Univ, Corvallis, OR 97331 USA. [Ravelli, Angelo] Univ Genoa, Genoa, Italy. [Ravelli, Angelo] IRCCS G Gaslini, Genoa, Italy. [Cabalar, Imelda] NIAMS, NIH, Bethesda, MD USA. [Feldman, Brian M.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Feldman, Brian M.] Univ Toronto, Toronto, ON, Canada. [Villalba, Maria L.] FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Myones, Barry L.] Texas Childrens Hosp, Houston, TX 77030 USA. [Myones, Barry L.] Baylor Coll Med, Houston, TX 77030 USA. [Pachman, Lauren M.] Childrens Mem Hosp, Chicago, IL 60614 USA. [Pachman, Lauren M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Rennebohm, Robert M.] Columbus Childrens Hosp, Columbus, OH 43205 USA. [Rennebohm, Robert M.] Ohio State Univ, Columbus, OH USA. [Reed, Ann M.] Mayo Clin, Rochester, MN USA. RP Rider, LG (reprint author), Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, NIH, CRC 4-2332,MSC 1301,10 Ctr Dr, Bethesda, MD 20892 USA. EM riderl@mail.nih.gov RI Feldman, Brian/A-8586-2011; Harris-Love, Michael/J-1359-2014; RAVELLI, ANGELO/J-8161-2016; OI Harris-Love, Michael/0000-0002-1842-3269; RAVELLI, ANGELO/0000-0001-9658-0385; Rider, Lisa/0000-0002-6912-2458 FU National Institute of Environmental Health Sciences; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH [1R-21-AR-048349-01]; Cure JM Foundation; Arthritis Foundation FX Supported in part by the intramural research programs of the National Institute of Environmental Health Sciences and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH. Dr. Lachenbruch's work was supported in part by a grant from the Cure JM Foundation. Dr. Pachman's work was supported in part by a grant from the Arthritis Foundation. The work of Dr. Reed and that of contributors from the International Myositis Assessment and Clinical Studies Group who are not employed by the US government was supported by the NIH (NIAMS grant 1R-21-AR-048349-01). NR 35 TC 40 Z9 44 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD NOV PY 2009 VL 60 IS 11 BP 3425 EP 3435 DI 10.1002/art.24904 PG 11 WC Rheumatology SC Rheumatology GA 519QF UT WOS:000271781400032 PM 19877055 ER PT J AU Yang, CH Valerio, LG Arvidson, KB AF Yang, Chihae Valerio, Luis G., Jr. Arvidson, Kirk B. TI Computational Toxicology Approaches at the US Food and Drug Administration SO ATLA-ALTERNATIVES TO LABORATORY ANIMALS LA English DT Article DE computational toxicology; database; knowledgebase; QSAR; risk assessment; safety assessment; SAR ID TOXICITY HAZARD IDENTIFICATION; COMPREHENSIVE MODEL; GENETIC TOXICITY; MDL-QSAR; E-STATE; DATABASES; CHEMICALS; RODENTS; PHARMACEUTICALS; PREDICTION AB For over a decade, the United States Food and Drug Administration (US FDA) has been engaged in the applied research, development, and evaluation of computational toxicology methods used to support the safety evaluation of a diverse set of regulated products. The basis for evaluating computational toxicology methods is multi-factorial, including the potential for increased efficiency, reduction in the numbers of animals used, lower costs, and the need to explore emerging technologies that support the goals of the US FDA's Critical Path Initiative (e.g. to make decision support information available early in the drug review process). The US FDA's efforts have been facilitated by agency-approved data-sharing agreements between government and commercial software developers. This commentary review describes former and current scientific initiatives at the agency, in the area of computational toxicology methods. In particular, toxicology-based QSAR models, ToxML databases and knowledgebases will be addressed. Notably, many of the computational toxicology tools available are commercial products - however, several are emerging as non-commercial products, which are freely-available to the public, and which will facilitate the understanding of how these programs work and avoid the "black box" paradigm. Through productive collaborations, the US FDA Center for Drug Evaluation and Research, and the Center for Food Safety and Applied Nutrition, have worked together to evaluate, develop and apply these methods to chemical toxicity endpoints of regulatory interest. C1 [Yang, Chihae; Arvidson, Kirk B.] US FDA, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Valerio, Luis G., Jr.] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Yang, CH (reprint author), US FDA, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, HFS 275,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM chihae.yang@fda.hhs.gov FU CFSAN OFAS FX The authors thank Molecular Networks for making their MOSES chemoinformatics library freely available for public use, and for making a portion of their ADRIANA.CODE available for the OFAS knowledgebase. The authors also acknowledge the members and management of the ICSAS and SAR groups at the FDA CDER and CFSAN, respectively, as well as the toxicologists at the CFSAN OFAS for their continued support of the development and use of QSARs within the US FDA. NR 32 TC 22 Z9 23 U1 0 U2 4 PU FRAME PI NOTTINGHAM PA RUSSELL & BURCH HOUSE 96-98 NORTH SHERWOOD ST, NOTTINGHAM NG1 4EE, NOTTS, ENGLAND SN 0261-1929 J9 ATLA-ALTERN LAB ANIM JI ATLA-Altern. Lab. Anim. PD NOV PY 2009 VL 37 IS 5 BP 523 EP 531 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 537BA UT WOS:000273086600017 PM 20017581 ER PT J AU DeMuth, JE Arnold, ME Booth, BP Fluhler, E Grant, R Hayes, M Huggins, T Ji, QC Turk, D AF DeMuth, James E. Arnold, Mark E. Booth, Brian P. Fluhler, Eric Grant, Russell Hayes, Michael Huggins, Thomas Ji, Qin C. Turk, Douglas TI 10th Annual University of Wisconsin Land O'Lakes Bioanalytical Conference SO BIOANALYSIS LA English DT Editorial Material AB This conference was arranged by the Extension Services in Pharmacy at the University of Wisconsin School of Pharmacy. The purpose of this annual 4-day conference is to provide an educational forum to discuss issues and applications associated with the analysis of xenobiotics and metabolites in biological matrices. The conference is designed to include and encourage an open exchange of scientific and methodological applications for bioanalysis. To increase the interactive nature of the conference, the program will be a mixture of lectures, poster sessions, round table discussions and workshops. This paper summarizes the presentations at the Tenth Annual Conference. C1 [DeMuth, James E.] Univ Wisconsin, Madison, WI 53705 USA. [Arnold, Mark E.; Ji, Qin C.] Bristol Myers Squibb Co, New Brunswick, NJ USA. [Booth, Brian P.] US FDA, Ctr Drug Res & Evaluat, Silver Spring, MD USA. [Fluhler, Eric] Wyeth Res, Pearl River, NY USA. [Grant, Russell] LabCorp, Burlington, NC USA. [Hayes, Michael] Novartis Pharmaceut, E Hanover, NJ USA. [Huggins, Thomas] Procter & Gamble Co, Mason, OH USA. [Turk, Douglas] NoAb BioDiscoveries Inc, Mississauga, ON, Canada. RP DeMuth, JE (reprint author), Univ Wisconsin, 777 Highland Ave, Madison, WI 53705 USA. EM jedemuth@pharmacy.wisc.edu OI Arnold, Mark/0000-0002-6961-433X NR 0 TC 1 Z9 1 U1 0 U2 0 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 J9 BIOANALYSIS JI Bioanalysis PD NOV PY 2009 VL 1 IS 8 BP 1397 EP 1401 DI 10.4155/BIO.09.125 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 644VN UT WOS:000281409900010 PM 21083088 ER PT J AU Schofield, T Krause, PR AF Schofield, Timothy Krause, Philip R. TI Stability evaluation of vaccines SO BIOLOGICALS LA English DT Editorial Material C1 [Schofield, Timothy] GlaxoSmithKline Biol, King Of Prussia, PA USA. [Krause, Philip R.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Schofield, T (reprint author), GlaxoSmithKline Biol, 2301 Renaissance Blvd,POB 61540, King Of Prussia, PA USA. EM timothy.l.schofield@gsk.com; philip.krause@fda.hhs.gov OI Krause, Philip/0000-0002-1045-7536 NR 0 TC 2 Z9 2 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD NOV PY 2009 VL 37 IS 6 BP 355 EP 355 DI 10.1016/j.biologicals.2009.09.001 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 528JM UT WOS:000272440200001 PM 19783158 ER PT J AU Krause, PR AF Krause, Philip R. TI Goals of stability evaluation throughout the vaccine life cycle SO BIOLOGICALS LA English DT Article; Proceedings Paper CT 57th Meeting of the WHO-Expert-Committee on Biological Standardization CY OCT 23-27, 2006 CL Geneva, SWITZERLAND SP WHO Expert Comm DE Potency; Development; Licensure; Monitoring; Manufacturing changes AB Stability studies play a critical role in assuring product quality at all points in the vaccine life cycle. At and after licensure, stability studies on quality attributes (including potency) provide a critical link between marketed and clinically evaluated vaccine product, addressing important regulatory concerns by assuring that product quality is maintained throughout the dating period. During development, stability studies are done to assure product quality and to obtain the data needed to support licensure. Stability studies may also be performed after licensure to assure that product continues to perform as it did pre-licensure, as well as to evaluate the effect on product quality of deliberately introduced manufacturing changes. At each phase in the product life cycle, it is important to consider the goals of stability evaluation and to perform appropriate statistical analyses in order to assure and reach appropriate conclusions about product quality. Published by Elsevier Ltd on behalf of The International Association for Biologicals. C1 US FDA, CBER, OVRR, DVP, Bethesda, MD 20892 USA. RP Krause, PR (reprint author), US FDA, CBER, OVRR, DVP, 29A 1C16,29 Lincoln Dr, Bethesda, MD 20892 USA. EM Philip.krause@fda.hhs.gov OI Krause, Philip/0000-0002-1045-7536 NR 8 TC 5 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD NOV PY 2009 VL 37 IS 6 BP 369 EP 378 DI 10.1016/j.biologicals.2009.08.015 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 528JM UT WOS:000272440200005 PM 19775911 ER PT J AU Smith, D Duchene, M Egan, W Jivapaisarnpong, T Knezevic, I Pierard, I Schofield, T Shin, JH Southern, J Krause, PR AF Smith, Dean Duchene, Michel Egan, William Jivapaisarnpong, Teeranart Knezevic, Ivana Pierard, Isabelle Schofield, Timothy Shin, Jinho Southern, James Krause, Philip R. TI Model format for a vaccine stability report and software solutions Panel discussion SO BIOLOGICALS LA English DT Editorial Material C1 [Smith, Dean; Duchene, Michel; Egan, William; Jivapaisarnpong, Teeranart; Knezevic, Ivana; Pierard, Isabelle; Schofield, Timothy; Shin, Jinho; Southern, James; Krause, Philip R.] US FDA, CBER, Bethesda, MD 20892 USA. RP Krause, PR (reprint author), US FDA, CBER, 29 Lincoln Dr, Bethesda, MD 20892 USA. EM philip.krause@fda.hhs.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD NOV PY 2009 VL 37 IS 6 BP 421 EP 423 DI 10.1016/j.biologicals.2009.08.005 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 528JM UT WOS:000272440200015 ER PT J AU Riordan, WT Heilmann, SM Brorson, K Seshadri, K Etzel, MR AF Riordan, William T. Heilmann, Steven M. Brorson, Kurt Seshadri, Kannan Etzel, Mark R. TI Salt Tolerant Membrane Adsorbers for Robust Impurity Clearance SO BIOTECHNOLOGY PROGRESS LA English DT Article DE membrane adsorbers; anion exchange chromatography; antibody purification; viral clearance; impurity removal ID SCALE ANTIBODY PURIFICATION; ION-EXCHANGE CHROMATOGRAPHY; PLASMID DNA; VIRUS; PERFORMANCE; BACTERIOPHAGES; ADSORPTION; CAPTURE; SYSTEMS; FILTERS AB Clearance of impurities such as viruses, host cell protein (HCP), and DNA is a critical purification design consideration for manufacture of monoclonal antibody therapeutics. Anion exchange chromatography has frequently been utilized to accompolish this goal; however, anion exchange adsorbents based on the traditional quaternary amine (Q) ligand are sensitive to salt concentration, leading to reduced clearance levels of impurities at moderate salt concentrations (50-150 mM). In this report, membrane adsorbers incorporating four alternative salt tolerant anion exchange ligands were examined for impurity clearance: agmatine. tris-2-aminoethyl amine, polyhexamethylene biguanide (PHMB), and polyethyleneimine. Each of these ligands provided greater than 5 log reduction value (LRV) for viral clearance of phage Phi X174 (pI similar to 6.7) at pH 7.5 and phage PR772 (pI similar to 4) at pH 4.2 in the presence of salt. Under these same conditions, the commercial Q membrane adsorber provided no clearance (zero LRV). Clearance of host-cell protein at pH 7.5 was the most challenging test case; only PHMB maintained 1.5 LRV in 150 mM salt. The salt tolerance of PHMB was attributed to its large positive net charge through the presence of multiple biguanide groups that participated in electrostatic and hydrogen bonding interactions with the impurity molecules. On the basis of the results of this study, membrane adsorbers that incorporate salt tolerant anion exchange ligands provide a robust approach to impurity clearance during the purification of monoclonal antibodies. (C) 2009 American Institute of Chemical Engineers Biotechnol. Prog., 25: 1695-1702, 2009 C1 [Riordan, William T.; Etzel, Mark R.] Univ Wisconsin, Dept Chem & Biol Engn, Madison, WI 53706 USA. [Heilmann, Steven M.; Seshadri, Kannan] 3M Co, Mat Res Lab, St Paul, MN 55144 USA. [Brorson, Kurt] CDER FDA, Div Monoclonal Antibodies, Silver Spring, MD 20903 USA. RP Etzel, MR (reprint author), Univ Wisconsin, Dept Chem & Biol Engn, Madison, WI 53706 USA. EM etzel@engr.wisc.edu NR 41 TC 17 Z9 17 U1 2 U2 24 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD NOV-DEC PY 2009 VL 25 IS 6 BP 1695 EP 1702 DI 10.1002/btpr.256 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 537ZA UT WOS:000273152000018 PM 19728393 ER PT J AU da Costa, GG Singh, R Arlt, VM Mirza, A Richards, M Takamura-Enya, T Schmeiser, HH Farmer, PB Phillips, DH AF da Costa, Goncalo Gamboa Singh, Rajinder Arlt, Volker M. Mirza, Amin Richards, Meirion Takamura-Enya, Takeji Schmeiser, Heinz H. Farmer, Peter B. Phillips, David H. TI Quantification of 3-Nitrobenzanthrone-DNA Adducts Using Online Column-Switching HPLC-Electrospray Tandem Mass Spectrometry SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID AIR-POLLUTANT 3-NITROBENZANTHRONE; ENVIRONMENTAL CONTAMINANT 3-NITROBENZANTHRONE; LUNG EPITHELIAL-CELLS; FORMS DNA-ADDUCTS; LIQUID-CHROMATOGRAPHY; METABOLIC-ACTIVATION; DIESEL EXHAUST; MUTAGEN 3-NITROBENZANTHRONE; INTRATRACHEAL INSTILLATION; HUMAN ACETYLTRANSFERASES AB The aromatic nitroketone 3-nitrobenzanthrone (3-nitro-7H-benz[de]anthracen-7-one; 3-NBA) is an extremely potent mutagen and a suspected human carcinogen detected in the exhaust of diesel engines and in airborne particulate matter. 3-NBA is metabolically activated via reduction of the nitro group to the hydroxylamine (N-OH-3-ABA) to form covalent DNA adducts. Thus far, the detection and quantification of covalent 3-NBA-DNA adducts has relied solely on (32)P-postlabeling methodologies. In order to expand the range of available techniques for the detection and improved quantification of 3-NBA-DNA adducts, we have developed a method based upon online column-switching HPLC coupled to electrospray tandem mass spectrometry, with isotopic dilution of (15)N-labeled internal standards. This methodology was applied to the determination of three 3-NBA-derived adducts: 2-(2'-deoxyguanosin-N(2)-yl)-3-aminobenzanthrone (dG-N(2)-3-ABA), N-(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone (dG-C8-N-3-ABA) and 2-(2'-deoxyguanosine-8-yl)-3-aminobenzanthrone (dG-C8-C2-3-ABA). Dose-dependent increases were observed for all three adducts when salmon testis DNA was reacted with N-acetoxy-3-aminobenzanthrone (N-AcO-3-ABA). dG-C8-C2-3-ABA was detected at much lower levels (overall 1%) than the other two adducts. DNA samples isolated from tissues of rats treated either intratracheally with 3-NBA or intraperitoneally with N-OH-3-ABA were analyzed by mass spectrometry, and the results compared to those obtained by (32)P-postlabeling. The method required 50 mu g of hydrolyzed animal DNA on column and the limit of detection was 2.0 fmol for each adduct. dG-C8-C2-3-ABA was not observed in any of the samples providing confirmation that it is not formed in vivo. Linear regression analysis of the levels of dG-N(2)-3-ABA and dG-C8-N-3-ABA in the rat DNA showed a reasonable correlation between the two methods (R(2) = 0.88 and 0.93, respectively). In summary, the mass spectrometric method is a faster, more automated analytical approach that also provides structural confirmation of the adducts detected by (32)P-postlabeling, and it has sufficient sensitivity and precision to analyze DNA adducts in animals exposed to 3-NBA or its hydroxylamine metabolite. C1 [da Costa, Goncalo Gamboa; Arlt, Volker M.; Phillips, David H.] Inst Canc Res, Sect Mol Carcinogenesis, Sutton SM2 5NG, Surrey, England. [Singh, Rajinder; Farmer, Peter B.] Univ Leicester, Dept Canc Studies & Mol Med, Bioctr, Canc Biomarkers & Prevent Grp, Leicester LE1 7RH, Leics, England. [Mirza, Amin; Richards, Meirion] Inst Canc Res, Canc Res UK Ctr Canc Therapeut, Sutton SM2 5NG, Surrey, England. [Takamura-Enya, Takeji] Kanagawa Inst Technol, Dept Appl Chem, Atsugi, Kanagawa 2430292, Japan. [Schmeiser, Heinz H.] German Canc Res Ctr, Res Grp Genet Alterat Carcinogenesis, D-69120 Heidelberg, Germany. RP da Costa, GG (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT 110,3900 NCTR Rd, Jefferson, AR 72079 USA. EM goncalo.gamboa@fda.hhs.gov RI Singh, Raj/A-5398-2011; OI Phillips, David/0000-0001-8509-3485; Arlt, Volker Manfred/0000-0003-4314-9318 FU Cancer Research UK; European Union Network of Excellence ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility [FOOD-CT-2005-513943]; Medical Research Council [G0100873] FX The authors acknowledge financial support from Cancer Research UK and from the European Union Network of Excellence ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility, www.ecnis.org, Contract No. FOOD-CT-2005-513943), and from the Medical Research Council (Grant No. G0100873). The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration. NR 44 TC 12 Z9 13 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD NOV PY 2009 VL 22 IS 11 BP 1860 EP 1868 DI 10.1021/tx900264v PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 517YD UT WOS:000271654100015 ER PT J AU Tang, SX Hewlett, IK AF Tang, Shixing Hewlett, Indira K. TI Europium nanoparticle-based immunoassays for sensitive detection of pathogens SO CHIMICA OGGI-CHEMISTRY TODAY LA English DT Article DE Nanoparticle; europium; immunoassay; detection; infectious pathogen ID TIME-RESOLVED FLUORESCENCE; PROSTATE-SPECIFIC ANTIGEN; SIGNAL AMPLIFICATION; ASSAYS; LABEL AB We describe and review the application of europium (Eu(3+)) nanoparticle (NP)-based immunoassays (ENIA) for rapid, sensitive, and quantitative detection of pathogens through antibody-antigen recognition. The extremely intense luminescence of the NPs can be directly detected without the need for enzymatic signal amplification or sample preparation. Incorporation of biotinylated anti-streptavidin (SA) and SA-coated Eu(3+) molecules or tyramide molecules for signal amplification (TSA) results in enhanced signal intensity, and further improves detection sensitivity of ENIAs. Our studies demonstrate that ENIA provides a highly specific, ultrasensitive and relatively simple format for detection of HIV-1 p24 antigen, anthrax toxin, and F1 factor and LcrV antigen of Y. pestis., and has the potential for broad application in clinical diagnosis and laboratory research. C1 [Tang, Shixing; Hewlett, Indira K.] US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Bethesda, MD 20892 USA. RP Tang, SX (reprint author), US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Bldg 29B,Room 4NN16,8800 Rockville Pike, Bethesda, MD 20892 USA. FU Biodefense Advanced Research and Development Agency (BARDA), DHHS; NHLBI; NIAID, NIH FX We wish to acknowledge the Biodefense Advanced Research and Development Agency (BARDA), DHHS for funding and/or supporting. This work was also supported in part by NHLBI and NIAID, NIH. We wish to acknowledge Robert Purcell, Steve Leppla, Karen Meysick and Harri Harma for providing reagents. We thank Eric Y. Wong, Krishna Devadas and Hira Nakhasi for review of the manuscript. The findings and conclusions in this article have not been formally disseminated by the FDA and should not be construed to represent any Agency determination or policy. NR 15 TC 1 Z9 2 U1 1 U2 7 PU TEKNOSCIENZE PUBL PI MILANO PA VIALE BRIANZA 22, 20127 MILANO, ITALY SN 1973-8250 J9 CHIM OGGI JI Chim. Oggi-Chem. Today PD NOV-DEC PY 2009 VL 27 IS 6 BP 50 EP 52 PG 3 WC Biotechnology & Applied Microbiology; Chemistry, Multidisciplinary SC Biotechnology & Applied Microbiology; Chemistry GA 648PQ UT WOS:000281706800011 ER PT J AU Atkinson, AJ Huang, SM AF Atkinson, A. J., Jr. Huang, S-M TI Nephropharmacology: Drugs and the Kidney SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID DISEASE; IMPACT C1 [Atkinson, A. J., Jr.] Northwestern Univ, Feinberg Sch Med, Dept Mol Pharmacol & Biochem, Chicago, IL 60611 USA. [Huang, S-M] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Atkinson, AJ (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Mol Pharmacol & Biochem, Chicago, IL 60611 USA. EM Art_Atkinson@msn.com NR 20 TC 13 Z9 13 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD NOV PY 2009 VL 86 IS 5 BP 453 EP 456 DI 10.1038/clpt.2009.191 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 511SB UT WOS:000271186000001 PM 19844216 ER PT J AU Throckmorton, DC AF Throckmorton, D. C. TI How a US Regulator Can Encourage New Science SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material AB The Center for Drug Evaluation and Research at the US Food and Drug Administration (FDA) is developing a process to qualify biomarkers for use under particular conditions. As part of this effort, Goodsaid et al. have carried out work, described in this issue, on the formal qualification of novel biomarkers of acute renal toxicity in animals. The authors' experiences highlight the importance of collaboration and the role of regulators. C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Throckmorton, DC (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM douglas.throckmorton@fda.hhs.gov NR 3 TC 2 Z9 2 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD NOV PY 2009 VL 86 IS 5 BP 471 EP 472 DI 10.1038/clpt.2009.188 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 511SB UT WOS:000271186000010 PM 19844222 ER PT J AU Huang, SM Temple, R Xiao, S Zhang, L Lesko, LJ AF Huang, S-M Temple, R. Xiao, S. Zhang, L. Lesko, L. J. TI When to Conduct a Renal Impairment Study During Drug Development: US Food and Drug Administration Perspective SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID GLOMERULAR-FILTRATION-RATE; IMPACT AB To optimize drug therapy for individuals, it is critical to understand how various intrinsic (e.g., age, gender, race, genetics, organ impairment) and extrinsic factors (e.g., diet, smoking, concomitantly administered drugs) affect drug exposure and response.(1) Up to now, it has been far easier to discover effects on exposure caused by these factors, and the US Food and Drug Administration (FDA) has published several guidance documents with recommendations on how to evaluate these factors during drug development. C1 [Huang, S-M; Zhang, L.; Lesko, L. J.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Temple, R.] US FDA, Off Med Policy, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Xiao, S.] US FDA, Div Cardiorenal Drug Prod, Off New Drugs, 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 15 TC 56 Z9 57 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 NOV PY 2009 VL 86 IS 5 BP 475 EP 479 DI 10.1038/clpt.2009.190 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 511SB UT WOS:000271186000012 PM 19844224 ER PT J AU Goodsaid, FM Blank, M Dieterle, F Harlow, P Hausner, E Sistare, F Thompson, A Vonderscher, J AF Goodsaid, F. M. Blank, M. Dieterle, F. Harlow, P. Hausner, E. Sistare, F. Thompson, A. Vonderscher, J. TI Novel Biomarkers of Acute Kidney Toxicity SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT News Item ID INJURY MOLECULE-1 KIM-1; PROXIMAL TUBULE INJURY; ACUTE-RENAL-FAILURE; INDUCED NEPHROTOXICITY; URINARY BIOMARKER; DRUG DEVELOPMENT; EXPRESSION; IDENTIFICATION; GENTAMICIN; RATS AB Novel biomarkers of kidney toxicity are powerful tools not only with respect to their clinical applications but also because of their impact on drug development. These biomarkers can influence the assessment of efficacy of new drugs for kidney diseases as well as the risk management for new drugs. The science behind these novel biomarkers reflects the evolution over the past decade of genomic and proteomic platforms that have transformed the discovery and development of new biomarkers for preclinical and clinical applications in drug development. Several of these biomarkers are in use as transcriptomic biomarkers in animal models as well as translational proteomic biomarkers in animal models and in humans. Their ability to detect kidney damage earlier than is possible with currently accessible biomarkers is being given qualification through regulatory biomarker-qualification programs, which will help establish consensus for their widespread use. C1 [Goodsaid, F. M.] US FDA, Genom Grp, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Blank, M.; Harlow, P.; Hausner, E.; Thompson, A.] Ctr Drug Evaluat & Res, Div Cardiovasc & Renal Prod, Off New Drugs, Silver Spring, MD USA. [Dieterle, F.] Novartis Pharma AG, Novartis Inst BioMed Res, Translat Sci, Basel, Switzerland. [Sistare, F.] Merck, Safety Assessment, Lab Sci & Investigat Toxicol, West Point, PA USA. [Vonderscher, J.] Roche, PDL, Basel, Switzerland. RP Goodsaid, FM (reprint author), US FDA, Genom Grp, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM Federico.Goodsaid@fda.hhs.gov NR 36 TC 30 Z9 30 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 NOV PY 2009 VL 86 IS 5 BP 490 EP 496 DI 10.1038/clpt.2009.149 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 511SB UT WOS:000271186000015 PM 19710639 ER PT J AU Brown, CK Buhse, L Friedel, HD Keitel, S Kraemer, J Morris, JM Stickelmeyer, M Yomota, C Shah, VP AF Brown, Cynthia K. Buhse, Lucinda Friedel, Horst-Dieter Keitel, Susanne Kraemer, Johannes Morris, J. Michael Stickelmeyer, Mary Yomota, Chikako Shah, Vinod P. TI FIP Position Paper on Qualification of Paddle and Basket Dissolution Apparatus SO DISSOLUTION TECHNOLOGIES LA English DT Article AB The qualification process for ensuring that a paddle or basket apparatus is suitable for its intended use is a highly debated and controversial topic. Different instrument qualification and suitability methods have been proposed by the pharmacopeias and regulatory bodies. In an effort to internationally harmonize dissolution apparatus suitability requirements, the International Pharmaceutical Federation's (FIP) Dissolution/Drug Release Special Interest Group (SIG) reviewed current instrument suitability requirements listed in the United States, European, and Japanese pharmacopeias and the International Conference on Harmonization (ICH) Topic Q4B on harmonization of pharmacopoeial methods in its Annex 7, Dissolution Test General. In addition, the SIG reviewed the Food and Drug Administration (FDA) Draft Guidance for Industry, "The Use of Mechanical Calibration of Dissolution Apparatus 1 and 2-Current Good Manufacturing Practice (CGMP)" and the related ASTM Standard E2503-07. Based on this review and several in-depth discussions, the FIP Dissolution/Drug Release SIG recommends that the qualification of a dissolution test instrument should be performed following the calibration requirements as indicated in the FDA (draft) guidance. If additional system performance information is desired, a performance verification test using U.S. Pharmacopeia Reference Standard tablets or an established in-house reference product can be conducted. Any strict requirement on the use of a specific performance verification test tablet is not recommended at this time. C1 [Brown, Cynthia K.; Stickelmeyer, Mary] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Buhse, Lucinda] US FDA, CDER, OPS, St Louis, MO USA. [Shah, Vinod P.] FIP Sci Secretary, The Hague, Netherlands. RP Brown, CK (reprint author), Eli Lilly & Co, Indianapolis, IN 46285 USA. EM brownck@lilly.com NR 10 TC 2 Z9 2 U1 0 U2 0 PU DISSOLUTION TECHNOLOGIES, INC PI HOCKESSIN PA 9 YORKRIDGE TRAIL, HOCKESSIN, DE 19707-9633 USA SN 1521-298X J9 DISSOLUT TECHNOL JI Dissolut. Technol. PD NOV PY 2009 VL 16 IS 4 BP 6 EP 9 PG 4 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 534PI UT WOS:000272909200001 ER PT J AU MacPherson, DW Gushulak, BD Baine, WB Bala, S Gubbins, PO Holtom, P Segarra-Newnham, M AF MacPherson, Douglas W. Gushulak, Brian D. Baine, William B. Bala, Shukal Gubbins, Paul O. Holtom, Paul Segarra-Newnham, Marisel TI Population Mobility, Globalization, and Antimicrobial Drug Resistance SO EMERGING INFECTIOUS DISEASES LA English DT Article ID PLASMODIUM-FALCIPARUM; CIPROFLOXACIN; SURVEILLANCE; TUBERCULOSIS; BACTERIA; WASTE; WATER AB Population mobility is a main factor in globalization of public health threats and risks, specifically distribution of antimicrobial drug-resistant organisms. Drug resistance is a major risk in healthcare settings and is emerging as a problem in community-acquired infections. Traditional health policy approaches have focused on diseases of global public health significance such as tuberculosis, yellow fever, and cholera; however, new diseases and resistant organisms challenge existing approaches. Clinical implications and health policy challenges associated with movement of persons across barriers permeable to products, pathogens, and toxins (e.g., geopolitical borders, patient care environments) are complex. Outcomes are complicated by high numbers of persons who move across disparate and diverse settings of disease threat and risk. Existing policies and processes lack design and capacity to prevent or mitigate adverse health outcomes. We propose an approach to global public health risk management that integrates population factors with effective and timely application of policies and processes. C1 [MacPherson, Douglas W.] Migrat Hlth Consultants Inc, Cheltenham, ON, Canada. [MacPherson, Douglas W.] McMaster Univ, Hamilton, ON, Canada. [Gushulak, Brian D.] Migrat Hlth Consultants Inc, Singapore, Singapore. [Baine, William B.] Agcy Healthcare Res & Qual, Rockville, MD USA. [Bala, Shukal] US FDA, Rockville, MD 20857 USA. [Gubbins, Paul O.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Holtom, Paul] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Segarra-Newnham, Marisel] Vet Affairs Med Ctr, W Palm Beach, FL USA. RP MacPherson, DW (reprint author), 14130 Creditview Rd, Cheltenham, ON L7C 1Y4, Canada. EM douglaswmacpherson@migrationhealth.com NR 40 TC 44 Z9 51 U1 1 U2 21 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD NOV PY 2009 VL 15 IS 11 BP 1727 EP 1732 DI 10.3201/eid1511.090419 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 518ML UT WOS:000271696600004 PM 19891858 ER PT J AU Lu, CS Schenck, F Wong, J AF Lu, Chensheng Schenck, Frank Wong, Jon TI Assessing Children's Dietary Pesticide Exposures-Pesticide Residues Measured in 24-Hour Duplicate Food Samples SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 21st Annual Conference of the International-Society-for-Environmental-Epidemiology CY AUG 25-29, 2009 CL Dublin, IRELAND C1 [Lu, Chensheng] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Schenck, Frank] US FDA, Atlanta, GA USA. [Wong, Jon] US FDA, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 SU S BP S88 EP S88 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SE UT WOS:000270874100235 ER PT J AU Kamikawa, T Mikolajczyk, M Kennedy, M Zhong, LL Zhang, P Scott, D Alocilja, E AF Kamikawa, Tracy Mikolajczyk, Malgorzata Kennedy, Michael Zhong, Lilin Zhang, Pei Scott, Dorothy Alocilja, Evangelyn TI Pandemic Influenza Detection by Surface Plasmon Resonance and Electrically Active Magnetic Nanoparticles SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2009 CL San Diego, CA SP Soc* Glycobiol C1 [Kamikawa, Tracy] Michigan State Univ, FDA CBER, Centreville, VA USA. [Mikolajczyk, Malgorzata; Kennedy, Michael; Zhong, Lilin; Zhang, Pei; Scott, Dorothy] FDA CBER, Bethesda, MD USA. [Alocilja, Evangelyn] Michigan State Univ, Dept BAE, E Lansing, MI 48824 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2009 VL 19 IS 11 MA 52 BP 1302 EP 1303 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505PX UT WOS:000270707700063 ER PT J AU Zou, XJ Patterson, TA Divine, RL Sadovova, N Zhang, X Hanig, JP Paule, MG Slikker, W Wang, C AF Zou, Xiaoju Patterson, Tucker A. Divine, Rebecca L. Sadovova, Natalya Zhang, Xuan Hanig, Joseph P. Paule, Merle G. Slikker, William, Jr. Wang, Cheng TI Prolonged exposure to ketamine increases neurodegeneration in the developing monkey brain SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Ketamine; NMDA receptor antagonist; Neurotoxicity ID DEVELOPING RAT-BRAIN; APOPTOTIC NEURODEGENERATION; FLUORO-JADE; CELL-DEATH; NEURONS; NEUROTOXICITY; RECEPTORS; BLOCKADE; DEFICITS; CULTURE AB Ketamine, a widely used pediatric anesthetic, has been associated with enhanced neuronal toxicity in the developing brain, but mechanisms and neuronal susceptibility to neurotoxic insult leading to neuronal cell death remain poorly defined. One of the main goals of this study was to determine whether there is a duration of ketamine-induced anesthesia below which no significant ketamine-induced neurodegeneration can be detected. Newborn rhesus monkeys (postnatal day 5 or 6) were administered ketamine intravenously for 3, 9 or 24 h to maintain a steady anesthetic plane, followed by a 6-h withdrawal period. The 9- and 24-h durations were selected as relatively long and extremely long exposures, respectively, while the 3-h treatment more closely approximates a typical duration of pediatric general anesthesia. Animals were subsequently perfused under anesthesia and brain tissue was processed for analyses using silver and Fluoro-Jade C stains and caspase-3 immunostain. The results indicated that no significant neurotoxic effects occurred if the anesthesia duration was 3 h. However, ketamine infusions for either 9 or 24 h significantly increased neuronal cell death in layers II and III of the frontal cortex. Although a few caspase-3- and Fluoro-Jade C-positive neuronal profiles were observed in some additional brain areas including the hippocampus, thalamus, striatum and amygdala, no significant differences were detected between ketamine-treated and control monkeys in these areas after 3, 9 or 24 h of exposure. These data show that treatment with ketamine up to 3 h is without adverse effects as determined by nerve cell death. However, anesthetic durations of 9 h or greater are associated with significant brain cell death in the frontal cortex. Thus, the threshold duration below which no neurotoxicity would be expected is somewhere between 3 and 9 h. Published by Elsevier Ireland Ltd on behalf of ISDN. C1 [Zou, Xiaoju; Patterson, Tucker A.; Zhang, Xuan; Paule, Merle G.; Slikker, William, Jr.; Wang, Cheng] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Divine, Rebecca L.; Sadovova, Natalya] Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Hanig, Joseph P.] US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, Silver Spring, MD 20993 USA. RP Wang, C (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM cheng.wang@fda.hhs.gov FU National Center for Toxicological Research (NCTR); U.S. Food and Drug Administration (FDA); Center for Drug Evaluation and Research (CDER)/FDA; National Institute of Child Health and Human Development (NICHD) FX This work was supported by the National Center for Toxicological Research (NCTR)/U.S. Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER)/FDA and the National Institute of Child Health and Human Development (NICHD). NR 28 TC 89 Z9 92 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD NOV PY 2009 VL 27 IS 7 BP 727 EP 731 DI 10.1016/j.ijdevneu.2009.06.010 PG 5 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 511AG UT WOS:000271135200014 PM 19580862 ER PT J AU Harp, BP Barrows, JN AF Harp, Bhakti Petigara Barrows, Julie N. TI Reversed-Phase Liquid Chromatographic Determination of Two Manufacturing Intermediates in D&C Red No. 34 and Its Lakes SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A reversed-phase LC method was developed to determine two manufacturing intermediates in the monosulfo monoazo color additive D&C Red No. 34 and its lakes. The analytes are 2-amino-1-naphthalenesulfonic acid (Tobias acid) and 3-hydroxy-2-naphthalenecarboxylic acid (3-hydroxy-2-naphthoic acid). This method can be used for batch certification of the color additives by the U.S. Food and Drug Administration to ensure that each lot meets published specifications for coloring drugs and cosmetics. The new method uses lithium oxalate in methanol-water to dissolve the color additives for analysis. The analytes were identified by comparison of their LC retention times and UV absorption spectra with those of standards. Peak area calibrations were generally linear (R > 0.999) and recoveries were 105% for Tobias acid and 103% for 3-hydroxy-2-naphthoic acid. The limits of determination (LOD) were 0.01% for Tobias acid and 0.03% for 3-hydroxy-2-naphthoic acid. The RSDs at the specification levels were 0.9% for Tobias acid and 3.2% for 3-hydroxy-2-naphthoic acid. Survey analyses of 14 samples of certified D&C Red No. 34 straight colors and lakes from six domestic and foreign manufacturers yielded results for Tobias acid that generally agreed with results previously obtained by using a gravity elution column chromatographic method. Nine of the results for 3-hydroxy-2-naphthoic acid were 2 to 5 times higher than the results obtained using the column chromatographic method. We attribute the lower accuracy of the column chromatographic method to incomplete solubility of the samples using the method conditions and difficulty with interpreting the UV spectrophotometric results. C1 [Harp, Bhakti Petigara; Barrows, Julie N.] US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, College Pk, MD 20740 USA. RP Harp, BP (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM bhakti.petigara@fda.hhs.gov NR 6 TC 3 Z9 3 U1 0 U2 3 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2009 VL 92 IS 6 BP 1639 EP 1643 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 543PV UT WOS:000273591600005 PM 20166580 ER PT J AU Hammack, T AF Hammack, Thomas TI The AOAC Research Institute Emergency Response Validation Program SO JOURNAL OF AOAC INTERNATIONAL LA English DT Editorial Material C1 US FDA, Gen Referee Methods Comm Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Hammack, T (reprint author), US FDA, Gen Referee Methods Comm Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV-DEC PY 2009 VL 92 IS 6 BP 1839 EP 1839 PG 1 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 543PV UT WOS:000273591600028 PM 20166603 ER PT J AU Patri, A Umbreit, T Zheng, J Nagashima, K Goering, P Francke-Carroll, S Gordon, E Weaver, J Miller, T Sadrieh, N McNeil, S Stratmeyer, M AF Patri, Anil Umbreit, Thomas Zheng, J. Nagashima, K. Goering, Peter Francke-Carroll, Sabine Gordon, Edward Weaver, James Miller, Terry Sadrieh, Nakissa McNeil, Scott Stratmeyer, Mel TI Energy dispersive X-ray analysis of titanium dioxide nanoparticle distribution after intravenous and subcutaneous injection in mice SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE EDS; electron microscopy; titanium dioxide; nanoparticles; mouse; TiO(2); distribution ID PARTICLES; TOXICITY; TISSUES; LUNGS; SIZE; EDX AB In an effort to understand the disposition and toxicokinetics of nanoscale materials, we used EDS (energy dispersive X-ray spectroscopy) to detect and map the distribution of titanium dioxide (TiO(2)) in tissue sections from mice following either subcutaneous (s.c.) or intravenous (i.v.) injection. TiO(2) nanoparticles were administered at a dose of 560 mg/kg (i.v.) or 5600 mg/kg (s.c.) to Balb/c female mice on two consecutive days. Tissues (liver, kidney, lung, heart, spleen, and brain) were examined by light microscopy, TEM (transmission electron microscopy), SEM (scanning electron microscopy), and EDS following necropsy one day after treatment. Particle agglomerates were detected by light microsopy in all tissues examined, EDS microanalysis was used to confirm that these tissues contained elemental titanium and oxygen. The TEM micrographs and EDS spectra of the aggregates were compared with in vitro measurements of TiO(2) nanoparticle injection solution (i.e., in water). The nanoparticles were also characterized using dynamic light scattering in water, 10 mM NaCl, and phosphate buffered saline (PBS). In low ionic strength solvents (water and 10 mM NaCl), the TiO(2) particles had average hydrodynamic diameters ranging from 114-122 nm. In PBS, however, the average diameter increases to 1-2 mu m, likely due to aggregation analogous to that observed in tissue by TEM and EDS. This investigation demonstrates the suitability of energy dispersive X-ray spectroscopy (EDS) for detection of nanoparticle aggregates in tissues and shows that disposition of TiO(2) nanoparticles depends on the route of administration (i.v. or s.c.). Published in 2009 by John Wiley and Sons, Ltd. C1 [Umbreit, Thomas; Goering, Peter; Gordon, Edward; Stratmeyer, Mel] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20903 USA. [Patri, Anil; Zheng, J.; Nagashima, K.; McNeil, Scott] SAIC Frederick Inc, Nonotechnol Characterizat Lab, NCI Frederick, Frederick, MD 21702 USA. [Francke-Carroll, Sabine] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Weaver, James; Miller, Terry; Sadrieh, Nakissa] US FDA, Ctr Drug Evaluat & Res, DAPR, Silver Spring, MD 20903 USA. RP Umbreit, T (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20903 USA. EM thomos.umbreit@fda.hhs.gov RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU National Cancer Institute, National Institutes of Health [N01-CO-12400, HHSN261200800001E] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contracts N01-CO-12400 and HHSN261200800001E. NR 11 TC 28 Z9 31 U1 3 U2 35 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD NOV PY 2009 VL 29 IS 8 BP 662 EP 672 DI 10.1002/jat.1454 PG 11 WC Toxicology SC Toxicology GA 526SQ UT WOS:000272314300004 PM 19626582 ER PT J AU Breger, JC Lyle, DB Shallcross, JC Langone, JJ Wang, NS AF Breger, Joyce C. Lyle, Daniel B. Shallcross, Jonathan C. Langone, John J. Wang, Nam Sun TI Defining Critical Inflammatory Parameters for Endotoxin Impurity in Manufactured Alginate Microcapsules SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE biomaterials; nitric oxide; inflammation; macrophage; alginate; NOEL; LOEL ID OXIDE SYNTHASE GENE; NITRIC-OXIDE; INTERFERON-GAMMA; BACTERIAL LIPOPOLYSACCHARIDE; RAW264.7 CELLS; IFN-GAMMA; MACROPHAGES; CONTAMINATION; EXPRESSION; INDUCTION AB Since current purification methods cannot completely remove all traces of endotoxin in biomaterials intended for use in implantable or blood-contacting devices, acceptable levels of endotoxin contamination that will not cause a significant inflammatory reaction need to be defined. Inflammatory reactions to biomaterials may include production of high concentrations of potentially harmful nitric oxide (NO) generated by macrophages. Nitrite accumulation was measured from RAW264.7 cells treated with either lipopolysaccharide (LPS) free in solution or defined quantities of LPS incorporated into alginate in the absence or presence of murine interferon-gamma (mrIFN-gamma). In the absence of IFN-gamma, significant NO production by RAW 264.7 cells occurred for LPS levels down to 0.0.18 EU/mL. In the presence of mrIFN-gamma, the lowest concentration of LPS tested in solution (0.006 EU/mL) elicited a significant increase in NO production. In the absence or presence of mrIFN-gamma, five times the concentration of LPS incorporated into alginate as compared to LPS free in solution was necessary to elicit a similar NO response by RAW264.7. These results demonstrate that very low concentrations of endotoxin can elicit significant NO responses from macrophages, particularly when inflammatory cytokines are present. Biomaterials may sequester endotoxin, resulting in lower inflammatory reactions that otherwise might be expected. (C) 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 91 B: 755-765, 2009 C1 [Breger, Joyce C.; Wang, Nam Sun] Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA. [Breger, Joyce C.; Lyle, Daniel B.; Shallcross, Jonathan C.; Langone, John J.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Breger, JC (reprint author), Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA. EM joyce.breger@fda.hhs.gov RI Wang, Nam Sun/E-4253-2016 NR 35 TC 6 Z9 6 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4973 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD NOV PY 2009 VL 91B IS 2 BP 755 EP 765 DI 10.1002/jbm.b.31452 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 507QE UT WOS:000270868600031 PM 19585560 ER PT J AU Hoffer, KJ Calogero, D Faaland, RW Ilev, IK AF Hoffer, Kenneth J. Calogero, Don Faaland, Robert W. Ilev, Ilko K. TI Testing the dioptric power accuracy of exact-power-labeled intraocular lenses SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article AB PURPOSE: To test the accuracy of exact-power-labeled intraocular lenses (IOLs) in a limited independent study. SETTING: U.S. Food and Drug Administration Optical Testing Lab. METHODS: Hydrophilic acrylic IOLs were measured using a new confocal laser method for dioptric power measurement per International Organization for Standards standard 11979-2 and American National Standards Institute standard Z80.7. Some of the IOLs were measured at 22 degrees C and 35 degrees C. RESULTS: For the 18 IOLs tested, the mean difference between the manufacturer's exact labeled power (D(EL)) and the power measured in the study (D(M)) was 0.18 diopter (D) +/- 0.12 (SD) and between D(M) and the usual normal rounded-off (0.50 D steps) dioptric power (D(UL)) labeling, 0.23 +/- 0.09 D (difference 0.05 D). For 15.00 to 20.0 D IOLs, the mean difference between D(M) and D(EL) was 0.08 +/- 0.05 D and between D(M) and D(UL), 0.17 +/- 0.06 D (difference 0.09 D). For IOLs of 20.00 D or greater, the mean difference between D(M) and D(EL) was 0.24 +/- 0.11 D and between D(M) and D(UL), 0.27 D +/- 0.08 D (difference 0.03 D). When the IOL hydration temperature increased from 22 degrees C to 35 degrees C (4 IOLs tested), the IOL power increase on average was approximately 0.13 D. CONCLUSIONS: The small improvement in power-prediction accuracy for exact-power-labeled IOLs decreased in IOLs of 20.00 D or greater. For IOLs of 15.00 to 20.00 D, the increased accuracy (+/- 0.09 D) was statistically significant and could increase predictability of postoperative retractions. Acrylic dioptric power was directly proportional to temperature. J Cataract Refract Surg 2009; 35:1995-1999 (C) 2009 ASCRS and ESCRS C1 [Hoffer, Kenneth J.] Univ Calif Los Angeles, Los Angeles, CA USA. [Calogero, Don] US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Faaland, Robert W.; Ilev, Ilko K.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Hoffer, KJ (reprint author), St Marys Eye Ctr, 1605 San Vicente Blvd, Santa Monica, CA 90402 USA. EM khoffermd@aol.com NR 6 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD NOV PY 2009 VL 35 IS 11 BP 1995 EP 1999 DI 10.1016/j.jcrs.2009.06.021 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 518WF UT WOS:000271725600023 PM 19878834 ER PT J AU Sun, JC Lynn, BC AF Sun, Jinchun Lynn, Bert C. TI Development of a LC/MS/MS method to analyze butyrylcholinesterase inhibition resulting from multiple pesticide exposure SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE LC/MS/MS; Butyrylcholinesterase; Organophosphate; Carbamate; Proteomics ID MASS-SPECTROMETRIC ANALYSIS; RETROSPECTIVE DETECTION; ADDUCTS; IDENTIFICATION; AGENTS AB A hybrid LC/MS/MS and proteomics method was developed for the assessment of multiple pesticide exposure. The methodology was based on the analysis of tryptic peptides resulting from inhibited butyrylcholinesterase (BChE) after exposure to pesticides including organophosphates (OPs) and carbamates (CBs). The primary advantage of the assay was its ability to simultaneously examine multiple pesticide exposures in a single analytical experiment. Application of tandem and MS(3) techniques provided identities of the inhibiting pesticide, confirmation and localization of the site of inhibition and relative quantification of phosphorylated peptides present in tryptic digests of equine BChE (eBChE). (C) 2009 Elsevier B.V. All rights reserved. C1 [Lynn, Bert C.] Univ Kentucky, UK Mass Spectrometry Facil, Dept Chem, Lexington, KY 40506 USA. [Sun, Jinchun] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. RP Lynn, BC (reprint author), Univ Kentucky, UK Mass Spectrometry Facil, Dept Chem, A052 ASTeCC Bldg, Lexington, KY 40506 USA. EM bclynn2@uky.edu NR 17 TC 5 Z9 5 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD NOV 1 PY 2009 VL 877 IS 29 BP 3681 EP 3685 DI 10.1016/j.jchromb.2009.09.009 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 511MA UT WOS:000271168100029 PM 19783488 ER PT J AU Huang, LY DuMontelle, JL Zolodz, M Deora, A Mozier, NM Golding, B AF Huang, Li-Yun DuMontelle, James L. Zolodz, Melissa Deora, Aparna Mozier, Ned M. Golding, Basil TI Use of Toll-Like Receptor Assays To Detect and Identify Microbial Contaminants in Biological Products SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID INNATE IMMUNE-RESPONSE; PATHOGEN RECOGNITION; CELL-LINE; INTERNATIONAL VALIDATION; EPITHELIAL-CELLS; FLAGELLIN; ACTIVATION; EXPRESSION; ORIGIN; DNA AB Toll-like receptor (TLR)-expressing cells, for the first time, detected and identified a microbial contaminant in a product made in Escherichia coli using an old manufacturing process. It was suspected of having a microbial contaminant(s) because, although it tested negative by standard pyrogen assays, it was associated with adverse events in early clinical trials. The assay readout is the induction of NF-kappa B and/or cytokines in response to TLR activation. Four coded samples, labeled A to D, including a sample prepared by the older manufacturing process, were submitted. The cell lines were activated only by samples B and D. Sample D stimulated only Mono-Mac 6 and HEK-human TLR4 (hTLR4) cells and was later identified as lipopolysaccharide. Except for TLR3 cells, sample B stimulated cells bearing the different TLRs (TLRs 2, 4, 5, 7, 8, and 9) and nontransfected HEK293 cells. These data suggested that flagellin was the microbial contaminant, since TLR5, the receptor for flagellin, is known to be expressed constitutively on HEK293 cells. Moreover, purified flagellin from Salmonella enterica serovar Typhimurium behaved like sample B, stimulating HEK293 and HEK-hTLR5 cells but not HEK-hTLR3 cells, and this stimulation by flagellin and sample B was blocked by an anti-hTLR5 neutralizing antibody. Western blots showed bands positive for flagellin and sample B with the molecular sizes expected for the flagellins from S. Typhimurium and E. coli, respectively. Mass spectrometry data were consistent with the presence of flagellin in the manufacturer's sample B. Taken together, these data indicate that the microbial contaminant in sample B was flagellin and may have been associated with adverse events when the recombinant product was administered. C1 [Huang, Li-Yun; Golding, Basil] US FDA, Div Hematol, Off Blood Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [DuMontelle, James L.; Zolodz, Melissa; Deora, Aparna; Mozier, Ned M.] Pfizer Global Biol, Res & Dev, Chesterfield, MO 63017 USA. RP Golding, B (reprint author), US FDA, Div Hematol, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 345, Rockville, MD 20852 USA. EM basil.golding@fda.hhs.gov FU DHHS NVPO FX This project was supported in part by DHHS NVPO funds for 2007-2008 (to L.- Y. Huang and B. Golding). NR 26 TC 21 Z9 21 U1 1 U2 6 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 NOV PY 2009 VL 47 IS 11 BP 3427 EP 3434 DI 10.1128/JCM.00373-09 PG 8 WC Microbiology SC Microbiology GA 514CZ UT WOS:000271373000005 PM 19726599 ER PT J AU Yancy, HF Washington, JD Callahan, L Mason, JA Deaver, CM Farrell, DE Ha, T Sespico, E Falmlen, D Myers, MJ AF Yancy, Haile F. Washington, Jewell D. Callahan, Lauren Mason, Jacquline A. Deaver, Christine M. Farrell, Dorothy E. Ha, Tai Sespico, Eric Falmlen, Daniel Myers, Michael J. TI Development, Evaluation, and Peer Verification of a Rapid Real-Time PCR Method for the Detection of Animal Material SO JOURNAL OF FOOD PROTECTION LA English DT Article ID IDENTIFICATION; FEEDSTUFFS; VALIDATION; MEAT; DNA AB Four real-time PCR assays that can be used with U.S.- and European Union-rendered materials to detect three ruminant species (bovine, caprine, and ovine) and a select set of avians (chicken, goose, and turkey) were developed. This method was evaluated against stringent acceptance criteria previously developed by the U.S. Food and Drug Administration, Center for Veterinary Medicine's Office of Research. Acceptance criteria for determining success used a statistical approach requiring a 90% probability of achieving the correct response, within a 95% confidence interval. A minimum detection level of 0.1% meat and bone meal (MBM) was required, consistent with the sensitivity of the validated PCR-based method currently used by the U.S. Food and Drug Administration as an aid in enforcement of the Agency's feed ban. PCR primer specificity was determined by using a panel of DNA samples derived from 16 different animal species. The method is able to detect 0.1% rendered material in complete feed in less than 1.5 h of total assay time, a significant improvement over the current method, which requires 7 to 8 h for completion. The real-time assay for the detection of animal material passed stringent acceptance criteria for sensitivity, selectivity, and specificity. The method also passed ruggedness, real-time platform, and second analyst trials. Two external laboratories participating in a peer-verification trial demonstrated 100% specificity in identifying bovine MBM, ovine MBM, or caprine meat meal, while exhibiting a 0.6% rate of false positives. These results demonstrated that this method was capable of being used by other laboratories. C1 [Yancy, Haile F.; Washington, Jewell D.; Deaver, Christine M.; Farrell, Dorothy E.; Myers, Michael J.] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. [Callahan, Lauren] St Marys Coll Maryland, St Marys City, MD 20686 USA. [Mason, Jacquline A.] Howard Univ, Washington, DC 20059 USA. [Ha, Tai] Nebraska Dept Agr, Lincoln, NE 68508 USA. [Sespico, Eric; Falmlen, Daniel] Florida State Dept Agr, Gainesville, FL 32614 USA. RP Yancy, HF (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM Hyancy@cvm.fda.gov NR 8 TC 17 Z9 18 U1 1 U2 7 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD NOV PY 2009 VL 72 IS 11 BP 2368 EP 2374 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 518UR UT WOS:000271720700019 PM 19903402 ER PT J AU Shieh, YC Stewart, DS Laird, DT AF Shieh, Y. Carol Stewart, Diana S. Laird, David T. TI Survival of Hepatitis A Virus in Spinach during Low Temperature Storage SO JOURNAL OF FOOD PROTECTION LA English DT Article ID MULTISTATE OUTBREAK; UNITED-STATES; GREEN ONIONS; PATHOGENS; LETTUCE AB Spinach leaves are frequently consumed raw and have been involved with past foodbome outbreaks. In this study, we examined the survival of hepatitis A virus (HAV) on fresh spinach leaves in moisture- and gas-permeable packages that were stored at 5.4 +/- 1.2 degrees C for up to 42 days. Different eluents including phosphate-buffered saline (PBS), pH 7.5 (with and without 2% serum), and 3% beef extract (pH 7.5 and 8) were compared for how efficiently they recovered viruses from spinach by using a simple elution procedure (<1 h). The recoveries were compared and determined by a plaque assay with FRhK-4 cells. Culture grade PBS containing 2% serum was found to be appropriate for HAV elution from spinach leaves, with an average recovery of 45% +/- 10%. Over 4 weeks of storage at 5.4 +/- 1.2 degrees C, HAV in spinach decreased slightly more than 1 log, with 6.75% of the original titer remaining. HAV survived under refrigerated temperatures on spinach leaves with a D-value of 28.6 days (equivalent to an inactivation rate of -0.035 log of HAV per day, r(2) = 0.88). In comparison, HAV in PBS containing 2% serum under the same storage conditions remained constant throughout 7 weeks. The inactivation rate of -0.035 log each day for HAV on spinach leaves was possibly due to the interaction of the virus and the leaf. C1 [Shieh, Y. Carol; Stewart, Diana S.; Laird, David T.] US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Shieh, YC (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM carol.shieh@fda.hhs.gov NR 20 TC 17 Z9 17 U1 0 U2 7 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD NOV PY 2009 VL 72 IS 11 BP 2390 EP 2393 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 518UR UT WOS:000271720700023 PM 19903406 ER PT J AU Adamo, JE Meseda, CA Weir, JP Merchlinsky, MJ AF Adamo, Joan E. Meseda, Clement A. Weir, Jerry P. Merchlinsky, Michael J. TI Smallpox vaccines induce antibodies to the immunomodulatory, secreted vaccinia virus complement control protein SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID IMMUNE EVASION; ENHANCED NEUTRALIZATION; VIRULENCE; VIRIONS; DRYVAX AB Vaccination with Dryvax elicits a broad humoral response against many viral proteins. Human vaccinia immune globulin was used to screen the secreted proteins from cells infected with Dryvax or the candidate smallpox vaccine LC16m8 to determine whether the protective humoral response included antibodies against secreted viral proteins. Many proteins were detected, with the primary band corresponding to a band of 28 or 30 kDa in cells infected with Dryvax or LC16m8, respectively. This was identified as the vaccinia virus complement protein (VCP), which migrated more slowly in LC16m8-infected cells due to post-translational glycosylation. Vaccinia virus deleted in VCP, vVCPko, protected mice from a lethal intranasal challenge of vaccinia Western Reserve strain. Mice vaccinated with purified VCP demonstrated a strong humoral response, but were not protected against a moderate lethal challenge of vaccinia virus, suggesting that the humoral response against VCP is not critical for protection. C1 [Adamo, Joan E.; Meseda, Clement A.; Weir, Jerry P.; Merchlinsky, Michael J.] US FDA, Ctr Biol Evaluat & Res, Lab DNA Viruses, Bethesda, MD 20892 USA. RP Merchlinsky, MJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab DNA Viruses, Bethesda, MD 20892 USA. EM michael.merchlinsky@hhs.gov FU MAID [Y1-A1-6153-01]; FDA FX We are grateful to Nga Nguyen (CBER core facility) for mass spectrometry analysis and to Joseph Campbell for assistance with the animal studies. We offer thanks to Dorothy Scott (CBER, FDA) for human VIG and to John D. Lambris (University of Pennsylvania) for the anti-VCP antibodies. This work was supported by an Interagency Agreement (Y1-A1-6153-01) between MAID and the FDA. NR 20 TC 9 Z9 9 U1 0 U2 3 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD NOV PY 2009 VL 90 BP 2604 EP 2608 DI 10.1099/vir.0.008474-0 PG 5 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 515BF UT WOS:000271440500003 PM 19587131 ER PT J AU Dogta, R Joshi, BH Puri, RK AF Dogta, Ritika Joshi, Bharat H. Puri, Raj K. TI Identification and Characterization of Interleukin-4 Receptor alpha Chain in Human Anaplaslic Thyroid Carcinoma and Targeting of IL-4 Receptor for Therapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Dogta, Ritika; Joshi, Bharat H.; Puri, Raj K.] US FDA, Ctr Biol Evaluat & Res, Tumor Vaccine & Biotechnol Branch, Div Cellular & Gene Therapies, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 955 EP 956 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100051 ER PT J AU Fujisawa, T Joshi, BH Nakajima, A Puri, RK AF Fujisawa, Toshio Joshi, Bharat H. Nakajima, Atsushi Puri, Raj K. TI Identification of Interleukin-13 Receptor alpha 2 Chain as a Biomarker for Tumor Invasion and Metastasis Using a Mouse Model of Human Pancreatic Cancer SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Fujisawa, Toshio; Joshi, Bharat H.] US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD USA. [Nakajima, Atsushi] Yokohama City Univ, Div Gastroenterol, Grad Sch Med, Yokohama, Kanagawa 232, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 956 EP 956 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100054 ER PT J AU Joshi, BH Leland, P Puri, RK AF Joshi, Bharat H. Leland, Pamela Puri, Raj K. TI In Vivo Overexpression of Interleukin-4 Receptor alpha in a Mouse Model of Human Bladder Carcinoma Sensitizes Tumors to Recombinant Chimeric Immunotoxin Consisting of Interleukin-4 and Pseudomonas Exotoxin SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Joshi, Bharat H.; Leland, Pamela; Puri, Raj K.] US FDA, Ctr Biol Evaluat & Res, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 957 EP 957 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100056 ER PT J AU Nakashima, H Fujisawa, T Husain, SR Puri, RK AF Nakashima, Hideyuki Fujisawa, Toshio Husain, Syed R. Puri, Raj K. TI DNA Vaccine Targeting Interleukin-13 Receptor alpha 2 Induces Tumor Immunity in Murine Solid Tumor Models SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Nakashima, Hideyuki; Fujisawa, Toshio; Husain, Syed R.; Puri, Raj K.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 973 EP 973 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100106 ER PT J AU Zhu, JD Xu, WJ Wang, J Ali, SF Angulo, JA AF Zhu, Judy Xu, Wenjing Wang, Jing Ali, Syed F. Angulo, Jesus A. TI The neurokinin-1 receptor modulates the methamphetamine-induced striatal apoptosis and nitric oxide formation in mice SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE apoptosis; methamphetamine; neurotoxicity; nitric oxide; striatum; substance P ID INDUCED DOPAMINERGIC NEUROTOXICITY; SUBSTANCE-P; IN-VIVO; EXPRESSING NEURONS; GLUTAMATE RELEASE; TERMINAL MARKERS; FREE-RADICALS; NK1 RECEPTOR; RAT-BRAIN; SYNTHASE AB In a previous study we showed that pharmacological blockade of the neurokinin-1 receptors attenuated the methamphetamine (METH)-induced toxicity of the striatal dopamine terminals. In the present study we examined the role of the neurokinin-1 receptors on the METH-induced apoptosis of some striatal neurons. To that end, we administered a single injection of METH (30 mg/kg, i.p.) to male mice. METH induced the apoptosis (terminal deoxyncleotidyl transferase-mediated dUTP nick end labeling) of approximately 20% of striatal neurons. This percentage of METH-induced apoptosis was significantly attenuated by either a single injection of the neurokinin-1 receptor antagonist, 17-beta-hydroxy-17-a-ethynyl-5-a-androstano[3,2-beta]pyrimido[1,2-a]benzimidazole (WIN-51,708) (5 mg/kg, i.p.), or the ablation of the striatal interneurons expressing the neurokinin-1 receptors (cholinergic and somatostatin) with the selective neurotoxin [Sar9,Met(O(2))11] substance P-saporin. Next we assessed the levels of striatal 3-nitrotyrosine (3-NT) by HPLC and immunohistochemistry. METH increased the levels of striatal 3-NT and this increase was attenuated by pre-treatment with WIN-51,708. Our data support the hypothesis that METH-induced striatal apoptosis occurs via a mechanism involving the neurokinin-1 receptors and the activation of nitric oxide synthesis. Our findings are relevant for the treatment of METH abuse and may be relevant to certain neurological disorders involving the dopaminergic circuitry of the basal ganglia. C1 [Zhu, Judy; Xu, Wenjing; Wang, Jing; Angulo, Jesus A.] CUNY Hunter Coll, Dept Biol Sci, New York, NY 10021 USA. [Ali, Syed F.] Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Angulo, JA (reprint author), CUNY Hunter Coll, Dept Biol Sci, 695 Pk Ave, New York, NY 10021 USA. EM Angulo@genectr.hunter.cuny.edu RI Wang, Jing/E-6217-2012 FU National Institute on Drug Abuse [R01 DA020142]; NCRR/NIH FX This work was supported by R01 DA020142 from the National Institute on Drug Abuse to JAA. Support for infrastructure came from the Research Centers in Minority Institutions grant awarded to Hunter College by NCRR/NIH. NR 66 TC 11 Z9 11 U1 4 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2009 VL 111 IS 3 BP 656 EP 668 DI 10.1111/j.1471-4159.2009.06330.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 505VY UT WOS:000270728600003 PM 19682209 ER PT J AU Anderson, DL AF Anderson, David L. TI Screening of foods and related products for toxic elements with a portable X-ray tube analyzer SO JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY LA English DT Article DE Portable XRF; Toxic elements; Foods; Thin films; Glazes ID CERAMIC GLAZES; SPECTROMETRY; HOUSEWARES; LEAD AB Capabilities of a portable X-ray tube-based analyzer were evaluated for screening foods, thin films, and ceramic glazes for toxic elements. A beverage spiked with Cr, Cu, and As and cocoa powder spiked with As and Pb could easily be distinguished from unadulterated products when analyzed through their original container walls. With calibration, results for thin films and ceramic glazes yielded accurate Pb results. Limits of detection (LODs) were 0.2-15 and 15 mu g cm(-2), respectively, for Pb and Cd in thin films and about 2 mu g cm(-2) for Pb in glazes. With analysis times of 0.5-1 min, sensitivities and LODs were superior to those obtained with radioisotopic X-ray fluorescence analysis. C1 US FDA, Off Regulatory Sci, Chem Contaminants Branch HFS 716, College Pk, MD 20740 USA. RP Anderson, DL (reprint author), US FDA, Off Regulatory Sci, Chem Contaminants Branch HFS 716, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM david.anderson@fda.hhs.gov NR 8 TC 8 Z9 8 U1 1 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0236-5731 J9 J RADIOANAL NUCL CH JI J. Radioanal. Nucl. Chem. PD NOV PY 2009 VL 282 IS 2 BP 415 EP 418 DI 10.1007/s10967-009-0161-0 PG 4 WC Chemistry, Analytical; Chemistry, Inorganic & Nuclear; Nuclear Science & Technology SC Chemistry; Nuclear Science & Technology GA 518ED UT WOS:000271672300018 ER PT J AU Barnard, DE Lewis, SM Teter, BB Thigpen, JE AF Barnard, Dennis E. Lewis, Sherry M. Teter, Beverly B. Thigpen, Julius E. TI Open- and Closed-Formula Laboratory Animal Diets and Their Importance to Research SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID PHYTOESTROGEN CONTENT; RODENT DIETS; CD-1 MICE; RATS; COMMITTEE; TIME AB Almost 40 y ago the scientific community was taking actions to control environmental factors that contribute to variation in the responses of laboratory animals to scientific manipulation. Laboratory animal diet was recognized as an important variable. During the 1970s, the American Institute of Nutrition, National Academy of Science, Institute of Laboratory Animal Resources, and Laboratory Animals Centre Diets Advisory Committee supported the use of 'standard reference diets' in biomedical research as a means to improve the ability to replicate research. As a result the AIN76 purified diet was formulated. During this same time, the laboratory animal nutritionist at the NIH was formulating open-formula, natural-ingredient diets to meet the need for standardized laboratory animal diets. Since the development of open-formula diets, fixed-formula and constant-nutrient-concentration closed-formula laboratory animal natural ingredient diets have been introduced to help reduce the potential variation diet can cause in research. C1 [Barnard, Dennis E.] NIH, Off Res Serv, Div Vet Resources, Bethesda, MD 20892 USA. [Lewis, Sherry M.] US FDA, Off Sci Coordinat, Natl Ctr Toxicol Res, Jefferson, AR USA. [Teter, Beverly B.] Univ Maryland, Dept Chem, College Pk, MD 20742 USA. [Thigpen, Julius E.] NIEHS, Comparat Med Branch, Res Triangle Pk, NC USA. RP Barnard, DE (reprint author), NIH, Off Res Serv, Div Vet Resources, Bldg 10, Bethesda, MD 20892 USA. EM barnardd@mail.nih.gov NR 37 TC 20 Z9 20 U1 1 U2 6 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD NOV PY 2009 VL 48 IS 6 BP 709 EP 713 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 522OR UT WOS:000272008100003 PM 19930817 ER PT J AU Mossoba, MM Seiler, A Kramer, JKG Milosevic, V Milosevic, M Azizian, H Steinhart, H AF Mossoba, Magdi M. Seiler, A. Kramer, J. K. G. Milosevic, V. Milosevic, M. Azizian, H. Steinhart, H. TI Nutrition Labeling: Rapid Determination of Total trans Fats by Using Internal Reflection Infrared Spectroscopy and a Second Derivative Procedure SO JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY LA English DT Article DE Fats and oils; Lipid chemistry; Lipid analysis; Trans fat; Food labeling; Infrared spectroscopy; Attenuated total reflection ID HYDROGENATED SOYBEAN OIL; LINOLEIC-ACID; GAS-CHROMATOGRAPHY; ISOMERS; IDENTIFICATION; MILK; MARGARINES; EMPHASIS; CLA AB In 2006, the US FDA mandated the declaration of the total trans fat content on the Nutrition Fact label of foods including dietary supplements when a product contained 0.5 or more grams of trans fatty acid per serving; the minimum corresponding trans fat content is estimated to be approximately 2% of total fat. The FDA definition is based on chemical structure and includes only fatty acids with one or more isolated double bonds in the trans configuration. Several issues negatively impacted the sensitivity of the current official infrared (IR) methods, thus limited the quantitation of trans fat to 5% of total fat. To improve sensitivity and accuracy and to meet the labeling requirement, a new internal reflection IR procedure called negative second derivative is described and evaluated for the quantitation of total trans fat in the present study. The enhanced spectral features of a second derivative resolved issues that traditionally limited the sensitivity of the IR methodology. Calibration standard mixtures starting at approximately 0.5% trielaidin in the total fat (tripalmitin or triarachidin) were successfully generated and used to determine the trans fat levels for unknown test samples with trans content as low as approximately 1% of total fat. Quantitative IR data were compared to those obtained by gas chromatography and were found to be in good agreement. C1 [Mossoba, Magdi M.; Seiler, A.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Kramer, J. K. G.] Agr & Agri Food Canada, Guelph, ON, Canada. [Milosevic, V.; Milosevic, M.] MeV Photon, Westport, CT USA. [Azizian, H.] NIR Technol, Oakville, ON, Canada. [Seiler, A.; Steinhart, H.] Univ Hamburg, Inst Food Chem, Hamburg, Germany. RP Mossoba, MM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Mail Stop HFS-717,Room BE-012,5100 Paint Branch P, College Pk, MD 20740 USA. EM magdi.mossoba@fda.hhs.gov NR 22 TC 16 Z9 19 U1 2 U2 13 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 NOV PY 2009 VL 86 IS 11 BP 1037 EP 1045 DI 10.1007/s11746-009-1444-x PG 9 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 507RK UT WOS:000270872100002 ER PT J AU Park, S Clarkson, E AF Park, Subok Clarkson, Eric TI Efficient estimation of ideal-observer performance in classification tasks involving high-dimensional complex backgrounds SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article ID CHANNELS; MODEL AB The Bayesian ideal observer is optimal among all observers and sets an absolute upper bound for the performance of any observer in classification tasks [Van Trees, Detection, Estimation, and Modulation Theory, Part I (Academic, 1968).]. Therefore, the ideal observer should be used for objective image quality assessment whenever possible. However, computation of ideal-observer performance is difficult in practice because this observer requires the full description of unknown, statistical properties of high-dimensional, complex data arising in real life problems. Previously, Markov-chain Monte Carlo (MCMC) methods were developed by Kupinski et al. [J. Opt. Soc. Am. A 20, 430(2003)] and by Park et al. [J. Opt. Sec. Am. A 24, B136 (2007) and IEEE Trans. Med. Imaging 28, 657 (2009)] to estimate the performance of the ideal observer and the channelized ideal observer (CIO), respectively, in classification tasks involving non-Gaussian random backgrounds. However, both algorithms had the disadvantage of long computation times. We propose a fast MCMC for real-time estimation of the likelihood ratio for the CIO. Our simulation results show that our method has the potential to speed up ideal-observer performance in tasks involving complex data when efficient channels are used for the CIO. (C) 2009 Optical Society of America C1 [Park, Subok] US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, DIAM, CDRH, Silver Spring, MD 20993 USA. [Clarkson, Eric] Univ Arizona, Ctr Opt Sci, Tucson, AZ 85724 USA. [Clarkson, Eric] Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA. RP Park, S (reprint author), US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, DIAM, CDRH, Silver Spring, MD 20993 USA. EM subok.park@fda.hhs.gov FU National Institute of Biomedical Imaging and Bioengineering; Radiological Health, FDA FX The authors thank Drs. Laura Thompson and Frank Samuelson at the FDA for their comments on the manuscript. This work is supported in part by the National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health intramural grant to the Center for Devices and Radiological Health, FDA. NR 15 TC 5 Z9 5 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1084-7529 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD NOV PY 2009 VL 26 IS 11 BP B59 EP B71 PG 13 WC Optics SC Optics GA 524LA UT WOS:000272143600006 PM 19884916 ER PT J AU Badano, A AF Badano, Aldo TI Effect of slow display on detectability when browsing large image datasets SO JOURNAL OF THE SOCIETY FOR INFORMATION DISPLAY LA English DT Article DE Temporal response; medical display; observer studies; psychophysics ID LIQUID-CRYSTAL DISPLAYS; HUMAN-OBSERVER; CT SCANS; PACS; NOISE; PRODUCTIVITY; SYSTEMS; PHANTOM; STACK; MODEL AB In this work, the effect of display temporal characteristics on detectability of signals was studied by comparing detection performance with a slow liquid-crystal-display (LCD) monitor and a fast, cathode-ray-tube (CRT) monitor when browsing multi-slice image datasets in stack-mode presentation. Thirteen readers evaluated 200 image sequence pairs in a two-alternative forced choice experiment. The image sets consisted of three-dimensional cluster lumpy backgrounds and were presented to the readers in two display devices: a three-million-pixel medical color LCD and a color desktop CRT. For the LCD, many inter-gray-level transitions are on the order of 50-60 msec, which was almost twice the frame time. The CRT had 2-5-msec inter-gray-level transitions. The reader study was performed with a graphical-user interface programmed using direct calls to OpenGL libraries to precisely control the browsing speed. The results were analyzed in terms of the difference in reader performance for each reader and each display, between a browsing speed of 20 and 50 frames per sec (fps). Average reader performance difference between 20 and 50 fps was measured to be 0.049 and 0.156 for the CRT and LCD monitors, respectively. The corresponding drop in reader performance associated with slow display was 0.11. C1 US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Badano, A (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62,Rm 3116, Silver Spring, MD 20993 USA. EM aldo.badano@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 NR 20 TC 3 Z9 3 U1 0 U2 2 PU SOC INFORMATION DISPLAY PI CAMPBELL PA 1475 S BASCOM AVE, STE 114, CAMPBELL, CA 95008 USA SN 1071-0922 J9 J SOC INF DISPLAY JI J. Soc. Inf. Disp. PD NOV PY 2009 VL 17 IS 11 BP 891 EP 896 DI 10.1889/JSID17.11.891 PG 6 WC Engineering, Electrical & Electronic; Materials Science, Multidisciplinary; Optics; Physics, Applied SC Engineering; Materials Science; Optics; Physics GA 510JP UT WOS:000271084800003 ER PT J AU Li, SY Nagothu, KK Desai, V Lee, T Branham, W Moland, C Megyesi, JK Crew, MD Portilla, D AF Li, Shenyang Nagothu, Kiran K. Desai, Varsha Lee, Taewon Branham, William Moland, Carrie Megyesi, Judit K. Crew, Mark D. Portilla, Didier TI Transgenic expression of proximal tubule peroxisome proliferator-activated receptor-alpha in mice confers protection during acute kidney injury SO KIDNEY INTERNATIONAL LA English DT Article DE acute kidney injury; cisplatin; ischemia-reperfusion; lipid peroxidation; mitochondrial fatty acid oxidation; PPAR alpha ID ACUTE-RENAL-FAILURE; LIPID-PEROXIDATION PRODUCTS; PPAR-ALPHA; ISCHEMIA/REPERFUSION INJURY; OXIDIZED PHOSPHOLIPIDS; ENERGY-METABOLISM; HUMAN RENIN; CISPLATIN; CELLS; MECHANISMS AB Our previous studies suggest that peroxisome proliferator-activated receptor-alpha (PPAR alpha) plays a critical role in regulating fatty acid beta-oxidation in kidney tissue and this directly correlated with preservation of kidney morphology and function during acute kidney injury. To further study this, we generated transgenic mice expressing PPAR alpha in the proximal tubule under the control of the promoter of KAP2 (kidney androgen-regulated protein 2). Segment-specific upregulation of PPAR alpha expression by testosterone treatment of female transgenic mice improved kidney function during cisplatin or ischemia-reperfusion-induced acute kidney injury. Ischemia-reperfusion injury or treatment with cisplatin in wild-type mice caused inhibition of fatty-acid oxidation, reduction of mitochondrial genes of oxidative phosphorylation, mitochondrial DNA, fatty-acid metabolism, and the tricarboxylic acid cycle. Similar injury in testosterone-treated transgenic mice resulted in amelioration of these effects. Similarly, there were increases in the levels of 4-hydroxy-2-hexenal-derived lipid peroxidation products in wild-type mice, which were also reduced in the transgenic mice. Similarly, necrosis of the S3 segment was reduced in the two injury models in transgenic mice compared to wild type. Our results suggest proximal tubule PPAR alpha activity serves as a metabolic sensor. Its increased expression without the use of an exogenous PPA R alpha ligand in the transgenic mice is sufficient to protect kidney function and morphology, and to prevent abnormalities in lipid metabolism associated with acute kidney injury. Kidney International (2009) 76, 1049-1062; doi:10.1038/ki.2009.330; published online 26 August 2009 C1 [Li, Shenyang; Nagothu, Kiran K.; Megyesi, Judit K.; Crew, Mark D.; Portilla, Didier] Univ Arkansas Med Sci, Div Nephrol, Dept Internal Med, Little Rock, AR 72205 USA. [Li, Shenyang; Nagothu, Kiran K.; Megyesi, Judit K.; Crew, Mark D.; Portilla, Didier] Univ Arkansas Med Sci, Div Nephrol, Dept Immunol, Little Rock, AR 72205 USA. [Li, Shenyang; Nagothu, Kiran K.; Megyesi, Judit K.; Crew, Mark D.; Portilla, Didier] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. [Desai, Varsha; Branham, William; Moland, Carrie] Natl Ctr Toxicol Res, Ctr Funct Genom, Div Syst Toxicol, Jefferson, AR 72079 USA. [Lee, Taewon] Korea Univ, Dept Math & Informat, Jochiwon, Chungnam, South Korea. RP Portilla, D (reprint author), Univ Arkansas Med Sci, Dept Med, Slot 501,4301 W Markham St, Little Rock, AR 72205 USA. EM portilladidier@uams.edu FU National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [RO1 DK075976] FX The views presented in this article do not necesssarily reflect those of the US Food and Drug Administration. This work was supported by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases grant RO1 DK075976 and a VA Merit Award to Dr Didier Portilla. We acknowledge C. Obrien and the Transgenic Mouse Facility at the University of Arkansas for Medical Sciences for their technical help with the generation of KAP2-PPAR alpha transgenic mice, and Neriman Gokden for her assistance with HHE staining. NR 48 TC 46 Z9 48 U1 0 U2 6 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 NOV PY 2009 VL 76 IS 10 BP 1049 EP 1062 DI 10.1038/ki.2009.330 PG 14 WC Urology & Nephrology SC Urology & Nephrology GA 514GS UT WOS:000271383000007 PM 19710628 ER PT J AU Hu, Y Arsov, I AF Hu, Y. Arsov, I. TI Nested real-time PCR for hepatitis A detection SO LETTERS IN APPLIED MICROBIOLOGY LA English DT Article DE hepatitis A virus; nested PCR; nested real-time PCR; real-time PCR ID SALAD VEGETABLES; RT-PCR; VIRUS; SHELLFISH; OUTBREAK; ASSAY; FOOD AB Aims: The hepatitis A virus (HAV) is one of the most important human foodborne pathogens causing a number of worldwide outbreaks each year. The detection of HAV in food samples remains a complex issue, because commonly used detection tools, such as conventional or even real-time PCR assays, are often unable to detect HAV with sufficient sensitivity. The aims of this study were to develop highly sensitive and specific nested real-time PCR (NRT-PCR)-based method for HAV detection in food and to compare it with currently available methods. Methods and Results: By combining conventional PCR, nested PCR and real-time PCR techniques, we have developed a specific NRT-PCR assay for the detection of HAV. The procedure involves two consecutive PCRs, the first of which is performed as a conventional RT-PCR using primers specific for HAV 5' noncoding region. The second reaction involves a real-time PCR using a nested primer pair specific for the first PCR product and a TaqMan probe. Conclusions: We have developed a novel NRT-PCR method capable of detecting as little as 0 center dot 2 PFU of HAV, which is significantly more sensitive than any other PCR technique tested in our system. Significance and Impact of the Study: NRT-PCR provides a potentially useful method for detecting HAV at extremely low levels, as frequently found in food samples, and can be potentially adopted as a regulatory method to ensure food safety. C1 [Hu, Y.] US FDA, NE Reg Lab, Microbiol Sci Branch, Jamaica, NY 11433 USA. [Arsov, I.] CUNY York Coll, Dept Biol, Jamaica, NY 11451 USA. RP Hu, Y (reprint author), US FDA, NE Reg Lab, Microbiol Sci Branch, 158-15 Liberty Ave, Jamaica, NY 11433 USA. EM yuan.hu@fda.hhs.gov NR 18 TC 11 Z9 11 U1 1 U2 11 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0266-8254 J9 LETT APPL MICROBIOL JI Lett. Appl. Microbiol. PD NOV PY 2009 VL 49 IS 5 BP 615 EP 619 DI 10.1111/j.1472-765X.2009.02713.x PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 505WK UT WOS:000270730000014 PM 19732327 ER PT J AU Badal, A Badano, A AF Badal, Andreu Badano, Aldo TI Accelerating Monte Carlo simulations of photon transport in a voxelized geometry using a massively parallel graphics processing unit SO MEDICAL PHYSICS LA English DT Article DE Monte Carlo; GPU; CUDA; PENELOPE ID DOSE CALCULATION; ELECTRON; CODE AB Purpose: It is a known fact that Monte Carlo simulations of radiation transport are computationally intensive and may require long computing times. The authors introduce a new paradigm for the acceleration of Monte Carlo simulations: The use of a graphics processing unit (GPU) as the main computing device instead of a central processing unit (CPU). Methods: A GPU-based Monte Carlo code that simulates photon transport in a voxelized geometry with the accurate physics models from PENELOPE has been developed using the CUDA T programming model (NVIDIA Corporation, Santa Clara, CA). Results: An outline of the new code and a sample x-ray imaging simulation with an anthropomorphic phantom are presented. A remarkable 27-fold speed up factor was obtained using a GPU compared to a single core CPU. Conclusions: The reported results show that GPUs are currently a good alternative to CPUs for the simulation of radiation transport. Since the performance of GPUs is currently increasing at a faster pace than that of CPUs, the advantages of GPU-based software are likely to be more pronounced in the future. [DOI: 10.1118/1.3231824] C1 [Badal, Andreu; 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, Silver Spring, MD 20993 USA. EM andreu.badal-soler@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 NR 15 TC 93 Z9 93 U1 0 U2 17 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 NOV PY 2009 VL 36 IS 11 BP 4878 EP 4880 DI 10.1118/1.3231824 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 512BR UT WOS:000271217900005 PM 19994495 ER PT J AU Freed, M Miller, S Tang, K Badano, A AF Freed, Melanie Miller, Stuart Tang, Katherine Badano, Aldo TI Experimental validation of Monte Carlo (MANTIS) simulated x-ray response of columnar CsI scintillator screens SO MEDICAL PHYSICS LA English DT Article DE Cesium Iodide; Monte Carlo simulation; experimental validation; scintillator blur ID IMAGING PERFORMANCE; BREAST TOMOSYNTHESIS; MEGAVOLTAGE CT; FLAT-PANEL; DETECTOR; RADIOGRAPHY; EFFICIENCY; IMAGER AB Purpose: MANTIS is a Monte Carlo code developed for the detailed simulation of columnar CsI scintillator screens in x-ray imaging systems. Validation of this code is needed to provide a reliable and valuable tool for system optimization and accurate reconstructions for a variety of x-ray applications. Whereas previous validation efforts have focused on matching of summary statistics, in this work the authors examine the complete point response function (PRF) of the detector system in addition to relative light output values. Methods: Relative light output values and high-resolution PRFs have been experimentally measured with a custom setup. A corresponding set of simulated light output values and PRFs have also been produced, where detailed knowledge of the experimental setup and CsI:Tl screen structures are accounted for in the simulations. Four different screens were investigated with different thicknesses, column tilt angles, and substrate types. A quantitative comparison between the experimental and simulated PRFs was performed for four different incidence angles (0 degrees, 15 degrees, 30 degrees, and 45 degrees) and two different x-ray spectra (40 and 70 kVp). The figure of merit (FOM) used measures the normalized differences between the simulated and experimental data averaged over a region of interest. Results: Experimental relative light output values ranged from 1.456 to 1.650 and were in approximate agreement for aluminum substrates, but poor agreement for graphite substrates. The FOMs for all screen types, incidence angles, and energies ranged from 0.1929 to 0.4775. To put these FOMs in context, the same FOM was computed for 2D symmetric Gaussians fit to the same experimental data. These FOMs ranged from 0.2068 to 0.8029. Our analysis demonstrates that MANTIS reproduces experimental PRFs with higher accuracy than a symmetric 2D Gaussian fit to the experimental data in the majority of cases. Examination of the spatial distribution of differences between the PRFs shows that the main reason for errors between MANTIS and the experimental data is that MANTIS-generated PRFs are sharper than the experimental PRFs. Conclusions: The experimental validation of MANTIS performed in this study demonstrates that MANTIS is able to reliably predict experimental PRFs, especially for thinner screens, and can reproduce the highly asymmetric shape seen in the experimental data. As a result, optimizations and reconstructions carried out using MANTIS should yield results indicative of actual detector performance. Better characterization of screen properties is necessary to reconcile the simulated light output values with experimental data. (C) 2009 American Association of Physicists in Medicine. [DOI: 10.1118/1.3233683] C1 [Freed, Melanie; Tang, Katherine; Badano, Aldo] US FDA, CDRH NIBIB Lab Assessment Med Imaging Syst, Div Imaging & Appl Math, Off Sci & Engn Labs,Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Freed, Melanie] Univ Maryland, College Pk, MD 20742 USA. [Miller, Stuart] RMD Inc, Watertown, MA 02472 USA. RP Freed, M (reprint author), US FDA, CDRH NIBIB Lab Assessment Med Imaging Syst, Div Imaging & Appl Math, Off Sci & Engn Labs,Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM melanie.freed@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 FU intramural program at NIBIB; FDA's Office of Women Health; Research Participation Program at the Center for Devices and Radiological Health FX The authors thank Eugene O'Bryan for invaluable help with the high voltage power supply triggering, Ilko Ilev, Erik Gorman, and Boris Vassilev for help in taking the digital optical microscopy images, Glenn Link for help with the electronic components, Mary Walker for help with the x-ray tube and polaroid camera, Bob Jennings for discussions of film and x-ray beam measurements, Annie Saha for initial experimental measurements, Kyle J. Myers and Brandon D. Gallas (CDRH, FDA) for support and discussions, Frank Samuelson (CDRH, FDA) for providing PERL scripts that allow parallel execution of MANTIS, Samta Thacker (RMD Inc.) for useful discussions regarding the details about the microscopic structures in CsI columnar screens, and the anonymous reviewers for their comments. The authors also acknowledge funding from the intramural program at NIBIB and from FDA's Office of Women Health. This project was supported in part by an appointment to the Research Participation Program at the Center for Devices and Radiological Health administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 25 TC 15 Z9 15 U1 0 U2 2 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 NOV PY 2009 VL 36 IS 11 BP 4944 EP 4956 DI 10.1118/1.3233683 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 512BR UT WOS:000271217900013 PM 19994503 ER PT J AU Yoshida, T Zhang, YQ Rosado, LAR Zhang, BL AF Yoshida, Tatsushi Zhang, Yaqin Rosado, Leslie A. Rivera Zhang, Baolin TI Repeated Treatment with Subtoxic Doses of TRAIL Induces Resistance to Apoptosis through Its Death Receptors in MDA-MB-231 Breast Cancer Cells SO MOLECULAR CANCER RESEARCH LA English DT Article ID HUMAN PROSTATE-CANCER; SIGNAL TRANSDUCER; LEUKEMIA-CELLS; CYTOCHROME-C; IN-VIVO; LIGAND; ACTIVATION; PROTEIN; ENDOCYTOSIS; CARCINOMA AB Recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL) is being evaluated clinically in treating various malignancies. Previous studies have shown that repeated application of high doses of rhTRAIL results in a subpopulation of parental cells that is unresponsive to the death ligand. However, it is not clear whether TRAIL-sensitive cancer cells could acquire resistance to TRAIL treatment. Here, we found that MDA-MB-231 breast cancer cells, which are highly sensitive to TRAIL-induced apoptosis, became resistant to TRAIL killing after a prolonged exposure to subtoxic doses of rhTRAIL. The resulting TRAIL-resistant cells were cross-resistant to antibodies against its death receptors (DR4 and DR5); however, they retained sensitivity to several clinically relevant chemotherapies. Surface expression of DR4 and DR5 was significantly reduced in the selected cells, resulting in failure in death-inducing signaling complex formation and caspase activation. In addition, real-time PCR analysis revealed an upregulation in multiple apoptosis-regulator genes, including c-FLIP, Stat5a, and Stat5b. Inhibition of Janus-activated kinase, an upstream activator of signal transducer and activator of transcription 5 (Stat5), or knockdown of Stat5 itself partially restored cellular sensitivity to TRAIL-induced apoptosis, suggesting that Stat5 signaling is also involved in the development of TRAIL resistance. Furthermore, we showed that acquired TRAIL resistance was effectively eliminated by combination with etoposide, doxorubicin, or paclitaxel. These results suggest that tumor cells could acquire resistance to TRAIL therapy especially when they are repeatedly exposed to low levels of the death ligand, highlighting the necessity of combination with therapies that target the resistance mechanisms. (Mol Cancer Res 2009;7(11):1835-44) C1 [Yoshida, Tatsushi; Zhang, Yaqin; Rosado, Leslie A. Rivera; Zhang, Baolin] US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Zhang, BL (reprint author), US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, 29 Lincoln Dr,Bldg 29A,Room 2A01, Bethesda, MD 20892 USA. EM Baolin.Zhang@fda.hhs.gov FU Food and Drug Administration Critical Patti fund FX Food and Drug Administration Critical Patti fund (B. Zhang). NR 48 TC 32 Z9 35 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD NOV PY 2009 VL 7 IS 11 BP 1835 EP 1844 DI 10.1158/1541-7786.MCR-09-0244 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 522NZ UT WOS:000272006300009 PM 19843632 ER PT J AU Zhang, L Zhang, YC Huang, SM AF Zhang, Lei Zhang, Yuanchao Huang, Shiew-Mei TI Scientific and Regulatory Perspectives on Metabolizing Enzyme-Transporter Interplay and Its Role in Drug Interactions: Challenges in Predicting Drug Interactions SO MOLECULAR PHARMACEUTICS LA English DT Review DE Enzyme-transporter interplay; drug-drug interaction; regulatory; guidance; new drug application; drug development; labeling; risk management ID P-GLYCOPROTEIN EXPRESSION; IN-VITRO DATA; HEALTHY-VOLUNTEERS; CYTOCHROME-P450 ENZYMES; QUANTITATIVE PREDICTION; PLASMA-CONCENTRATIONS; MAJOR DETERMINANT; CYP3A ACTIVITY; HIV-INFECTION; PHARMACOKINETICS AB Both metabolizing enzymes and drug transporters play important roles in modulating drug absorption, distribution, metabolism and elimination. Acting alone or in concert with each other they can affect the pharmacokinetics and pharmacodynamics of a drug. This paper will present cases from recent reviews of new drug application (NDA) and literature that exemplify the role of metabolizing enzyme-transporter interplay in a drug's disposition, and discuss challenges in predicting drug interactions. Finally, the discussion will focus on the need to leverage current knowledge to obtain more meaningful drug interaction information. C1 [Zhang, Lei; Zhang, Yuanchao; 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, Bldg 51,Room 3106,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM leik.zhang@fda.hhs.gov NR 64 TC 37 Z9 38 U1 0 U2 3 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 NOV-DEC PY 2009 VL 6 IS 6 BP 1766 EP 1774 DI 10.1021/mp900132e PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 528QJ UT WOS:000272461300011 PM 19839641 ER PT J AU Beland, FA AF Beland, Frederick A. TI Abstracts of the 32nd Annual Meeting of the United Kingdom Environmental Mutagen society, 12-15 July 2009 at the University of Leeds, UK SO MUTAGENESIS LA English DT Meeting Abstract C1 [Beland, Frederick A.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD NOV PY 2009 VL 24 IS 6 BP 523 EP 523 DI 10.1093/mutage/gep046 PG 1 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 516XD UT WOS:000271575700010 ER PT J AU Manjanatha, MG Shelton, SD Dobrovolsky, VN Shaddock, JG McGarrity, LG Twaddle, NW Moore, MM Mattison, DR Slikker, W Morris, SM AF Manjanatha, Mugimane G. Shelton, Sharon D. Dobrovolsky, Vasily N. Shaddock, Joseph G. McGarrity, Lynda G. Twaddle, Nathan W. Moore, Martha M. Mattison, Donald R. Slikker, William, Jr. Morris, Suzanne M. TI Evaluation of mutagenic mode of action in Big Blue mice fed methylphenidate for 24 weeks SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Methylphenidate hydrochloride; Big Blue mice; cII mutant frequency; Micronucleus frequency; Hprt mutations ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; TRANSGENIC MICE; CHILDREN; HYDROCHLORIDE; MUTATIONS; PHARMACOKINETICS; LYMPHOCYTES; SPECTRA; MONKEY; DAMAGE AB Methylphenidate hydrochloride (MPH), a widely prescribed pediatric drug for attention deficit hyperactivity disorder, induced liver adenocarcinomas in B6C3F1 mice exposed to 500 ppm in feed for 2 years (Dunnick and Hailey (1995) [14]). In order to determine if the induction of liver tumors was by a mutagenic mode of action, groups of male Big Blue (BB) mice (B6C3F1 background) were fed diets containing 50-4000 ppm MPH for 4, 12, or 24 weeks. At sacrifice, the livers were removed and the cII mutant frequency (MF) and spectrum of cII mutations were determined. In addition, the frequencies of micronucleated reticulocytes (MN-RETs) and normochromatic erythrocytes (MN-NCEs) were measured in peripheral blood erythrocytes as was the Hprt MF in splenic lymphocytes. Food consumption and body weight gain/loss were recorded weekly for each animal. The levels of MPH and RA were determined immediately before sacrifice in the serum of mice fed MPH for 24 weeks. A significant loss in body weights (p <= 0.01) was found in mice fed the 2000 and 4000 ppm doses of MPH; however, there was no significant difference in the food consumption by any of the MPH-treated groups. The average liver cII MF in control animals was 20 +/- 4.5 x 10(-6) where as in MPH-treated animals, the average cII MFs ranged between 20 +/- 2.5 and 32 +/- 6.7 x 10(-6). None of the cII MFs in livers from any of the MPH treatment was significantly higher than the concurrent controls at either 4, 12 or 24 weeks. Further, there was no significant increase in either the Hprt MF or the micronucleus frequency at any time point in the treated animals. These results suggest that MPH is not mutagenic in mice and that the induction of tumors as previously reported in the liver is probably through a nongenotoxic mode of action. Published by Elsevier B.V. C1 [Manjanatha, Mugimane G.; Shelton, Sharon D.; Dobrovolsky, Vasily N.; Shaddock, Joseph G.; McGarrity, Lynda G.; Moore, Martha M.; Morris, Suzanne M.] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Twaddle, Nathan W.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Slikker, William, Jr.] US FDA, Natl Ctr Toxicol Res, Off Director, Jefferson, AR 72079 USA. [Mattison, Donald R.] NICHD, NIH, Bethesda, MD 20892 USA. RP Manjanatha, MG (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Mugimane.manjanatha@fda.hhs.gov RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 FU InterAgency Agreement between NICHD/NIH; NCTR/FDA FX All work was funded by an InterAgency Agreement between NICHD/NIH and NCTR/FDA. NR 28 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD NOV-DEC PY 2009 VL 680 IS 1-2 BP 43 EP 48 DI 10.1016/j.mrgentox.2009.09.004 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 534DK UT WOS:000272875500007 PM 19778631 ER PT J AU Wang, JY Rahman, MF Duhart, HM Newport, GD Patterson, TA Murdock, RC Hussain, SM Schlager, JJ Ali, SF AF Wang, Jianyong Rahman, Mohammed F. Duhart, Helen M. Newport, Glenn D. Patterson, Tucker A. Murdock, Richard C. Hussain, Saber M. Schlager, John J. Ali, Syed F. TI Expression changes of dopaminergic system-related genes in PC12 cells induced by manganese, silver, or copper nanoparticles SO NEUROTOXICOLOGY LA English DT Article DE Manganese; Silver; Copper; Nanoparticles; Dopamine; Neurotoxicity; Gene expression; PC 12 cells ID ENDOPLASMIC-RETICULUM STRESS; CENTRAL-NERVOUS-SYSTEM; PARKINSONS-DISEASE; ALPHA-SYNUCLEIN; REAL-TIME; ULTRAFINE PARTICLES; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; PAEL-R; NEUROTOXICITY AB Nanoparticles have received a great deal of attention for producing new engineering applications due to their novel physicochemical characteristics. However, the broad application of nanomaterials has also produced concern for nanoparticle toxicity due to increased exposure from large-scale industry production. This study was conducted to investigate the potential neurotoxicity of manganese (Mn), silver (Ag), and copper (Cu) nanoparticles using the dopaminergic neuronal cell line, PC12. Selective genes associated with the dopaminergic system were investigated for expression changes and their correlation with dopamine depletion. PC12 cells were treated with 10 mu g/ml Mn-40 nm, Ag-15 nm, or Cu-90 nm nanoparticles for 24 h. Cu-90 nanoparticles induced dopamine depletion in PC12 cells, which is similar to the effect induced by Mn-40 shown in a previous study. The expression of 11 genes associated with the dopaminergic system was examined using real-time RT-PCR. The expression of Txnrd1 was up-regulated after the Cu-90 treatment and the expression of Gpx1 was down-regulated after Ag-15 or Cu-90 treatment. These alterations are consistent with the oxidative stress induced by metal nanoparticles. Mn-40 induced a down-regulation of the expression of Th; Cu-90 induced an up-regulation of the expression of Maoa. This indicates that besides the oxidation mechanism, enzymatic alterations may also play important roles in the induced dopamine depletion. Mn-40 also induced a down-regulation of the expression of Park2; while the expression of Snca was up-regulated after Mn-40 or Cu-90 treatment. These data suggest that Mn and Cu nanoparticles-induced dopaminergic neurotoxicity may share some common mechanisms associated with neurodegeneration. Published by Elsevier Inc. C1 [Wang, Jianyong; Rahman, Mohammed F.; Duhart, Helen M.; Newport, Glenn D.; Patterson, Tucker A.; Ali, Syed F.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. [Murdock, Richard C.; Hussain, Saber M.; Schlager, John J.] AFRL HEPB, Human Effectiveness Directorate, Appl Biotechnol Branch, Dayton, OH 45433 USA. RP Ali, SF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, HFT 132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM jianyong.wang@fda.hhs.gov; mohammed.rahman@fda.hhs.gov; helen.duhart@fda.hhs.gov; glenn.newport@fda.hhs.gov; tucker.patterson@fda.hhs.gov; Saber.Hussain@wpafb.af.mil; John.Schlager@wpafb.af.mil; syed.ali@fda.hhs.gov NR 52 TC 74 Z9 82 U1 2 U2 40 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD NOV PY 2009 VL 30 IS 6 BP 926 EP 933 DI 10.1016/j.neuro.2009.09.005 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 534CS UT WOS:000272873700007 PM 19781568 ER PT J AU Dmytrijuk, A Robie-Suh, K Rieves, D Pazdur, R AF Dmytrijuk, Andrew Robie-Suh, Kathy Rieves, Dwaine Pazdur, Richard TI Eltrombopag for the Treatment of Chronic Immune (Idiopathic) Thrombocytopenic Purpura SO ONCOLOGY-NEW YORK LA English DT Article AB Purpose: On November 20, 2008, eltrombopag (Promacta) received approval from the US Food and Drug Administration (FDA) for the treatment of thrombocytopenia in patients with chronic immune thrombocytopenic purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. This report summarizes the FDA analyses of the clinical data supporting this approval. Experimental Design: The FDA reviewed data from two double-blind, placebo-controlled clinical studies, an uncontrolled extension study, and exploratory supportive studies. One study randomized patients among placebo or one of three daily doses of eltrombopag (30, 50, or 75 mg). The other study randomized patients between placebo or eltrombopag, 50 mg daily. Study drugs were administered for 6 weeks. The primary endpoint was response rate. Patients who completed these and other studies were eligible to enroll in the extension study. Results: Overall, 231 patients were randomized within the two controlled studies (67 to placebo; 164 to eltrombopag). A platelet response was observed among 59% and 70% of the patients receiving eltrombopag, 50 mg daily. Corresponding placebo response rates were 16% and 11%, respectively. Serious hemorrhages occurred among two patients receiving eltrombopag and one patient receiving placebo, and among five patients following discontinuation of eltrombopag. In the extension study, eltrombopag was administered to 109 patients; median platelet counts were > 50 x 10(9)/L throughout the study's quarterly follow-up points. Major safety findings pertained to a risk for hepatotoxicity, worsened thrombocytopenia with hemorrhage following eltrombopag discontinuation, and bone marrow reticulin formation. Conclusions: The US FDA approved eltrombopag for use among certain patients with chronic ITP based upon demonstration of a favorable risk-to-benefit profile, where the major benefit pertained to demonstration of a clinically important increase in blood platelets among a population of patients relatively refractory to prior therapies. C1 [Dmytrijuk, Andrew; Robie-Suh, Kathy; Rieves, Dwaine; Pazdur, Richard] US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Dmytrijuk, A (reprint author), US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM andrew.dmytrijuk@fda.hhs.gov NR 17 TC 7 Z9 7 U1 0 U2 0 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD NOV PY 2009 VL 23 IS 13 BP 1171 EP 1177 PG 7 WC Oncology SC Oncology GA V18PW UT WOS:000208017700008 PM 20043468 ER PT J AU Shimamura, T Nakajima, A Kato, S Ogawa, M Kobayashi, N Saito, S Kubota, K Puri, RK AF Shimamura, T. Nakajima, A. Kato, S. Ogawa, M. Kobayashi, N. Saito, S. Kubota, K. Puri, R. K. TI The Combination Therapy of Gemcitabine With an IL-4 Cytotoxin in a Mouse Model of Pancreatic Ductal Adenocarcinoma SO PANCREAS LA English DT Meeting Abstract C1 [Shimamura, T.; Nakajima, A.; Kato, S.; Ogawa, M.; Kobayashi, N.; Saito, S.; Kubota, K.] Yokohama City Univ, Grad Sch Med, Div Gastroenterol, Yokohama, Kanagawa 232, Japan. [Puri, R. K.] FDA, CBER, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2009 VL 38 IS 8 BP 1046 EP 1047 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 512DZ UT WOS:000271225300331 ER PT J AU Hua, W Izurieta, HS Slade, B Belay, ED Haber, P Tiernan, R Woo, EJ Iskander, J Braun, MM Ball, R AF Hua, Wei Izurieta, Hector S. Slade, Barbara Belay, Ermias D. Haber, Penina Tiernan, Rosemary Woo, Emily Jane Iskander, John Braun, M. Miles Ball, Robert TI Kawasaki Disease After Vaccination Reports to the Vaccine Adverse Event Reporting System 1990-2007 SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE Kawasaki disease; vaccine adverse event ID EVENT-REPORTING-SYSTEM; INFANTS; EPIDEMIOLOGY; SAFETY; JAPAN; VAERS; AGE AB Background: Kawasaki disease (KD) is a multisystemic vasculitis primarily affecting children <5 years. A review of RotaTeq (rotavirus vaccine live) clinical trial data revealed higher, though not statistically significantly, KD rates among RotaTeq vaccines than placebo recipients. In June 2007, the RotaTeq label was revised accordingly. Objectives: To describe and assess KD reported to Vaccine Adverse Event Reporting System (VAERS) for all US licensed vaccines. Methods: We reviewed all KD reports received by VAERS from 1990 through mid-October 2007. Cases were characterized by age, gender, onset interval, and vaccine type. Proportional reporting ratio (PRR) was used to evaluate KD reporting for each vaccine compared with all others. Reporting rates were calculated using number of doses distributed as denominator. Results: Through October14, 2007, 107 KD reports were received by VAERS: 26 were categorized as classic cases, 19 atypical, 52 possible, and 10 were noncases. Of the 97 cases, 91 % were children <5 years. There was no clustering of onset intervals after day 1 postvaccination. Before the RotaTeq label revision, the KD PRR was elevated only for Pediarix (DTaP, hepB, and IPV combined) but the KD reporting rate for Pediarix (0.59/100,000 person-years) was much lower than the background incidence rate (9-19/100,000 person-years) for children <5 years in the United States. After the revision, reporting of KD for RotaTeq was stimulated but the reporting rate for RotaTeq (1.47/100,000 person-years) was still much lower than the background rate. Conclusions: Our review does not suggest an elevated KD risk for RotaTeq or other vaccines. Continued postmarketing monitoring for KD is ongoing. C1 [Hua, Wei] FDA, CBER, OBE, Vaccine Safety Branch,Div Epidemiol, Rockville, MD 20852 USA. [Slade, Barbara; Haber, Penina; Iskander, John] Ctr Dis Control & Prevent, Immunizat Safety Off, Atlanta, GA USA. [Belay, Ermias D.] Ctr Dis Control & Prevent, Coordinating Ctr Infect Dis, Natl Ctr Zoonot Vector Borne & Enter Dis, Atlanta, GA USA. [Tiernan, Rosemary] FDA, CBER, Off Vaccines Res & Review, Rockville, MD 20852 USA. RP Hua, W (reprint author), FDA, CBER, OBE, Vaccine Safety Branch,Div Epidemiol, 1401 Rockville Pike,Suite 264S,HFM-222, Rockville, MD 20852 USA. EM wei.hua@fda.hhs.gov RI Belay, Ermias/A-8829-2013 NR 30 TC 27 Z9 28 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD NOV PY 2009 VL 28 IS 11 BP 943 EP 947 DI 10.1097/INF.0b013e3181a66471 PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 512MO UT WOS:000271253800001 PM 19755926 ER PT J AU Adhikary, R Schonenbrucher, H Rasmussen, MA Casey, TA Hamir, AN Kehrli, ME Richt, JA Petrich, JW AF Adhikary, Ramkrishna Schoenenbruecher, Holger Rasmussen, Mark A. Casey, Thomas A. Hamir, Amir N. Kehrli, Marcus E. Richt, Juergen A. Petrich, Jacob W. TI A Comparison of the Fluorescence Spectra of Murine and Bovine Central Nervous System and Other Tissues SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID RETINAL-PIGMENT EPITHELIUM; CREUTZFELDT-JAKOB-DISEASE; AGE PIGMENT; LIPOFUSCIN; MALONDIALDEHYDE; GENERATION; ADDUCTS AB We describe a comparison of the fluorescence spectra of bovine tissues with murine tissues in order to determine whether spectral features are conserved and whether an appropriate and practical laboratory small animal model system could be identified to be used for investigation of tissue- and age-related fluorescence signal patterns. Recently it has been shown that spectral signatures of lipofuscin have enabled the detection of bovine central nervous system (CNS) tissue in meat products with high sensitivity (Schonenbrucher, H., Adhikary, R., Mukherjee, P., Casey, T. A., Rasmussen, M. A., Maistrovich, F. D., Hamir, A.N., Kehrli, M.J., Richt, J., Petrich, J. W. [2008] J Agric Food Chem 56, 6220-6226). We report that brain and spinal cord of mice provide fluorescence spectra similar to those of bovine brain and spinal cord. It is concluded that murine CNS tissue is an appropriate model system for bovine CNS tissue for the development of fluorometric CNS detection assays. C1 [Schoenenbruecher, Holger; Hamir, Amir N.; Kehrli, Marcus E.; Richt, Juergen A.] ARS, Virus & Pr Dis Livestock Res Unit, Natl Anim Dis Ctr, USDA, Ames, IA 50011 USA. [Adhikary, Ramkrishna; Petrich, Jacob W.] Iowa State Univ, Dept Chem, Ames, IA USA. [Rasmussen, Mark A.] US FDA, Res Off, Ctr Vet Med, Laurel, MD USA. [Rasmussen, Mark A.; Casey, Thomas A.] ARS, Preharvest Food Safety & Enter Dis Res Unit, Natl Anim Dis Ctr, USDA, Ames, IA USA. [Richt, Juergen A.] Kansas State Univ, Coll Vet Med, Dept Diagnost Med Pathobiol, Manhattan, KS 66506 USA. RP Richt, JA (reprint author), ARS, Virus & Pr Dis Livestock Res Unit, Natl Anim Dis Ctr, USDA, Ames, IA 50011 USA. EM jricht@ksu.edu; jwp@iastate.edu RI Adhikary, Ramkrishna/F-3002-2011; Petrich, Jacob/L-1005-2015 FU Iowa State University Meat Laboratory FX The support of local slaughterhouses and the Iowa State University Meat Laboratory in sample collection is gratefully acknowledged. We thank Hannah Polashek and Kevin Hassal for technical assistance. NR 24 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD NOV-DEC PY 2009 VL 85 IS 6 BP 1322 EP 1326 DI 10.1111/j.1751-1097.2009.00593.x PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 509UX UT WOS:000271045200006 PM 19656327 ER PT J AU Mettler, FA Bhargavan, M Faulkner, K Gilley, DB Gray, JE Ibbott, GS Lipoti, JA Mahesh, M McCrohan, JL Stabin, MG Thomadsen, BR Yoshizumi, TT AF Mettler, Fred A., Jr. Bhargavan, Mythreyi Faulkner, Keith Gilley, Debbie B. Gray, Joel E. Ibbott, Geoffrey S. Lipoti, Jill A. Mahesh, Mahadevappa McCrohan, John L. Stabin, Michael G. Thomadsen, Bruce R. Yoshizumi, Terry T. TI Radiologic and Nuclear Medicine Studies in the United States and Worldwide: Frequency, Radiation Dose, and Comparison with Other Radiation Sources-1950-2007 SO RADIOLOGY LA English DT Article ID IONIZING-RADIATION; POPULATION EXPOSURE; DIAGNOSTIC USE; TRENDS AB The U.S. National Council on Radiation Protection and Measurements and United Nations Scientific Committee on Effects of Atomic Radiation each conducted respective assessments of all radiation sources in the United States and worldwide. The goal of this article is to summarize and combine the results of these two publicly available surveys and to compare the results with historical information. In the United States in 2006, about 377 million diagnostic and interventional radiologic examinations and 18 million nuclear medicine examinations were performed. The United States accounts for about 12% of radiologic procedures and about one-half of nuclear medicine procedures performed worldwide. In the United States, the frequency of diagnostic radiologic examinations has increased almost 10-fold (1950-2006). The U.S. per-capita annual effective dose from medical procedures has increased about sixfold (0.5 mSv [1980] to 3.0 mSv [2006]). Worldwide estimates for 2000-2007 indicate that 3.6 billion medical procedures with ionizing radiation (3.1 billion diagnostic radiologic, 0.5 billion dental, and 37 million nuclear medicine examinations) are performed annually. Worldwide, the average annual per-capita effective dose from medicine (about 0.6 mSv of the total 3.0 mSv received from all sources) has approximately doubled in the past 10-15 years. (C) RSNA, 2009 C1 [Mettler, Fred A., Jr.] Radiol & Nucl Med Serv, Albuquerque, NM 87108 USA. [Bhargavan, Mythreyi] Amer Coll Radiol, Dept Res, Reston, VA USA. [Faulkner, Keith] NHS Qual Assurance Reference Ctr, Dept Qual Assurance, Wallsend, Tyne & Wear, England. [Gilley, Debbie B.] Dept Hlth, Tallahassee, FL USA. [Gray, Joel E.] DIQUAD, Steger, IL USA. [Ibbott, Geoffrey S.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. [Lipoti, Jill A.] New Jersey Dept Environm Protect, Dept Radiat Protect Programs, Trenton, NJ USA. [Mahesh, Mahadevappa] Johns Hopkins Univ, Dept Diagnost Radiol, Baltimore, MD USA. [McCrohan, John L.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Stabin, Michael G.] Vanderbilt Univ, Dept Radiol, Nashville, TN USA. [Thomadsen, Bruce R.] Univ Wisconsin, Dept Med Phys, Madison, WI 53706 USA. [Yoshizumi, Terry T.] Duke Univ, Sch Med, Dept Radiol, Durham, NC USA. RP Mettler, FA (reprint author), Mexico VA Hlth Care Syst, 1501 San Pedro Blvd SE, Albuquerque, NM 87108 USA. EM fmettler@salud.unm.edu NR 28 TC 311 Z9 319 U1 3 U2 17 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 2009 VL 253 IS 2 BP 520 EP 531 DI 10.1148/radiol.2532082010 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 512UH UT WOS:000271275800029 PM 19789227 ER PT J AU Knight, AW Little, S Houck, K Dix, D Judson, R Richard, A McCarroll, N Akerman, G Yang, CH Birrell, L Walmsley, RM AF Knight, Andrew W. Little, Stephen Houck, Keith Dix, David Judson, Richard Richard, Ann McCarroll, Nancy Akerman, Gregory Yang, Chihae Birrell, Louise Walmsley, Richard M. TI Evaluation of high-throughput genotoxicity assays used in profiling the US EPA ToxCast (TM) chemicals SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE Genotoxicity; In vitro; High-throughput screening; ToxCast; Pesticides; Hazard assessment; GreenScreen HC; CellCiphr; CellSensor; p53; GADD45 alpha ID DNA-DAMAGE RESPONSE; NONGENOTOXIC CARCINOGENS; TEST SYSTEM; GENETIC TOXICOLOGY; DRUG DISCOVERY; SOS/UMU-TEST; CELL-LINE; TOXICITY; TESTS; MUTAGENS AB Three high-throughput screening (HTS) genotoxicity assays-GreenScreen HC GADD45a-GFP (Gentronix Ltd.), CellCiphr p53 (Cellumen Inc.) and CellSensor p53RE-bla (Invitrogen Corp.)-were used to analyze the collection of 320 predominantly pesticide active compounds being tested in Phase I of US. Environmental Protection Agency's ToxCast (TM) research project. Between 9% and 12% of compounds were positive for genotoxicity in the assays. However, results of the varied tests only partially overlapped, suggesting a strategy of combining data from a battery of assays. The HTS results were compared to mutagenicity (Ames) and animal tumorigenicity data. Overall, the HTS assays demonstrated low sensitivity for rodent tumorigens, likely due to: screening at a low concentration, coverage of selected genotoxic mechanisms, lack of metabolic activation and difficulty detecting non-genotoxic carcinogens. Conversely, HTS results demonstrated high specificity, >88%. Overall concordance of the HTS assays with tumorigenicity data was low, around 50% for all tumorigens, but increased to 74-78% (vs. 60% for Ames) for those compounds producing tumors in rodents at multiple sites and, thus, more likely genotoxic carcinogens. The aim of the present study was to evaluate the utility of HTS assays to identify potential genotoxicity hazard in the larger context of the ToxCast project, to aid prioritization of environmentally relevant chemicals for further testing and assessment of carcinogenicity risk to humans. (C) 2009 Elsevier Inc. All rights reserved C1 [Knight, Andrew W.; Birrell, Louise; Walmsley, Richard M.] Gentronix Ltd, Manchester M13 9NT, Lancs, England. [Little, Stephen; Houck, Keith; Dix, David; Judson, Richard; Richard, Ann] US EPA, Natl Ctr Computat Toxicol D343 03, Off Res & Dev, Res Triangle Pk, NC 27711 USA. [McCarroll, Nancy; Akerman, Gregory] US EPA, Div Hlth Effects, Off Pesticide Programs, Washington, DC 20460 USA. [Yang, Chihae] US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety HFS 275, College Pk, MD 20740 USA. RP Knight, AW (reprint author), Gentronix Ltd, CFF Bldg,46 Grafton St, Manchester M13 9NT, Lancs, England. EM andrew.knight@gentronix.co.uk OI Birrell, Louise/0000-0003-0688-2342 NR 60 TC 60 Z9 61 U1 2 U2 26 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD NOV PY 2009 VL 55 IS 2 BP 188 EP 199 DI 10.1016/j.yrtph.2009.07.004 PG 12 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 507OF UT WOS:000270863300009 PM 19591892 ER PT J AU Latendresse, JR Bucci, TJ Olson, G Mellick, P Weis, CC Thorn, B Newbold, RR Delclos, KB AF Latendresse, John R. Bucci, Thomas J. Olson, Greg Mellick, Paul Weis, Constance C. Thorn, Brett Newbold, Retha R. Delclos, K. Barry TI Genistein and ethinyl estradiol dietary exposure in multigenerational and chronic studies induce similar proliferative lesions in mammary gland of male Sprague-Dawley rats SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE Genistein; Ethinyl estradiol; Rat; Multigenerational; Reproductive toxicity; Mammary gland toxicity; Soy-free diet; Endocrine disrupter ID GUIDELINE NO. 407; CD BR RATS; REPRODUCTIVE-SYSTEM; CELL HYPERPLASIA; SOY ISOFLAVONES; DRAFT PROTOCOL; ORAL TOXICITY; MICE; ESTROGENS; ETHINYLESTRADIOL AB Genistein and ethinyl estradiol (EE2) were examined in multigenerational reproductive and 2-yr chronic toxicity studies with different exposure durations across generations F-0 through F-4. Sprague-Dawley rats were exposed to genistein (0, 5, 100, or 500ppm) or EE2 (0, 2, 10, or 50ppb). Effects in the male mammary gland are described here. In the multigeneration studies, mammary hyperplasia was induced by both compounds; the chronic studies had a lower incidence, without proportionate neoplasia. Sexual dimorphism (predominant tubuloalveolar growth in females and lobuloalveolar in males) was retained without feminization in high dose genistein or EE2. In the continuously exposed generations, mammary hyperplasia was sustained but not amplified, appeared morphologically similar across all generations, and was not carried over into unexposed offspring of previously exposed generations. The hyperplasia in male rats was similar whether induced by genistein or EE2. Results substantiate and extend previous reports that mammary gland hyperplasia in the male rat is one of the most sensitive markers of estrogenic endocrine disruption. Published by Elsevier Inc. C1 [Latendresse, John R.; Bucci, Thomas J.; Olson, Greg; Mellick, Paul] Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Weis, Constance C.; Thorn, Brett; Delclos, K. Barry] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Newbold, Retha R.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Latendresse, JR (reprint author), Toxicol Pathol Associates, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM john.latendresse@fda.hhs.gov RI Olson, Gregory/B-7529-2009 FU Interagency Agreement IAG [224-07-007]; U.S. Food and Drug Administration; National Institute for Environmental Health Sciences FX This work was supported by Interagency Agreement IAG 224-07-007 between the U.S. Food and Drug Administration and the National Institute for Environmental Health Sciences. The extensive and expert technical assistance of the NCTR support staff in providing diet preparation, chemical analysis, animal care, computer support, and pathology services for these studies is gratefully acknowledged. The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration. NR 59 TC 41 Z9 42 U1 2 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD NOV PY 2009 VL 28 IS 3 BP 342 EP 353 DI 10.1016/j.reprotox.2009.04.006 PG 12 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 514YS UT WOS:000271433400007 PM 19383540 ER PT J AU Ananyeva, NM Lee, TK Jain, N Shima, M Saenko, EL AF Ananyeva, Natalya M. Lee, Timothy K. Jain, Nisha Shima, Midori Saenko, Evgueni L. TI Inhibitors in Hemophilia A: Advances in Elucidation of Inhibitory Mechanisms and in Inhibitor Management with Bypassing Agents SO SEMINARS IN THROMBOSIS AND HEMOSTASIS LA English DT Review DE Factor VIII; hemophilia A; inhibitor; epitope; bypass therapy ID HUMAN-FACTOR-VIII; RECOMBINANT FACTOR VIIA; VON-WILLEBRAND-FACTOR; ACTIVATED FACTOR-VII; PREVIOUSLY UNTREATED PATIENTS; COAGULATION-FACTOR-VIII; SYNTHETIC PEPTIDE ARRAYS; WHOLE-BLOOD COAGULATION; HIGH-TITER INHIBITOR; PORCINE FACTOR-VIII AB Development of inhibitory antibodies (inhibitors) to factor VIII (FVIII) is the most serious adverse event in replacement therapy of hemophilia A patients. The etiology and management of this condition remain major challenges for both researchers and clinicians. In the present review, we discuss recent advances in understanding the molecular mechanisms by which inhibitors inactivate FVIII and experimental approaches used for the mapping of inhibitor epitopes. We also present a comparative analysis of treatment of hemophilia A patients with inhibitors with currently available bypassing agents-activated prothrombin complex concentrate (FEIBA VH; Baxter Healthcare Corp., Westlake Village, CA) and recombinant activated factor VII (NovoSeven; Novo Nordisk, Princeton, NJ)-and describe some ongoing research programs aimed at developing new treatment options for these patients. Availability of sensitive and standardized laboratory assays that would assist in monitoring the effectiveness of bypass therapies is essential for designing customized treatment regimens and improvement in the management of health conditions of hemophilia patients with inhibitors. C1 [Ananyeva, Natalya M.; Lee, Timothy K.] US FDA, Lab Hemostasis, Div Hematol, Off Blood Res & Review,Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Jain, Nisha] US FDA, Clin Review Branch, Div Hematol, Off Blood Res & Review,CBER, Rockville, MD 20852 USA. [Shima, Midori] Nara Med Univ, Dept Pediat, Nara, Japan. [Saenko, Evgueni L.] Russian Acad Sci, Ctr Theoret Problems Physicochem Pharmacol, Moscow, Russia. RP Ananyeva, NM (reprint author), US FDA, Lab Hemostasis, Div Hematol, Off Blood Res & Review,Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM Natalya.Ananyeva@fda.hhs.gov NR 121 TC 13 Z9 14 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0094-6176 J9 SEMIN THROMB HEMOST JI Semin. Thromb. Hemost. PD NOV PY 2009 VL 35 IS 8 BP 735 EP 751 DI 10.1055/s-0029-1245106 PG 17 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 550RD UT WOS:000274145200005 PM 20169510 ER PT J AU Wang, SJ AF Wang, Sue-Jane TI Commentary on "Personalized Medicine in Oncology: Hype or Hope?" SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH LA English DT Editorial Material C1 [Wang, Sue-Jane] US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Wang, Sue-Jane] Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Wang, SJ (reprint author), US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM suejane.wang@fda.hhs.gov NR 29 TC 0 Z9 0 U1 0 U2 1 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 1946-6315 J9 STAT BIOPHARM RES JI Stat. Biopharm. Res. PD NOV PY 2009 VL 1 IS 4 BP 457 EP 461 DI 10.1198/sbr.2009.0065 PG 5 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA V17ZL UT WOS:000207975000016 ER PT J AU Wang, SJ AF Wang, Sue-Jane TI Commentary on "Experiences in Model/Simulation for Early Phase or Late Phase Study Planning Aimed to Learn Key Design Elements" SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH LA English DT Editorial Material C1 [Wang, Sue-Jane] US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Wang, Sue-Jane] Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Wang, SJ (reprint author), US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM suejane.wang@fda.hhs.gov NR 25 TC 2 Z9 2 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 1946-6315 J9 STAT BIOPHARM RES JI Stat. Biopharm. Res. PD NOV PY 2009 VL 1 IS 4 BP 462 EP 467 DI 10.1198/sbr.2009.0066 PG 6 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA V17ZL UT WOS:000207975000017 ER PT J AU Roberts, RA Laskin, DL Smith, CV Robertson, FM Allen, EMG Doorn, JA Slikkerk, W AF Roberts, Ruth A. Laskin, Debra L. Smith, Charles V. Robertson, Fredika M. Allen, Erin M. G. Doorn, Jonathan A. Slikkerk, William TI Nitrative and Oxidative Stress in Toxicology and Disease SO TOXICOLOGICAL SCIENCES LA English DT Review DE cytokine signaling; carcinogenesis; developmental toxicity; prenatal; inflammation ID NITRIC-OXIDE SYNTHASE; NECROSIS-FACTOR-ALPHA; INFLAMMATORY BREAST-CANCER; RAT FOREBRAIN CULTURE; TISSUE-INJURY; REACTIVE INTERMEDIATE; PARKINSONS-DISEASE; APOPTOTIC NEURODEGENERATION; INDUCED NEUROTOXICITY; KINASE PHOSPHATASE-1 AB Persistent inflammation and the generation of reactive oxygen and nitrogen species play pivotal roles in tissue injury during disease pathogenesis and as a reaction to toxicant exposures. The associated oxidative and nitrative stress promote diverse pathologic reactions including neurodegenerative disorders, atherosclerosis, chronic inflammation, cancer, and premature labor and stillbirth. These effects occur via sustained inflammation, cellular proliferation and cytotoxicity and via induction of a proangiogenic environment. For example, exposure to the ubiquitous air pollutant ozone leads to generation of reactive oxygen and nitrogen species in lung macrophages that play a key role in subsequent tissue damage. Similarly, studies indicate that genes involved in regulating oxidative stress are altered by anesthetic treatment resulting in brain injury, most notable during development. In addition to a role in tissue injury in the brain, inflammation, and oxidative stress are implicated in Parkinson's disease, a neurodegenerative disease characterized by the loss of dopamine neurons. Recent data suggest a mechanistic link between oxidative stress and elevated levels of 3,4-dihydroxyphenylacetaldehyde, a neurotoxin endogenous to dopamine neurons. These findings have significant implications for development of therapeutics and identification of novel biomarkers for Parkinson's disease pathogenesis. Oxidative and nitrative stress is also thought to play a role in creating the proinflammatory microenvironment associated with the aggressive phenotype of inflammatory breast cancer. An understanding of fundamental concepts of oxidative and nitrative stress can underpin a rational plan of treatment for diseases and toxicities associated with excessive production of reactive oxygen and nitrogen species. C1 [Laskin, Debra L.] Rutgers State Univ, Dept Pharmacol & Toxicol, Piscataway, NJ 08854 USA. [Smith, Charles V.] Seattle Childrens Res Inst, Ctr Dev Therapeut, Seattle, WA USA. [Robertson, Fredika M.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Slikkerk, William] USFDA, NCTR, Jefferson, AR 72079 USA. [Allen, Erin M. G.; Doorn, Jonathan A.] Univ Iowa, Coll Pharm, Iowa City, IA 52242 USA. EM ruth.roberts@astrazeneca.com FU National Institutes of Health [ES004738, GM034310, CA132624, AR055073, ES005022, R01 ES15507] FX National Institutes of Health grants (ES004738, GM034310, CA132624, AR055073, and ES005022) to D. L. L.; and National Institutes of Health Grant (R01 ES15507) to J. A. D. NR 79 TC 105 Z9 114 U1 0 U2 25 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD NOV PY 2009 VL 112 IS 1 BP 4 EP 16 DI 10.1093/toxsci/kfp179 PG 13 WC Toxicology SC Toxicology GA 514IO UT WOS:000271387900002 PM 19656995 ER PT J AU Bowyer, JF Latendresse, JR Delongchamp, RR Warbritton, AR Thomas, M Divine, B Doerge, DR AF Bowyer, John F. Latendresse, John R. Delongchamp, Robert R. Warbritton, Alan R. Thomas, Monzy Divine, Becky Doerge, Daniel R. TI The mRNA expression and histological integrity in rat forebrain motor and sensory regions are minimally affected by acrylamide exposure through drinking water SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Acrylamide; Neurotoxicity; Basal ganglia; Dopamine; Gene expression ID CDNA ARRAY DATA; PARKINSONS-DISEASE; GENE-EXPRESSION; BASAL GANGLIA; NEURONAL DEGENERATION; DOPAMINERGIC NEUROTOXICITY; MOVEMENT-DISORDERS; AXONAL-TRANSPORT; BRAIN-REGIONS; RECEPTORS AB A Study was undertaken to determine whether alterations in the gene expression or overt histological signs of neurotoxicity in selected regions of the forebrain might occur from acrylamide exposure via drinking water. Gene expression at the mRNA level was evaluated by cDNA array and/or RT-PCR analysis in the striatum, substantia nigra and parietal cortex of rat after a 2-week acrylamide exposure. The highest dose tested (maximally tolerated) of approximately 44 mg/kg/day resulted in a significant decreased body weight, sluggishness, and locomotor activity reduction. These physiological effects were not accompanied by prominent changes in gene expression in the forebrain. All the expression changes seen in the 1200 genes that were evaluated in the three brain regions were <= 1.5-fold, and most not significant. Very few, if any, statistically significant changes were seen in mRNA levels of the more than 50 genes directly related to the cholinergic, noradrenergic, GABAergic or glutamatergic neurotransmitter systems in the striatum, substantia nigra or parietal cortex. All the expression changes observed in genes related to dopaminergic function were less than 1.5-fold and not statistically significant and the 5HT1b receptor was the only serotonin-related gene affected. Therefore, gene expression changes were few and modest in basal ganglia and sensory cortex at a time when the behavioral manifestations of acrylamide toxicity had become prominent. No histological evidence of axonal, dendritic or neuronal cell body damage was found in the forebrain due to the acrylamide exposure. As well, microglial activation was not present. These findings are consistent with the absence of expression changes in genes related to changes in neuroinflammation or neurotoxicity. Over all, these data suggest that oral ingestion of acrylamide in drinking water or food, even at maximally tolerable levels, induced neither marked changes in gene expression nor neurotoxicity in the motor and somatosensory areas of the central nervous system. Published by Elsevier Inc. C1 [Bowyer, John F.; Thomas, Monzy] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Latendresse, John R.; Warbritton, Alan R.; Divine, Becky] Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Doerge, Daniel R.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Delongchamp, Robert R.] Univ Arkansas Med Sci, Dept Epidemiol, Coll Publ Hlth, Little Rock, AR 72205 USA. RP Bowyer, JF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM john.bowyer@fda.hhs.gov FU U.S. Food and Drug Administration/NCTR and the National Institute for Environmental Health Sciences/NTP [224-07-0007]; Oak Ridge Institute for Science and Education FX This research was supported in part by Interagency Agreement #224-07-0007 between the U.S. Food and Drug Administration/NCTR and the National Institute for Environmental Health Sciences/NTP. MT acknowledges support of a fellowship from the Oak Ridge Institute for Science and Education, administered through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration. NR 83 TC 8 Z9 9 U1 2 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 1 PY 2009 VL 240 IS 3 BP 401 EP 411 DI 10.1016/j.taap.2009.07.036 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 507TC UT WOS:000270876800010 PM 19664650 ER PT J AU MacPherson, J Kochman, S McCullough, J AF MacPherson, Jim Kochman, Sheryl McCullough, Jeffrey TI Regulating blood manufacturing software: report of a conference SO TRANSFUSION LA English DT Editorial Material C1 [McCullough, Jeffrey] Univ Minnesota, Amer Red Cross, Minneapolis, MN 55455 USA. Univ Minnesota, Inst Engn Med, Minneapolis, MN 55455 USA. Amer Blood Ctr, Washington, DC USA. US FDA, Div Blood Applicat, Off Blood Res & Review, Rockville, MD 20857 USA. RP McCullough, J (reprint author), Univ Minnesota, Amer Red Cross, 609 May Bldg,420 Delaware St SE, Minneapolis, MN 55455 USA. EM mccul001@umn.edu NR 1 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD NOV PY 2009 VL 49 IS 11 BP 2490 EP 2494 DI 10.1111/j.1537-2995.2009.02287.x PG 5 WC Hematology SC Hematology GA 509UJ UT WOS:000271043600028 PM 19903297 ER PT J AU Silverman, TA Weiskopf, RB AF Silverman, Toby A. Weiskopf, Richard B. TI Hemoglobin-based oxygen carriers: current status and future directions SO TRANSFUSION LA English DT Editorial Material ID CROSS-LINKED HEMOGLOBIN; HUMAN POLYMERIZED HEMOGLOBIN; RECOMBINANT HUMAN HEMOGLOBIN; CELL-FREE HEMOGLOBIN; TRAUMATIC HEMORRHAGIC-SHOCK; ABDOMINAL AORTIC-ANEURYSM; TARGETED O-2 DELIVERY; ACUTE ISCHEMIC-STROKE; ACUTE KIDNEY INJURY; BOVINE HEMOGLOBIN C1 [Silverman, Toby A.] US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. RP Silverman, TA (reprint author), US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM toby.silverman@fda.hhs.gov OI Silverman, Toby/0000-0003-4893-9984 NR 93 TC 38 Z9 39 U1 1 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD NOV PY 2009 VL 49 IS 11 BP 2495 EP 2515 DI 10.1111/j.1537-2995.2009.02356.x PG 21 WC Hematology SC Hematology GA 509UJ UT WOS:000271043600029 PM 19903298 ER PT J AU Shoaibi, A Tavris, DR McNulty, S AF Shoaibi, Azadeh Tavris, Dale R. McNulty, Steven TI Gender differences in correlates of troponin assay in diagnosis of myocardial infarction SO TRANSLATIONAL RESEARCH LA English DT Article ID ACUTE CORONARY SYNDROMES; CREATINE-KINASE-MB; CARDIOVASCULAR-DISEASE; CLINICAL-SIGNIFICANCE; UNIVERSAL DEFINITION; RISK STRATIFICATION; EUROPEAN-SOCIETY; ARTERY DISEASE; HEART-DISEASE; CHEST PAIN AB Cardiac troponins are the most sensitive and specific biomarker for myocardial infarction (MI) diagnosis. If there is a gender bias in MI diagnosis, it could be reduced by more consistently applying objective diagnostic criteria to improve women's outcomes. This study set out to assess the accuracy and correlates of the cardiac troponin I (cTnI) assay in the diagnosis of non-ST-segment elevation MI, to determine how the assay accuracy and correlates vary by gender, and to explore the interaction between factors that may influence cTnI accuracy and affect gender differences in diagnosis. The data were obtained from the CHECKMATE study. It included 924 patients with possible myocardial ischemia excluding subjects with ST-segment elevation. The Dade-Behring Stratus CS STAT near-patient instrument (Dade Behring, Inc, Newark, Del) was used to measure cTnI. We assessed baseline troponin accuracy using a standard MI definition. There were 125 subjects with a definite MI diagnosis. Baseline troponin was 44% sensitive and 97% specific in predicting MI, with no significant gender differences. In contrast, other positive cardiac markers, namely rising or falling creatine-kinase MB fraction and positive electrocardiogram, occurred more frequently in men. Sensitivity (SE) of baseline troponin was higher in subjects where baseline troponin was obtained longer than 2 hours after the chest pain onset. The study did not observe a significant difference in the assay SE or specificity by gender. This observation, plus the fact that other positive cardiac markers occurred more frequently in men, suggest the troponin test may help to improve the diagnosis of MI in women. (Translational Research 2009; 154:250-256) C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. RP Shoaibi, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,W066-4212, Silver Spring, MD 20993 USA. EM azadeh.shoaibi@fda.hhs.gov FU U.S. Food and Drug Administration Office of Women's Health FX Supported by the U.S. Food and Drug Administration Office of Women's Health. NR 38 TC 2 Z9 3 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1931-5244 J9 TRANSL RES JI Transl. Res. PD NOV PY 2009 VL 154 IS 5 BP 250 EP 256 DI 10.1016/j.trsl.2009.07.004 PG 7 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA 515QA UT WOS:000271485900005 PM 19840766 ER PT J AU Rothman, M Burke, L Erickson, P Leidy, NK Patrick, DL Petrie, CD AF Rothman, Margaret Burke, Laurie Erickson, Pennifer Leidy, Nancy Kline Patrick, Donald L. Petrie, Charles D. TI Use of Existing Patient-Reported Outcome (PRO) Instruments and Their Modification: The ISPOR Good Research Practices for Evaluating and Documenting Content Validity for the Use of Existing Instruments and Their Modification PRO Task Force Report SO VALUE IN HEALTH LA English DT Article DE content validity; instruments; outcomes; patient-reported outcomes; validity ID RECOMMENDATIONS; SELECTION; CLAIMS AB Background: Patient-reported outcome (PRO) instruments are used to evaluate the effect of medical products on how patients feel or function. This article presents the results of an ISPOR task force convened to address good clinical research practices for the use of existing or modified PRO instruments to support medical product labeling claims. The focus of the article is on content validity, with specific reference to existing or modified PRO instruments, because of the importance of content validity in selecting or modifying an existing PRO instrument and the lack of consensus in the research community regarding best practices for establishing and documenting this measurement property. Methods: Topics addressed in the article include: definition and general description of content validity; PRO concept identification as the important first step in establishing content validity; instrument identification and the initial review process; key issues in qualitative methodology; and potential threats to content validity, with three case examples used to illustrate types of threats and how they might be resolved. A table of steps used to identify and evaluate an existing PRO instrument is provided, and figures are used to illustrate the meaning of content validity in relationship to instrument development and evaluation. Results & Recommendations: Four important threats to content validity are identified: unclear conceptual match between the PRO instrument and the intended claim, lack of direct patient input into PRO item content from the target population in which the claim is desired, no evidence that the most relevant and important item content is contained in the instrument, and lack of documentation to support modifications to the PRO instrument. In some cases, careful review of the threats to content validity in a specific application may be reduced through additional well documented qualitative studies that specifically address the issue of concern. Conclusion: Published evidence of the content validity of a PRO instrument for an intended application is often limited. Such evidence is, however, important to evaluating the adequacy of a PRO instrument for the intended application. This article provides an overview of key issues involved in assessing and documenting content validity as it relates to using existing instruments in the drug approval process. C1 [Rothman, Margaret] Johnson & Johnson Pharmaceut Serv LLC, WW Patient Reported Outcomes Ctr Excellence, Raritan, NJ USA. [Burke, Laurie] US FDA, Study Endpoints & Labeling, Off New Drugs, CDER, Silver Spring, MD USA. [Erickson, Pennifer] On Line Guide Qual Of Life Assessment, State Coll, PA USA. [Leidy, Nancy Kline] United BioSource Corp, Sci Affairs, Bethesda, MD USA. [Patrick, Donald L.] Univ Washington, Seattle, WA 98195 USA. [Petrie, Charles D.] Pfizer Inc, New London, CT USA. RP Rothman, M (reprint author), JJPS, WW PRO COE, 301 S Alexander Ave, Washington, GA 30673 USA. EM mrothman@its.jnj.com FU Johnson Johnson; FDA; OLGA; United BioSource Corporation; University of Washington; Pfizer FX The views expressed herein represent those of the authors and not those of Johnson & Johnson, the FDA, OLGA, United BioSource Corporation, University of Washington, or Pfizer. NR 17 TC 90 Z9 90 U1 3 U2 16 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV-DEC PY 2009 VL 12 IS 8 BP 1075 EP 1083 DI 10.1111/j.1524-4733.2009.00603.x PG 9 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 515TH UT WOS:000271495300007 PM 19804437 ER PT J AU Erickson, P Willke, R Burke, L AF Erickson, Pennifer Willke, Richard Burke, Laurie TI A Concept Taxonomy and an Instrument Hierarchy: Tools for Establishing and Evaluating the Conceptual Framework of a Patient-Reported Outcome (PRO) Instrument as Applied to Product Labeling Claims SO VALUE IN HEALTH LA English DT Article DE classification system; conceptual framework; patient-reported outcomes; PRO concept taxonomy; PRO instrument hierarchy ID QUALITY-OF-LIFE; HEALTH ASSESSMENT QUESTIONNAIRE; RHEUMATOID-ARTHRITIS; CLINICAL-TRIALS; DISABILITY; IMPACT; INDEX; IMPROVEMENT; VALIDATION; ISSUES AB Objective: To facilitate development and evaluation of a PRO instrument conceptual framework, we propose two tools-a PRO concept taxonomy and a PRO instrument hierarchy. FDA's draft guidance on patient reported outcome (PRO) measures states that a clear description of the conceptual framework of an instrument is useful for evaluating its adequacy to support a treatment benefit claim for use in product labeling the draft guidance, however does not propose tools for establishing or evaluationg a PRO instrument's conceptual framework. Methods: We draw from our review of PRO concepts and instruments that appear in prescription drug labeling approved in the United States from 1997 to 2007. Results: We propose taxonomy terms that define relationships between PRO concepts, including "family," "compound concept," and "singular concept." Based on the range of complexity represented by the concepts, as defined by the taxonomy, we propose nine instrument orders for PRO measurement. The nine orders range from individual event counts to multiitem, multiscale instruments. Conclusion: This analysis of PRO concepts and instruments illustrates that the taxonomy and hierarchy are applicable to PRO concepts across a wide range of therapeutic areas and provide a basis for defining the instrument conceptual framework complexity. Although the utility of these tools in the drug development, review, and approval processes has not yet been demonstrated, these tools could be useful to improve communication and enhance efficiency in the instrument development and review process. C1 [Erickson, Pennifer] OLGA, State Coll, PA USA. [Willke, Richard] Pfizer Inc, Global Outcomes Res, Peapack, NJ USA. [Burke, Laurie] US FDA, Study Endpoints & Labeling, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Erickson, P (reprint author), Penn State Coll Med, Dept Publ Hlth Sci, 1316 Deerfield Dr, State Coll, PA 16803 USA. EM pae6@psu.edu NR 46 TC 7 Z9 7 U1 5 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV-DEC PY 2009 VL 12 IS 8 BP 1158 EP 1167 DI 10.1111/j.1524-4733.2009.00609.x PG 10 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 515TH UT WOS:000271495300017 PM 19744289 ER PT J AU Tareke, E Heinze, TM da Costa, GG Ali, S AF Tareke, Eden Heinze, Thomas M. da Costa, Goncalo Gamboa Ali, Syed TI Acrylamide Formed at Physiological Temperature as a Result of Asparagine Oxidation SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Acrylamide; asparagine; hydrogen peroxide ID HYDROGEN-PEROXIDE; MAILLARD REACTION AB Acrylamide is a probable human carcinogen that is neurotoxic to both humans and animals. It is known to be formed during cooking of foods at temperatures higher than 120 degrees C. The present study demonstrates that acrylamide can also be formed at, physiological conditions (37 degrees C, pH 7.4) when asparagine is incubated in the presence of hydrogen peroxide (H(2)O(2)). The formation of acrylamide under these conditions is dependent on the incubation time and the concentration of H(2)O(2). Thus, the results raise the question of the possible endogenous formation of acrylamide in pathological conditions that are associated with long-term oxidative stress. Further studies are therefore warranted to clarify the possible endogenous formation of acrylamide and its significance in chronic conditions that are known to be associated with oxidative stress. C1 [Tareke, Eden; Ali, Syed] US FDA, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. [Heinze, Thomas M.; da Costa, Goncalo Gamboa] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Tareke, E (reprint author), US FDA, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. EM edunatar@hotmail.com FU Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS); Oak Ridge Institute for Science and Education FX This work is supported by the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS) and by the 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 U.S. FDA/NCTR. The views presented in this paper do not necessarily reflect those of the U.S. Food and Drug Administration. NR 12 TC 9 Z9 12 U1 0 U2 6 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 OCT 28 PY 2009 VL 57 IS 20 BP 9730 EP 9733 DI 10.1021/jf901812u PG 4 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 507ML UT WOS:000270858200053 PM 19772296 ER PT J AU Silberstein, E Konduru, K Kaplan, GG AF Silberstein, Erica Konduru, Krishnamurthy Kaplan, Gerardo G. TI The interaction of hepatitis A virus (HAV) with soluble forms of its cellular receptor 1 (HAVCR1) share the physiological requirements of infectivity in cell culture SO VIROLOGY JOURNAL LA English DT Article ID MONOCLONAL-ANTIBODY; RICH REGION; NEUTRALIZATION; ATTACHMENT; POLIOVIRUS; PARTICLES; BINDING; ASTHMA; LINES; ASSAY AB Background: Hepatitis A virus (HAV), an atypical Picornaviridae that causes acute hepatitis in humans, usurps the HAV cellular receptor 1 (HAVCR1) to infect cells. HAVCR1 is a class 1 integral membrane glycoprotein that contains two extracellular domains: a virus-binding immunoglobulinlike (IgV) domain and a mucin-like domain that extends the IgV from the cell membrane. Soluble forms of HAVCR1 bind, alter, and neutralize cell culture-adapted HAV, which is attenuated for humans. However, the requirements of the HAV-HAVCR1 interaction have not been fully characterized, and it has not been determined whether HAVCR1 also serves as a receptor for wildtype (wt) HAV. Here, we used HAV soluble receptor neutralization and alteration assays to study the requirements of the HAV-HAVCR1 interaction and to determine whether HAVCR1 is also a receptor for wt HAV. Results: Treatment of HAV with a soluble form of HAVCR1 that contained the IgV and two-thirds of the mucin domain fused to the Fc fragment of human IgG1 (D1 muc-Fc), altered particles at 37 C but left a residual level of unaltered particles at 4 degrees C. The kinetics of neutralization of HAV by D1 muc-Fc was faster at 37 C than at 4 degrees C. Alteration of HAV particles by D1 muc-Fc required Ca, which could not be replaced by Li, Na, Mg, Mn, or Zn. Neutralization of HAV by D1 muc-Fc occurred at pH 5 to 8 but was more efficient at pH 6 to 7. D1 muc-Fc neutralized wt HAV as determined by a cell culture system that allows the growth of wt HAV. Conclusion: The interaction of HAV with soluble forms of HAVCR1 shares the temperature, Ca, and pH requirements for infectivity in cell culture and therefore mimics the cell entry process of HAV. Since soluble forms of HAVCR1 also neutralized wt HAV, this receptor may play a significant role in pathogenesis of HAV. C1 [Silberstein, Erica; Konduru, Krishnamurthy; Kaplan, Gerardo G.] US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis & Related Emerging Agents, Bethesda, MD 20892 USA. RP Kaplan, GG (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis & Related Emerging Agents, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM erica.silberstein@fda.hhs.gov; krishnamurthy.konduru@fda.hhs.gov; gk@helix.nih.gov FU FDA intramural funds FX The work was supported by FDA intramural funds to GGK. NR 27 TC 5 Z9 5 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD OCT 27 PY 2009 VL 6 AR 175 DI 10.1186/1743-422X-6-175 PG 8 WC Virology SC Virology GA 518GX UT WOS:000271679900004 PM 19860892 ER PT J AU Kleinman, SH Glynn, SA Lee, TH Tobler, LH Schlumpf, KS Todd, DS Qiao, H Yu, MYW Busch, MP AF Kleinman, Steven H. Glynn, Simone A. Lee, Tzong-Hae Tobler, Leslie H. Schlumpf, Karen S. Todd, Deborah S. Qiao, Hannah Yu, Mei-ying W. Busch, Michael P. CA NHLBI REDS II TI A linked donor-recipient study to evaluate parvovirus B19 transmission by blood component transfusion SO BLOOD LA English DT Article ID POLYMERASE-CHAIN-REACTION; HUMAN ERYTHROVIRUS B19; HIGH-PURITY; INFECTION; DNA; PREVALENCE; INDIVIDUALS; EXPOSURE; PATIENT; VIRUS AB Parvovirus B19V infection can be a serious infection for hematology patients with underlying hemolysis or compromised erythropoiesis syndromes. Although case reports of B19V transmission by blood component transfusion (as contrasted to manufactured plasma derivatives) are rare, no studies have systematically determined a rate of transmission to recipients transfused with B19V DNA-positive components. We used a linked donor and recipient repository and a sensitive, quantitative B19V DNA polymerase chain reaction (PCR) assay to assess such transmission in B19V-susceptible (ie, anti-B19V immunoglobulin G [IgG] negative) recipients. We assessed 112 B19V DNA-positive components from 105 donors (of 12 529 tested donations) transfused into a population of surgical patients with a pretransfusion B19V IgG seroprevalence of 78%. We found no transmission to 24 susceptible recipients from transfusion of components with B19V DNA at concentrations less than 10(6) IU/mL (upper 95% confidence interval, 11.7%). We found an anamnestic IgG response in one pretransfusion seropositive recipient transfused with a component containing greater than 10(10) IU/mL B19V DNA. These findings show either that transmission from components with less than 10(6) IU/mL does not occur, or, if it does, it is an uncommon event. These data do not support the need to routinely screen blood donations with a sensitive B19V DNA nucleic acid assay. (Blood. 2009114:3677-3683) C1 [Kleinman, Steven H.; Schlumpf, Karen S.; Todd, Deborah S.; Qiao, Hannah] Westat Corp, Rockville, MD USA. [Kleinman, Steven H.] Univ British Columbia, Dept Pathol, Vancouver, BC, Canada. [Glynn, Simone A.] NHLBI, Rockville, MD USA. [Lee, Tzong-Hae; Tobler, Leslie H.; Busch, Michael P.] Blood Syst Res Inst, San Francisco, CA USA. [Yu, Mei-ying W.] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. [Busch, Michael P.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. RP Kleinman, SH (reprint author), 1281 Rockcrest Ave, Victoria, BC V9A 4W4, Canada. EM skleinman@shaw.ca FU NHLBI REDS-II [N01-HB-47175, N01-HB-57181] FX This work was supported by NHLBI REDS-II (contracts N01-HB-47175 and N01-HB-57181). NR 37 TC 36 Z9 39 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD OCT 22 PY 2009 VL 114 IS 17 BP 3677 EP 3683 DI 10.1182/blood-2009-06-225706 PG 7 WC Hematology SC Hematology GA 509NK UT WOS:000271024500024 PM 19687508 ER PT J AU Calhoun, JV AF Calhoun, John V. TI THE COMPLEX HISTORY OF "INSECTS INJURIOUS TO VEGETATION" BY THADDEUS W. HARRIS, WITH A DATE CORRECTION AND LECTOTYPE DESIGNATION FOR VANESSA COMMA HARRIS (NYMPHALIDAE) SO JOURNAL OF THE LEPIDOPTERISTS SOCIETY LA English DT Article DE Charles W. Johnson; Lepidoptera; Samuel Henshaw; Thomas Say; type locality AB In 1841, Thaddeus W. Harris (1795-1856) published A Report on the Insects of Massachusetts, Injurious to Vegetation. Three more editions of the book were issued, one posthumously. Many taxa of Lepidoptera were described in the book, including twelve butterflies. The book's complex history is reviewed and publication dates of each edition are proposed. The publication date of Vanessa comma Harris is corrected and a lectotype of this taxon is designated. It is also revealed that Samuel Henshaw (1852-1941) and Charles W. Johnson (1863-1932) prepared determination and hype labels contained in the insect collection of T. W. Harris C1 [Calhoun, John V.] Univ Florida, Florida Museum Nat Hist, Res Associate McGuire Ctr Lepidoptera & Biodivers, Gainesville, FL 32611 USA. [Calhoun, John V.] FDACS, DPI, Gainesville, FL USA. RP Calhoun, JV (reprint author), 977 Wicks Dr, Palm Harbor, FL 34684 USA. NR 88 TC 0 Z9 0 U1 1 U2 2 PU LEPIDOPTERISTS SOC PI LOS ANGELES PA 900 EXPOSITION BLVD, LOS ANGELES, CA 90007-4057 USA SN 0024-0966 J9 J LEPID SOC JI J. Lepid. Soc. PD OCT 22 PY 2009 VL 63 IS 3 BP 154 EP 163 PG 10 WC Entomology SC Entomology GA 512IW UT WOS:000271242400004 ER PT J AU Chan-Tack, KM Murray, JS Birnkrant, DB AF Chan-Tack, Kirk M. Murray, Jeffrey S. Birnkrant, Debra B. TI Use of Ribavirin to Treat Influenza SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Chan-Tack, Kirk M.; Murray, Jeffrey S.; Birnkrant, Debra B.] US FDA, Silver Spring, MD USA. RP Chan-Tack, KM (reprint author), US FDA, Silver Spring, MD USA. NR 5 TC 20 Z9 23 U1 3 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 22 PY 2009 VL 361 IS 17 BP 1713 EP 1714 DI 10.1056/NEJMc0905290 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 508YW UT WOS:000270977400026 PM 19846864 ER PT J AU Rafii, F Williams, AJ Park, M Sims, LM Heinze, TM Cerniglia, CE Sutherland, JB AF Rafii, Fatemeh Williams, Anna J. Park, Miseon Sims, Lillie M. Heinze, Thomas M. Cerniglia, Carl E. Sutherland, John B. TI Isolation of bacterial strains from bovine fecal microflora capable of degradation of ceftiofur SO VETERINARY MICROBIOLOGY LA English DT Article DE Beta-lactamases; Biodegradation; Ceftiofur; Cephalosporins ID BETA-LACTAM ANTIBIOTICS; ESCHERICHIA-COLI; RESISTANCE; PENICILLIN; SODIUM; GENE; IDENTIFICATION; CEPHALOSPORIN; EVOLUTION; PROTEINS AB Ceftiofur, a third-generation cephalosporin used to treat bacterial infections in animals, is degraded in bovine feces but the specific bacteria involved are unknown. To find the bacteria involved in ceftiofur metabolism, the bovine fecal microflora was screened. Twenty-one nonidentical strains of bovine fecal bacteria were isolated on media containing 1-32 mu g ml(-1) of ceftiofur. The cultures were incubated with 5 mu g ml(-1) ceftiofur for different times, then centrifuged and analyzed by high-performance liquid chromatography. Three strains of Bacillus spp., two strains of Roseomonas spp., and one strain of Azospirillum sp. metabolized 5 mu g ml(-1) ceftiofur in broth cultures in less than 24 h: ten other strains of Roseomonas and one strain of Bacillus pumilus had metabolized it by 120 h. After the ceftiofur had been metabolized by these bacteria, the filter-sterilized supernatants of centrifuged cultures no longer inhibited the growth of a ceftiofur-sensitive strain of Kocuria rhizophila, which indicated that ceftiofur had been transformed to compounds without bactericidal activity. Each isolate was also found to be able to grow in the presence of other beta-lactams, and a nitrocefin assay showed beta-lactamase activity in the 17 strains that metabolized ceftiofur. The results show that some beta-lactamase-producing bacteria from the bovine fecal microflora are capable of transforming ceftiofur to metabolites lacking bactericidal activity. Published by Elsevier B.V. C1 [Rafii, Fatemeh; Williams, Anna J.; Park, Miseon; Sims, Lillie M.; Cerniglia, Carl E.; Sutherland, John B.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Heinze, Thomas M.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Sutherland, JB (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM john.sutherland@fda.hhs.gov FU Pfizer, Inc. FX This study was supported in part by a cooperative research and development agreement at the National Center for Toxicological Research funded by Pfizer, Inc., through an agreement between Pfizer and the U.S. Food and Drug Administration. The views presented in this article do not necessarily reflect those of either the Food and Drug Administration or Pfizer, Inc. NR 35 TC 8 Z9 8 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1135 J9 VET MICROBIOL JI Vet. Microbiol. PD OCT 20 PY 2009 VL 139 IS 1-2 BP 89 EP 96 DI 10.1016/j.vetmic.2009.04.023 PG 8 WC Microbiology; Veterinary Sciences SC Microbiology; Veterinary Sciences GA 511MG UT WOS:000271168800010 PM 19428193 ER PT J AU Choudhuri, S AF Choudhuri, Supratim TI Lesser known relatives of miRNA SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Review DE piRNA; ra-siRNA; ta-siRNA; nat-siRNA; hc-siRNA; scnRNA; qiRNA ID SMALL RNAS; ANTISENSE TRANSCRIPTS; SILENCING PATHWAYS; ARABIDOPSIS; BIOGENESIS; SIRNAS; PLANTS; DROSOPHILA; GERMLINE AB Since the discovery of RNAi (RNA interference) major attention has focused on studying miRNA (microRNA) and siRNA (small interfering RNA). However, within the last few years, several other small ncRNAs (non-coding RNAs) have been discovered and thus various newer acronyms representing these 'other' classes of small ncRNAs have populated the literature. Of these, piRNA (Piwi-interacting RNA) has been gaining importance because of its role as the guardian of the germline genome. Some of the other newly discovered small ncRNAs have been mostly reported in plants, and they are yet to be studied more comprehensively. Nevertheless, piRNA and the 'other' small ncRNAs deserve some discussion because they are members of the increasingly large family of small ncRNAs. (C) Published by Elsevier Inc. C1 [Choudhuri, Supratim] US FDA, Ctr Food Safety & Appl Nutr, Div Biotechnol, College Pk, MD 20740 USA. [Choudhuri, Supratim] DBGNR, GRAS Notice Review, OFAS, College Pk, MD 20740 USA. RP Choudhuri, S (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Biotechnol, HFS 255,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Supratim.Choudhuri@fda.hhs.gov NR 20 TC 16 Z9 17 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 16 PY 2009 VL 388 IS 2 BP 177 EP 180 DI 10.1016/j.bbrc.2009.08.039 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 555SI UT WOS:000274534300001 PM 19679101 ER PT J AU Zaitseva, M Kapnick, SM Scott, J King, LR Manischewitz, J Sirota, L Kodihalli, S Golding, H AF Zaitseva, Marina Kapnick, Senta M. Scott, John King, Lisa R. Manischewitz, Jody Sirota, Lev Kodihalli, Shantha Golding, Hana TI Application of Bioluminescence Imaging to the Prediction of Lethality in Vaccinia Virus-Infected Mice SO JOURNAL OF VIROLOGY LA English DT Article ID SMALLPOX VACCINE; IMMUNE-RESPONSES; ANKARA; IMMUNOGENICITY; ANTIBODIES; MONKEYPOX; CELLS AB To find an alternative endpoint for the efficacy of antismallpox treatments, bioluminescence was measured in live BALB/c mice following lethal challenge with a recombinant WR vaccinia virus expressing luciferase. Intravenous vaccinia immunoglobulin treatments were used to confer protection on a proportion of animals. Using known lethality outcomes in 200 animals and total fluxes recorded daily in live animals, we performed univariate receiver operating characteristic (ROC) curve analysis to assess whether lethality can be predicted based on bioluminescence. Total fluxes in the spleens on day 3 and in the livers on day 5 generated accurate predictive models; the area under the ROC curve (AUC) was 0.91. Multiple logistic regression analysis utilizing a linear combination of six measurements: total flux in the liver on days 2, 3, and 5; in the spleen on days 1 and 3; and in the nasal cavity on day 4 generated the most accurate predictions (AUC = 0.96). This model predicted lethality in 90% of animals with only 10% of nonsurviving animals incorrectly predicted to survive. Compared with bioluminescence, ROC analysis with 25% and 30% weight loss as thresholds accurately predicted survival on day 5, but lethality predictions were low until day 9. Collectively, our data support the use of bioimaging for lethality prediction following vaccinia virus challenge and for gaining insight into protective mechanisms conferred by vaccines and therapeutics. C1 [Zaitseva, Marina; Kapnick, Senta M.; Scott, John; King, Lisa R.; Manischewitz, Jody; Sirota, Lev; Golding, Hana] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. [Kodihalli, Shantha] Cangene Corp, Dept Clin Res, Winnipeg, MB R3T 5X8, Canada. RP Zaitseva, M (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bldg 29B,Room 4NN06,8800 Rockville Pike, Bethesda, MD 20892 USA. EM marina.zaitseva@fda.hhs.gov OI Scott, John/0000-0002-9116-948X FU National Institute of Allergy and Infectious Diseases; National Institutes of Health, Department of Health and Human Services [IAA 224-06-1322] FX This project was funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under IAA 224-06-1322. NR 27 TC 24 Z9 25 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT 15 PY 2009 VL 83 IS 20 BP 10437 EP 10447 DI 10.1128/JVI.01296-09 PG 11 WC Virology SC Virology GA 498FC UT WOS:000270121600012 PM 19656894 ER PT J AU Tsong, Y Zhang, J Zhong, JL AF Tsong, Yi Zhang, Joanne Zhong, Jinglin TI Comment on 'New confidence bounds for QT studies' SO STATISTICS IN MEDICINE LA English DT Letter ID QT/QTC C1 [Tsong, Yi; Zhang, Joanne; Zhong, Jinglin] US FDA, Div Biometr 6, Off Biostat, Ctr Drug Evaluat & Res,Off Translat Sci, Silver Spring, MD 20993 USA. RP Tsong, Y (reprint author), US FDA, Div Biometr 6, Off Biostat, Ctr Drug Evaluat & Res,Off Translat Sci, 10903 New Hampshire Blvd, Silver Spring, MD 20993 USA. NR 4 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD OCT 15 PY 2009 VL 28 IS 23 BP 2936 EP 2938 DI 10.1002/sim.3579 PG 3 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 507EB UT WOS:000270833000007 PM 19777537 ER PT J AU Gambus, A van Deursen, F Polychronopoulos, D Foltman, M Jones, RC Edmondson, RD Calzada, A Labib, K AF Gambus, Agnieszka van Deursen, Frederick Polychronopoulos, Dimitrios Foltman, Magdalena Jones, Richard C. Edmondson, Ricky D. Calzada, Arturo Labib, Karim TI A key role for Ctf4 in coupling the MCM2-7 helicase to DNA polymerase alpha within the eukaryotic replisome SO EMBO JOURNAL LA English DT Article DE Ctf4; DNA polymerase alpha; GINS; MCM2-7; replisome progression complex ID S-PHASE CHECKPOINT; REPLICATION FORK PROGRESSION; SISTER-CHROMATID COHESION; SACCHAROMYCES-CEREVISIAE; BUDDING YEAST; CATALYTIC SUBUNIT; CHROMOSOMAL DNA; TOPOISOMERASE-I; FISSION YEAST; GINS COMPLEX AB The eukaryotic replisome is a crucial determinant of genome stability, but its structure is still poorly understood. We found previously that many regulatory proteins assemble around the MCM2-7 helicase at yeast replication forks to form the replisome progression complex (RPC), which might link MCM2-7 to other replisome components. Here, we show that the RPC associates with DNA polymerase alpha that primes each Okazaki fragment during lagging strand synthesis. Our data indicate that a complex of the GINS and Ctf4 components of the RPC is crucial to couple MCM2-7 to DNA polymerase alpha. Others have found recently that the Mrc1 subunit of RPCs binds DNA polymerase epsilon, which synthesises the leading strand at DNA replication forks. We show that cells lacking both Ctf4 and Mrc1 experience chronic activation of the DNA damage checkpoint during chromosome replication and do not complete the cell cycle. These findings indicate that coupling MCM2-7 to replicative polymerases is an important feature of the regulation of chromosome replication in eukaryotes, and highlight a key role for Ctf4 in this process. The EMBO Journal (2009) 28, 2992-3004. doi: 10.1038/emboj.2009.226; Published online 6 August 2009 C1 [Gambus, Agnieszka; van Deursen, Frederick; Foltman, Magdalena; Labib, Karim] Univ Manchester, Paterson Inst Canc Res, Manchester M20 4BX, Lancs, England. [Polychronopoulos, Dimitrios] Univ Athens, Fac Biol, Dept Cell Biol & Biophys, Athens, Greece. [Jones, Richard C.; Edmondson, Ricky D.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Calzada, Arturo] Ctr Nacl Biotecnol, Madrid, Spain. RP Labib, K (reprint author), Univ Manchester, Paterson Inst Canc Res, Wilmslow Rd, Manchester M20 4BX, Lancs, England. EM klabib@picr.man.ac.uk RI Polychronopoulos, Dimitris/G-8214-2014; Calzada, Arturo/M-1168-2014 OI Polychronopoulos, Dimitris/0000-0001-9427-3082; Calzada, Arturo/0000-0002-3190-688X FU Cancer Research UK; EMBO Young Investigator Programme; Sir Henry Wellcome Postdoctoral Fellowship FX We are very grateful to Cancer Research UK who funded this work, and thank the EMBO Young Investigator Programme for their support. AG is now supported by a Sir Henry Wellcome Postdoctoral Fellowship. NR 56 TC 121 Z9 121 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 7 PY 2009 VL 28 IS 19 BP 2992 EP 3004 DI 10.1038/emboj.2009.226 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 503DY UT WOS:000270514000013 PM 19661920 ER PT J AU Pogribny, IP Shpyleva, SI Muskhelishvili, L Bagnyukova, TV James, SJ Beland, FA AF Pogribny, Igor P. Shpyleva, Svitlana I. Muskhelishvili, Levan Bagnyukova, Tetyana V. James, S. Jill Beland, Frederick A. TI Role of DNA damage and alterations in cytosine DNA methylation in rat liver carcinogenesis induced by a methyl-deficient diet SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE Oxidative DNA damage; DNA methylation; Liver carcinogenesis; Methyl-deficiency ID ACID-DEFINED DIET; CHOLINE-DEFICIENT; OXIDATIVE STRESS; GLOBAL DNA; INDUCED HEPATOCARCINOGENESIS; HEPATOCELLULAR-CARCINOMA; CHEMICAL CARCINOGENESIS; HEPATIC PRENEOPLASIA; EPIGENETIC CHANGES; FOLATE-DEFICIENCY AB Currently, cancer is recognized as a disease provoked by both genetic and epigenetic events. However, the significance of early genetic and epigenetic alterations with respect to carcinogenic process in general and to liver carcinogenesis in particular remains unexplored. A lack of knowledge regarding how specific alterations during early preneoplasia, may be mechanistically related to tumor formation creates a major gap in understanding the role of these genetic and epigenetic abnormalities in carcinogenesis. In the present study we investigated the contribution of DNA damage and epigenetic alterations to liver carcinogenesis induced by a methyl-deficient diet. Feeding Fisher 344 rats a methyl-deficient diet for 9 weeks resulted in DNA damage and aberrant DNA methylation. This was evidenced by an early upregulation of the base excision DNA repair genes, accumulation of 8-oxodeoxyguanosine and 3'OH-end strand breaks in DNA, pronounced global loss of DNA methylation, and hypermethylation of CpG islands in the livers of methyl-deficient rats. These abnormalities were completely restored in the livers of rats exposed to methyl-deficiency for 9 weeks after removal of the methyl-deficient diet and re-feeding a methyl-sufficient diet. However, when rats were fed a methyl-deficient diet for 18 week and then given a methyl-sufficient diet, only DNA lesions were repaired. The m ethyl-sufficient diet failed to restore completely the altered DNA methylation status and prevent the progression of liver carcinogenesis. These results suggest that stable alterations in DNA methylation are a factor that promotes the progression of liver carcinogenesis Additionally, the results indicate that epigenetic changes may be more reliable markers than DNA lesions of the carcinogenic process and carcinogen exposure Published by Elsevier B.V. C1 [Pogribny, Igor P.; Shpyleva, Svitlana I.; Bagnyukova, Tetyana V.; Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Shpyleva, Svitlana I.] RE Kavetsky Inst Expt Pathol Oncol & Radiobiol, Dept Mech Anticanc Therapy, UA-03022 Kiev, Ukraine. [James, S. Jill] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhsgov NR 49 TC 25 Z9 27 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD OCT 2 PY 2009 VL 669 IS 1-2 BP 56 EP 62 DI 10.1016/j.mrfmmm.2009.05.003 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 510CO UT WOS:000271065800009 PM 19442675 ER PT J AU Contreras, CA Ochoa, TJ Lacher, DW Lanata, CF Donnemberg, MS Cleary, TG AF Contreras, C. A. Ochoa, T. J. Lacher, D. W. Lanata, C. F. Donnemberg, M. S. Cleary, T. G. TI ALLELE VARIABILITY OF CRITICAL VIRULENCE GENES IN TYPICAL AND ATYPICAL EPEC IN PERUVIAN CHILDREN SO ACTA PAEDIATRICA LA English DT Meeting Abstract C1 [Contreras, C. A.; Ochoa, T. J.] Univ Peruana Cayetano Heredia, Inst Med Trop Alexander von Humboldt, Lima, Peru. [Ochoa, T. J.; Cleary, T. G.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Lacher, D. W.] US FDA, Rockville, MD 20857 USA. [Lanata, C. F.] Inst Invest Nutr, Lima, Peru. [Lanata, C. F.] Univ Peruana Ciencias Aplicadas, Lima, Peru. [Donnemberg, M. S.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD OCT PY 2009 VL 98 BP 106 EP 107 PG 2 WC Pediatrics SC Pediatrics GA 495AR UT WOS:000269862100276 ER PT J AU Wojas, AM Graham, AS AF Wojas, Anna M. Graham, Angie S. TI Drug Information Services: The Answer to Your Drug-Related Questions SO AMERICAN FAMILY PHYSICIAN LA English DT Editorial Material ID CLINICAL PHARMACY SERVICES C1 [Wojas, Anna M.] US FDA, Rockville, MD 20857 USA. [Graham, Angie S.] Stanford Hosp & Clin, Palo Alto, CA USA. RP Wojas, AM (reprint author), US FDA, Rockville, MD 20857 USA. EM wojas@fda.hhs.gov NR 4 TC 0 Z9 1 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD OCT 1 PY 2009 VL 80 IS 7 BP 670 EP + PG 2 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 505QP UT WOS:000270709700002 PM 19817334 ER PT J AU Wollscheid, KA Kremzner, ME AF Wollscheid, Kristine A. Kremzner, Mary E. TI Electronic cigarettes: Safety concerns and regulatory issues SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Editorial Material C1 [Wollscheid, Kristine A.] US FDA, Div Drug Informat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Wollscheid, KA (reprint author), US FDA, Div Drug Informat, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM kristine.wollscheid@fda.hhs.gov NR 5 TC 27 Z9 28 U1 1 U2 56 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD OCT 1 PY 2009 VL 66 IS 19 BP 1740 EP 1742 DI 10.2146/ajhp090127 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 496EJ UT WOS:000269951900013 PM 19767381 ER PT J AU Griffin, MR Braun, MM Bart, KJ AF Griffin, Marie R. Braun, M. Miles Bart, Kenneth J. TI What Should an Ideal Vaccine Postlicensure Safety System Be? SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID ADVERSE EVENTS; UNITED-STATES; ASSOCIATION; LICENSURE; MEASLES; AUTISM; MUMPS AB In 2007 the National Vaccine Program, along with the Centers for Disease Control and Prevention, the Food and Drug Administration, the National Institutes of Health, and the Health Resources and Services Administration, sponsored a public conference titled "Vaccine Safety Evaluation: Post Marketing Surveillance "The objective was to discuss enhanced approaches to postlicensure evaluation of vaccine safety, including active and passive surveillance systems and special studies. The conference participants reviewed the evolution of the assessment of vaccine safety, detailed current national approaches to postmarketing safety, and offered new approaches to evaluating vaccine safety. A number of the participants recommended that information systems be expanded to include reliable information on vaccination and health outcomes in large populations. We summarize the major meeting presentations and discussions. (Am J Public Health. 2009;99:S345-S350. doi.10.2105/AJPH.2008.143081) C1 [Griffin, Marie R.] Vanderbilt Univ, Sch Med, Dept Prevent Med, Nashville, TN 37212 USA. [Griffin, Marie R.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. [Griffin, Marie R.] Mid S Geriatr Res Educ & Clin Ctr, Nashville, TN USA. [Griffin, Marie R.] VA Tennessee Valley Healthcare Syst, Clin Res Ctr Excellence, Nashville, TN USA. [Braun, M. Miles] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Bart, Kenneth J.] Off Secretary Hlth & Human Serv, Natl Vaccine Program Off, Off Publ Hlth & Sci, Washington, DC USA. RP Bart, KJ (reprint author), 9917 Conestoga Way, Potomac, MD 20854 USA. FU MedImmune, Pfiza, the Centers for Disease Control and Prevention [5U01Ip000022-04]; Veterans Adminstration [1.TPS[CSP 403C]]; Agency for Healthcare Research and Quality [HHSA290-2005-0042.ITO2] FX Marie R Griflin received grant support from MedImmune, Pfiza, the Centers for Disease Control and Prevention (5U01Ip000022-04), the Veterans Adminstration (1.TPS[CSP#403C]), and the Agency for Healthcare Research and Quality (HHSA290-2005-0042.ITO2). In addition she is a consultant for Merck. NR 25 TC 10 Z9 10 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 2009 VL 99 SU 2 BP S345 EP S350 DI 10.2105/AJPH.2008.143081 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 512BY UT WOS:000271218800021 PM 19797747 ER PT J AU Davit, BM Nwakama, PE Buehler, GJ Conner, DP Haidar, SH Patel, DT Yang, YS Yu, LX Woodcock, J AF Davit, Barbara M. Nwakama, Patrick E. Buehler, Gary J. Conner, Dale P. Haidar, Sam H. Patel, Devvrat T. Yang, Yongsheng Yu, Lawrence X. Woodcock, Janet TI Comparing Generic and Innovator Drugs: A Review of 12 Years of Bioequivalence Data from the United States Food and Drug Administration SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE bioequivalence; Food and Drug Administration; generic drugs; pharmacoeconomics ID HIGHLY VARIABLE DRUGS; MONTE-CARLO SIMULATIONS; ANTIEPILEPTIC DRUGS; SUBSTITUTION; ABSORPTION; SINGLE; BIOAVAILABILITY; WARFARIN; EPILEPSY; CMAX AB BACKGROUND: In the US, manufacturers seeking approval to market a generic drug product must submit data demonstrating that the generic formulation provides the same rate and extent of absorption as (ie, is bioequivalent to) the innovator drug product. Thus, most orally administered generic drug products in the US are approved based on results of one or more clinical bioequivalence studies. OBJECTIVE: To evaluate how well the bioequivalence measures of generic drugs approved in the US over a 12-year period compare with those of their corresponding innovator counterparts, METHODS: This retrospective analysis compared the generic and innovator bioequivalence measures from 2070 single-dose clinical bioequivalence studies of orally administered generic drug products approved by the Food and Drug Administration (FDA) from 1996 to 2007 (12 y). Bioequivalence measures evaluated were drug peak plasma concentration (C(max)) and area under the plasma drug concentration versus time curve (AUC), representing drug rate and extent of absorption, respectively. The generic/innovator C(max) and AUC geometric mean ratios (GMRs) were determined from each of the bioequivalence studies, which used from 12 to 170 subjects. The GMRs from the 2070 studies were averaged. In addition, the distribution of differences between generic means and innovator means was determined for both C(max) and AUC. RESULTS: The mean +/- SD of the GMRs from the 2070 studies was 1.00 +/- 0.06 for C(max) and 1.00 +/- 0.04 for AUC. The average difference in C(max) and AUC between generic and innovator products was 4.35% and 3.56%, respectively In addition, in nearly 98% of the bioequivalence studies conducted during this period, the generic product AUC differed from that of the innovator product by less than 10%. CONCLUSIONS: The criteria used to evaluate generic drug bioequivalence studies support the FDA's objective of approving generic drug formulations that are therapeutically equivalent to their innovator counterparts. C1 [Davit, Barbara M.; Nwakama, Patrick E.] US FDA, Div Bioequivalence 2, Off Gener Drugs, Ctr Drug Evaluat & Res,Off Pharmaceut Sci, Derwood, MD 20855 USA. [Conner, Dale P.; Patel, Devvrat T.] US FDA, Div Bioequivalence 1, Off Gener Drugs, Ctr Drug Evaluat & Res,Off Pharmaceut Sci, Derwood, MD 20855 USA. RP Davit, BM (reprint author), US FDA, Div Bioequivalence, Off Gener Drugs, Ctr Drug Evaluat & Res, 7520 Standish Pl,Metro Pk N 1, Derwood, MD 20855 USA. EM barbara.davit@fda.hhs.gov RI Yu, Lawrence/L-6280-2016 NR 65 TC 97 Z9 100 U1 2 U2 14 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD OCT PY 2009 VL 43 IS 10 BP 1583 EP 1597 DI 10.1345/aph.1M141 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 503YR UT WOS:000270579100003 PM 19776300 ER PT J AU Wang, SY Deng, KP Zaremba, S Deng, XY Lin, CH Wang, Q Tortorello, ML Zhang, W AF Wang, Siyun Deng, Kaiping Zaremba, Sam Deng, Xiangyu Lin, Chiahui Wang, Qian Tortorello, Mary Lou Zhang, Wei TI Transcriptomic Response of Escherichia coli O157:H7 to Oxidative Stress SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID REDOX-REGULATED CHAPERONE; COMPLETE GENOME SEQUENCE; HYDROGEN-PEROXIDE; CHLORINATED WATER; UNITED-STATES; LISTERIA-MONOCYTOGENES; STAPHYLOCOCCUS-AUREUS; BIOFILM FORMATION; MAMMALIAN-CELLS; GENE-EXPRESSION AB Chlorinated water is commonly used in industrial operations to wash and sanitize fresh-cut, minimally processed produce. Here we compared 42 human outbreak strains that represented nine distinct Escherichia coli O157:H7 genetic lineages (or clades) for their relative resistance to chlorine treatment. A quantitative measurement of resistance was made by comparing the extension of the lag phase during growth of each strain under exposure to sublethal concentrations of sodium hypochlorite in Luria-Bertani or brain heart infusion broth. Strains in clade 8 showed significantly (P < 0.05) higher resistance to chlorine than strains from other clades of E. coli O157: H7. To further explore how E. coli O157: H7 responds to oxidative stress at transcriptional levels, we analyzed the global gene expression profiles of two strains, TW14359 (clade 8; associated with the 2006 spinach outbreak) and Sakai (clade 1; associated with the 1996 radish sprout outbreak), under sodium hypochlorite or hydrogen peroxide treatment. We found over 380 genes were differentially expressed (more than twofold; P < 0.05) after exposure to low levels of chlorine or hydrogen peroxide. Significantly upregulated genes included several regulatory genes responsive to oxidative stress, genes encoding putative oxidoreductases, and genes associated with cysteine biosynthesis, iron-sulfur cluster assembly, and antibiotic resistance. Identification of E. coli O157: H7 strains with enhanced resistance to chlorine decontamination and analysis of their transcriptomic response to oxidative stress may improve our basic understanding of the survival strategy of this human enteric pathogen on fresh produce during minimal processing. C1 [Wang, Siyun; Deng, Xiangyu; Lin, Chiahui; Wang, Qian; Zhang, Wei] IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. [Deng, Kaiping; Tortorello, Mary Lou] US FDA, Summit Argo, IL 60501 USA. [Zaremba, Sam] SRA Int, Enteropathogen Resource Integrat Ctr, Rockville, MD 20852 USA. RP Zhang, W (reprint author), IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. EM zhangw@iit.edu FU U. S. Food and Drug Administration; National Center for Food Safety; Technology of the Illinois Institute of Technology FX This study was supported by a U. S. Food and Drug Administration cooperative agreement research grant to the National Center for Food Safety and Technology of the Illinois Institute of Technology. NR 86 TC 52 Z9 54 U1 0 U2 16 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 OCT 1 PY 2009 VL 75 IS 19 BP 6110 EP 6123 DI 10.1128/AEM.00914-09 PG 14 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 498CE UT WOS:000270113200010 PM 19666735 ER PT J AU Robison, TW Jacobs, A AF Robison, Timothy W. Jacobs, Abigail TI Metabolites in safety testing SO BIOANALYSIS LA English DT Article ID DAWLEY CRL-CD(SD) RATS; 2 DISTINCT PHENOTYPES; METABONOMIC IDENTIFICATION; MASS-SPECTROMETRY; DRUG METABOLITES; QUANTIFICATION; ACETAMINOPHEN; ACID AB Traditionally, only circulating concentrations of parent drug have been measured in the rodent and nonrodent test species used for drug safety assessments and served as an index of systemic exposure for comparisons to human exposures. Circulating concentrations of metabolites have generally only been measured in specialized circumstances (e.g., parent compound was extensively metabolized). Measurement of only the parent compound is usually sufficient when the metabolite profile in humans is similar to that in at least one of the animal species used in the nonclinical safety assessment. However, it is possible that metabolites formed in humans might not be present in the rodent and nonrodent test species used for drug safety assessments or the metabolites are formed at disproportionately higher concentrations in humans than in the animal test species. Generally, metabolites identified only in human plasma or metabolites present at disproportionately higher concentrations in humans than in any of the animal test species should be considered for safety assessment. The Center for Drug Evaluation and Research (CDER) published a Guidance for Industry on Safety Testing of Drug Metabolites that provides current thinking within CDER on the nonclinical safety assessment of human drug metabolites derived from drug products. The CDER guidance defines human metabolites that can raise a safety concern as those formed at greater than 10% of parent drug systemic exposure at a steady state. By contrast, the more recent International Conference on Harmonization: Guideline on Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals (ICH M3[R2]) describes the threshold as 10% of total drug-related exposure. Where they differ, the ICH guidance supersedes the CDER Guidance. The purpose of this article is to provide a perspective on the important details of these guidances from a regulatory review standpoint, as well as discuss some concerns that have arisen from the regulated industry regarding the CDER guidance. Such issues include parent drug that is extensively metabolized, metabolism by intestinal bacteria and metabolites formed by nonclinical test species but not humans. C1 [Robison, Timothy W.; Jacobs, Abigail] US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Silver Spring, MD 20993 USA. RP Robison, TW (reprint author), US FDA, Ctr Drug Evaluat & Res, Off New Drugs, 10993 New Hampshire Ave, Silver Spring, MD 20993 USA. EM timothy.robison@fda.hhs.gov NR 34 TC 28 Z9 28 U1 0 U2 5 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 J9 BIOANALYSIS JI Bioanalysis PD OCT PY 2009 VL 1 IS 7 BP 1193 EP 1200 DI 10.4155/BIO.09.98 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 644VM UT WOS:000281409800008 PM 21083045 ER PT J AU Lute, S Wang, H Sanchez, D Barletta, J Chen, Q Brorson, K AF Lute, Scott Wang, Hua Sanchez, Davonie Barletta, Janet Chen, Qi Brorson, Kurt TI Multiplex RT Q-PCR assay for simultaneous quantification of three viruses used for validation of virus clearance by biopharmaceutical production SO BIOLOGICALS LA English DT Article DE Q-PCR; Viral safety; Monoclonal antibodies ID TIME QUANTITATIVE PCR; PHARMACEUTICAL PROTEIN-PURIFICATION; CLINICAL SPECIMENS; REMOVAL; SIMIAN-VIRUS-40; CHROMATOGRAPHY; INFECTIONS; SAMPLES; MEDIA AB Virus removal studies are used to insure the safety of biopharmaceutical products by quantitatively estimating the viral clearance capacity by the manufacturing process. Virus quantification assays are used to measure the log(10) clearance factor of individual purification unit operations in spike recovery studies. We have developed a multiplex RT Q-PCR assay that detects and quantifies three commonly used model viruses X-MuLV, SV40, and MMV simultaneously. This RT Q-PCR multiplex assay has a 6 log(10) dynamic range with a limit of detection (LOD) of approximate to 1 genome copy/mu L. Amplification profiles are similar to existing singleplex assays. Overall, this RT Q-PCR multiplex assay is highly quantitative, accurately identifies multiple viruses simultaneously, and may prove useful to validate viral clearance of biological products in small scale studies. Published by Elsevier Ltd on behalf of The International Association for Biologicals. C1 [Lute, Scott; Barletta, Janet; Brorson, Kurt] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Wang, Hua; Sanchez, Davonie; Chen, Qi] Genentech Inc, Late Stage Purificat, Proc Res & Dev, San Francisco, CA 94080 USA. RP Lute, S (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM scott.lute@fda.hhs.gov FU CDER/FDA Regulatory Science and Review Enhancement Program [07-62] FX The authors thank Drs. Lixin Xu and Chu Chieh Hsia of FDA for carefully reviewing this manuscript. This study was partially funded by a CDER/FDA Regulatory Science and Review Enhancement Program award (RSR #07-62). The authors thank Travis J. Antes of Applied BioSystems Inc. for critical assistance during the design of the multiplex primers and probes. NR 24 TC 4 Z9 4 U1 1 U2 5 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD OCT PY 2009 VL 37 IS 5 BP 331 EP 337 DI 10.1016/j.biologicals.2009.07.002 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 504SS UT WOS:000270638500009 PM 19683941 ER PT J AU Mendrick, DL Schnackenberg, L AF Mendrick, Donna L. Schnackenberg, Laura TI Genomic and metabolomic advances in the identification of disease and adverse event biomarkers SO BIOMARKERS IN MEDICINE LA English DT Review DE biomarker; genomic; metabolomic; metabonomic; personalized; medicine; pharmacogenomic ID NUCLEAR-MAGNETIC-RESONANCE; CHROMATOGRAPHY-MASS-SPECTROMETRY; BLOOD MONONUCLEAR-CELLS; CONTROL MAQC PROJECT; GENE-EXPRESSION; PERIPHERAL-BLOOD; ISCHEMIC-STROKE; DRUG TOXICITY; PERSONALIZED MEDICINE; H-1-NMR SPECTROSCOPY AB Incomplete knowledge of tissue pathogenesis is hampering the identification of biomarkers for the appropriate therapeutic targets to prevent or inhibit disease processes, and the prediction and diagnosis of injury due to disease and adverse events of drug therapy. The revolution in genomics and metabolomics, combined with advanced bioinformatics and computational methods for mining such large, complex data sets, are beginning to provide critical insights into tissue injury. Such results will move us closer to the promise of personalized medicine. C1 [Mendrick, Donna L.; Schnackenberg, Laura] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. RP Mendrick, DL (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, BFT-230,3900 NCTR Rd, Jefferson, AR 72079 USA. EM donna.mendrick@fda.hhs.gov NR 102 TC 13 Z9 16 U1 2 U2 10 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 J9 BIOMARK MED JI Biomark. Med. PD OCT PY 2009 VL 3 IS 5 BP 605 EP 615 DI 10.2217/BMM.09.43 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 511CA UT WOS:000271140300019 PM 20477528 ER PT J AU Myers, MB Mittelstaedt, RA Heflich, RH AF Myers, Meagan B. Mittelstaedt, Roberta A. Heflich, Robert H. TI Using Phi X174 DNA as an exogenous reference for measuring mitochondrial DNA copy number SO BIOTECHNIQUES LA English DT Article DE quantitative PCR; mitochondrial DNA copy number; exogenous reference; Phi X174 DNA; DNA extraction ID TOXICITY; POLYPLOIDY; DEPLETION; MARKER; MUSCLE AB Quantitative real-time PCR has become a popular method to analyze and quantify changes in the copy number of mitochondrial DNA (mtDNA), and nuclear DNA (nDNA) is often used as an endogenous reference for mtDNA abundance. In our experience, using nDNA as a reference is problematic, due to differences in the extraction efficiency of nDNA and mtDNA and variation in the ploidy of experimental samples. Here, we report that the ratio of mtDNA to nDNA varies in repeated DNA extractions but that Phi X174 DNA, added before DNA extraction, is extracted with a similar efficiency to mtDNA, making it a suitable alternative reference for quantifying mtDNA copy number. C1 [Myers, Meagan B.; Mittelstaedt, Roberta A.; Heflich, Robert H.] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Myers, MB (reprint author), 3900 NCTR Rd,HFT 120, Jefferson, AR 72079 USA. EM meagan.myers@fda.hhs.gov FU National Center for Toxicological Research/Food and Drug Administration; National Institute for Environmental Health Sciences/National Toxicology Program [224-07-0007]; Oak Ridge Institute for Science and Education FX This research was supported by the National Center for Toxicological Research/Food and Drug Administration and National Institute for Environmental Health Sciences/National Toxicology Program (Interagency Agreement No. 224-07-0007). M. B. M. received fellowship support from the Oak Ridge Institute for Science and Education, administered though an interagency agreement between the Department of Energy and the Food and Drug Administration. The views expressed in this article do not necessarily reflect those of the Food and Drug Administration. NR 13 TC 8 Z9 10 U1 0 U2 1 PU BIOTECHNIQUES OFFICE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD OCT PY 2009 VL 47 IS 4 BP 867 EP 869 DI 10.2144/000113222 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 594TC UT WOS:000277559900010 PM 19852770 ER PT J AU Strauss, DM Lute, S Tebaykina, Z Frey, DD Ho, C Blank, GS Brorson, K Chen, Q Yang, B AF Strauss, Daniel M. Lute, Scott Tebaykina, Zinaida Frey, Douglas D. Ho, Cintia Blank, Gregory S. Brorson, Kurt Chen, Qi Yang, Bin TI Understanding the Mechanism of Virus Removal by Q Sepharose Fast Flow Chromatography During the Purification of CHO-Cell Derived Biotherapeutics SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE viral clearance; virus chromatography; anion exchange chromatograogt (AEX); Q sepharose fast flow (QSFF); chromatofocusing ID ANION-EXCHANGE CHROMATOGRAPHY; TIME QUANTITATIVE PCR; PHARMACEUTICAL PROTEIN-PURIFICATION; ADENOASSOCIATED VIRAL VECTORS; RETROVIRAL VECTORS; MEMBRANE FILTERS; HUMAN ALBUMIN; MINUTE VIRUS; ADSORPTION; POLIOVIRUS AB During production of therapeutic monoclonal antibodies (mAbs) in mammalian cell culture, it is important to ensure that viral impurities and potential viral contaminants will be removed during downstream purification. Anion exchange chromatography provides a high degree of virus removal from mAb feedstocks, but the mechanism by which this is achieved has not been characterized. In this work, we have investigated the binding of three viruses to Q sepharose fast flow (QSFF) resin to determine the degree to which electrostatic interactions are responsible for viral clearane by this process. We first used a chromatofocusing technique to determine the isoelectric points of the viruses and established that they are negatively charged under standard QSFF conditions. We then determined that virus removal by this chromatography resin is strongly disrupted by the presence of high salt concentrations or by the absence of the positively charged Q ligand, indicating that binding of the virus to the resin is primarily due to electrostatic forces, and that any non-electrostatic interactions which may be present are not sufficient to provide virus removal. Finally, we determined the binding profile of a virus in a QSFF column after a viral clearance process. These data indicate that viruus particles generally behave similarly to proteins, but they also illustrate the high degree of performance necessary to achieve several logs of virus reduction. Overall, this mechanistic understanding of an important viral clearance process provides the foundation for the development of science-based process validation strategies to ensure viral safety of biotechnology products. Biotechnol. Bioeng. 2009;104: 371-380. (C) 2009 Wiley Periodicals, Inc. C1 [Strauss, Daniel M.; Tebaykina, Zinaida; Ho, Cintia; Blank, Gregory S.; Chen, Qi; Yang, Bin] Genentech Inc, Proc Res & Dev, San Francisco, CA 94080 USA. [Lute, Scott; Brorson, Kurt] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Frey, Douglas D.] Univ Maryland Baltimore Cty, Dept Chem & Biochem Engn, Baltimore, MD 21228 USA. RP Yang, B (reprint author), Genentech Inc, Proc Res & Dev, 1 DNA Way, San Francisco, CA 94080 USA. EM yang.bin@gene.com OI Good, Zinaida/0000-0003-2343-5771 NR 49 TC 22 Z9 23 U1 1 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD OCT 1 PY 2009 VL 104 IS 2 BP 371 EP 380 DI 10.1002/bit.22416 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 494VI UT WOS:000269846900015 PM 19575414 ER PT J AU Verma, A Ngundi, MM Meade, BD De Pascalis, R Elkins, KL Burns, DL AF Verma, Anita Ngundi, Miriam M. Meade, Bruce D. De Pascalis, Roberto Elkins, Karen L. Burns, Drusilla L. TI Analysis of the Fc Gamma Receptor-Dependent Component of Neutralization Measured by Anthrax Toxin Neutralization Assays SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID LETHAL TOXIN; PROTECTIVE ANTIGEN; MONOCLONAL-ANTIBODY; IMMUNE-RESPONSES; MOUSE MACROPHAGE; RIV; IGG; COMPLEXES; VACCINE AB Anthrax toxin neutralization assays are used to measure functional antibody levels elicited by anthrax vaccines in both preclinical and clinical studies. In this study, we investigated the magnitude and molecular nature of Fc gamma (Fc gamma) receptor-dependent toxin neutralization observed in commonly used forms of the anthrax toxin neutralization assay. Significantly more Fc gamma receptor-dependent neutralization was observed in the J774A.1 cell-based assay than in the RAW 264.7 cell-based assay, a finding that could be due to the larger numbers of Fc gamma receptors that we found on J774A.1 cells by using flow cytometry. Thus, the extent to which Fc gamma receptor-dependent neutralization contributes to the total neutralization measured by the assay depends on the specific cell type utilized in the assay. Using Fc gamma receptor blocking monoclonal antibodies, we found that at least three murine Fc gamma receptor classes, IIB, III, and IV, can contribute to Fc gamma receptor-dependent neutralization. When antibodies elicited by immunization of rabbits with protective-antigen-based anthrax vaccines were analyzed, we found that the magnitude of Fc gamma receptor-dependent neutralization observed in the J774A.1 cell-based assay was dependent on the concentration of protective antigen utilized in the assay. Our results suggest that the characteristics of the antibodies analyzed in the assay (e. g., species of origin, isotype, and subclass), as well as the assay design (e. g., cell type and protective antigen concentration), could significantly influence the extent to which Fc gamma receptor-dependent neutralization contributes to the total neutralization measured by anthrax toxin neutralization assays. These findings should be considered when interpreting anthrax toxin neutralization assay output. C1 [Verma, Anita; Ngundi, Miriam M.; De Pascalis, Roberto; Elkins, Karen L.; Burns, Drusilla L.] US FDA, CBER, Bethesda, MD 20892 USA. [Meade, Bruce D.] Meade Biol, Hillsborough 27278, North Ireland. RP Burns, DL (reprint author), US FDA, CBER, HFM 434,Bldg 29,Room 130,8800 Rockville Pike, Bethesda, MD 20892 USA. EM drusilla.burns@fda.hhs.gov FU CBER/FDA-NIAID/NIH [YI-AI-6153-01] FX The following reagents were obtained from the NIH Biodefense and Emerging Infections Research Resources Repository, NIAID, NIH: anthrax LF, recombinant from B. anthracis, NR-142; anthrax PA, recombinant from B. anthracis, NR-140; J774A. 1 monocyte/macrophage (mouse) Working Cell Bank, NR-28; and rabbit anti-PA reference serum pool, NR-3839. MAb 9E9 was the generous gift of Jeffrey Ravetch, Rockefeller University. We thank Tod Merkel, Vanessa Kelly, and Siobha ' n Cowley for expert help and advice. NR 31 TC 17 Z9 17 U1 2 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD OCT PY 2009 VL 16 IS 10 BP 1405 EP 1412 DI 10.1128/CVI.00194-09 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 501IQ UT WOS:000270375500004 PM 19656993 ER PT J AU Wisner, KL Appelbaum, PS Uhl, K Goldkind, SF AF Wisner, K. L. Appelbaum, P. S. Uhl, K. Goldkind, S. F. TI Pharmacotherapy for Depressed Pregnant Women: Overcoming Obstacles to Gathering Essential Data SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID ANTIDEPRESSANT TREATMENT; MAJOR DEPRESSION AB Approximately 3% of pregnant women take antidepressant medications. Information on the impact of antidepressants on short- and long-term maternal and offspring outcomes is highly desirable but neglected. The position that the dearth of treatment information is of greater concern than the risks to pregnant subjects involved in medical research is gaining support. Mandating the collection of reproductive outcome data in exposed childbearing women is an overdue step toward societal responsibility to our most vulnerable members. C1 [Wisner, K. L.] Dept Psychiat, Pittsburgh, PA USA. [Wisner, K. L.] Dept Obstet, Pittsburgh, PA USA. [Wisner, K. L.] Dept Gynecol & Reprod Sci, Pittsburgh, PA USA. [Wisner, K. L.] Dept Epidemiol, Pittsburgh, PA USA. [Wisner, K. L.] Dept Womens Studies, Pittsburgh, PA USA. [Wisner, K. L.] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA USA. [Appelbaum, P. S.] Columbia Univ, Dept Psychiat, Div Law Eth & Psychiat, New York, NY USA. [Appelbaum, P. S.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Uhl, K.] US FDA, Off Womens Hlth, Rockville, MD 20857 USA. [Goldkind, S. F.] US FDA, Good Clin Practice Program, Off Commissioner, Rockville, MD 20857 USA. RP Wisner, KL (reprint author), Dept Psychiat, Pittsburgh, PA USA. EM wisnerkl@upmc.edu NR 5 TC 9 Z9 9 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 OCT PY 2009 VL 86 IS 4 BP 362 EP 365 DI 10.1038/clpt.2009.160 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 500LO UT WOS:000270303500011 PM 19763116 ER PT J AU Kannan, P John, C Zoghbi, SS Halldin, C Gottesman, MM Innis, RB Hall, MD AF Kannan, P. John, C. Zoghbi, S. S. Halldin, C. Gottesman, M. M. Innis, R. B. Hall, M. D. TI Imaging the Function of P-Glycoprotein With Radiotracers: Pharmacokinetics and In Vivo Applications SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT News Item ID BLOOD-BRAIN-BARRIER; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL AMYLOID ANGIOPATHY; MULTIDRUG-RESISTANCE; DRUG TRANSPORTERS; BREAST-CANCER; QUANTITATIVE ASSESSMENT; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; TC-99M SESTAMIBI AB P-glycoprotein (P-gp), an efflux transporter, controls the pharmacokinetics of various compounds under physiological conditions. P-gp-mediated drug efflux has been suggested as playing a role in various disorders, including multidrug-resistant cancer and medication-refractory epilepsy. However, P-gp inhibition has had, to date, little or no clinically significant effect in multidrug-resistant cancer. To enhance our understanding of its in vivo function under pathophysiological conditions, substrates of P-gp have been radiolabeled and imaged using single-photon emission computed tomography (SPECT) and positron emission tomography (PET). To accurately quantify P-gp function, a radiolabeled P-gp substrate should be selective for P-gp, produce a large signal after P-gp blockade, and generate few radiometabolites that enter the target tissue. Furthermore, quantification of P-gp function via imaging requires pharmacological inhibition of P-gp, which requires knowledge of P-gp density at the target site. By meeting these criteria, imaging can elucidate the function of P-gp in various disorders and improve the efficacy of treatments. C1 [Kannan, P.; Zoghbi, S. S.; Innis, R. B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Kannan, P.; Halldin, C.] Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, Stockholm, Sweden. [John, C.] US FDA, Off Clin Pharmacol, Rockville, MD 20857 USA. [Gottesman, M. M.; Hall, M. D.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Innis, RB (reprint author), NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. EM robert.innis@nih.gov RI Hall, Matthew/B-2132-2010; OI Kannan, Pavitra/0000-0002-9170-6062 FU Intramural NIH HHS [Z01 MH002852-03]; NIMH NIH HHS [Z01-MH-002852-04, Z01 MH002852] NR 52 TC 104 Z9 109 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 OCT PY 2009 VL 86 IS 4 BP 368 EP 377 DI 10.1038/clpt.2009.138 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 500LO UT WOS:000270303500013 PM 19625998 ER PT J AU Crowe, BJ Xia, HA Berlin, JA Watson, DJ Shi, HL Lin, SL Kuebler, J Schriver, RC Santanello, NC Rochester, G Porter, JB Oster, M Mehrotra, DV Li, ZQ King, EC Harpur, ES Hall, DB AF Crowe, Brenda J. Xia, H. Amy Berlin, Jesse A. Watson, Douglas J. Shi, Hongliang Lin, Stephen L. Kuebler, Juergen Schriver, Robert C. Santanello, Nancy C. Rochester, George Porter, Jane B. Oster, Manfred Mehrotra, Devan V. Li, Zhengqing King, Eileen C. Harpur, Ernest S. Hall, David B. TI Recommendations for safety planning, data collection, evaluation and reporting during drug, biologic and vaccine development: a report of the safety planning, evaluation, and reporting team SO CLINICAL TRIALS LA English DT Article ID CUMULATIVE METAANALYSIS; MYOCARDIAL-INFARCTION; ITERATED LOGARITHM; RANDOMIZED-TRIALS; HETEROGENEITY; RISK; LAW AB Background The Safety Planning, Evaluation and Reporting Team (SPERT) was formed in 2006 by the Pharmaceutical Research and Manufacturers of America. Purpose SPERT's goal was to propose a pharmaceutical industry standard for safety planning, data collection, evaluation, and reporting, beginning with planning first-in- human studies and continuing through the planning of the post-product-approval period. Methods SPERT's recommendations are based on our review of relevant literature and on consensus reached in our discussions. Results An important recommendation is that sponsors create a Program Safety Analysis Plan early in development. We also give recommendations for the planning of repeated, cumulative meta-analyses of the safety data obtained from the studies conducted within the development program. These include clear definitions of adverse events of special interest and standardization of many aspects of data collection and study design. We describe a 3-tier system for signal detection and analysis of adverse events and highlight proposals for reducing "false positive" safety findings. We recommend that sponsors review the aggregated safety data on a regular and ongoing basis throughout the development program, rather than waiting until the time of submission. Limitations We recognize that there may be other valid approaches. Conclusions The proactive approach we advocate has the potential to benefit patients and health care providers by providing more comprehensive safety information at the time of new product marketing and beyond. Clinical Trials 2009; 6: 430-440. http://ctj.sagepub.com C1 [Crowe, Brenda J.] Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. [Xia, H. Amy] Amgen Inc, Thousand Oaks, CA 91320 USA. [Berlin, Jesse A.] Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ USA. [Watson, Douglas J.; Santanello, Nancy C.; Mehrotra, Devan V.] Merck & Co Inc, N Wales, PA USA. [Shi, Hongliang; Porter, Jane B.] Millennium Pharmaceut Inc, Cambridge, MA USA. [Lin, Stephen L.; Oster, Manfred] Sanofi Aventis, Bridgewater, NJ USA. [Kuebler, Juergen] Novartis Pharma AG, Basel, Switzerland. [Schriver, Robert C.] GlaxoSmithKline Inc, King Of Prussia, PA USA. [Rochester, George] US FDA, Silver Spring, MD USA. [Li, Zhengqing] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [King, Eileen C.] Procter & Gamble Pharmaceut, Mason, OH USA. [Harpur, Ernest S.] Sanofi Aventis, Alnwick, Northd, England. [Hall, David B.] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. RP Crowe, BJ (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. EM crowe_brenda_j@lilly.com RI King, Eileen/Q-1815-2015 NR 32 TC 37 Z9 38 U1 1 U2 8 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD OCT PY 2009 VL 6 IS 5 BP 430 EP 440 DI 10.1177/1740774509344101 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 510KD UT WOS:000271086500004 PM 19846894 ER PT J AU Ghosh, P Huang, L Yu, BB Tiwari, RC AF Ghosh, Pulak Huang, Lan Yu, Binbing Tiwari, Ram C. TI Semiparametric Bayesian approaches to joinpoint regression for population-based cancer survival data SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article ID DIRICHLET PROCESS PRIOR; NONPARAMETRIC PROBLEMS; MODELS; RATES; BREAKTHROUGH; SELECTION; MIXTURES; PRIORS; POINT AB According to the American Cancer Society report (1999), cancer surpasses heart disease as the leading cause of death in the United States of America (USA) for people of age less than 85. Thus, medical research in cancer is an important public health interest. Understanding how medical improvements are affecting cancer incidence, mortality and survival is critical for effective cancer control. In this paper, we study the cancer survival trend on the population level cancer data. In particular, we develop a parametric Bayesian joinpoint regression model based on a Poisson distribution for the relative survival. To avoid identifying the cause of death, we only conduct analysis based on the relative survival. The method is further extended to the semiparametric Bayesian joinpoint regression models wherein the parametric distributional assumptions of the joinpoint regression models are relaxed by modeling the distribution of regression slopes using Dirichlet process mixtures. We also consider the effect of adding covariates of interest in the joinpoint model. Three model selection criteria, namely, the conditional predictive ordinate (CPO), the expected predictive deviance (EPD), and the deviance information criteria (DIC), are used to select the number of joinpoints. We analyze the grouped survival data for distant testicular cancer from the Surveillance, Epidemiology, and End Results (SEER) Program using these Bayesian models. (C) 2009 Elsevier B.V. All rights reserved. C1 [Ghosh, Pulak] Georgia State Univ, Dept Math & Stat, Atlanta, GA 30303 USA. [Huang, Lan] NCI, Stat Res & Applicat Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Yu, Binbing] NIA, Bethesda, MD 20892 USA. [Tiwari, Ram C.] US FDA, Off Biostat, Silver Spring, MD USA. RP Ghosh, P (reprint author), Georgia State Univ, Dept Math & Stat, Atlanta, GA 30303 USA. EM pulakghosh@gmail.com FU National Institutes of Health (NIH) [263-MQ-610994]; Intramural Research Program of the National Institute on Aging FX The views expressed by the last author do not necessarily reflect those of the FDA and NCL The research of Dr. Ghosh was supported in part by National Institutes of Health (NIH) contract 263-MQ-610994. Dr. Yu was supported in part by the Intramural Research Program of the National Institute on Aging. NR 43 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD OCT 1 PY 2009 VL 53 IS 12 BP 4073 EP 4082 DI 10.1016/j.csda.2009.04.011 PG 10 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 504NV UT WOS:000270624600014 PM 22210971 ER PT J AU Yousef, WA Kundu, S Wagner, RF AF Yousef, Waleed A. Kundu, Subrata Wagner, Robert F. TI Nonparametric estimation of the threshold at an operating point on the ROC curve SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article ID MAXIMUM-LIKELIHOOD-ESTIMATION; QUANTILE ESTIMATOR AB In the problem of binary classification (or medical diagnosis), the classification rule (or diagnostic test) produces a continuous decision variable which is compared to a critical value (or threshold). Test values above (or below) that threshold are called positive (or negative) for disease. The two types of errors associated with every threshold value are Type I (false positive) and Type II (false negative) errors. The Receiver Operating Curve (ROC) describes the relationship between probabilities of these two types of errors. The inverse problem is considered; i.e., given the ROC curve (or its estimate) of a particular classification rule, one is interested in finding the value of the threshold that leads to a specific operating point on that curve. A nonparametric method for estimating the threshold is proposed. Asymptotic distribution is derived for the proposed estimator. Results from simulated data and real-world data are presented for finite sample size. Finding a particular threshold value is crucial in medical diagnoses, among other fields, where a medical test is used to classify a patient as "diseased" or "nondiseased" based on comparing the test result to a particular threshold value. When the ROC is estimated, an operating point is obtained by fixing probability of one type of error, and obtaining the other one from the estimated curve. Threshold estimation can then be viewed as a quantile estimation for one distribution but with the utilization of the second one. (C) 2009 Elsevier B.V. All rights reserved. C1 [Yousef, Waleed A.] Helwan Univ, Fac Comp & Informat, Dept Comp Sci, Helwan 11795, Egypt. [Kundu, Subrata] George Washington Univ, Dept Stat, Washington, DC 20052 USA. [Wagner, Robert F.] Food & Drug Adm CDRH, Silver Spring, MD 20993 USA. RP Yousef, WA (reprint author), Helwan Univ, Fac Comp & Informat, Dept Comp Sci, Helwan 11795, Egypt. EM wyousef@GWmail.gwu.edu RI Yousef, Waleed/A-9082-2009 NR 20 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD OCT 1 PY 2009 VL 53 IS 12 BP 4370 EP 4383 DI 10.1016/j.csda.2009.06.006 PG 14 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 504NV UT WOS:000270624600041 ER PT J AU Rani, A Kelly, A Berhan, LT Jurevic, S Ragheb, J Lavender, P John, S AF Rani, Aradhana Kelly, Audrey Berhan, Lemlem Tewolde Jurevic, Stipo Ragheb, Jack Lavender, Paul John, Susan TI Regulation of c-maf by IL-2 SO CYTOKINE LA English DT Meeting Abstract CT Tri-Society Annual Conference of the International-Cytokine-Society/International-Society-of-Interferon-and-C ytokine-Research/Society-of-Leukocyte-Biology CY OCT 17-21, 2009 CL Lisbon, PORTUGAL SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res, Soc Leukocyte Biol C1 [Rani, Aradhana; Berhan, Lemlem Tewolde; John, Susan] Kings Coll London, Dept Immunobiol, London SE1 9RT, England. [Kelly, Audrey; Lavender, Paul] Kings Coll London, Dept Asthma Allergy & Resp Dis, London SE1 9RT, England. [Jurevic, Stipo] Kings Coll London, Dept Nephrol & Transplantat, London SE1 9RT, England. [Ragheb, Jack] NIH, US FDA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2009 VL 48 IS 1-2 BP 11 EP 11 DI 10.1016/j.cyto.2009.07.049 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 507LN UT WOS:000270855100034 ER PT J AU Michel, PA Kase, JA AF Michel, Pierre A. Kase, Julie A. TI Genetic profiles of Shiga toxin and intimin genes found in stool broth cultures: a 2-year reference laboratory study SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE STEC; Molecular detection; Stx1; Stx2; Intimin ID ESCHERICHIA-COLI STRAINS; VIRULENCE GENES; INTESTINAL MUCUS; EPITHELIAL-CELLS; IDENTIFICATION; SEROTYPES; VARIANT; HUMANS; CATTLE; ASSOCIATION AB Shiga toxin (Stx)-producing Escherichia coli (STEC) are associated with potentially serious illness in humans. STEC detection is often based on the presence of Stxs, Six(1) and/or Stx(2), and intimin, encoded by the eae gene. A 2-year collection of stool broth Cultures was tested for variants of stx(1), stx(2), and eae. Approximately 80% (138 of 174) were positive for stx(1), and/or stx(2), with sty, as the most prevalent (66%). Of the stx(1), variants, sty, was the most common (76%) followed by stx(1c) (22%). Analysis of stx(2)-positive isolates found 20 (53%) stx(2), 13 (34%) stx(2)/stx(2v-ha),, 3 (8%) stx(2-ha), 1 (3%) stx(2v-hb), and 1 (3%) stx(2d-activatable) . Findings Of stx(2)/stx(2v-ha), and stx(2d-activatable) are noteworthy given associations with hemolytic uremic syndrome and increased cytotoxicity, respectively. Of the Stx positive, 94 (68%) were eae positive with 31 (33%) eae(epsilon 1), 19 (20%) eae(gamma 1), and 18 (19%) eae(beta 1). A predominance of eae(epsilon 1) may suggest a new pathogenic significance because, reportedly, eae(beta 1) is one of the most widespread variants. Published by Elsevier Inc. C1 [Michel, Pierre A.; Kase, Julie A.] N Carolina State Lab Publ Hlth, Raleigh, NC 27601 USA. RP Kase, JA (reprint author), US FDA, Microbial Methods Dev Branch, Div Microbiol, Off Regulatory Sci,Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM julie.kase@fda.hhs.gov NR 49 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD OCT PY 2009 VL 65 IS 2 BP 85 EP 92 DI 10.1016/j.diagmicrobio.2009.06.006 PG 8 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 499XP UT WOS:000270260400001 PM 19748416 ER PT J AU Peer, CJ Younis, IR Bukowski, VC Leonard, SS Petros, WP Callery, PS AF Peer, Cody J. Younis, Islam R. Bukowski, Valerie C. Leonard, Stephen S. Petros, William P. Callery, Patrick S. TI Gamma-glutamyldehydroalanylglycine is an electrophilic metabolite of glutathione SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 16th North American Regional ISSX Meeting CY OCT 18-22, 2009 CL Baltimore, MD C1 [Peer, Cody J.; Petros, William P.; Callery, Patrick S.] W Virginia Univ, Sch Pharm, Morgantown, WV 26506 USA. [Younis, Islam R.] US FDA, Off Clin Pharmacol, CDER, Silver Spring, MD 20993 USA. [Bukowski, Valerie C.; Leonard, Stephen S.] NIOSH, Pathol & Physiol Res Branch, Hlth Effects Lab Div, Morgantown, WV 26505 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PD OCT PY 2009 VL 41 SU 3 MA 264 BP 129 EP 130 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 629AB UT WOS:000280165300251 ER PT J AU Planitzer, CB Modrof, J Yu, MYW Kreil, TR AF Planitzer, Christina B. Modrof, Jens Yu, Mei-ying W. Kreil, Thomas R. TI West Nile Virus Infection in Plasma of Blood and Plasma Donors, United States SO EMERGING INFECTIOUS DISEASES LA English DT Article ID EPIDEMIC; SEROPREVALENCE; ANTIBODIES AB This study investigated the association of ongoing West Nile virus (WNV) infections with neutralizing antibody titers in US plasma-derived intravenous immune globulin released during 2003-2008. Titers correlated closely with the prevalence of past WNV infection in blood donors, with 2008 lots indicating a prevalence of 1%. C1 [Planitzer, Christina B.; Modrof, Jens; Kreil, Thomas R.] Baxter BioSci, A-1221 Vienna, Austria. [Yu, Mei-ying W.] US FDA, Bethesda, MD 20014 USA. RP Kreil, TR (reprint author), Baxter BioSci, Benatzkygasse 2-6, A-1221 Vienna, Austria. EM thomas_kreil@baxter.com NR 14 TC 19 Z9 19 U1 0 U2 1 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD OCT PY 2009 VL 15 IS 10 BP 1668 EP 1670 DI 10.3201/eid1510.080711 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 503ZD UT WOS:000270580600027 PM 19861071 ER PT J AU Whittaker, P AF Whittaker, Paul TI Comparison of Yersinia pestis to other closely related Yersinia species using fatty acid profiles SO FOOD CHEMISTRY LA English DT Article DE Gas chromatography; Fatty acids; Yersinia pestis; Yersinia species ID ENTEROCOLITICA-LIKE; STRAINS; PSEUDOTUBERCULOSIS AB Capillary gas chromatography with flame ionisation detection (GC-FID) was used to determine the cellular fatty acid (CFA) profiles of six Yersinia pestis strains. The profiles were then compared with the CFA profiles of other closely related Yersinia species including: Y. pseudotuberculosis, Y. enterocolitica, Y. intermedii, Y. kristensenii and Y. frederiksenii. For GC-FID analysis, whole cell fatty acid methyl esters (FAMEs) from cells cultured on brain-heart infusion (BHI) agar at 35 degrees C for 24 h were obtained by saponification, methylation and extraction into hexane/methyl tert-butyl ether. A data set for each Yersinia species was prepared using fatty acid profiles from five replicates prepared on different days. Major fatty acids of the 26 Yersinia strains evaluated in this study were straight-chain 12:0, 14:0, 15:0, 16:0 and unsaturated Summed 16:1 omega 7c/16:1 omega 6c, 18:1 omega 7c, and summed 14:0 3OH/16:1 iso, and 17:0 omega cyclo 7-8. The CFA profiles for Y. pestis and Y. pseudotuberculosis are similar, but there are several fatty acids, 16:1 omega 5c, 16:0, 17:1 omega 7c, 17:0 omega cyclo 7-8, 19:0 and summed 18:2 omega 6c, 9c/18:0 ante, that differ significantly between these two species. Analysis of FAMEs from Yersinia strains grown on BHI agar by a rapid GC-FID method can provide a sensitive procedure for the identification of these organisms, and this analytical method provides a procedure for the differentiation of Y. pestis strains from closely related Yersinia species. Published by Elsevier Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Whittaker, P (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM paul.whittaker@fda.hhs.gov NR 21 TC 7 Z9 7 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0308-8146 J9 FOOD CHEM JI Food Chem. PD OCT 1 PY 2009 VL 116 IS 3 BP 629 EP 632 DI 10.1016/j.foodchem.2009.02.073 PG 4 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA 460YO UT WOS:000267229500005 ER PT J AU Al-Khaldi, SF Mossoba, MM Burke, TL Fry, FS AF Al-Khaldi, Sufian F. Mossoba, Magdi M. Burke, Tara L. Fry, Frederick S. TI Differentiation of Whole Bacterial Cells Based on High-Throughput Microarray Chip Printing and Infrared Microspectroscopic Readout SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID PATHOGENIC YERSINIA-ENTEROCOLITICA; IDENTIFICATION; SPECTROSCOPY; GENE; PCR; DISCRIMINATION; PROTEOMICS; MEMBRANE; GENOMICS; LISTERIA AB Using robotic automation, a microarray printing protocol for whole bacterial cells was developed for subsequent label-free and nondestructive infrared microspectroscopic detection. Using this contact microspotting system, 24 microorganisms were printed on zinc selenide slides; these were 6 species of Listeria, 10 species of Vibrio, 2 strains of Photobacterium damselae, Yersinia enterocolitica 289, Bacillus cereus ATCC 14529, Staphylococcus aureus, ATCC 19075 (serotype 104 B), Shigella sonnei 20143, Klebsiella pneumoniae KP73, Enterobacter cloacae, Citrobacter freundii 200, and Escherichia coli. Microarrays consisting of separate spots of bacterial deposits gave consistent and reproducible infrared spectra, which were differentiated by unsupervised pattern recognition algorithms. Two multivariate analysis algorithms, principal component analysis and hierarchical cluster analysis, successfully separated most, but not all, the bacteria investigated down to the species level. C1 [Mossoba, Magdi M.; Fry, Frederick S.] US FDA, Div Analyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Al-Khaldi, Sufian F.; Burke, Tara L.] US FDA, Div Microbiol, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Mossoba, MM (reprint author), US FDA, Div Analyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM magdi.mossoba@fda.hhs.gov NR 24 TC 2 Z9 2 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1535-3141 J9 FOODBORNE PATHOG DIS JI Foodborne Pathog. Dis. PD OCT PY 2009 VL 6 IS 8 BP 1001 EP 1007 DI 10.1089/fpd.2009.0276 PG 7 WC Food Science & Technology SC Food Science & Technology GA 501XE UT WOS:000270416900011 PM 19630511 ER PT J AU Hardy, SE McGurl, D Degenholz, HB AF Hardy, S. E. McGurl, D. Degenholz, H. B. TI DIFFICULTY WALKING 1/4 MILE PREDICTS SUBSEQUENT DISABILITY AND DEATH SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Hardy, S. E.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Degenholz, H. B.] Univ Pittsburgh, Sch Publ Hlth, Pittsburgh, PA 15260 USA. [McGurl, D.] Fed Drug Adm, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2009 VL 49 SU 2 BP 128 EP 128 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 519UI UT WOS:000271793900601 ER PT J AU Csanaky, IL Lu, H Choudhuri, S Ogura, K Zhang, YC Klaassen, CD AF Csanaky, Ivan L. Lu, Hong Choudhuri, Supratim Ogura, Kenichiro Zhang, Youcai Klaassen, Curtis D. TI OATP1B2 IS IMPORTANT FOR THE HEPATIC UPTAKE OF UNCONJUGATED BILE ACIDS AS WELL AS MAINTAINING THE EXPRESSION OF CYP7A1 IN MICE: STUDIES ON THE OATP1B2-NULL MICE SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Csanaky, Ivan L.; Lu, Hong; Zhang, Youcai; Klaassen, Curtis D.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Choudhuri, Supratim] US FDA, Ctr Food Safety & Nutr, College Pk, MD USA. [Ogura, Kenichiro] Tokyo Univ Pharm & Life Sci, Dept Drug Metab & Mol Toxicol, Tokyo, Japan. RI Csanaky, Ivan/N-5312-2015 OI Csanaky, Ivan/0000-0001-7870-4129 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 14 BP 308A EP 309A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456000015 ER PT J AU Shin, EC Nascimbeni, M Mihalik, K Feinstone, SM Rice, CM Rehermann, B AF Shin, Eui-Cheol Nascimbeni, Michelina Mihalik, Kathleen Feinstone, Stephen M. Rice, Charles M. Rehermann, Barbara TI DELAYED INDUCTION NOT IMPAIRED RECRUITMENT OF HEPATITIS C VIRUS-SPECIFIC CD8 T CELLS IS RESPONSIBLE FOR THE LATE ONSET OF ACUTE HEPATITIS SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Shin, Eui-Cheol; Nascimbeni, Michelina; Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, NIH, Bethesda, MD USA. [Mihalik, Kathleen; Feinstone, Stephen M.] US FDA, Lab Hepatitis Viruses, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Rice, Charles M.] Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 179 BP 387A EP 387A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456000180 ER PT J AU Formeister, EJ Tsuchiya, M Pogribny, I Rusyn, I AF Formeister, Eric J. Tsuchiya, Masato Pogribny, Igor Rusyn, Ivan TI METHYLATION FREQUENCY OF P16, SOCS-1, RASSF1A, APC AND GSTP1 PROMOTERS IN TUMOROUS, NON-TUMOROUS AND METASTATIC LIVER TUMOR SAMPLES FROM HCV-POSITIVE PATIENTS WITH HCC IN JAPAN SO HEPATOLOGY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 30-NOV 03, 2009 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Formeister, Eric J.; Tsuchiya, Masato; Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Pogribny, Igor] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RI Rusyn, Ivan/S-2426-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2009 VL 50 IS 4 MA 1769 BP 1122A EP 1122A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502JV UT WOS:000270456001763 ER PT J AU Hughes, MA Burns, DL Juris, SJ Tang, WJ Clement, KH Eaton, LJ Kelly-Cirino, CD Mckee, ML Powell, BS Bishop, BL Rudge, TL Shine, N Verma, A Willis, MS Morse, SA AF Hughes, Molly A. Burns, Drusilla L. Juris, Stephen J. Tang, Wei-Jen Clement, Kristin H. Eaton, Linda J. Kelly-Cirino, Cassandra D. McKee, Marian L. Powell, Bradford S. Bishop, Brian L. Rudge, Thomas L. Shine, Nancy Verma, Anita Willis, Melissa Swope Morse, Stephen A. TI The Case for Developing Consensus Standards for Research in Microbial Pathogenesis: Bacillus anthracis Toxins as an Example SO INFECTION AND IMMUNITY LA English DT Editorial Material ID PUBLIC-HEALTH MANAGEMENT; RESISTANT STAPHYLOCOCCUS-AUREUS; LETHAL TOXIN; BIOLOGICAL WEAPON; TRANSCRIPTIONAL RESPONSES; MURINE MACROPHAGES; GENE ONTOLOGY; EDEMA TOXIN; CELL-TYPE; A TOXIN C1 [Hughes, Molly A.] Univ Virginia Hlth Sci Syst, Dept Med, Div Infect Dis, Charlottesville, VA 22908 USA. [Burns, Drusilla L.; Verma, Anita] US FDA, Lab Resp & Special Pathogens Ctr, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Juris, Stephen J.] Cent Michigan Univ, Dept Biol, Mt Pleasant, MI 48859 USA. [Juris, Stephen J.] Cent Michigan Univ, Dept Chem, Mt Pleasant, MI 48859 USA. [Tang, Wei-Jen; Bishop, Brian L.] Univ Chicago, Ctr Integrat Sci, Ben May Dept Canc Res, Chicago, IL 60637 USA. [Clement, Kristin H.; Rudge, Thomas L.] Battelle Biomed Res Ctr, Battelle Mem Inst, W Jefferson, OH 43162 USA. [Eaton, Linda J.; Shine, Nancy] List Biol Labs Inc, Campbell, CA 95008 USA. [Kelly-Cirino, Cassandra D.] New York State Dept Hlth, Wadsworth Ctr, Div Infect Dis, Biodefense Lab,David Axelrod Inst, Albany, NY 12201 USA. [McKee, Marian L.; Willis, Melissa Swope] ATCC, Manassas, VA 20110 USA. [Powell, Bradford S.] USA, Med Res Inst Infect Dis, Bacteriol Div, Frederick, MD 21702 USA. [Morse, Stephen A.] Ctr Dis Control & Prevent, Div Bioterrorism Preparedness & Response, Natl Ctr Preparedness Detect & Control Infect Dis, Atlanta, GA 30333 USA. RP Hughes, MA (reprint author), Univ Virginia Hlth Syst, Dept Med, Div Infect Dis & Int Hlth, POB 800513, Charlottesville, VA 22908 USA. EM mah3x@virginia.edu OI Tang, Wei-Jen/0000-0002-8267-8995; Kelly-Cirino, Cassandra/0000-0002-4526-8487 NR 31 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 2009 VL 77 IS 10 BP 4182 EP 4186 DI 10.1128/IAI.00368-09 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 496ER UT WOS:000269952800002 PM 19651858 ER PT J AU Loving, CL Osorio, M Kim, YG Nunez, G Hughes, MA Merkel, TJ AF Loving, Crystal L. Osorio, Manuel Kim, Yun-Gi Nunez, Gabriel Hughes, Molly A. Merkel, Tod J. TI Nod1/Nod2-Mediated Recognition Plays a Critical Role in Induction of Adaptive Immunity to Anthrax after Aerosol Exposure SO INFECTION AND IMMUNITY LA English DT Article ID LETHAL FACTOR CLEAVES; NECROSIS-FACTOR-ALPHA; NOD-LIKE RECEPTORS; BACILLUS-ANTHRACIS; DENDRITIC CELLS; BACTERIAL PEPTIDOGLYCAN; MURINE MACROPHAGES; CHALLENGE MODEL; INNATE IMMUNITY; CYCLIC-AMP AB Toll-like receptors and Nod-like receptors (NLR) play an important role in sensing invading microorganisms for pathogen clearance and eliciting adaptive immunity for protection against rechallenge. Nod1 and Nod2, members of the NLR family, are capable of detecting bacterial peptidoglycan motifs in the host cytosol for triggering proinflammatory cytokine production. In the current study, we sought to determine if Nod1/Nod2 are involved in sensing Bacillus anthracis infection and eliciting protective immune responses. Using mice deficient in both Nod1 and Nod2 proteins, we showed that Nod1/Nod2 are involved in detecting B. anthracis for production of tumor necrosis factor alpha, interleukin-1 alpha (IL-1 alpha), IL-1 beta, CCL5, IL-6, and KC. Proinflammatory responses were higher when cells were exposed to viable spores than when they were exposed to irradiated spores, indicating that recognition of vegetative bacilli through Nod1/Nod2 is significant. We also identify a critical role for Nod1/Nod2 in priming responses after B. anthracis aerosol exposure, as mice deficient in Nod1/Nod2 were impaired in their ability to mount an anamnestic antibody response and were more susceptible to secondary lethal challenge than wild-type mice. C1 [Loving, Crystal L.; Merkel, Tod J.] US FDA, Lab Resp & Special Pathogens, Div Bacterial Parasit & Allergen Prod, CBER, Bethesda, MD 20014 USA. [Osorio, Manuel] US FDA, Lab Enter & Sexually Transmitted Dis, Div Bacterial Parasit & Allergen Prod, CBER, Bethesda, MD 20014 USA. [Kim, Yun-Gi; Nunez, Gabriel] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA. [Kim, Yun-Gi; Nunez, Gabriel] Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI USA. [Hughes, Molly A.] Univ Virginia Hlth Sci Syst, Dept Internal Med, Div Infect Dis, Charlottesville, VA USA. RP Merkel, TJ (reprint author), Bldg 29,Room 418,29 Lincoln Dr, Bethesda, MD 20892 USA. EM tod.merkel@fda.hhs.gov FU CBER/FDA-NIAID/NIH Interagency Agreement [Y1-AI-6153-01, DK61707, R21AI072469-01]; NIAID-NIH Middle Atlantic Regional Centers for Excellence [U54 AI57168] FX This work was supported by CBER/FDA-NIAID/NIH Interagency Agreement Y1-AI-6153-01, NIH RO1 grant DK61707, NIH R21 grant R21AI072469-01, and NIAID-NIH Middle Atlantic Regional Centers for Excellence grant U54 AI57168. NR 58 TC 15 Z9 19 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 2009 VL 77 IS 10 BP 4529 EP 4537 DI 10.1128/IAI.00563-09 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 496ER UT WOS:000269952800039 PM 19620350 ER PT J AU Palumbo, S Toscano, CD Silva, A Bosetti, F AF Palumbo, S. Toscano, C. D. Silva, A. Bosetti, F. TI Brain arachidonic acid metabolic pathway is altered during cuprizone-induced demyelination SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th International Conference on Quantification of Brain Function with PET CY JUN 29-JUL 03, 2009 CL Chicago, IL SP Int Soc Cerebral Blood Flow & Metabolism ID REMYELINATION C1 [Palumbo, S.; Bosetti, F.] NIA, BPMS, NIH, Bethesda, MD 20892 USA. [Toscano, C. D.] US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Div Neurol Prod,Off Drug Evaluat 1, Silver Spring, MD USA. [Silva, A.] NINDS, NIH, Bethesda, MO USA. NR 2 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 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2009 VL 29 BP S281 EP S282 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 500UB UT WOS:000270329900342 ER PT J AU Zhang, X Newport, G Patterson, T Paule, M Slikker, W Wang, C AF Zhang, X. Newport, G. Patterson, T. Paule, M. Slikker, W. Wang, C. TI Quantitative assessment of [F-18]-annexin V uptake by micropet imaging as a biomarker of ketamine-induced neuronal death SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Meeting Abstract CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th International Conference on Quantification of Brain Function with PET CY JUN 29-JUL 03, 2009 CL Chicago, IL SP Int Soc Cerebral Blood Flow & Metabolism C1 [Zhang, X.; Newport, G.; Patterson, T.; Paule, M.; Slikker, W.; Wang, C.] NCTR FDA, Jefferson, AR 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 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2009 VL 29 SU S1 BP S255 EP S255 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 500UB UT WOS:000270329900308 ER PT J AU Jones, JL Noe, KE Byars, R DePaola, A AF Jones, Jessica L. Noe, Kathy E. Byars, Robin DePaola, Angelo TI Evaluation of DNA Colony Hybridization and Real-Time PCR for Detection of Vibrio parahaemolyticus and Vibrio vulnificus in Postharvest-Processed Oysters SO JOURNAL OF FOOD PROTECTION LA English DT Article AB The applicability of real-time PCR was examined for detection of vibrios from postharvest-processed (PHP) oysters to allow for a more rapid assay and higher sample throughput than currently used. During June to October 2004, 68 PHP oyster samples were collected directly from PHP firms or from retail markets across the United States. PHP oysters were examined to determine the effectiveness of treatments in the reduction of vibrio levels and to compare the analytical methods utilized. The latter is the focus of the data presented here. Each sample was analyzed for Vibrio parahaemolyticus and V. vulnificus by using a 2-dilution, three-tube most-probable-number (MPN) and a 25-g presence/absence enrichment in alkaline peptone water. Following 6-h and overnight enrichment, aliquots from each MPN tube and the 25-g sample were streaked onto selective media and tested by real-time PCR. Colonies from the selective agar were confirmed as V. parahaemolyticus or V. vulnificus by DNA colony hybridization. DNA hybridization and real-time PCR results for each MPN tube and the 25-g enrichment at both time points were analyzed individually for each organism. The methods were in agreement for 857 (95%) of 901 and for 882 (98%) of 903 tubes for detection of V. parahaemolyticus and V. vulnificus, respectively. Overall, there was 96% agreement between real-time and DNA colony hybridization. The results obtained by real-time PCR were comparable to those from DNA colony hybridization, but analysis time was significantly reduced for the detection of vibrios in PHP-treated oysters. C1 [Jones, Jessica L.; DePaola, Angelo] US FDA, Div Seafood Sci & Technol, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. [Noe, Kathy E.; Byars, Robin] US FDA, SE Reg Lab, Atlanta, GA 30309 USA. RP Jones, JL (reprint author), US FDA, Div Seafood Sci & Technol, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. EM Jessica.Jones@fda.hhs.gov NR 7 TC 5 Z9 5 U1 1 U2 4 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD OCT PY 2009 VL 72 IS 10 BP 2106 EP 2109 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 503GM UT WOS:000270521600010 PM 19833033 ER PT J AU DePaola, A Jones, JL Noe, KE Byars, RH Bowers, JC AF DePaola, Angelo Jones, Jessica L. Noe, Kathy E. Byars, Robin H. Bowers, John C. TI Survey of Postharvest-Processed Oysters in the United States for Levels of Vibrio vulnificus and Vibrio parahaemolyticus SO JOURNAL OF FOOD PROTECTION LA English DT Article ID TIME PCR ASSAY; GENE AB From June through October 2004, the U.S. Food and Drug Administration collected oysters (61 samples) that had been subjected to postharvest processing (PHP) methods, including mild heat treatment, freezing, and high hydrostatic pressure, from processors and retail markets in various states to determine Vibrio vulnificus and V. parahaemolyticus levels. Presence in a 25-g sample and most probable number (MPN) using standard enrichment and selective isolation procedures were utilized. Suspect colonies were isolated and identified using DNA probe colony hybridization. Neither species of vibrio was detected in 25-g portions of most samples regardless of the PHP. The lowest frequency of isolation of either pathogen (< 10%) was observed with the mild heat process. Few (12 to 13%) frozen samples collected at the processor but not at retail contained >30 MPN/g of either pathogen. The mean levels of either organism in PHP oysters observed in the present study were 5 to 6 log less than in unprocessed raw Gulf Coast oysters. Of the 70 V. vulnificus isolates examined, only 5 possessed the putative virulence marker, type B 16S rRNA. Neither the thermostable direct hemolysin (tdh) nor the tdh-related hemolysin (trh) virulence gene was detected in any of the 40 V. parahaemolyticus isolates examined in the present study. These data suggest that if there is any selective advantage to pathogenic strains of V. vulnificus and V. parahaemolyticus, these differences are minimal. These results indicate that all PHP treatments greatly reduce exposure of V. vulnificus and V. parahaemolyticus to raw-oyster consumers. Consequently, these PHP oysters pose a much lower risk of illness to consumers due to these pathogens. C1 [DePaola, Angelo; Jones, Jessica L.] US FDA, Div Seafood Sci & Technol, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. [Noe, Kathy E.; Byars, Robin H.] US FDA, SE Reg Lab, Atlanta, GA 30309 USA. [Bowers, John C.] US FDA, Ctr Food Safety & Appl Nutr, Div Publ Hlth & Biostat, College Pk, MD 20740 USA. RP DePaola, A (reprint author), US FDA, Div Seafood Sci & Technol, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. EM angelo.depaola@fda.hhs.gov NR 14 TC 20 Z9 20 U1 0 U2 7 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD OCT PY 2009 VL 72 IS 10 BP 2110 EP 2113 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 503GM UT WOS:000270521600011 PM 19833034 ER PT J AU Hong, Y Liu, TR Lee, MD Hofacre, CL Maier, M White, DG Ayers, S Wang, LH Berghaus, R Maurer, J AF Hong, Yang Liu, Tongrui Lee, Margie D. Hofacre, Charles L. Maier, Marie White, David G. Ayers, Sherry Wang, Lihua Berghaus, Roy Maurer, John TI A Rapid Screen of Broth Enrichments for Salmonella enterica Serovars Enteritidis, Hadar, Heidelberg, and Typhimurium by Using an Allelotyping Multiplex PCR That Targets O- and H-Antigen Alleles SO JOURNAL OF FOOD PROTECTION LA English DT Article ID POLYMERASE-CHAIN-REACTION; IDENTIFICATION; CHICKENS; HOUSES; GENES; ASSAY; SPP.; COLI AB Salmonella continues to cause significant foodborne outbreaks, best illustrated with recent outbreaks associated with peanut butter, raw tomatoes, and serrano peppers. To ascertain the likely source of the outbreak, bacterial typing is essential to this process. While PCR has become an important detection tool for pathogens in foods, PCR can also identify strain differences by targeting gene(s) or sequences exhibiting polymorphisms or variability in its distribution within the bacterial population. Over 2,500 Salmonella enterica serovars identified based on antigenic differences in lipopolysaccharide, and flagellin have been identified to date. We developed an allelotyping PCR scheme that identifies the O and H alleles associated with S. enterica serovars Enteritidis, Hadar, Heidelberg, Typhimurium, and others, with the same antigen alleles but in different O- and H-allele combinations (e.g., S. enterica Kentucky), and validated it as a screen to identify samples contaminated with these Salmonella serovars. We correctly identified poultry samples containing S. enterica serovars Enteritidis, Kentucky, and Typhimurium from our multiplex screen of primary enrichments of environmental drag swabs. PCR agreed well (kappa values = 0.81 to 1.0) with conventional serotyping methods used to type salmonellae isolated from primary enrichment. Coupled with Salmonella-specific PCR, such as invA, this allelotyping PCR could prove useful in the identification of Salmonella and specific S. enterica serovars present in foods or the environment and could decrease the time and cost associated with conventional serotyping methods. C1 [Hong, Yang; Liu, Tongrui; Lee, Margie D.; Hofacre, Charles L.; Maier, Marie; Berghaus, Roy; Maurer, John] Univ Georgia, Dept Populat Hlth, Athens, GA 30602 USA. [Hong, Yang] Univ Georgia, Coll Vet Med, Dept Infect Dis, Athens, GA 30602 USA. [Wang, Lihua] Univ Georgia, Sch Arts & Sci, Dept Stat, Athens, GA 30602 USA. [Lee, Margie D.; Hofacre, Charles L.; Maurer, John] Univ Georgia, Coll Agr & Environm Sci, Ctr Food Safety & Qual Enhancement, Griffin, GA 30223 USA. [White, David G.; Ayers, Sherry] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Maurer, J (reprint author), Univ Georgia, Dept Populat Hlth, Athens, GA 30602 USA. EM jmaurer@uga.edu FU U.S. Department of Agriculture, National Research Initiative Competitive Grants Program [99-35212-8680]; U.S. Department of Agriculture Formula Funds; State of Georgia's Veterinary Medicine Agricultural Research FX U.S. Department of Agriculture, National Research Initiative Competitive Grants Program grant no. 99-35212-8680, U.S. Department of Agriculture Formula Funds, and the State of Georgia's Veterinary Medicine Agricultural Research Grant supported this work. NR 28 TC 6 Z9 6 U1 1 U2 5 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X EI 1944-9097 J9 J FOOD PROTECT JI J. Food Prot. PD OCT PY 2009 VL 72 IS 10 BP 2198 EP 2201 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 503GM UT WOS:000270521600023 PM 19833046 ER PT J AU Principato, M Boyle, T Njoroge, J Jones, RL O'Donnell, M AF Principato, Maryann Boyle, Thomas Njoroge, Joyce Jones, Robert L., Jr. O'Donnell, Michael TI Effect of Thermal Processing during Yogurt Production upon the Detection of Staphylococcal Enterotoxin B SO JOURNAL OF FOOD PROTECTION LA English DT Article ID HEAT INACTIVATION; VERONAL BUFFER; GOATS MILK; SKIM MILK; OUTBREAK; AUREUS; CULTURES; GROWTH AB This research was conducted to examine the inherent properties of yogurt contaminated with staphylococcal enterotoxin B (SEB). Two types of yogurts were produced for this study. Type I yogurts were produced by adding SEB at the start of yogurt production, and type H yogurts were produced by adding SEB after the milk base had been boiled. Biochemical characteristics inherent to yogurt, including pH, lactic acid and acetaldehyde concentrations, were analyzed weekly for each batch beginning at a time just after production and throughout a storage period of at least 4 weeks. The presence of toxin during yogurt production did not result in any significant biochemical or physical changes in yogurt. However, we were unable to detect SEB toxin in type I yogurt using a commercially available enzyme-linked immunosorbent assay (ELISA). In contrast, SEB was easily detectable by our ELISA in type II yogurt samples. Higher levels of SEB were recovered from type II yogurt that had been stored for I week than from type II yogurt that had been stored for any other length of time. These results indicate that the biochemical characteristics of yogurt did not change significantly (relative to control yogurt) in the presence of either thermally processed SEB or native SEB. However, the ability to detect SEB by ELISA was dependent on whether the toxin had been processed. C1 [Principato, Maryann; Boyle, Thomas; Njoroge, Joyce; Jones, Robert L., Jr.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [O'Donnell, Michael] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20708 USA. RP Principato, M (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM maryann.principato@fda.hhs.gov FU U.S. Food and Drug Administration Food Defense Research FX We are grateful to our colleagues Drs. Robert Sprando and Paddy Wiesenfeld for helpful reading of this material. We also thank Dr. Lauren Jackson for valuable consultations regarding yogurt production and for providing the Chr. Hansen bacterial yogurt cultures used in these studies' Funding was provided by an U.S. Food and Drug Administration Food Defense Research grant. NR 30 TC 3 Z9 3 U1 1 U2 5 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD OCT PY 2009 VL 72 IS 10 BP 2212 EP 2216 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 503GM UT WOS:000270521600026 PM 19833049 ER PT J AU Fleischer, RD Lok, ASF AF Fleischer, Russell D. Lok, Anna S. F. TI Myopathy and neuropathy associated with nucleos(t)ide analog therapy for hepatitis B SO JOURNAL OF HEPATOLOGY LA English DT Article DE Clevudine; Telbivudine; Mitochondrial toxicity; Pegylated interferon ID ADENINE-ARABINOSIDE MONOPHOSPHATE; LONG-TERM THERAPY; ANTIVIRAL ACTIVITY; MITOCHONDRIAL TOXICITY; ADEFOVIR DIPIVOXIL; NUCLEOSIDE ANALOG; SHOWED POTENT; PHASE-II; CLEVUDINE; FIALURIDINE AB The development of clevudine as a treatment for hepatitis B was terminated recently because of case reports of myopathy. In each case, the onset of symptoms occurred between 8 and 13 months after the initiation of treatment. Electromyography and muscle biopsy confirmed the presence of myonecrosis. One report also found evidence of mitochondrial toxicity. The delayed onset and the finding of mitochondrial damage are reminiscent of fialuridine toxicity. Telbivudine has also been reported to be associated with myopathy and neuropathy, particularly when used in combination with pegylated interferon. These findings serve as a sober reminder of the lack of data on long-term safety of nucleos(t)ide analogs for hepatitis B, the importance of balancing benefits versus risks before initiating treatment, and the need for more stringent post-marketing surveillance for drug toxicities. (C) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 [Lok, Anna S. F.] Univ Michigan Hlth Syst, Div Gastroenterol & Hepatol, Taubman Ctr 3912, Ann Arbor, MI 48109 USA. [Fleischer, Russell D.] US FDA, Div Antiviral Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Lok, ASF (reprint author), Univ Michigan Hlth Syst, Div Gastroenterol & Hepatol, Taubman Ctr 3912, SPC 5362, Ann Arbor, MI 48109 USA. EM aslok@umich.edu OI Yang, Shuman/0000-0002-9638-0890 FU Bristol-Myers Squibb; GlaxoSmithKline; Schering; Novartis; Gilead FX R.D.F. declared that he does not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. A.S.F.L. receives research support from Bristol-Myers Squibb, GlaxoSmithKline, Schering, Novartis and Gilead and serves as an advisor for Gilcad, Pharamasset. Schering and Roche. NR 30 TC 42 Z9 49 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD OCT PY 2009 VL 51 IS 4 BP 787 EP 791 DI 10.1016/j.jhep.2009.06.011 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 506BV UT WOS:000270749000026 PM 19665816 ER PT J AU Ponnamperuma, RM King, KE Elsir, T Glick, AB Wahl, GM Nister, M Weinberg, WC AF Ponnamperuma, Roshini M. King, Kathryn E. Elsir, Tamador Glick, Adam B. Wahl, Geoffrey M. Nister, Monica Weinberg, Wendy C. TI The transcriptional regulatory function of p53 is essential for suppression of mouse skin carcinogenesis and can be dissociated from effects on TGF-beta-mediated growth regulation SO JOURNAL OF PATHOLOGY LA English DT Article DE p53; squamous cell carcinoma; epidermis; senescence; tumour suppression; TGF-beta; transactivation ID MUTANT P53; HOMOLOGOUS RECOMBINATION; MALIGNANT PROGRESSION; APOPTOTIC ACTIVITY; TUMOR-DEVELOPMENT; GENE DOSAGE; IN-VIVO; TRANSACTIVATION; DEFICIENT; KERATINOCYTES AB Transcriptional regulation by p53 is critical for p53-mediated tumour suppression; however, p53-mediated transactivation has been dissociated from p53-mediated biological processes including apoptosis, DNA repair, and differentiation. We compared the effects of a mutant allele, p53(QS-val135), containing a double mutation in the amino-terminus abrogating transactivation activity and a modification at amino acid 135 partially affecting DNA binding, to complete loss of p53. We applied in vitro endpoints correlated with epithelial tumourigenesis and an in vivo assay of tumour phenotype to assess whether loss of p53-mediated transcriptional regulation underlies the malignant phenotype of p53(-/-)/v-ras(Ha)-overexpressing keratinocytes. Transactivation deficiency of p53(QS-val135) was confirmed by reporter gene assays in fibroblasts and differentiating keratinocytes. Ras oncogene-induced senescence was lost in both p53(QS-val135/QS-val135) and p53(-/-) keratinocytes. Similarly, p53(QS-val135/QS-val135), like p53(-/-), cooperated with v-ras(Ha) to enhance malignant conversion. The tumours arising in p53(QS-val135/QS-val135) keratinocytes displayed strong nuclear p53 expression; thus, the p53(QS-val135) allele was maintained and the deficient transactivation function of the expressed p53QS mutant protein was supported by absence of p21(waf1) in these tumours. The p53(QS-val135) allele did not confer a dominant-negative phenotype, as p53(+/QS-val135) keratinocytes senesced normally in response to v-ras(Ha) expression and formed benign tumours. While p53(-/-) keratinocytes displayed diminished response to TGF-beta, p53(QS-val135/QS-val135) and p53(+/+) keratinocytes responded equivalently, indicating that the requirement for p53 in maximizing TGF-beta-mediated growth regulation is independent of its transactivation domain and that the ability of keratinocytes to respond to TGF-beta is insufficient to suppress the malignant phenotype in this model. Furthermore, TGF-beta enhances p53QS-induced activation of a dual p53-TGF-beta responsive reporter in a keratinocyte cell line. These findings support an essential role for p53-mediated transcriptional regulation in suppressing malignancies arising from ras-induced skin tumours, consistent with previous findings in spontaneous carcinogenesis in other organs, and highlight the potential importance of senescence for tumour suppression in vivo. Copyright (C) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Weinberg, Wendy C.] US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Elsir, Tamador; Nister, Monica] Karolinska Inst, Stockholm, Sweden. [Glick, Adam B.] Penn State Univ, University Pk, PA 16802 USA. [Wahl, Geoffrey M.] Salk Inst Biol Studies, La Jolla, CA 92037 USA. RP Weinberg, WC (reprint author), US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Ctr Drug Evaluat & Res, 29 Lincoln Dr,NIH Bldg 29B,Room 3NN04, Bethesda, MD 20892 USA. EM wendy.weinberg@fda.hhs.gov FU FDA Intramural Funds [Z01 BO 04006-06 LIMB]; Swedish Cancer Foundation; Karolinska Institutet; Karolinska University Hospital; Cancer Society in Stockholm; Erik and Edith Fernstrom Foundation for Medical Research FX We wish to acknowledge Michelle Beeche for her assistance in establishing the p53QS-val135 colony, Dr Kinnimulki Vijayachandra for help with the in vitro senescence assay, Dr Anna Eriksson for advice regarding the immunohistochemical analyses, and Dr Stefano Piccolo for providing the Mix.2 plasmid. We are deeply indebted to Dr Ulrike Lichti for her advice and guidance in setting up the grafting model. This work was supported by FDA Intramural Funds for project Z01 BO 04006-06 LIMB (WCW, RMP, KEK), the Swedish Cancer Foundation (MN), Karolinska Institutet (MN, TE), Karolinska University Hospital (MN), the Cancer Society in Stockholm (MN), and the Erik and Edith Fernstrom Foundation for Medical Research (MN, TE). Tissue analysis was partly performed at the KI/Karolinska University Hospital-supported core facility for mouse tissue analysis. NR 42 TC 3 Z9 3 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD OCT PY 2009 VL 219 IS 2 BP 263 EP 274 DI 10.1002/path.2600 PG 12 WC Oncology; Pathology SC Oncology; Pathology GA 501YZ UT WOS:000270421900013 PM 19718706 ER PT J AU Spencer, JA Kauffman, JF Reepmeyer, JC Gryniewicz, CM Ye, W Toler, DY Buhse, LF Westenberger, BJ AF Spencer, John A. Kauffman, John F. Reepmeyer, John C. Gryniewicz, Connie M. Ye, Wei Toler, Duckhee Y. Buhse, Lucinda F. Westenberger, Benjamin J. TI Screening of Heparin API by Near Infrared Reflectance and Raman Spectroscopy SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE near infrared; Raman; heparin; oversulfated chondroitin sulfate (OSCS); chemometrics; partial least squares (PLS) ID ADVERSE CLINICAL EVENTS; LOW-MOLECULAR-WEIGHT; CAPILLARY-ELECTROPHORESIS; CHONDROITIN SULFATE; CONTAMINANT; SEPARATION; DEATHS AB Near infrared (NIR) reflectance and laser Raman spectra for a set of 69 heparin powder samples obtained from several foreign and domestic suppliers were measured. Both the NIR and Raman spectra of individual heparin API powder samples were correlated with sample compositions determined from response corrected relative peak areas of the capillary electropherograms of the samples using a partial least squares (PLS) regression model. Twenty-eight sample spectra were used to develop PLS models for the three major sample components; heparin, oversulfated chondroitin sulfate (OSCS) and glycosaminoglycans (GAGs). The PLS models were then used to successfully predict the compositions of 41 additional heparin samples. The success of these rapid, nondestructive technologies to identify contamination of heparin with OSCS demonstrates the potential of spectroscopy and chemometrics for screening of processed raw materials. These technologies are meant for screening purposes and not meant to replace either of the methods (capillary electrophoresis and NMR) currently required by USP and FDA. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3540-3547, 2009 C1 [Spencer, John A.; Kauffman, John F.; Reepmeyer, John C.; Gryniewicz, Connie M.; Ye, Wei; Toler, Duckhee Y.; Buhse, Lucinda F.; Westenberger, Benjamin J.] US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Spencer, JA (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, 1114 Market St, St Louis, MO 63101 USA. EM john.spencer@fda.hhs.gov NR 23 TC 22 Z9 23 U1 2 U2 10 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD OCT PY 2009 VL 98 IS 10 BP 3540 EP 3547 DI 10.1002/jps.21660 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 500QP UT WOS:000270319100004 PM 19117047 ER PT J AU Mahmood, I AF Mahmood, Iftekhar TI Pharmacokinetic Allometric Scaling of Antibodies: Application to the First-In-Human Dose Estimation SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE interspecies pharmacokinetic scaling; antibodies; clearance; volume of distribution; elimination half-life; first-in-human dose ID HUMANIZED MONOCLONAL-ANTIBODY; RESPIRATORY SYNCYTIAL VIRUS; ENDOTHELIAL GROWTH-FACTOR; DIGOXIN-SPECIFIC FAB; HUMAN DRUG CLEARANCE; PRECLINICAL PHARMACOKINETICS; TISSUE DISTRIBUTION; PREDICTION; VOLUME; PARAMETERS AB The objectives of this study are: (i) to evaluate the predictive performance of interspecies scaling for antibodies to predict clearance, volume of distribution at steady state, and half-life in humans from animal data and (ii) to estimate first-inhuman dose based on the predicted human clearance. Four methods were used to predict clearance in humans: (1) clearance versus body weight (simple allometry), (2) the product of clearance and maximum life-span potential (MLP) versus body weight, (3) the product of clearance and brain weight versus body weight, and (4) the application of a fixed exponent of 0.75. Based on the predicted human clearance, six methods were used to estimate the first-in-human dose. The predicted pharmacokinetic parameters and the estimated first-in-human dose of antibodies were compared with the observed human values. The results of the study indicated that the clearance of antibodies can be predicted with reasonable accuracy in humans and a good estimate of first human dose can be obtained from the predicted human clearance. (C) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3850-3861, 2009 C1 US FDA, OBRR, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Mahmood, I (reprint author), US FDA, OBRR, Ctr Biol Evaluat & Res, 1451 Rockville Pike, Rockville, MD 20857 USA. EM iftekhar.mahmood@fda.hhs.gov NR 31 TC 30 Z9 31 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD OCT PY 2009 VL 98 IS 10 BP 3850 EP 3861 DI 10.1002/jps.21682 PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 500QP UT WOS:000270319100031 PM 19177515 ER PT J AU Anderson, DL AF Anderson, David L. TI Use of l-cysteine for minimization of inorganic Hg loss during thermal neutron irradiation SO JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY LA English DT Article DE Mercury; INAA; L-cysteine ID ACTIVATION ANALYSIS; MERCURY AB Thermal neutron irradiation experiments performed with cellulose-based l-cysteine-treated and untreated Hg standards showed Hg losses of 59-81% for untreated standards but only about a 0.2% loss for treated standards. These results and others for multielement standards showed that Hg loss is highly dependent on total mass and placement of materials in the irradiation vessel and that distribution of volatilized Hg was fairly uniform throughout the sample-containing region of the vessel. Polyethylene trapped volatile Hg much more efficiently than cellulose and a multielement standard containing inorganic Se selectively trapped Hg lost from a co-irradiated multielement standard containing Hg. C1 US FDA, Off Regulatory Sci, Chem Contaminants Branch HFS 716, College Pk, MD 20740 USA. RP Anderson, DL (reprint author), US FDA, Off Regulatory Sci, Chem Contaminants Branch HFS 716, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM david.anderson@fda.hhs.gov NR 8 TC 7 Z9 7 U1 3 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0236-5731 J9 J RADIOANAL NUCL CH JI J. Radioanal. Nucl. Chem. PD OCT PY 2009 VL 282 IS 1 BP 11 EP 14 DI 10.1007/s10967-009-0160-1 PG 4 WC Chemistry, Analytical; Chemistry, Inorganic & Nuclear; Nuclear Science & Technology SC Chemistry; Nuclear Science & Technology GA 509OM UT WOS:000271027400004 ER PT J AU Anderson, DL AF Anderson, David L. TI Analytical capabilities of anticoincidence INAA for biological materials SO JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY LA English DT Article DE Anticoincidence INAA; Biologicals; LODs ID SPECTROMETRY AB Sensitivities and limits of detection (LODs) for 39 elements were determined for cellulose filters, foods, and biological reference materials by anticoincidence instrumental neutron activation analysis. Compton background reduction improved many LODs by about a factor of 2, but increased LODs for elements whose radioisotopes decay with cascading gamma-rays. As and Hg analyses were aided by reduction of Br and Se photopeak intensities, respectively. LODs of 0.03-0.8 mu g/kg were achieved for 16 elements in cellulose filters. Typical biological material and food LODs were higher by factors of about 10-600. C1 US FDA, Off Regulatory Sci, Chem Contaminants Branch HFS 716, College Pk, MD 20740 USA. RP Anderson, DL (reprint author), US FDA, Off Regulatory Sci, Chem Contaminants Branch HFS 716, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM david.anderson@fda.hhs.gov NR 7 TC 7 Z9 7 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0236-5731 EI 1588-2780 J9 J RADIOANAL NUCL CH JI J. Radioanal. Nucl. Chem. PD OCT PY 2009 VL 282 IS 1 BP 75 EP 79 DI 10.1007/s10967-009-0162-z PG 5 WC Chemistry, Analytical; Chemistry, Inorganic & Nuclear; Nuclear Science & Technology SC Chemistry; Nuclear Science & Technology GA 509OM UT WOS:000271027400017 ER PT J AU Martinez, M Mahmood, I Hunter, RP AF Martinez, M. Mahmood, I. Hunter, R. P. TI Allometric scaling of clearance in dogs SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID COMPARATIVE PHARMACOKINETICS; ANTIPYRINE CLEARANCE; CYNOMOLGUS MONKEYS; BEAGLE DOGS; METABOLISM; HUMANS; DISPOSITION; GREYHOUND; DRUG; RATS AB Most drugs indicated for use in dogs are labeled for administration on a mg/kg basis. Such dosing recommendations are grounded on an assumption that total body clearance (Cl) scales in a manner directly proportional to body weight (i.e. that it scales with an allometric exponent of 1). Despite the critical nature of this assumption (the range of normal canine body weights can go from as small as 2 lbs to almost 200 lbs), the validity of this assumption has not been rigorously challenged. Therefore, this manuscript provides an initial assessment of the potential ramifications of this assumption. This objective was accomplished through the following three sets of analysis: (i) examining the observed vs. predicted Cl values across 10 drugs based upon interspecies scaling; (ii) estimating the difference in area under the concentration vs. time curve values if Cl scaled directly in proportion to body weight vs. in a manner consistent with the allometric exponent estimated in the first data analysis; and (iii) exploring the impact of breed differences in drug metabolism that may further confound the problem of exposure assessment. Based upon this assessment, we conclude that if Cl does not scale directly in proportion to body weight, the actual drug exposure in large or small dogs could differ markedly from those concentrations estimated on the basis of studies conducted in beagle-sized dogs. C1 [Martinez, M.; Mahmood, I.] US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Div Therapeut Drugs Food Anim HFV 130, Rockville, MD 20855 USA. [Mahmood, I.] US FDA, Ctr Biol Evaluat & Res, Off Blood Review & Res, Rockville, MD 20855 USA. [Hunter, R. P.] Elanco Anim Hlth, Greenfield, IN USA. RP Martinez, M (reprint author), US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Div Therapeut Drugs Food Anim HFV 130, 7500 Standish Pl, Rockville, MD 20855 USA. EM marilyn.martinez@fda.hhs.gov RI Hunter, Robert/A-2306-2008 OI Hunter, Robert/0000-0003-1224-2376 NR 25 TC 7 Z9 7 U1 0 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD OCT PY 2009 VL 32 IS 5 BP 411 EP 416 DI 10.1111/j.1365-2885.2009.01062.x PG 6 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 493IY UT WOS:000269731200001 PM 19754905 ER PT J AU Gonzalez, JF Shaikh, B Reimschuessel, R Kane, AS AF Gonzalez, J. F. Shaikh, B. Reimschuessel, R. Kane, A. S. TI In vitro kinetics of hepatic albendazole sulfoxidation in channel catfish (Ictalurus punctatus), tilapia (Oreochromis sp.), rainbow trout (Oncorhynchus mykiss) and induction of EROD activity in ABZ-dosed channel catfish SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID GLUTATHIONE-S-TRANSFERASE; HUMAN-LIVER-MICROSOMES; LIQUID-CHROMATOGRAPHY; ATLANTIC SALMON; METABOLISM; RAT; PHARMACOKINETICS; ENZYMES; PLASMA; CATTLE AB Liver microsomes from market-size (n = 6) rainbow trout, channel catfish and tilapia were used to investigate in vitro biotransformation kinetics of albendazole (ABZ). ABZ was transformed to a single metabolite, ABZ sulfoxide (ABZ-SO). Catfish displayed the highest maximal velocity (V(max) = 264.0 +/- 58.6 pmols ABZ-SO/min/mg protein) followed by tilapia (112.3 +/- 8.2) and rainbow trout (73.3 +/- 10.3). V(max) in catfish was significantly different (P < 0.05) from the other two species. Michaelis-Menten constant (K(m)) values (mu m) varied significantly among the species: rainbow trout (3.9 +/- 0.5), tilapia (9.2 +/- 1.7) and catfish (22.0 +/- 3.2). However, V(max)/K(m) ratios showed no difference among the three species, making them equally efficient performing this phase I biotransformation reaction. In a second series of experiments, channel catfish (n = 6 per treatment) were dosed in vivo with gel-food containing ABZ (10 mg/kg, p.o.). Fish were killed at 24, 48, 72 and 120 h after dosage. Control fish were fed ABZ-free feed. Induction of ethoxyresorufin-o-deethylase activity was significant (P < 0.05) in all ABZ-dosed treatments as compared with controls. C1 [Gonzalez, J. F.] Univ Nacl Colombia, Sch Vet Med & Anim Sci, Bogota, Colombia. [Shaikh, B.; Reimschuessel, R.] US FDA, Ctr Vet Med, Laurel, MD USA. [Kane, A. S.] Univ Florida, Coll Publ Hlth & Hlth Profess, Gainesville, FL USA. RP Gonzalez, JF (reprint author), Calle 23 A 59-72 T4 Ap 704, Bogota, Colombia. EM jfgonzalezma@unal.edu.co FU Joint Institute of Food Safety and Nutrition (JIFSAN) [FDU001418] FX This work was funded by the Joint Institute of Food Safety and Nutrition (JIFSAN) - Contract # FDU001418. The authors thank Charlie Gieseker and Stanley Serfling for their help with the acclimation of fish specimens and Nathan Rummel for HPLC analysis at the Center for Veterinary Medicine at FDA (Laurel, MD, USA). NR 40 TC 4 Z9 5 U1 1 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD OCT PY 2009 VL 32 IS 5 BP 429 EP 435 DI 10.1111/j.1365-2885.2009.01056.x PG 7 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 493IY UT WOS:000269731200004 PM 19754908 ER PT J AU Bertke, AS Patel, A Imai, Y Apakupakul, K Margolis, TP Krause, PR AF Bertke, Andrea S. Patel, Amita Imai, Yumi Apakupakul, Kathleen Margolis, Todd P. Krause, Philip R. TI Latency-Associated Transcript (LAT) Exon 1 Controls Herpes Simplex Virus Species-Specific Phenotypes: Reactivation in the Guinea Pig Genital Model and Neuron Subtype-Specific Latent Expression of LAT SO JOURNAL OF VIROLOGY LA English DT Article ID EPINEPHRINE-INDUCED REACTIVATION; RABBIT EYE MODEL; INFECTED-RABBITS; IN-VIVO; TYPE-1; PROMOTER; REGION; HSV-1; DOWNSTREAM; SEQUENCES AB Herpes simplex virus 1 (HSV-1) and HSV-2 cause similar acute infections but differ in their abilities to reactivate from trigeminal and lumbosacral dorsal root ganglia. During latency, HSV-1 and HSV-2 also preferentially express their latency-associated transcripts (LATs) in different sensory neuronal subtypes that are positive for A5 and KH10 markers, respectively. Chimeric virus studies showed that LAT region sequences influence both of these viral species-specific phenotypes. To further map the LAT region sequences responsible for these phenotypes, we constructed the chimeric virus HSV2-LAT-E1, in which exon 1 (from the LAT TATA to the intron splice site) was replaced by the corresponding sequence from HSV-1 LAT. In intravaginally infected guinea pigs, HSV2-LAT-E1 reactivated inefficiently relative to the efficiency of its rescuant and wild-type HSV-2, but it yielded similar levels of viral DNA, LAT, and ICP0 during acute and latent infection. HSV2-LAT-E1 preferentially expressed the LAT in A5+ neurons (as does HSV-1), while the chimeric viruses HSV2-LAT-P1 (LAT promoter swap) and HSV2-LAT-S1 (LAT sequence swap downstream of the promoter) exhibited neuron subtype-specific latent LAT expression phenotypes more similar to that of HSV-2 than that of HSV-1. Rescuant viruses displayed the wild-type HSV-2 phenotypes of efficient reactivation in the guinea pig genital model and a tendency to express LAT in KH10+ neurons. The region that is critical for HSV species-specific differences in latency and reactivation thus lies between the LAT TATA and the intron splice site, and minor differences in the 5' ends of chimeric sequences in HSV2-LAT-E1 and HSV2-LAT-S1 point to sequences immediately downstream of the LAT TATA. C1 [Krause, Philip R.] FDA CBER, HFM 457, Bethesda, MD 20892 USA. [Imai, Yumi; Apakupakul, Kathleen; Margolis, Todd P.] Univ Calif San Francisco, Francis I Proctor Fdn, San Francisco, CA 94143 USA. RP Krause, PR (reprint author), FDA CBER, HFM 457, 29 Lincoln Dr, Bethesda, MD 20892 USA. EM philip.krause@fda.hhs.gov OI Krause, Philip/0000-0002-1045-7536 NR 34 TC 14 Z9 17 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2009 VL 83 IS 19 BP 10007 EP 10015 DI 10.1128/JVI.00559-09 PG 9 WC Virology SC Virology GA 491WX UT WOS:000269614300034 PM 19641003 ER PT J AU Naum, M Brown, EW Mason-Gamer, RJ AF Naum, Marianna Brown, Eric W. Mason-Gamer, Roberta J. TI Phylogenetic evidence for extensive horizontal gene transfer of type III secretion system genes among enterobacterial plant pathogens SO MICROBIOLOGY-SGM LA English DT Article ID BACTERIAL EVOLUTION; SEQUENCES; ISLANDS; ERWINIA; IDENTIFICATION; LIKELIHOOD; POSITION; FAMILY; TREES AB This study uses sequences from four genes, which are involved in the formation of the type III secretion apparatus, to determine the role of horizontal gene transfer in the evolution of virulence genes for the enterobacterial plant pathogens. Sequences of Erwinia, Brenneria, Pectobacterium, Dickeya and Pantoea were compared (a) with one another, (b) with sequences of enterobacterial animal pathogens, and (c) with sequences of plant pathogenic gamma and beta proteobacteria, to evaluate probable paths of lateral exchange leading to the current distribution of virulence determinants among these micro-organ isms. Phylogenies were reconstructed based on hrcC, hrcR, hrcJ and hrcV gene sequences using parsimony and maximum-likelihood algorithms. Virulence gene phylogenies were also compared with several housekeeping gene loci in order to evaluate patterns of lateral versus vertical acquisition. The resulting phylogenies suggest that multiple horizontal gene transfer events have occurred both within and among the enterobacterial plant pathogens and plant pathogenic gamma and beta proteobacteria. hrcJ sequences are the most similar, exhibiting anywhere from 2 to 50% variation at the nucleotide level, with the highest degree of variation present between plant and animal pathogen sequences. hrcV sequences are conserved among plant and animal pathogens at the N terminus. The C-terminal domain is conserved only among the enterobacterial plant pathogens, as are the hrcC and hrcR sequences. Additionally, hrcJ and hrcV sequence phylogenies suggest that at least some type III secretion system virulence genes from enterobacterial plant pathogens are related more closely to those of the genus Pseudomonas, a conclusion neither supported nor refuted by hrcC or hrcR. C1 [Naum, Marianna; Mason-Gamer, Roberta J.] Univ Illinois, Dept Biol Sci, Chicago, IL 60611 USA. [Naum, Marianna; Brown, Eric W.] US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Naum, M (reprint author), Univ Illinois, Dept Biol Sci, Chicago, IL 60611 USA. EM marianna.naum@fda.hhs.gov FU National Science Foundation (NSF) [DEB 0426194]; University of Illinois at Chicago (UIC) FX Thanks to A. Charkowski of the University of Wisconsin, Madison, for very generously providing the Pectobacterium strains used in this Study, and to Diane McCarthy, Michael Jorgensen and Keith Lampel for valuable comments on an earlier version of the manuscript. Also, a special thanks to Peter Naum and Sergio Mojica for helping us create the illustration in Fig. 1. The research was supported by National Science Foundation (NSF) grant number DEB 0426194 to R. J. M.-G., and a University of Illinois at Chicago (UIC) Provosts Award to M. N. NR 40 TC 16 Z9 16 U1 0 U2 6 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD OCT PY 2009 VL 155 BP 3187 EP 3199 DI 10.1099/mic.0.029892-0 PG 13 WC Microbiology SC Microbiology GA 510DZ UT WOS:000271069500004 PM 19643761 ER PT J AU Wang, X Zhao, JQ Tang, SX Lee, S Glazer, RI Hewlett, I AF Wang, Xue Zhao, Jiangqin Tang, Shixing Lee, Sherwin Glazer, Robert I. Hewlett, Indira TI c-FLIPL regulates PKC via AP-2 to inhibit Bax-mediated apoptosis induced by HIV-1 gp120 in Jurkat cells SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE Apoptosis; AP-2; HIV-1 gp120; c-FLIPL; PKC; Bax ID PROTEIN-KINASE-C; GLYCOPROTEIN COMPLEX; CANCER CELLS; T-CELLS; FAS; ENVELOPE; DEATH; ACTIVATION; DEPLETION; LYMPHOCYTES AB c-FLIPL, an inhibitor of caspase 8, is known to inhibit the Fas/caspase 8 apoptotic pathway; however, its involvement of Bax/mitochondrial apoptosis is not well understood. Using human cells, Jurkat cell line, induced with HIV-1 gp120, we studied the effects of c-FLIPL on Bax/mitochondrial apoptosis. We found that the induction of apoptosis by HIV-1 envelope protein, gp120, involved the activation of both Bax-dependent and death receptor-mediated pathways, and HIV-1 infection deceased c-FLIPL expression. Interestingly, c-FLIPL expression downregulated protein kinase C (PKC) expression at the transcript level involving activated protein-2 (AP-2). c-FLIPL expression reduced AP-2 protein levels required to promote PKC protein expression and PKC-associated inactive form of Bax, and inhibited Bax activation, suggesting that c-FLIPL inhibits Bax activation via modulating PKC expression at the transcriptional level involving AP-2 during gp120 treatment. Collectively, these findings further corroborate the concept that gp120 plays an important role, via involvement of molecules such as c-FLIPL, in apoptotic cell death due to HIV-1 infection. C1 [Wang, Xue; Zhao, Jiangqin; Tang, Shixing; Lee, Sherwin; Hewlett, Indira] US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Glazer, Robert I.] Georgetown Univ, Sch Med, Dept Pharmacol & Oncol, Washington, DC USA. [Glazer, Robert I.] Georgetown Univ, Sch Med, Lombardi Canc Ctr, Washington, DC USA. RP Wang, X (reprint author), US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bldg 29B,Rm 4NN16,8800 Rockville Pike, Bethesda, MD 20892 USA. EM xue.wang@fda.hhs.gov; indira.hewlett@fda.hhs.gov NR 25 TC 6 Z9 6 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD OCT PY 2009 VL 330 IS 1-2 BP 23 EP 29 DI 10.1007/s11010-009-0096-3 PG 7 WC Cell Biology SC Cell Biology GA 505IV UT WOS:000270687500003 PM 19363595 ER PT J AU Klamt, F Zdanov, S Levine, RL Pariser, A Zhang, YQ Zhang, BL Yu, LR Veenstra, TD Shacter, E AF Klamt, Fabio Zdanov, Stephanie Levine, Rodney L. Pariser, Ashley Zhang, Yaqin Zhang, Baolin Yu, Li-Rong Veenstra, Timothy D. Shacter, Emily TI Oxidant-induced apoptosis is mediated by oxidation of the actin-regulatory protein cofilin SO NATURE CELL BIOLOGY LA English DT Article ID HYPOCHLOROUS ACID; CELL-DEATH; PERMEABILITY TRANSITION; HYDROGEN-PEROXIDE; MITOCHONDRIAL PERMEABILITY; LYMPHOMA-CELLS; STRESS; CYSTEINE; CANCER; CHLORAMINES AB Physiological oxidants that are generated by activated phagocytes comprise the main source of oxidative stress during inflammation(1,2). Oxidants such as taurine chloramine (TnCl) and hydrogen peroxide (H(2)O(2)) can damage proteins and induce apoptosis, but the role of specific protein oxidation in this process has not been defined. We found that the actin-binding protein cofilin is a key target of oxidation. When oxidation of this single regulatory protein is prevented, oxidant-induced apoptosis is inhibited. Oxidation of cofilin causes it to lose its affinity for actin and to translocate to the mitochondria, where it induces swelling and cytochrome c release by mediating opening of the permeability transition pore (PTP). This occurs independently of Bax activation and requires both oxidation of cofilin Cys residues and dephosphorylation at Ser 3. Knockdown of endogenous cofilin using targeted siRNA inhibits oxidant-induced apoptosis, which is restored by re-expression of wild-type cofilin but not by cofilin containing Cys to Ala mutations. Exposure of cofilin to TnCl results in intramolecular disulphide bonding and oxidation of Met residues to Met sulphoxide, but only Cys oxidation causes cofilin to induce mitochondrial damage. C1 [Klamt, Fabio; Zdanov, Stephanie; Pariser, Ashley; Zhang, Yaqin; Zhang, Baolin; Shacter, Emily] US FDA, Biochem Lab, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Klamt, Fabio] Univ Fed Rio Grande do Sul, Ctr Oxidat Stress Res, Dept Biochem, ICBS, BR-90035003 Porto Alegre, RS, Brazil. [Levine, Rodney L.] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. [Yu, Li-Rong] US FDA, Ctr Prote, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Yu, Li-Rong; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Shacter, E (reprint author), US FDA, Biochem Lab, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. EM emily.shacter@fda.hhs.gov RI Zdanov, Stephanie/G-2524-2012; Levine, Rodney/D-9885-2011 FU Intramural NIH HHS [Z01 HL000225-31]; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 38 TC 114 Z9 115 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD OCT PY 2009 VL 11 IS 10 BP 1241 EP U193 DI 10.1038/ncb1968 PG 18 WC Cell Biology SC Cell Biology GA 501KZ UT WOS:000270382000014 PM 19734890 ER PT J AU Bocchini, JA Bernstein, HH Bradley, JS Brady, MT Byington, CL Fisher, MC Glode, MP Jackson, MA Keyserling, HL Kimberlin, DW Orenstein, WA Schutze, GE Willoughby, RE Dennehy, PH Frenck, RW Rubin, LG Bell, B Bortolussi, R Clover, RD Fischer, MA Gellin, B Gorman, RL Pratt, RD Lee, L Read, JS Starke, JR Swanson, J Baker, CJ Long, SS Pickering, LK Ledbetter, EO Meissner, HC O'Dell, JD Weinberg, ST Frantz, J AF Bocchini, Joseph A., Jr. Bernstein, Henry H. Bradley, John S. Brady, Michael T. Byington, Carrie L. Fisher, Margaret C. Glode, Mary P. Jackson, Mary Anne Keyserling, Harry L. Kimberlin, David W. Orenstein, Walter A. Schutze, Gordon E. Willoughby, Rodney E. Dennehy, Penelope H. Frenck, Robert W., Jr. Rubin, Lorry G. Bell, Beth Bortolussi, Robert Clover, Richard D. Fischer, Marc A. Gellin, Bruce Gorman, Richard L. Pratt, R. Douglas Lee, Lucia Read, Jennifer S. Starke, Jeffrey R. Swanson, Jack Baker, Carol J. Long, Sarah S. Pickering, Larry K. Ledbetter, Edgar O. Meissner, H. Cody O'Dell, J. Dennis Weinberg, Stuart T. Frantz, Jennifer CA Comm Infect Dis TI Policy Statement-Recommendations for the Prevention and Treatment of Influenza in Children, 2009-2010 SO PEDIATRICS LA English DT Article DE influenza; novel influenza A (H1N1) virus; immunization; live-attenuated influenza vaccine; trivalent inactivated influenza vaccine; vaccine; children; pediatrics ID INFECTIOUS-DISEASES AB The purpose of this statement is to update current recommendations for routine use of trivalent seasonal influenza vaccine and antiviral medications for the prevention and treatment of influenza in children. Pediatrics 2009; 124: 1216-1226 C1 [Bell, Beth; Fischer, Marc A.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Bortolussi, Robert] Canadian Paediat Soc, Ottawa, ON, Canada. [Clover, Richard D.] Amer Acad Family Phys, Leawood, KS USA. [Gorman, Richard L.; Read, Jennifer S.] NIH, Bethesda, MD USA. [Pratt, R. Douglas; Lee, Lucia] US FDA, Rockville, MD 20857 USA. EM jfrantz@aap.org OI Dennehy, Penelope/0000-0002-2259-5370; Byington, Carrie/0000-0002-7350-9495 NR 5 TC 24 Z9 24 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2009 VL 124 IS 4 BP 1216 EP 1226 DI 10.1542/peds.2009-1806 PG 11 WC Pediatrics SC Pediatrics GA 500CI UT WOS:000270274300028 ER PT J AU Shellock, FG Woods, TO Crues, JV AF Shellock, Frank G. Woods, Terry O. Crues, John V., III TI MR Labeling Information for Implants and Devices: Explanation of Terminology SO RADIOLOGY LA English DT Editorial Material ID SAFETY; RADIOLOGY C1 [Shellock, Frank G.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90045 USA. [Woods, Terry O.] Hlth Food & Drug Adm, Ctr Devices & Radiol, Silver Spring, MD USA. [Crues, John V., III] Radnet, Los Angeles, CA USA. RP Shellock, FG (reprint author), Univ So Calif, Keck Sch Med, 7511 McConnell Ave, Los Angeles, CA 90045 USA. EM frank.shellock@mrisafety.com NR 13 TC 57 Z9 58 U1 1 U2 3 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2009 VL 253 IS 1 BP 26 EP 30 DI 10.1148/radiol.2531091030 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 512UB UT WOS:000271275200006 PM 19789253 ER PT J AU Thomas, M George, NI Patterson, TA Bowyer, JF AF Thomas, Monzy George, Nysia I. Patterson, Tucker A. Bowyer, John F. TI Amphetamine and Environmentally Induced Hyperthermia Differentially Alter the Expression of Genes Regulating Vascular Tone and Angiogenesis in the Meninges and Associated Vasculature SO SYNAPSE LA English DT Article DE amphetamines; vasculature; meninges; blood-brain barrier; gene expression ID BLOOD-BRAIN-BARRIER; GLUTAMINE ANDROGEN RECEPTOR; MICROGLIAL ACTIVATION; NEURONAL DEGENERATION; ISCHEMIC-STROKE; METHAMPHETAMINE NEUROTOXICITY; DOPAMINERGIC NEUROTOXICITY; CAUDATE-PUTAMEN; RAT-BRAIN; IN-VIVO AB An amphetamine (AMPH) regimen that does not produce a prominent blood-brain barrier breakdown was shown to significantly alter the expression of genes regulating vascular tone, immune function, and angiogenesis in vasculature associated with arachnoid and pia membranes of the forebrain. Adult-male Sprague-Dawley rats were given either saline injections during environmentally-induced hyperthermia (EIH) or four doses of AMPH with 2 h between each dose (5, 7.5, 10, and 10 mg/kg d-AMPH, s.c.) that produced hyperthermia. Rats were sacrificed either 3 h or 1 day after dosing, and total RNA and protein was isolated from the meninges, arachnoid and pia membranes, and associated vasculature (MAV) that surround the forebrain. Vip, eNos, Drd1a, and Edn1 (genes regulating vascular tone) were increased by either EIH or AMPH to varying degrees in MAV, indicating that EIH and AMPH produce differential responses to enhance vasodilatation. AMPH, and EIH to a lesser extent, elicited a significant inflammatory response at 3 h as indicated by an increased MAV expression of cytokines Il1b, Il6, Ccl-2, Cxcl1, and Cxcl2. Also, genes related to heat shock/stress and disruption of vascular homeostasis such as Icam1 and Hsp72 were also observed. The increased expression of Ctgf and Timp1 and the decreased expression of Akt1, Anpep, and Mmp2 and Tek (genes involved in stimulating angiogenesis) from AMPH exposure suggest that angiogenesis was arrested or disrupted in MAV to a greater extent by AMPH compared to EIH. Alterations in vascular-related gene expression in the parietal cortex and striatum after AMPH were less in magnitude than in MAV, indicating less of a disruption of vascular homeostasis in these two regions. Changes in the levels of insulin-like growth factor binding proteins Igfbp1, 2, and 5 in MAV, compared to those in striatum and parietal cortex, imply an interaction between these regions to regulate the levels of insulin-like growth factor after AMPH damage. Thus, the vasculature and meninges surrounding the surface of the forebrain may be an important region in which AMPHs can disrupt vascular homeostasis. Synapse 63:881-894, 2009. Published 2009 Wiley-Liss, Inc.(dagger) C1 [Thomas, Monzy; Patterson, Tucker A.; Bowyer, John F.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [George, Nysia I.] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Bowyer, JF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM john.bowyer@fda.hhs.gov NR 75 TC 9 Z9 10 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD OCT PY 2009 VL 63 IS 10 BP 881 EP 894 DI 10.1002/syn.20661 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 488UC UT WOS:000269374600007 PM 19582783 ER PT J AU Schafer, K Francke-Carroll, S Hutto, D Neef, N Silverman, L Vahle, J Whitney, K AF Schafer, Ken Francke-Carroll, Sabine Hutto, David Neef, Natasha Silverman, Lee Vahle, John Whitney, Katharine TI Regulatory Forum for Toxicologic Pathology: A Two-year Update SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material C1 [Schafer, Ken] Vet Path Serv Inc, Greenfield, IN USA. [Francke-Carroll, Sabine] US FDA, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Hutto, David; Silverman, Lee] Millennium Pharmaceut Cambridge, Cambridge, MA USA. [Vahle, John] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Whitney, Katharine] Abbott Labs, Abbott Pk, IL 60064 USA. RP Schafer, K (reprint author), 30 E North St, Greenfield, IN 46140 USA. EM kschafer@vetpathservicesinc.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD OCT PY 2009 VL 37 IS 6 BP 826 EP 826 DI 10.1177/0192623309346747 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 503AS UT WOS:000270503800015 ER PT J AU Zhang, X Paule, MG Newport, GD Zou, XJ Sadovova, N Berridge, MS Apana, SM Hanig, JP Slikker, W Wang, C AF Zhang, Xuan Paule, Merle G. Newport, Glenn D. Zou, Xiaoju Sadovova, Natalya Berridge, Marc S. Apana, Scott M. Hanig, Joseph P. Slikker, William, Jr. Wang, Cheng TI A Minimally Invasive, Translational Biomarker of Ketamine-Induced Neuronal Death in Rats: microPET Imaging Using F-18-Annexin V SO TOXICOLOGICAL SCIENCES LA English DT Article DE ketamine; apoptosis; microPET ID ANNEXIN-V; DEVELOPING BRAIN; IN-VIVO; APOPTOTIC NEURODEGENERATION; ANESTHETIC AGENTS; PET; PHOSPHATIDYLSERINE; EXPOSURE; NEUROTOXICITY; STIMULATION AB It has been reported that suppression of N-methyl-D-aspartate (NMDA) receptor function by ketamine may trigger apoptosis of neurons when given repeatedly during the brain growth spurt period. Because microPET scans can provide in vivo molecular imaging at sufficient resolution, it has been proposed as a minimally invasive method for detecting apoptosis using the tracer F-18-labeled annexin V. In this study, the effect of ketamine on the metabolism and integrity of the rat brain were evaluated by investigating the uptake and retention of F-18-fluorodeoxyglucose (FDG) and F-18-annexin V using microPET imaging. On postnatal day (PND) 7, rat pups in the experimental group were exposed to six injections of ketamine (20 mg/kg at 2-h intervals) and control rat pups received six injections of saline. On PND 35, 37 MBq (1 mCi) of F-18-FDG or F-18-annexin V was injected into the tail vein of treated and control rats, and static microPET images were obtained over I (FDG) and 2 In (annexin V) following the injection. No significant difference was found in F-18-FDG uptake in the regions of interest (ROIs) in the brains of ketamine-treated rats compared with saline-treated controls. The uptake of F-18-annexin V, however, was significantly increased in the ROI of ketamine-treated rats. Additionally, the duration of annexin V tracer washout was prolonged in the ketamine-treated animals. These results demonstrate that microPET imaging is capable of distinguishing differences in retention (if F-18-annexin V in different brain regions and suggests that this approach may provide a minimally invasive biomarker of neuronal apoptosis in rats. C1 [Zhang, Xuan; Paule, Merle G.; Newport, Glenn D.; Zou, Xiaoju; Slikker, William, Jr.; Wang, Cheng] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Sadovova, Natalya] Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Berridge, Marc S.; Apana, Scott M.] 3D Imaging LLC, Little Rock, AR 72113 USA. [Hanig, Joseph P.] US FDA, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Wang, C (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM cheng.wang@fda.hhs.gov FU U.S. Food and Drug Administration [E7264] FX National Center for Toxicological Research/U.S. Food and Drug Administration (E7264). NR 40 TC 19 Z9 20 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD OCT PY 2009 VL 111 IS 2 BP 355 EP 361 DI 10.1093/toxsci/kfp167 PG 7 WC Toxicology SC Toxicology GA 503BU UT WOS:000270507500016 PM 19638431 ER PT J AU Sauder, CJ Zhang, CX Link, MA Duprex, WP Carbone, KM Rubin, SA AF Sauder, Christian J. Zhang, Cheryl X. Link, Malen A. Duprex, W. Paul Carbone, Kathryn M. Rubin, Steven A. TI Presence of lysine at aa 335 of the hemagglutinin-neuraminidase protein of mumps virus vaccine strain Urabe AM9 is not a requirement for neurovirulence SO VACCINE LA English DT Article DE Mumps virus; Urabe AM9 vaccine; Neurovirulence ID NUCLEOTIDE-SEQUENCE; POSITION 1081; SAFETY TEST; IN-VITRO; SH GENE; P-GENE; F-GENE; PARAMYXOVIRUS; TRANSCRIPTION; MUTATIONS AB The recent global resurgence of mumps has drawn attention to the continued need for robust mumps immunization programs. Unfortunately, some vaccines derived from inadequately attenuated vaccine strains of mumps virus have caused meningitis in vaccinees, leading to withdrawal of certain vaccine strains from the market, public resistance to vaccination, or in some cases, cessation of national mumps vaccination programs. The most widely implicated mumps vaccine in cases of postvaccination meningitis is derived from the Urabe AM9 strain, which remains in use in some countries. The Urabe AM9 vaccine virus has been shown to exhibit a considerable degree of nucleotide and amino acid heterogeneity. Some studies have specifically implicated variants containing a lysine residue at amino acid position 335 in the hemagglutinin-neuraminidase (HN) protein with neurotoxicity, whereas a glutamic acid residue at this position was associated with attenuation. To test this hypothesis we generated two modified Urabe AM9 cDNA clones coding either for a lysine or a glutamic acid at position 335 in the HN gene. The two viruses were rescued by reverse genetics and characterized in vitro and in vivo. Both viruses exhibited similar growth kinetics in neuronal and non-neuronal cell lines and were of similar neurotoxicity when tested in rats, suggesting that amino acid 335 is not a crucial determinant of Urabe AM9 growth or neurovirulence. Published by Elsevier Ltd. C1 [Sauder, Christian J.; Zhang, Cheryl X.; Link, Malen A.; Rubin, Steven A.] US FDA, DVP, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Duprex, W. Paul] Queens Univ Belfast, Sch Biomed Sci, Belfast BT9 7BL, Antrim, North Ireland. [Carbone, Kathryn M.] Natl Inst Dent & Craniefacial Res, NIH, Bethesda, MD 20892 USA. RP Sauder, CJ (reprint author), US FDA, DVP, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, 8800 Rockville Pike,Bldg 29A,HFM 460,Room 2C20, Bethesda, MD 20892 USA. EM christian.sauder@fda.hhs.gov OI Duprex, W Paul/0000-0003-1716-6376 NR 42 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD SEP 25 PY 2009 VL 27 IS 42 BP 5822 EP 5829 DI 10.1016/j.vaccine.2009.07.051 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 502ON UT WOS:000270469900017 PM 19660591 ER PT J AU Jackson, LS AF Jackson, Lauren S. TI Chemical Food Safety Issues in the United States: Past, Present, and Future SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Review DE Adulteration; food safety; chemical contaminants ID PERFORMANCE LIQUID-CHROMATOGRAPHY; TANDEM MASS-SPECTROMETRY; BISPHENOL-A; GOVERNMENT-REGULATION; GAS-CHROMATOGRAPHY; HEALTH-RISKS; TOTAL DIET; PET FOOD; ACRYLAMIDE; MELAMINE AB Considerable advances have been made over the past century in the understanding of the chemical hazards in food and ways for assessing and managing these risks. At the turn of the 20th century, many Americans were exposed to foods adulterated with toxic compounds. In the 1920s the increasing use of insecticides led to concerns of chronic ingestion of heavy metals such as lead and arsenic from residues remaining on crops. By the 1930s, a variety of agrochemicals were commonly used, and food additives were becoming common in processed foods. During the 1940s and 1950s advances were made in toxicology, and more systematic approaches were adopted for evaluating the safety of chemical contaminants in food. Modern gas chromatography and liquid chromatography, both invented in the 1950s and 1960s, were responsible for progress in detecting, quantifying, and assessing the risk of food contaminants and adulterants. In recent decades, chemical food safety issues that have been the center of media attention include the presence of natural toxins, processing-produced toxins (e.g., acrylamide, heterocyclic aromatic amines, and furan), food allergens, heavy metals (e.g., lead, arsenic, mercury, cadmium), industrial chemicals (e.g., benzene, perchlorate), contaminants from packaging materials, and unconventional contaminants (melamine) in food and feed. Due to the global nature of the food supply and advances in analytical capabilities, chemical contaminants will continue to be an area of concern for regulatory agencies, the food industry, and consumers in the future. C1 US FDA, NCFST, Summit Argo, IL 60501 USA. RP Jackson, LS (reprint author), US FDA, NCFST, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM Lauren.Jackson@fda.hhs.gov NR 109 TC 29 Z9 32 U1 9 U2 55 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 SEP 23 PY 2009 VL 57 IS 18 BP 8161 EP 8170 DI 10.1021/jf900628u PG 10 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 493OS UT WOS:000269747500013 PM 19719131 ER PT J AU Armstrong, DJ AF Armstrong, David J. TI Food Chemistry and US Food Regulations SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Food chemistry; food regulation; food history; FDA food regulations; nutrition ID ACRYLAMIDE AB The Agriculture and Food Chemistry Division (AGFD) was founded in 1908 shortly after passage of the first U.S. food regulations in 1906. Modem food regulations started with the passage of the Food Drug and Cosmetic Act in 1938. This Act has been amended several times to keep pace with developments in food chemistry. In 1958 the Food Additives Amendment was enacted to control substances added to food. Since 1958 scientific techniques have been developed to evaluate the safety and carcinogenicity of substances in the food supply. In the 1970s and 1980s AGFD symposia and books addressed compounds of concern in foods. In the 1990s food safety and nutrition regulations followed new developments in food and nutrition chemistry. Recently, the well-studied toxin acrylamide was discovered in food and presented regulators with new questions on safety and control in the food supply. Discoveries and developments in chemistry such as those in nanotechnology will continue to present challenges to food regulators. C1 [Armstrong, David J.] NCFST, FDA, Summit Argo, IL 60501 USA. RP Armstrong, DJ (reprint author), 206 Ranch Circle Rd, Kendalia, TX 78027 USA. EM darmstrongncfst@gvte.com NR 20 TC 13 Z9 14 U1 3 U2 34 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 EI 1520-5118 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD SEP 23 PY 2009 VL 57 IS 18 BP 8180 EP 8186 DI 10.1021/jf900014h PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 493OS UT WOS:000269747500015 PM 19719129 ER PT J AU Jin, TC Albillos, SM Guo, F Howard, A Fu, TJ Kothary, MH Zhang, YZ AF Jin, Tengchuan Albillos, Silvia M. Guo, Feng Howard, Andrew Fu, Tong-Jen Kothary, Mahendra H. Zhang, Yu-Zhu TI Crystal Structure of Prunin-1, a Major Component of the Almond (Prunus dulcis) Allergen Amandin SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Almond (Prunus dulcis); prunin; Pru1; amandin; food allergy; X-ray crystallography ID INITIAL CRYSTALLOGRAPHIC CHARACTERIZATION; ARA H 3; FOOD ALLERGY; 11S GLOBULIN; MOLECULAR GRAPHICS; STORAGE PROTEINS; TREE NUTS; PEANUT; CRYSTALLIZATION; IDENTIFICATION AB Seed storage proteins are accumulated during seed development and act as a reserve of nutrition for seed germination and young sprout growth. Plant seeds play an important role in human nutrition by providing a relatively inexpensive source of protein. However, many plant foods contain allergenic proteins, and the number of people suffering from food allergies has increased rapidly in recent years. The 11S globulins are the most widespread seed storage proteins, present in monocotyledonous and dicotyledonous seeds as well as in gymnosperms (conifers) and other spermatophytes, This family of proteins accounts for a number of nown major food allergens. They are of interest to both the public and industry due to food safety concerns. Because of the interests in the structural basis of the allergenicity of food allergens, we sought to determine the crystal structure of Pru1, the major component of the 11 S storage protein from almonds. The structure was refined to 2.4 angstrom, and the R/Rfree for the final refined structure is 17.2/22.9. Pru1 is a hexamer made of two trimers, Most of the bac -to-bac trimer-trimer association was contributed by monomer-monomer interactions. An alpha helix (helix 6) at the C-terminal end of the acidic domain of one of the interacting monomers lies at the cleft of the two protomers. The residues in this helix correspond to a flexible region in the peanut allergen Ara h 3 that encompasses a previously defined linear gE epitope. C1 [Fu, Tong-Jen] US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. [Jin, Tengchuan; Guo, Feng; Howard, Andrew; Zhang, Yu-Zhu] IIT, Dept Biol Chem & Phys Sci, Chicago, IL 60616 USA. [Albillos, Silvia M.; Zhang, Yu-Zhu] IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. [Kothary, Mahendra H.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Fu, TJ (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM tong.fu@fda.hhs.gov; yuzhu.zhang@iit.edu RI Zhang, Yuzhu/A-7109-2009; Jin, Tengchuan/B-5883-2014; Albillos, Silvia/D-1276-2016 OI Zhang, Yuzhu/0000-0001-7882-5692; Jin, Tengchuan/0000-0002-1395-188X; Albillos, Silvia/0000-0002-3273-0126 NR 63 TC 21 Z9 22 U1 4 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 SEP 23 PY 2009 VL 57 IS 18 BP 8643 EP 8651 DI 10.1021/jf9017355 PG 9 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 493OS UT WOS:000269747500081 PM 19694440 ER PT J AU Fang, H AF Fang, Hong TI The FDA Genomics Tool - ArrayTrack SO MOLECULAR & CELLULAR TOXICOLOGY LA English DT Meeting Abstract C1 [Fang, Hong] US FDA, ICF Z Tech Corp, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. NR 0 TC 2 Z9 3 U1 0 U2 0 PU KOREAN SOC TOXICOGENOMICS & TOXICOPROTEOMICS PI SEOUL PA KOREA INST SCIENCE & TECHNOLOGY, PO BOX 131 CHEONGRYANG, SEOUL, 130-650, SOUTH KOREA SN 1738-642X J9 MOL CELL TOXICOL JI Mol. Cell. Toxicol. PD SEP 20 PY 2009 VL 5 IS 3 BP 40 EP 40 PG 1 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 497BG UT WOS:000270028200003 ER PT J AU Shi, LM AF Shi, Leming TI The MicroArray Quality Control (MAQC) Project: Enabling Personalized Medicine with Genomics and Bioinformatics SO MOLECULAR & CELLULAR TOXICOLOGY LA English DT Meeting Abstract C1 [Shi, Leming] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KOREAN SOC TOXICOGENOMICS & TOXICOPROTEOMICS PI SEOUL PA KOREA INST SCIENCE & TECHNOLOGY, PO BOX 131 CHEONGRYANG, SEOUL, 130-650, SOUTH KOREA SN 1738-642X J9 MOL CELL TOXICOL JI Mol. Cell. Toxicol. PD SEP 20 PY 2009 VL 5 IS 3 BP 41 EP 41 PG 1 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 497BG UT WOS:000270028200006 ER PT J AU Warfel, JM D'Agnillo, F AF Warfel, Jason M. D'Agnillo, Felice TI Anthrax Lethal Toxin Enhances I kappa B Kinase Activation and Differentially Regulates Pro-inflammatory Genes in Human Endothelium SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BACILLUS-ANTHRACIS; PROTECTIVE ANTIGEN; TNF-ALPHA; INHALATIONAL ANTHRAX; SIGNALING PATHWAYS; VCAM-1 EXPRESSION; MESSENGER-RNA; MAP KINASES; IKK-BETA; T-CELLS AB Anthrax lethal toxin (LT) was previously shown to enhance transcriptional activity of NF-kappa B in tumor necrosis factor-alpha-activated primary human endothelial cells. Here we show that this LT-mediated increase in NF-kappa B activation is associated with the enhanced degradation of the inhibitory proteins I kappa B alpha and I kappa B beta but not I kappa B epsilon. Moreover, this was accompanied by enhanced activation of the I kappa B kinase complex (IKK), which is responsible for targeting I kappa B proteins for degradation. Importantly, LT enhancement of I kappa B alpha degradation was completely blocked by a selective IKK beta inhibitor, whereas I kappa B beta degradation was attenuated, suggesting a mechanistic link. Consistent with the above data, LT-cotreated cells show elevated phosphorylation of two IKK substrates, I kappa B alpha and p65, both of which were blocked by incubation with the IKK beta inhibitor. Consistent with NF-kappa B activation, LT increased transcription of the NF-kappa B regulated gene CD40. Conversely, LT inhibited transcription of another NF-kappa B-regulated gene, CCL2. This inhibition was linked to the LT-mediated suppression of another CCL2-regulating transcription factor, AP-1 (activator protein-1). These data suggest that LT-mediated enhancement of NF-kappa B is IKK-dependent, but importantly, the net effect of LT on the transcription of proinflammatory genes is driven by the cumulative effect of LT on the particular set of transcription factors that regulate a given promoter. Together, these findings provide new mechanistic insight on how LT may disrupt the host response to anthrax. C1 [Warfel, Jason M.; D'Agnillo, Felice] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Biochem & Vasc Biol, Bethesda, MD 20892 USA. [Warfel, Jason M.] Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20007 USA. RP D'Agnillo, F (reprint author), 29 Lincoln Dr,Bldg 29,Rm 129, Bethesda, MD 20892 USA. EM felice.dagnillo@fda.hhs.gov RI Warfel, Jason/D-2557-2011 FU National Institutes of Health-Georgetown University Graduate Partnership Program; Oak Ridge Institute for Science and Education FX This work was supported, in whole or in part, by the National Institutes of Health-Georgetown University Graduate Partnership Program ( to J. M. W.) and by the Research Fellowship Program administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the United States Department of Energy and United States Food and Drug Administration. NR 71 TC 6 Z9 6 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 18 PY 2009 VL 284 IS 38 BP 25761 EP 25771 DI 10.1074/jbc.M109.036970 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 493LK UT WOS:000269738000034 PM 19620708 ER PT J AU Fricke, WF McDermott, PF Mammel, MK Zhao, SH Johnson, TJ Rasko, DA Fedorka-Cray, PJ Pedroso, A Whichard, JM LeClerc, JE White, DG Cebula, TA Ravel, J AF Fricke, W. Florian McDermott, Patrick F. Mammel, Mark K. Zhao, Shaohua Johnson, Timothy J. Rasko, David A. Fedorka-Cray, Paula J. Pedroso, Adriana Whichard, Jean M. LeClerc, J. Eugene White, David G. Cebula, Thomas A. Ravel, Jacques TI Antimicrobial Resistance-Conferring Plasmids with Similarity to Virulence Plasmids from Avian Pathogenic Escherichia coli Strains in Salmonella enterica Serovar Kentucky Isolates from Poultry SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID FOOD ANIMALS POSE; R64 THIN-PILUS; HUMAN HEALTH; GENOME SEQUENCE; PUBLISHED DATA; DNA-SEQUENCE; O78 STRAIN; GENES; ANTIBIOTICS; PRODUCTS AB Salmonella enterica, a leading cause of food-borne gastroenteritis worldwide, may be found in any raw food of animal, vegetable, or fruit origin. Salmonella serovars differ in distribution, virulence, and host specificity. Salmonella enterica serovar Kentucky, though often found in the food supply, is less commonly isolated from ill humans. The multidrug-resistant isolate S. Kentucky CVM29188, isolated from a chicken breast sample in 2003, contains three plasmids (146,811 bp, 101,461 bp, and 46,121 bp), two of which carry resistance determinants (pCVM29188_146 [strAB and tetRA] and pCVM29188_101 [bla(CMY-2) and sugE]). Both resistance plasmids were transferable by conjugation, alone or in combination, to S. Kentucky, Salmonella enterica serovar Newport, and Escherichia coli recipients. pCVM29188_146 shares a highly conserved plasmid backbone of 106 kb (>90% nucleotide identity) with two virulence plasmids from avian pathogenic Escherichia coli strains (pAPEC-O1-ColBM and pAPEC-O2-ColV). Shared avian pathogenic E. coli (APEC) virulence factors include iutA iucABCD, sitABCD, etsABC, iss, and iroBCDEN. PCR analyses of recent (1997 to 2005) S. Kentucky isolates from food animal, retail meat, and human sources revealed that 172 (60%) contained similar APEC-like plasmid backbones. Notably, though rare in human-and cattle-derived isolates, this plasmid backbone was found at a high frequency (50 to 100%) among S. Kentucky isolates from chickens within the same time span. Ninety-four percent of the APEC-positive isolates showed resistance to tetracycline and streptomycin. Together, our findings of a resistance-conferring APEC virulence plasmid in a poultry-derived S. Kentucky isolate and of similar resistance/virulence plasmids in most recent S. Kentucky isolates from chickens and, to lesser degree, from humans and cattle highlight the need for additional research in order to examine the prevalence and spread of combined virulence and resistance plasmids in bacteria in agricultural, environmental, and clinical settings. C1 [Fricke, W. Florian; Rasko, David A.; Ravel, Jacques] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. [McDermott, Patrick F.; Zhao, Shaohua; White, David G.] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [Mammel, Mark K.; Whichard, Jean M.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Johnson, Timothy J.] Univ Minnesota, St Paul, MN 55108 USA. [Fedorka-Cray, Paula J.] USDA ARS, Bacterial Epidemiol & Antimicrobial Resistance Re, Athens, GA 30605 USA. [Pedroso, Adriana] Univ Georgia, Dept Populat Hlth, Athens, GA 30223 USA. [Whichard, Jean M.] Ctr Dis Control & Prevent, Div Foodborne Bacterial & Mycot Dis, Atlanta, GA 30333 USA. [Cebula, Thomas A.] Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Ravel, J (reprint author), Univ Maryland, Sch Med, Inst Genome Sci, 801 W Baltimore St, Baltimore, MD 21201 USA. EM jravel@som.umaryland.edu RI Ravel, Jacques/D-2530-2009; OI Ravel, Jacques/0000-0002-0851-2233; David, Rasko/0000-0002-7337-7154 FU National Institute of Allergy and Infectious Diseases (NIAID) [pCVM29188_146, pCVM29188_101, pCVM29188_46]; National Institutes of Health, Department of Health and Human Services [N01-AI-30071] FX The sequencing of pCVM29188_146, pCVM29188_101, and pCVM29188_46 was supported with federal funds from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Department of Health and Human Services, under NIAID contract N01-AI-30071. NR 46 TC 74 Z9 76 U1 2 U2 18 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 SEP 15 PY 2009 VL 75 IS 18 BP 5963 EP 5971 DI 10.1128/AEM.00786-09 PG 9 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 491VF UT WOS:000269608000025 PM 19648374 ER PT J AU Kwon, D Mucci, D Langlais, KK Americo, JL DeVido, SK Cheng, YZ Kassis, JA AF Kwon, Deborah Mucci, Diane Langlais, Kristofor K. Americo, Jeffrey L. DeVido, Sarah K. Cheng, Yuzhong Kassis, Judith A. TI Enhancer-promoter communication at the Drosophila engrailed locus SO DEVELOPMENT LA English DT Article DE Promoter specificity; Regulatory DNA; Transcriptional control; Drosophila ID II CORE PROMOTER; RESPONSE ELEMENTS; GENE-EXPRESSION; BITHORAX COMPLEX; REGULATORY DNA; TATA-BOX; MELANOGASTER; SPECIFICITY; TRANSCRIPTION; PATTERN AB Enhancers are often located many tens of kilobases away from the promoter they regulate, sometimes residing closer to the promoter of a neighboring gene. How do they know which gene to activate? We have used homing P[en] constructs to study the enhancer-promoter communication at the engrailed locus. Here we show that engrailed enhancers can act over large distances, even skipping over other transcription units, choosing the engrailed promoter over those of neighboring genes. This specificity is achieved in at least three ways. First, early acting engrailed stripe enhancers exhibit promoter specificity. Second, a proximal promoter-tethering element is required for the action of the imaginal disc enhancer(s). Our data suggest that there are two partially redundant promoter-tethering elements. Third, the long-distance action of engrailed enhancers requires a combination of the engrailed promoter and sequences within or closely linked to the promoter proximal Polycomb-group response elements. These data show that multiple mechanisms ensure proper enhancer-promoter communication at the Drosophila engrailed locus. C1 [Kwon, Deborah; Langlais, Kristofor K.; Americo, Jeffrey L.; DeVido, Sarah K.; Cheng, Yuzhong; Kassis, Judith A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. [Mucci, Diane] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Kassis, JA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. EM jkassis@mail.nih.gov OI Kassis, Judith/0000-0001-9268-3213 FU Cystic Fibrosis Foundation; Food and Drug Administration; NIH, NICHD FX We thank Renato Paro for the pUZ vector; Pat O'Farrell and Nikita Yakubovich for the anti-En antibody; Miki Fujioka, Jim Jaynes, Karl Pfeifer, Mark Mortin and the Kassis lab members for comments on this manuscript. Diane Mucci was supported by a grant from the Cystic Fibrosis Foundation and by internal funds from the Food and Drug Administration. This research was supported by the Intramural Research Program of the NIH, NICHD. Deposited in PMC for release after 12 months. NR 44 TC 31 Z9 31 U1 0 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD SEP 15 PY 2009 VL 136 IS 18 BP 3067 EP 3075 DI 10.1242/dev.036426 PG 9 WC Developmental Biology SC Developmental Biology GA 486AN UT WOS:000269167800004 PM 19675130 ER PT J AU Huang, P Goetz, CG Woolson, RF Tilley, B Kerr, D Palesch, Y Elm, J Ravina, B Bergmann, KJ Kleburtz, K AF Huang, Peng Goetz, Christopher G. Woolson, Robert F. Tilley, Barbara Kerr, Douglas Palesch, Yuko Elm, Jordan Ravina, Bernard Bergmann, Kenneth J. Kleburtz, Karl CA Parkinson Study Grp TI Using Global Statistical Tests in Long-Term Parkinson's Disease Clinical Trials SO MOVEMENT DISORDERS LA English DT Article DE multiple outcomes; global treatment effect ID MULTIPLE END-POINTS; RANDOMIZED CONTROLLED-TRIAL; BINARY OUTCOMES; BONFERRONI PROCEDURE; METHOTREXATE; ENDPOINTS; DESIGN; ERROR; SIZE AB Parkinson's disease (PD) impairments are multidimensional, making it difficult to choose a single primary outcome when evaluating treatments to stop or lessen the long-term decline in PD. We review commonly used multivariate statistical methods for assessing a treatment's global impact, and we highlight the novel Global Statistical Test (GST) methodology. We compare the GST to other multivariate approaches using data from two PD trials. In one trial where the treatment showed consistent improvement on all primary and secondary outcomes, the GST was more powerful than other methods in demonstrating significant improvement. In the trial where treatment induced both improvement and deterioration in key outcomes, the GST failed to demonstrate statistical evidence even though other techniques showed significant improvement. Based on the statistical properties of the GST and its relevance to overall treatment benefit, the GST appears particularly well Suited for a disease like PD where disability and impairment reflect dysfunction of diverse brain systems and where both disease and treatment side effects impact quality of life. In future long term trials, use of GST for primary statistical analysis Would allow the assessment of clinically relevant outcomes rather than the artificial selection of a single primary outcome. (C) 2009 Movement Disorder Society C1 [Huang, Peng; Kerr, Douglas] Johns Hopkins Univ, Div Oncol Biostat, Baltimore, MD 21209 USA. [Goetz, Christopher G.] Rush Univ, Med Ctr, Dept Med, Chicago, IL 60612 USA. [Woolson, Robert F.; Tilley, Barbara; Palesch, Yuko; Elm, Jordan] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. [Ravina, Bernard; Kleburtz, Karl] Univ Rochester, Dept Neurol, Rochester, NY USA. [Bergmann, Kenneth J.] US FDA, Silver Spring, MD USA. RP Huang, P (reprint author), Johns Hopkins Univ, SKCCC Biostat Div, Sch Med, 550 N Broadway,STE 1103, Baltimore, MD 21209 USA. EM phuang12@jhmi.edu FU NINDS NIH HHS [R21 NS043569-02, U01 NS043127, U01 NS043127-01, U01 NS043127-01S1, U01NS043127, U01 NS043128, R21 NS043569-01, U01NS043128] NR 38 TC 17 Z9 17 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP 15 PY 2009 VL 24 IS 12 BP 1732 EP 1739 DI 10.1002/mds.22645 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 509EG UT WOS:000270996500003 PM 19514076 ER PT J AU Antunes, AMM Godinho, A Marques, MM Martins, I Beland, FA AF Antunes, Alexandra M. M. Godinho, Ana Marques, M. Matilde Martins, Ines Beland, Frederick A. TI Protein adduct formation by the nevirapine metabolite, 12-hydroxynevirapine-A possible factor in nevirapine toxicity SO TOXICOLOGY LETTERS LA English DT Meeting Abstract CT 46th Congress of the European-Societies-of-Toxicology CY SEP 13-16, 2009 CL Dreden, GERMANY SP European Soc Toxicol C1 [Antunes, Alexandra M. M.; Godinho, Ana; Marques, M. Matilde; Martins, Ines] Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, P-1096 Lisbon, Portugal. [Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RI Marques, M. Matilde/E-2535-2012; PTMS, RNEM/C-1589-2014; Antunes, Alexandra/B-7871-2009 OI Marques, M. Matilde/0000-0002-7526-4962; Antunes, Alexandra/0000-0003-1827-7369 NR 0 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD SEP 13 PY 2009 VL 189 SI SI BP S103 EP S103 DI 10.1016/j.toxlet.2009.06.334 PG 1 WC Toxicology SC Toxicology GA 493ZM UT WOS:000269778800301 ER PT J AU Chen, T AF Chen, Tao TI MicroRNA Biomarkers for Carcinogen Exposure in Rodents SO TOXICOLOGY LETTERS LA English DT Meeting Abstract CT 46th Congress of the European-Societies-of-Toxicology CY SEP 13-16, 2009 CL Dreden, GERMANY SP European Soc Toxicol C1 [Chen, Tao] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 1 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD SEP 13 PY 2009 VL 189 BP S151 EP S151 DI 10.1016/j.toxlet.2009.06.746 PG 1 WC Toxicology SC Toxicology GA 493ZM UT WOS:000269778800442 ER PT J AU Marques, MM Sidarus, MC Beland, FA Antunes, AMM AF Marques, M. Matilde Sidarus, Muna C. Beland, Frederick A. Antunes, Alexandra M. M. TI Chemical and enzymatic oxidation of 2-hydroxynevirapine, a metabolite of the HIV-1 reverse transcriptase inhibitor nevirapine SO TOXICOLOGY LETTERS LA English DT Meeting Abstract CT 46th Congress of the European-Societies-of-Toxicology CY SEP 13-16, 2009 CL Dreden, GERMANY SP European Soc Toxicol C1 [Marques, M. Matilde; Sidarus, Muna C.; Antunes, Alexandra M. M.] Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, P-1096 Lisbon, Portugal. [Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RI Marques, M. Matilde/E-2535-2012; PTMS, RNEM/C-1589-2014; Antunes, Alexandra/B-7871-2009 OI Marques, M. Matilde/0000-0002-7526-4962; Antunes, Alexandra/0000-0003-1827-7369 NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD SEP 13 PY 2009 VL 189 SI SI BP S102 EP S102 DI 10.1016/j.toxlet.2009.06.333 PG 1 WC Toxicology SC Toxicology GA 493ZM UT WOS:000269778800300 ER PT J AU Mendrick, D AF Mendrick, Donna TI Towards improvement in understanding hepatotoxicity using Omics SO TOXICOLOGY LETTERS LA English DT Meeting Abstract CT 46th Congress of the European-Societies-of-Toxicology CY SEP 13-16, 2009 CL Dreden, GERMANY SP European Soc Toxicol C1 [Mendrick, Donna] NCTR FDA, Div Syst Toxicol, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD SEP 13 PY 2009 VL 189 BP S32 EP S32 DI 10.1016/j.toxlet.2009.06.061 PG 1 WC Toxicology SC Toxicology GA 493ZM UT WOS:000269778800092 ER PT J AU Wang, RS McDaniel, L Manjanatha, M Shelton, S Mei, N AF Wang, Rui-Sheng McDaniel, Lea Manjanatha, Mugimane Shelton, Sharon Mei, Nan TI Mutagenic toxicity of acrylamide and glycidamide in germ cells of mice SO TOXICOLOGY LETTERS LA English DT Meeting Abstract CT 46th Congress of the European-Societies-of-Toxicology CY SEP 13-16, 2009 CL Dreden, GERMANY SP European Soc Toxicol C1 [Wang, Rui-Sheng] NIOSH, Hlth Effects Res Grp, Kawasaki, Kanagawa, Japan. [Wang, Rui-Sheng; McDaniel, Lea; Manjanatha, Mugimane; Shelton, Sharon; Mei, Nan] Natl Ctr Toxicol Res FDA, Div Genet & Reprod Toxicol, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD SEP 13 PY 2009 VL 189 BP S137 EP S138 DI 10.1016/j.toxlet.2009.06.727 PG 2 WC Toxicology SC Toxicology GA 493ZM UT WOS:000269778800402 ER PT J AU Harel, L Costa, B Tcherpakov, M Zapatka, M Oberthuer, A Hansford, LM Vojvodic, M Levy, Z Chen, ZY Lee, FS Avigad, S Yaniv, I Shi, LM Eils, R Fischer, M Brors, B Kaplan, DR Fainzilber, M AF Harel, Liraz Costa, Barbara Tcherpakov, Marianna Zapatka, Marc Oberthuer, Andre Hansford, Loen M. Vojvodic, Milijana Levy, Zehava Chen, Zhe-Yu Lee, Francis S. Avigad, Smadar Yaniv, Isaac Shi, Leming Eils, Roland Fischer, Matthias Brors, Benedikt Kaplan, David R. Fainzilber, Mike TI CCM2 Mediates Death Signaling by the TrkA Receptor Tyrosine Kinase SO NEURON LA English DT Article ID CEREBRAL CAVERNOUS MALFORMATIONS; P75 NEUROTROPHIN RECEPTOR; 2-HIT MECHANISM; CELL-DEATH; APOPTOSIS; MEDULLOBLASTOMA; ACTIVATION; NEUROBLASTOMA; EXPRESSION; PATHWAY AB The TrkA receptor tyrosine kinase is crucial for differentiation and survival of nerve-growth-factor-dependent neurons. Paradoxically, TrkA also induces cell death in pediatric tumor cells of neural origin, via an unknown mechanism. Here, we show that CCM2, a gene product associated with cerebral cavernous malformations, interacts with the juxtamembrane region of TrkA via its phosphotyrosine binding (PTB) domain and mediates TrkA-induced death in diverse cell types. Both the PTB and Karet domains of CCM2 are required for TrkA-dependent cell death, such that the PTB domain determines the specificity of the interaction, and the Karet domain links to death pathways. Downregulation of CCM2 in medulloblastoma or neuroblastoma cells attenuates TrkA-dependent death. Combined high expression levels of CCM2 and TrkA are correlated with long-term survival in a large cohort of human neuroblastoma patients. Thus, CCM2 is a key mediator of TrkA-dependent cell death in pediatric neuroblastic tumors. C1 [Harel, Liraz; Costa, Barbara; Tcherpakov, Marianna; Levy, Zehava; Fainzilber, Mike] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. [Zapatka, Marc; Eils, Roland; Brors, Benedikt] German Canc Res Ctr, Dept Theoret Bioinformat B080, D-69120 Heidelberg, Germany. [Oberthuer, Andre; Fischer, Matthias] Univ Cologne, Childrens Hosp, Dept Pediat Oncol & Hematol, D-50924 Cologne, Germany. [Oberthuer, Andre; Fischer, Matthias] Univ Cologne, Childrens Hosp, CMMC, D-50924 Cologne, Germany. [Hansford, Loen M.; Vojvodic, Milijana; Kaplan, David R.] Hosp Sick Children, Cell Biol Program, Toronto, ON M5G 1L7, Canada. [Chen, Zhe-Yu] Shandong Univ, Sch Med, Dept Neurobiol, Jinan 250012, Shandong, Peoples R China. [Lee, Francis S.] Cornell Univ, Weill Med Coll, Dept Psychiat, New York, NY 10021 USA. [Lee, Francis S.] Cornell Univ, Weill Med Coll, Dept Pharmacol, New York, NY 10021 USA. [Avigad, Smadar; Yaniv, Isaac] Schneider Childrens Med Ctr Israel, Felsenstein Med Res Ctr, IL-49202 Petah Tiqwa, Israel. [Shi, Leming] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Eils, Roland] Univ Heidelberg, Dept Bioinformat & Funct Genom, IPMB, D-69120 Heidelberg, Germany. RP Fainzilber, M (reprint author), Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. EM mike.fainzilber@weizmann.ac.il RI Brors, Benedikt/E-5620-2013; Zapatka, Marc/G-9896-2013; Eils, Roland/B-6121-2009; OI Brors, Benedikt/0000-0001-5940-3101; Zapatka, Marc/0000-0001-8287-5967; Eils, Roland/0000-0002-0034-4036; Fainzilber, Mike/0000-0001-8173-8557 FU Israel Science Foundation; M.D. Moross Institute for Cancer Research; National Cancer Institute of Canada; European Commission [CT-2006-037260]; German Federal Ministry of Research and Education [01 GS0895, 01 GS0896]; Deutsche Krebshilfe [50-2719]; Auerbachstiftung; Competence Network Pediatric Oncology and Hematology (KPOH); U.S. Food and Drug Administration (FDA) Office of Critical Path Programs FX We thank Moses Chao, Carlos Ibanez, Virginia Lee, and Louis Reichardt for generous gifts of cell lines or reagents. Supported by the Israel Science Foundation, the M.D. Moross Institute for Cancer Research, the National Cancer Institute of Canada, the European Commission (FP6 RTN Endocyte and FP6 LSHC CT-2006-037260), the German Federal Ministry of Research and Education (National Genome Research Network Plus, grants 01 GS0895 and 01 GS0896), the Deutsche Krebshilfe (grant 50-2719), the Auerbachstiftung, and the Competence Network Pediatric Oncology and Hematology (KPOH). M. Fainzilber is the incumbent of the Chaya Professorial Chair in Molecular Neuroscience at the Weizmann Institute of Science. L. Shi acknowledges support from the U.S. Food and Drug Administration (FDA) Office of Critical Path Programs, however the views presented in this article do not necessarily reflect those of the U.S. FDA. NR 30 TC 33 Z9 33 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD SEP 10 PY 2009 VL 63 IS 5 BP 585 EP 591 DI 10.1016/j.neuron.2009.08.020 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 494XH UT WOS:000269852300006 PM 19755102 ER PT J AU Dang, X Keeton, SL Peng, HX AF Dang, Xin Keeton, Stephine Lena Peng, Hanxiang TI A unified approach for analyzing exchangeable binary data with applications to developmental toxicity studies SO STATISTICS IN MEDICINE LA English DT Article DE beta-binomial; binomial mixture; complete monotonicity; exchangeability; link function ID TOXICOLOGICAL EXPERIMENTS; LIKELIHOOD INFERENCE; CLUSTER SIZES; REGRESSION; MODELS; PROPORTIONS; RESPONSES AB In this article, we present a general procedure to analyze exchangeable binary data that may also be viewed as realizations of binomial mixtures. Our approach unifies existing models and is practical and computationally easy. Resulting from completely monotonic functions, we introduce a rich family of parametric parsimonious binomial mixtures, including the incomplete Beta-, Gamma-, Normal-, and Poisson-binomial, generalizing the Beta-binomial. We show that the. family is closed under convex linear combinations, products, and composites. We also give the moments and the Markov property of the family. With such distributions, we can perform statistical inference on correlated binary data and, in particular, overdispersed data. We propose a regression procedure that generalizes logistic regression. We provide a forward model selection procedure. We run a small simulation to validate the inclusion of the binomial distribution. Finally, we apply the proposed procedure to analyze the 2, 4, 5-Trichlorophenoxyacetic acid and E2 data and compare the results with existing procedures. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Peng, Hanxiang] Indiana Univ Purdue Univ, Dept Math Sci, Purdue Sch Sci, Indianapolis, IN 46202 USA. [Dang, Xin] Univ Mississippi, Dept Math, University, MS 38677 USA. [Keeton, Stephine Lena] US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Peng, HX (reprint author), Indiana Univ Purdue Univ, Dept Math Sci, Purdue Sch Sci, Indianapolis, IN 46202 USA. EM hpeng@math.iupui.edu FU US National Science Foundation [DMS-0707074] FX Contract/grant sponsor: US National Science Foundation; contract/grant number: DMS-0707074 NR 33 TC 4 Z9 4 U1 1 U2 9 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD SEP 10 PY 2009 VL 28 IS 20 BP 2580 EP 2604 DI 10.1002/sim.3638 PG 25 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 487LH UT WOS:000269275200005 PM 19548299 ER PT J AU Nie, L Chu, HT Feng, SB AF Nie, Lei Chu, Haitao Feng, Shibao TI Estimating variance parameters from multivariate normal variables subject to limits of detection: MLE, REML, or Bayesian approaches? SO STATISTICS IN MEDICINE LA English DT Article DE Bayesian methods; censoring; frailty model; limit of detection; mixed effect models; maximum likelihood estimator (MLE); restricted maximum likelihood estimator (REML) ID MIXED-EFFECTS MODELS; CENSORED-DATA; LAPLACES APPROXIMATION; CONVERGENCE; ZEROS AB Likelihood-based approaches, which naturally incorporate left censoring due to limits of detection, are commonly utilized to analyze censored multivariate normal data. However, the maximum likelihood estimator (MLE) typically underestimates variance parameters. The restricted maximum likelihood estimator (REML), which corrects the underestimation of variance parameters, cannot be easily extended to analyze censored multivariate normal data. In the light of the connection between the REML and a Bayesian approach discovered in 1974 by Dr Harville, this paper describes a Bayesian approach to censored multivariate normal data. This Bayesian approach is justified through its link to the REML via Laplace's approximation and its performance is evaluated through a simulation study. We consider the Bayesian approach as a valuable alternative because it yields less biased variance parameter estimates than the MLE, and because a solid REML is technically difficult when data are left censored. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Nie, Lei] US FDA, Div Biometr 4, Off Biometr, CDER,OTS, Spring, MD 20993 USA. [Chu, Haitao] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. [Chu, Haitao] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Feng, Shibao] Genentech Inc, San Francisco, CA 94080 USA. [Nie, Lei] Georgetown Univ, Washington, DC 20057 USA. RP Nie, L (reprint author), US FDA, Div Biometr 4, Off Biometr, CDER,OTS, Spring, MD 20993 USA. EM lei.nie@fda.hhs.gov RI Chu, Haitao /J-7576-2012; OI Chu, Haitao/0000-0003-0932-598X FU U.S. National Cancer Institute [CA16086]; U.S. National Institutes of Health [P30-AI-50410] FX Contract/grant sponsor: U.S. National Cancer Institute; contract/grant number: CA16086 Contract/grant sponsor: U.S. National Institutes of Health; contract/grant number: P30-AI-50410 NR 26 TC 2 Z9 2 U1 0 U2 5 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD SEP 10 PY 2009 VL 28 IS 20 BP 2605 EP 2616 DI 10.1002/sim.3644 PG 12 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 487LH UT WOS:000269275200006 PM 19598183 ER PT J AU Gratz, SR Zeller, M Mincey, DW Flurer, CL AF Gratz, Samuel R. Zeller, Matthias Mincey, Daryl W. Flurer, Cheryl L. TI Structural characterization of sulfoaildenafil, an analog of sildenafil SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Sulfoaildenafil; PDE-5 inhibitors; Dietary supplement; Liquid chromatography-mass spectrometry (LC-MS); Nuclear magnetic resonance (NMR); X-ray crystallography; Accurate mass ID HERBAL DIETARY-SUPPLEMENT; TANDEM MASS-SPECTROMETRY; SYNTHETIC PHOSPHODIESTERASE-5 INHIBITORS; PERFORMANCE LIQUID-CHROMATOGRAPHY; STRUCTURE ELUCIDATION; ELECTROSPRAY-IONIZATION; DESIGNER DRUG; HUMAN PLASMA; TADALAFIL; VARDENAFIL AB Phosphodiesterase type 5 (PDE-5) inhibitors represent a class of drugs used primarily in the treatment of erectile dysfunction. Currently, three PDE-5 inhibitors have been approved by the U.S. Food and Drug Administration (FDA) for use in the United States: sildenafil citrate, tadalafil, and vardenafil hydrochloride trihydrate. A bulk material, labeled as an ingredient for a dietary supplement, was analyzed for the presence of PDE-5 inhibitors. The compound that was detected displayed structural similarities to sildenafil, and was characterized further using LC-MS(n), FTICRMS, X-ray crystallography and NMR. The compound was given the name sulfoaildenafil. When compared to sildenafil, sulfoaildenafil contains a sulfur atom substitution for the oxygen atom in the pyrazolopyrimidine portion of the molecule, and a 3,5-dimethyl substitution on the piperazine ring, rather than the 4-methyl moiety. The X-ray crystallographic data indicate that the material in this sample is comprised of two polymorphs, which may affect the chemical and/or biological properties of any product formulated with this compound. Published by Elsevier B.V. C1 [Gratz, Samuel R.; Flurer, Cheryl L.] US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. [Zeller, Matthias; Mincey, Daryl W.] Youngstown State Univ, Dept Chem, Youngstown, OH 44555 USA. RP Flurer, CL (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. EM cheryl.flurer@fda.hhs.gov RI Zeller, Matthias/C-2255-2009 OI Zeller, Matthias/0000-0002-3305-852X NR 26 TC 20 Z9 20 U1 2 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD SEP 8 PY 2009 VL 50 IS 2 BP 228 EP 231 DI 10.1016/j.jpba.2009.04.003 PG 4 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 458QD UT WOS:000267037700018 PM 19427155 ER PT J AU Unger, EF AF Unger, Ellis F. TI Weighing Benefits and Risks -- The FDA's Review of Prasugrel. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ACUTE CORONARY SYNDROMES C1 US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Unger, EF (reprint author), US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 4 TC 43 Z9 43 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 SEP 3 PY 2009 VL 361 IS 10 BP 942 EP 945 DI 10.1056/NEJMp0907122 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 490EI UT WOS:000269480400003 PM 19726770 ER PT J AU Lee, SL Adams, WP Li, BV Conner, DP Chowdhury, BA Yu, LX AF Lee, Sau Lawrence Adams, Wallace P. Li, Bing V. Conner, Dale P. Chowdhury, Badrul A. Yu, Lawrence X. TI In Vitro Considerations to Support Bioequivalence of Locally Acting Drugs in Dry Powder Inhalers for Lung Diseases SO AAPS JOURNAL LA English DT Article DE bioequivalence (BE); dry powder inhaler (DPI); locally acting drugs; particle size distribution; single inhalation (actuation) content ID OPTIMAL PARTICLE-SIZE; AUTORADIOGRAPHIC VISUALIZATION; INTERACTIVE MIXTURES; MILD ASTHMATICS; AEROSOLS; DELIVERY; DEVICES; DEPOSITION; DISPERSION; SUBTYPES AB Dry powder inhalers (DPIs) are used to deliver locally acting drugs (e.g., bronchodilators and corticosteroids) for treatment of lung diseases such as asthma and chronic obstructive pulmonary disease (COPD). Demonstrating bioequivalence (BE) for DPI products is challenging, primarily due to an incomplete understanding of the relevance of drug concentrations in blood or plasma to equivalence in drug delivery to the local site(s) of action. Thus, BE of these drug/device combination products is established based on an aggregate weight of evidence, which utilizes in vitro studies to demonstrate equivalence of in vitro performance, pharmacokinetic or pharmacodynamic studies to demonstrate equivalence of systemic exposure, and pharmacodynamic and clinical endpoint studies to demonstrate equivalence in local action. This review discusses key aspects of in vitro studies in supporting the establishment of BE for generic locally acting DPI products. These aspects include comparability in device resistance and equivalence in in vitro testing for single inhalation (actuation) content and aerodynamic particle size distribution. C1 [Lee, Sau Lawrence; Adams, Wallace P.; Li, Bing V.; Conner, Dale P.; Yu, Lawrence X.] US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20855 USA. [Chowdhury, Badrul A.] US FDA, Div Pulm & Allergy Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Lee, SL (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 35 TC 36 Z9 37 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD SEP PY 2009 VL 11 IS 3 BP 414 EP 423 DI 10.1208/s12248-009-9121-4 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 503NV UT WOS:000270544500003 PM 19495991 ER PT J AU Bhattaram, VA Siddiqui, O Kapcala, LP Gobburu, JVS AF Bhattaram, Venkatesh Atul Siddiqui, Ohidul Kapcala, Leonard P. Gobburu, Jogarao V. S. TI Endpoints and Analyses to Discern Disease-Modifying Drug Effects in Early Parkinson's Disease SO AAPS JOURNAL LA English DT Article DE delayed start; disease modification; neuroprotection; Parkinson's disease; randomized start ID CONTROLLED-TRIAL; COENZYME Q(10); CLINICAL-TRIAL; DOUBLE-BLIND; PROGRESSION; LEVODOPA; RASAGILINE AB Parkinson's disease is an age-related degenerative disorder of the central nervous system that often impairs the sufferer's motor skills and speech, as well as other functions. Symptoms can include tremor, stiffness, slowness of movement, and impaired balance. An estimated four million people worldwide suffer from the disease, which usually affects people over the age of 60. Presently, there is no precedent for approving any drug as having a modifying effect (i.e., slowing or delaying) for disease progression of Parkinson's disease. Clinical trial designs such as delayed start and withdrawal are being proposed to discern symptomatic and protective effects. The current work focused on understanding the features of delayed start design using prior knowledge from published and data submitted to US Food and Drug Administration (US FDA) as part of drug approval or protocol evaluation. Clinical trial simulations were conducted to evaluate the false-positive rate, power under a new statistical analysis methodology, and various scenarios leading to patient discontinuations from clinical trials. The outcome of this work is part of the ongoing discussion between the US FDA and the pharmaceutical industry on the standards required for demonstrating disease-modifying effect using delayed start design. C1 [Bhattaram, Venkatesh Atul; Gobburu, Jogarao V. S.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Siddiqui, Ohidul] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Kapcala, Leonard P.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Div Neurol Drug Prod, Silver Spring, MD 20993 USA. RP Gobburu, JVS (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51,Rm 3186, Silver Spring, MD 20993 USA. EM jogarao.gobburu@fda.hhs.gov FU American Association of Pharmaceutical Scientists (AAPS); Michael J Fox Foundation for Parkinson's Research FX The authors wish to acknowledge Parkinson's Study Group, NIH Exploratory Trials in Parkinson's Disease (NET-PD) Group for providing access to clinical trial data. We are also grateful for the insightful discussions and feedback provided by numerous FDA and academic colleagues, and by professional organizations such as American Association of Pharmaceutical Scientists (AAPS) and Michael J Fox Foundation for Parkinson's Research. NR 23 TC 35 Z9 37 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD SEP PY 2009 VL 11 IS 3 BP 456 EP 464 DI 10.1208/s12248-009-9123-2 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 503NV UT WOS:000270544500008 PM 19521783 ER PT J AU Brown, CK Buhse, L Friedel, HD Keitel, S Kraemer, J Morris, JM Stickelmeyer, M Yomota, C Shah, VP AF Brown, Cynthia K. Buhse, Lucinda Friedel, Horst-Dieter Keitel, Susanne Kraemer, Johannes Morris, J. Michael Stickelmeyer, Mary Yomota, Chikako Shah, Vinod P. TI FIP Position Paper on Qualification of Paddle and Basket Dissolution Apparatus SO AAPS PHARMSCITECH LA English DT Article DE basket apparatus; chemical qualification; dissolution; mechanical qualification; paddle apparatus; performance verification test AB The qualification process for ensuring that a paddle or basket apparatus is suitable for its intended use is a highly debated and controversial topic. Different instrument qualification and suitability methods have been proposed by the pharmacopeias and regulatory bodies. In an effort to internationally harmonize dissolution apparatus suitability requirements, the International Pharmaceutical Federation's (FIP) Dissolution/Drug Release Special Interest Group (SIG) reviewed current instrument suitability requirements listed in the US, European, and Japanese pharmacopeias and the International Conference on Harmonization (ICH) Topic Q4B on harmonization of pharmacopoeial methods, in its Annex 7, Dissolution Test General. In addition, the SIG reviewed the Food and Drug Administration (FDA) Draft Guidance for Industry, "The Use of Mechanical Calibration of Dissolution Apparatus 1 and 2-Current Good Manufacturing Practice (CGMP)" and the related ASTM Standard E2503-07. Based on this review and several in-depth discussions, the FIP Dissolution/Drug Release SIG recommends that the qualification of a dissolution test instrument should be performed following the calibration requirements as indicated in the FDA (draft) guidance. If additional system performance information is desired, a performance verification test using US Pharmacopeia Reference Standard tablet or an established in-house reference product can be conducted. Any strict requirement on the use of a specific performance verification test tablet is not recommended at this time. C1 [Brown, Cynthia K.; Stickelmeyer, Mary] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Buhse, Lucinda] US FDA, CDER, OPS, St Louis, MO USA. [Friedel, Horst-Dieter] Bayer Schering Pharma AG, Berlin, Germany. [Keitel, Susanne] European Directorate Qual Med & Healthcare, Strasbourg, France. [Kraemer, Johannes] PHAST, Homburg, Germany. [Morris, J. Michael] Irish Med Board, Dublin, Ireland. [Yomota, Chikako] Natl Inst Hlth Sci, Tokyo, Japan. [Shah, Vinod P.] FIP Sci Secretary, The Hague, Netherlands. RP Brown, CK (reprint author), Eli Lilly & Co, Indianapolis, IN 46285 USA. EM brownck@lilly.com NR 11 TC 1 Z9 2 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PD SEP PY 2009 VL 10 IS 3 BP 924 EP 927 DI 10.1208/s12249-009-9291-5 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 503MQ UT WOS:000270539100026 PM 19609681 ER PT J AU Paquerault, S Samuelson, FW Petrick, N Myers, KJ Smith, RC AF Paquerault, Sophie Samuelson, Frank W. Petrick, Nicholas Myers, Kyle J. Smith, Robert C. TI Investigation of Reading Mode and Relative Sensitivity as Factors That Influence Reader Performance When Using Computer-Aided Detection Software SO ACADEMIC RADIOLOGY LA English DT Article DE Observer study evaluation; computer-aided detection; reading mode; relative sensitivity; free-response receiver operating characteristic ID BREAST-CANCER DETECTION; SCREENING MAMMOGRAPHY; DETECTION SYSTEM; CAD; RADIOLOGISTS; IMPROVEMENT; DIAGNOSIS; TRIAL AB Rationale and Objectives. The aim of this study was to investigate the effects of relative sensitivity (reader without computer-aided detection [CAD] vs stand-alone CAD) and reading mode on reader performance when using CAD software. Materials and Methods. Two sets of 100 images (low-contrast and high-contrast sets) were created by adding low-contrast or high-contrast simulated masses to random locations in 100 normal mammograms. This produced a relative sensitivity, substantially less for the low-contrast set and similar for the high-contrast set. Seven readers reviewed every image in each set and specified location and probability scores using three reading modes (without CAD, second read with CAD, and concurrent read with CAD). Reader detection accuracy was analyzed using areas under free-response receiver operating characteristic curves, sensitivity, and the number of false-positive findings per image. Results. For the low-contrast set, average differences in areas under free-response receiver operating characteristic curves, sensitivity, and false-positive findings per image without CAD were 0.02, 0.12, and 0.11, respectively, compared to second read and 0.05, 0.17, and 0.09 (not statistically significant), respectively, compared to concurrent read. For the high-contrast set, average differences were 0.002 (not statistically significant), 0.04, and 0.05, respectively, compared to second read and -0.004 (not statistically significant), 0.04, and 0.08 (not statistically significant), respectively, compared to concurrent read (all differences were statistically significant except as noted). Differences were greater in the low-contrast set than the high-contrast set. Differences between second read and concurrent read were not significant. Conclusions. Relative sensitivity is a critical factor that determines incremental improvement in reader performance when using CAD and appears to be more important than reading mode. Relative sensitivity may determine the clinical usefulness of CAD in different clinical applications and for different types of users. C1 [Paquerault, Sophie; Samuelson, Frank W.; Petrick, Nicholas; Myers, Kyle J.; Smith, Robert C.] US FDA, Ctr Devices & Radiol Hlth, Natl Inst Biomed Imaging & Bioengn, Joint Lab Assessment Med Imaging Syst, Silver Spring, MD 20993 USA. RP Paquerault, S (reprint author), US FDA, Ctr Devices & Radiol Hlth, Natl Inst Biomed Imaging & Bioengn, Joint Lab Assessment Med Imaging Syst, 10903 New Hampshire Ave,Bldg 62,Room 3110, Silver Spring, MD 20993 USA. EM sophie.paquerault@fda.hhs.gov FU National Institute of Biomedical Imaging and Bioengineering (Bethesda, MD) FX The Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering (Bethesda, MD) provided Partial support for this work. NR 28 TC 5 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD SEP PY 2009 VL 16 IS 9 BP 1095 EP 1107 DI 10.1016/j.acra.2009.03.024 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 484SF UT WOS:000269067000009 PM 19523855 ER PT J AU Piccini, JP Whellan, DJ Berridge, BR Finkle, JK Pettit, SD Stockbridge, N Valentin, JP Vargas, HM Krucoff, MW AF Piccini, Jonathan P. Whellan, David J. Berridge, Brian R. Finkle, John K. Pettit, Syril D. Stockbridge, Norman Valentin, Jean-Pierre Vargas, Hugo M. Krucoff, Mitchell W. CA CSRC HESI Writing Grp TI Current challenges in the evaluation of cardiac safety during drug development: Translational medicine meets the Critical Path Initiative SO AMERICAN HEART JOURNAL LA English DT Article ID TORSADES-DE-POINTES; RENAL-TRANSPLANT RECIPIENTS; QT INTERVAL PROLONGATION; MYOCARDIAL INJURY; POTASSIUM CURRENT; BLOOD-PRESSURE; WITHDRAWAL; TROPONIN; INHIBITION; DIFFERENCE AB In October 2008, in a public forum organized by the Cardiac Safety Research Consortium and the Health and Environmental Sciences Institute, leaders from government, the pharmaceutical industry, and academia convened in Bethesda, MD, to discuss current challenges in evaluation of short- and long-term cardiovascular safety during drug development. The current paradigm for premarket evaluation of cardiac safety begins with preclinical animal modeling and progresses to clinical biomarker or biosignature assays. Preclinical evaluations have clear limitations but provide an important opportunity to identify safety hazards before administration of potential new drugs to human subjects. Discussants highlighted the need to identify, develop, and validate serum and electrocardiogram biomarkers indicative of early drug-induced myocardial toxicity and proarrhythmia. Specifically, experts identified a need to build consensus regarding the use and interpretation of troponin assays in preclinical evaluation of myocardial toxicity. With respect to proarrhythmia, the panel emphasized a need for better qualitative and quantitative biomarkers for arrhythmogenicity, including more streamlined human thorough QT study designs and a universal definition of the end of the T wave. Toward many of these ends, large shared data repositories and a more seamless integration of preclinical and clinical testing could facilitate the development of novel approaches to both cardiac safety biosignatures. In addition, more thorough and efficient early clinical studies could enable better estimates of cardiovascular risk and better inform phase II and phase III trial design. Participants also emphasized the importance of establishing formal guidelines for data standards and transparency in postmarketing surveillance. Priority pursuit of these consensus-based directions should facilitate both safer drugs and accelerated access to new drugs, as concomitant public health benefits. (Am Heart J 2009; 158:3 17-26.) C1 [Krucoff, Mitchell W.] Duke Clin Res Inst, eECG Core Lab, Durham, NC 27705 USA. [Piccini, Jonathan P.; Krucoff, Mitchell W.] Duke Univ, Med Ctr, Durham, NC USA. [Whellan, David J.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Philadelphia, PA 19107 USA. [Berridge, Brian R.] GlaxoSmithKline Inc, Res Triangle Pk, NC USA. [Finkle, John K.] GlaxoSmithKline Inc, Collegeville, PA USA. [Pettit, Syril D.] ILSI Hlth & Environm Sci Inst, Washington, DC USA. [Stockbridge, Norman] US FDA, CDER, Div Cardiovasc & Renal Prod, Silver Spring, MD USA. [Valentin, Jean-Pierre] AstraZeneca, London, Cheshire, England. [Vargas, Hugo M.] Amgen Inc, Thousand Oaks, CA 91320 USA. RP Krucoff, MW (reprint author), Duke Clin Res Inst, eECG Core Lab, 508 Fulton St, Durham, NC 27705 USA. EM kruco001@mc.duke.edu NR 50 TC 48 Z9 51 U1 0 U2 9 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 SEP PY 2009 VL 158 IS 3 BP 317 EP 326 DI 10.1016/j.ahj.2009.06.007 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 492FV UT WOS:000269641200001 PM 19699852 ER PT J AU Lanzarotta, A Baumann, L Story, GM Witkowski, MR Khan, F Sommers, A Sommer, AJ AF Lanzarotta, Adam Baumann, Liesl Story, Gloria M. Witkowski, Mark R. Khan, Fazeel Sommers, Andrew Sommer, Andre J. TI Rapid Molecular Imaging Using Attenuated Total Internal Reflection Planar Array Infrared Spectroscopy for the Analysis of Counterfeit Pharmaceutical Tablets SO APPLIED SPECTROSCOPY LA English DT Article DE Counterfeit Pharmaceuticals; Forensics; Infrared imaging; Planar array infrared; PA-IR; Attenuated total reflection; ATR ID ANTIMALARIAL TABLETS; SPECTROGRAPH; DISSOLUTION; FORMULATIONS; PERFORMANCE; RESOLUTION; DESIGN; REGION AB A planar array infrared (PA-IR) spectrograph containing an attenuated total internal reflection (ATR) accessory has been constructed in order to permit rapid analysis of poorly transmitting materials. The technique has been optimized to allow molecular spectroscopic information to be collected in roughly 2 seconds with a corresponding peak-to-peak noise value as low as 2.14 X 10(-4) absorbance units. Additionally, up to 150 spectra could be extracted from sample sizes as large as 6 mm where each spatial element measured 40 X 200 mu m at the sample position. An application study for this technique entailed developing an embedding method that allows cross-sectioned pharmaceutical tablets to be brought into intimate contact with the internal reflection element (IRE) of the accessory. A supplemental investigation involved calculating the yield strength of multiple IRE materials in order to determine the maximum amount of pressure that can be applied to a sample without damaging the IRE. Finally, feasibility was demonstrated for using the instrument/accessory as a means to rapidly authenticate suspected counterfeit pharmaceutical tablets. C1 [Lanzarotta, Adam; Baumann, Liesl; Sommer, Andre J.] Miami Univ, Mol Microspect Lab, Dept Chem & Biochem, Oxford, OH 45056 USA. [Lanzarotta, Adam; Witkowski, Mark R.] US FDA, Trace Examinat Sect, Forens Chem Ctr, Cincinnati, OH 45237 USA. [Story, Gloria M.] Procter & Gamble Co, Mason Business Ctr, Mason, OH 45040 USA. [Khan, Fazeel; Sommers, Andrew] Miami Univ, Dept Mech & Mfg Engn, Oxford, OH 45056 USA. RP Lanzarotta, A (reprint author), Miami Univ, Mol Microspect Lab, Dept Chem & Biochem, Oxford, OH 45056 USA. EM lanzarotta@yahoo.com NR 29 TC 8 Z9 8 U1 0 U2 5 PU SOC APPLIED SPECTROSCOPY PI FREDERICK PA 201B BROADWAY ST, FREDERICK, MD 21701 USA SN 0003-7028 J9 APPL SPECTROSC JI Appl. Spectrosc. PD SEP PY 2009 VL 63 IS 9 BP 979 EP 991 PG 13 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA 497AG UT WOS:000270023200004 PM 19796479 ER PT J AU Wu, CF Retta, SM Robinson, RA Herman, BA Grossman, LW AF Wu, Changfu Retta, Stephen M. Robinson, Ronald A. Herman, Bruce A. Grossman, Laurence W. TI A Novel Study of Mechanical Heart Valve Cavitation in a Pressurized Pulsatile Duplicator SO ASAIO JOURNAL LA English DT Article ID CLOSING SOUNDS; PROSTHESIS AB Submission of data regarding the cavitation potential of a mechanical heart valve is recommended by the U.S. Food and Drug Administration in the device-review process. An acoustic method has long been proposed for cavitation detection. However, the question as to whether such a method can differentiate the cavitation noise from the mechanical closing sound has not been sufficiently addressed. in this study, cavitation near a Medtronic Hall tilting disc valve was investigated in a pressurized pulsatile duplicator. The purpose of pressurizing the testing chambers was to prevent cavitation under a normally cavitating loading condition to isolate the mechanical closing sound. By comparing the sound signals before and after pressurization, some noticeable differences were found between them. In the time domain, the intensity of the sound under a cavitating condition was much higher. In the frequency domain, the energy distribution of a sound signal was distinctively different depending on whether cavitation occurred or not. The valve closing sound had a large amount of energy in the low-frequency range (less than about 25 kHz). When cavitation took place, the sound energy shifted toward the high-frequency range (from 25 to 500 kHz). ASAIO Journal 2009; 55:445-451. C1 [Wu, Changfu] Florida Atlantic Univ, Ctr Appl Stochast Res, Coll Engn & Comp Sci, Boca Raton, FL 33431 USA. [Retta, Stephen M.; Robinson, Ronald A.; Herman, Bruce A.; Grossman, Laurence W.] US FDA, Off Sci & Engn Labs, Div Solid & Fluid Mech, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Wu, CF (reprint author), Florida Atlantic Univ, Ctr Appl Stochast Res, Coll Engn & Comp Sci, 777 Glades Rd, Boca Raton, FL 33431 USA. EM cwu70@yahoo.com FU National Science Foundation (NSF) [BES-0049040]; NSF/FDA [NSF 03-525] FX Supported by the National Science Foundation (NSF) under Grant BES-0049040 and NSF/FDA Scholar-in-Residence at FDA program (NSF 03-525). NR 34 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1058-2916 J9 ASAIO J JI Asaio J. PD SEP-OCT PY 2009 VL 55 IS 5 BP 445 EP 451 DI 10.1097/MAT.0b013e3181b4c44f PG 7 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 496UI UT WOS:000270004100004 PM 19701083 ER PT J AU Luo, XD Tsai, WY Xu, Q AF Luo, Xiaodong Tsai, Wei Yann Xu, Qiang TI Pseudo-partial likelihood estimators for the Cox regression model with missing covariates SO BIOMETRIKA LA English DT Article DE Augmented estimator; Biased sampling data; Embedding missing data; Left-truncation; Martingale structure; Right censoring; U-statistic ID NORTHERN MANHATTAN STROKE; HAZARDS REGRESSION; ISCHEMIC-STROKE; CASE-COHORT AB By embedding the missing covariate data into a left-truncated and right-censored survival model, we propose a new class of weighted estimating functions for the Cox regression model with missing covariates. The resulting estimators, called the pseudo-partial likelihood estimators, are shown to be consistent and asymptotically normal. A simulation study demonstrates that, compared with the popular inverse-probability weighted estimators, the new estimators perform better when the observation probability is small and improve efficiency of estimating the missing covariate effects. Application to a practical example is reported. C1 [Luo, Xiaodong] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Tsai, Wei Yann] Columbia Univ, Dept Biostat, New York, NY 10032 USA. [Xu, Qiang] Food & Drug Adm, Silver Spring, MD 20993 USA. RP Luo, XD (reprint author), Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. EM Xiaodong.Luo@mssm.edu; wt5@columbia.edu; Qiang.Xu@fda.hhs.gov FU U.S. National Institutes of Health; U.S. National Institute on Aging FX The authors thank the reviewers for their helpful comments. The authors also thank Dr. Ralph L. Sacco and Dr. Mitchell Elkind for providing the dataset in 5 and Dr. Myunghee C. Paik for her helpful comments and suggestions. Qiang Xu was partially supported by the U.S. National Institutes of Health. Wei Yann Tsai was partially supported by the U.S. National Institute on Aging. The paper was partially completed during Wei Yann Tsai's visit to the Department of Statistics, National Cheng Kung University, Taiwan. NR 20 TC 5 Z9 5 U1 3 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD SEP PY 2009 VL 96 IS 3 BP 617 EP 633 DI 10.1093/biomet/asp027 PG 17 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 486KZ UT WOS:000269196300009 ER PT J AU Baek, S Tsai, CA Chen, JJ AF Baek, Songjoon Tsai, Chen-An Chen, James J. TI Development of biomarker classifiers from high-dimensional data SO BRIEFINGS IN BIOINFORMATICS LA English DT Article DE class prediction; cross-validation; feature selection; frequency of selection; stable feature set ID GENE-EXPRESSION DATA; SUPPORT VECTOR MACHINES; MICROARRAY DATA; CANCER CLASSIFICATION; PERSONALIZED MEDICINE; FEATURE-SELECTION; VALIDATION; TUMOR; ALGORITHMS; PREDICTION AB Recent development of high-throughput technology has accelerated interest in the development of molecular biomarker classifiers for safety assessment, disease diagnostics and prognostics, and prediction of response for patient assignment. This article reviews and evaluates some important aspects and key issues in the development of biomarker classifiers. Development of a biomarker classifier for high-throughput data involves two components: (i) model building and (ii) performance assessment. This article focuses on feature selection in model building and cross validation for performance assessment. A frequency approach to feature selection is presented and compared to the conventional approach in terms of the predictive accuracy and stability of the selected feature set. The two approaches are compared based on four biomarker classifiers, each with a different feature selection method and well-known classification algorithm. In each of the four classifiers the feature predictor set selected by the frequency approach is more stable than the feature set selected by the conventional approach. C1 [Baek, Songjoon] HFT 20, Jefferson, AR 72079 USA. [Tsai, Chen-An] China Med Univ, Shenyang, Taiwan. [Chen, James J.] US FDA, NCTR, Rockville, MD 20857 USA. RP Chen, JJ (reprint author), HFT 20, Jefferson, AR 72079 USA. EM jamesj.chen@fda.hhs.gov OI Tsai, Chen-An/0000-0002-7490-4331 FU China Medical University of Taiwan, ROC [CMU 96-127] FX China Medical University of Taiwan, ROC (grant CMU 96-127, in part). NR 40 TC 31 Z9 32 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1467-5463 J9 BRIEF BIOINFORM JI Brief. Bioinform. PD SEP PY 2009 VL 10 IS 5 BP 537 EP 546 DI 10.1093/bib/bbp016 PG 10 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 484BE UT WOS:000269017300006 PM 19346320 ER PT J AU Torosian, SD Regan, PM Doran, T Taylor, MA Margolin, A AF Torosian, Stephen D. Regan, Patrick M. Doran, Tara Taylor, Michael A. Margolin, Aaron TI A refrigeration temperature of 4 degrees C does not prevent static growth of Yersinia pestis in heart infusion broth SO CANADIAN JOURNAL OF MICROBIOLOGY LA English DT Article DE Yersinia pestis; refrigeration; static growth; foods; heart infusion broth ID ESCHERICHIA-COLI; RAPID DETECTION; CSPA-FAMILY; ENTEROCOLITICA; PLAGUE; IDENTIFICATION; EXPRESSION; DIVERSITY; DILUTION; GENES AB Multiple barriers such as inspections, testing, and proper storage conditions are used to minimize the risk of contaminated food. Knowledge of which barriers, such as refrigeration, are effective in preventing pathogen growth and persistence, can help direct the focus of efforts during food sampling. In this study, the doubling times were evaluated for 10 strains of Yersinia pestis of different genetic background cultured in heart infusion broth (HIB) kept at 4 degrees C +/- 1 degrees C under static conditions. Nine out of the 10 strains were able to grow at 4 degrees C +/- 1 degrees C. Apparent doubling times for 7 of the strains ranged from 41 to 50 h. Strain Harbin and strain DI had apparent doubling times of 65 and 35 h, respectively, and strain O19 Ca(-6) did not grow at all. Analysis of variance showed that the averaged growth data (colony forming units per mL) between strains that grew were not significantly different. The data presented here demonstrate that refrigeration alone is not an effective barrier to prevent static growth of Y. pestis in HIB. These findings provide the preliminary impetus to investigate Y. pestis growth in a variety of food matrices that may provide a similar environment as HIB. C1 [Taylor, Michael A.; Margolin, Aaron] Univ New Hampshire, Dept Microbiol, Durham, NH 03824 USA. [Torosian, Stephen D.; Regan, Patrick M.] US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. [Doran, Tara] State Lab Inst, Dept Publ Hlth, Jamaica Plain, MA 02130 USA. RP Taylor, MA (reprint author), Univ New Hampshire, Dept Microbiol, Durham, NH 03824 USA. EM info@unhmicrolab.com NR 27 TC 5 Z9 5 U1 0 U2 2 PU NATL RESEARCH COUNCIL CANADA-N R C RESEARCH PRESS PI OTTAWA PA BUILDING M 55, OTTAWA, ON K1A 0R6, CANADA SN 0008-4166 J9 CAN J MICROBIOL JI Can. J. Microbiol. PD SEP PY 2009 VL 55 IS 9 BP 1119 EP 1124 DI 10.1139/W09-060 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology GA 513IM UT WOS:000271315900012 PM 19898555 ER PT J AU Torosian, SD Regan, PM Taylor, MA Margolin, A AF Torosian, Stephen D. Regan, Patrick M. Taylor, Michael A. Margolin, Aaron TI Detection of Yersinia pestis over time in seeded bottled water samples by cultivation on heart infusion agar SO CANADIAN JOURNAL OF MICROBIOLOGY LA English DT Article DE Yersinia pestis; bottled water; heart infusion agar; cultivation ID BUBONIC PLAGUE; PSEUDOTUBERCULOSIS; VIRULENCE; BACTERIA AB The viable persistence of Yersinia pestis seeded in bottled spring water was evaluated by performing 2 studies that involved inoculating a total of 21 different test strains into individual 500 mL reservoirs. Approximately 2 x 10(4) CFU/mL of Y. pestis was inoculated into each reservoir and held for sampling at 26 degrees C +/- 1 degrees C. In study No. 2, 9 strains (Harbin, Nepal, UNH 1A, UNH 1B, ZE94, CO92, PB6, PB6 DP, and Pexu) could no longer be recovered using a plate count assay between 79 and 138 days post-seeding; other strains (K25 lcr, O19 Ca(-6), and K25 pst) could no longer be recovered between 112 and 160 days post seeding. The data generated in this study demonstrate that certain strains of Y. pestis can remain viable in bottled water for extended periods of time. C1 [Taylor, Michael A.; Margolin, Aaron] Univ New Hampshire, Dept Microbiol, Durham, NH 03824 USA. [Torosian, Stephen D.; Regan, Patrick M.] US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. RP Taylor, MA (reprint author), Univ New Hampshire, Dept Microbiol, Durham, NH 03824 USA. EM info@unhmicrolab.com NR 19 TC 7 Z9 7 U1 0 U2 7 PU NATL RESEARCH COUNCIL CANADA-N R C RESEARCH PRESS PI OTTAWA PA BUILDING M 55, OTTAWA, ON K1A 0R6, CANADA SN 0008-4166 J9 CAN J MICROBIOL JI Can. J. Microbiol. PD SEP PY 2009 VL 55 IS 9 BP 1125 EP 1129 DI 10.1139/W09-061 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology GA 513IM UT WOS:000271315900013 PM 19898556 ER PT J AU Alper, O Stetler-Stevenson, WG Harris, LN Leitner, WW Ozdemirli, M Hartmann, D Raffeld, M Abu-Asab, M Byers, S Zhuang, Z Oldfield, EH Tong, Y Bergmann-Leitner, E Criss, WE Nagasaki, K Mol, SC Cramer, DW Karaveli, FS Goldbach-Mansky, R Leo, P Stromberg, K Weil, RJ AF Alper, Oezge Stetler-Stevenson, William G. Harris, Lyndsay N. Leitner, Wolfgang W. Ozdemirli, Metin Hartmann, Dan Raffeld, Mark Abu-Asab, Mones Byers, Stephen Zhuang, Zhengping Oldfield, Edward H. Tong, Yanhe Bergmann-Leitner, Elke Criss, Wayne E. Nagasaki, Koichi Mol, Samuel C. Cramer, Daniel W. Karaveli, F. Seyda Goldbach-Mansky, Raphaela Leo, Paul Stromberg, Kurt Weil, Robert J. TI Novel anti-filamin-A antibody detects a secreted variant of filamin-A in plasma from patients with breast carcinoma and high-grade astrocytoma SO CANCER SCIENCE LA English DT Article ID CATHEPSIN-B; SERUM HER-2/NEU; CANCER CELLS; EXPRESSION; BINDING; TRAFFICKING; ABP-280 AB Identification of tumor-derived proteins in the circulation may allow for early detection of cancer and evaluation of therapeutic responses. To identify circulating tumor-derived proteins, mice were immunized with concentrated culture medium conditioned by human breast cancer cells. Antibodies generated by hybridomas were screened against conditioned media from both normal epithelial cells and tumor cells. Antibody selectively reacting with tumor cell-conditioned media was further characterized. This led to the development of a monoclonal antibody (Alper-p280) that reacts with a newly identified 280-kDa secreted variant of human filamin-A. Circulating filamin-A was detected in patient plasma samples using Alper-p280 in an ELISA assay. Human plasma samples from 134 patients with brain, breast, or ovarian cancer, 15 patients with active arthritis, and 76 healthy controls were analyzed. Filamin-A protein levels in human cell lines and tissues were analyzed by western blotting, immunohistochemistry, and electron and confocal microscopy. Circulating filamin-A was detected in the plasma of 109 of 143 patients with breast cancer and primary brain tumors. Plasma levels of filamin-A showed 89.5% sensitivity (95% confidence interval [CI] = 0.67% to 0.99%) and 97.8% specificity (95% CI = 0.88% to 0.99%) for glioblastoma at a cut-off of 21.0 ng/mL. Plasma levels of filamin-A (> 36.0 ng/mL) had 96.7% sensitivity (95% CI = 0.80% to 0.99%) and 67.8% specificity (95% CI = 0.54% to 0.79%) for metastatic breast cancer. Filamin-A levels were increased in malignant breast or brain tissues, but not in normal control tissues. Filamin-A localized to lysosomes in MDA.MB.231 breast cancer cells, but not in normal human mammary epithelial cells, suggesting that filamin-A may undergo cancer-specific processing. Plasma filamin-A appears to be a specific and sensitive marker for patients with high-grade astrocytoma or metastatic breast cancer. Additional novel cancer biomarkers have been identified and are being developed alongside Alper-p280 for use in diagnosis of breast carcinoma and high-grade astrocytoma, and for use in the evaluation of therapeutic responses. (Cancer Sci 2009; 100: 1748-1756). C1 [Alper, Oezge] Alper Biotech LLC, Rockville, MD USA. [Stetler-Stevenson, William G.] NCI, Cell & Canc Biol Branch, Bethesda, MD 20892 USA. [Harris, Lyndsay N.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Leitner, Wolfgang W.] NCI, Dermatol Branch, Bethesda, MD 20892 USA. [Ozdemirli, Metin; Hartmann, Dan] Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Dept Pathol, Washington, DC 20007 USA. [Raffeld, Mark; Abu-Asab, Mones] NCI, Pathol Branch, Bethesda, MD 20892 USA. [Byers, Stephen] Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Dept Oncol, Washington, DC 20007 USA. [Zhuang, Zhengping; Oldfield, Edward H.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Tong, Yanhe] VaxGen Inc, San Francisco, CA USA. [Bergmann-Leitner, Elke] Walter Reed Army Inst Res, Dept Immunol, Silver Spring, MD USA. [Criss, Wayne E.] Hacettepe Univ, Dept Biochem, Ankara, Turkey. [Nagasaki, Koichi] Natl Genome Res Ctr, Tokyo, Japan. [Mol, Samuel C.; Cramer, Daniel W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Karaveli, F. Seyda] Akdeniz Univ, Sch Med, Dept Pathol, TR-07058 Antalya, Turkey. [Goldbach-Mansky, Raphaela] NIAMSD, NIH, Bethesda, MD 20892 USA. [Leo, Paul] NIH, Human Genome Res Ctr, Bethesda, MD 20892 USA. [Stromberg, Kurt] US FDA, Div Therapeut Prot, Bethesda, MD 20014 USA. [Weil, Robert J.] Cleveland Clin Fdn, Neurol Inst, Dept Neurosurg, Brain Tumor & Neurooncol Ctr, Cleveland, OH 44195 USA. RP Alper, O (reprint author), Alper Biotech LLC, Rockville, MD USA. EM oalper@alperbiotech.com RI Bergmann-Leitner, Elke/B-3548-2011; Leitner, Wolfgang/F-5741-2011; Stetler-Stevenson, William/H-6956-2012; Leo, Paul/B-3470-2011; KARAVELI, FATMA SEYDA/C-6335-2016; OI Bergmann-Leitner, Elke/0000-0002-8571-8956; Leitner, Wolfgang/0000-0003-3125-5922; Stetler-Stevenson, William/0000-0002-5500-5808; Leo, Paul/0000-0001-8325-4134; Abu-Asab, Mones/0000-0002-4047-1232 FU National Institute Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA FX This research was supported in part by the Intramural Research Program of the National Institute Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. The authors thank Dianne Hirsch, PhD, for critical reading and editing of the manuscript. The authors thank Ken Yamaguchi, MD, for scientific discussions and support during the early stages of project development. NR 27 TC 25 Z9 27 U1 1 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD SEP PY 2009 VL 100 IS 9 BP 1748 EP 1756 DI 10.1111/j.1349-7006.2009.01244.x PG 9 WC Oncology SC Oncology GA 482XL UT WOS:000268923800028 PM 19594548 ER PT J AU Gray, RA Wikswo, JP Otani, NF AF Gray, Richard A. Wikswo, John P. Otani, Niels F. TI Origin choice and petal loss in the flower garden of spiral wave tip trajectories SO CHAOS LA English DT Article DE nonlinear differential equations; nonlinear dynamical systems; partial differential equations; wave propagation; waves ID ISOLATED RABBIT HEART; VENTRICULAR-FIBRILLATION; CARDIAC FIBRILLATION; PHASE SINGULARITIES; EXCITABLE MEDIA; REENTRANT ACTIVITY; DYNAMICS; MODEL; MECHANISM; TISSUE AB Rotating spiral waves have been observed in numerous biological and physical systems. These spiral waves can be stationary, meander, or even degenerate into multiple unstable rotating waves. The spatiotemporal behavior of spiral waves has been extensively quantified by tracking spiral wave tip trajectories. However, the precise methodology of identifying the spiral wave tip and its influence on the specific patterns of behavior remains a largely unexplored topic of research. Here we use a two-state variable FitzHugh-Nagumo model to simulate stationary and meandering spiral waves and examine the spatiotemporal representation of the system's state variables in both the real (i.e., physical) and state spaces. We show that mapping between these two spaces provides a method to demarcate the spiral wave tip as the center of rotation of the solution to the underlying nonlinear partial differential equations. This approach leads to the simplest tip trajectories by eliminating portions resulting from the rotational component of the spiral wave. C1 [Gray, Richard A.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Phys, Silver Spring, MD 20993 USA. [Gray, Richard A.] Univ Alabama, Dept Biomed Engn, Birmingham, AL 35294 USA. [Wikswo, John P.] Vanderbilt Univ, Vanderbilt Inst Integrat Biosyst Res & Educ, Dept Biomed Engn, Nashville, TN 37235 USA. [Wikswo, John P.] Vanderbilt Univ, Vanderbilt Inst Integrat Biosyst Res & Educ, Dept Mol Physiol & Biophys, Nashville, TN 37235 USA. [Wikswo, John P.] Vanderbilt Univ, Vanderbilt Inst Integrat Biosyst Res & Educ, Dept Phys & Astron, Nashville, TN 37235 USA. [Otani, Niels F.] Cornell Univ, Dept Biomed Sci, Ithaca, NY 14853 USA. RP Gray, RA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Phys, Silver Spring, MD 20993 USA. EM richard.gray@fda.hhs.edu RI Gray, Richard/F-3916-2015 OI Gray, Richard/0000-0003-2798-6378 FU National Institutes of Health [R01-HL63267, R01-HL58241]; National Science Foundation FX We would like to thank Michael Cross for valuable discussions and comments on the manuscript. This work was supported by the National Institutes of Health (Grant Nos. R01-HL63267 to R. A. G. and R01-HL58241 to J. P. W.) and the National Science Foundation (CAREER Award to R. A. G.). NR 37 TC 7 Z9 7 U1 1 U2 6 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 1054-1500 J9 CHAOS JI Chaos PD SEP PY 2009 VL 19 IS 3 AR 033118 DI 10.1063/1.3204256 PG 8 WC Mathematics, Applied; Physics, Mathematical SC Mathematics; Physics GA 501KV UT WOS:000270381500018 PM 19791998 ER PT J AU Meseda, CA Mayer, AE Kumar, A Garcia, AD Campbell, J Listrani, P Manischewitz, J King, LR Golding, H Merchlinsky, M Weir, JP AF Meseda, Clement A. Mayer, Anne E. Kumar, Arunima Garcia, Alonzo D. Campbell, Joseph Listrani, Paul Manischewitz, Jody King, Lisa R. Golding, Hana Merchlinsky, Michael Weir, Jerry P. TI Comparative Evaluation of the Immune Responses and Protection Engendered by LC16m8 and Dryvax Smallpox Vaccines in a Mouse Model SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID VIRUS ENVELOPE PROTEINS; MEMBRANE-PROTEINS; ANTIBODY-RESPONSES; POXVIRUS CHALLENGE; HUMAN MONKEYPOX; DNA VACCINE; MICE; NEUTRALIZATION; IDENTIFICATION; ANTIGENS AB The immune response elicited by LC16m8, a candidate smallpox vaccine that was developed in Japan by cold selection during serial passage of the Lister vaccine virus in primary rabbit kidney cells, was compared to Dryvax in a mouse model. LC16m8 carries a mutation resulting in the truncation of the B5 protein, an important neutralizing target of the extracellular envelope form of vaccinia virus (EV). LC16m8 elicited a broad-spectrum immunoglobulin G (IgG) response that neutralized both EV and the intracellular mature form of vaccinia virus and provoked cell-mediated immune responses, including the activation of CD4(+) and CD8(+) cells, similarly to Dryvax. Mice inoculated with LC16m8 had detectable but low levels of anti-B5 IgG compared to Dryvax, but both Dryvax and LC16m8 sera neutralized vaccinia virus EV in vitro. A truncated B5 protein (similar to 8 kDa) was expressed abundantly in LC16m8-infected cells, and both murine immune sera and human vaccinia virus immunoglobulin recognized the truncated recombinant B5 protein in antigen-specific enzyme-linked immunosorbent assays. At a high-dose intranasal challenge (100 or 250 50% lethal doses), LC16m8 and Dryvax conferred similar levels of protection against vaccinia virus strain WR postvaccination. Taken together, the results extend our current understanding of the protective immune responses elicited by LC16m8 and indicate that the relative efficacy in a mouse model rivals that of previously licensed smallpox vaccines. C1 [Meseda, Clement A.; Mayer, Anne E.; Kumar, Arunima; Garcia, Alonzo D.; Campbell, Joseph; Listrani, Paul; Merchlinsky, Michael; Weir, Jerry P.] US FDA, Lab DNA Viruses, Div Viral Prod, HFM 457,Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Manischewitz, Jody; King, Lisa R.; Golding, Hana] US FDA, Lab Retrovirus Res, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Meseda, CA (reprint author), US FDA, Lab DNA Viruses, Div Viral Prod, HFM 457,Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM clement.meseda@fda.hhs.gov FU NIAID/NIH [10F5]; Biodefense and Emerging Infections Research Resources Repository (BEI Resources), Manassas, VA [VMC-30, NR2624] FX We thank Karen Elkins, CBER/FDA, for advice on developing the intracellular cytokine staining assay and Kaketsuken (Kumamoto, Japan) for the LC16m8 vaccine. We thank Bernard Moss, NIAID/NIH, for the 10F5 hybridomas and Yong He, CBER/FDA, for the anti-A27 antibody. Anti-B5 antibody NR-561 (VMC-30) and B5 protein (NR2624) were obtained from the Biodefense and Emerging Infections Research Resources Repository (BEI Resources), Manassas, VA. We are grateful to Joan Adamo and Carol Weiss, CBER/FDA, for critically reviewing the manuscript. NR 41 TC 17 Z9 17 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD SEP PY 2009 VL 16 IS 9 BP 1261 EP 1271 DI 10.1128/CVI.00040-09 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 491LL UT WOS:000269580200001 PM 19605597 ER PT J AU Reynolds, KS AF Reynolds, K. S. TI Drug Development for Emerging Infections SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID RETROVIRUS; VIRUS C1 US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Reynolds, KS (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM kellie.reynolds@fda.hhs.gov NR 19 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD SEP PY 2009 VL 86 IS 3 BP 225 EP 229 DI 10.1038/clpt.2009.148 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 491AL UT WOS:000269549100001 PM 19707209 ER PT J AU Bergman, KL AF Bergman, K. L. TI The Animal Rule and Emerging Infections: The Role of Clinical Pharmacology in Determining an Effective Dose SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID HUMANS; MODEL AB Drug development for emerging infections offers challenges in translational pharmacology. For drugs and biologics for which adequate and well-controlled efficacy studies in humans cannot be ethically conducted or are not feasible, as would be the case with many emerging infections, translation of preclinical information to humans is the cornerstone of drug development. This article focuses on the role of the clinical pharmacologist in translating pharmacology information to support approval of new agents for emerging infections, under the US Food and Drug Administration's (FDA's) Animal Rule. C1 US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Clin Pharmacol, Silver Spring, MD USA. RP Bergman, KL (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Clin Pharmacol, Silver Spring, MD USA. EM kimberly.bergman@fda.hhs.gov NR 8 TC 9 Z9 9 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 SEP PY 2009 VL 86 IS 3 BP 328 EP 331 DI 10.1038/clpt.2009.106 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 491AL UT WOS:000269549100023 PM 19571806 ER PT J AU Siddique, N Sharma, D Al-Khaldi, SF AF Siddique, Nusrat Sharma, Devang Al-Khaldi, Sufian F. TI Detection of Yersinia enterocolitica in Alfalfa, Mung Bean, Cilantro, and Mamey Sapote (Pouteria sapota) Food Matrices Using DNA Microarray Chip Hybridization SO CURRENT MICROBIOLOGY LA English DT Article ID OLIGONUCLEOTIDE MICROARRAY; SALMONELLA; IDENTIFICATION; PLATFORMS; PATHOGENS; SEEDS; ASSAY; MILK; COLI AB Four different food matrices (alfalfa, cilantro, mamey sapote, and mung bean) were contaminated with three different dilutions 10(6), 10(4), and 10(3) cfu/g of Yersinia enterocolitica. DNA was isolated from each food mix and used in chromosomal amplifications. The amplified DNA was used as templates in single PCR reactions of the four genes (virF, ail, yst, and blaA) followed by mixing the four reactions for one PCR primer extension reaction. The presence and the limit of detection of four genes in four food matrices were established by microarray hybridization. Data revealed the diversity of signal intensities. Neither the microarray chip hybridization nor the single PCR amplification could detect virF's presence located on a plasmid. Ail was detected in 10(3) cfu/g, whereas blaA and yst were detected from 10(5) to 10(6) cfu/g in all food matrices. Therefore, the ail gene could be the gene of choice in identifying Y. enterocolitica in alfalfa, cilantro, mamey, and mung bean. Other genes-blaA, yst, virF-exhibited wide variability in hybridization signals, highlighting the need of a better DNA purification step prior to DNA microarray hybridization. C1 [Al-Khaldi, Sufian F.] US FDA, Div Microbiol, Off Regulatory Sci ORS, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Siddique, Nusrat] Univ Maryland, Dept Mol Genet & Cell Biol, Sch Life Sci, College Pk, MD 20742 USA. [Sharma, Devang] Univ Maryland, Fischell Dept Bioengn, A James Clark Sch Engn, College Pk, MD 20742 USA. RP Al-Khaldi, SF (reprint author), US FDA, Div Microbiol, Off Regulatory Sci ORS, Ctr Food Safety & Appl Nutr, HFS 712,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Sufian.AlKhaldi@fda.hhs.gov FU Joint Institute for Food Safety and Applied Nutrition (JIFSAN) FX We would like to thank the Joint Institute for Food Safety and Applied Nutrition (JIFSAN) for financial support of Nusrat Siddique and Devang Sharma. We also would like to thank Thomas Hammack (FDA) for providing mamey food matrix. NR 27 TC 10 Z9 10 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0343-8651 J9 CURR MICROBIOL JI Curr. Microbiol. PD SEP PY 2009 VL 59 IS 3 BP 233 EP 239 DI 10.1007/s00284-009-9413-z PG 7 WC Microbiology SC Microbiology GA 480ZK UT WOS:000268775800003 PM 19504157 ER PT J AU Hu, JX Green, D Swoveland, J Grant, M Boyle, DS AF Hu, Jinxin Green, Donna Swoveland, Jennifer Grant, Michael Boyle, David S. TI Preliminary evaluation of a procedure for improved detection of Shiga toxin-producing Escherichia coli in fecal specimens SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE Shiga-Toxin Producing E. Coli (STEC); Acid Enrichment; Clinical fecal specimens; Rainbow agar plus tellurite and novobiocin (RTN); Sorbitol MacConkey agar plus cefixime and tellurite (TCSMAC); Enzyme Immunoassay (EIA) ID SEROGROUP O157; ENRICHMENT; NON-O157; STRAINS; SAMPLES; GENES; ASSAY AB Culture confirmation of Shiga toxin-producing Escherichia coli (STEC) is very important for epidemiologic analysis. However, isolation of non-O157 STEC on conventional selective media such as sorbitol-MacConkey agar (SMAC) can be difficult because of heavy growth of competing bacteria and its phenotypical similarity to commensal nonpathogenic E. coli. An acid enrichment procedure was introduced in this study to facilitate detection of STEC from patients who were symptomatic. Forty-seven clinical fecal broths, which tested positive for Shiga toxin by commercial immunoassay, were processed for the isolation of STEC by both conventional and the acid enrichment methods. The acid enrichment method and conventional culture recovered STEC from 91% (43/47) and 70% (33/47) of the fecal broths, respectively. Neither method retrieved STEC in 3 specimens. Thirty-six STEC were successfully serogrouped, which included 026 (n = 11), 0 157 (n = 9), O103 (n = 7), O121 (n = 3), O111 (n = 2 each), O28AC, O146, O76, and O undetermined (n = 1 each). The analysis of STEC isolates by real-time PCR indicated that all 9 E. coli O157 contained stx2 gene alone or in combination with stx1. Non-O157 STEC more frequently contained stx1 only, and about one-third possessed stx2. The novel acid enrichment protocol greatly reduced the growth of competitor colonies on RTN and TCSMAC. The study demonstrated that incorporation of an acid enrichment procedure in clinical testing improved the isolation of STEC in fecal specimens. Published by Elsevier Inc. C1 [Hu, Jinxin; Grant, Michael] US FDA, Bothell, WA 98021 USA. [Green, Donna; Swoveland, Jennifer; Boyle, David S.] Washington State Dept Hlth, Shoreline, WA 98155 USA. RP Hu, JX (reprint author), US FDA, Bothell, WA 98021 USA. EM jinxin.hu@fda.hhs.gov NR 17 TC 8 Z9 9 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD SEP PY 2009 VL 65 IS 1 BP 21 EP 26 DI 10.1016/j.diagmicrobio.2009.05.012 PG 6 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 487AT UT WOS:000269243400004 PM 19679231 ER PT J AU Koti, KM AF Koti, Kallappa M. TI Weibull Failure-Time Mixture Models for Evaluating Efficacy in the Presence of a Biomarker SO DRUG INFORMATION JOURNAL LA English DT Article DE Biomarker development; Survival data; Gordon's model; Extreme value distribution; Subroutine NLPTR; Likelihood ratio test; Wald test ID SURROGATE END-POINTS; VALIDATION; TRIALS AB A predictive marker is a marker that predicts the differential efficacy of a particular therapy based on marker status. Standard statistical methods compare treatments, not validate prediction. We propose a failure-time mixture model that achieves both objectives. We also explain how to evaluate efficacy in biomarker subpopulations. We use the maximum likelihood method to estimate the mixture model. We explain the computational aspects of the model and discuss the underlying statistical inference. We discuss sample size determination. We illustrate the methodology with a computer-generated data set. The proposed mixture model is simple and capable of assisting investigators seeking to design marker-based clinical trials in their analyses. C1 US FDA, Off Biostat, Silver Spring, MD 20993 USA. RP Koti, KM (reprint author), US FDA, Off Biostat, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM kallappa.koti@fda.hhs.gov NR 15 TC 1 Z9 1 U1 0 U2 0 PU DRUG INFORMATION ASSOC PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD SEP PY 2009 VL 43 IS 5 BP 585 EP 593 PG 9 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 499WZ UT WOS:000270258800007 ER PT J AU Dinh, P Yang, PL AF Dinh, Phillip Yang, Peiling TI Repeated Measures Analyses in Clinical Trials With Titration Visits SO DRUG INFORMATION JOURNAL LA English DT Article DE Longitudinal data; Missing data; MMRM; Titration ID LONGITUDINAL DATA; MODELS; LIKELIHOOD; INFERENCE AB In longitudinal clinical studies, after randomization at baseline, subjects are followed for a period of time for development of symptoms. A mixed model for repeated measures (MMRM) can be used to analyze such data. To accommodate safety and tolerability, in some studies, the treatment has to be titrated to the optimal dose. Then subjects will stay on their optimal dose until the end of the study. In an MMRM analysis, one may attempt to ignore the titration visits because including them could add extra variability unnecessarily. However, when patients drop out during the titration period, ignoring the titration visits would exclude these patients from the analyses. In this article, we evaluate the impact of excluding and including titration visits in an MMPM analysis by a simulation study. We evaluate the approaches based on the bias and the coverage accuracy of the confidence interval. The results suggest that excluding titration visits may result in undercovered confidence intervals and biased estimates. C1 [Dinh, Phillip; Yang, Peiling] US FDA, Div Biometr 1, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Dinh, P (reprint author), US FDA, Div Biometr 1, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM Phillip.Dinh@fda.hhs.gov NR 13 TC 0 Z9 0 U1 0 U2 1 PU DRUG INFORMATION ASSOC PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD SEP PY 2009 VL 43 IS 5 BP 595 EP 602 PG 8 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 499WZ UT WOS:000270258800008 ER PT J AU Mahmood, I AF Mahmood, I. TI Pharmacokinetic allometric scaling of coagulation factors and tissue-type plasminogen activators SO HAEMOPHILIA LA English DT Article DE clearance; coagulation factors; elimination half-life; interspecies pharmacokinetic scaling; tissue-type plasminogen activators; volume of distribution ID FACTOR-IX; FACTOR-VIII; CLEARANCE; HUMANS; DOGS; PAMITEPLASE; PREDICTION; SELECTION; MONKEYS; RATS AB The objective of this study was to evaluate the predictive performance of pharmacokinetic interspecies scaling of coagulation factors and tissue-type plasminogen activators to predict clearance, volume of distribution at steady-state and half-life in humans from animal data. The human pharmacokinetic parameters were predicted using one, two or at least three animal species. The results of the study indicated that the pharmacokinetic parameters of coagulation factors and tissue-type plasminogen activators can be predicted with reasonable accuracy in humans when three or more animal species are available. Two-species scaling can also be performed, but the accuracy of predicted parameters is less than three-species scaling. C1 US FDA, OBRR, Ctr Biol Evaluat & Res, Rockville, MD USA. RP Mahmood, I (reprint author), US FDA, OBRR, Ctr Biol Evaluat & Res, 1451 Rockville Pike, Rockville, MD USA. EM iftekhar.mahmood@fda.hhs.gov NR 27 TC 8 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD SEP PY 2009 VL 15 IS 5 BP 1109 EP 1117 DI 10.1111/j.1365-2516.2009.02054.x PG 9 WC Hematology SC Hematology GA 488RP UT WOS:000269367800017 PM 19523109 ER PT J AU Sandbulte, MR Gao, J Straight, TM Eichelberger, MC AF Sandbulte, Matthew R. Gao, Jin Straight, Timothy M. Eichelberger, Maryna C. TI A miniaturized assay for influenza neuraminidase-inhibiting antibodies utilizing reverse genetics-derived antigens SO INFLUENZA AND OTHER RESPIRATORY VIRUSES LA English DT Article DE Influenza virus; miniaturized assay; neuraminidase; reverse genetics ID A VIRUS; INFECTION; VACCINE; HEMAGGLUTININ; IMMUNITY; MICE AB Background Antibodies to neuraminidase (NA) contribute to protection during influenza virus infection, but NA inhibition (NI) titers are not routinely analyzed in vaccine trials. One reason is the cumbersome nature of the conventional thiobarbituric acid (TBA) NI assay, which uses chemical methods to quantify free sialic acid following incubation of NA with substrate in the presence of serum. In addition, the assay is complicated by the need to use virus of a hemagglutinin (HA) subtype novel to the host to detect NA-specific antibodies only. Objectives Our primary objectives were to miniaturize the colorimetric NI assay to a format suitable for quantitative analysis of large numbers of samples, and validate the specificity and sensitivity of the miniaturized format with ferret and human sera. An additional aim was to use reverse genetics to construct HA-mismatched viral reagents bearing NA of recent influenza A vaccine strains and H6 HA. Results Analysis of ferret antisera by the miniaturized assay demonstrated sensitivity and specificity comparable with the conventional assay. Similar increases in the NI titers in sera from vaccinated human volunteers were measured in miniaturized and conventional assays. Inactivated and live-attenuated vaccines increased NI titers against a given subtype at approximately the same rate. Conclusions The reagents and miniaturized format of the TBA method described here provide a platform for practical serological monitoring of functional antibodies against NA. C1 [Sandbulte, Matthew R.; Gao, Jin; Eichelberger, Maryna C.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Straight, Timothy M.] Brooke Army Med Ctr, Ft Sam Houston, TX 78234 USA. RP Sandbulte, MR (reprint author), Room 1D20,Bldg 29A,8800 Rockville Pike, Bethesda, MD 20892 USA. EM matthew.sandbulte@fda.hhs.gov NR 25 TC 45 Z9 45 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1750-2640 J9 INFLUENZA OTHER RESP JI Influenza Other Respir. Viruses PD SEP PY 2009 VL 3 IS 5 BP 233 EP 240 DI 10.1111/j.1750-2659.2009.00094.x PG 8 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA 484YM UT WOS:000269086700008 PM 21462400 ER PT J AU Mossoba, MM Moss, J Kramer, JKC AF Mossoba, Magdi M. Moss, Julie Kramer, John K. C. TI Trans Fat Labeling and Levels in US Foods: Assessment of Gas Chromatographic and Infrared Spectroscopic Techniques for Regulatory Compliance SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT 21st Conference on Design of Circuits and Integrated Systems (DCIS 2006) CY NOV 22-24, 2006 CL Barcelona, SPAIN ID CONJUGATED LINOLEIC-ACID; CP-SIL 88; HUMAN-MILK LIPIDS; LIQUID-CHROMATOGRAPHY; ADIPOSE-TISSUE; RAPID-DETERMINATION; OCTADECENOIC ACIDS; METHYL-ESTERS; CIS-FATTY; FISH-OIL AB Trans fatty acids are found in a variety of foods like dairy and meat products, but the major dietary sources are products that contain commercially hydrogenated fats. There has been a renewed need for accurate analytical methods for the quantitation of total trans fat since mandatory requirements to declare the amount of trans fat present in food products and dietary supplements were issued in many countries. Official capillary GC and IR methodologies are the two most common validated methods used to identify and quantify trans fatty acids for regulatory compliance. The present article provides a comprehensive discussion of the GC and IR techniques, including the latest attenuated total reflection (ATR)-FTIR methodology called the negative second derivative ATR-FTIR procedure, which is currently being validated in an international collaborative study. The identification and quantitation of trans fatty acid isomers by GC is reviewed and an alternative GC method is proposed using two temperature programs and combining their results; this proposed method deals more effectively with the resolution of large numbers of geometric and positional monoene, diene, and triene fatty acid isomers present in ruminant fats. In addition, the different methylation procedures that affect quantitative conversion to fatty acid methyl esters are reviewed. There is also a lack of commercial chromatographic standards for many trans fatty acid isomers. This review points to potential sources of interferences in the FTIR determination that may lead to inaccurate results, particularly at low trans levels. The presence of high levels of saturated fats may lead to interferences in the FTIR spectra observed for trans triacylglycerols (TAGS). TAGS require no derivatization, but have to be melted prior to IR measurement. While GC is currently the method of choice, ATR-FTIR spectroscopy is a viable, rapid alternative, and a complementary method to GC for a more rapid determination of total trans fats for food labeling purposes. C1 [Mossoba, Magdi M.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. [Moss, Julie] US FDA, Ctr Food Safety & Appl Nutr, Off Nutr Labeling & Dietary Supplements, College Pk, MD 20740 USA. [Kramer, John K. C.] Agr & Agri Food Canada, Guelph Food Res Ctr, Guelph, ON N1G 5C9, Canada. RP Mossoba, MM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. EM magdi.mossoba@fda.hhs.gov NR 95 TC 26 Z9 26 U1 0 U2 7 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2009 VL 92 IS 5 BP 1284 EP 1300 PG 17 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 510SH UT WOS:000271111200006 PM 19916366 ER PT J AU Delmonte, P Kia, ARF Hu, Q Rader, JI AF Delmonte, Pierluigi Kia, Ali-Reza Fardin Hu, Qing Rader, Jeanne I. TI Review of Methods for Preparation and Gas Chromatographic Separation of trans and cis Reference Fatty Acids SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT 21st Conference on Design of Circuits and Integrated Systems (DCIS 2006) CY NOV 22-24, 2006 CL Barcelona, SPAIN ID PERFORMANCE LIQUID-CHROMATOGRAPHY; TANDEM MASS-SPECTROMETRY; SILVER-ION HPLC; CENTRIFUGAL PARTITION CHROMATOGRAPHY; COUNTER-CURRENT CHROMATOGRAPHY; METHYL-ESTERS; INFRARED-SPECTROSCOPY; GEOMETRICAL-ISOMERS; CLA ISOMERS; MILK-FAT AB In recent years, several countries have implemented new regulations regarding the limitation or labeling of the trans fatty acid (TFA) content of foods and dietary supplements. GC methods for fatty acid (FA) analysis have been updated by improving the separation of TFAs from other FAs, especially trans- and cis-18:1, and by focusing more attention on the FAs contained in fats and oils in lower amounts. FA analysis is affected by the limited availability of reference materials. Identifications are frequently made simply by comparison with separations reported in the literature. This report describes the preparation of mixtures containing fatty acid methyl esters (FAMES) that are not available as reference materials. These mixtures can be used for FAME identifications. The prepared mixtures are analyzed under the experimental conditions of the American Oil Chemists' Society (AOCS) Official Method Ce 1h-05 and AOCS Recommended Practice Ce 1j-07. C1 [Delmonte, Pierluigi; Kia, Ali-Reza Fardin; 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, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Pierluigi.delmonte@fda.hhs.gov NR 70 TC 24 Z9 25 U1 2 U2 19 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2009 VL 92 IS 5 BP 1310 EP 1326 PG 17 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 510SH UT WOS:000271111200008 PM 19916368 ER PT J AU Reepmeyer, JC d'Avignon, DA AF Reepmeyer, John C. d'Avignon, D. Andre TI Use of a Hydrolytic Procedure and Spectrometric Methods in the Structure Elucidation of a Thiocarbonyl Analogue of Sildenafil Detected as an Adulterant in an Over-the-Counter Herbal Aphrodisiac SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID CHROMATOGRAPHY-MASS SPECTROMETRY; DIETARY-SUPPLEMENT; DESIGNER DRUG; IDENTIFICATION; THIOSILDENAFIL; VARDENAFIL; PRODUCTS; MATRICES AB A sildenafil-related compound was detected in an herbal dietary supplement marketed as an aphrodisiac. The compound was identified as an analogue of sildenafil in which the carbonyl group in the pyrimidine ring of sildenafil was substituted with a thiocarbonyl group, and the methyl group on the piperazine ring was substituted with a hydroxyethyl group. Based on this structure, the compound was named thiohydroxyhomosildenafil. The structure of the compound was established using HPLC/MS, UV spectrometry, electrospray ionization-MS/MS, NMR spectrometry, and a hydrolytic process. One key product of hydrolysis was 1-(2-hydroxyethyl)-piperazine; the identification of this product defined the amine portion of the compound. Another key product of hydrolysis was hydroxyhomosildenafil, generated by hydrolysis of the thiocarbonyl group to a carbonyl group (C = S -> C = 0). Hydroxyhomosildenafil was detected as a minor component in the dietary supplement. C1 [Reepmeyer, John C.] US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. [d'Avignon, D. Andre] Washington Univ, Dept Chem, St Louis, MO 63130 USA. RP Reepmeyer, JC (reprint author), US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. EM reepmeyer@gmail.com NR 16 TC 6 Z9 7 U1 0 U2 0 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2009 VL 92 IS 5 BP 1336 EP 1342 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 510SH UT WOS:000271111200010 PM 19916370 ER PT J AU McClure, FD Lee, JK AF McClure, Foster D. Lee, Jung K. TI Determination of a Two-Tailed 100(1-alpha)% Upper Limit on the Relative Error in the Laboratory-to-Laboratory Standard Deviation Obtained from an Interlaboratory Study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB For some classes of analytical methods, it is assumed that the error in the laboratory-to-laboratory standard deviation (SL) is appreciable. To demonstrate the magnitude of this error in SL for such methods, formulas were derived to obtain a two-tailed 100(1-alpha)% upper limit on the relative error in SL obtained from an interlaboratory study, assuming that the laboratory-to-laboratory variance (s(L)(2)) obtained in the validation of an analytical method is approximately normal and/or Chi-square distributed. This 100(1-alpha)% upper limit (Delta 1-alpha/2) is referred to as a margin of relative error in S(L) (MRE(s(L))). Monte Carlo simulations were performed, and the results compared satisfactorily with the formula calculations. To aid in designing future interlaboratory studies in which concern is focused on the magnitude of the uncertainty in SL, expressed as a proportion of the true value (sigma(L)), a formula was derived to determine the number of laboratories needed to attain a given MRE in SL for a stated number of replicates per laboratory. C1 [McClure, Foster D.; Lee, Jung K.] US FDA, Ctr Food Safety & Appl Nutr, Off Food Def Commun & Emergency Response, Div Publ Hlth & Biostat, College Pk, MD 20740 USA. RP McClure, FD (reprint author), POB 413, Frederick, MD 21705 USA. EM fdmc5100@yahoo.com NR 12 TC 2 Z9 2 U1 0 U2 1 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2009 VL 92 IS 5 BP 1593 EP 1601 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 510SH UT WOS:000271111200038 PM 19916398 ER PT J AU Zou, W Frye, JG Chang, CW Liu, J Cerniglia, CE Nayak, R AF Zou, W. Frye, J. G. Chang, C. -W. Liu, J. Cerniglia, C. E. Nayak, R. TI Microarray analysis of antimicrobial resistance genes in Salmonella enterica from preharvest poultry environment SO JOURNAL OF APPLIED MICROBIOLOGY LA English DT Article DE antimicrobial resistance genes; hierarchical analysis; microarray; poultry; Salmonella; turkey ID DNA MICROARRAY; ANTIBIOTIC-RESISTANCE; OLIGONUCLEOTIDE MICROARRAY; TECHNOLOGY; PREVALENCE; PATHOGENS; BACTERIA; SEROVARS; DESIGN AB Aims: To detect antimicrobial resistance genes in Salmonella isolates from turkey flocks using the microarray technology. Methods and Results: A 775 gene probe oligonucleotide microarray was used to detect antimicrobial resistance genes in 34 isolates. All tetracycline-resistant Salmonella harboured tet(A), tet(C) or tet(R), with the exception of one Salmonella serotype Heidelberg isolate. The sul1 gene was detected in 11 of 16 sulfisoxazole-resistant isolates. The aadA, aadA1, aadA2, strA or strB genes were found in aminoglycoside-resistant isolates of Salm. Heidelberg, Salmonella serotype Senftenberg and untypeable Salmonella. The prevalence of mobile genetic elements, such as class I integron and transposon genes, in drug-resistant Salmonella isolates suggested that these elements may contribute to the dissemination of antimicrobial resistance genes in the preharvest poultry environment. Hierarchical clustering analysis demonstrated a close relationship between drug-resistant phenotypes and the corresponding antimicrobial resistance gene profiles. Conclusions: Salmonella serotypes isolated from the poultry environment carry multiple genes that can render them resistant to several antimicrobials used in poultry and humans. Significance and Impact of the Study: Multiple antimicrobial resistance genes in environmental Salmonella isolates could be identified efficiently by microarray analysis. Hierarchical clustering analysis of the data was also found to be a useful tool for analysing emerging patterns of drug resistance. C1 [Zou, W.; Cerniglia, C. E.; Nayak, R.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Frye, J. G.] ARS, Bacterial Epidemiol & Antimicrobial Resistance Re, USDA, Athens, GA USA. [Chang, C. -W.] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Liu, J.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. RP Nayak, R (reprint author), US FDA, Natl Ctr Toxicol Res HFT 250, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Rajesh.Nayak@fda.hhs.gov RI Frye, Jonathan/I-6382-2013 OI Frye, Jonathan/0000-0002-8500-3395 FU West Virginia University; US Department of Health and Human Services FX The authors thank Dr Brett Kenney from West Virginia University for providing the Salmonella strains. The authors thank Jennifer Bauer-Turpin and Jonathan Cudnik (USDA) for their technical assistance. The authors are grateful to Drs Charlene Jackson, John Sutherland, James Fuscoe and Saeed A. Khan for critical reading of this manuscript. Wen Zou acknowledges support of a fellowship from the Oak Ridge Institute for Science and Education, administered through an interagency agreement between the US Department of Energy and the US Food and Drug Administration. The use of trade names is for identification purposes only and does not imply endorsement by the Food and Drug Administration, United States Department of Agriculture or US Department of Health and Human Services. The findings and conclusions in this manuscript do not necessarily represent the views of the Food and Drug Administration or the United States Department of Agriculture. NR 33 TC 19 Z9 19 U1 1 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1364-5072 J9 J APPL MICROBIOL JI J. Appl. Microbiol. PD SEP PY 2009 VL 107 IS 3 BP 906 EP 914 DI 10.1111/j.1365-2672.2009.04270.x PG 9 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 481ZY UT WOS:000268854000021 PM 19320942 ER PT J AU Stine, CB Jacobs, JM Rhodes, MR Overton, A Fast, M Baya, AM AF Stine, Cynthia B. Jacobs, John M. Rhodes, Matt R. Overton, Anthony Fast, Mark Baya, Ana M. TI Expanded Range and New Host Species of Mycobacterium shottsii and M. pseudoshottsii SO JOURNAL OF AQUATIC ANIMAL HEALTH LA English DT Article ID BASS MORONE-SAXATILIS; POLYMERASE-CHAIN-REACTION; CHESAPEAKE-BAY; STRIPED BASS; SP-NOV.; FISH; TUBERCULOSIS; INFECTIONS; DIAGNOSIS AB Mycobacterium shottsii and M. pseudoshottsii are recently described mycobacteria commonly isolated from Chesapeake Bay striped bass Morone saxatilis. However, their distribution in striped bass outside of the Chesapeake region and their ability to infect alternative hosts have not been described. Mycobacteria identified as M. shottsii (based on fatty acid methyl ester analysis and multigene sequencing) were isolated from striped bass collected in Albemarle Sound, North Carolina, and white perch Morone americana in the Rhode River, Maryland, and detected in striped bass from the New York Bight off Long Island, New York. Mycobacterium pseudoshottsii were isolated from white perch in the Rhode and Corsica rivers, Maryland, and detected in striped bass in the New York Bight. This work demonstrates that these mycobacteria can be found outside of the Chesapeake Bay as well as in hosts other than striped bass. C1 [Stine, Cynthia B.; Baya, Ana M.] Univ Maryland, Virginia Maryland Coll Vet Med, College Pk, MD 20742 USA. [Jacobs, John M.; Rhodes, Matt R.] NOAA, Natl Ctr Coastal Ocean Sci, Cooperat Oxford Lab, Oxford, MD USA. [Overton, Anthony] E Carolina Univ, Dept Biol, Greenville, NC USA. [Fast, Mark] SUNY Stony Brook, Sch Marine & Atmospher Sci, Stony Brook, NY 11794 USA. RP Stine, CB (reprint author), US FDA, Laurel, MD USA. EM cynthia.stine@fda.hhs.gov RI Stine, Cynthia/F-1040-2011 FU National Oceanic Atmospheric Administration; National Ocean Service Cooperative Oxford Laboratory; NY [MOU AMOU 177]; Maryland Sea Grant FX The authors thank Eric Diaddorio, Jim Saupe, and Ken Riley (East Carolina University) for collection assistance; Mark Sokolowski and Mike Taddeo (School of Marine and Atmospheric Sciences-Stony Brook) for assistance in field collections and histology processing; Jennifer O'Dwyer, Julia Socrates, Todd Abenante, and Michael Bernstein (New York State Department of Environmental Conservation [NYS DEC]) for collections and aging work; the University of Maryland Center of Marine Biotechnology Bio-Analytical Services Laboratory for sequencing isolates; Mamuka Kotetishvili for tree assistance; and the University of North Carolina Coastal Studies Institute Laboratory in Manteo, North Carolina, for providing work-up facilities. Protocols were approved by the Institutional Care and Use Committee of Stony Brook University, Stony Brook, New York. Portions of this study were supported by the National Oceanic Atmospheric Administration, National Ocean Service Cooperative Oxford Laboratory and by the NY under MOU AMOU 177 (2007-2009). Support for C.S. was also provided by Program Development Funds from Maryland Sea Grant. NR 22 TC 7 Z9 7 U1 0 U2 2 PU AMER FISHERIES SOC PI BETHESDA PA 5410 GROSVENOR LANE SUITE 110, BETHESDA, MD 20814-2199 USA SN 0899-7659 J9 J AQUAT ANIM HEALTH JI J. Aquat. Anim. Health PD SEP PY 2009 VL 21 IS 3 BP 179 EP 183 DI 10.1577/H09-005.1 PG 5 WC Fisheries; Veterinary Sciences SC Fisheries; Veterinary Sciences GA 524ND UT WOS:000272149100008 PM 20043404 ER PT J AU Akbulut, H Tang, Y Deisseroth, A AF Akbulut, H. Tang, Y. Deisseroth, A. TI Vector vaccination and vector targeted chemotherapy in solid tumors SO JOURNAL OF BUON LA English DT Article DE adenoviral vectors; cytosine deaminase; gene therapy; tumor vaccines ID SUICIDE GENE-THERAPY; L-PLASTIN PROMOTER; PHASE-I TRIAL; DENDRITIC CELLS; CYTOSINE DEAMINASE; OVARIAN-CANCER; RECURRENT HEAD; NECK-CANCER; ADENOVIRUS; 5-FLUOROURACIL AB Gene therapy is one of the promising treatment modalities in cancer therapy. The current gene therapy modalities are mainly focused on the introduction of suppressed tumor suppressor genes into cancer cells, modulation of anti-tumoral immune response, and the suicide gene therapy by introducing pro-drug-activating enzyme genes into the tumor cells. Currently, various gene therapy trials arc, being conducted in cancer patients. However the early results of these trials conducted so far are not so encouraging. Combination of gene therapy strategies with conventional treatment modalities such as chemotherapy, immunotherapy or radiotherapy has yielded encouraging results in experimental models and early clinical trials. C1 [Akbulut, H.] Ankara Univ, Sch Med, Dept Med Oncol, TR-06100 Ankara, Turkey. [Tang, Y.] Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92103 USA. [Deisseroth, A.] US FDA, Silver Spring, MD USA. RP Akbulut, H (reprint author), Ankara Univ, Sch Med, Dept Med Oncol, Cebeci Hosp, TR-06100 Ankara, Turkey. EM akbulut@medicine.ankara.edu.tr NR 32 TC 0 Z9 0 U1 0 U2 1 PU ZERBINIS MEDICAL PUBL PI ATHENS PA 42 ANTIFILOU STR, ATHENS, 157 71, GREECE SN 1107-0625 J9 J BUON JI J. BUON PD SEP PY 2009 VL 14 BP S141 EP S146 PG 6 WC Oncology SC Oncology GA 501YV UT WOS:000270421500016 PM 19785056 ER PT J AU Wang, DD Zhang, SZ Zhao, H Men, AY Parivar, K AF Wang, Diane D. Zhang, Shuzhong Zhao, Hong Men, Angela Y. Parivar, Kourosh TI Fixed Dosing Versus Body Size-Based Dosing of Monoclonal Antibodies in Adult Clinical Trials SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE Fixed dosing; body size-based dosing; body weight; body surface area; biologics; monoclonal antibodies; population pharmacokinetics; pharmacodynamics ID POPULATION PHARMACOKINETICS; SURFACE AREA; CANCER-PATIENTS; RHEUMATOID-ARTHRITIS; ANTICANCER DRUGS; DOSE CALCULATION; BREAST-CANCER; PHARMACODYNAMICS; CETUXIMAB AB Although without clear scientific rationale, body size based dosing is often used for administering monoclonal antibodies (mAbs). This simulation study compared the performance of body size-based and fixed dosing in reducing pharmacokinetic (PK) and/or pharmacodynamic (PD) variability in adults for 12 mAbs with published population PK and/or PD models. At the population level, 95th percentile intervals of concentration-time profiles, distribution, and variability of exposure for 1000 subjects after both dosing approaches were examined. At the individual level, the difference between the exposures of patients with extreme body sizes from the typical exposure following both approaches was compared. The results show that the 2 dosing approaches perform similarly across the mAbs investigated with fixed dosing being better for some mAbs and body size-based dosing being better for the others. Based on this finding, we recommend using fixed dosing in first-in-human (FIH) adult studies because it offers other advantages. When sufficient data become available, a full assessment of body size effect on PK/PD should be conducted to determine the optimal dosing approach for phase 3 trials. Other factors that may affect the selection of dosing approach were also discussed. Dosing approach for mAbs in the pediatric population is out of the scope of this study. C1 [Wang, Diane D.; Zhang, Shuzhong; Parivar, Kourosh] Pfizer Oncol, San Diego, CA USA. [Zhao, Hong; Men, Angela Y.] Ctr Drug Evaluat & Res, Off Clin Pharmacol, Off Translat Sci, Food & Drug Adm, Silver Spring, MD USA. RP Wang, DD (reprint author), 10646 Sci Ctr Dr, San Diego, CA 92121 USA. EM diane.wang@pfizer.com NR 30 TC 48 Z9 51 U1 2 U2 11 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2009 VL 49 IS 9 BP 1012 EP 1024 DI 10.1177/0091270009337512 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 488PI UT WOS:000269361600002 PM 19620385 ER PT J AU Kaur, P Davit, BM Chaurasia, CS AF Kaur, Paramjeet Davit, Barbara M. Chaurasia, Chandra S. TI CURRENT CHALLENGES FACED BY OFFICE OF GENERIC DRUGS IN RECOMMENDING OPTIMAL BIOEQUIVALENCE STUDIES FOR LOCALLY ACTING GASTROINTESTINAL DRUGS SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 38th Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 13-15, 2009 CL San Antonio, TX SP Amer Coll Clin Pharmacol C1 [Kaur, Paramjeet; Davit, Barbara M.; Chaurasia, Chandra S.] US FDA, Div Bioequivalence, Off Gener Drugs, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2009 VL 49 IS 9 MA 119 BP 1118 EP 1118 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 488PI UT WOS:000269361600112 ER PT J AU Moon, YJ Garnett, C Rahman, A Farrell, A McGuinn, W Liu, Q Booth, B AF Moon, Young Jin Garnett, Christine Rahman, Atiqur Farrell, Ann McGuinn, William Liu, Qi Booth, Brian TI OBSERVATION BASED ON EARLY QT ASSESSMENT OF HDAC INHIBITORS (HDACi) SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 38th Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 13-15, 2009 CL San Antonio, TX SP Amer Coll Clin Pharmacol C1 [McGuinn, William] US FDA, DCPS, OCP, OTS,CDER, Silver Spring, MD USA. [Moon, Young Jin; Rahman, Atiqur; Farrell, Ann; Liu, Qi; Booth, Brian] US FDA, DDOP, OND, CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2009 VL 49 IS 9 MA 128 BP 1120 EP 1120 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 488PI UT WOS:000269361600120 ER PT J AU Hubinger, JC AF Hubinger, Jean C. TI Determination of retinol, retinyl palmitate, and retinoic acid in consumer cosmetic products SO JOURNAL OF COSMETIC SCIENCE LA English DT Article ID VITAMIN-A PALMITATE; ISOMERS; HPLC; SKIN AB Retinol and retinyl palmitate are frequently used in cosmetic products. A simple, rapid, and sensitive reversed-phase high-performance liquid chromatography (HPLC) method With ultraviolet (UV) detection was developed for the quantitation of retinol, retinyl palmitate, and retinoic acid in cosmetic preparations. The analytes were extracted from a cosmetic/Celite Mixture using a solvent system composed of equal amounts of hexane, isopropanol, and ethyl acetate, and the extract was injected directly into an HPLC chromatograph with a C18 column and UV detector set at 330 nm. Chromatographic separation was achieved by gradient elution with a mobile phase, starting with aqueous ammonium acetate buffer/methanol that was gradually changed to methanol/dichloromethane. The average recoveries of retinol, retinyl palmitate, and retinoic acid from spiked cosmetic products were 9576 or higher. In a Survey of twenty-nine consumer cosmetic skin care Products labeled to contain retinoids, most products were Found to contain either retinol or retinyl palmitate at concentrations up to 2.2% (w/w), while a few products contained both ingredients. A number of products also contained cis isomers of retinol that could be quantitatively distinguished from the all-trans compound. The method can be used to quantitate several retinoids and their isomers in cosmetic products. The method will be useful for obtaining information needed to estimate levels of exposure to retinoids from cosmetic products. C1 US FDA, College Pk, MD USA. RP Hubinger, JC (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD USA. NR 22 TC 4 Z9 4 U1 2 U2 11 PU SOC COSMETIC CHEMISTS PI NEW YORK PA 120 WALL STREET, SUITE 2400, NEW YORK, NY 10005-4088 USA SN 1525-7886 J9 J COSMET SCI JI J. Cosmet. Sci. PD SEP-OCT PY 2009 VL 60 IS 5 BP 485 EP 500 PG 16 WC Chemistry, Applied; Dermatology SC Chemistry; Dermatology GA 515SQ UT WOS:000271493600002 PM 19822106 ER PT J AU Miller, VA Reynolds, WW Ittenbach, RF Luce, MF Beauchamp, TL Nelson, RM AF Miller, Victoria A. Reynolds, William W. Ittenbach, Richard F. Luce, Mary Frances Beauchamp, Tom L. Nelson, Robert M. TI CHALLENGES IN MEASURING A NEW CONSTRUCT: PERCEPTION OF VOLUNTARINESS FOR RESEARCH AND TREATMENT DECISION MAKING SO JOURNAL OF EMPIRICAL RESEARCH ON HUMAN RESEARCH ETHICS LA English DT Article DE voluntariness; decision making; methodology; scale development ID SELF-EFFICACY SCALE; VALIDITY; VALIDATION; PREFERENCES; INFORMATION; CONVERGENT; AUTONOMY; TRUST; LOCUS AB RELIABLE AND VALID MEASURES OF RELEVANT constructs are critical in the developing field of the empirical study of research ethics. The early phases of scale development for such constructs can be complex. We describe the methodological challenges of construct definition and operationalization and how we addressed them in our study to develop a measure of perception of voluntariness. We also briefly present our conceptual approach to the construct of voluntariness, which we defined as the perception of control over decision making. Our multifaceted approach to scale development ensured that we would develop a construct definition of sufficient breadth and depth, that our new measure of voluntariness would be applicable across disciplines, and that there was a clear link between our construct definition and items. The strategies discussed here can be adapted by other researchers who are considering a scale development study related to the empirical study of ethics. C1 [Miller, Victoria A.] Childrens Hosp, Philadelphia, PA 19104 USA. [Reynolds, William W.] Richard Stockton Coll New Jersey, Pomona, NJ USA. [Ittenbach, Richard F.] Cincinnati Childrens Hosp Med Ctr, Div Biostat & Epidemiol, Cincinnati, OH USA. [Luce, Mary Frances] Duke Univ, Fuqua Sch Business, Durham, NC 27706 USA. [Beauchamp, Tom L.] Georgetown Univ, Kennedy Inst Eth, Washington, DC 20057 USA. [Nelson, Robert M.] US FDA, Off Commissioner, Off Pediat Therapeut, Rockville, MD 20857 USA. RP Miller, VA (reprint author), Childrens Hosp, 34th St & Civ Ctr Blvd,CHOP N Room 1515, Philadelphia, PA 19104 USA. EM millerv@email.chop.edu RI Ittenbach, Richard/Q-1806-2015 FU National Science Foundation [SES-0527618]; National Institutes of Health/National Cancer Institute [R21CA118377-01A1]; Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia FX This research was supported in part by grants from the National Science Foundation (SES-0527618; Drs. Nelson, Luce,and Beauchamp) and the National Institutes of Health/National Cancer Institute (R21CA118377-01A1; Dr. Nelson) and an Institutional Development Grant to The Center for Research Integrity, Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia. NR 29 TC 14 Z9 14 U1 18 U2 28 PU UNIV CALIFORNIA PRESS PI BERKELEY PA C/O JOURNALS DIVISION, 2000 CENTER ST, STE 303, BERKELEY, CA 94704-1223 USA SN 1556-2646 J9 J EMPIR RES HUM RES JI J. Empir. Res. Hum. Res. Ethics PD SEP PY 2009 VL 4 IS 3 BP 21 EP 31 DI 10.1525/jer.2009.4.3.21 PG 11 WC Ethics; Medical Ethics SC Social Sciences - Other Topics; Medical Ethics GA 512EI UT WOS:000271226300003 PM 19754231 ER PT J AU Grant, MA Mogler, MA Harris, DL AF Grant, Michael A. Mogler, Mark A. Harris, Delbert L. TI Comparison of Enrichment Procedures for Shiga Toxin-Producing Escherichia coli in Wastes from Commercial Swine Farms SO JOURNAL OF FOOD PROTECTION LA English DT Article ID AGAR O157; CATTLE; FECES; PREVALENCE; SAMPLES; SHEEP; FOOD; BEEF AB Three methods for enrichment of Shiga toxin-producing Escherichia coli (STEC) were compared using waste pit samples from swine production facilities housing 50 to 3,000 animals. The STEC gene stx(2) was detected in 5 of 17 pooled samples using a U.S. Department of Agriculture (USDA) enrichment procedure, 6 of 17 samples using a U.S. Food and Drug Administration (FDA) enrichment procedure, and 8 of 17 samples using an experimental acid enrichment. All isolates were non-O157 and 5 of 6 were positive for enterotoxigenic E. coli-associated heat stable toxins a and b. The three enrichment procedures were also tested for their ability to support growth of 31 strains of STEC. The acid enrichment media supported growth of 100% of the strains, the FDA medium supported 77% of the strains, and the USDA medium supported 16% of the strains. C1 [Grant, Michael A.] US FDA, Bothell, WA 98021 USA. [Mogler, Mark A.; Harris, Delbert L.] Iowa State Univ, Dept Anim Sci, Ames, IA 50010 USA. RP Grant, MA (reprint author), US FDA, Bothell, WA 98021 USA. EM mike.grant@fda.hhs.gov NR 24 TC 7 Z9 7 U1 0 U2 5 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD SEP PY 2009 VL 72 IS 9 BP 1982 EP 1986 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 492CN UT WOS:000269632000024 PM 19777903 ER PT J AU Cowley, SC AF Cowley, Siobhan C. TI Proinflammatory cytokines in pneumonic tularemia: too much too late? SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Editorial Material DE respiratory; lung; bacterial ID INTRANASAL INTERLEUKIN-12 TREATMENT; A FRANCISELLA-TULARENSIS; LIVE VACCINE STRAIN; IMMUNE-RESPONSE; INFECTION; CELLS; SEPSIS; MICE; LVS C1 US FDA, LMDCI, DBPAP, OVRR,CBER, Rockville, MD 20852 USA. RP Cowley, SC (reprint author), US FDA, LMDCI, DBPAP, OVRR,CBER, 1401 Rockville Pike,HFM-431, Rockville, MD 20852 USA. EM siobhan.cowley@fda.hhs.gov NR 15 TC 14 Z9 14 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD SEP PY 2009 VL 86 IS 3 BP 469 EP 470 DI 10.1189/jlb.0309119 PG 2 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 488VA UT WOS:000269377200003 PM 19720615 ER PT J AU Ali, S Karunakaran, C Kanthasamy, A Kanthasamy, A Antholine, W Kalyanaraman, B Gonzalez, C AF Ali, S. Karunakaran, C. Kanthasamy, A. Kanthasamy, A. Antholine, W. Kalyanaraman, B. Gonzalez, C. TI OXIDATION OF MITOCHONDRIAL IRON-SULFUR CLUSTER CONTRIBUTES TO ENHANCED MPTP/METH-INDUCED OXIDATIVE DAMAGE IN AGED MICE: AN EX VIVO SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 22nd Biennial Meeting of the International-Society-of-Neurochemistry/Asian-Pacific-Society-for-Neuroc hemistry CY AUG 23-29, 2009 CL Busan, SOUTH KOREA SP Int Soc Neurochem, Asian Pacific Soc C1 [Karunakaran, C.; Antholine, W.; Kalyanaraman, B.] Med Coll Wis, Free Rad Res Ctr, Milwaukee, WI USA. [Kanthasamy, A.] Iowa State Univ, Dept Biomed, Ames, IA USA. [Gonzalez, C.] Autonomous Univ, Slp, Mexico. [Ali, S.; Kanthasamy, A.] NCTR, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2009 VL 110 BP 49 EP 49 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 477WT UT WOS:000268550400133 ER PT J AU Kanthasamy, AG Ali, S Huang, D Anantharam, V Tukov, F Kanthasamy, A AF Kanthasamy, A. G. Ali, S. Huang, D. Anantharam, V Tukov, F. Kanthasamy, A. TI REPIN INHIBITS UBIQUITIN-PROTEASOME AND INDUCES PROTEIN AGGREGATION AND PROTEASOME DYSFUNCTION IN PARKINSON'S DISEASE MODEL SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 22nd Biennial Meeting of the International-Society-of-Neurochemistry/Asian-Pacific-Society-for-Neuroc hemistry CY AUG 23-29, 2009 CL Busan, SOUTH KOREA SP Int Soc Neurochem, Asian Pacific Soc C1 [Kanthasamy, A. G.; Huang, D.; Anantharam, V; Kanthasamy, A.] Iowa State Univ, Dept Biomed Sci, Iowa Ctr Adv Neurotoxicol, Ames, IA USA. [Ali, S.] US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. [Tukov, F.] Univ Mississippi, Dept Med Chem, University, MS 38677 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2009 VL 110 BP 51 EP 51 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 477WT UT WOS:000268550400140 ER PT J AU Gish, P Mosholder, AD Truffa, M Johann-Liang, R AF Gish, Paula Mosholder, Andrew D. Truffa, Melissa Johann-Liang, Rosemary TI Spectrum of Central Anticholinergic Adverse Effects Associated with Oxybutynin: Comparison of Pediatric and Adult Cases SO JOURNAL OF PEDIATRICS LA English DT Article ID TROSPIUM CHLORIDE AB We reviewed Food and Drug Administration postmarketing reports of central nervous system (CNS) anticholinergic effects in association with oxybutynin. Taking domestic usage by age group into account, there is a disproportionately higher number of CNS adverse event cases reported in pediatric patients as compared with adult patients. CNS stimulation was prominent in the pediatric cases. (J Pediatr 2009; 155:432-4) C1 [Gish, Paula; Mosholder, Andrew D.; Truffa, Melissa] US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. [Johann-Liang, Rosemary] US Hlth Resources & Serv Adm, Dept Hlth & Human Serv, Rockville, MD 20857 USA. RP Gish, P (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, White Oak Bldg 22,Room 3404,10903 New Hampshire A, Silver Spring, MD 20993 USA. EM paula.gish@fda.hhs.gov NR 9 TC 13 Z9 13 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 2009 VL 155 IS 3 BP 432 EP 434 DI 10.1016/j.jpeds.2009.01.074 PG 3 WC Pediatrics SC Pediatrics GA 489NQ UT WOS:000269427400031 PM 19732583 ER PT J AU Lewis, SM Ali, AA Badgley, HL Allaben, WT Latendresse, JR Patton, R Leakey, JE AF Lewis, S. M. Ali, A. A. Badgley, H. L. Allaben, W. T. Latendresse, J. R. Patton, R. Leakey, J. E. TI The Zucker Rat: A Model for Diabetic Renal Nephropathy SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Lewis, S. M.; Ali, A. A.; Allaben, W. T.; Leakey, J. E.] Natl Ctr Toxicol Res, Off Sci Coordinat, Jefferson, AR 72079 USA. [Badgley, H. L.; Latendresse, J. R.; Patton, R.] Natl Ctr Toxicol Res, Toxicol Pathol Associates Inc, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 582 EP 582 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000175 ER PT J AU Ali, AA Lewis, SM Badgley, HL Allaben, WT Frankos, VH Leakey, JE AF Ali, A. A. Lewis, S. M. Badgley, H. L. Allaben, W. T. Frankos, V. H. Leakey, J. E. TI Potential Toxicity of Glucosamine Mediated through Transforming Growth Factor beta SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Ali, A. A.; Lewis, S. M.; Badgley, H. L.; Allaben, W. T.; Leakey, J. E.] Natl Ctr Toxicol Res, Off Sci Coordinat, Jefferson, AR 72079 USA. [Frankos, V. H.] FDA CFSAN, Off Dietary Supplements, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 635 EP 636 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000347 ER PT J AU Leonard-Segal, A Shay, LE Shetty, D Schiffenbauer, J AF Leonard-Segal, Andrea Shay, Laura E. Shetty, Daiva Schiffenbauer, Joel TI Unique role of consumer studies in nonprescription drug development SO JOURNAL OF THE AMERICAN PHARMACISTS ASSOCIATION LA English DT Article DE Nonprescription medications; pharmaceutical development; regulations; consumers AB Objective: To inform the health care community about nonprescription drug labeling and consumer studies unique and integral to the nonprescription drug development process. Summary: Data from consumer studies are essential for many nonprescription drug approvals. These studies are conducted to help predict actual consumer behavior in the marketplace if the product is approved. They test whether potential consumers understand a label (label comprehension study), can properly decide if a product is appropriate for them to use (self-selection study), and can use a product in accordance with the label (actual use study). The design and interpretation of these studies often pose unique challenges. Conclusion: Consumer studies are often part of a nonprescription drug development program. Continued efforts to improve consumer research should result in greater access to safe and effective nonprescription drug products for the American public. C1 [Leonard-Segal, Andrea; Shay, Laura E.; Shetty, Daiva; Schiffenbauer, Joel] US FDA, Div Nonprescript Clin Evaluat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Shay, LE (reprint author), US FDA, Div Nonprescript Clin Evaluat, Ctr Drug Evaluat & Res, Bldg 22,Rm 5466,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM laura.shay@fda.hhs.gov NR 3 TC 5 Z9 5 U1 0 U2 2 PU AMER PHARMACEUTICAL ASSOC PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 USA SN 1544-3191 J9 J AM PHARM ASSOC JI J. Am. Pharm. Assoc. PD SEP-OCT PY 2009 VL 49 IS 5 BP 670 EP 673 DI 10.1331/JAPhA.2009.08068 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 501NZ UT WOS:000270389900020 PM 19748876 ER PT J AU Huang, L Tiwari, RC Zou, ZH Kulldorff, M Feuer, EJ AF Huang, Lan Tiwari, Ram C. Zou, Zhaohui Kulldorff, Martin Feuer, Eric J. TI Weighted Normal Spatial Scan Statistic for Heterogeneous Population Data SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Breast cancer mortality; Cluster detection; Continuous regional data; Geographic variation; Lung cancer survival; Weighted normal spatial scan statistic ID CANCER SURVIVAL; DISEASE; CLUSTERS; POINT; TESTS; MORTALITY; CHOICE; WOMEN; RATES; RISK AB In geographical spatial epidemiology and disease surveillance, all the existing spatial scan methods for cluster detection using continuous data are designed for evaluating clusters of individuals and analyzing individual-level data. Motivated by growing demands to study the spatial heterogeneity of continuous measures in population data, such as mortality rates, survival rates, average body mass indexes and pollution at state, county, and census tract levels. we propose a weighted normal scan statistic for investigating the clusters of the cells (geographic units such as counties) with unusual high/low continuous regional measures, where the weights reflect the uncertainty of the regional measures or sample size (number of observed cases) in the cells. Power, precision, the effect of the weights, and the sensitivity of the proposed test statistic to data from various distributions are investigated through intensive simulation. The method is applied to 1988-2002 stage I and II lung cancer survival data in Los Angeles County in order to search for clusters of geographic units with high/low survival rates in a short-term/long-term survival after diagnosis, and to 1999-2003 breast cancer age-adjusted mortality rate data in the U.S. collected by the Surveillance, Epidemiology and End Results (SEER) program in order to evaluate the clustering pattern of counties with high mortality rate, The proposed method is included in the latest release of the SaTScan software (www.satscan.org). C1 [Huang, Lan; Feuer, Eric J.] NCI, Stat Res & Applicat Branch, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. [Tiwari, Ram C.] US FDA, Off Biostat, CDER, Silver Spring, MD 20993 USA. [Zou, Zhaohui] Informat Management Serv Inc, Silver Spring, MD 20904 USA. [Kulldorff, Martin] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Kulldorff, Martin] Harvard Pilgrim Hlth Care, Boston, MA 02215 USA. RP Huang, L (reprint author), NCI, Stat Res & Applicat Branch, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. EM huangla@mail.nih.gov; ram.tiwari@fda.hhs.gov; zouj@imsweb.com; martin_kulldorff@hms.Harvard.edu; feuerr@mail.nih.gov RI Kulldorff, Martin/H-4282-2011; OI Kulldorff, Martin/0000-0002-5284-2993 FU National Institute of Child Health and Human Development [R01 HD048852] FX Eric J. Feuer is Chief, Statistical Research and Applications Branch, Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD 20852 (E-mail: feuerr@mail.nih.gov). Most of Ram C. Tiwari's work was done while he was at the National Cancer Institute, NIH. The views expressed in this article do not necessarily represent those of the U.S. Food and Drug Administration, and of the National Cancer Institute. The authors wish to thank the editor, associate editor, and the referees for their valuable comments and suggestions. Kulldorff gratefully acknowledge the support of National Institute of Child Health and Human Development grant R01 HD048852. NR 42 TC 16 Z9 18 U1 2 U2 7 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD SEP PY 2009 VL 104 IS 487 BP 886 EP 898 DI 10.1198/jasa.2009.ap07613 PG 13 WC Statistics & Probability SC Mathematics GA 508FX UT WOS:000270916100002 ER PT J AU Xu, Q Paik, MC Luo, XD Tsai, WY AF Xu, Qiang Paik, Myunghee Cho Luo, Xiaodong Tsai, Wei-Yann TI Reweighting Estimators for Cox Regression With Missing Covariates SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Missing covariate; Proportional hazards model; Weighted estimating equation ID PROPORTIONAL HAZARDS REGRESSION; MODEL; LIKELIHOOD; EQUATIONS AB Missingness in covariates is a common problem in survival data. In this article we propose a reweighting method for estimating the regression parameters in the Cox model with missing covariates. We also consider the augmented reweighting method by subtracting the projection term onto the nuisance tangent space. The proposed method provides consistent and asymptotically normally distributed estimators when the missing-data mechanism depends on the outcome variables, its well as on the observed covariates with either monotone or arbitrary nonmonotone missingness patterns. Simulation results indicate that in most Situations, the proposed reweighting estimators are more efficient than the inverse probability weighting estimators for the regression coefficients of the missing covariates and are as efficient its or more efficient than the inverse probability weighting estimators for the regression coefficients of the completely observed covariates. The simple reweighting estimators can be easily implemented in standard statistical packages. C1 [Xu, Qiang] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Paik, Myunghee Cho; Tsai, Wei-Yann] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY 10032 USA. [Luo, Xiaodong] Mt Sinai Sch Med, Dept Psychiat, Bronx, NY 10468 USA. RP Xu, Q (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM Qiang.Xu@fda.hhs.gov; mp9@columbia.edu; Xiaodong.Luo@mssm.edu; wyt@biostat.cpmc.columbia.edu FU National Institute of Neurological Disorders and Stroke (NINDS) [5R01NS36928-6]; NOMAS [2R37 NS029993-16] FX Qiang Xu is Mathematical Statistician, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993 (E-mail: Qiang.Xu@fda.hhs.gov). Myunghee Cho Paik is Professor (E-mail: mp9@columbia.edu) and Wei-Yann Tsai is Professor (E-mail: wyt@biostat.cpmc.columbia.edu), Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY 10032. Xiaodong Luo is Assistant Professor, Department of Psychiatry, Mount Sinai School of Medicine, Bronx, NY 10468 (E-mail: Xiaodong.Luo@mssm.edu). Myunghee Cho Paik is supported by grant 5R01NS36928-6 from National Institute of Neurological Disorders and Stroke (NINDS). The authors thank Ralph Sacco and Mitchell Elkind for providing the NOMAS resources funded by grant 2R37 NS029993-16. They also thank Stephen L. Portnoy, the associate editor, and two referees for their constructive comments and suggestions, which greatly improved the article. NR 24 TC 6 Z9 6 U1 3 U2 6 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD SEP PY 2009 VL 104 IS 487 BP 1155 EP 1167 DI 10.1198/jasa.2009.tm07172 PG 13 WC Statistics & Probability SC Mathematics GA 508FX UT WOS:000270916100028 ER PT J AU Othus, M Li, Y Tiwari, RC AF Othus, Megan Li, Yi Tiwari, Ram C. TI A Class of Semiparametric Mixture Cure Survival Models With Dependent Censoring SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Estimating equation; Proportional hazards model; Proportional odds model; Right censoring; Transformation model ID COMPETING RISKS MODEL; PROSTATE-CANCER CELLS; SUFFICIENT FOLLOW-UP; TRANSFORMATION MODELS; REGRESSION-MODELS; FAILURE TIMES; IDENTIFIABILITY; PROBABILITY; CHOLESTEROL; DISEASE AB Modern cancer treatments have substantially improved cure rates and have generated a great interest in and need for proper statistical tools to analyze survival data with nonnegligible cure fractions. Data with Cure fractions often ire complicated by dependent censoring, and the analysis of this type of data typically involves untestable parametric assumptions on the dependence of the censoring mechanism and the true survival times. Motivated by the analysis of prostate cancer survival trends, we propose a class of semiparametric transformation cure models that allows for dependent censoring without making parametric assumptions on the dependence relationship. The proposed class of models encompasses a number of common models for the latency survival function, including the proportional hazards model and the proportional odds model, and also allows for time-dependent covariates. An inverse censoring probability reweighting scheme is used to derive unbiased estimating equations. Small-sample properties with simulations are derived, and the method is demonstrated with a data application. C1 [Othus, Megan; Li, Yi] Harvard Univ, Dept Biostat, Boston, MA 02115 USA. [Othus, Megan; Li, Yi] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Tiwari, Ram C.] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Tiwari, Ram C.] NCI, Bethesda, MD 20892 USA. RP Othus, M (reprint author), Harvard Univ, Dept Biostat, Boston, MA 02115 USA. EM mothus@fas.harvard.edu; yili@jimmy.harvard.edu; ram.tiwari@fda.hhs.gov FU National Institutes of Health [CA09337-25, ES07142-24] FX Megan Othus is Graduate Student, Department of Biostatistics, Harvard University and Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115 (E-mail: mothus@fas.harvard.edu). Yi Li is Associate Professor, Department of Biostatistics, Harvard University, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115 (E-mail: yili@jimmy.harvard.edu). Ram Tiwari is Associate Director for Statistical Science and Policy, Office of Biostatistics, Center for Drug Evaluation & Research, Food and Drug Administration, Silver Springs, MD 20993 (E-mail: ram.tiwari@fda.hhs.gov). The work of Tiwari was conducted while he was at the National Cancer Institute. The views expressed in this article are his own and do not necessarily represent those of the National Cancer Institue or the Food and Drug Administration. This work was supported in part by National Institutes of Health grants CA09337-25 and ES07142-24. The authors thank Eric (Rocky) Feuer and Angela Mariotto for their extensive and insightful comments on the manuscript. NR 61 TC 6 Z9 6 U1 0 U2 3 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD SEP PY 2009 VL 104 IS 487 BP 1241 EP 1250 DI 10.1198/jasa.2009.tm08033 PG 10 WC Statistics & Probability SC Mathematics GA 508FX UT WOS:000270916100036 PM 20706564 ER PT J AU Malik, S Justice, R Farrell, AT Sridhara, R Pazdur, R AF Malik, Shakun Justice, Robert Farrell, Ann T. Sridhara, Rajeshwari Pazdur, Richard TI Approved therapies for advanced non-small cell lung cancer, food and drug administration overview SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Farrell, Ann T.] US FDA, CEDR, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S538 EP S539 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001439 ER PT J AU Sridhara, R Malik, S AF Sridhara, Rajeshwari Malik, Shakuntala TI Challenges in regulatory marketing approval of drugs for the treatment of advanced non-small cell lung cancer based on non-inferiority trials SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Sridhara, Rajeshwari; Malik, Shakuntala] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S540 EP S540 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001441 ER PT J AU Feng, SB Nie, L Wolfe, RA AF Feng, Shibao Nie, Lei Wolfe, Robert A. TI Laplace's approximation for relative risk frailty models SO LIFETIME DATA ANALYSIS LA English DT Article DE Multivariate survival analysis; Mixed Poisson regression models ID MIXED-EFFECTS MODELS; SURVIVAL; TRANSPLANT; LIKELIHOOD; VARIANCE AB Relative risk frailty models are used extensively in analyzing clustered and/or recurrent time-to-event data. In this paper, Laplace's approximation for integrals is applied to marginal distributions of data arising from parametric relative risk frailty models. Under regularity conditions, the approximate maximum likelihood estimators (MLE) are consistent with a rate of convergence that depends on both the number of subjects and number of members per subject. We compare the approximate MLE against alternative estimators using limited simulation and demonstrate the utility of Laplace's approximation approach by analyzing U.S. patient waiting time to deceased kidney transplant data. C1 [Feng, Shibao] Genentech Inc, San Francisco, CA 94080 USA. [Nie, Lei] US FDA, Off Biometr, CDER, Silver Spring, MD 20993 USA. [Wolfe, Robert A.] Arbor Res Collaborat Hlth, Ann Arbor, MI 48103 USA. RP Feng, SB (reprint author), Genentech Inc, San Francisco, CA 94080 USA. EM shibaof@gene.com FU U.S. Food and Drug Administration FX We would like to thank an Associate Editor and two referees for their constructive comments and suggestions, which have improved the presentation and the quality of the paper. We would also like to thank Dr. Abie Craiu for carefully checking the grammar and spelling of the manuscript. This research work was completed in 2007 while Dr. Nie was a faculty member at Georgetown University. Views expressed in this paper are the authors' professional opinions and do not necessarily represent the official positions of the U.S. Food and Drug Administration. NR 17 TC 6 Z9 6 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD SEP PY 2009 VL 15 IS 3 BP 343 EP 356 DI 10.1007/s10985-009-9112-x PG 14 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 461TY UT WOS:000267296000004 PM 19184420 ER PT J AU Chapman, K Pullen, N Coney, L Dempster, M Andrews, L Bajramovic, J Baldrick, P Buckley, L Jacobs, A Hale, G Green, C Ragan, I Robinson, V AF Chapman, Kathryn Pullen, Nick Coney, Lee Dempster, Maggie Andrews, Laura Bajramovic, Jeffrey Baldrick, Paul Buckley, Lorrene Jacobs, Abby Hale, Geoff Green, Colin Ragan, Ian Robinson, Vicky TI Preclinical development of monoclonal antibodies Considerations for the use of non-human primates SO MABS LA English DT Article DE mAb; non-human primate; species selection; ICHS6; homologous protein; preclinical; toxicology studies; potency; relevance ID CD4 TRANSGENIC MICE; CHRONIC TOXICITY; DOSE SELECTION; SAFETY; THERAPEUTICS; CANCER; INFECTIONS; KELIXIMAB; RELEVANCE AB The development of mAbs remains high on the therapeutic agenda for the majority of pharmaceutical and biotechnology companies. Often, the only relevant species for preclinical safety assessment of mAbs are non-human primates (NHPs), and this raises important scientific, ethical and economic issues. To investigate evidence-based opportunities to minimize the use of NHPs, an expert working group with representatives from leading pharmaceutical and biotechnology companies, contract research organizations and institutes from Europe and the USA, has shared and analyzed data on rnAbs for a range of therapeutic areas. This information has been applied to hypothetical examples to recommend scientifically appropriate development pathways and study designs for a variety of potential mAbs. The addendum of ICHS6 provides a timely opportunity for the scientific and regulatory community to embrace strategies which minimize primate use and increase efficiency of mAb development. C1 [Chapman, Kathryn; Robinson, Vicky] Natl Ctr Replacement Refinement & Reduct Anim Res, London, England. [Pullen, Nick] Pfizer, Sandwich, Kent, England. [Coney, Lee] Huntingdon Life Sci, Huntingdon, Cambs, England. [Dempster, Maggie] GlaxoSmithKline Inc, Ware, Herts, England. [Andrews, Laura] Genzyme, Framingham, MA USA. [Bajramovic, Jeffrey] Biomed Primate Res Ctr, Rijswijk, Netherlands. [Baldrick, Paul] Sci & Regulatory Consulting, Covance Labs, Harrogate, Yorks, England. [Buckley, Lorrene] Eli Lilly & Co, Greenfield, IN USA. [Jacobs, Abby] US FDA, Rockville, MD 20857 USA. [Hale, Geoff] BioAnaLab Ltd, Oxford, England. [Green, Colin] Antisoma, London, England. [Ragan, Ian] CIR Consulting Ltd, London, England. RP Chapman, K (reprint author), Natl Ctr Replacement Refinement & Reduct Anim Res, London, England. EM kathryn.chapman@nc3rs.org.uk NR 44 TC 43 Z9 44 U1 1 U2 5 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1942-0862 J9 MABS JI mAbs PD SEP-OCT PY 2009 VL 1 IS 5 BP 505 EP 516 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 522HU UT WOS:000271989300012 PM 20065651 ER PT J AU Beger, RD Hansen, DK Schnackenberg, LK Cross, BM Fatollahi, JJ Lagunero, FT Sarnyai, Z Boros, LG AF Beger, Richard D. Hansen, Deborah K. Schnackenberg, Laura K. Cross, Brandie M. Fatollahi, Javad J. Lagunero, F. Tracy Sarnyai, Zoltan Boros, Laszlo G. TI Single valproic acid treatment inhibits glycogen and RNA ribose turnover while disrupting glucose-derived cholesterol synthesis in liver as revealed by the [U-C-13(6)]-d-glucose tracer in mice SO METABOLOMICS LA English DT Article DE Valproic acid; Stable isotope-based dynamic metabolic profiling (SiDMAP); [U-C-13(6)]-D-glucose ID MASS ISOTOPOMER; SODIUM VALPROATE; IN-VITRO; GLUCONEOGENESIS; METABOLISM; HEPATOTOXICITY; LIPOGENESIS; EXPRESSION; PATHWAYS; EPILEPSY AB Previous genetic and proteomic studies identified altered activity of various enzymes such as those of fatty acid metabolism and glycogen synthesis after a single toxic dose of valproic acid (VPA) in rats. In this study, we demonstrate the effect of VPA on metabolite synthesis flux rates and the possible use of abnormal C-13 labeled glucose-derived metabolites in plasma or urine as early markers of toxicity. Female CD-1 mice were injected subcutaneously with saline or 600 mg/kg) VPA. Twelve hours later, the mice were injected with an intraperitoneal load of 1 g/kg [U-C-13]-d-glucose. C-13 isotopomers of glycogen glucose and RNA ribose in liver, kidney and brain tissue, as well as glucose disposal via cholesterol and glucose in the plasma and urine were determined. The levels of all of the positional C-13 isotopomers of glucose were similar in plasma, suggesting that a single VPA dose does not disturb glucose absorption, uptake or hepatic glucose metabolism. Three-hour urine samples showed an increase in the injected tracer indicating a decreased glucose re-absorption via kidney tubules. C-13 labeled glucose deposited as liver glycogen or as ribose of RNA were decreased by VPA treatment; incorporation of C-13 via acetyl-CoA into plasma cholesterol was significantly lower at 60 min. The severe decreases in glucose-derived carbon flux into plasma and kidney-bound cholesterol, liver glycogen and RNA ribose synthesis, as well as decreased glucose re-absorption and an increased disposal via urine all serve as early flux markers of VPA-induced adverse metabolic effects in the host. C1 [Beger, Richard D.; Hansen, Deborah K.; Schnackenberg, Laura K.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Cross, Brandie M.; Fatollahi, Javad J.; Lagunero, F. Tracy; Boros, Laszlo G.] SiDMAP LLC, Los Angeles, CA USA. [Sarnyai, Zoltan] Univ Cambridge, Dept Pharmacol, Cambridge CB2 1QJ, England. [Boros, Laszlo G.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Beger, RD (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM Richard.Beger@fda.hhs.gov; lboros@sidmap.com RI Sarnyai, Zoltan/A-3283-2009 NR 38 TC 15 Z9 16 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1573-3882 J9 METABOLOMICS JI Metabolomics PD SEP PY 2009 VL 5 IS 3 BP 336 EP 345 DI 10.1007/s11306-009-0159-1 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 487XS UT WOS:000269312400007 ER PT J AU Salerno, E Scaglione, BJ Coffman, FD Brown, BD Baccarini, A Fernandes, H Marti, G Raveche, ES AF Salerno, Erica Scaglione, Brian J. Coffman, Frederick D. Brown, Brian D. Baccarini, Alessia Fernandes, Helen Marti, Gerald Raveche, Elizabeth S. TI Correcting miR-15a/16 genetic defect in New Zealand Black mouse model of CLL enhances drug sensitivity SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MANTLE CELL LYMPHOMA; MALIGNANT B-1 CELLS; B-CELL; LYMPHOPROLIFERATIVE DISORDERS; TUMOR-SUPPRESSOR; CYCLIN D1; TRANSGENE EXPRESSION; ENDOGENOUS MICRORNA; LENTIVIRAL VECTORS AB Alterations in the human 13q14 genomic region containing microRNAs mir-15a and mir-16-1 are present in Most human chronic lymphocytic leukemia (CLL). We have previously found the development of CLL in the New Zealand Black murine model to be associated with a point mutation in the primary mir-15a/16-1 region, which correlated with a decrease in mature miR-16 and miR-15a levels. In this study, addition of exogenous miR-15a and miR-16 led to an accumulation of cells in G(1) in non-New Zealand Black B cell and New Zealand Black-derived malignant B-1 cell lines. However, the New Zealand Black line had significantly greater G(1) accumulation, suggesting a restoration of cell cycle control upon exogenous miR-15a/16 addition. Our experiments showed a reduction in protein levels of cyclin D1, a miR-15a/16 target and cell cycle regulator of G(1)/S transition, in the New Zealand Black cell line following miR-15a/16 addition. These microRNAs were shown to directly target the cyclin D1 3' untranslated region using a green fluorescent protein lentiviral expression system. miR-16 was also shown to augment apoptosis induction by nutlin, a mouse double minute 2 (MDM2) antagonist, and genistein, a tyrosine kinase inhibitor, when added to a B-1 cell line derived from multiple in vivo pas-sages of malignant B-1 cells from New Zealand Black mice with CLL. miR-16 synergized with nutlin and genistein to induce apoptosis. Our data support a role for the mir-15a/16-1 cluster in cell cycle regulation and suggest that these mature microRNAs in both the New Zealand Black model and human CLL may be targets for therapeutic efficacy in this disease. [Mol Cancer Ther 2009;8(9):2684-92] C1 [Salerno, Erica; Scaglione, Brian J.; Coffman, Frederick D.; Fernandes, Helen; Raveche, Elizabeth S.] Univ Med & Dent New Jersey, Dept Pathol & Lab Med, New Jersey Med Sch, Newark, NJ 07103 USA. [Scaglione, Brian J.; Brown, Brian D.; Baccarini, Alessia] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Marti, Gerald] NIH, Ctr Biol Evaluat & Res, US FDA, Bethesda, MD 20892 USA. RP Raveche, ES (reprint author), Univ Med & Dent New Jersey, Dept Pathol & Lab Med, New Jersey Med Sch, MSB C512,185 S Orange Ave, Newark, NJ 07103 USA. EM raveches@umdnj.edu FU New Jersey Commission on Cancer Research FX This research was funded in part by the New Jersey Commission on Cancer Research predoctoral fellowship awarded (E. Salerno). NR 49 TC 37 Z9 41 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD SEP PY 2009 VL 8 IS 9 BP 2684 EP 2692 DI 10.1158/1535-7163.MCT-09-0127 PG 9 WC Oncology SC Oncology GA 496JY UT WOS:000269968900021 PM 19723889 ER PT J AU Banugaria, SG Goldenberg, PC DeArmey, SL Heller, J Benjamin, D Young, S Bali, D Smith, SA Li, JS Mandel, H Koeberl, D Rosenberg, A Chen, YT Kishnani, PS AF Banugaria, S. G. Goldenberg, P. C. DeArmey, S. L. Heller, J. Benjamin, D. Young, S. Bali, D. Smith, S. A. Li, J. S. Mandel, H. Koeberl, D. Rosenberg, A. Chen, Y. T. Kishnani, P. S. TI INFLUENCE OF CROSS-REACTING IMMUNOLOGIC MATERIAL STATUS ON TREATMENT OUTCOMES IN INFANTILE POMPE PATIENTS TREATED WITH RECOMBINANT HUMAN ACID ALPHA-GLUCOSIDASE SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 11th International Conference of Inborn Errors of Metabolism CY AUG 29-SEP 02, 2009 CL San Diego, CA C1 [Banugaria, S. G.; Goldenberg, P. C.; DeArmey, S. L.; Young, S.; Bali, D.; Koeberl, D.; Chen, Y. T.; Kishnani, P. S.] Duke Univ, Med Ctr, Dept Pediat, Div Med Genet, Durham, NC 27710 USA. [Heller, J.] Duke Univ, Med Ctr, Dept Surg, Div Speech & Hearing, Durham, NC 27710 USA. [Benjamin, D.] Duke Univ, Dept Pediat Med, Durham, NC USA. [Benjamin, D.] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Smith, S. A.] Oregon Hlth & Sci Univ, Dept Pediat, Div Neonatol, Portland, OR 97201 USA. [Li, J. S.] Duke Univ, Med Ctr, Dept Pediat, Div Cardiol, Durham, NC 27710 USA. [Mandel, H.] Rambam Med Ctr, Dept Pediat & Med Genet, Haifa, Israel. [Rosenberg, A.] US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. [Chen, Y. T.] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2009 VL 98 IS 1-2 MA 344 BP 59 EP 59 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 483DQ UT WOS:000268942600244 ER PT J AU Liu, W Ding, JH Gibbs, JR Wang, SJ Hardy, J Singleton, A AF Liu, Wei Ding, Jinhui Gibbs, Jesse Raphael Wang, Sue Jane Hardy, John Singleton, Andrew TI A simple and efficient algorithm for genome-wide homozygosity analysis in disease SO MOLECULAR SYSTEMS BIOLOGY LA English DT Article DE disease network; homozygous segments; risk loci; statistical algorithm; whole-genome screening ID ALZHEIMERS-DISEASE; ASSOCIATION; GENE; AGE; POLYMORPHISMS; GENOTYPE; REVEALS; APOE; DNA AB Here we propose a simple statistical algorithm for rapidly scoring loci associated with disease or traits due to recessive mutations or deletions using genome-wide single nucleotide polymorphism genotyping case-control data in unrelated individuals. This algorithm identifies loci by defining homozygous segments of the genome present at significantly different frequencies between cases and controls. We found that false positive loci could be effectively removed from the output of this procedure by applying different physical size thresholds for the homozygous segments. This procedure is then conducted iteratively using random sub-datasets until the number of selected loci converges. We demonstrate this method in a publicly available data set for Alzheimer's disease and identify 26 candidate risk loci in the 22 autosomes. In this data set, these loci can explain 75% of the genetic risk variability of the disease. Molecular Systems Biology 5: 304; published online 15 September 2009; doi:10.1038/msb.2009.53 C1 [Liu, Wei; Wang, Sue Jane] US FDA, Off Biostat, OTS, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Liu, Wei; Ding, Jinhui; Gibbs, Jesse Raphael; Singleton, Andrew] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Gibbs, Jesse Raphael; Hardy, John] UCL, Dept Mol Neurosci, London, England. [Gibbs, Jesse Raphael; Hardy, John] UCL, Inst Neurol, Reta Lila Weston Labs, London, England. RP Liu, W (reprint author), US FDA, Off Biostat, OTS, Ctr Drug Evaluat & Res, DB2,WO 21,Mail Stop 3562, Silver Spring, MD 20993 USA. EM Wei.Liu@fda.hhs.gov RI Gibbs, J. Raphael/A-3984-2010; Hardy, John/C-2451-2009; Singleton, Andrew/C-3010-2009; Sincan, Murat /A-3794-2010 FU National Institute on Aging; National Institutes of Health and Department of Health and Human Services [AG000950-07] FX This study was supported by the Intramural Program of the National Institute on Aging, National Institutes of Health and Department of Health and Human Services, project number AG000950-07. This study used high-performance computational capabilities of the Biowulf Systems at the National Institutes of Health, Bethesda, MD (http://helix.nih.gov). NR 20 TC 1 Z9 1 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1744-4292 J9 MOL SYST BIOL JI Mol. Syst. Biol. PD SEP PY 2009 VL 5 AR 304 DI 10.1038/msb.2009.53 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 502JZ UT WOS:000270456400004 PM 19756043 ER PT J AU Semberova, J Lacerda, SHDP Simakova, O Holada, K Gelderman, MP Simak, J AF Semberova, Jana Lacerda, Silvia H. De Paoli Simakova, Olga Holada, Karel Gelderman, Monique P. Simak, Jan TI Carbon Nanotubes Activate Blood Platelets by Inducing Extracellular Ca2+ Influx Sensitive to Calcium Entry Inhibitors SO NANO LETTERS LA English DT Article ID CELL-MEMBRANE MICROPARTICLES; TOXICITY; NANOPARTICLES; NANOMATERIALS; AGGREGATION; MECHANISM; PENETRATION; PARTICLES; CHANNELS; RELEASE AB To elucidate a mechanism of prothrombotic effects of carbon nanotubes (CNTs), we report here that multiwalled CNTs activate blood platelets by inducing extracellular Ca2+ influx that could be inhibited by calcium channel blockers; SKF 96365 and 2-APB. We also demonstrate platelet aggregating activity of different single-walled and multiwalled CNTs. In addition, we show that CNT-induced platelet activation is associated with a marked release of platelet membrane microparticles positive for the granular secretion markers CD62P and CD63. C1 [Semberova, Jana; Lacerda, Silvia H. De Paoli; Gelderman, Monique P.; Simak, Jan] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Semberova, Jana] Inst Care Mother & Child, Prague, Czech Republic. [Holada, Karel] Charles Univ Prague, Sch Med 1, Prague, Czech Republic. [Simakova, Olga] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Simak, J (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. EM jan.simak@fda.hhs.gov RI Simak, Jan/C-1153-2011 FU Ministry of Education, Youth, and Sport of the Czech Republic [MSM 0021620806] FX We thank Gerald Sando, Ph.D., Malvern Instruments, Columbia, MD, for the flow particle image analysis of nanomaterial suspensions. K.H. was supported by grant MSM 0021620806 of the Ministry of Education, Youth, and Sport of the Czech Republic. 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 35 TC 54 Z9 54 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1530-6984 J9 NANO LETT JI Nano Lett. PD SEP PY 2009 VL 9 IS 9 BP 3312 EP 3317 DI 10.1021/nl901603k PG 6 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 492KQ UT WOS:000269654900039 PM 19736974 ER PT J AU Aquilante, CL Beitelshees, AL Cavallari, LH Lee, CR Maciejewski, S Momary, KM Vardeny, O Zineh, I AF Aquilante, Christina L. Beitelshees, Amber L. Cavallari, Larisa H. Lee, Craig R. Maciejewski, Stephanie Momary, Kathryn M. Vardeny, Orly Zineh, Issam TI Key Articles Relative to Cardiovascular Pharmacogenomics SO PHARMACOTHERAPY LA English DT Article DE cardiovascular disease; pharmacogenomics; pharmacogenetics AB Significant progress has been made in the field of cardiovascular pharmacogenomics over the past 10 years. As a result, important pharmacogenomic literature is now available for most major cardiovascular disease states. In addition, the results of some studies have prompted inclusion of pharmacogenomic information into the package inserts of specific cardiovascular agents such as warfarin. This compilation provides annotated bibliographies of high-impact cardiovascular pharmacogenomics articles. C1 [Aquilante, Christina L.] Univ Colorado, Denver Sch Pharm, Dept Pharmaceut Sci, Aurora, CO 80045 USA. [Beitelshees, Amber L.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Cavallari, Larisa H.] Univ Illinois, Dept Pharm Practice, Chicago, IL USA. [Lee, Craig R.] Univ N Carolina, Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC USA. [Maciejewski, Stephanie] Creighton Univ, Cardiac Ctr, Omaha, NE 68178 USA. [Momary, Kathryn M.] Mercer Univ, Coll Pharm & Hlth Sci, Dept Pharm Practice, Atlanta, GA USA. [Vardeny, Orly] Univ Wisconsin, Sch Pharm, Div Pharm Practice, Madison, WI 53706 USA. [Zineh, Issam] US FDA, Genom Grp, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Aquilante, CL (reprint author), Univ Colorado, Denver Sch Pharm, Dept Pharmaceut Sci, 12700 E 19th Ave,Box C238-P15, Aurora, CO 80045 USA. EM Christina.aquilante@ucdenver.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD SEP PY 2009 VL 29 IS 9 BP 1110 EP 1151 PG 42 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 489QV UT WOS:000269437500012 ER PT J AU Chu, C Lugovtsev, V Golding, H Betenbaugh, M Shiloach, J AF Chu, Chia Lugovtsev, Vladimir Golding, Hana Betenbaugh, Michael Shiloach, Joseph TI Conversion of MDCK cell line to suspension culture by transfecting with human siat7e gene and its application for influenza virus production SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE anchorage-independent; hemagglutinin; sialyltransferase; vaccine ID SCALE MICROCARRIER CULTURE; CYCLE PROGRESSION; CATIONIZED FERRITIN; HIGH GROWTH; B VIRUSES; VACCINES; EXPRESSION; ADHESION; VERO; GANGLIOSIDES AB MDCK cells are currently being considered as an alternative to embryonated eggs for influenza virus propagation and hemagglutinin ( HA) production intended for vaccine manufacturing. MDCK cells were found suitable for the virus production but their inability to grow in suspension burdens the process of scale up and hence their production capability. Anchorage-dependent MDCK cells were converted to anchorage-independent cells, capable of growing in suspension as a result of transfection with the human siat7e gene (ST6GaINac V). This gene was previously identified as having an important role in cellular adhesion when the transcriptions of genes from anchorage-dependent and anchorage-independent HeLa cells were compared. Unlike the parental MDCK cells, the siat7e-expressing cells were capable of growing in shake flasks as suspension cultures, achieving maximum concentration of 7 x 10(5) cells/mL while keeping close to 100% viability throughout the growth phase. In production experiments, the siat7e-expressing cells were infected with the Influenza B/Victoria/504/2000 strain. It was determined that the cell-derived viruses retained similar antigenic properties as those obtained from egg-derived viruses and their nucleotide sequences were identical. The specific production of hemagglutinin (expressed in hemagglutination units per 106 cells) from the siat7e-expressing cells was approximately 20 times higher than the specific production from the parental MDCK cells. If this suspension process scales up, the production potential of HA from 10 L of siat7e-expressing cells at a concentration of 106 cells/mL would be equivalent to the amount of HA obtained from 10,000 embryonated eggs. C1 [Chu, Chia; Shiloach, Joseph] NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA. [Chu, Chia; Betenbaugh, Michael] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA. [Lugovtsev, Vladimir; Golding, Hana] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Shiloach, J (reprint author), NIDDK, Biotechnol Core Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM yossi@nih.gov RI Betenbaugh, Michael J./A-3252-2010 OI Betenbaugh, Michael J./0000-0002-6336-4659 FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health FX We thank Dr. Bruce Raaka for his assistance with the FACS measurements and Dr. Pratik Jaluria for his communications on technical aspects of the experiments and formulation of the manuscript. This work was supported by the Intramural program at the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NR 37 TC 27 Z9 29 U1 2 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 2009 VL 106 IS 35 BP 14802 EP 14807 DI 10.1073/pnas.0905912106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 490EM UT WOS:000269481000015 PM 19706449 ER PT J AU Mischak, H Espandiari, P Sadrieh, N Hanig, J AF Mischak, Harald Espandiari, Parvaneh Sadrieh, Nakissa Hanig, Joseph TI Profiling of rat urinary proteomic patterns associated with drug-induced nephrotoxicity using CE coupled with MS as a potential model for detection of drug-induced adverse effects SO PROTEOMICS CLINICAL APPLICATIONS LA English DT Article DE Animal models; Mass spectrometry; Nephrotoxicity; Preclinical testing; Urine ID ELECTRON-TRANSFER DISSOCIATION; MASS-SPECTROMETRY; CAPILLARY-ELECTROPHORESIS; BIOMARKER DISCOVERY; DISEASE; CISPLATIN; PEPTIDES; PROTEINS; THERAPY; MARKERS AB We have investigated urine obtained from Sprague Dawley rats before and after administration of cis-Platin, aiming at the definition of biomarkers for drug-induced cytotoxicity. Rats were treated with 3 or 6 mg/kg cis-Platin (i.p., single injection) and urine samples were collected before and after drug or saline treatment. Analysis of the low molecular weight proteome (< 20 kDa) using capillary-electrophoresis coupled mass spectrometry allowed us to tentatively identify 34 urinary peptides that show significant differences between control and treated animals, and hence may serve as a potential biomarker for cis-Platin-induced nephrotoxicity. These biomarkers were confirmed in a blinded assessment of additional samples. The blinded data also revealed time-dependency of induced changes. Some of the potential biomarkers could be sequenced. This information revealed great similarity between cis-Platin-induced changes and significant changes in the urinary proteome of patients suffering from tubular injury (Fanconi syndrome). Our study strongly suggests that (drug-induced) nephrotoxicity can be detected with high accuracy in laboratory rodents using urinary proteome analysis. The effects observed are very similar to those seen in corresponding human diseases and similar approaches may be very helpful in evaluating drug-induced organ damage in preclinical animal models. This study aiming at the definition of biomarkers for drug-induced cytotoxicity may serve as a proof-of-principle for the use of urinary proteomics in assessment of drug-induced nephrotoxicity. C1 [Mischak, Harald] Mosaiques Diagnost GmbH, Hannover, Germany. [Espandiari, Parvaneh; Sadrieh, Nakissa; Hanig, Joseph] US FDA, CDER, Silver Spring, MD USA. RP Mischak, H (reprint author), Mosaiques Diagnost & Therapeut AG, Mellendorfer Str 7-9, D-30625 Hannover, Germany. EM mischak@mosaiques-diagnostics.com RI Mischak, Harald/E-8685-2011 FU U.S. Food and Drug Administration FX This report is not an official U.S. Food and Drug Administration guidance or policy statement. No official support or endorsement by the U.S. Food and Drug Administration is intended or should be inferred. NR 32 TC 11 Z9 11 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1862-8346 J9 PROTEOM CLIN APPL JI Proteom. Clin. Appl. PD SEP PY 2009 VL 3 IS 9 BP 1062 EP 1071 DI 10.1002/prca.200900030 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 500VL UT WOS:000270333600005 PM 21137006 ER PT J AU Thompson, AM Oliver, JA AF Thompson, Aliza M. Oliver, Juan A. TI Endogenous and Exogenous Vasopressin during Hemodialysis SO SEMINARS IN DIALYSIS LA English DT Editorial Material ID INDUCED HYPOTENSION; PLASMA VASOPRESSIN; BLOOD-PRESSURE; ARGININE VASOPRESSIN; DIALYSIS; VOLUME; OSMOLALITY; ULTRAFILTRATION; HYPERTENSION; STANDARD AB Intradialytic hypotension likely results from hypovolemia as well as patient and dialysis-specific factors. An impaired vasoconstrictive response to volume loss during hemodialysis has been demonstrated and increasing evidence suggests that deficiency in the hormone arginine vasopressin may be a contributing factor. Although vasopressin is widely recognized for its role in the regulation of serum osmolality, vasopressin is also an important regulator of blood pressure in health and in various disease states. That vasopressin deficiency contributes to the pathogenesis of intradialytic hypotension is suggested by several observations. First, vasopressin levels typically fall during hemodialysis when a rise might be expected as a result of volume loss. Second, therapies that prevent a fall in osmolality during dialysis, including dialysis against a high sodium bath and isolated ultrafiltration, have been shown to improve intradialytic blood pressure stability. Finally, and perhaps most importantly, the administration of low-dose exogenous vasopressin during dialysis has been shown to support blood pressure and improve volume removal. Further research is needed to determine the effect of chronic vasopressin (or selective V1a agonist) administration during dialysis on volume removal, inter- and intradialytic blood pressure control, and, ultimately, clinical outcomes in end-stage renal disease patients on dialysis. C1 [Oliver, Juan A.] Columbia Univ, Dept Med, New York, NY 10032 USA. [Thompson, Aliza M.] Food & Drug Adm, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Oliver, JA (reprint author), Columbia Univ, Dept Med, New York, NY 10032 USA. EM jao7@columbia.edu FU NIDDK NIH HHS [5F32DK066927-02] NR 31 TC 8 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD SEP-OCT PY 2009 VL 22 IS 5 BP 472 EP 475 DI 10.1111/j.1525-139X.2009.00615.x PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 505XG UT WOS:000270734100002 PM 19522759 ER PT J AU Cohen, SM Storer, RD Criswell, KA Doerrer, NG Dellarco, VL Pegg, DG Wojcinski, ZW Malarkey, DE Jacobs, AC Klaunig, JE Swenberg, JA Cook, JC AF Cohen, Samuel M. Storer, Richard D. Criswell, Kay A. Doerrer, Nancy G. Dellarco, Vicki L. Pegg, David G. Wojcinski, Zbigniew W. Malarkey, David E. Jacobs, Abigail C. Klaunig, James E. Swenberg, James A. Cook, Jon C. TI Hemangiosarcoma in Rodents: Mode-of-Action Evaluation and Human Relevance SO TOXICOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT International Workshop on Hemangiosarcoma in Rodents - Mode-of-Action Evaluation and Human Relevance CY DEC 04-05, 2008 CL Arlington, VA SP ILSI, Hlth & Environm Sci Inst DE hemangiosarcoma; angiogenesis; endothelial cells; endothelial precursor cells; mode of action; human relevance; PPAR agonists ID ACTIVATED-RECEPTOR-GAMMA; ENDOTHELIAL PROGENITOR CELLS; ERUPTIVE CHERRY ANGIOMAS; ADIPOSE-TISSUE MASS; GROWTH-FACTOR; DIFFERENTIAL EXPRESSION; CANINE HEMANGIOSARCOMA; CHUVASH POLYCYTHEMIA; UNCOUPLING PROTEIN; VASCULAR TUMORS AB Although rarely occurring in humans, hemangiosarcomas (HS) have become important in evaluating the potential human risk of several chemicals, including industrial, agricultural, and pharmaceutical agents. Spontaneous HS arise frequently in mice, less commonly in rats, and frequently in numerous breeds of dogs. This review explores knowledge gaps and uncertainties related to the mode of action (MOA) for the induction of HS in rodents, and evaluates the potential relevance for human risk. For genotoxic chemicals (vinyl chloride and thorotrast), significant information is available concerning the MOA. In contrast, numerous chemicals produce HS in rodents by nongenotoxic, proliferative mechanisms. An overall framework is presented, including direct and indirect actions on endothelial cells, paracrine effects in local tissues, activation of bone marrow endothelial precursor cells, and tissue hypoxia. Numerous obstacles are identified in investigations into the MOA for mouse HS and the relevance of the mouse tumors to humans, including lack of identifiable precursor lesions, usually late occurrence of the tumors, and complexities of endothelial biology. This review proposes a working MOA for HS induced by nongenotoxic compounds that can guide future research in this area. Importantly, a common MOA appears to exist for the nongenotoxic induction of HS, where there appears to be a convergence of multiple initiating events (e.g., hemolysis, decreased respiration, adipocyte growth) leading to either dysregulated angiogenesis and/or erythropoiesis that results from hypoxia and macrophage activation. These later events lead to the release of angiogenic growth factors and cytokines that stimulate endothelial cell proliferation, which, if sustained, provide the milieu that can lead to HS formation. C1 [Doerrer, Nancy G.] ILSI Hlth & Environm Sci Inst, Washington, DC 20005 USA. [Cohen, Samuel M.] Univ Nebraska Med Ctr, Omaha, NE 68198 USA. [Storer, Richard D.] Merck Res Labs, West Point, PA 19486 USA. [Criswell, Kay A.; Cook, Jon C.] Pfizer Inc, Groton, CT 06340 USA. [Dellarco, Vicki L.] US EPA, Washington, DC 20460 USA. [Malarkey, David E.] Michigan Technol & Res Inst, Ann Arbor, MI 48104 USA. [Wojcinski, Zbigniew W.] Fulcrum Pharma Dev Inc, Ann Arbor, MI 48103 USA. [Malarkey, David E.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Jacobs, Abigail C.] US FDA, Silver Spring, MD 20993 USA. [Klaunig, James E.] Indiana Univ, Sch Med, Indianapolis, IN 46202 USA. [Swenberg, James A.] Univ N Carolina, Chapel Hill, NC 27599 USA. RP Doerrer, NG (reprint author), ILSI Hlth & Environm Sci Inst, 1156 15th St NW,2nd Floor, Washington, DC 20005 USA. EM ndoerrer@hesiglobal.org NR 99 TC 39 Z9 41 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD SEP PY 2009 VL 111 IS 1 BP 4 EP 18 DI 10.1093/toxsci/kfp131 PG 15 WC Toxicology SC Toxicology GA 483WM UT WOS:000269002200002 PM 19525443 ER PT J AU Gopee, NV Roberts, DW Webb, P Cozart, CR Siitonen, PH Latendresse, JR Warbitton, AR Yu, WW Colvin, VL Walker, NJ Howard, PC AF Gopee, Neera V. Roberts, Dean W. Webb, Peggy Cozart, Christy R. Siitonen, Paul H. Latendresse, John R. Warbitton, Alan R. Yu, William W. Colvin, Vicki L. Walker, Nigel J. Howard, Paul C. TI Quantitative Determination of Skin Penetration of PEG-Coated CdSe Quantum Dots in Dermabraded but not Intact SKH-1 Hairless Mouse Skin SO TOXICOLOGICAL SCIENCES LA English DT Article DE quantum dots; nanoscale materials; dermabrasion ID SILVER NANOPARTICLES; MURINE MODEL; RAT SKIN; PROTEIN; FULLERENES; NANOTECHNOLOGY; NANOMATERIALS; PARTICLES; STABILITY; EXPOSURE AB Many cosmetics, sunscreens, and other consumer products are reported to contain nanoscale materials. The possible transdermal absorption of nanoscale materials and the long-term consequences of the absorption have not been determined. We used polyethylene glycol coated cadmium selenide (CdSe) core quantum dots (QD; 37 nm diameter) to evaluate the penetration of nanoscale material into intact, tape stripped, acetone treated, or dermabraded mouse skin. QD were suspended in an oil-in-water emulsion (approximately 9 mu M) and the emulsion was applied at 2 mg/cm(2) to mouse dorsal skin pretreated as follows: intact; tape stripped to remove the stratum corneum; acetone pretreated; dermabraded to remove stratum corneum and epidermis. QD penetration into the skin was monitored in sentinel organs (liver and regional draining lymph nodes) using inductively coupled plasma mass spectrometry analysis of cadmium (from the CdSe QD). No consistent cadmium elevation was detected in the sentinel organs of mice with intact, acetone pretreated, or tape-stripped skin at 24- and 48-h post-QD application; however, in dermabraded mice, cadmium elevations were detected in the lymph nodes and liver. QD accumulation (as cadmium) in the liver was approximately 2.0% of the applied dose. The passing of QD through the dermabraded skin was confirmed using confocal fluorescence microscopy. These results suggest that transdermal absorption of nanoscale materials depends on skin barrier quality, and that the lack of an epidermis provided access to QD penetration. Future dermal risk assessments of nanoscale materials should consider key barrier aspects of skin and its overall physiologic integrity. C1 [Howard, Paul C.] US FDA, Div Biochem Toxicol, Natl Toxicol Program, Ctr Phototoxicol,Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Latendresse, John R.; Warbitton, Alan R.] Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Yu, William W.; Colvin, Vicki L.] Rice Univ, Ctr Biol & Environm Nanotechnol, Houston, TX 77005 USA. [Walker, Nigel J.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Howard, PC (reprint author), US FDA, Div Biochem Toxicol, Natl Toxicol Program, Ctr Phototoxicol,Natl Ctr Toxicol Res, 3900 NCTR Rd,HFT 110, Jefferson, AR 72079 USA. EM Paul.Howard@fda.hhs.gov RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 FU U. S. Food & Drug Administration [IAG 224-93-001]; National Institute of Environmental Health Sciences (NIEHS); National Institutes of Health (NIH) [2 P20 RR 16460]; Intramural Research Program of the NIEHS/NIH; NIH/NCRR [1 S10 RR 19395]; LSM [510] FX Interagency agreement (IAG 224-93-001) between the U. S. Food & Drug Administration and the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), and in part by the Intramural Research Program of the NIEHS/NIH; and University of Arkansas for Medical Sciences Digital and Confocal Microscopy Laboratory supported by NIH Grant (2 P20 RR 16460) (L. Cornett, PI, INBRE, Partnerships for Biomedical Research in Arkansas) and NIH/NCRR Grant (1 S10 RR 19395) (R. Kurten, PI, "Zeiss LSM 510 META Confocal Microscope System''). NR 56 TC 58 Z9 59 U1 3 U2 21 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD SEP PY 2009 VL 111 IS 1 BP 37 EP 48 DI 10.1093/toxsci/kfp139 PG 12 WC Toxicology SC Toxicology GA 483WM UT WOS:000269002200005 PM 19574408 ER PT J AU Fang, JL Beland, FA AF Fang, Jia-Long Beland, Frederick A. TI Long-Term Exposure to Zidovudine Delays Cell Cycle Progression, Induces Apoptosis, and Decreases Telomerase Activity in Human Hepatocytes SO TOXICOLOGICAL SCIENCES LA English DT Article DE AZT; cell cycle; apoptosis; telomerase activity; checkpoint kinases ID COLORECTAL-CANCER PATIENTS; IN-VITRO EXPOSURE; REVERSE-TRANSCRIPTASE; DNA-POLYMERASES; STRAND-BREAKS; PHASE-I; AZIDOTHYMIDINE; AZT; 3'-AZIDO-3'-DEOXYTHYMIDINE; COMBINATION AB Zidovudine (3'-azido-3'-deoxythymidine; AZT), which is currently used in the treatment of acquired immunodeficiency syndrome, has been shown to have anticancer properties. In the present study, we examined the mechanisms contributing to increased sensitivity of cancer cells to the growth-inhibitory effects of AZT. This was accomplished by incubating a hepatoma cell line (HepG2) and a normal liver cell line (THLE2) with AZT in continuous culture for up to 4 weeks and evaluating the number of viable and necrotic cells, the induction of apoptosis, cell cycle alterations, and telomerase activity. In HepG2 cells, AZT (2-100 mu M) caused significant dose-dependent decreases in the number of viable cells at exposures > 24 h. During a 1-week recover period, there was only a slight increase in the number of viable cells treated with AZT. The decrease in viable cells was associated with an induction of apoptosis, a decrease in telomerase activity, and S and G2/M phase arrest of the cell cycle. During the recovery period, the extent of apoptosis and telomerase activity returned to control levels, whereas the disruption of cell cycle progression persisted. Western blot analysis indicated that AZT caused a decrease in checkpoint kinase 1 (Chk1) and kinase 2 (Chk2) and an increase in phosphorylated Chk1 (Ser345) and Chk2 (Thr68). Similar effects, to lesser extent, were observed in THLE2 cells given much higher concentrations of AZT (50-2500 mu M). These data show that HepG2 cells are much more sensitive than THLE2 cells to AZT. They also indicate that a combination of a delay of cell cycle progression, an induction of apoptosis, and a decrease in telomerase activity is contributing to the decrease in the number of viable cells from AZT treatment, and that checkpoint enzymes Chk1 and Chk2 may play an important role in the delay of cell cycle progression. C1 [Fang, Jia-Long; Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Fang, JL (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM jia-long.fang@fda.hhs.gov FU National Center for Toxicological Research [224-07-0007]; U. S. Food and Drug Administration; National Institute for Environmental Health Sciences/National Toxicology Program FX Interagency Agreement (224-07-0007) between the National Center for Toxicological Research, U. S. Food and Drug Administration, and the National Institute for Environmental Health Sciences/National Toxicology Program. NR 43 TC 28 Z9 29 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD SEP PY 2009 VL 111 IS 1 BP 120 EP 130 DI 10.1093/toxsci/kfp136 PG 11 WC Toxicology SC Toxicology GA 483WM UT WOS:000269002200013 PM 19541796 ER PT J AU Jia, Y Lucena, S Cantu, E Sanchez, EE Perez, JC AF Jia, Ying Lucena, Sara Cantu, Esteban, Jr. Sanchez, Elda E. Perez, John C. TI cDNA cloning, expression and fibrin(ogen)olytic activity of two low-molecular weight snake venom metalloproteinases SO TOXICON LA English DT Article DE Snake venom metalloproteinase; Agkistrodon piscivorus leucostoma; cDNA library; Fibrin(ogen)olytic activity ID FACTOR-X ACTIVATOR; RUSSELLS VIPER VENOM; HEMORRHAGIC METALLOPROTEINASE; BIOCHEMICAL-CHARACTERIZATION; FUNCTIONAL-CHARACTERIZATION; DIMERIC DISINTEGRIN; BOTHROPS-JARARACA; CRYSTAL-STRUCTURE; PROTEINASE; PURIFICATION AB Two cDNA clones, ApIVMP1 and ApIVMP2, were isolated from a snake (Agkistrodon piscivorus leucostoma) venom gland cDNA library. The full-length cDNA sequence of ApIVMP1 with a calculated molecular mass of 46.61 kDa is 1233 bp in length. ApIVMP1 encodes PI class metalloproteinase with an open reading frame of 411 amino acid residues that includes signal peptide, pro-domain and metalloproteinase domains. The full-length cDNA of the ApIVMP2 (1371 bp) has a calculated molecular mass of 51.16 kDa and encodes PII class metalloproteinase. The open reading frame of ApIVMP2 with a 457 amino acid residues is composed of signal peptide, pro-domain, metalloproteinase and disintegrin domains. ApIVMP1 and ApIVMP2 showed 85% and 93% amino acid identical to PI class enzyme Agkistrodon contortrix laticinctus ACLPREF and PII class enzyme Agkistrodon piscivorus piscivorus piscivostatin, respectively. When expressed in Escherichia coli, most of recombinant proteins of ApIVMP1 and ApIVMP2 were in insoluble inclusion bodies, with soluble yields of 0.7 mg/l and 0.4 mg/l bacterial culture, respectively. Both affinity purified recombinant proteins show proteolytic activity on fibrinogen, although having an activity lower than that of crude A. P. leucostoma venom. Proteolytic activities of ApIVMP1 and ApIVMP2 were completely abolished after incubation with a final concentration of 100 mu M of EDTA or 1,10-phenanthroline. Both ApIVMP1 and ApIVMP2 were active in a fibrin-agarose plate but devoid of hemorrhagic activity when injected (up to 50 mu g) subcutaneously into mice, and had no capacity to inhibit platelet aggregation. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Perez, John C.] Texas A&I Univ, Natl Ctr Toxicol Res, Dept Biol, Coll Arts & Sci, Kingsville, TX 78363 USA. RP Perez, JC (reprint author), Texas A&I Univ, Natl Ctr Toxicol Res, Dept Biol, Coll Arts & Sci, MSC 158,975 W Ave B, Kingsville, TX 78363 USA. EM kfjcp00@tamuk.edu FU Natural Toxins Research Center at Texas A&M University-Kingsville; NIH [P40RR018300-06] FX We thank Nora Diaz De Leon, Angela Wyro and Lucy Arispe for their technique assistances. This research was supported by Natural Toxins Research Center at Texas A&M University-Kingsville; NIH# 2 P40RR018300-06. NR 45 TC 12 Z9 14 U1 1 U2 1 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 SEP 1 PY 2009 VL 54 IS 3 BP 233 EP 243 DI 10.1016/j.toxicon.2009.04.008 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 476JS UT WOS:000268436900005 PM 19375443 ER PT J AU Costa, PR Baugh, KA Wright, B RaLonde, R Nance, SL Tatarenkova, N Etheridge, SM Lefebvre, KA AF Costa, Pedro Reis Baugh, Keri A. Wright, Bruce RaLonde, Raymond Nance, Shelly L. Tatarenkova, Natalia Etheridge, Stacey M. Lefebvre, Kathi A. TI Comparative determination of paralytic shellfish toxins (PSTs) using five different toxin detection methods in shellfish species collected in the Aleutian Islands, Alaska SO TOXICON LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the North-Pacific-Marine-Science-Organization (PICES) CY OCT 24-NOV 02, 2008 CL Dalian, PEOPLES R CHINA SP N Pacific Marine Sci Org DE Paralytic shellfish toxins; Paralytic shellfish poisoning; Saxitoxin ID RECEPTOR-BINDING ASSAY; POISONING TOXINS; PSP TOXINS; PRECHROMATOGRAPHIC OXIDATION; SAXITOXIN AB Paralytic shellfish poisoning (PSP), a human illness caused by the ingestion of shellfish contaminated with paralytic shellfish toxins (PSTs), has been reported in Alaska for decades. These poisoning incidents have resulted in losses to local economies due to shellfish harvest closures. Thus the development of an effective biotoxin monitoring program designed specifically for the remote regions of Alaska would provide protection for public health and allow for a viable shellfish industry. The present study provides data useful for the development of an effective toxin screening protocol by comparing PST levels quantified in shellfish by many of the currently available PST detection techniques. Seven bivalve species were collected along beaches of the Aleutian Islands from June 2006 to September 2007. The concentration of PSTs was quantified and compared using five different analytical methods: the mouse bioassay, high performance liquid chromatography (HPLC), receptor-binding assay, the commercially available Jellett Rapid PSP Test strips, and an enzyme linked immunosorbent assay technique. The Association of Official Analytical Chemists (AOAC)-approved HPLC method proved to be valuable for characterizing the suite of individual PSTs in each species for research purposes, but was not considered practical for rapid toxin screening in remote Alaskan regions due to its time-consuming nature and requirement of expensive equipment and considerable expertise. In the present study, Jellett test strips were shown to be an effective tool for rapid screening, however due to the high percentage of false positives, subsequent validation via AOAC-approved methods would be required to prevent unnecessary closures. Published by Elsevier Ltd. C1 [Costa, Pedro Reis; Baugh, Keri A.; Nance, Shelly L.; Lefebvre, Kathi A.] NOAA Fisheries, NW Fisheries Sci Ctr, Biotoxins Program, Seattle, WA 98112 USA. [Wright, Bruce; Tatarenkova, Natalia] Aleutian Pribilof Isl Assoc, Anchorage, AK 99518 USA. [RaLonde, Raymond] Alaska Sea Grant Marine Advisory Program, Anchorage, AK 99501 USA. [Etheridge, Stacey M.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. RP Lefebvre, KA (reprint author), NOAA Fisheries, NW Fisheries Sci Ctr, Biotoxins Program, 2725 Montlake Blvd E, Seattle, WA 98112 USA. EM kathi.lefebvre@noaa.gov RI Costa, Pedro/F-2192-2011; OI Costa, Pedro/0000-0001-6083-470X; DeGrasse, Stacey/0000-0001-7808-4193 NR 36 TC 25 Z9 29 U1 4 U2 19 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD SEP 1 PY 2009 VL 54 IS 3 BP 313 EP 320 DI 10.1016/j.toxicon.2009.04.023 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 476JS UT WOS:000268436900014 PM 19450616 ER PT J AU Grinev, A Chancey, C Daniel, S Caglioti, S Winkelman, V Land, KJ Rios, M AF Grinev, A. Chancey, C. Daniel, S. Caglioti, S. Winkelman, V. Land, K. J. Rios, M. TI Genetic Evolution of West Nile Virus in Clinical Isolates from the US, 2006-2007 SO TRANSFUSION LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-of-Blood-Banks CY OCT 24-27, 2009 CL New Orleans, LA SP Amer Assoc Blood Banks C1 [Grinev, A.; Chancey, C.; Daniel, S.; Rios, M.] US FDA, Ctr Biol Evaluat & Res, OBRR, Bethesda, MD USA. [Caglioti, S.; Winkelman, V.] Blood Syst Labs, Tampe, AZ USA. [Land, K. J.] Bonfils Blood Ctr, Denver, CO USA. EM Andriyan.Grinev@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2009 VL 49 BP 30A EP 31A PG 2 WC Hematology SC Hematology GA 490XU UT WOS:000269542200078 ER PT J AU Gelderman-Fuhrmann, M Yazer, MH Jia, Y Wood, FB Alayash, A Vostal, J AF Gelderman-Fuhrmann, M. Yazer, M. H. Jia, Y. Wood, F. B. Alayash, A. Vostal, J. TI Serial Evaluation of RBC Biochemical Parameters During Routine Cold Storage SO TRANSFUSION LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-of-Blood-Banks CY OCT 24-27, 2009 CL New Orleans, LA SP Amer Assoc Blood Banks C1 [Yazer, M. H.] Univ Pittsburgh, Pittsburgh, PA USA. [Gelderman-Fuhrmann, M.; Vostal, J.] US FDA, LCH, CBER, Rockville, MD 20857 USA. [Jia, Y.; Wood, F. B.; Alayash, A.] US FDA, LBVB, CBER, Rockville, MD 20857 USA. EM monique.gelderman-fuhrmann@fda.hhs.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2009 VL 49 BP 109A EP 109A PG 1 WC Hematology SC Hematology GA 490XU UT WOS:000269542200275 ER PT J AU Virata-Theimer, M Yan, H Yu, MW AF Virata-Theimer, M. Yan, H. Yu, M. W. TI Levels of Anti-A and Anti-B in US-Licensed Immune Globulin Products SO TRANSFUSION LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-of-Blood-Banks CY OCT 24-27, 2009 CL New Orleans, LA SP Amer Assoc Blood Banks C1 [Virata-Theimer, M.; Yan, H.; Yu, M. W.] FDA CBER, Hematol, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2009 VL 49 BP 115A EP 115A PG 1 WC Hematology SC Hematology GA 490XU UT WOS:000269542200290 ER PT J AU Menis, M Burwen, DR Izurieta, HS Anderson, SA Silverman, TA Holness, LG Ball, R AF Menis, M. Burwen, D. R. Izurieta, H. S. Anderson, S. A. Silverman, T. A. Holness, L. G. Ball, R. TI Transfusion-Related Acute Lung Injury (TRALI) as Recorded Among the Inpatient US Elderly in Medicare Claims Data, 2007 SO TRANSFUSION LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-of-Blood-Banks CY OCT 24-27, 2009 CL New Orleans, LA SP Amer Assoc Blood Banks C1 [Menis, M.; Burwen, D. R.; Izurieta, H. S.; Anderson, S. A.; Ball, R.] FDA CBER, OBE, Rockville, MD USA. [Silverman, T. A.; Holness, L. G.] FDA CBER, OBRR, Rockville, MD USA. EM Mikhail.Menis@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2009 VL 49 BP 197A EP 197A PG 1 WC Hematology SC Hematology GA 490XU UT WOS:000269542200517 ER PT J AU Grinev, A Chancey, C Daniel, S Caglioti, S Winkelman, V Land, KJ Rios, M AF Grinev, A. Chancey, C. Daniel, S. Caglioti, S. Winkelman, V. Land, K. J. Rios, M. TI Genetic Evolution of West Nile Virus in Clinical Isolates from the US, 2006-2007 SO TRANSFUSION LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-of-Blood-Banks CY OCT 24-27, 2009 CL New Orleans, LA SP Amer Assoc Blood Banks C1 [Grinev, A.; Chancey, C.; Daniel, S.; Rios, M.] US FDA, OBRR CBER, Bethesda, MD 20014 USA. [Caglioti, S.; Winkelman, V.] Blood Syst Labs, Tempe, AZ USA. [Land, K. J.] Bonfils Blood Ctr, Denver, CO USA. EM Andriyan.Grinev@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2009 VL 49 BP 207A EP 207A PG 1 WC Hematology SC Hematology GA 490XU UT WOS:000269542200543 ER PT J AU Taylor, DR Silberstein, EM AF Taylor, D. R. Silberstein, E. M. TI Growth of Plasma-Derived Hepatitis C Virus in Cell Culture SO TRANSFUSION LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-of-Blood-Banks CY OCT 24-27, 2009 CL New Orleans, LA SP Amer Assoc Blood Banks C1 [Taylor, D. R.; Silberstein, E. M.] US FDA, CBER, Bethesda, MD 20014 USA. EM deborah.taylor@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2009 VL 49 BP 209A EP 209A PG 1 WC Hematology SC Hematology GA 490XU UT WOS:000269542200549 ER PT J AU Nagarkatti, R Duncan, R Kumar, S Rios, M Hewlett, I Nakhasi, HL Debrabant, A AF Nagarkatti, R. Duncan, R. Kumar, S. Rios, M. Hewlett, I. Nakhasi, H. L. Debrabant, A. TI Selection of RNA Aptamers Against the Blood Borne Pathogen Trypanosoma cruzi SO TRANSFUSION LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-of-Blood-Banks CY OCT 24-27, 2009 CL New Orleans, LA SP Amer Assoc Blood Banks C1 [Nagarkatti, R.; Duncan, R.; Kumar, S.; Rios, M.; Hewlett, I.; Nakhasi, H. L.; Debrabant, A.] US FDA, CBER, DETTD, Bethesda, MD 20014 USA. EM rana.nagarkatti@fda.hhs.gov NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2009 VL 49 BP 230A EP 231A PG 2 WC Hematology SC Hematology GA 490XU UT WOS:000269542200603 ER PT J AU Duncan, R Fisher, C Riggs, LE Nagarkatti, R Nakhasi, HL Cardo, LJ AF Duncan, R. Fisher, C. Riggs, L. E. Nagarkatti, R. Nakhasi, H. L. Cardo, L. J. TI High Sensitivity, Pan-Species Detection of Leishmania Parasites in Blood Through Advances in Sample Preparation and Real-Time PCR SO TRANSFUSION LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-of-Blood-Banks CY OCT 24-27, 2009 CL New Orleans, LA SP Amer Assoc Blood Banks C1 [Duncan, R.; Nagarkatti, R.; Nakhasi, H. L.] US FDA, CBER, Rockville, MD 20857 USA. [Fisher, C.; Riggs, L. E.; Cardo, L. J.] Walter Reed Army Inst Res, Silver Spring, MD USA. EM robert.duncan@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2009 VL 49 BP 232A EP 232A PG 1 WC Hematology SC Hematology GA 490XU UT WOS:000269542200607 ER PT J AU Schoeb, TR McConnell, EE Juliana, MM Davis, JK Davidson, MK Lindsey, JR AF Schoeb, T. R. McConnell, E. E. Juliana, M. M. Davis, J. K. Davidson, M. K. Lindsey, J. R. TI Mycoplasma pulmonis and Lymphoma in Bioassays in Rats SO VETERINARY PATHOLOGY LA English DT Article DE Bioassay; lung; lymphoma; Mycoplasma pulmonis; rats ID SPRAGUE-DAWLEY RATS; BUTYL ETHER MTBE; RESPIRATORY MYCOPLASMOSIS; SPONTANEOUS TUMORS; ASPARTAME; CARCINOGENICITY; NEOPLASMS; AMMONIA; MICE AB Lymphomas were reported to be induced in rats in bioassays of aspartame, methyl-tertiary-butyl ether (MTBE), and other chemicals conducted by a nonprofit cancer research organization. European regulatory authorities concluded that lymphomas in the aspartame study were caused by Mycoplasma pulmonis and suggested that this also was the case for the MTBE bioassay. To assess the role of M. pulmonis in these bioassays, we reviewed the tumor data for the aspartame and MTBE bioassays and, additionally, the organization's bioassay of methanol. For all 3 studies, the most frequently reported hematopoietic neoplasm was lympho-immunoblastic lymphoma, the most frequently affected organ was the lung, and, in almost half of the rats with this diagnosis, the lung was the only affected organ. Lesions diagnosed Lis lymphoma in published illustrations had pleomorphic cellular morphology and appeared to contain neutrophils. Information from these reports and other sources indicated that lesions typical of M. pulmonis disease were prevalent among the aspartame and MTBE Study rats and that the rats were not specific-pathogen-free. Because the lymphoma type, cellular morphology, and organ distribution reported in these studies are atypical of lymphoma in rats, because lymphocyte and plasma cell accumulation in the lung is characteristic of M. pulmonis disease, and because M. pulmonis disease can be exacerbated by experimental manipulations, including chemical treatment, we suggest that a plausible alternative explanation for the reported results of these bioassays is that the studies were confounded by M. pulmonis disease and that lesions of the disease were interpreted as lymphoma. C1 [Schoeb, T. R.; Juliana, M. M.] UAB, Dept Genet, Birmingham, AL 35294 USA. [Lindsey, J. R.] UAB, Dept Emeritus, Birmingham, AL 35294 USA. [McConnell, E. E.] ToxPath Inc, Raleigh, NC USA. [Davis, J. K.] Purdue Univ, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA. [Davidson, M. K.] US FDA, Silver Spring, MD USA. RP Schoeb, TR (reprint author), UAB, Dept Genet, 724 Kaul Human Genet Bldg,720 S 20th St, Birmingham, AL 35294 USA. EM trs@uab.edu NR 46 TC 18 Z9 18 U1 1 U2 8 PU AMER COLL VET PATHOLOGIST PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD SEP PY 2009 VL 46 IS 5 BP 952 EP 959 DI 10.1354/vp.08-VP-0240-S-COM PG 8 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA 493XM UT WOS:000269772600022 PM 19430000 ER PT J AU Major, ME AF Major, Marian E. TI Prophylactic and Therapeutic Vaccination against Hepatitis C Virus (HCV): Developments and Future Perspectives SO VIRUSES-BASEL LA English DT Review DE vaccine; immune responses; immunotherapy; T cells; neutralizing antibody ID T-CELL RESPONSES; CROSS-GENOTYPE NEUTRALIZATION; MONOCLONAL-ANTIBODY AP33; HUMORAL IMMUNE-RESPONSE; SINGLE-SOURCE OUTBREAK; NONSTRUCTURAL PROTEIN-3; HYPERVARIABLE REGION-1; ENVELOPE GLYCOPROTEIN; VIRAL CLEARANCE; IN-VIVO AB Studies in patients and chimpanzees that spontaneously clear Hepatitis C Virus (HCV) have demonstrated that natural immunity to the virus is induced during primary infections and that this immunity can be cross protective. These discoveries led to optimism regarding prophylactic HCV vaccines and a number of studies in the chimpanzee model have been performed, all of which resulted in modified infections after challenge but did not always prevent persistence of the virus. Therapeutic vaccine strategies have also been pursued in an effort to reduce the costs and side effects associated with anti-viral drug treatment. This review summarizes the studies performed thus far in both patients and chimpanzees for prophylactic and therapeutic vaccination, assesses the progress made and future perspectives. C1 US FDA, Ctr Biol, Div Viral Prod, Bethesda, MD 20892 USA. RP Major, ME (reprint author), US FDA, Ctr Biol, Div Viral Prod, Bldg29A Rm1D10,8800 Rockville Pike, Bethesda, MD 20892 USA. EM marian.major@fda.hhs.gov NR 121 TC 5 Z9 5 U1 0 U2 2 PU MDPI AG PI BASEL PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND SN 1999-4915 J9 VIRUSES-BASEL JI Viruses-Basel PD SEP PY 2009 VL 1 IS 2 BP 144 EP 165 DI 10.3390/v1020144 PG 22 WC Virology SC Virology GA 631HL UT WOS:000280337300005 PM 21994543 ER PT J AU Oakley, MS Majam, V Mahajan, B Gerald, N Anantharaman, V Ward, JM Faucette, LJ McCutchan, TF Zheng, H Terabe, M Berzofsky, JA Aravind, L Kumar, S AF Oakley, Miranda S. Majam, Victoria Mahajan, Babita Gerald, Noel Anantharaman, Vivek Ward, Jerrold M. Faucette, Lawrence J. McCutchan, Thomas F. Zheng, Hong Terabe, Masaki Berzofsky, Jay A. Aravind, L. Kumar, Sanjai TI Pathogenic Roles of CD14, Galectin-3, and OX40 during Experimental Cerebral Malaria in Mice SO PLOS ONE LA English DT Article AB An in-depth knowledge of the host molecules and biological pathways that contribute towards the pathogenesis of cerebral malaria would help guide the development of novel prognostics and therapeutics. Genome-wide transcriptional profiling of the brain tissue during experimental cerebral malaria (ECM) caused by Plasmodium berghei ANKA parasites in mice, a well established surrogate of human cerebral malaria, has been useful in predicting the functional classes of genes involved and pathways altered during the course of disease. To further understand the contribution of individual genes to the pathogenesis of ECM, we examined the biological relevance of three molecules -CD14, galectin-3, and OX40 that were previously shown to be overexpressed during ECM. We find that CD14 plays a predominant role in the induction of ECM and regulation of parasite density; deletion of the CD14 gene not only prevented the onset of disease in a majority of susceptible mice (only 21% of CD14-deficient compared to 80% of wildtype mice developed ECM, p < 0.0004) but also had an ameliorating effect on parasitemia (a 2 fold reduction during the cerebral phase). Furthermore, deletion of the galectin-3 gene in susceptible C57BL/6 mice resulted in partial protection from ECM (47% of galectin-3-deficient versus 93% of wildtype mice developed ECM, p < 0.0073). Subsequent adherence assays suggest that galectin-3 induced pathogenesis of ECM is not mediated by the recognition and binding of galectin-3 to P. berghei ANKA parasites. A previous study of ECM has demonstrated that brain infiltrating T cells are strongly activated and are CD44(+) CD62L(-) differentiated memory T cells [1]. We find that OX40, a marker of both T cell activation and memory, is selectively upregulated in the brain during ECM and its distribution among CD4(+) and CD8(+) T cells accumulated in the brain vasculature is approximately equal. RP Oakley, MS (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20014 USA. EM sanjai.kumar@fda.hhs.gov OI Anantharaman, Vivek/0000-0001-8395-0009 FU Intramural NIH HHS NR 62 TC 12 Z9 12 U1 3 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 27 PY 2009 VL 4 IS 8 AR e6793 DI 10.1371/journal.pone.0006793 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 489JE UT WOS:000269415600007 PM 19710907 ER PT J AU Nielsen, JA Lau, P Maric, D Barker, JL Hudson, LD AF Nielsen, Joseph A. Lau, Pierre Maric, Dragan Barker, Jeffery L. Hudson, Lynn D. TI Integrating microRNA and mRNA expression profiles of neuronal progenitors to identify regulatory networks underlying the onset of cortical neurogenesis SO BMC NEUROSCIENCE LA English DT Article ID DEVELOPING CEREBRAL-CORTEX; FIBROBLAST-GROWTH-FACTOR; NEURAL STEM-CELLS; GENE-EXPRESSION; BRAIN; DIFFERENTIATION; REPRESSION; FOREBRAIN; MIGRATION; NEOCORTEX AB Background: Cortical development is a complex process that includes sequential generation of neuronal progenitors, which proliferate and migrate to form the stratified layers of the developing cortex. To identify the individual microRNAs (miRNAs) and mRNAs that may regulate the genetic network guiding the earliest phase of cortical development, the expression profiles of rat neuronal progenitors obtained at embryonic day 11 (E11), E12 and E13 were analyzed. Results: Neuronal progenitors were purified from telencephalic dissociates by a positive-selection strategy featuring surface labeling with tetanus-toxin and cholera-toxin followed by fluorescence-activated cell sorting. Microarray analyses revealed the fractions of miRNAs and mRNAs that were up-regulated or down-regulated in these neuronal progenitors at the beginning of cortical development. Nearly half of the dynamically expressed miRNAs were negatively correlated with the expression of their predicted target mRNAs. Conclusion: These data support a regulatory role for miRNAs during the transition from neuronal progenitors into the earliest differentiating cortical neurons. In addition, by supplying a robust data set in which miRNA and mRNA profiles originate from the same purified cell type, this empirical study may facilitate the development of new algorithms to integrate various "-omics" data sets. C1 [Nielsen, Joseph A.; Lau, Pierre; Hudson, Lynn D.] NINDS, Sect Dev Genet, NIH, Bethesda, MD 20892 USA. [Nielsen, Joseph A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Maric, Dragan; Barker, Jeffery L.] NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Nielsen, JA (reprint author), NINDS, Sect Dev Genet, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM joseph.nielsen@fda.hhs.gov; laup@ninds.nih.gov; maricd@ninds.nih.gov; jeffery.barker@nih.hhs.gov; hudsonl1@od.nih.gov FU NINDS FX We thank Dr. Abdel Elkahloun (NHGRI) and his staff for carrying out the microarray hybridization, washing and scanning. This research was supported by the Intramural Research Program of the NINDS. NR 42 TC 39 Z9 41 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2202 J9 BMC NEUROSCI JI BMC Neurosci. PD AUG 19 PY 2009 VL 10 AR 98 DI 10.1186/1471-2202-10-98 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 491EO UT WOS:000269560600001 PM 19689821 ER PT J AU Slade, BA Leidel, L Vellozzi, C Woo, EJ Hua, W Sutherland, A Izurieta, HS Ball, R Miller, N Braun, MM Markowitz, LE Iskander, J AF Slade, Barbara A. Leidel, Laura Vellozzi, Claudia Woo, Emily Jane Hua, Wei Sutherland, Andrea Izurieta, Hector S. Ball, Robert Miller, Nancy Braun, M. Miles Markowitz, Lauri E. Iskander, John TI Postlicensure Safety Surveillance for Quadrivalent Human Papillomavirus Recombinant Vaccine SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID GUILLAIN-BARRE-SYNDROME; EVENT-REPORTING-SYSTEM; UNITED-STATES; PARTICLE VACCINE; IMMUNIZATION; SYNCOPE; DRUGS; RISK AB Context In June 2006, the Food and Drug Administration licensed the quadrivalent human papillomavirus (types 6, 11, 16, and 18) recombinant vaccine (qHPV) in the United States for use in females aged 9 to 26 years; the Advisory Committee on Immunization Practices then recommended qHPV for routine vaccination of girls aged 11 to 12 years. Objective To summarize reports to the Vaccine Adverse Event Reporting System (VAERS) following receipt of qHPV. Design, Setting, and Participants Review and describe adverse events following immunization (AEFIs) reported to VAERS, a national, voluntary, passive surveillance system, from June 1, 2006, through December 31, 2008. Additional analyses were performed for some AEFIs in prelicensure trials, those of unusual severity, or those that had received public attention. Statistical data mining, including proportional reporting ratios (PRRs) and empirical Bayesian geometric mean methods, were used to detect disproportionality in reporting. Main Outcome Measures Numbers of reported AEFIs, reporting rates (reports per 100 000 doses of distributed vaccine or per person-years at risk), and comparisons with expected background rates. Results VAERS received 12 424 reports of AEFIs following qHPV distribution, a rate of 53.9 reports per 100 000 doses distributed. A total of 772 reports (6.2% of all reports) described serious AEFIs, including 32 reports of death. The reporting rates per 100 000 qHPV doses distributed were 8.2 for syncope; 7.5 for local site reactions; 6.8 for dizziness; 5.0 for nausea; 4.1 for headache; 3.1 for hypersensitivity reactions; 2.6 for urticaria; 0.2 for venous thromboembolic events, autoimmune disorders, and Guillain-Barre syndrome; 0.1 for anaphylaxis and death; 0.04 for transverse myelitis and pancreatitis; and 0.009 for motor neuron disease. Disproportional reporting of syncope and venous thromboembolic events was noted with data mining methods. Conclusions Most of the AEFI rates were not greater than the background rates compared with other vaccines, but there was disproportional reporting of syncope and venous thromboembolic events. The significance of these findings must be tempered with the limitations (possible underreporting) of a passive reporting system. JAMA. 2009;302(7):750-757 C1 [Slade, Barbara A.; Leidel, Laura; Vellozzi, Claudia; Markowitz, Lauri E.; Iskander, John] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Woo, Emily Jane; Hua, Wei; Sutherland, Andrea; Izurieta, Hector S.; Ball, Robert; Miller, Nancy; Braun, M. Miles] US FDA, Washington, DC 20204 USA. RP Slade, BA (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd NE,Mailstop D-26, Atlanta, GA 30333 USA. EM bfs9@cdc.gov FU CDC; FDA FX The study was implemented by the Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA). The only funds used were from CDC and FDA budgets. This study had no external sponsors. NR 33 TC 221 Z9 232 U1 1 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 19 PY 2009 VL 302 IS 7 BP 750 EP 757 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 484UT UT WOS:000269073800023 PM 19690307 ER PT J AU Abraham, SJ Nolet, RP Calvert, RJ Anderson, LM Gaponenko, V AF Abraham, Sherwin J. Nolet, Ryan P. Calvert, Richard J. Anderson, Lucy M. Gaponenko, Vadim TI The Hypervariable Region of K-Ras4B Is Responsible for Its Specific Interactions with Calmodulin SO BIOCHEMISTRY LA English DT Article ID RAS-BINDING DOMAIN; K-RAS; AKT ACTIVATION; H-RAS; COMPLEX; TARGET; EXPRESSION; CA2+/CALMODULIN; TUMORIGENESIS; FIBROBLASTS AB K-Ras4B belongs to the family of p21 Ras GTPases, which play all important role in cell proliferation, survival, and motility. The p21 Ras proteins, such as K-Ras4B, K-Ras4A, H-Ras, and N-Ras, share 85% sequence homology and activate very similar signaling pathways. Only the C-terminal hypervariable regions differ significantly. A growing body of literature demonstrates that each Ras isoform possesses unique functions in normal physiological processes as well as in pathogenesis. One of the central questions in the field of Ras biology is how these very Similar proteins achieve such remarkable specificity in protein-protein interactions that regulate signal transduction pathways. Here we explore specific binding of K-Ras4B to calmodulin. Using NMR techniques and isothermal titration calorimetry, we demonstrate that the hypervariable region of K-Ras4B contributes in a major way to the interaction with calmodulin, while the catalytic domain of K-Ras4B provides a way to control the interaction by nucleotide binding. The hypervariable region of K-Ras4B binds specifically to the C-terminal domain of Ca(2+)-loaded calmodulin With micromolar affinity, while the GTP-gamma-S-loaded catalytic domain of K-Ras4B may interact with the N-terminal domain or calmodulin. C1 [Abraham, Sherwin J.; Nolet, Ryan P.; Gaponenko, Vadim] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA. [Calvert, Richard J.; Anderson, Lucy M.] NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. [Calvert, Richard J.] US FDA, Div Bioanalyt Chem, College Pk, MD 20740 USA. RP Gaponenko, V (reprint author), Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA. EM vadimg@uic.edu FU American Cancer Society [ACS 08-14]; U.S. Department of Health and Human Services FX Supported by the American Cancer Society, Illinois Division Grant ACS 08-14 (to.G.), and the U.S. Department of Health and Human Services. NR 34 TC 24 Z9 24 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 18 PY 2009 VL 48 IS 32 BP 7575 EP 7583 DI 10.1021/bi900769j PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 480GK UT WOS:000268720300003 PM 19583261 ER PT J AU Kostov, Y Yang, MH Rasooly, A AF Kostov, Yordan Yang, Minghui Rasooly, Avraham TI High sensitivity carbon nanotubes based assay for detection of Staphylococcal enterotoxin B in food SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Kostov, Yordan] Univ Maryland Baltimore Cty, Dept Chem & Biochem Engn, Ctr Adv Sensor Technol, Baltimore, MD 21227 USA. [Rasooly, Avraham] Food & Drug Adm, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM kostov@umbc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 16-AGFD BP 142 EP 142 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861900134 ER PT J AU Trucksess, MW Abbas, HK Weaver, CM Shier, WT AF Trucksess, Mary W. Abbas, Hamed K. Weaver, Carol M. Shier, W. T. TI Distribution of mycotoxins in rice milling fractions SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Trucksess, Mary W.; Weaver, Carol M.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Abbas, Hamed K.] ARS, Crop Genet & Prod Res Unit, USDA, NBCL, Stoneville, MS 38776 USA. [Shier, W. T.] Univ Minnesota Twin Cities, Dept Med Chem, Minneapolis, MN 55454 USA. EM mary.trucksess@fda.hhs.gov; hamed.abbas@ars.usda.gov; carol.weaver@fda.hhs.gov; shier001@umn.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 42-AGFD BP 175 EP 175 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861900167 ER PT J AU Evans, RL Siitonen, PH AF Evans, Ronald L. Siitonen, Paul H. TI Screening of complex dietary supplements for chondroitin and glucosamine by size exclusion chromatography with refractive index and uv detection with confirmation using multiangle laser light scattering SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Evans, Ronald L.; Siitonen, Paul H.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Food & Drug Adm, Jefferson, AR 72079 USA. EM ronald.evans@fda.hhs.gov; paul.siitonen@fda.hhs.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 159-AGFD BP 272 EP 272 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861900264 ER PT J AU Nochetto, CB Stine, CB Rummel, NG Heller, DN Reimschuessel, R AF Nochetto, Cristina B. Stine, Cynthia B. Rummel, Nathan G. Heller, David N. Reimschuessel, Renate TI Simultaneous determination and confirmation of melamine and cyanuric acid in fish kidneys by LC/MS/MS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Nochetto, Cristina B.; Stine, Cynthia B.; Rummel, Nathan G.; Heller, David N.; Reimschuessel, Renate] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. EM cristina.nochetto@fda.hhs.gov; cynthia.stine@fda.hhs.gov; nathansummel@fda.hhs.gov; david.heller@fda.hhs.gov; renate.reimschuessel@fda.hhs.gov RI Stine, Cynthia/F-1040-2011 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 36-AGRO BP 417 EP 417 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861900377 ER PT J AU Evans, ER Andersen, WC Karbiwnyk, CM Turnipseed, SB Charles, GM Mayer, TD Nochetto, CB Rummel, NG Reimschuessel, R AF Evans, Eric R. Andersen, Wendy C. Karbiwnyk, Christine M. Turnipseed, Sherri B. Charles, Gieseker M. Mayer, Tamara D. Nochetto, Cristina B. Rummel, Nathan G. Reimschuessel, Renate TI Depletion of the triazine compounds melamine and cyanuric acid following single oral administration in catfish, Ictalurus punctatus, and trout, Oncorhynchus mykiss SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Evans, Eric R.; Charles, Gieseker M.; Mayer, Tamara D.; Nochetto, Cristina B.; Rummel, Nathan G.; Reimschuessel, Renate] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. [Andersen, Wendy C.; Karbiwnyk, Christine M.] US FDA, Off Regulatory Affairs, Denver, CO 80225 USA. [Turnipseed, Sherri B.] US FDA, Anim Drugs Res Ctr, Denver, CO 80225 USA. EM eric.evans@fda.hhs.gov; wendy.andersen@fda.hhs.gov; christine.karbiwnyk@fda.hhs.gov; charles.gieseker@fda.hhs.gov; tamara.mayer@fda.hhs.gov; cristina.nochetto@fda.hhs.gov; nathan.rummel@fda.hhs.gov; renate.reimschuessel@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 268-AGRO BP 468 EP 468 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861900428 ER PT J AU Antunes, AMM Sidarus, MC Beland, FA Marques, MM AF Antunes, Alexandra M. M. Sidarus, Muna C. Beland, Frederick A. Matilde Marques, M. TI TOXI 87-Synthesis and oxidation of 2-hydroxynevirapine, a metabolite of the HIV-1 reverse transcriptase inhibitor nevirapine SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Antunes, Alexandra M. M.; Sidarus, Muna C.; Matilde Marques, M.] Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, P-1049001 Lisbon, Portugal. [Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM alexandra.antunes@ist.utl.pt; msidarus@gmail.com; frederick.beland@fda.hhs.gov; matilde.marques@ist.utl.pt RI Marques, M. Matilde/E-2535-2012; PTMS, RNEM/C-1589-2014; Antunes, Alexandra/B-7871-2009 OI Marques, M. Matilde/0000-0002-7526-4962; Antunes, Alexandra/0000-0003-1827-7369 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 87-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861906700 ER PT J AU Atrakchi, A AF Atrakchi, Aisar TI TOXI 40-FDA guidance on the safety testing of drug metabolites: Scientific recommendations with flexible interpretation SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Atrakchi, Aisar] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM Aisar.atrakchi@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 40-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861906754 ER PT J AU Breger, JC Isayeva, I Langone, JJ Pollack, SK Wang, NS AF Breger, Joyce C. Isayeva, Irada Langone, John J. Pollack, Steven K. Wang, Nam Sung TI Novel click alginate hydrogels for use as biomaterials SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Breger, Joyce C.; Wang, Nam Sung] Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA. [Isayeva, Irada; Pollack, Steven K.] US FDA, Div Chem & Mat Sci, CDRH, OSEL, Silver Spring, MD 20993 USA. [Langone, John J.] US FDA, Div Biol, CDRH, OSEL, Silver Spring, MD 20993 USA. EM jbreger@umd.edu; irada.isayeva@fda.hhs.gov RI Wang, Nam Sun/E-4253-2016 NR 0 TC 0 Z9 0 U1 0 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 138-PMSE PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861905693 ER PT J AU Callahan, JH McFarland, MA Musser, SM Bell, R Andrzejewski, D AF Callahan, John H. McFarland, Melinda A. Musser, Steven M. Bell, Rebecca Andrzejewski, Denis TI ANYL 282-Intact protein liquid chromatography mass spectrometry for bacterial identification and differentiation SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [McFarland, Melinda A.; Andrzejewski, Denis] US FDA, Spect & Mass Spectrometry Branch, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Musser, Steven M.] Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. [Bell, Rebecca] US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol, College Pk, MD 20740 USA. EM john.callahan@fda.hhs.gov; melinda.mcfarland@fda.hhs.gov; Steven.Musser@fda.hhs.gov; Rebecca.Bell@fda.hhs.gov; Denis.Andrzejewski@fda.hhs.gov RI McFarland, Melinda/A-1866-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 282-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861901169 ER PT J AU Ciavarella, AB Del Grosso, A AF Ciavarella, Anthony B. Del Grosso, Alfred TI ANYL 191-ICH validated method for the analysis of 2-phenoxyethanol in biological products with robustness testing using experimental design SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Ciavarella, Anthony B.] US FDA, Ctr Drug Evaluat & Res, Div Prod Qual Res, Silver Spring, MD 20993 USA. [Del Grosso, Alfred] US FDA, Div Prod Qual, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. EM anthony.ciavarella@fda.hhs.gov; alfred.del-grosso@cber.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 191-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861901102 ER PT J AU Cobb, J Lee, A Roger, TST Sarntinoranont, M Luu, HMD AF Cobb, Jessica Lee, Alexandra Roger Tran-Son-Tay Sarntinoranont, Malisa Luu, Hoan-My D. TI TOXI 50-Evaluation of hyaluronic acid-based ocular viscosurgical devices (OVDs) using an in vitro human corneal epithelial cell line model SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Cobb, Jessica] Univ Florida, Dept Biomed Engn, Gainesville, FL 32611 USA. [Lee, Alexandra] Univ Florida, Dept Agr & Biol Engn, Gainesville, FL 32611 USA. [Roger Tran-Son-Tay; Sarntinoranont, Malisa] Univ Florida, Dept Bioengn, Gainesville, FL 32611 USA. [Roger Tran-Son-Tay; Sarntinoranont, Malisa] Univ Florida, Dept Mech & Aerosp Engn, Gainesville, FL 32611 USA. [Luu, Hoan-My D.] US FDA, Off Sci & Engn Labs, Div Chem & Mat Sci, Silver Spring, MD 20903 USA. EM Hoan-My.Luu@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 50-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861906774 ER PT J AU Conklin, SD Cheng, J Capar, SG AF Conklin, Sean D. Cheng, John Capar, Stephen G. TI ANYL 49-Arsenic speciation in fruit juice by HPLC-ICP-MS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Conklin, Sean D.; Cheng, John; Capar, Stephen G.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM sean.conklin@fda.hhs.gov; john.cheng@fda.hhs.gov; stephen.capar@fda.hhs.gov NR 0 TC 0 Z9 0 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 49-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861901100 ER PT J AU Dair, BJ Saylor, DM French, GR Cargal, TE Kennedy, KM Casas, R Pollack, SK AF Dair, Benita J. Saylor, David M. French, Grace R. Cargal, T. Eric Kennedy, Kristen M. Casas, Rachel Pollack, Steven K. TI COLL 559-Effect of substrate material on nanoparticulate silver efficacy SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Dair, Benita J.; Saylor, David M.; Pollack, Steven K.] US FDA, OSEL, Div Chem & Mat Sci, CDRH, Silver Spring, MD 20993 USA. [French, Grace R.] Springbrook High Sch, Silver Spring, MD 20904 USA. [Cargal, T. Eric] Westminster Coll, New Wilmington, PA 16172 USA. [Kennedy, Kristen M.] Catholic Univ Amer, Washington, DC 20064 USA. [Casas, Rachel] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. EM benita.dair@fda.hhs.gov; david.saylor@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 559-COLL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861903207 ER PT J AU Getahun, Z AF Getahun, Zelleka TI FDA drug approval: Chemistry review of new drug application, abbreviated new drug application, and botanical drug products SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Getahun, Zelleka] FDA, Off Gener Drugs, Ctr Drug Evaluat CDER, Rockville, MD 20855 USA. EM zelleka.getahun@fda.hhs.gov NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 7-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907032 ER PT J AU Gonzales, J MacMahon, S Lohne, J Svoronos, P AF Gonzales, Junior MacMahon, Shaun Lohne, Jack Svoronos, Paris TI CHED 142-Liquid chromatography-tandem mass spectrometry method for the detection of nitrofuran metabolites in shrimp SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Gonzales, Junior; Svoronos, Paris] CUNY Queensborough Community Coll, Dept Chem, New York, NY 11364 USA. NE Reg Lab, Food & Drug Adm, Jamaica, NY 11433 USA. EM psvoronos@qcc.cuny.edu NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 142-CHED PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861902529 ER PT J AU Harp, BP Barrows, JN AF Harp, Bhakti Petigara Barrows, Julie N. TI ANYL 175-Reversed-phase liquid chromatographic determination of two manufacturing intermediates in D&C Red No. 34 and its lakes SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Harp, Bhakti Petigara; Barrows, Julie N.] US FDA, Off Cosmet & Colors, College Pk, MD 20740 USA. EM bhakti.petigara@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 175-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861901095 ER PT J AU Heitkemper, DT AF Heitkemper, Douglas T. TI ANYL 263-Case studies in chemical food analysis at FDA's Forensic Chemistry Center SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Heitkemper, Douglas T.] US FDA, Inorgan Lab Branch, Forens Chem Ctr, Cincinnati, OH 45237 USA. EM Douglas.Heitkemper@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 263-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861901369 ER PT J AU Lute, S Wang, H Sanchez, D Barletta, J Chen, Q Brorson, K AF Lute, Scott Wang, Hua Sanchez, Davonie Barletta, Janet Chen, Qi Brorson, Kurt TI BIOT 138-Multiplex RT Q-PCR assay for simultaneous quantification of three biopharmaceutical validation viruses SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Lute, Scott; Brorson, Kurt] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. [Wang, Hua; Sanchez, Davonie] Genentech Inc, Late Stage Purificat Proc Res & Dev, San Francisco, CA 94080 USA. [Barletta, Janet] Genentech Inc, Ctr Dis Control, San Francisco, CA 94080 USA. [Chen, Qi] Genentech Inc, Proc Res & Dev, San Francisco, CA 94080 USA. EM scott.lute@fda.hhs.gov; wang.hua@gene.com; kurt.brorson@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 138-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861901657 ER PT J AU McDermott, MK Kim, CS Butziger, L Patel, L Patwardhan, DV Pollack, SK Saylor, DM AF McDermott, Martin K. Kim, Chang-Soo Butziger, Lauren Patel, Lakir Patwardhan, Dinesh V. Pollack, Steven K. Saylor, David M. TI Effect of drug loading and polymer chemistry on the structure formation of drug-polymer coatings: Experiments and simulations SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [McDermott, Martin K.; Kim, Chang-Soo; Butziger, Lauren; Patel, Lakir; Patwardhan, Dinesh V.; Pollack, Steven K.; Saylor, David M.] US FDA, Div Chem & Mat Sci, CDRH, OSEL, Silver Spring, MD 20903 USA. EM Martin.McDermott@fda.hhs.gov; chang-soo.kim@fda.hhs.gov; Lauren_Butziger@verizon.net; lakir.p@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 430-PMSE PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861905628 ER PT J AU Miesegaes, G Lute, S Brorson, K AF Miesegaes, George Lute, Scott Brorson, Kurt TI BIOT 75-Meta-analysis of a viral clearance regulatory database SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Miesegaes, George; Lute, Scott; Brorson, Kurt] US FDA, Div Monoclonal Antibodies, CDER, Silver Spring, MD 20903 USA. EM george.miesegaes@fda.hhs.gov; scottlute@fda.hhs.gov; kurt.brorson@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 75-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861901594 ER PT J AU Palaima, E Costello, CE Hodgkin, J Gravato-Nobre, M Leymarie, N Cipollo, J AF Palaima, Elizabeth Costello, Catherine E. Hodgkin, Jonathan Gravato-Nobre, Maria Leymarie, Nancy Cipollo, John TI CARB 109-Caenorhabditis elegans bus-2 mutant reveals a new class of O-glycans involved in bacterial resistance SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Palaima, Elizabeth; Costello, Catherine E.] Boston Univ, Sch Med, Ctr Biomed Mass Spectrometry, Boston, MA 02118 USA. [Hodgkin, Jonathan; Gravato-Nobre, Maria] Univ Oxford, Genet Unit, Dept Biochem, Oxford OX1 3QU, England. [Leymarie, Nancy] Ctr Biomed Mass Spectrometry, Dept Biochem, Boston, MA 02118 USA. [Cipollo, John] US FDA, DBPAP, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM cecmsms@bu.edu; jonathan.hodgkin@bioch.ox.ac.uk; john.cipollo@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 109-CARB PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861902060 ER PT J AU Park, JT Read, EK Brorson, K AF Park, Jun T. Read, Erik K. Brorson, Kurt TI BIOT 76-Meta-analysis of a regulatory database of aggregates and particles for biopharmaceutical proteins SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Park, Jun T.; Read, Erik K.; Brorson, Kurt] US FDA, Div Monoclonal Antibodies, OBP, CDER, Bethesda, MD 20892 USA. EM jun.park@fda.hhs.gov; erik.read@fda.hhs.gov; Kurt.Brorson@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 76-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861901529 ER PT J AU Read, EK Park, JT Brorson, K AF Read, Erik K. Park, Jun T. Brorson, Kurt TI BIOT 77-Meta-analysis of a glycosylation regulatory database SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Read, Erik K.; Park, Jun T.] US FDA, Div Monoclonal Antibodies OBP CDER, Bethesda, MD 20892 USA. [Brorson, Kurt] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. EM erik.read@fda.hhs.gov; jun.park@fda.hhs.gov; kurt.brorson@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 77-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861901503 ER PT J AU Reimschuessel, R Evans, E Stine, CB Mayer, T Hasbrouck, N Gieseker, C AF Reimschuessel, Renate Evans, Eric Stine, Cynthia B. Mayer, Tamara Hasbrouck, Nicholas Gieseker, Charles TI TOXI 7-Fish: A nonmammalian model for determining a "No Observable Effect Level" (NOEL) for crystal formation in kidneys after exposure to melamine and cyanuric acid SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Reimschuessel, Renate; Evans, Eric; Stine, Cynthia B.; Mayer, Tamara; Hasbrouck, Nicholas; Gieseker, Charles] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. EM renate.reimschuessel@fda.hhs.gov; eric.evans@fda.hhs.gov; cynthia.stine@fda.hhs.gov; tamara.mayer@fda.hhs.gov; nicholas.hasbrouck@fda.hhs.gov; charles.gieseker@fda.hhs.gov RI Stine, Cynthia/F-1040-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 7-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861906699 ER PT J AU Rickard, JD Vu, NT Sullivan, MP Richfield-Fratz, N Weisz, A AF Rickard, James D. Vu, Nga T. Sullivan, Michael P. Richfield-Fratz, Naomi Weisz, Adrian TI ANYL 183-Determination of intermediates and subsidiary colors in the color additive FD&C Red No. 4 (Ponceau SX) using high-performance liquid chromatography SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Rickard, James D.; Vu, Nga T.; Sullivan, Michael P.; Richfield-Fratz, Naomi; Weisz, Adrian] US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM James.Rickard@fda.hhs.gov; Nga.Vu@fda.hhs.gov; Michael.Sullivan@fda.hhs.gov; Naomi.RichfieldFratz@fda.hhs.gov; adrian.weisz@fda.hhs.gov NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 183-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861901196 ER PT J AU Riordan, WT Heilmann, SM Brorson, K Seshadri, K Etzel, MR AF Riordan, William T. Heilmann, Steven M. Brorson, Kurt Seshadri, Kannan Etzel, Mark R. TI BIOT 144-Salt tolerant membrane adsorbers for robust impurity clearance SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Riordan, William T.; Etzel, Mark R.] Univ Wisconsin, Dept Chem & Biol Engn, Madison, WI 53706 USA. [Heilmann, Steven M.; Seshadri, Kannan] 3M Co, Corp Res Mat Lab 3M, Ctr 3M, St Paul, MN 55144 USA. [Brorson, Kurt] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. EM kurt.brorson@fda.hhs.gov; kseshadri@mmm.com; etzel@engr.wisc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 144-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861901744 ER PT J AU Siburt, CJP Bonaventura, C Alayash, AI Crumbliss, AL AF Siburt, Claire J. Parker Bonaventura, C. Alayash, A. I. Crumbliss, Alvin L. TI Spectroelectrochemical analysis confirms that steric hindrance dictates the extreme rates of nitrite-induced oxidation of the functionally distinct hemoglobins from Lucina pectinata SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Siburt, Claire J. Parker; Crumbliss, Alvin L.] Duke Univ, Dept Chem, Durham, NC 27708 USA. [Bonaventura, C.] Duke Univ, Nicholas Sch Environm, Marine Lab, Beaufort, NC 28516 USA. [Alayash, A. I.] US FDA, Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, Bethesda, MD 20892 USA. EM cps7@duke.edu; alc@chem.duke.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 6-INOR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HZ UT WOS:000207862000722 ER PT J AU Swann, PG AF Swann, Patrick G. TI BIOT 74-Using QbD concepts to categorize biotechnology product quality attributes SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Swann, Patrick G.] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. EM patrick.swann@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 74-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861901772 ER PT J AU Tareke, E Gamboa, G Heinz, T Ali, S AF Tareke, Eden Gamboa, Goncalo Heinz, Thomas Ali, Syed TI TOXI 70-Formation of acrylamide at 37C: Role of oxidative stress SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Tareke, Eden; Ali, Syed] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Gamboa, Goncalo; Heinz, Thomas] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM edunatar@hotmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 70-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861906736 ER PT J AU Uplekar, SD Brorson, K Frey, DD LaCourse, WR Moreira, AR Rao, G AF Uplekar, Shaunak D. Brorson, Kurt Frey, Douglas D. LaCourse, William R. Moreira, Antonio R. Rao, Govind TI BIOT 242-Glycosylation profiles of a monoclonal antibody produced using a high-throughput bioreactor system for mammalian cell culture SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Uplekar, Shaunak D.; Frey, Douglas D.; Moreira, Antonio R.; Rao, Govind] Univ Maryland Baltimore Cty, Dept Chem & Biochem Engn, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Brorson, Kurt] US FDA, Off Biotechnol Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM shaunak1@umbc.edu; kurt.brorson@fda.hhs.gov; grao@umbc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 242-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861901582 ER PT J AU Vallejos, JR Brorson, K Moreira, AR Rao, G AF Vallejos, Jose R. Brorson, Kurt Moreira, Antonio R. Rao, Govind TI BIOT 343-Oxygen transfer characterization of process scouting devices using a noninvasive optical sensor and its bioprocess design implications for mammalian cell cultures SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Vallejos, Jose R.; Moreira, Antonio R.; Rao, Govind] Univ Maryland, Dept Chem & Biochem Engn, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Brorson, Kurt] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. EM jose7@umbc.edu; kurt.brorson@fda.hhs.gov; moreira@umbc.edu; grao@umbc.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 343-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861901417 ER PT J AU Yakes, BJ Poli, M Etheridge, S AF Yakes, Betsy Jean Poli, Mark Etheridge, Stacey TI ANYL 261-Developing improved immunoassays for seafood toxins: The need for superior antibodies SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Yakes, Betsy Jean] US FDA, College Pk, MD 20740 USA. [Poli, Mark] USAMRIID, Integrated Toxicol Div, Ft Detrick, MD 21702 USA. [Etheridge, Stacey] US Food & Drug, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM betsy.yakes@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 261-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861901365 ER PT J AU Zhao, YW Xia, QS Yin, JJ Yu, HT Fu, PP AF Zhao, Yuewei Xia, Qingsu Yin, Jun Jie Yu, Hongtao Fu, Peter P. TI ENVR 105-Photoirradiation of polycyclic aromatic hydrocarbon diones by UVA light leading to lipid peroxidation SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Zhao, Yuewei; Xia, Qingsu; Fu, Peter P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Yin, Jun Jie] FDA, CFSAN, College Pk, MD 20740 USA. [Yu, Hongtao] Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. EM yuewei.zhao@fda.hhs.gov; qingsu.xia@fda.hhs.gov; junjie.yin@fda.hhs.gov; hongtao.yu@jsums.edu; peter.fu@fda.hhs.gov RI Yin, Jun Jie /E-5619-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 105-ENVR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861903615 ER PT J AU Day, JB Basavanna, U Sharma, SK AF Day, J. B. Basavanna, U. Sharma, S. K. TI Development of a Cell Culture Method To Isolate and Enrich Salmonella enterica Serotype Enteritidis from Shell Eggs for Subsequent Detection by Real-Time PCR SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; LINKED-IMMUNOSORBENT-ASSAY; SEROVAR TYPHIMURIUM; PHAGE TYPE-4; FOOD; INFECTION; SAMPLES; MILK; MEAT; HYBRIDIZATION AB Salmonella enterica serotype Enteritidis is a major cause of nontyphoidal salmonellosis from ingestion of contaminated raw or undercooked shell eggs. Current techniques used to identify Salmonella serotype Enteritidis in eggs are extremely laborious and time-consuming. In this study, a novel eukaryotic cell culture system was combined with real-time PCR analysis to rapidly identify Salmonella serotype Enteritidis in raw shell eggs. The system was compared to the standard microbiological method of the International Organization for Standardization (Anonymous, Microbiology of food and animal feeding stuffs-horizontal method for the detection of Salmonella, 2002). The novel technique utilizes a mouse macrophage cell line (RAW 264.7) as the host for the isolation and intracellular replication of Salmonella serotype Enteritidis. Exposure of macrophages to Salmonella serotype Enteritidis-contaminated eggs results in uptake and intracellular replication of the bacterium, which can subsequently be detected by real-time PCR analysis of the DNA released after disruption of infected macrophages. Macrophage monolayers were exposed to eggs contaminated with various quantities of Salmonella serotype Enteritidis. As few as 10 CFU/ml was detected in cell lysates from infected macrophages after 10 h by real-time PCR using primer and probe sets specific for DNA segments located on the Salmonella serotype Enteritidis genes sefA and orgC. Salmonella serotype Enteritidis could also be distinguished from other non-serogroup D Salmonella serotypes by using the sefA-and orgC-specific primer and probe sets. Confirmatory identification of Salmonella serotype Enteritidis in eggs was also achieved by isolation of intracellular bacteria from lysates of infected macrophages on xylose lysine deoxycholate medium. This method identifies Salmonella serotype Enteritidis from eggs in less than 10 h compared to the more than 5 days required for the standard reference microbiological method of the International Organization for Standardization (Microbiology of food and animal feeding stuffs-horizontal method for the detection of Salmonella, 2002). C1 [Day, J. B.; Basavanna, U.; Sharma, S. K.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Day, JB (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-712,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM james.day@fda.hhs.gov NR 41 TC 10 Z9 10 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD AUG 15 PY 2009 VL 75 IS 16 BP 5321 EP 5327 DI 10.1128/AEM.02422-08 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 479LE UT WOS:000268660000018 PM 19561188 ER PT J AU Yang, MH Kostov, Y Bruck, HA Rasooly, A AF Yang, Minghui Kostov, Yordan Bruck, Hugh A. Rasooly, Avraham TI Gold nanoparticle-based enhanced chemiluminescence immunosensor for detection of Staphylococcal Enterotoxin B (SEB) in food SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE Staphylococcal enterotoxins; Enhanced chemiluminescence; Food safety; CCD point-of-care detector; Gold nanoparticles ID BIOMOLECULAR IMMOBILIZATION METHOD; ASSAY KIT TECRA; POTENTIOMETRIC IMMUNOSENSOR; ATOPIC-DERMATITIS; REAL-TIME; ELECTROCHEMICAL IMMUNOSENSOR; RHEUMATOID-ARTHRITIS; CYCLIC VOLTAMMETRY; CARBON NANOTUBES; SOL-GEL AB Staphylococcal enterotoxins (SEs) are major cause of foodborne diseases, so sensitive detection (<1 ng/ml) methods are needed for SE detection in food, The surface area, geometric and physical properties of gold nanoparticles make them well-suited for enhancing interactions with biological molecules in assays. To take advantage of the properties of gold nanoparticles for immunodetection, we have developed a gold nanoparticle-based enhanced chemiluminescence (ECL) immunosensor for detection of Staphylococcal Enterotoxin B (SEB) in food. Anti-SEB primary antibodies were immobilized onto a gold nanoparticle surface through physical adsorption and then the antibody-gold nanoparticle mixture was immobilized onto a polycarbonate surface. SEB was detected by a "sandwich-type" ELISA assay on the polycarbonate surface with a secondary antibody and ECL detection. The signal from ECL was read using a point-of-care detector based on a cooled charge-coupled device (CCD) sensor or a plate reader. The system was used to test for SEB in buffer and various foods (mushrooms, tomatoes, and baby food meat). The limit of detection was found to be similar to 0.01 ng/ml, which is similar to 10 times more sensitive than traditional ELISA. The gold nanoparticles were relatively easy to use for antibody immobilization because of their physical adsorption mechanism; no other reagents were required for immobilization. The use of our simple and inexpensive detector combined with the gold nanoparticle-based ECL method described here is adaptable to simplify and increase sensitivity of any immunological assay and for point-of-care diagnostics. Published by Elsevier B.V. C1 [Rasooly, Avraham] FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. [Yang, Minghui; Kostov, Yordan] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Bruck, Hugh A.] UMCP, College Pk, MD 20742 USA. [Rasooly, Avraham] NCI, Bethesda, MD 20892 USA. RP Rasooly, A (reprint author), FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. EM rasoolya@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 53 TC 51 Z9 56 U1 2 U2 34 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 AUG 15 PY 2009 VL 133 IS 3 BP 265 EP 271 DI 10.1016/j.ijfoodmicro.2009.05.029 PG 7 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 485IT UT WOS:000269115200008 PM 19540011 ER PT J AU Sun, JC Von Tungeln, LS Hines, W Beger, RD AF Sun, Jinchun Von Tungeln, Linda S. Hines, Wade Beger, Richard D. TI Identification of metabolite profiles of the catechol-O-methyl transferase inhibitor tolcapone in rat urine using LC/MS-based metabonomics analysis SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE UPLC/MS; Metabonomics; Tolcapone; Metabolite/metabolism; Urine ID MULTIVARIATE STATISTICAL-ANALYSIS; PARKINSONS-DISEASE; LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRY; DRUG METABOLITES; COMT INHIBITORS; LIVER TOXICITY; NMR; NEPHROTOXICITY; H-1-NMR AB The process of drug metabolite identification is extremely important for drug efficacy, safety and pharmacokinetics. The traditional method usually involves using a drug with a radioactive labeled nuclei and/or isolating major drug metabolites by HPLC before applying MS and NMR analyses, which requires trained specialists to handle the radioactive compounds and is time consuming for offline-HPLC separation. A method using mass spectrometry-based metabonomics combined with multivariate statistical analysis was applied to rapidly identify metabolite profiles of tolcapone, a catechol-O-methyl transferase inhibitor for Parkinson's disease treatment. The tolcapone metabolites were identified based on the accurate mass measurement (<3 ppm) and MS(2) mass spectrum. In total, 16 tolcapone metabolites were detected and identified, 6 of which have not been reported previously. Our results indicate that the method has the capability to accelerate the process of identifying drug metabolites, ultimately reduce drug development costs, and make the process safer without requiring a drug with radioactive nuclei. Most importantly, the assay can detect the major and minor drug metabolites in a global view. Furthermore, since tolcapone has been associated with idiosyncratic drug induced liver toxicity the rapid detection of tolcapone-related metabolites can provide mechanistic toxicity information related to drug metabolism and the formation of reactive drug metabolites. Published by Elsevier B.V. C1 [Sun, Jinchun; Beger, Richard D.] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. [Von Tungeln, Linda S.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Hines, Wade] BG Med, Waltham, MA 02451 USA. RP Beger, RD (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. EM Richard.Beger@fda.hhs.gov NR 21 TC 18 Z9 21 U1 3 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD AUG 15 PY 2009 VL 877 IS 24 BP 2557 EP 2565 DI 10.1016/j.jchromb.2009.06.033 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 484DJ UT WOS:000269023200021 PM 19615953 ER PT J AU Imai, Y Apakupakul, K Krause, PR Halford, WP Margolis, TP AF Imai, Yumi Apakupakul, Kathleen Krause, Philip R. Halford, William P. Margolis, Todd P. TI Investigation of the Mechanism by Which Herpes Simplex Virus Type 1 LAT Sequences Modulate Preferential Establishment of Latent Infection in Mouse Trigeminal Ganglia SO JOURNAL OF VIROLOGY LA English DT Article ID RABBIT EYE MODEL; GENE MESSENGER-RNA; TO-CELL SPREAD; IN-VIVO; TRANSCRIPT GENE; SPONTANEOUS REACTIVATION; ZOSTERIFORM SPREAD; SENSORY NEURONS; IMMUNOHISTOCHEMICAL ANALYSIS; NEUROBLASTOMA-CELLS AB We previously demonstrated that herpes simplex virus type 1 (HSV-1) preferentially establishes latent infection in monoclonal antibody (MAb) A5-positive ganglionic neurons and that a 2.8-kb portion of the HSV-1 genome, corresponding to the 5' end of the LAT (latency-associated transcript) coding region, is responsible for this phenotype (38, 65). In the current study we carried out further genetic mapping of this latency phenotype and investigated some of the mechanisms that might be responsible. Studies with the chimeric virus HSV-1 17syn+/LAT2, an HSV-1 virus engineered to express HSV-2 LAT, demonstrated that this virus exhibited an HSV-2 latency phenotype, preferentially establishing latency in MAb KH10-positive neurons. This result is complementary to that previously described for the chimeric virus HSV-2 333/LAT1 and indicate that the HSV-1 latency phenotype can be changed to that of HSV-2 by substitution of a 2.8-kb piece of complementary viral DNA. Sequential studies in which we evaluated the pattern of HSV-1 latent infection of the mouse trigeminal ganglion following ocular inoculation with viruses with deletions of functional thymidine kinase, glycoprotein E, ICP0, and US9 protein demonstrate that preferential establishment of HSV-1 latent infection in A5-positive neurons is not a consequence of (i) differential access of HSV-1 to A5-positive neurons,(ii) differential cell-to-cell spread of HSV-1 to A5-positive neurons, (iii) differential "round-trip" spread of HSV-1 to A5-positive neurons, or (iv) expression of ICP0. Additional mapping studies with the HSV-1 LAT deletion viruses dLAT371, 17 Delta Sty, and 17 Delta 348 indicate that most of the LAT 5' exon is not required for HSV-1 to preferentially establish latent infection in A5-positive neurons. C1 [Margolis, Todd P.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA. [Imai, Yumi; Apakupakul, Kathleen; Margolis, Todd P.] Univ Calif San Francisco, FI Proctor Fdn, San Francisco, CA 94143 USA. [Krause, Philip R.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Halford, William P.] So Illinois Univ, Sch Med, Dept Microbiol & Immunol, Springfield, IL USA. RP Margolis, TP (reprint author), Univ Calif San Francisco, Dept Ophthalmol, Med Sci Bldg,S-310,513 Parnassus Ave, San Francisco, CA 94143 USA. EM todd.margolis@ucsf.edu OI Krause, Philip/0000-0002-1045-7536 FU NIH [EY10008, EY02162]; Research to Prevent Blindness (New York, NY); Ralph and Sophie Heintz laboratory fund; Littlefield 2000 Trust FX We are deeply grateful to D. Johnson, D. Coen, D. Bloom, N. Fraser, P. Schaffer, and S. Wechsler for their generous supply of viruses used in the course of our studies. MAbs A5, developed by B. Fenderson, and KH10, developed by T. M. Jessell and J. Dodd, were obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the National Institute of Child Health and Human Development and maintained by The University of Iowa, Department of Biological Sciences, Iowa, IA 52242.; This work was supported by NIH EY10008 and EY02162, Research to Prevent Blindness (New York, NY), the Ralph and Sophie Heintz laboratory fund, and the Littlefield 2000 Trust. NR 67 TC 11 Z9 12 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG 15 PY 2009 VL 83 IS 16 BP 7873 EP 7882 DI 10.1128/JVI.00043-09 PG 10 WC Virology SC Virology GA 473LR UT WOS:000268208700008 PM 19493993 ER PT J AU Chu, HT Nie, L Cole, SR Poole, C AF Chu, Haitao Nie, Lei Cole, Stephen R. Poole, Charles TI Meta-analysis of diagnostic accuracy studies accounting for disease prevalence: Alternative parameterizations and model selection SO STATISTICS IN MEDICINE LA English DT Article DE meta-analysis; diagnostic tests; sensitivity and specificity; predictive values; sensitivity; specificity ID LONGITUDINAL DATA-ANALYSIS; SYSTEMATIC REVIEWS; LIKELIHOOD RATIOS; SPECIFICITY; SENSITIVITY; BIAS; REGRESSION; EFFICACY; SPECTRUM; CANCER AB In a meta-analysis of diagnostic accuracy studies, the sensitivities and specificities of a diagnostic test may depend on the disease prevalence since the severity and definition of disease may differ from study to study due to the design and the population considered. In this paper, we extend the bivariate nonlinear random effects model on sensitivities and specificities to jointly model the disease prevalence, sensitivities and specificities using trivariate nonlinear random-effects models. Furthermore, as an alternative parameterization, we also propose jointly modeling the test prevalence and the predictive values, which reflect the clinical utility of a diagnostic test. These models allow investigators to study the complex relationship among the disease prevalence, sensitivities and specificities; or among test prevalence and the predictive values, which can reveal hidden information about test performance. We illustrate the proposed two approaches by reanalyzing the data from a meta-analysis of radiological evaluation of lymph node metastases in patients with cervical cancer and a simulation study. The latter illustrates the importance of carefully choosing an appropriate normality assumption for the disease prevalence, sensitivities and specificities, or the test prevalence and the predictive values. In practice, it is recommended to use model selection techniques to identify a best-fitting model for making statistical inference. In summary, the proposed trivariate random effects models are novel and can be very useful in practice for meta-analysis of diagnostic accuracy studies. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Chu, Haitao] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Chu, Haitao] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. [Chu, Haitao; Cole, Stephen R.] Univ N Carolina, Ctr AIDS Res, Chapel Hill, NC 27599 USA. [Nie, Lei] FDA, OTS, CDER, Off Biometr,Div Biometr 4, Spring, MD 20993 USA. [Cole, Stephen R.; Poole, Charles] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. RP Chu, HT (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. EM hchu@bios.unc.edu RI Chu, Haitao /J-7576-2012; OI Chu, Haitao/0000-0003-0932-598X FU National Institute of Environmental Health Sciences [P30ES10126]; Lineberger Cancer Center Core, U.S. National Cancer Institute [CA16086]; U.S. National Institutes of Health [P30-AI-50410]; National Institute of Allergy and Infectious Diseases [R03-AI-071763]; National Institute of Alcohol Abuse and Alcoholism [R01-AA-01759] FX Dr Poole was supported in part by a grant from the National Institute of Environmental Health Sciences (P30ES10126). Dr Chu was supported in part by the Lineberger Cancer Center Core Grant CA16086 from the U.S. National Cancer Institute and P30-AI-50410 from the U.S. National Institutes of Health. Dr Cole was supported in part by National Institute of Allergy and Infectious Diseases, R03-AI-071763, National Institute of Alcohol Abuse and Alcoholism, R01-AA-01759, and P30-AI-50410. The authors are grateful to the associate editor and referees for their constructive comments and suggestions which have greatly improved this manuscript. This work is completed before Dr Nie joined FDA. Views expressed in this paper are the author's professional opinions and do not necessarily represent the official positions of the U.S. Food and Drug Administration. NR 35 TC 34 Z9 34 U1 2 U2 5 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD AUG 15 PY 2009 VL 28 IS 18 BP 2384 EP 2399 DI 10.1002/sim.3627 PG 16 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 474MC UT WOS:000268287000007 PM 19499551 ER EF